A method for screening groundwater vulnerability from subsurface hydrocarbon extraction practices.

This paper describes a new screening method for assessing groundwater vulnerability to pollution from hydrocarbon exploitation in the subsurface. The method can be used for various hydrocarbon energy sources, including conventional oil and gas, shale gas and oil, coal bed methane and underground coal gasification. Intrinsic vulnerability of potential receptors is assessed at any particular location by identifying possible geological pathways for contaminant transport. This is followed by an assessment of specific vulnerability which takes into account the nature of the subsurface hydrocarbon activity and driving heads. A confidence rating is attached to each parameter in the assessment to provide an indication of the confidence in the screening. Risk categories and associated confidence ratings are designed to aid in environmental decision making, regulation and management, highlighting where additional information is required. The method is demonstrated for conventional gas and proposed shale gas operations in northern England but can be adapted for use in any geological or hydrogeological setting and for other subsurface activities.

A Nonlocal Model for Contact Attraction and Repulsion in Heterogeneous Cell Populations.

Instructing others to move is fundamental for many populations, whether animal or cellular. In many instances, these commands are transmitted by contact, such that an instruction is relayed directly (e.g. by touch) from signaller to receiver: for cells, this can occur via receptor-ligand mediated interactions at their membranes, potentially at a distance if a cell extends long filopodia. Given that commands ranging from attractive to repelling can be transmitted over variable distances and between cells of the same (homotypic) or different (heterotypic) type, these mechanisms can clearly have a significant impact on the organisation of a tissue. In this paper, we extend a system of nonlocal partial differential equations (integrodifferential equations) to provide a general modelling framework to explore these processes, performing linear stability and numerical analyses to reveal its capacity to trigger the self-organisation of tissues. We demonstrate the potential of the framework via two illustrative applications: the contact-mediated dispersal of neural crest populations and the self-organisation of pigmentation patterns in zebrafish.

The nitrate time bomb: a numerical way to investigate nitrate storage and lag time in the unsaturated zone.

Nitrate pollution in groundwater, which is mainly from agricultural activities, remains an international problem. It threatens the environment, economics and human health. There is a rising trend in nitrate concentrations in many UK groundwater bodies. Research has shown it can take decades for leached nitrate from the soil to discharge into groundwater and surface water due to the 'store' of nitrate and its potentially long travel time in the unsaturated and saturated zones. However, this time lag is rarely considered in current water nitrate management and policy development. The aim of this study was to develop a catchment-scale integrated numerical method to investigate the nitrate lag time in the groundwater system, and the Eden Valley, UK, was selected as a case study area. The method involves three models, namely the nitrate time bomb-a process-based model to simulate the nitrate transport in the unsaturated zone (USZ), GISGroundwater--a GISGroundwater flow model, and N-FM--a model to simulate the nitrate transport in the saturated zone. This study answers the scientific questions of when the nitrate currently in the groundwater was loaded into the unsaturated zones and eventually reached the water table; is the rising groundwater nitrate concentration in the study area caused by historic nitrate load; what caused the uneven distribution of groundwater nitrate concentration in the study area; and whether the historic peak nitrate loading has reached the water table in the area. The groundwater nitrate in the area was mainly from the 1980s to 2000s, whilst the groundwater nitrate in most of the source protection zones leached into the system during 1940s-1970s; the large and spatially variable thickness of the USZ is one of the major reasons for unevenly distributed groundwater nitrate concentrations in the study area; the peak nitrate loading around 1983 has affected most of the study area. For areas around the Bowscar, Beacon Edge, Low Plains, Nord Vue, Dale Springs, Gamblesby, Bankwood Springs, and Cliburn, the peak nitrate loading will arrive at the water table in the next 34 years; statistical analysis shows that 8.7 % of the Penrith Sandstone and 7.3 % of the St Bees Sandstone have not been affected by peak nitrate. This research can improve the scientific understanding of nitrate processes in the groundwater system and support the effective management of groundwater nitrate pollution for the study area. With a limited number of parameters, the method and models developed in this study are readily transferable to other areas.

How does cellular contact affect differentiation mediated pattern formation?

In this paper, we present a two-population continuous integro-differential model of cell differentiation, using a non-local term to describe the influence of the local environment on differentiation. We investigate three different versions of the model, with differentiation being cell autonomous, regulated via a community effect, or weakly dependent on the local cellular environment. We consider the spatial patterns that such different modes of differentiation produce, and investigate the formation of both stripes and spots by the model. We show that pattern formation only occurs when differentiation is regulated by a strong community effect. In this case, permanent spatial patterns only occur under a precise relationship between the parameters characterising cell dynamics, although transient patterns can persist for biologically relevant timescales when this condition is relaxed. In all cases, the long-lived patterns consist only of stripes, not spots.

