Ionic liquids via reaction of the zwitterionic 1,3-dimethylimidazolium-2-carboxylate with protic acids. Overcoming synthetic limitations and establishing new halide free protocols for the formation of ILs

The previously reported preparation of 1,3-dimethylimidazolium salts by the reaction of 1,3-dialkylimidazolium-2-carboxylate zwitterions with protic acids has been reinvestigated in detail, leading to the identification of two competing reactions: isomerisation and decarboxylation. The ability to control both pathways allows this methodology to be used as an effective, green, waste-free approach to readily prepare a wide range of ionic liquids in high yields. Additionally, this reaction protocol opens new possibilities in the formation of other imidazolium salts, whose syntheses were previously either very expensive (due to ion exchange protocols involving metals like Ag) or difficult to achieve (due to multiple extractions and large quantities of hard to remove inorganic by-products).

Monitoring microbial sulfate reduction in porous media using multi-purpose electrodes

There is growing interest in the application of electrode-based measurements for monitoring microbial processes in the Earth using biogeophysical methods. In this study, reactive electrode measurements were combined to electrical geophysical measurements during microbial sulfate reduction occurring in a column of silica beads saturated with natural river water. Electrodic potential (EP), self potential (SP) and complex conductivity signals were recorded using a dual electrode design (Ag/AgCl metal as sensing/EP electrode, Ag/AgCl metal in KCl gel as reference/SP electrode). Open-circuit potentials, representing the tendency for electrochemical reactions to occur on the electrode surfaces, were recorded between sensing/EP electrode and reference/SP electrode and showed significant spatiotemporal variability associated with microbial activity. The dual electrode design isolates the microbial driven sulfide reactions to the sensing electrode and permits removal of any SP signal from the EP measurement. Based on the known sensitivity of a Ag electrode to dissolved sulfide, we interpret EP signals exceeding 550 mV recorded in this experiment in terms of bisulfide (HS-) concentration near multiple sensing electrodes. Complex conductivity measurements capture an imaginary conductivity (s?) signal interpreted as the response of microbial growth and biomass formation in the column. Our results suggest that the implementation of multipurpose electrodes, combining reactive measurements with electrical geophysical measurements, could improve efforts to monitor microbial processes in the Earth using electrodes.

Stratification and Monitoring of Juvenile Idiopathic Arthritis Patients by Synovial Proteome Analysis

Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic, childhood onset, autoimmune diseases with variable clinical outcomes. We investigated whether profiling of the synovial fluid (SF) proteome by a fluorescent dye based, two-dimensional gel (DIGE) approach could distinguish patients in whom inflammation extends to affect a large number of joints, early in the disease process. SF samples from 22 JIA patients were analyzed: 10 with oligoarticular arthritis, 5 extended oligoarticular and 7 polyarticular disease. SF samples were labeled with Cy dyes and separated by two-dimensional electrophoresis. Multivariate analyses were used to isolate a panel of proteins which distinguish patient subgroups. Proteins were identified using MALDI-TOF mass spectrometry with expression further verified by Western immunoblotting and immunohistochemistry. Hierarchical clustering based on the expression levels of a set of 40 proteins segregated the extended oligoarticular from the oligoarticular patients (p <0.05). Expression patterns of the isolated protein panel have also been observed over time, as disease spreads to multiple joints. The data indicates that synovial fluid proteome profiles could be used to stratify patients based on risk of disease extension. These protein profiles may also assist in monitoring therapeutic responses over time and help predict joint damage. © 2009 American Chemical Society.

Comparative tracing experiments to investigate epikarst structural and compositional heterogeneity

Comparative tracer testing may be used to evaluate the vulnerability of groundwater to specific contaminants by comparing reactive tracer response to that of a simultaneously injected non-reactive “conservative” substance. Conversely, knowledge of tracer reaction with specific materials permits information about subsurface heterogeneity to be inferred. A series of tests completed in the vadose zone overlying a limestone aquifer employed a cocktail of particles along with reactive and non-reactive solute tracers to investigate transport rates between the ground surface and monitoring points approximately 10 m below ground. Short pulse tests revealed both solutes and particulate contaminants could travel at rates of over 10 m/h. Comparison of particle (microorganisms) and non-reactive solute tracer breakthrough revealed that particle tracers experience pore exclusion resulting in higher peak relative concentrations which arrive earlier than those of the solute. Prolonged tracer injection during subsequent experiments confirmed the response observed and illustrated that over 40 % of flow paths between injection and monitoring points were inaccessible to particles, but could allow solutes to pass through them. Similarly, the difference in response between various reactive tracers demonstrated tracers reached monitoring points via multiple flow paths and suggests geochemical heterogeneity plays an important role in influencing tracer behaviour. The results of this investigation highlight the complexity of water flow through the epikarst and the vulnerability of groundwater in karst aquifers to contamination when soil cover is thin to absent.

