Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis.

Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.

Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05).

Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics. (C) 2015 Published by Elsevier Inc. on behalf of The Alzheimer's Association.

King David’s City at Khirbet Qeiyafa: Results of the Second Radiocarbon Dating Project

Fifteen samples of burnt olive pits discovered inside a jar in the destruction layer of the Iron Age city of Khirbet Qeiyafa were analyzed by accelerator mass spectrometry (AMS) radiocarbon dating. Of these, four were halved and sent to two different laboratories to minimize laboratory bias. The dating of these samples is ~1000 BC. Khirbet Qeiyafa is currently the earliest known example of a fortified city in the Kingdom of Judah and contributes direct evidence to the heated debate on the biblical narrative relating to King David. Was he the real historical ruler of an urbanized state-level society in the early 10th century BC or was this level of social development reached only at the end of the 8th century BC? We can conclude that there were indeed fortified centers in the Davidic kingdom from the studies presented. In addition, the dating of Khirbet Qeiyafa has far-reaching implications for the entire Levant. The discovery of Cypriot pottery at the site connects the 14C datings to Cyprus and the renewal of maritime trade between the island and the mainland in the Iron Age. A stone temple model from Khirbet Qeiyafa, decorated with triglyphs and a recessed doorframe, points to an early date for the development of this typical royal architecture of the Iron Age Levant.

Late-Glacial and early Holocene marine 14C reservoir ages off North Iceland (16-9 cal kyr BP)

Tephrochronological age models and 48 14C age determinations on molluscs and foraminifera (planktonic and benthic) are applied for the calculation of marine 14C reservoir age variability during a time period covering the Heinrich event H1 to early Holocene (16–9 cal kyr BP). Our data source consists of four high-resolution marine sediment cores (HM107-04, HM107-05, MD99-2271, MD99-2275) from the North Icelandic shelf. The marine reservoir age (ΔR) is found to be extremely variable, ranging from 385 to 1065 14C years. Extreme ΔR values occur at the end of H1, with values around 1000 14C years (~15 cal kyr BP), probably due to reduced northward flow of well-ventilated subtropical surface waters and a southward expansion of polar waters, as well as an expansion of sea ice limiting air-sea gas exchange. With the onset of the Bølling-Allerød interstadial, the ΔR values decrease towards 0 14C years suggesting a more vigorous North Atlantic Current and an active meridional overturning circulation system. During the Younger Dryas stadial, ΔR values are consistently around 700 14C years suggesting e renewed expansion of polar waters and a weakened meridional overtuning circulation. Interestingly, ΔR values remain high (~200 14C years) at the onset of the Holocene suggesting continued high influence of polar waters. Subsequently, ΔR values rapidly decrease to ~¬ 250 14C years around 11 cal kyr BP, indicating increased air-sea CO2 exchange with the coeval atmosphere. The ΔR values average around 0 14C years from around 10.5 to 9.0 cal kyr BP.

A systematic review and meta-analysis of the survival of non-feldspathic porcelain veneers over 5 and 10 years

PURPOSE: This systematic review aimed to report and explore the survival of dental veneers constructed from non-feldspathic porcelain over 5 and 10 years.

MATERIALS AND METHODS: A total of 4,294 articles were identified through a systematic search involving all databases in the Cochrane Library, MEDLINE (OVID), EMBASE, Web of Knowledge, specific journals (hand-search), conference proceedings, clinical trials registers, and collegiate contacts. Articles, abstracts, and gray literature were sought by two independent researchers. There were no language limitations. One hundred sixteen studies were identified for full-text assessment, with 10 included in the analysis (5 qualitative, 5 quantitative). Study characteristics and survival (Kaplan-Meier estimated cumulative survival and 95% confidence interval [CI]) were extracted or recalculated. A failed veneer was one which required an intervention that disrupted the original marginal integrity, had been partially or completely lost, or had lost retention more than twice. A meta-analysis and sensitivity analysis of Empress veneers was completed, with an assessment of statistical heterogeneity and publication bias. Clinical heterogeneity was explored for results of all veneering materials from included studies.

RESULTS: Within the 10 studies, veneers were fabricated with IPS Empress, IPS Empress 2, Cerinate, and Cerec computer-aided design/computer-assisted manufacture (CAD/CAM) materials VITA Mark I, VITA Mark II, Ivoclar ProCad. The meta-analysis showed the pooled estimate for Empress veneers to be 92.4% (95% CI: 89.8% to 95.0%) for 5-year survival and 66% to 94% (95% CI: 55% to 99%) for 10 years. Data regarding other non-feldspathic porcelain materials were lacking, with only a single study each reporting outcomes for Empress 2, Cerinate, and various Cerec porcelains over 5 years. The sensitivity analysis showed data from one study had an influencing and stabilizing effect on the 5-year pooled estimate.

CONCLUSION: The long-term outcome (> 5 years) of non-feldspathic porcelain veneers is sparsely reported in the literature. This systematic review indicates that the 5-year cumulative estimated survival for etchable non-feldspathic porcelain veneers is over 90%. Outcomes may prove clinically acceptable with time, but evidence remains lacking and the use of these materials for veneers remains experimental.

