Hydrological controls of in situ preservation of waterlogged archaeological deposits

Environmental change caused by urban development, land drainage, agriculture or climate change may result in accelerated decay of in situ archaeological remains. This paper reviews research into impacts of environmental change on hydrological processes of relevance to preservation of archaeological remains in situ. It compares work at rural sites with more complex urban environments. The research demonstrates that both the quantity and quality of data on preservation status, and hydrological and chemical parameters collected during routine archaeological surveys need to be improved. The work also demonstrates the necessity for any archaeological site to be placed within its topographic and geological context. In order to understand preservation potential fully, it is necessary to move away from studying the archaeological site as an isolated unit, since factors some distance away from the site of interest can be important for determining preservation. The paper reviews what is known about the hydrological factors of importance to archaeological preservation and recommends research that needs to be conducted so that archaeological risk can be more adequately predicted and mitigated. Any activity that changes either source pathways or the dominant water input may have an impact not just because of changes to the water balance or the water table, but because of changes to water chemistry. Therefore, efforts to manage threatened waterlogged environments must consider the chemical nature of the water input into the system. Clearer methods of assessing the degree to which buried archaeological sites can withstand changing hydrological conditions are needed, in addition to research which helps us understand what triggers decay and what controls thresholds of response for different sediments and types of artefact

Transitioning roadways from high-speed to low-speed environments when approaching regional towns in North Queensland

This project combines a desktop study and field sampling to assess the effectiveness of traffic control devices currently in place to transition motorists from high-speed to low-speed environments. The project focuses on regional town approaches within North Queensland as there is limited research and experimentation on this sector of road safety in the area. Speed sampling, crash data and the analysis of relevant environmental factors form the basis of the evaluation of the effectiveness of traffic control devices in place. Background information presented includes the physical and psychological elements which dictate the speed environment, speed and transition zones, current gateway treatments and other management strategies. International case study experiments relevant to transition zones approaching regional towns are evaluated and signal the performance of different treatments. The experimentation methodology employed was the speed sampling of five transition zones throughout North Queensland. Crash data within the five transition zones was critically evaluated to ascertain if a link between speed and crash data could be established. Speed sample results indicate that the current traffic control devices are ineffective in achieving acceptable speed compliance. However, the evaluation also indicates that the crash rates in the focus areas are not significant enough to be considered high priority as current traffic control devices are effective in limiting ‘fatal crashes’. Site specific recommendations are provided for changes to improve speed compliance throughout the focus areas

Geophysical-geotechnical sensor networks for landslide monitoring

Landslides are often the result of complex, multi-phase processes where gradual deterioration of shear strength within the sub-surface precedes the appearance of surface features and slope failure. Moisture content increases and the build-up of associated pore water pressures are invariably associated with a loss of strength, and thus are a precursor to failure. Consequently, hydraulic processes typically play a major role in the development of landslides. Geoelectrical techniques, such as resistivity and self-potential are being increasingly applied to study landslide structure and the hydraulics of landslide processes. The great strengths of these techniques are that they provide spatial or volumetric information at the site scale, which, when calibrated with appropriate geotechnical and hydrogeological data, can be used to characterise lithological variability and monitor hydraulic changes in the subsurface. In this study we describe the development of an automated time-lapse electrical resistivity tomography (ALERT) and geotechnical monitoring system on an active inland landslide near Malton, North Yorkshire, UK. The overarching objective of the research is to develop a 4D landslide monitoring system that can characterise the subsurface structure of the landslide, and reveal the hydraulic precursors to movement. The site is a particularly import research facility as it is representative of many lowland UK situations in which weak mudrocks have failed on valley sides. Significant research efforts have already been expended at the site, and a number of baseline data sets have been collected, including ground and airborne LIDAR, geomorphologic and geological maps, and geophysical models. The monitoring network comprises an ALERT monitoring station connected to a 3D monitoring electrode array installed across an area of 5,500 m2, extending from above the back scarp to beyond the toe of the landslide. The ALERT instrument uses wireless telemetry (in this case GPRS) to communicate with an office based server, which runs control software and a database management system. The control software is used to schedule data acquisition, whilst the database management system stores, processes and inverts the remotely streamed ERT data. Once installed and configured, the system operates autonomously without manual intervention. Modifications to the ALERT system at this site have included the addition of environmental and geotechnical sensors to monitor rainfall, ground movement, ground and air temperature, and pore pressure changes within the landslide. The system is housed in a weatherproof enclosure and is powered by batteries charged by a wind turbine & solar panels. 3D ERT images generated from the landslide have been calibrated against resistivity information derived from laboratory testing of borehole core recovered from the landslide. The calibrated images revealed key aspects of the 3D landslide structure, including the lateral extent of slipped material and zones of depletion and accumulation; the surface of separation and the thickness of individual earth flow lobes; and the dipping in situ geological boundary between the bedrock formations. Time-lapse analysis of resistivity signatures has revealed artefacts within the images that are diagnostic of electrode movement. Analytical models have been developed to simulate the observed artefacts, from which predictions of electrode movement have been derived. This information has been used to correct the ERT data sets, and has provided a means of using ERT to monitor landslide movement across the entire ALERT imaging area. Initial assessment of seasonal changes in the resistivity signature has indicated that the system is sensitive to moisture content changes in the body of the landslide, thereby providing a basis for further development of the system with the aim of monitoring hydraulic precursors to failure