Environmental policy. Counting the cost of deforestation.

To halt the dramatic alteration in our climate, there must be a reduction in the emission of greenhouse gases. As Bonnie and colleagues discuss in their Perspective, conservation of forests will increase carbon sequestration and decrease greenhouse gas emissions. In this issue, a cost-benefit analysis by Kremen et al. demonstrates the benefits of forest conservation on a local and global scale.

Global biodiversity scenarios for the year 2100.

Scenarios of changes in biodiversity for the year 2100 can now be developed based on scenarios of changes in atmospheric carbon dioxide, climate, vegetation, and land use and the known sensitivity of biodiversity to these changes. This study identified a ranking of the importance of drivers of change, a ranking of the biomes with respect to expected changes, and the major sources of uncertainties. For terrestrial ecosystems, land-use change probably will have the largest effect, followed by climate change, nitrogen deposition, biotic exchange, and elevated carbon dioxide concentration. For freshwater ecosystems, biotic exchange is much more important. Mediterranean climate and grassland ecosystems likely will experience the greatest proportional change in biodiversity because of the substantial influence of all drivers of biodiversity change. Northern temperate ecosystems are estimated to experience the least biodiversity change because major land-use change has already occurred. Plausible changes in biodiversity in other biomes depend on interactions among the causes of biodiversity change. These interactions represent one of the largest uncertainties in projections of future biodiversity change.

Combined impacts of future land-use and climate stressors on water resources and quality in groundwater and surface waterbodies of the upper Thames river basin, UK.

It is widely acknowledged that waterbodies are becoming increasingly affected by a wide range of drivers of change arising from human activity. To illustrate how this can be quantified a linked modelling approach was applied in the Thames river basin in southern UK. Changes to river flows, water temperature, river and reservoir quality were predicted under three contrasting future "storylines"; one an extension of present day rates of economic development, the others representing more extreme and less sustainable visions. Modelling revealed that lower baseflow conditions will arise under all storylines. For the less extreme storyline river water quality is likely to deteriorate but reservoir quality will improve slightly. The two more extreme futures could not be supported by current management strategies to meet water demand. To satisfy these scenarios, transfer of river water from outside the Thames river basin would be necessary. Consequently, some improvement over present day water quality in the river may be seen, and for most indicators conditions would be better than in the less extreme storyline. However, because phosphorus concentrations will rise, the invoked changes in water demand management would not be of a form suitable to prevent a marked deterioration in reservoir water quality.

Impacts of climate change on the fate and behaviour of pesticides in surface and groundwater--A UK perspective.

Over the last two decades significant effort has been dedicated to understanding the fate and transport of pesticides in surface water and groundwater and to use this understanding in the development of environmental policy and regulation. However, there have been few studies that have investigated the relationships between pesticides and climate change, and where this work has been undertaken it has principally been in relation to the impacts of climate change on agricultural production rather than in the context of environmental protection. This study addresses that gap by reviewing how climate change may impact the fate and transport of pesticides in surface and groundwaters as a pre-cursor to quantitative studies. In order to structure the review, we have adopted a source-pathway-receptor approach where climate sensitivities of pesticide source terms, environmental pathways and receptors are reviewed. The main climate drivers for changing pesticide fate and behaviour are thought to be changes in rainfall seasonality and intensity and increased temperatures, but the effect of climate change on pesticide fate and transport is likely to be very variable and difficult to predict. In the long-term, indirect impacts, such as land-use change driven by changes in climate, may have a more significant effect on pesticides in surface and groundwaters than the direct impacts of climate change on pesticide fate and transport. The review focuses on climate change scenarios and case studies from the UK; however, the general conclusions can be applied more widely.

The effects of a low extracellular concentration of potassium on the activity and numbers of Na+/K+ pumps in an EB-virus transformed human lymphocyte cell line.

The BM1A EB-virus transformed human lymphocyte cell line contains approximately 950,000 Na+/K(+)-ATPase sites per cell. The turnover number of each site is approx. 2240 molecules of rubidium per min. When cells are exposed to a low extracellular concentration of potassium the intracellular concentration of sodium rises, and the cells respond in the short term by increasing the Vmax of 86Rb+ uptake. In the longer term the cells respond by increasing both the Vmax of 86Rb+ uptake and the Bmax of [3H]ouabain binding. The suggestion that increases in the intracellular concentration of sodium is responsible for these changes is supported by the finding that monensin, which increases intracellular sodium without affecting intracellular potassium, is capable of inducing both the short- and long-term changes associated with a low external concentration of potassium.