Simple method for the rapid simultaneous screening of photocatalytic activity over multiple positions of self-cleaning films

An intelligent ink, previously shown to be capable of rapidly assessing photocatalytic activity, was simply applied via a felt-pen onto a commercially available piece of Activ (TM) self-cleaning glass. The ink, comprising of redox dye resazurin and the sacrificial electron donor glycerol within an aqueous hydroxy ethyl cellulose (HEC) polymer media, was photocatalytically degraded in a two-step process. The key initial stage was the photo-reductive conversion of resazurin to resorufin, whereby a colour change from blue to pink occurred. The latter stage was the subsequent photo-reduction of the resorufin, where a slower change from pink to colourless was seen. Red and green components of red-green-blue colour extracted from flat-bed scanner digital images of resazurin ink coated photocatalytic films at intervals during the photocatalysis reaction were inversely proportional to the changes seen via UV-visible absorption spectroscopy and indicative of reaction kinetics. A 3 x 3 grid of intelligent ink was drawn onto a piece of Activ (TM) and a glass blank. The photocatalysis reaction was monitored solely by flat-bed digital scanning. Red-green-blue values of respective positions on the grid were extracted using a custom-built program entitled RGB Extractor (c). The program was capable of extracting a number of 5 x 5 pixel averages of red-green-blue components simultaneously. Allocation of merely three coordinates allowed for the automatic generation of a grid, with scroll-bars controlling the number of positions to be extracted on the grid formed. No significant change in red and green components for any position on the glass blank was observed; however, the Activ (TM) film displayed a homogenous photo-reduction of the dye, reaching maxima in red and minima in green components in 23 +/- 3 and 14 +/- 2 min, respectively. A compositionally graded N-doped titania film synthesised in house via a combinatorial APCVD reaction was also photocatalytically tested by this method where 247 positions on a 13 x 19 grid were simultaneously analysed. The dramatic variation in photocatalysis observed was rapidly quantified for all positions (2-3 hours) allowing for correlations to be made between thicknesses and N : Ti% compositions attained from Swanepoel and WDX analysis, respectively. N incorporation within this system was found to be detrimental to film activity for the photocatalysis reaction of intelligent ink under 365 nm light.

Interlaboratory comparison of real-time polymerase chain reaction methods to detect Coxiella burnetii, the causative agent of Q fever

The bacterium Coxiella burnetii, which has a wide host range, causes Q fever. Infection with C burnetii can cause abortions, stillbirth, and the delivery of weak offspring in ruminants. Coxiella burnetii infection is zoonotic, and in human beings it can cause chronic, potentially fatal disease. Real-time polymerase chain reaction (PCR) is increasingly being used to detect the organism and to aid in diagnosis both in human and animal cases. Many different real-time PCR methods, which target different genes, have been described. To assess the comparability of the C. burnetii real-time PCR assays in use in different European laboratories, a panel of nucleic acid extracts was dispatched to 7 separate testing centers. The testing centers included laboratories from both human and animal health agencies. Each laboratory tested the samples using their in-house real-time PCR methods. The results of this comparison show that the most common target gene for real-time PCR assays is the IS1111 repeat element that is present in multiple copies in the C. burnetii genome. Many laboratories also use additional real-time PCR tests that target single-copy genes. The results of the current study demonstrate that the assays in use in the different laboratories are comparable, with general agreement of results for the panel of samples.

Assessment of cell-mediated immunity in a British population using multiple skin test antigens

An in vivo method of assessing the competence of the cell-mediated immune system (Multitest CMI) was used in 200 healthy volunteers (age range 17-88 years). The profile of reactivity to seven individual antigens was determined. A positive reaction was obtained in 96.5% of the subjects who reacted positively to at least one antigen with 78% reacting to two or more antigens. The number of positive responses and the degree of reactivity was significantly reduced in elderly subjects and in females aged 17-65 years. The Multitest CMI system provides a rapid and convenient method of assessing cell-mediated immunity (CMI) in vivo and could have a wide range of applications in the investigation of immunological, infective and neoplastic conditions.

