The engineering geology of the Nottingham area, UK

Nottingham was built near a crossing point on the River Trent in the East Midlands of England. Initially, the City developed on a low sandstone hill close to the north bank of the river, which provided a secure, well-drained location above the marshes that bordered the river. Geologically, Nottingham stands at the boundary between Palaeozoic rocks to the north and west, and Mesozoic and Cainozoic strata to the south and east. The area is underlain by coal-bearing Carboniferous Coal Measures, Permian dolomitic limestones, Permo-Triassic mudstones and weak sandstones, Jurassic clays and Quaternary glacial and alluvial deposits. Artificial deposits, resulting from the social, industrial and mineral extraction activities of the past cover the natural deposits over much of the area. This geological environment has underpinned the economic development of the area through the mining of coal (now largely ceased), oil extraction that was important during the Second World War, brickmaking from clays, alluvial sand and gravel extraction from the Trent Valley and gypsum extraction from the Permo-Triassic mudstones. The Permo-Triassic sandstone is a nationally important aquifer and has also been exploited at the surface and from shallow mines for sand. However, this history of the use and exploitation of mineral deposits has created a number of environmental problems including rising groundwater levels, abandoned mine shafts and mining subsidence, and, within the City itself, the occasional collapse of artificial cavities in the sandstone and contaminated land left by industrial activities. Natural constraints on development include gypsum dissolution, landslides, rockfalls, swell-shrink problems in Jurassic clays and flooding. Occasional minor earthquakes are attributed to movements due to coal mining or natural, deep geological structures. Thus, Nottingham’s geological context remains an important consideration when planning its future regeneration and development

Gravitational quasinormal modes of AdS black branes in d spacetime dimensions

The AdS/CFT duality has established a mapping between quantities in the bulk AdS black-hole physics and observables in a boundary finite-temperature field theory. Such a relationship appears to be valid for an arbitrary number of spacetime dimensions, extrapolating the original formulations of Maldacena's correspondence. In the same sense properties like the hydrodynamic behavior of AdS black-hole fluctuations have been proved to be universal. We investigate in this work the complete quasinormal spectra of gravitational perturbations of $d$-dimensional plane-symmetric AdS black holes (black branes). Holographically the frequencies of the quasinormal modes correspond to the poles of two-point correlation functions of the field-theory stress-energy tensor. The important issue of the correct boundary condition to be imposed on the gauge-invariant perturbation fields at the AdS boundary is studied and elucidated in a fully $d$-dimensional context. We obtain the dispersion relations of the first few modes in the low-, intermediate- and high-wavenumber regimes. The sound-wave (shear-mode) behavior of scalar (vector)-type low-frequency quasinormal mode is analytically and numerically confirmed. These results are found employing both a power series method and a direct numerical integration scheme.Comment: added references, typos corrected, minor changes, final version for JHE

Crossover and scaling in a nearly antiferromagnetic Fermi liquid in two dimensions

We consider two-dimensional Fermi liquids in the vicinity of a quantum transition to a phase with commensurate, antiferromagnetic long-range order. Depending upon the Fermi surface topology, mean-field spin-density-wave theory predicts two different types of such transitions, with mean-field dynamic critical exponents $z=1$ (when the Fermi surface does not cross the magnetic zone boundary, type $A$) and $z=2$ (when the Fermi surface crosses the magnetic zone boundary, type $B$). The type $A$ system only displays $z=1$ behavior at all energies and its scaling properties are similar (though not identical) to those of an insulating Heisenberg antiferromagnet. Under suitable conditions precisely stated in this paper, the type $B$ system displays a crossover from relaxational behavior at low energies to type $A$ behavior at high energies. A scaling hypothesis is proposed to describe this crossover: we postulate a universal scaling function which determines the entire, temperature-, wavevector-, and frequency-dependent, dynamic, staggered spin susceptibility in terms of 4 measurable, $T=0$, parameters (determining the distance, energy, and order parameter scales, plus one crossover parameter). The scaling function contains the full scaling behavior in all regimes for both type $A$ and $B$ systems. The crossover behavior of the uniform susceptibility and the specific heat is somewhat more complicated and is also discussed. Explicit computation of the crossover functions is carried out in a large $N$ expansion on a mean-field model. Some new results for the critical properties on the ordered side of the transition are also obtained in a spin-density wave formalism. The possible relevance of our results to the doped cuprate compounds is briefly discussed.Comment: 20 pages, REVTeX, 6 figures (uuencoded compressed PostScript file for figures is appended

Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options.

TCF3-HLF-positive acute lymphoblastic leukemia (ALL) is currently incurable. Using an integrated approach, we uncovered distinct mutation, gene expression and drug response profiles in TCF3-HLF-positive and treatment-responsive TCF3-PBX1-positive ALL. We identified recurrent intragenic deletions of PAX5 or VPREB1 in constellation with the fusion of TCF3 and HLF. Moreover somatic mutations in the non-translocated allele of TCF3 and a reduction of PAX5 gene dosage in TCF3-HLF ALL suggest cooperation within a restricted genetic context. The enrichment for stem cell and myeloid features in the TCF3-HLF signature may reflect reprogramming by TCF3-HLF of a lymphoid-committed cell of origin toward a hybrid, drug-resistant hematopoietic state. Drug response profiling of matched patient-derived xenografts revealed a distinct profile for TCF3-HLF ALL with resistance to conventional chemotherapeutics but sensitivity to glucocorticoids, anthracyclines and agents in clinical development. Striking on-target sensitivity was achieved with the BCL2-specific inhibitor venetoclax (ABT-199). This integrated approach thus provides alternative treatment options for this deadly disease

Making use of transcription factor enrichment to identify functional microRNA-regulons

microRNAs (miRNAs) are important modulators of messenger RNA stability and translation, controlling wide gene networks. Albeit generally modest on individual targets, the regulatory effect of miRNAs translates into meaningful pathway modulation through concurrent targeting of regulons with functional convergence. Identification of miRNA-regulons is therefore essential to understand the function of miRNAs and to help realise their therapeutic potential, but it remains challenging due to the large number of false positive target sites predicted per miRNA. In the current work, we investigated whether genes regulated by a given miRNA were under the transcriptional control of a predominant transcription factor (TF). Strikingly we found that for ~50% of the miRNAs analysed, their targets were significantly enriched in at least one common TF. We leveraged such miRNA-TF co-regulatory networks to identify pathways under miRNA control, and demonstrated that filtering predicted miRNA-target interactions (MTIs) relying on such pathways significantly enriched the proportion of predicted true MTIs. To our knowledge, this is the first description of an in- silico pipeline facilitating the identification of miRNA-regulons, to help understand miRNA function.Pacôme B. Prompsy, John Toubia, Linden J. Gearing, Randle L. Knight, Samuel C. Forster, Cameron P. Bracken, Michael P. Gantie

Neutrino Propagation in a Fluctuating Sun

We adapt to neutrino physics a general formulation for particle propagation in fluctuating media, initially developed for applications to electromagnetism and neutron optics. In leading approximation this formalism leads to the usual MSW effective hamiltonian governing neutrino propagation through a medium. Next-to-leading contributions describe deviations from this description, which arise due to neutrino interactions with fluctuations in the medium. We compute these corrections for two types of fluctuations: ($i$) microscopic thermal fluctuations, and ($ii$) macroscopic fluctuations in the medium's density. While the first of these reproduces standard estimates, which are negligible for applications to solar neutrinos, we find the second can be quite large, since it grows in size with the correlation length of the fluctuation. We consider two models in some detail. For fluctuations whose correlations are extend only over a local region in space of length $l$, appreciable effects for MSW oscillations arise if (\delta n/n)^2 l\gsim 100 m or so. Alternatively, a crude model of helioseismic $p$-waves gives appreciable effects only when (\delta n/n) \gsim 1%. In general the dominant effect is to diminish the quality of the resonance, making the suppression of the ${}^7$Be neutrinos a good experimental probe of fluctuations deep within the sun. Fluctuations can also provide a new mechanism for reducing the solar neutrino flux, giving an energy-independent suppression factor of $1/2$, away from the resonant region, even for small vacuum mixing angles.Comment: 45 pages, including 2 postscript figures. (We had a subsection in section 2 to detail the approximations leading to our results. We also fixed some typography and added some references