Analysis of age, stature, body mass, BMI and quality of elite soccer players from 4 European Leagues.

AIM: The aim was to identify which league (English Premier League, Spanish La Liga Division, Italian Serie A and German Bundesliga) contained the highest quality players and whether differences in age, stature, body mass and BMI existed between the different positions in different leagues. METHODS: Data were collected concerning 2,085 professional soccer players playing in these 4 leagues during the 2001-2002 season. Player quality was determined by the leagues' number of international players and their nations' FIFA World Ranking (FWR). RESULTS: The La Liga Division contained the highest quality players (mean FWR) (11.5+/-13.8), followed by the Serie A (13.3+/-21.3), the Premier League (30.6+/-27.3) and the Bundesliga (30.7+/-27.1), respectively. Also, differences were found between the age, stature, body mass and BMI of players in different positions and in the different leagues. Age had a significant influence on position with goalkeepers (years) (27.4+/-5.3) being older than midfielders (26.2+/-4.3) and forwards (25.8+/-4.2) and defenders (26.8+/-4.3) being older than forwards. Players from the Bundesliga had the greatest stature (m) (1.83+/-0.06), body mass (kg) (77.5+/-6.4) and BMI (kg x m(-2)) (23.2+/-1.1) of the 4 leagues. In reflection, La Liga's players had the shortest stature (1.80+/-0.06) and the Serie A players had the least body mass (74.3+/-5.4) and BMI (22.8+/-1.1). CONCLUSIONS: The differences discovered suggest either differences in playing style and physical demands of the different leagues, different physical conditioning methods or, alternatively, that there are desirable characteristics of players with teams in all 4 leagues seeking such players.

Inducing pluripotency in vitro: recent advances and highlights in induced pluripotent stem cells generation and pluripotency reprogramming.

Induced pluripotent stem cells (iPSCs) are considered patient-specific counterparts of embryonic stem cells as they originate from somatic cells after forced expression of pluripotency reprogramming factors Oct4, Sox2, Klf4 and c-Myc. iPSCs offer unprecedented opportunity for personalized cell therapies in regenerative medicine. In recent years, iPSC technology has undergone substantial improvement to overcome slow and inefficient reprogramming protocols, and to ensure clinical-grade iPSCs and their functional derivatives. Recent developments in iPSC technology include better reprogramming methods employing novel delivery systems such as non-integrating viral and non-viral vectors, and characterization of alternative reprogramming factors. Concurrently, small chemical molecules (inhibitors of specific signalling or epigenetic regulators) have become crucial to iPSC reprogramming; they have the ability to replace putative reprogramming factors and boost reprogramming processes. Moreover, common dietary supplements, such as vitamin C and antioxidants, when introduced into reprogramming media, have been found to improve genomic and epigenomic profiles of iPSCs. In this article, we review the most recent advances in the iPSC field and potent application of iPSCs, in terms of cell therapy and tissue engineering.

Monoclonal antibodies against defined regions of the muscular dystrophy protein, dystrophin.

Nineteen monoclonal antibodies which bind to native dystrophin in the plasma membrane of frozen muscle sections were obtained using a recombinant fusion protein as immunogen. On Western blots of normal mouse muscle extracts, the antibodies bind specifically to a 400,000 Mr protein which is absent from dystrophic mouse (mdx) muscle. At least four distinct epitopes have been identified by cleavage mapping methods. Although the fusion protein contained 25% of the human dystrophin sequence (Cys816-Asp1747; Mr 108,000), most of the monoclonal antibodies (15 out of 19) recognize a single fragment of Mr 27,500.

The influence of L-triiodothyronine (T3) on the effects of repeated administration of desipramine or electroconvulsive shock on alpha 2- and beta-adrenoceptor function in the brain of the rat: implications for the potentiation of antidepressant therapy by T3.