Metal Oxide Nanoparticle Mediated Enhanced Raman Scattering and Its Use in Direct Monitoring of Interfacial Chemical Reactions

Metal oxide nanoparticles (MONPs) have widespread usage across many disciplines, but monitoring molecular processes at their surfaces in situ has not been possible. Here we demonstrate that MONPs give highly enhanced (X10(4)) Raman scattering signals from molecules at the interface permitting direct monitoring of their reactions, when placed on top of flat metallic surfaces. Experiments with different metal oxide materials and molecules indicate that the enhancement is generic and operates at the single nanoparticle level. Simulations confirm that the amplification is principally electromagnetic and is a result of optical modulation of the underlying plasmonic metallic surface by MONPs, which act as scattering antennae and couple light into the confined region sandwiched by the underlying surface. Because of additional functionalities of metal oxides as magnetic, photoelectrochemical and catalytic materials, enhanced Raman scattering mediated by MONPs opens up significant opportunities in fundamental science, allowing direct tracking and understanding of application-specific transformations at such interfaces. We show a first example by monitoring the MONP-assisted photocatalytic decomposition reaction of an organic dye by individual nanoparticles.

Monitoring daily MLC positional errors using trajectory log files and EPID measurements for IMRT and VMAT deliveries

This work investigated the differences between multileaf collimator (MLC) positioning accuracy determined using either log files or electronic portal imaging devices (EPID) and then assessed the possibility of reducing patient specific quality control (QC) via phantom-less methodologies. In-house software was developed, and validated, to track MLC positional accuracy with the rotational and static gantry picket fence tests using an integrated electronic portal image. This software was used to monitor MLC daily performance over a 1 year period for two Varian TrueBeam linear accelerators, with the results directly compared with MLC positions determined using leaf trajectory log files. This software was validated by introducing known shifts and collimator errors. Skewness of the MLCs was found to be 0.03 ± 0.06° (mean ±1 standard deviation (SD)) and was dependent on whether the collimator was rotated manually or automatically. Trajectory log files, analysed using in-house software, showed average MLC positioning errors with a magnitude of 0.004 ± 0.003 mm (rotational) and 0.004 ± 0.011 mm (static) across two TrueBeam units over 1 year (mean ±1 SD). These ranges, as indicated by the SD, were lower than the related average MLC positioning errors of 0.000 ± 0.025 mm (rotational) and 0.000 ± 0.039 mm (static) that were obtained using the in-house EPID based software. The range of EPID measured MLC positional errors was larger due to the inherent uncertainties of the procedure. Over the duration of the study, multiple MLC positional errors were detected using the EPID based software but these same errors were not detected using the trajectory log files. This work shows the importance of increasing linac specific QC when phantom-less methodologies, such as the use of log files, are used to reduce patient specific QC. Tolerances of 0.25 mm have been created for the MLC positional errors using the EPID-based automated picket fence test. The software allows diagnosis of any specific leaf that needs repair and gives an indication as to the course of action that is required.

Minimal residual disease detection in childhood acute lymphoblastic leukaemia patients at multiple time-points reveals high levels of concordance between molecular and immunophenotypic approaches

In this single centre study of childhood acute lymphoblastic leukaemia (ALL) patients treated on the Medical Research Council UKALL 97/99 protocols, it was determined that minimal residual disease (MRD) detected by real time quantitative polymerase chain reaction (RQ-PCR) and 3-colour flow cytometry (FC) displayed high levels of qualitative concordance when evaluated at multiple time-points during treatment (93.38%), and a combined use of both approaches allowed a multi time-point evaluation of MRD kinetics for 90% (53/59) of the initial cohort. At diagnosis, MRD markers with sensitivity of at least 0.01% were identified by RQ-PCR detection of fusion gene transcripts, IGH/TRG rearrangements, and FC. Using a combined RQ-PCR and FC approach, the evaluation of 367 follow-up BM samples revealed that the detection of MRD >1% at Day 15 (P = 0.04), >0.01% at the end of induction (P = 0.02), >0.01% at the end of consolidation (P = 0.01), >0.01% prior to the first delayed intensification (P = 0.01), and >0.1% prior to the second delayed intensification and continued maintenance (P = 0.001) were all associated with relapse and, based on early time-points (end of induction and consolidation) a significant log-rank trend (P = 0.0091) was noted between survival curves for patients stratified into high, intermediate and low-risk MRD groups.