Radical chemistry and ozone production at a UK coastal receptor site

OH, HO2, total and partially speciated RO2, and OH reactivity (kOH′) were measured during the July 2015 ICOZA (Integrated Chemistry of OZone in the Atmosphere) project that took place at a coastal site in north Norfolk, UK. Maximum measured daily OH, HO2 and total RO2 radical concentrations were in the range 2.6–17 × 106, 0.75–4.2 × 108 and 2.3–8.0 × 108 molec. cm−3, respectively. kOH′ ranged from 1.7 to 17.6 s−1, with a median value of 4.7 s−1. ICOZA data were split by wind direction to assess differences in the radical chemistry between air that had passed over the North Sea (NW–SE sectors) and that over major urban conurbations such as London (SW sector). A box model using the Master Chemical Mechanism (MCMv3.3.1) was in reasonable agreement with the OH measurements, but it overpredicted HO2 observations in NW–SE air in the afternoon by a factor of ∼ 2–3, although slightly better agreement was found for HO2 in SW air (factor of ∼ 1.4–2.0 underprediction). The box model severely underpredicted total RO2 observations in both NW–SE and SW air by factors of ∼ 8–9 on average. Measured radical and kOH′ levels and measurement–model ratios displayed strong dependences on NO mixing ratios, with the results suggesting that peroxy radical chemistry is not well understood under high-NOx conditions. The simultaneous measurement of OH, HO2, total RO2 and kOH′ was used to derive experimental (i.e. observationally determined) budgets for all radical species as well as total ROx (i.e. OH + HO2 + RO2). In NW–SE air, the ROx budget could be closed during the daytime within experimental uncertainty, but the rate of OH destruction exceeded the rate of OH production, and the rate of HO2 production greatly exceeded the rate of HO2 destruction, while the opposite was true for RO2. In SW air, the ROx budget analysis indicated missing daytime ROx sources, but the OH budget was balanced, and the same imbalances were found with the HO2 and RO2 budgets as in NW–SE air. For HO2 and RO2, the budget imbalances were most severe at high-NO mixing ratios, and the best agreement between HO2 and RO2 rates of production and destruction rates was found when the RO2 + NO rate coefficient was reduced by a factor of 5. A photostationary-steady-state (PSS) calculation underpredicted daytime OH in NW–SE air by ∼ 35 %, whereas agreement (∼ 15 %) was found within instrumental uncertainty (∼ 26 % at 2σ) in SW air. The rate of in situ ozone production (P(Ox)) was calculated from observations of ROx, NO and NO2 and compared to that calculated from MCM-modelled radical concentrations. The MCM-calculated P(Ox) significantly underpredicted the measurement-calculated P(Ox) in the morning, and the degree of underprediction was found to scale with NO

Quantifying soil carbon stocks and greenhouse gas fluxes in the sugarcane agrosystem: point of view

Strategies to mitigate climate change through the use of biofuels (such as ethanol) are associated not only to the increase in the amount of C stored in soils but also to the reduction of GHG emissions to the atmosphere.This report mainly aimed to propose appropriate methodologies for the determinations of soil organic carbon stocks and greenhouse gas fluxes in agricultural phase of the sugarcane production. Therefore, the text is a piece of contribution that may help to obtain data not only on soil carbon stocks but also on greenhouse gas emissions in order to provide an accurate life cycle assessment for the ethanol. Given that the greenhouse gas value is the primary measure of biofuel product quality, biorefiners that can show a higher offset of their product will have an advantage in the market place