Taking risks with translational research

The recent bankruptcy filing by deCODE, a company with an exceptional pedigree in associating genetic variance with disease onset, highlights the commercial risks of translational research. Indeed, deCODE's approach was similar to that adapted by academic researchers who seek to connect genetics and disease. We argue here that neither a purely corporate nor purely academic model is entirely appropriate for such research. Instead, we suggest that the private sector undertake the high-throughput elements of translational research, while the public sector and governments assume the role of providing long-term funding to develop gifted scientists with the confidence to attempt to use genetic data as a stepping stone to a truly mechanistic understanding of complex disease.

The effects of lichen cover upon the rate of solutional weathering of limestone

The contribution of lichens to the biomodification of limestone surfaces is an area of conflict within bioweathering studies, with some researchers suggesting a protective effect induced by lichen coverage and others a deteriorative effect induced by the same organisms.Data are reported demonstrating the potential role of endolithic lichen, in particular of Bagliettoa baldensis, in the active protection of Carboniferous limestone surfaces from rainfall-induced solutional weathering. During a 12-month microcatchment exposure period in the west of Northern Ireland, average dissolutional losses of calciumare greater from a lichen-free limestone surface compared with a predominantly endolithic lichen-covered surface by just under 1.25 times. During colderwintermonths, the lichen free surface experiences calcium loss almost 1.5 times greater than the lichen-covered surface. Using extrapolation to upscale from the micro-catchment sample scale, for the year of sample exposure, the rate of calcium loss is 1.001 g m−2 a−1 from lichen-covered limestone surfaces and 1.228 gm−2 a−1 from lichen-free bare limestone surfaces. This research has implications for our understanding of karst environments, the contribution of lichens to karren development and the conservation of lichen-colonised dimension stone within a cultural setting.

Building sandstone surface modification by biofilm and iron precipitation: emerging block-scale heterogeneity and system response

Stone surfaces are sensitive to their environment. This means that they will often respond to exposure conditions by manifesting a change in surface characteristics. Such changes can be more than simply aesthetic, creating surface/subsurface heterogeneity in stone at the block scale, promoting stress gradients to be set up as surface response to, for example, temperature fluctuations, can diverge from subsurface response. This paper reports preliminary experiments investigating the potential of biofilms and iron precipitation as surface-modifiers on stone, exploring the idea of block-scale surface-to-depth heterogeneity, and investigating how physical alteration in the surface and near-surface zone can have implications for subsurface response and potentially for long-term decay patterns. Salt weathering simulations on fresh and surface-modified stone suggest that even subtle surface modification can have significant implications for moisture uptake and retention, salt concentration and distribution from surface to depth, over the period of the experimental run. The accumulation of salt may increase the retention of moisture, by modifying vapour pressure differentials and the rate of evaporation.
Temperature fluctuation experiments suggest that the presence of a biofilm can have an impact on energy transfer processes that occur at the stone surface (for example, buffering against temperature fluctuation), affecting surface-to-depth stress gradients. Ultimately, fresh and surface-modified blocks mask different kinds of system, which respond to inputs differently because of different storage mechanisms, encouraging divergent behaviour between fresh and surface modified stone over time.

Les techniques du dinandier: formes et fonction des outils lithiques spécifiques à la déformation plastique des métaux

In recent years, the proliferation of discoveries has enabled studies of stone tools used in metal working to develop. The increasing number of tools, made mostly from Neolithic polished axes, reveals a typological and functional diversity that remained largely unsuspected. This diversity is an opportunity to understand the tools and address the technical issues relating to the plastic deformation of metals. The operations that are represented here demonstrate the techniques used by coppersmiths with specialised tools.

Catchment and in-stream influences on metal concentration and ochre deposit density in upland streams, Northern Ireland

Metal concentrations from stream waters in two geological blocks in Northern Ireland were compared to determine the contributions of catchment characteristics and in-stream conditions. One block is composed of metamorphosed schist and unconsolidated glacial drift with peat or peaty podzol (mainly humic) soils, while the other block consists of tertiary basalt with brown earth and gley soils. Water samples were collected from 52 stream sites and analysed for Fe, Mn and Al as well as a range of other chemical determinands known to affect metal solubility. Densities of metal-rich ochre deposit were determined for stream bed stone samples. Higher conductivities and concentrations of bicarbonate, alkalinity, Ca and Mg occurred on basalt than on schist. Despite higher Fe and Mn oxide concentrations in basalt-derived non-humic soils, stream water concentrations were much lower and ochre deposit densities only one third of those on schist overlain by humic soils. Neither rock nor soil type predicted Al concentrations, but pH and dissolved oxygen did. Peat-generated acidity and the limited acid neutralising capacity of base-poor metamorphosed schist have resulted in elevated concentrations of metals and ochre deposit in surface waters.

