The ubiquitin-proteasome system in retinal health and disease

The ubiquitin–proteasome system (UPS) is the main intracellular pathway for modulated protein turnover, playing an important role in the maintenance of cellular homeostasis. It also exerts a protein quality control through degradation of oxidized, mutant, denatured, or misfolded proteins and is involved in many biological processes where protein level regulation is necessary. This system allows the cell to modulate its protein expression pattern in response to changing physiological conditions and provides a critical protective role in health and disease. Impairments of UPS function in the central nervous system (CNS) underlie an increasing number of genetic and idiopathic diseases, many of which affect the retina. Current knowledge on the UPS composition and function in this tissue, however, is scarce and dispersed. This review focuses on UPS elements reported in the retina, including ubiquitinating and deubiquitinating enzymes (DUBs), and alternative proteasome assemblies. Known and inferred roles of protein ubiquitination, and of the related, SUMO conjugation (SUMOylation) process, in normal retinal development and adult homeostasis are addressed, including modulation of the visual cycle and response to retinal stress and injury. Additionally, the relationship between UPS dysfunction and human neurodegenerative disorders affecting the retina, including Alzheimer's, Parkinson's, and Huntington's diseases, are dealt with, together with numerous instances of retina-specific illnesses with UPS involvement, such as retinitis pigmentosa, macular degenerations, glaucoma, diabetic retinopathy (DR), and aging-related impairments. This information, though still basic and limited, constitutes a suitable framework to be expanded in incoming years and should prove orientative toward future therapy design targeting sight-affecting diseases with a UPS underlying basis.

Intelligent Decision-Making System Frameworks for a Digital Plan of Work: A Theoretical Investigation for the Construction Industry

The construction industry is characterised by fragmentation and suffers from lack of collaboration, often adopting adversarial working practices to achieve deliverables. For the UK Government and construction industry, BIM is a game changer aiming to rectify this fragmentation and promote collaboration. However it has become clear that there is an essential need to have better controls and definitions of both data deliverables and data classification. Traditional methods and techniques for collating and inputting data have shown to be time consuming and provide little to improve or add value to the overall task of improving deliverables. Hence arose the need in the industry to develop a Digital Plan of Work (DPoW) toolkit that would aid the decision making process, providing the required control over the project workflows and data deliverables, and enabling better collaboration through transparency of need and delivery. The specification for the existing Digital Plan of Work (DPoW) was to be, an industry standard method of describing geometric, requirements and data deliveries at key stages of the project cycle, with the addition of a structured and standardised information classification system. However surveys and interviews conducted within this research indicate that the current DPoW resembles a digitised version of the pre-existing plans of work and does not push towards the data enriched decision-making abilities that advancements in technology now offer. A Digital Framework is not simply the digitisation of current or historic standard methods and procedures, it is a new intelligent driven digital system that uses new tools, processes, procedures and work flows to eradicate waste and increase efficiency. In addition to reporting on conducted surveys above, this research paper will present a theoretical investigation into usage of Intelligent Decision Support Systems within a digital plan of work framework. Furthermore this paper will present findings on the suitability to utilise advancements in intelligent decision-making system frameworks and Artificial Intelligence for a UK BIM Framework. This should form the foundations of decision-making for projects implemented at BIM level 2. The gap identified in this paper is that the current digital toolkit does not incorporate the intelligent characteristics available in other industries through advancements in technology and collation of vast amounts of data that a digital plan of work framework could have access to and begin to develop, learn and adapt for decision-making through the live interaction of project stakeholders.