Transcriptome Analysis of Targeted Mouse Mutations Reveals the Topography of Local Changes in Gene Expression.

The unintended consequences of gene targeting in mouse models have not been thoroughly studied and a more systematic analysis is needed to understand the frequency and characteristics of off-target effects. Using RNA-seq, we evaluated targeted and neighboring gene expression in tissues from 44 homozygous mutants compared with C57BL/6N control mice. Two allele types were evaluated: 15 targeted trap mutations (TRAP); and 29 deletion alleles (DEL), usually a deletion between the translational start and the 3' UTR. Both targeting strategies insert a bacterial beta-galactosidase reporter (LacZ) and a neomycin resistance selection cassette. Evaluating transcription of genes in +/- 500 kb of flanking DNA around the targeted gene, we found up-regulated genes more frequently around DEL compared with TRAP alleles, however the frequency of alleles with local down-regulated genes flanking DEL and TRAP targets was similar. Down-regulated genes around both DEL and TRAP targets were found at a higher frequency than expected from a genome-wide survey. However, only around DEL targets were up-regulated genes found with a significantly higher frequency compared with genome-wide sampling. Transcriptome analysis confirms targeting in 97% of DEL alleles, but in only 47% of TRAP alleles probably due to non-functional splice variants, and some splicing around the gene trap. Local effects on gene expression are likely due to a number of factors including compensatory regulation, loss or disruption of intragenic regulatory elements, the exogenous promoter in the neo selection cassette, removal of insulating DNA in the DEL mutants, and local silencing due to disruption of normal chromatin organization or presence of exogenous DNA. An understanding of local position effects is important for understanding and interpreting any phenotype attributed to targeted gene mutations, or to spontaneous indels

Co-benefits of global, domestic, and sectoral greenhouse gas mitigation for US air quality and human health in 2050

Policies to reduce greenhouse gas (GHG) emissions can bring ancillary benefits of improved air quality and reduced premature mortality, in addition to slowing climate change. Here we study the co-benefits of global and domestic GHG mitigation on US air quality and human health in 2050 at fine resolution using dynamical downscaling, and quantify for the first time the co-benefits from foreign GHG mitigation. Relative to a reference scenario, global GHG reductions in RCP4.5 avoid 16000 PM2.5-related all-cause deaths yr-1 (90% confidence interval, 11700-20300), and 8000 (3600-12400) O3-related respiratory deaths yr-1 in the US in 2050. Foreign GHG mitigation avoids 15% and 62% of PM2.5- and O3-related total avoided deaths, highlighting the importance of foreign GHG mitigation on US human health benefits. GHG mitigation in the US residential sector brings the largest co-benefits for PM2.5-related deaths (21% of total domestic co-benefits), and industry for O3 (17%). Monetized benefits, for avoided deaths from ozone, PM2.5, and heat stress from a related study, are $148 ($96-201) per ton CO2 at high valuation and $49 ($32-67) at low valuation, of which 36% are from foreign GHG reductions. These benefits likely exceed the marginal cost of GHG reductions in 2050. The US gains significantly greatermore » co-benefits when coordinating GHG reductions with foreign countries. Similarly, previous studies estimating co-benefits locally or regionally may greatly underestimate the full co-benefits of coordinated global actions.« les