Monitoring of a novel FlexiArchTM bridge system to investigate soil-structure interaction

Masonry arch bridges are one of the oldest forms of bridge construction and have been around for thousands of years. Brick and stone arch bridges have proven to be highly durable as most of them have remained serviceable after hundreds of years. In contrast, many bridges built of modern materials have required extensive repair and strengthening after being in service for a relatively short part of their design life. This paper describes the structural monitoring of a novel flexible concrete arch known as: FlexiArchTM. This is a bridge system that can be transported as a flat-pack system to form an arch in-situ by the use of a flexible polymeric membrane. The system has been developed under a Knowledge Transfer Partnership between Queen’s University Belfast (QUB) and Macrete Ltd. Tievenameena Bridge in Northern Ireland was a replacement bridge for the Northern Ireland Roads Service and was monitored under different axle loadings using a range of sensors including discrete fiber optic Bragg gratings to measure the change in strain in the arch ring under live loading. This paper discusses the results of a laboratory model study carried out at QUB. A scaled arch system was loaded with a simulated moving axle. Various techniques were used to monitor the arch under the moving axle load with particular emphasis on the interaction of the arch ring and engineered backfill.

Northern Ireland

Northern Ireland has been considered a conflict-resolution success story. The 1998 Belfast/Good Friday Agreement provided a framework for managing a long-standing ethnonational conflict, and has ushered in relative political stability. The consociational features of the Northern Ireland Assembly can be seen either as necessary for managing conflict or as institutionalizing sectarianism so that politics along left–right lines cannot emerge. Although there is evidence for the development of a “Northern Irish” identity to counter competing British and Irish identities, Northern Ireland is a long way from transcending the sectarian structures that shape almost all aspects of social and political life. Northern Ireland remains segregated along religious lines and is also prone to tensions around the anniversaries of atrocities and the public use of symbols and rituals. The failure to systematically “deal with the past” through public information recovery and truth-telling mechanisms also seems to have hindered progress toward reconciliation.

The influence of substrate texture on early biological colonization

Biological colonization of stone is a major concern in the preservation and presentation of cultural heritage. Colonization is typically associated with unpleasant soiling, and varying degrees of biodeterioration. A better understanding of why organisms grow where they do, will aid in
developing preventative, and treatment methods for biosoiling of cultural heritage. Sandstone exposure trials were set up at nine different locations across Northern Ireland to investigate the influences of local climate, local environmental,and micro-climatic factors on the early stages (up to 21 months) of biological colonization.
Results showed that, green and yellow soiling occurred on tooled stone surfaces, whereas darkening occurred preferentially on smooth surfaces. It is likely that different populations of organisms occur on these surfaces with green algae occurring on tooled surfaces due to slower drying rates (i.e. prolonged moisture retention), and cyanobacteria and fungi thriving on smooth surfaces due to their ability to withstand moisture fluctuation.

Biological phosphorus removal during high-rate, low-temperature, anaerobic digestion of wastewater.

We report, for the first time, extensive biologically-mediated phosphate removal from wastewater during high-rate anaerobic digestion (AD). A hybrid sludge bed/fixed-film (packed pumice stone) reactor was employed for low-temperature (12°C) anaerobic treatment of synthetic sewage wastewater. Successful phosphate removal from the wastewater (up to 78% of influent phosphate) was observed, mediated by biofilms in the reactor. Scanning electron microscopy and energy dispersive X-ray analysis revealed the accumulation of elemental phosphorus (~2%) within the sludge bed and fixed-film biofilms. 4’, 6-diamidino-2-phenylindole (DAPI) staining indicated phosphorus accumulation was biological in nature and mediated through the formation of intracellular inorganic polyphosphate (polyP) granules within these biofilms. DAPI staining further indicated that polyP accumulation was rarely associated with free cells. Efficient and consistent chemical oxygen demand (COD) removal was recorded, throughout the 732-day trial, at applied organic loading rates between 0.4-1.5 kg COD m-3 d-1 and hydraulic retention times of 8-24 hours, while phosphate removal efficiency ranged from 28-78% on average per phase. Analysis of protein hydrolysis kinetics and the methanogenic activity profiles of the biomass revealed the development, at 12˚C, of active hydrolytic and methanogenic populations. Temporal microbial changes were monitored using Illumina Miseq analysis of bacterial and archaeal 16S rRNA gene sequences. The dominant bacterial phyla present in the biomass at the conclusion of the trial were the Proteobacteria and Firmicutes and the dominant archaeal genus was Methanosaeta. Trichococcus and Flavobacterium populations, previously associated with low temperature protein degradation, developed in the reactor biomass. The presence of previously characterised polyphosphate accumulating organisms (PAOs) such as Rhodocyclus, Chromatiales, Actinobacter and Acinetobacter was recorded at low numbers. However, it is unknown as yet if these were responsible for the luxury polyP uptake observed in this system. The possibility of efficient phosphate removal and recovery from wastewater during AD would represent a major advance in the scope for widespread application of anaerobic wastewater treatment technologies.