Diabetic gastroparesis: Therapeutic options

Gastroparesis is a condition characterized by delayed gastric emptying and the most common known underlying cause is diabetes mellitus. Symptoms include nausea, vomiting, abdominal fullness, and early satiety, which impact to varying degrees on the patient’s quality of life. Symptoms and deficits do not necessarily relate to each other, hence despite significant abnormalities in gastric emptying, some individuals have only minimal symptoms and, conversely, severe symptoms do not always relate to measures of gastric emptying. Prokinetic agents such as metoclopramide, domperidone, and erythromycin enhance gastric motility and have remained the mainstay of treatment for several decades, despite unwanted side effects and numerous drug interactions. Mechanical therapies such as endoscopic pyloric botulinum toxin injection, gastric electrical stimulation, and gastrostomy or jejunostomy are used in intractable diabetic gastroparesis (DG), refractory to prokinetic therapies. Mitemcinal and TZP-101 are novel investigational motilin receptor and ghrelin agonists, respectively, and show promise in the treatment of DG. The aim of this review is to provide an update on prokinetic and mechanical therapies in the treatment of DG

Objectively measured physical activity in european adults: cross-sectional findings from the Food4Me study

Introduction Physical inactivity has been estimated to be responsible for more than 5.3 million deaths worldwide [1]. Moreover, among European men and women, approximately 7.3% of all deaths in 2008 might be attributable to inactivity compared with 3.7% to obesity [2] and there is strong evidence to suggest that even small increases in physical activity (PA) would lower the risk for many non-communicable diseases [1–3]. Yet, levels of PA across populations remain low [4]. To tackle this public health issue, the US Centers for Disease Control and Prevention and the American College of Sports Medicine produced standardized PA guidelines 20 years ago [5]. Since then, the World Health Organization (WHO), the European Union, and most countries around the world, have included PA guidelines in their health policies. Guidelines for Americans and Europeans have been updated to include recommendations for adolescents and for older adults [6–9]. For adults aged 18–64 years old, the WHO recommends a minimum of 150 min of moderate intensity PA per week, 75 min of vigorous intensity PA or an equivalent amount of moderate and vigorous PA (MVPA) [9]. In 2008, 34.8% of adults 15 years or older were insufficiently active in Europe [4]. Regular surveillance is needed to update these prevalence estimates and to evaluate the effectiveness of PA policies and promotion programs in European countries. In this context, the objective assessment of PA is a key issue. Prevalence of physical inactivity has been mainly derived from self-reported measures such as the Baecke questionnaire [10] or the International Physical Activity Questionnaire (IPAQ) [11]. These questionnaires have been, and still are, widely used due to their simple administration and low cost [12]. However, PA is frequently misreported, which leads to considerable measurement error [13–15]. Accelerometers offer a potential solution because they measure PA objectively. Given that they are small and easy to wear, store data up to several weeks and are acceptable in terms of reliability, these devices are now used increasingly in large studies to assess PA in children, adolescents and adults [16]. Although some European countries have reported adherence to PA guidelines using accelerometers in large cohorts [17–19], comparisons between European countries measured according to the same standardized protocols and concurrently are lacking. Between 2012 and 2014, PA was assessed objectively by accelerometry in the participants of the Food4Me Proof-of-Principle (PoP) study. The Food4Me Study was a web-based randomized controlled trial on personalized nutrition, across seven European countries: Germany, Greece, Ireland, The Netherlands, Poland, Spain and the United Kingdom. The aim of the current paper is to describe and compare PA in adults from these countries, and evaluate adherence to PA guidelines, using baseline data from the Food4Me PoP study