Wilms' tumor gene 1 (WT1) expression in childhood acute lymphoblastic leukemia:a wide range of WT1 expression levels, its impact on prognosis and minimal residual disease monitoring

Wilms' tumor gene 1 (WT1) is overexpressed in the majority (70-90%) of acute leukemias and has been identified as an independent adverse prognostic factor, a convenient minimal residual disease (MRD) marker and potential therapeutic target in acute leukemia. We examined WT1 expression patterns in childhood acute lymphoblastic leukemia (ALL), where its clinical implication remains unclear. Using a real-time quantitative PCR designed according to Europe Against Cancer Program recommendations, we evaluated WT1 expression in 125 consecutively enrolled patients with childhood ALL (106 BCP-ALL, 19 T-ALL) and compared it with physiologic WT1 expression in normal and regenerating bone marrow (BM). In childhood B-cell precursor (BCP)-ALL, we detected a wide range of WT1 levels (5 logs) with a median WT1 expression close to that of normal BM. WT1 expression in childhood T-ALL was significantly higher than in BCP-ALL (P<0.001). Patients with MLL-AF4 translocation showed high WT1 overexpression (P<0.01) compared to patients with other or no chromosomal aberrations. Older children (> or =10 years) expressed higher WT1 levels than children under 10 years of age (P<0.001), while there was no difference in WT1 expression in patients with peripheral blood leukocyte count (WBC) > or =50 x 10(9)/l and lower. Analysis of relapsed cases (14/125) indicated that an abnormal increase or decrease in WT1 expression was associated with a significantly increased risk of relapse (P=0.0006), and this prognostic impact of WT1 was independent of other main risk factors (P=0.0012). In summary, our study suggests that WT1 expression in childhood ALL is very variable and much lower than in AML or adult ALL. WT1, thus, will not be a useful marker for MRD detection in childhood ALL, however, it does represent a potential independent risk factor in childhood ALL. Interestingly, a proportion of childhood ALL patients express WT1 at levels below the normal physiological BM WT1 expression, and this reduced WT1 expression appears to be associated with a higher risk of relapse.

Using geotechnical and LIDAR spatial monitoring to determine key environmental slope instability thresholds of a Jurassic coastal landslide: Straidkilly Point, Northern Ireland, UK.

The Antrim Coast Road stretching from the seaport of Larne in the East of Northern Ireland to the famous Giant’s Causeway in the North has a well-deserved reputation for being one of the most spectacular roads in Europe (Day, 2006). At various locations along the route, fluid interactions between the problematic geology, Jurassic Lias Clay and Triassic Mudstone overlain by Cretaceous Limestone and Tertiary Basalt, and environmental variables result in frequent instances of slope instability within the vadose zone. During such instances of instability, debris flows and composite mudflows encroach on the carriageway posing a hazard to road users. This paper examines the site investigative, geotechnical and spatial analysis techniques currently being implemented to monitor slope stability for one site at Straidkilly Point, Glenarm, Northern Ireland. An in-depth understanding of the geology was obtained via boreholes, resistivity surveys and laboratory testing. Environmental variables recorded by an on-site weather station were correlated with measured pore water pressure and soil moisture infiltration dynamic data.
Terrestrial LiDAR (TLS) was applied to the slope for the monitoring of failures, with surveys carried out on a bi-monthly basis. TLS monitoring allowed for the generation of Digital Elevation Models (DEMs) of difference, highlighting areas of recent movement, erosion and deposition. Morphology parameters were generated from the DEMs and include slope, curvature and multiple measures of roughness. Changes in the structure of the slope coupled with morphological parameters are characterised and linked to progressive failures from the temporal monitoring. In addition to TLS monitoring, Aerial LiDARi datasets were used for the spatio-morphological characterisation of the slope on a macro scale. Results from the geotechnical and environmental monitoring were compared with spatial data obtained through Terrestrial and Airborne LiDAR, providing a multi-faceted approach to slope stability characterization, which facilitates more informed management of geotechnical risk by the Northern Ireland Roads Service.

Geotechnical monitoring using a combination of LIDAR, real-time dGPS, and electrical tomography to assess geotechnical risk of a coastal landslide.