Co-benefits of global and regional greenhouse gas mitigation for US air quality in 2050

Policies to mitigate greenhouse gas (GHG) emissions will not only slow climate change but can also have ancillary benefits of improved air quality. Here we examine the co-benefits of both global and regional GHG mitigation for US air quality in 2050 at fine resolution, using dynamical downscaling methods, building on a previous global co-benefits study (West et al., 2013). The co-benefits for US air quality are quantified via two mechanisms: through reductions in co-emitted air pollutants from the same sources and by slowing climate change and its influence on air quality, following West et al. (2013). Additionally, we separate the total co-benefits into contributions from domestic GHG mitigation vs. mitigation in foreign countries. We use the Weather Research and Forecasting (WRF) model to dynamically downscale future global climate to the regional scale and the Sparse Matrix Operator Kernel Emissions (SMOKE) program to directly process global anthropogenic emissions to the regional domain, and we provide dynamical boundary conditions from global simulations to the regional Community Multi-scale Air Quality (CMAQ) model. The total co-benefits of global GHG mitigation from the RCP4.5 scenario compared with its reference are estimated to be higher in the eastern US (ranging from 0.6 to 1.0 µg m−3) than the west (0–0.4 µg m−3) for fine particulate matter (PM2.5), with an average of 0.47 µg m−3 over the US; for O3, the total co-benefits are more uniform at 2–5 ppb, with a US average of 3.55 ppb. Comparing the two mechanisms of co-benefits, we find that reductions in co-emitted air pollutants have a much greater influence on both PM2.5 (96 % of the total co-benefits) and O3 (89 % of the total) than the second co-benefits mechanism via slowing climate change, consistent with West et al. (2013). GHG mitigation from foreign countries contributes more to the US O3 reduction (76 % of the total) than that from domestic GHG mitigation only (24 %), highlighting the importance of global methane reductions and the intercontinental transport of air pollutants. For PM2.5, the benefits of domestic GHG control are greater (74 % of total). Since foreign contributions to co-benefits can be substantial, with foreign O3 benefits much larger than those from domestic reductions, previous studies that focus on local or regional co-benefits may greatly underestimate the total co-benefits of global GHG reductions. We conclude that the US can gain significantly greater domestic air quality co-benefits by engaging with other nations to control GHGs.</html

Longitudinal Variations in Antibody Responses against SARS-CoV-2 Spike Epitopes upon Serial Vaccinations

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted healthcare, the workforce, and worldwide socioeconomics. Multi-dose mono- or bivalent mRNA vaccine regimens have shown high efficacy in protection against SARSCoV- 2 and its emerging variants with varying degrees of efficacy. Amino acid changes, primarily in the receptor-binding domain (RBD), result in selection for viral infectivity, disease severity, and immune evasion. Therefore, many studies have centered around neutralizing antibodies that target the RBD and their generation achieved through infection or vaccination. Here, we conducted a unique longitudinal study, analyzing the effects of a three-dose mRNA vaccine regimen exclusively using the monovalent BNT162b2 (Pfizer/BioNTech) vaccine, systematically administered to nine previously uninfected (naïve) individuals. We compare changes in humoral antibody responses across the entire SARS-CoV-2 spike glycoprotein (S) using a high-throughput phage display technique (VirScan). Our data demonstrate that two doses of vaccination alone can achieve the broadest and highest magnitudes of anti-S response. Moreover, we present evidence of novel highly boosted non-RBD epitopes that strongly correlate with neutralization and recapitulate independent findings. These vaccine-boosted epitopes could facilitate multi-valent vaccine development and drug discovery

