Detailed Visual Cortical Responses Generated by Retinal Sheet Transplants in Rats with Severe Retinal Degeneration.

To combat retinal degeneration, healthy fetal retinal sheets have been successfully transplanted into both rodent models and humans, with synaptic connectivity between transplant and degenerated host retina having been confirmed. In rodent studies, transplants have been shown to restore responses to flashes of light in a region of the superior colliculus corresponding to the location of the transplant in the host retina. To determine the quality and detail of visual information provided by the transplant, visual responsivity was studied here at the level of visual cortex where higher visual perception is processed. For our model, we used the transgenic Rho-S334ter line-3 rat (both sexes), which loses photoreceptors at an early age and is effectively blind at postnatal day 30. These rats received fetal retinal sheet transplants in one eye between 24 and 40 d of age. Three to 10 months following surgery, visually responsive neurons were found in regions of primary visual cortex matching the transplanted region of the retina that were as highly selective as normal rat to stimulus orientation, size, contrast, and spatial and temporal frequencies. Conversely, we found that selective response properties were largely absent in nontransplanted line-3 rats. Our data show that fetal retinal sheet transplants can result in remarkably normal visual function in visual cortex of rats with a degenerated host retina and represents a critical step toward developing an effective remedy for the visually impaired human population.SIGNIFICANCE STATEMENT Age-related macular degeneration and retinitis pigmentosa lead to profound vision loss in millions of people worldwide. Many patients lose both retinal pigment epithelium and photoreceptors. Hence, there is a great demand for the development of efficient techniques that allow for long-term vision restoration. In this study, we transplanted dissected fetal retinal sheets, which can differentiate into photoreceptors and integrate with the host retina of rats with severe retinal degeneration. Remarkably, we show that transplants generated visual responses in cortex similar in quality to normal rats. Furthermore, transplants preserved connectivity within visual cortex and the retinal relay from the lateral geniculate nucleus to visual cortex, supporting their potential application in curing vision loss associated with retinal degeneration

Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill's epidemiologic criteria for causality

<p>Abstract</p> <p>Background</p> <p>Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill's criteria.</p> <p>Methods</p> <p>Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined.</p> <p>Results</p> <p>Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 <it>in vitro </it>cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy). The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism functioning at physiological pH. Finally, randomized studies did not provide evidence for an adverse role of phosphate, milk, and grain foods in osteoporosis.</p> <p>Conclusions</p> <p>A causal association between dietary acid load and osteoporotic bone disease is not supported by evidence and there is no evidence that an alkaline diet is protective of bone health.</p

Towards a fullerene-based quantum computer

Molecular structures appear to be natural candidates for a quantum technology: individual atoms can support quantum superpositions for long periods, and such atoms can in principle be embedded in a permanent molecular scaffolding to form an array. This would be true nanotechnology, with dimensions of order of a nanometre. However, the challenges of realising such a vision are immense. One must identify a suitable elementary unit and demonstrate its merits for qubit storage and manipulation, including input / output. These units must then be formed into large arrays corresponding to an functional quantum architecture, including a mechanism for gate operations. Here we report our efforts, both experimental and theoretical, to create such a technology based on endohedral fullerenes or 'buckyballs'. We describe our successes with respect to these criteria, along with the obstacles we are currently facing and the questions that remain to be addressed.Comment: 20 pages, 13 figs, single column forma

Cover Crop Effect on Subsequent Wheat Yield in the Central Great Plains

Crop production systems in the water-limited environment of the semiarid central Great Plains may not have potential to profitably use cover crops because of lowered subsequent wheat (Triticum asestivum L.) yields following the cover crop. Mixtures have reportedly shown less yield-reducing effects on subsequent crops than single-species plantings. This study was conducted to determine winter wheat yields following both mixtures and single-species plantings of spring-planted cover crops. The study was conducted at Akron, CO, and Sidney, NE, during the 2012–2013 and 2013–2014 wheat growing seasons under both rainfed and irrigated conditions. Precipitation storage efficiency before wheat planting, wheat water use, biomass, and yield were measured and water use efficiency and harvest index were calculated for wheat following four single-species cover crops (flax [Linum usitatissimum L.], oat [Avena sativa L.], pea [Pisum sativum ssp. arvense L. Poir], rapeseed [Brassica napus L.]), a 10-species mixture, and a fallow treatment with proso millet (Panicum miliaceum L.) residue. There was an average 10% reduction in wheat yield following a cover crop compared with following fallow, regardless of whether the cover crop was grown in a mixture or in a single-species planting. Yield reductions were greater under drier conditions. The slope of the wheat water use–yield relationship was not significantly different for wheat following the mixture (11.80 kg ha–1 mm–1) than for wheat following single-species plantings (12.32–13.57 kg ha–1 mm–1). The greater expense associated with a cover crop mixture compared with a single species is not justified