The Antrim Coast Road stretching from the seaport of Larne in the East of Northern Ireland has a well-deserved reputation for being one of the most spectacular roads in Europe (Day, 2006). However the problematic geology; Jurassic Lias Clay and Triassic Mudstone overlain by Cretaceous Limestone and Tertiary Basalt, and environmental variables result in frequent instances of slope instability manifested in both shallow debris flows and occasional massive rotational movements, creating a geotechnical risk to this highway. This paper describes how a variety of techniques are being used to both assess instability and monitor movement of these active slopes near one site at Straidkilly Point, Glenarm. An in-depth understanding of the geology was obtained via boreholes, resistivity surveys and laboratory testing. Environmental variables recorded by an on-site weather station were correlated with measured pore water pressure and soil moisture infiltration data. Terrestrial LiDAR (TLS), with surveys carried out on a bi-monthly basis allowed for the generation of Digital Elevation Models (DEMs) of difference, highlighting areas of recent movement, accumulation and depletion. Morphology parameters were generated from the DEMs and include slope, curvature and multiple measures of roughness. Changes in the structure of the slope coupled with morphological parameters were characterised and linked to progressive failures from the temporal monitoring. In addition to TLS monitoring, Aerial LiDAR datasets were used for the spatio-morphological characterisation of the slope on a macro scale. A Differential Global Positioning System (dGPS) was also deployed on site to provide a real-time warning system for gross movements, which were also correlated with environmental conditions. Frequent electrical resistivity tomography (ERT) surveys were also implemented to provide a better understanding of long-term changes in soil moisture and help to define the complex geology. The paper describes how the data obtained via a diverse range of methods has been combined to facilitate a more informed management regime of geotechnical risk by the Northern Ireland Roads Service.

CSI 2264: Simultaneous Optical and Infrared Light Curves of Young Disk-bearing Stars in NGC 2264 with CoRoT and Spitzer—Evidence for Multiple Origins of Variability

We present the Coordinated Synoptic Investigation of NGC 2264, a continuous 30 day multi-wavelength photometric monitoring campaign on more than 1000 young cluster members using 16 telescopes. The unprecedented combination of multi-wavelength, high-precision, high-cadence, and long-duration data opens a new window into the time domain behavior of young stellar objects. Here we provide an overview of the observations, focusing on results from Spitzer and CoRoT. The highlight of this work is detailed analysis of 162 classical T Tauri stars for which we can probe optical and mid-infrared flux variations to 1% amplitudes and sub-hour timescales. We present a morphological variability census and then use metrics of periodicity, stochasticity, and symmetry to statistically separate the light curves into seven distinct classes, which we suggest represent different physical processes and geometric effects. We provide distributions of the characteristic timescales and amplitudes and assess the fractional representation within each class. The largest category (>20%) are optical "dippers" with discrete fading events lasting ~1-5 days. The degree of correlation between the optical and infrared light curves is positive but weak; notably, the independently assigned optical and infrared morphology classes tend to be different for the same object. Assessment of flux variation behavior with respect to (circum)stellar properties reveals correlations of variability parameters with Hα emission and with effective temperature. Overall, our results point to multiple origins of young star variability, including circumstellar obscuration events, hot spots on the star and/or disk, accretion bursts, and rapid structural changes in the inner disk. Based on data from the Spitzer and CoRoT missions. The CoRoT space mission was developed and is operated by the French space agency CNES, with participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain.

Time-lapse monitoring of fluid induced geophysical property variations within an unstable earthwork using P-wave refraction

A significant portion of the UK’s transportation system relies on a network of geotechnical earthworks (cuttings and embankments) that were constructed more than 100 years ago, whose stability is affected by the change in precipitation patterns experienced over the past few decades. The vulnerability of these structures requires a reliable, cost- and time-effective monitoring of their geomechanical condition. We have assessed the potential application of P-wave refraction for tracking the seasonal variations of seismic properties within an aged clay-filled railway embankment, located in southwest England. Seismic data were acquired repeatedly along the crest of the earthwork at regular time intervals, for a total period of 16 months. P-wave first-break times were picked from all available recorded traces, to obtain a set of hodocrones referenced to the same spatial locations, for various dates along the surveyed period of time. Traveltimes extracted from each acquisition were then compared to track the pattern of their temporal variability. The relevance of such variations over time was compared with the data experimental uncertainty. The multiple set of hodocrones was subsequently inverted using a tomographic approach, to retrieve a time-lapse model of VPVP for the embankment structure. To directly compare the reconstructed VPVP sections, identical initial models and spatial regularization were used for the inversion of all available data sets. A consistent temporal trend for P-wave traveltimes, and consequently for the reconstructed VPVP models, was identified. This pattern could be related to the seasonal distribution of precipitation and soil-water content measured on site.