System Costs of Variable Renewable Energy in the European Union. Bruges European Economic Policy (BEEP) Briefings 37/2015

To shift to a low-carbon economy, the EU has been encouraging the deployment of variable renewable energy sources (VRE). However, VRE lack of competitiveness and their technical specificities have substantially raised the cost of the transition. Economic evaluations show that VRE life-cycle costs of electricity generation are still today higher than those of conventional thermal power plants. Member States have consequently adopted dedicated policies to support them. In addition, Ueckerdt et al. (2013) show that when integrated to the power system, VRE induce supplementary not-accounted-for costs. This paper first exposes the rationale of EU renewables goals, the EU targets and current deployment. It then explains why the LCOE metric is not appropriate to compute VRE costs by describing integration costs, their magnitude and their implications. Finally, it analyses the consequences for the power system and policy options. The paper shows that the EU has greatly underestimated VRE direct and indirect costs and that policymakers have failed to take into account the burden caused by renewable energy and the return of State support policies. Indeed, induced market distortions have been shattering the whole power system and have undermined competition in the Internal Energy Market. EU policymakers can nonetheless take full account of this negative trend and reverse it by relying on competition rules, setting-up a framework to collect robust EU-wide data, redesigning the architecture of the electricity system and relying on EU regulators.

Tambora 1815 as a test case for high impact volcanic eruptions: Earth system effects

The eruption of Tambora (Indonesia) in April 1815 had substantial effects on global climate and led to the ‘Year Without a Summer’ of 1816 in Europe and North America. Although a tragic event — tens of thousands of people lost their lives — the eruption also was an ‘experiment of nature’ from which science has learned until today. The aim of this study is to summarize our current understanding of the Tambora eruption and its effects on climate as expressed in early instrumental observations, climate proxies and geological evidence, climate reconstructions, and model simulations. Progress has been made with respect to our understanding of the eruption process and estimated amount of SO2 injected into the atmosphere, although large uncertainties still exist with respect to altitude and hemispheric distribution of Tambora aerosols. With respect to climate effects, the global and Northern Hemispheric cooling are well constrained by proxies whereas there is no strong signal in Southern Hemisphere proxies. Newly recovered early instrumental information for Western Europe and parts of North America, regions with particularly strong climate effects, allow Tambora’s effect on the weather systems to be addressed. Climate models respond to prescribed Tambora-like forcing with a strengthening of the wintertime stratospheric polar vortex, global cooling and a slowdown of the water cycle, weakening of the summer monsoon circulations, a strengthening of the Atlantic Meridional Overturning Circulation, and a decrease of atmospheric CO₂. Combining observations, climate proxies, and model simulations for the case of Tambora, a better understanding of climate processes has emerged.

Rates of organic matter transformation within the production-destruction cycle of the White Sea

Rates of organic matter (OM) transformation within the production-destruction cycle of the White Sea were estimated on the basis of measured activity values of redox enzymes of the electron transport system and of hydrolytic enzymes (phosphatase and protease). It was found that OM oxidation processes were the most intensive in the Kandalaksha Bay, while minimum oxidation rates were characteristic of central parts of the Dvina and Onega bays. It was revealed that the highest rates of phosphate mineralization were characteristic of the central part of the sea and near-mouth areas of the Onega and Kandalaksha bays, with the lowest rates in the Dvina Bay. During the period of intense primary production when resources of inorganic phosphorus were practically depleted, high rates of phosphate regeneration were observed. It was shown that populations of micro- and zooplankton in the White Sea were characterized by low activation energies of the principal metabolism reactions (3-6 kcal/mol), which allowed these populations to provide exchange intensity comparable to that of inhabitants of warm waters during all the seasons.

NASS investigator training - evaluation of the first training cycle. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Life cycle program management & evaluation : an heuristic approach /

"Prepared for use by the Cooperative Extension System"--Cover.