Repeated, daily administration of either an electroconvulsive shock (ECS; 110 V, 1 sec) or desipramine (DMI; 5 mg/kg X 2) to rats caused a progressive decrease in the function of presynaptic alpha 2-adrenoceptors, assessed by the hypoactivity (sedation) response to clonidine (0.2 mg/kg). This attenuation required approximately 7 days' administration of either treatment for maximum effect. A single injection of triiodothyronine (T3; 100 micrograms/kg) on day 1 of the treatment markedly accelerated the decreased responses to clonidine induced by DMI or electroconvulsive shock, but did not alter the maximum attenuation. By itself T3 did not affect the hypoactivity responses. alpha 2-Adrenoceptors, measured by the binding of [3H]idazoxan in the cortex, which are believed to be predominantly postsynaptic, were decreased by 14 days of DMI or electroconvulsive shock for 10 days, but not 2 days of either treatment. Triiodothyronine did not influence the decreased number of alpha 2-adrenoceptors induced by DMI or electroconvulsive shock but may have delayed the onset produced by DMI. Binding to beta-adrenoceptors in the cortex was measured using [3H]dihydroalprenolol. This was significantly decreased by 14 days administration of DMI, but not significantly by electroconvulsive shock for 10. Down-regulation of beta-adrenoceptors, induced by DMI was rapid, being observed after 1 day of treatment. Injection of T3 did not influence the final decreases produced by DMI or electroconvulsive shocks but moderately delayed their onset. Triiodothyronine alone caused a 25% reduction in cortical beta-adrenoceptors 24 hr after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of injection of oestradiol to female rats on changes in alpha 2- and beta-adrenoceptor function induced by repeated administration of desipramine or electroconvulsive shock.

Repeated daily administration to female rats of either an electroconvulsive shock (110 V, 1 sec) or desipramine (DMI; 5 mg/kg x 2) caused a progressive decrease in presynaptic alpha 2-adrenoceptor function assessed by the hypoactivity (sedation) response to clonidine (0.5 mg/kg). This reduction was maximal after approximately seven electroshocks or 8-12 days of injection of DMI. Daily administration of oestradiol (100 micrograms s.c.), starting one day prior to the commencement of administration of DMI or treatment with electroshock, markedly accelerated the onset of decreased hypoactivity responses to clonidine, but did not alter the maximum reduction induced by repeated injection of DMI or administration of electroshock. Injection of oestradiol alone had no effect on the responses to clonidine. Administration of DMI for 14 days decreased the number of both alpha 2- and beta-adrenoceptors in the cortex. Cortical beta-, but not alpha 2-adrenoceptors, were also decreased after 4 days of injection of DMI. Two and ten electroshocks moderately increased and decreased cortical alpha 2-adrenoceptors, respectively. beta-Adrenoceptors were also decreased by ten electroshocks, but two were without effect. Simultaneous administration of oestradiol had little influence on the changes in the binding of alpha 2- or beta-adrenoceptors induced by repeated administration of DMI or treatment with electroshock. Oestradiol increased the numbers of cortical alpha 2- and beta-adrenoceptors 3 and 15 days after injection, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Reversal of the effects of a low extracellular potassium concentration on the number and activity of Na+/K+ pumps in an Epstein-Barr virus-transformed human lymphocyte cell line.

A reduction in the extracellular concentration of potassium to 0.5 mM (low K) in Epstein-Barr (EB) virus-transformed lymphocytes caused changes in the number and activity of Na+/K+ pumps in the cell membrane, with increases in the Bmax and apparent Kd of ouabain binding, and concomitant increases in the Vmax and apparent Km of potassium (rubidium) influx. However, recovery from the effects of low K occurred more quickly than the original up-regulation. Furthermore, there were differences in the time-courses of the separate rates of recovery of the Bmax and Kd of ouabain binding after the cells were returned to normal K, the rate of recovery of the Kd being quicker than that of the Bmax, which was biphasic, with slow and fast rates of recovery. Inhibition of protein synthesis by emetine caused an increase in the rate of recovery of the Bmax of ouabain binding, but no effect on the Kd, suggesting that the slow phase of recovery of the Bmax is attributable to the synthesis and insertion of new protein, while the rapid phase of recovery is independent of protein synthesis and may represent internalization. The results suggested that during up-regulation of pump number in response to low K about 40% of the newly inserted Na+/K+ pumps are normal and the rest are abnormal. The half-time of removal of the abnormal pumps from the cell membrane during recovery from low K stress was 2.8 hr and the half-time of internalization of the normal pumps was 4.3 hr.

Characterization of deletions in the dystrophin gene giving mild phenotypes.

We have characterized deletions of the dystrophin gene in patients suffering from relatively mild muscular dystrophy. Our data show that most of the Becker muscular dystrophy (BMD) patients have intragenic deletions which leave the protein reading frame in phase. Remarkably, large deletions of the region corresponding to the central triple helical repeats in the protein can result in an exceptionally mild phenotype. Three brothers suffering from BMD, glycerol kinase deficiency, and adrenal hypoplasia possess a deletion at the 3' end of the gene. They also display developmental delay. Thus the 3' processing of the gene must be necessary for the correct function of the dystrophin molecule.

Therapeutic potential of fish oil in the treatment of ulcerative colitis.

