Increased phosphorylation of Cx36 gap junctions in the AII amacrine cells of RD retina

Retinal degeneration (RD) encompasses a family of diseases that lead to photoreceptor death and visual impairment. Visual decline due to photoreceptor cell loss is further compromised by emerging spontaneous hyperactivity in inner retinal cells. This aberrant activity acts as a barrier to signals from the remaining photoreceptors, hindering therapeutic strategies to restore light sensitivity in RD. Gap junctions, particularly those expressed in AII amacrine cells, have been shown to be integral to the generation of aberrant activity. It is unclear whether gap junction expression and coupling are altered in RD. To test this, we evaluated the expression and phosphorylation state of connexin36, the gap junction subunit predominantly expressed in AII amacrine cells, in two mouse models of RD, rd10 (slow degeneration) and rd1 (fast degeneration). Using Ser293-P antibody, which recognizes a phosphorylated form of connexin36, we found that phosphorylation of connexin36 in both slow and fast RD models was significantly greater than in wildtype controls. This elevated phosphorylation may underlie the increased gap junction coupling of AII amacrine cells exhibited by RD retina

Network Deficiency Exacerbates Impairment in a Mouse Model of Retinal Degeneration

Neural oscillations play an important role in normal brain activity, but also manifest during Parkinson’s disease, epilepsy, and other pathological conditions. The contribution of these aberrant oscillations to the function of the surviving brain remains unclear. In recording from retina in a mouse model of retinal degeneration (RD), we found that the incidence of oscillatory activity varied across different cell classes, evidence that some retinal networks are more affected by functional changes than others. This aberrant activity was driven by an independent inhibitory amacrine cell oscillator. By stimulating the surviving circuitry at different stages of the neurodegenerative process, we found that this dystrophic oscillator further compromises the function of the retina. These data reveal that retinal remodeling can exacerbate the visual deficit, and that aberrant synaptic activity could be targeted for RD treatment

Fast calibrated additive quantile regression

We propose a novel framework for fitting additive quantile regression models, which provides well calibrated inference about the conditional quantiles and fast automatic estimation of the smoothing parameters, for model structures as diverse as those usable with distributional GAMs, while maintaining equivalent numerical efficiency and stability. The proposed methods are at once statistically rigorous and computationally efficient, because they are based on the general belief updating framework of Bissiri et al. (2016) to loss based inference, but compute by adapting the stable fitting methods of Wood et al. (2016). We show how the pinball loss is statistically suboptimal relative to a novel smooth generalisation, which also gives access to fast estimation methods. Further, we provide a novel calibration method for efficiently selecting the 'learning rate' balancing the loss with the smoothing priors during inference, thereby obtaining reliable quantile uncertainty estimates. Our work was motivated by a probabilistic electricity load forecasting application, used here to demonstrate the proposed approach. The methods described here are implemented by the qgam R package, available on the Comprehensive R Archive Network (CRAN)

Season of the year influences infection rates following total hip arthroplasty

To research the influence of season of the year on periprosthetic joint infections. METHODS We conducted a retrospective review of the entire Medicare files from 2005 to 2014. Seasons were classified as spring, summer, fall or winter. Regional variations were accounted for by dividing patients into four geographic regions as per the United States Census Bureau (Northeast, Midwest, West and South). Acute postoperative infection and deep periprosthetic infections within 90 d after surgery were tracked. RESULTS In all regions, winter had the highest incidence of periprosthetic infections (mean 0.98%, SD 0.1%) and was significantly higher than other seasons in the Midwest, South and West (P \u3c 0.05 for all) but not the Northeast (P = 0.358). Acute postoperative infection rates were more frequent in the summer and were significantly affected by season of the year in the West. CONCLUSION Season of the year is a risk factor for periprosthetic joint infection following total hip arthroplasty (THA). Understanding the influence of season on outcomes following THA is essential when risk-stratifying patients to optimize outcomes and reduce episode of care costs. © The Author(s) 2017

Computer automation of ultrasonic testing

Report describes a prototype computer-automated ultrasonic system developed for the inspection of weldments. This system can be operated in three modes: manual, automatic, and computer-controlled. In the computer-controlled mode, the system will automatically acquire, process, analyze, store, and display ultrasonic inspection data in real-time. Flaw size (in cross-section), location (depth), and type (porosity-like or crack-like) can be automatically discerned and displayed. The results and pertinent parameters are recorded

The Orbit of WASP-12b Is Decaying

WASP-12b is a transiting hot Jupiter on a 1.09 day orbit around a late-F star. Since the planet's discovery in 2008, the time interval between transits has been decreasing by 29 ± 2 ms yr⁻¹. This is a possible sign of orbital decay, although the previously available data left open the possibility that the planet's orbit is slightly eccentric and is undergoing apsidal precession. Here, we present new transit and occultation observations that provide more decisive evidence for orbital decay, which is favored over apsidal precession by a ΔBIC of 22.3 or Bayes factor of 70,000. We also present new radial-velocity data that rule out the Rømer effect as the cause of the period change. This makes WASP-12 the first planetary system for which we can be confident that the orbit is decaying. The decay timescale for the orbit is P/P˙=3.25±0.23. Interpreting the decay as the result of tidal dissipation, the modified stellar tidal quality factor is Q′⋆=1.8×10⁵

Elevated glutamatergic compounds in pregenual anterior cingulate in pediatric autism spectrum disorder demonstrated by 1H MRS and 1H MRSI.