Use of stable-isotope probing, full-cycle rRNA analysis, and fluorescence in situ hybridization-microautoradiography to study a methanol-fed denitrifying microbial community

A denitrifying microbial consortium was enriched in an anoxically operated, methanol-fed sequencing batch reactor (SBR) fed with a mineral salts medium containing methanol as the sole carbon source and nitrate as the electron acceptor. The SBR was inoculated with sludge from a biological nutrient removal activated sludge plant exhibiting good denitrification. The SBR denitrification rate improved from less than 0.02 mg of NO3-.N mg of mixed-liquor volatile suspended solids (MLVSS)(-1) h(-1) to a steady-state value of 0.06 mg of NO3-.N mg of MLVSS-1 h(-1) over a 7-month operational period. At this time, the enriched microbial community was subjected to stable-isotope probing (SIP) with [C-13] methanol to biomark the DNA of the denitrifiers. The extracted [C-13]DNA and [C-12]DNA from the SIP experiment were separately subjected to full-cycle rRNA analysis. The dominant 16S rRNA gene phylotype (group A clones) in the [C-13]DNA clone library was closely related to those of the obligate methylotrophs Methylobacillus and Methylophilus in the order Methylophilales of the Betaproteobacteria (96 to 97% sequence identities), while the most abundant clone groups in the [C-12]DNA clone library mostly belonged to the family Saprospiraceae in the Bacteroidetes phylum. Oligonucleotide probes for use in fluorescence in situ hybridization (FISH) were designed to specifically target the group A clones and Methylophilales (probes DEN67 and MET1216, respectively) and the Saprospiraceae clones (probe SAP553). Application of these probes to the SBR biomass over the enrichment period demonstrated a strong correlation between the level of SBR denitrification and relative abundance of DEN67-targeted bacteria in the SBR community. By contrast, there was no correlation between the denitrification rate and the relative abundances of the well-known denitrifying genera Hyphomicrobium and Paracoccus or the Saprospiraceae clones visualized by FISH in the SBR biomass. FISH combined with microautoradiography independently confirmed that the DEN67-targeted cells were the dominant bacterial group capable of anoxic [C-14] methanol uptake in the enriched biomass. The well-known denitrification lag period in the methanol-fed SBR was shown to coincide with a lag phase in growth of the DEN67-targeted denitrifying population. We conclude that Methylophilales bacteria are the dominant denitrifiers in our SBR system and likely are important denitrifiers in full-scale methanol-fed denitrifying sludges.

Embedding partial G-designs where G is a 4-cycle with a pendant edge

Let D denote the graph consisting of a cycle of length 4 with a pendant edge. In this paper, two very different small embeddings of partial D-designs are presented. (c) 2005 Elsevier B.V. All rights reserved.

Life Cycle Assessment (LCA) Applied to the Design of an Innovative Drying Process for Sewage Sludge

Most adverse environmental impacts result from design decisions made long before manufacturing or usage. In order to prevent this situation, several authors have proposed the application of life cycle assessment (LCA) at the very first phases of the design of a process, a product or a service. The study in this paper presents an innovative thermal drying process for sewage sludge called fry-drying, in which dewatered sludge is directly contacted in the dryer with hot recycled cooking oils (RCO) as the heat medium. Considering the practical difficulties for the disposal of these two wastes, fry-drying presents a potentially convenient method for their combined elimination by incineration of the final fry-dried sludge. An analytical comparison between a conventional drying process and the new proposed fry-drying process is reported, with reference to some environmental impact categories. The results of this study, applied at the earliest stages of the design of the process, assist evaluation of the feasibility of such system compared to a current disposal process for the drying and incineration of sewage sludge.

Patched1 functions as a gatekeeper by promoting cell cycle progression

Mutations in the Hedgehog receptor, Patched 1 (Ptch1), have been linked to both familial and sporadic forms of basal cell carcinoma (BCC), leading to the hypothesis that loss of Ptch1 function is sufficient for tumor progression. By combining conditional knockout technology with the inducible activity of the Keratin6 promoter, we provide in vivo evidence that loss of Ptch1 function from the basal cell population of mouse skin is sufficient to induce rapid skin tumor formation, reminiscent of human BCC. Elimination of Ptch1 does not promote the nuclear translocation of beta-catenin and does not induce ectopic activation or expression of Notch pathway constituents. In the absence of Ptch1, however, a large proportion of basal cells exhibit nuclear accumulation of the cell cycle regulators cyclin D1 and B1. Collectively, our data suggest that Ptch1 likely functions as a tumor suppressor by inhibiting G(1)-S phase and G(2)-M phase cell cycle progression, and the rapid onset of tumor progression clearly indicates Ptch1 functions as a gatekeeper. In addition, we note the high frequency and rapid onset of tumors in this mouse model makes it an ideal system for testing therapeutic strategies, such as Patched pathway inhibitors.