Visual contrast sensitivity is associated with the presence of cerebral amyloid and tau deposition

Visual deficits are common in neurodegenerative diseases including Alzheimer’s disease. We sought to determine the association between visual contrast sensitivity and neuroimaging measures of Alzheimer’s disease-related pathophysiology, including cerebral amyloid and tau deposition and neurodegeneration. A total of 74 participants (7 Alzheimer’s disease, 16 mild cognitive impairment, 20 subjective cognitive decline, 31 cognitively normal older adults) underwent the frequency doubling technology 24-2 examination, a structural MRI scan and amyloid PET imaging for the assessment of visual contrast sensitivity. Of these participants, 46 participants (2 Alzheimer’s disease, 9 mild cognitive impairment, 12 subjective cognitive decline, 23 cognitively normal older adults) also underwent tau PET imaging with [18F]flortaucipir. The relationships between visual contrast sensitivity and cerebral amyloid and tau, as well as neurodegeneration, were assessed using partial Pearson correlations, covaried for age, sex and race and ethnicity. Voxel-wise associations were also evaluated for amyloid and tau. The ability of visual contrast sensitivity to predict amyloid and tau positivity were assessed using forward conditional logistic regression and receiver operating curve analysis. All analyses first were done in the full sample and then in the non-demented at-risk individuals (subjective cognitive decline and mild cognitive impairment) only. Significant associations between visual contrast sensitivity and regional amyloid and tau deposition were observed across the full sample and within subjective cognitive decline and mild cognitive impairment only. Voxel-wise analysis demonstrated strong associations of visual contrast sensitivity with amyloid and tau, primarily in temporal, parietal and occipital brain regions. Finally, visual contrast sensitivity accurately predicted amyloid and tau positivity. Alterations in visual contrast sensitivity were related to cerebral deposition of amyloid and tau, suggesting that this measure may be a good biomarker for detecting Alzheimer’s disease-related pathophysiology. Future studies in larger patient samples are needed, but these findings support the power of these measures of visual contrast sensitivity as a potential novel, inexpensive and easy-to-administer biomarker for Alzheimer’s disease-related pathology in older adults at risk for cognitive decline

Comparing the fate and transport of MS2 bacteriophage and sodium fluorescein in a karstic chalk aquifer

Groundwater flow and contaminant migration tracing is a vital method of identifying and characterising pollutant source-pathway-receptor linkages in karst aquifers. Bacteriophages are an attractive alternative tracer to non-reactive fluorescent dye tracers, as high titres (>10¹² pfu mL−¹) can be safely released into the aquifer, offering improved tracer detectability. However, the interpretation of bacteriophage tracer breakthrough curves is complicated as their fate and transport are impacted by aquifer physicochemical conditions. A comparative tracer migration experiment was conducted in a peri-urban catchment in southeast England to characterise the behaviour of MS2 bacteriophage relative to sodium fluorescein dye in a karstic chalk aquifer. Tracers were released into a stream sink and detected at two abstraction boreholes located 3 km and 10 km away. At both sites, the loss of MS2 phage greatly exceeded that of the solute tracer. In contrast, the qualitative shape of the dye and phage breakthrough curves were visually very similar, suggesting that the bacteriophage arriving at each site was governed by comparable transport parameters to the non-reactive dye tracer. The colloid filtration theory was applied to explain the apparent contradiction of comparable tracer breakthrough patterns despite massive phage losses in the subsurface. One-dimensional transport models were also fitted to each breakthrough curve to facilitate a quantitative comparison of the transport parameter values. The model results suggest that the bacteriophage migrates through the conduit system slightly faster than the fluorescent dye, but that the former is significantly less dispersed. These results suggest that whilst the bacteriophage tracer cannot be used to predict receptor concentrations from transport via karstic flow paths, it can provide estimates for groundwater flow and solute contaminant transit times. This study also provides insight into the attenuation and transport of pathogenic viruses in karstic chalk aquifers