In a pilot study six patients with active ulcerative colitis and six healthy controls were given fish oil (MaxEPA) containing 3-4 g of eicosapentaenoic acid daily for a period of 12 weeks. There was a significant improvement in the patients' symptoms and histological appearance of the rectal mucosa by the end of the treatment period. There was significant fall in neutrophil chemiluminescence during treatment in patients, whereas no change was observed in the control group. Neutrophil leukotriene B4 levels fell significantly during treatment. Serum from patients receiving fish oil was significantly less chemotactic for neutrophils compared with control serum. Eicosapentaenoic acid inhibited neutrophil chemotaxis and chemiluminescence in vitro. The omega-3 fatty acids, which occur naturally in fish oils, may exert a beneficial effect by decreasing the production of inflammatory mediators.

Driving simulation study: bilateral array multifocal versus bilateral AMO monofocal intraocular lenses.

PURPOSE: To determine whether differences exist in the driving performance of patients with bilateral Array multifocal intraocular lenses (IOLs) and those with bilateral AMO monofocal IOLs under low-contrast environmental conditions. SETTING: The Iowa Driving Simulator at the Center for Computer Aided Design, the University of Iowa, Iowa City, Iowa, USA. METHODS: This prospective study was a test-operator-masked, parallel-group comparison of the driving performance of 33 bilateral multifocal IOL patients and 33 bilateral monofocal IOL patients from the U.S. Array Multifocal study. Driving performance was evaluated under 3 poor visibility conditions (clear weather at night, clear weather at night in the presence of a glare source, and fog). Measures of performance included recognition rates and distances for signs, as well as detection rates, distances, and avoidance behaviors for hazards. Contrast acuity and sensitivity were also measured to evaluate possible correlations with driving performance. RESULTS: No statistically significant differences between the IOL groups were found in 26 of 30 comparisons (86.7%). The monofocal group performed better than the multifocal group in comparisons in which there were statistically significant differences: the percentage of correctly recognized warning signs at night in clear weather (P = .028), sign recognition distances for guide (P = .030) and warning (P = .036) signs in fog, and the detection distance for 1 of 4 hazards (suitcase; P = .026). Correlation coefficients between driving performance and low-contrast acuity and sensitivity were statistically significant; however, they were low and not likely predictive of driving performance. CONCLUSION: Differences between patients with bilateral multifocal IOLs and those with bilateral monofocal IOLs were detected; however, the results indicate no consistent difference in driving performance and safety.

Inertial characteristics of adolescent male body segments.

In response to the presently limited information on body segment inertial characteristics of children and adolescents this investigation estimated the mass, centre of mass and principal moments of inertia of adolescent male body segments. Significant prediction equations based on anthropometric measurements were then sought. Thirteen subjects were measured at 6-monthly intervals for 2.5 yr to provide inertial characteristics for the leg, thigh, lower trunk and upper trunk segments. These characteristics were derived using an elliptical zone modelling technique. Following a correlation analysis, significant prediction equations of segment inertial parameters were derived from five, or fewer, anthropometric measurements. For all cases, more than 84% of the variance in the dependent variable was accounted for with a maximum R2 value of 94% being recorded for the prediction of thigh segment mass. The use of these prediction equations offered accurate and convenient estimates of body segment inertial characteristics within the limitations applicable to all modelling approaches. In contrast to recent studies, these equations accommodated the current morphological status of the subject.

Sediment filled fractures in the Permo-Triassic sandstones of the Cheshire basin: observations and implications for pollutant transport.

Fracture mapping in a tunnel system and at nearby outcrop on the Runcorn Penninsula, UK, suggests the need for a review of the potential pathways for pollutant transport in Permo-Triassic sandstone aquifers. Sediment infilling is pervasive in the largest sub-vertical multi-layer fractures in the study area, both at the surface and to a depth of about 40 m below ground level. Sediment infill is inferred to have formed in situ. The conventional models of pollutant transport in fracture networks assume that they comprise open fractures, with pollutant mobility depending on fracture connectivity (a function of density, length, orientation and intersection) and aperture. The presence of extensive sediment fills in fractures will materially change their permeability, thereby reducing pollutant flux, and be of significance in the assessment of risks arising from chemical spillages. There has been little or no substantive evidence for such fills in Permo-Triassic sandstones in the UK, apart from observations at outcrop and anecdotes of sand being pumped from boreholes. Here, we report surface and rare, but complementary, subsurface observations of extensive fills in the Cheshire basin, and argue that they will only act as preferential pathways where they crosscut low-permeability horizons such as mudstones.