Taylor dispersion of gyrotactic swimming micro-organisms in a linear flow

The theory of generalized Taylor dispersion for suspensions of Brownian particles is developed to study the dispersion of gyrotactic swimming micro-organisms in a linear shear flow. Such creatures are bottom-heavy and experience a gravitational torque which acts to right them when they are tipped away from the vertical. They also suffer a net viscous torque in the presence of a local vorticity field. The orientation of the cells is intrinsically random but the balance of the two torques results in a bias toward a preferred swimming direction. The micro-organisms are sufficiently large that Brownian motion is negligible but their random swimming across streamlines results in a mean velocity together with diffusion. As an example, we consider the case of vertical shear flow and calculate the diffusion coefficients for a suspension of the alga <i>Chlamydomonas nivalis</i>. This rational derivation is compared with earlier approximations for the diffusivity

Infrastructure Hydromentalities:Water Sharing, Water Control and Water (In)Security

The purpose of this book is to present an overview of the latest research, policy, practitioner, academic and international thinking on water security—an issue that, like water governance a few years ago, has developed much policy awareness and momentum with a wide range of stakeholders. As a concept it is open to multiple interpretations, and the authors here set out the various approaches to the topic from different perspectives. Key themes addressed include: Water security as a foreign policy issue The interconnected variables of water, food, and human security Dimensions other than military and international relations concerns around water security Water security theory and methods, tools and audits. The book is loosely based on a masters level degree plus a short professional course on water security both given at the University of East Anglia, delivered by international authorities on their subjects. It should serve as an introductory textbook as well as be of value to professionals, NGOs, and policy-makers

Threats to groundwater supplies from contamination in Sierra Leone, with special reference to Ebola care facilities

The outbreak of Ebola virus disease in West Africa in 2014 is the worst single outbreak recorded, and has resulted in more fatalities than all previous outbreaks combined. This outbreak has resulted in a large humanitarian effort to build new health care facilities, with associated water supplies. Although Ebola is not a water-borne disease, care facilities for Ebola patients may become sources of outbreaks of other, water-borne, diseases spread through shallow groundwater from hazard sources such as open defecation, latrines, waste dumps and burial sites to water supplies. The focus of this rapid desk study is to assess from existing literature the evidence for sub-surface transport of pathogens in the context of the hydrogeological and socio-economic environment of Sierra Leone. In particular, the outputs are to advise on the robustness of the evidence for an effective single minimum distance for lateral spacing between hazard sources and water supply, and provide recommendations for protecting water supplies for care facilities as well as other private and public water supplies in this region. Preliminary conclusions were: Considering the climate (heavy intense rainfall for 8 months), the hydrogeological conditions (prevalent shallow and rapidly fluctuating water tables, permeable tropical soils), the pervasive and widespread sources of hazards (very low improved sanitation coverage), and the widespread use of highly vulnerable water points there is little evidence that simply using an arbitrary lateral spacing between hazard sources and water point of 30 – 50 m would provide effective protection for groundwater points. An alternative framework that considers vertical as well as lateral separation and the integrity of the construction and casing of the deeper water points is recommended to protect water supplies from contamination by pathogens. The shallow aquifer, accessed by wells and springs, must be treated as highly vulnerable to pollution, both from diffuse sources and from localised sources. Diffuse pollution of groundwater from surface-deposited wastes including human excreta is likely to be at least as important as pollution from pit latrines and other point sources, given the low sanitation coverage in Sierra Leone. Even though conditions are not optimal for pathogen survival (e.g. temperatures of >25° C), given the very highly permeable shallow tropical soil zone, and the high potential surface and subsurface loading of pathogens, it is likely that shallow water sources are at risk from pathogen pollution, particularly during periods of intense rainfall and high water table conditions. Extending improved sanitation must be a high priority, in conjunction with improved vertical separation between hazard sources and water points, in order to reduce environmental contamination and provide a basis for improved public health. We recommend that risk assessments of water points are undertaken for health care facilities as soon as possible including: detailed sanitary inspections of water points within the 30 – 50 m radius suggested by the Ministry of Water Resource; assessments of the construction and integrity of the water points; a wider survey of contaminant load and rapid surface / sub surface transit routes within a wider 200 m radius of water points. Analysis of key water quality parameters and monitoring of water levels should be undertaken at each water point in parallel with the risk assessments. The translation of policy on water, sanitation and hygiene into implementation needs complementary research to understand key hydrogeological processes as well as barriers and failings of current practice for reducing contamination in water points. A baseline assessment of water quality status and sanitary risks for e.g. wells vs boreholes, improved vs unimproved sources in Sierra Leone is needed. Understanding the role of the tropical soil zone in the rapid migration of pollutants in the shallow subsurface, i.e. tracing rapid pathways, and quantifying residence times of shallow and deep groundwater systems are key knowledge gaps

Instability modes and transition of pulsatile stenotic flow: pulse-period dependence

Accepted versio

Are sanitation interventions a threat to drinking water supplies in rural India? An application of tryptophan-like fluorescence.