The Cloud Services Innovation Platform-Enabling Service-Based Environmental Modelling Using Infrastructure-As-A-Service Cloud Computing

Service oriented architectures allow modelling engines to be hosted over the Internet abstracting physical hardware configuration and software deployments from model users. Many existing environmental models are deployed as desktop applications running on user\u27s personal computers (PCs). Migration to service - based modelling centralizes the modelling functions to service hosts on the Internet . Users no longer require high-end PCs to run models and model updates encapsulating science advances can be disseminated more rapidly by hosting the modelling functions centrally via an Internet host instead of requiring software updates to user\u27s PCs . In this paper we present the Cloud Services Innovation Platform (CSIP), an Infrastructure -as -a -Service cloud application architecture , used to prototype development of distributed and scalable environmental modelling services. CSIP aims to provide modelling as a service to support both interactive (synchronous) and batch (asynchronous) modelling. CSIP enables c loud-based computing resources to be harnessed for both new and existing environmental models supporting the disaggregation of work into subtasks which execute in parallel using a scalable number of virtual machines. This paper presents CSIP \u27s implementation using the RUSLE2 model as a prototype model. RUSLE2 model service benchmarks are presented to demonstrate performance gains from using cloud resources. We also provide benchmarks for virtualization overhead observed using popular virtual machine hypervisors and demonstrate how application profile characteristics significantly impact performance when virtualized

The operating regime of local computations in primary visual cortex

[Abstract] In V1, local circuitry depends on the position in the orientation map: close to pinwheel centers, recurrent inputs show variable orientation preferences; within iso-orientation domains, inputs are relatively uniformly tuned. Physiological properties such as cell's membrane potentials, spike outputs, and temporal characteristics change systematically with map location. We investigate in a firing rate and a Hodgkin–Huxley network model what constraints these tuning characteristics of V1 neurons impose on the cortical operating regime. Systematically varying the strength of both recurrent excitation and inhibition, we test a wide range of model classes and find the likely models to account for the experimental observations. We show that recent intracellular and extracellular recordings from cat V1 provide the strongest evidence for a regime where excitatory and inhibitory recurrent inputs are balanced and dominate the feed-forward input. Our results are robust against changes in model assumptions such as spatial extent and strength of lateral inhibition. Intriguingly, the most likely recurrent regime is in a region of parameter space where small changes have large effects on the network dynamics, and it is close to a regime of “runaway excitation,” where the network shows strong self-sustained activity. This could make the cortical response particularly sensitive to modulation

A Mixed Methods Study of Individual and Organizational Factors that Affect Implementation of Interventions for Children with Autism in Public Schools

Background: The significant lifelong impairments associated with autism spectrum disorder (ASD), combined with the growing number of children diagnosed with ASD, have created urgency in improving school-based quality of care. Although many interventions have shown efficacy in university-based research, few have been effectively implemented and sustained in schools, the primary setting in which children with ASD receive services. Individual- and organizational-level factors have been shown to predict the implementation of evidence-based interventions (EBIs) for the prevention and treatment of other mental disorders in schools, and may be potential targets for implementation strategies in the successful use of autism EBIs in schools. The purpose of this study is to examine the individual- and organizational-level factors associated with the implementation of EBIs for children with ASD in public schools. Methods: We will apply the Domitrovich and colleagues (2008) framework that examines the influence of contextual factors (i.e., individual- and organizational-level factors) on intervention implementation in schools. We utilize mixed methods to quantitatively test whether the factors identified in the Domitrovich and colleagues (2008) framework are associated with the implementation of autism EBIs, and use qualitative methods to provide a more comprehensive understanding of the factors associated with successful implementation and sustainment of these interventions with the goal of tailoring implementation strategies. Discussion: The results of this study will provide an in-depth understanding of individual- and organizational-level factors that influence the successful implementation of EBIs for children with ASD in public schools. These data will inform potential implementation targets and tailoring of strategies that will help schools overcome barriers to implementation and ultimately improve the services and outcomes for children with ASD