Recent research in autism spectrum disorder (ASD) has aroused interest in anterior cingulate cortex and in the neurometabolite glutamate. We report two studies of pregenual anterior cingulate cortex (pACC) in pediatric ASD. First, we acquired in vivo single-voxel proton magnetic resonance spectroscopy ((1)H MRS) in 8 children with ASD and 10 typically developing controls who were well matched for age, but with fewer males and higher IQ. In the ASD group in midline pACC, we found mean 17.7% elevation of glutamate + glutamine (Glx) (p<0.05) and 21.2% (p<0.001) decrement in creatine + phosphocreatine (Cr). We then performed a larger (26 subjects with ASD, 16 controls) follow-up study in samples now matched for age, gender, and IQ using proton magnetic resonance spectroscopic imaging ((1)H MRSI). Higher spatial resolution enabled bilateral pACC acquisition. Significant effects were restricted to right pACC where Glx (9.5%, p<0.05), Cr (6.7%, p<0.05), and N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (10.2%, p<0.01) in the ASD sample were elevated above control. These two independent studies suggest hyperglutamatergia and other neurometabolic abnormalities in pACC in ASD, with possible right-lateralization. The hyperglutamatergic state may reflect an imbalance of excitation over inhibition in the brain as proposed in recent neurodevelopmental models of ASD

Automatic Code Placement Alternatives for Ad-Hoc And Sensor Networks

Developing applications for ad-hoc and sensor networks poses significant challenges. Many interesting applications in these domains entail collaboration between components distributed throughout an ad-hoc network. Defining these components, optimally placing them on nodes in the ad-hoc network and relocating them in response to changes is a fundamental problem faced by such applications. Manual approaches to code and data migration are not only platform-dependent and error-prone, but also needlessly complicate application development. Further, locally optimal decisions made by applications that share the same network can lead to globally unstable and energy inefficient behavior. In this paper we describe the design and implementation of a distributed operating system for ad-hoc and sensor networks whose goal is to enable power-aware, adaptive, and easy-to-develop ad-hoc networking applications. Our system achieves this goal by providing a single system image of a unified Java virtual machine to applications over an ad-hoc collection of heterogeneous nodes. It automatically and transparently partitions applications into components and dynamically finds a placement of these components on nodes within the ad-hoc network to reduce energy consumption and increase system longevity. This paper outlines the design of our system and evaluates two practical, power-aware, online algorithms for object placement that form the core of our system. We demonstrate that our algorithms can increase system longevity by a factor of four to five by effectively distributing energy consumption, and are suitable for use in an energy efficient operating system in which applications are distributed automatically and transparently

Ethnic Differences in Bladder Cancer Survival

ObjectiveTo examine trends in bladder cancer survival among whites, blacks, Hispanics, and Asian/Pacific Islanders in the United States over a 30-year period. Racial disparities in bladder cancer outcomes have been documented with poorer survival observed among blacks. Bladder cancer outcomes in other ethnic minority groups are less well described.MethodsFrom the Surveillance, Epidemiology and End Results cancer registry data, we identified patients diagnosed with transitional cell carcinoma of the bladder between 1975 and 2005. This cohort included 163,973 white, 7731 black, 7364 Hispanic, and 5934 Asian/Pacific Islander patients. We assessed the relationship between ethnicity and patient characteristics. Disease-specific 5-year survival was estimated for each ethnic group and for subgroups of stage and grade.ResultsBlacks presented with higher-stage disease than whites, Hispanics, and Asian/Pacific Islanders, although a trend toward earlier-stage presentation was observed in all groups over time. Five-year disease-specific survival was consistently worse for blacks than for other ethnic groups, even when stratified by stage and grade. Five-year disease-specific survival was 82.8% in whites compared with 70.2% in blacks, 80.7% in Hispanics, and 81.9% in Asian/Pacific Islanders. There was a persistent disease-specific survival disadvantage in black patients over time that was not seen in the other ethnic groups.ConclusionEthnic disparities in bladder cancer survival persist between whites and blacks, whereas survival in other ethnic minority groups appears similar to that of whites. Further study of access to care, quality of care, and treatment decision making among black patients is needed to better understand these disparities

Photovoltaic power system simulation for small industry area

In this paper, modeling and simulation of 1MW grid connected PV system is simulated using National Renewable Energy Laboratory's (NREL) HOMER software, and the optimum system is analyzed to see the economic feasibility of the system in a small industry area in Malacca, Malaysia. The system is expected to foresee reduced grid energy consumption. Emphasis is also placed on reduction of green house gases emission. HOMER will simulate the system and perform optimization of system according to the available usage data and the available renewable energy (sun radiation) data. The lifecycle and cost of each system modules will also affect the optimization duly. In addition, HOMER also performs optimizations according to different assumption of uncertain factors to gauge the effect of sensitivity list