Open defecation is practised by over 600 million people in India and there is a strong political drive to eliminate this through the provision of on-site sanitation in rural areas. However, there are concerns that the subsequent leaching of excreta from subsurface storage could be adversely impacting underlying groundwater resources upon which rural populations are almost completely dependent for domestic water supply. We investigated this link in four villages undergoing sanitary interventions in Bihar State, India. A total of 150 supplies were sampled for termotolerant (faecal) coliforms (TTC) and tryptophanlike fluorescence (TLF): an emerging real-time indicator of faecal contamination. Sanitary risk inspections were also performed at all sites, including whether a supply was located within 10 m of a toilet, the recommended minimum separation. Overall, 18% of water supplies contained TTCs, 91% of which were located within 10 m of a toilet, 58% had TLF above detection limit, and sanitary risk scores were high. Statistical analysis demonstrated TLF was an effective indicator of TTC presence-absence, with a possibility of TTCs only where TLF exceeded 0.4 mg/L dissolved tryptophan. Analysis also indicated proximity to a toilet was the only significant sanitary risk factor predicting TTC presence-absence and the most significant predictor of TLF. Faecal contamination was considered a result of individual water supply vulnerability rather than indicative of widespread leaching into the aquifer. Therefore, increasing faecal contamination of groundwater-derived potable supplies is inevitable across the country as uptake of onsite sanitation intensifies. Communities need to be aware of this link and implement suitable decentralised low-cost treatment of water prior to consumption and improve the construction and protection of new supplies

Decomposition of spontaneous fluctuations in tumour oxygenation using BOLD MRI and independent component analysis

Solid tumours can undergo cycles of hypoxia, followed by reoxygenation, which can have significant implications for the success of anticancer therapies. A need therefore exists to develop methods to aid its detection and to further characterise its biological basis. We present here a novel method for decomposing systemic and tumour-specific contributions to fluctuations in tumour deoxyhaemoglobin concentration, based on magnetic resonance imaging measurements

Oncogenic transformation of mesenchymal stem cells decreases Nrf2 expression favoring in vivo tumor growth and poorer survival

BACKGROUND: The transcription factor Nrf2 is a key regulator of the cellular antioxidant response, and its activation by chemoprotective agents has been proposed as a potential strategy to prevent cancer. However, activating mutations in the Nrf2 pathway have been found to promote tumorigenesis in certain models. Therefore, the role of Nrf2 in cancer remains contentious. METHODS: We employed a well-characterized model of stepwise human mesenchymal stem cell (MSC) transformation and breast cancer cell lines to investigate oxidative stress and the role of Nrf2 during tumorigenesis. The Nrf2 pathway was studied by microarray analyses, qRT-PCR, and western-blotting. To assess the contribution of Nrf2 to transformation, we established tumor xenografts with transformed MSC expressing Nrf2 (n = 6 mice per group). Expression and survival data for Nrf2 in different cancers were obtained from GEO and TCGA databases. All statistical tests were two-sided. RESULTS: We found an accumulation of reactive oxygen species during MSC transformation that correlated with the transcriptional down-regulation of antioxidants and Nrf2-downstream genes. Nrf2 was repressed in transformed MSC and in breast cancer cells via oncogene-induced activation of the RAS/RAF/ERK pathway. Furthermore, restoration of Nrf2 function in transformed cells decreased reactive oxygen species and impaired in vivo tumor growth (P = 0.001) by mechanisms that included sensitization to apoptosis, and a decreased hypoxic/angiogenic response through HIF-1α destabilization and VEGFA repression. Microarray analyses showed down-regulation of Nrf2 in a panel of human tumors and, strikingly, low Nrf2 expression correlated with poorer survival in patients with melanoma (P = 0.0341), kidney (P = 0.0203) and prostate (P = 0.00279) cancers. CONCLUSIONS: Our data indicate that oncogene-induced Nrf2 repression is an adaptive response for certain cancers to acquire a pro-oxidant state that favors cell survival and in vivo tumor growth