Short-term effects of cycle and treadmill training on exercise tolerance in peripheral arterial disease

Background. To explore the efficacy of cycle training in the treatment of intermittent claudication, the present study compared performance and physiologic effects of cycle training with more conventional treadmill walking training in a group of patients with claudication. Method: Forty-two individuals with peripheral arterial disease and intermittent claudication (24 men, 18 women) were stratified by gender and the presence or absence of type 2 diabetes mellitus and then randomized to a treadmill (n = 13), cycle (n = 15), or control group (n = 14). Treadmill and cycle groups trained three times a week for 6 weeks, whereas the control group did not train during this period. Maximal and pain-free exercise times were measured on graded treadmill and cycle tests before and after training. Results. Treadmill training significantly improved maximal and pain-free treadmill walking times but did not improve cycle performance. Cycle training significantly improved maximal cycle time but did not improve treadmill performance. However, there was evidence of a stronger cross-transfer effect between the training modes for patients who reported a common limiting symptom during cycling and walking at baseline. There was also considerable variation in the training response to cycling, and a subgroup of responsive patients in the cycle group improved their walking performance by more than the average response observed in the treadmill group. Conclusion: These findings suggest that cycle exercise is not effective in improving walking performance in all claudication patients but might be an effective alternative to walking in those who exhibit similar limiting symptoms during both types of exercise.

Nitrogen balance for an agroforestry system irrigated with saline, high nitrogen effluent

Land disposal is commonly used for urban and industrial wastewater, largely due to the high costs involved in alternative treatments or disposal systems. However, the viability of such systems depends on many factors, including the composition of the effluent water, soil type, the plant species grown, growth rate, and planting density. The objective of this study is to establish whether land disposal of nitrogen (N) rich effluent using an agroforestry system is sustainable, and determine the effect of irrigation rate and tree planting density on the N cycle and subsequent N removal. We examined systems for the sustainable disposal of a high strength industrial effluent. The challenge was to leach the salt, by using a sufficiently high rate of irrigation, while simultaneously ensuring that N did not leach from the soil profile. We describe the N balance for two plant systems irrigated with effluent, one comprising Eucalyptus tereticornis and Eucalyptus moluccana and a Rhodes grass (Chloris gayana) pasture, and the other, Rhodes grass pasture alone. Nitrogen balance was assessed from N inputs in effluent and rainfall, accumulation of N in the plant biomass, changes in soil N storage, N loss in run-off water, denitrification and N loss to the groundwater by deep-drainage. Biomass production was estimated from allometric relationships derived from yearly destructive harvesting of selected trees. The N content of that biomass was then calculated from measured N content of the various plant parts, and their mass. Approximately 300 kg N/ha/yr was assimilated into tree biomass at a planting density of 2500 tree/ha of E. moluccana. In addition to tree assimilation, pasture growth between the tree rows, which was regularly harvested, contributed substantially to N uptake. If the trees were harvested after two years of growth and grass harvested regularly, biomass removal of N by the mixed system would be about 700 kg N/ha/yr. The results of this study show that the current system of effluent disposal is not sustainable as the nitrate leaching from the soil profile far exceeds standards set out by the ANZECC guidelines. Hence additional means of N removal will need to be implemented. Biological N removal is an area that warrants further studies as it is aimed at reducing N levels in the effluent before irrigation. This will complement the current agroforestry system.