Urban groundwater quality in sub-Saharan Africa: current status and implications for water security and public health

Groundwater resources are important sources of drinking water in Africa, and they are hugely important in sustaining urban livelihoods and supporting a diverse range of commercial and agricultural activities. Groundwater has an important role in improving health in sub-Saharan Africa (SSA). An estimated 250 million people (40% of the total) live in urban centres across SSA. SSA has experienced a rapid expansion in urban populations since the 1950s, with increased population densities as well as expanding geographical coverage. Estimates suggest that the urban population in SSA will double between 2000 and 2030. The quality status of shallow urban groundwater resources is often very poor due to inadequate waste management and source protection, and poses a significant health risk to users, while deeper borehole sources often provide an important source of good quality drinking water. Given the growth in future demand from this finite resource, as well as potential changes in future climate in this region, a detailed understanding of both water quantity and quality is required to use this resource sustainably. This paper provides a comprehensive assessment of the water quality status, both microbial and chemical, of urban groundwater in SSA across a range of hydrogeological terrains and different groundwater point types. Lower storage basement terrains, which underlie a significant proportion of urban centres in SSA, are particularly vulnerable to contamination. The relationship between mean nitrate concentration and intrinsic aquifer pollution risk is assessed for urban centres across SSA. Current knowledge gaps are identified and future research needs highlighted

Urban groundwater quality in sub-Saharan Africa: current status and implications for water security and public health

Groundwater resources are important sources of drinking water in Africa, and they are hugely important in sustaining urban livelihoods and supporting a diverse range of commercial and agricultural activities. Groundwater has an important role in improving health in sub-Saharan Africa (SSA). An estimated 250 million people (40% of the total) live in urban centres across SSA. SSA has experienced a rapid expansion in urban populations since the 1950s, with increased population densities as well as expanding geographical coverage. Estimates suggest that the urban population in SSA will double between 2000 and 2030. The quality status of shallow urban groundwater resources is often very poor due to inadequate waste management and source protection, and poses a significant health risk to users, while deeper borehole sources often provide an important source of good quality drinking water. Given the growth in future demand from this finite resource, as well as potential changes in future climate in this region, a detailed understanding of both water quantity and quality is required to use this resource sustainably. This paper provides a comprehensive assessment of the water quality status, both microbial and chemical, of urban groundwater in SSA across a range of hydrogeological terrains and different groundwater point types. Lower storage basement terrains, which underlie a significant proportion of urban centres in SSA, are particularly vulnerable to contamination. The relationship between mean nitrate concentration and intrinsic aquifer pollution risk is assessed for urban centres across SSA. Current knowledge gaps are identified and future research needs highlighted

Measurement of the critical DNA lesions produced by antibody-directed enzyme prodrug therapy (ADEPT) in vitro, in vivo and in clinical material

An antibody-directed enzyme prodrug therapy (ADEPT) system against CEA-positive tumours is currently in phase I clinical trials. It consists of a prodrug, 4-[N,N-bis(2-iodoethyl) amino] phenoxycarbonyl L -glutamic acid (ZD2767P) and a conjugate of the F(ab')2 anti-CEA antibody A5B7 and the bacterial enzyme carboxypeptidase G2 (CPG2). ZD2767P is converted by antibody-targeted CPG2 into an active bifunctional alkylating drug (ZD2767) at the tumour site. The IC 50 value of the prodrug against the human colorectal tumour LS174T cell line was 55 ± 9 μM following a 1 h exposure. In contrast, co-incubation of ZD2767P with CPG2 resulted in 229-fold increase in activity. Using a modified comet assay, DNA interstrand cross links (ISC) were detected within 1 h of ZD2767P + CPG2 treatment and were repaired by 24 h. A clear dose–response was seen between the level of ISC, growth inhibition and ZD2767 concentration. Administration of a therapeutic dose of ZD2767P 72 h after the F(ab′)2 A5B7 conjugate to mice bearing LS147T xenografts resulted in extensive ISC in the tumour after 1 h; repair was seen at 24 h. Tumour biopsies and peripheral lymphocytes were studied in 5 patients on the ADEPT phase I clinical trial. In 4 patients no ISC were detected. These patients also demonstrated poor localization of conjugate and no tumour response was seen. However a significant level of ISC was detected in one tumour biopsy, which also showed evidence of conjugate localization and clinical response. These studies demonstrate the application of the comet assay in the measurement of ISC in vitro and in clinical material and confirm that activation of ZD2767P results in the formation of DNA crosslinks. © 2001 Cancer Research Campaign http://www.bjcancer.co