Dynamics of nitrate and nitrite in saturated sand filters with enhanced substrate conditions for denitrifying bacteria

Substrate conditions for denitrifying bacteria were enhanced by adding carbon sources to a laboratory-scale sand filter system. Temperature, oxidation–reduction potential, and hydrogen ion concentration were measured through the recirculation of nitrogen-dosed wastewater and carbon sources that were mixed to encourage microbial growth, with denitrifying bacteria identified by standard plate counts. Two different external carbon sources (sucrose and ethanol) were added, with and without activated sludge amendments. Nitrate, nitrite, and chemical oxygen demand (COD) concentrations were monitored relative to an untreated control and a treatment with activated sludge under an initial hydraulic loading rate of 0.508 m3 /m2 d and a hydraulic retention time of 2.5 h. Nitrate decay rates were only significantly enhanced for the ethanol treatment without addition of activated sludge. Nitrite initially accumulated when carbon sources were added, but no accumulation was evident by the end of the experiment after 150 min. COD declined when carbon sources were added, but activated sludge had no effect on the rate at which the COD declined. The increased rate of nitrate removal with the addition of ethanol is of technical interest, as the volume of wastewater treated in a unit volume of filter medium for denitrification doubled with ethanol compared with sucrose at the same concentration

Expression of chimeric HCV peptide in transgenic tobacco plants infected with recombinant alfalfa mosaic virus for development of a plant-derived vaccine against HCV

Hepatitis C virus (HCV) is the major etiologic agent of blood transfusion–associated and sporadic non-A non-B hepatitis affecting more than 180 million worldwide. Vaccine development for HCV has been difficult and there is no vaccine or effective therapy against this virus. In this paper, we describe the development of an experimental plant-derived subunit vaccine against HCV. Our subunit vaccine originates from a consensus HCV-HVR1 epitope (R9) that antigenically mimics many natural HVR1 variants. This HVR1 sequence was cloned into the open reading frame of a plant virus, Alfalfa Mosaic Virus (ALMV) coat protein (CP). The chimeric ALMV RNA4 containing sequence-encoding R9 epitope was introduced into full-length infectious ALMV-RNA3 that was utilized as an expression vector. The recombinant chimeric protein is expressed in transgenic tobacco plants (P12) expressing ALMV RNA1 and 2. Plant–derived HVR1/ALMV-CP reacted with HVR1 and/or ALMV-CP specific monoclonal antibodies and immune sera from individuals infected with HCV. Using plant-virus based transient expression to produce this unique chimeric antigen will facilitate the development and production of an experimental HCV vaccine. A plant derived recombinant HCV vaccine can potentially reduce expenses normally associated with production and delivery of conventional vaccine. Key Words: Hepatitis C virus (HCV), transgenic tobacco plants (P12), consensus HCV HVR1 epitope (R9), and chimeric ALMV-RNA4. African Journal of Biotechnology Vol.3(11) 2004: 588-59

Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

Background: A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. <p/>Methods: Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). <p/>Results: 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m2. MTD was 10 mg/m2; DLTs at 12 (2/4 patients) and 10 mg/m2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and Cmax from 1--10 mg/m2. Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. <p/>Conclusions: TP300 had predictable hematologic toxicity, and diarrhea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage

Institutional strategies for capturing socio-economic impact of academic research

Evaluation of socio-economic impact is an emerging theme for publicly-funded academic research. Within this context the paper suggests that the concept of institutional research capital be expanded to include the capture and evaluation of socio-economic impact. Furthermore, it argues that understanding the typology of impacts and the tracking from research to impact will assist the formulation of institutional strategies for capturing socio-economic impact. A three-stage approach is proposed for capturing and planning activities to enhance the generation of high-quality impact. Stage one outlines the critical role of user engagement that facilitates the tracking of such impact. Stage two employs an analytical framework based on the criteria of ‘depth’ and ‘spread’ to evaluate impacts that have been identified. Stage three utilizes the outcomes of the framework to devise strategies, consisting of either further research (to increase depth) or more engagement (to increase spread) that will improve the generation of higher quality impact

Revisiting the 'Missing Middle' in English Sub-National Governance

In the light of the new Coalition Government’s proposed ‘rescaling’ of sub-national governance away from the regional level, it is an opportune time to re-consider the strength and weaknesses of the city or sub-regional approach to economic development and to search, once more, for the ‘missing middle’ in English Governance. In this context, the article initially assesses the case for city or sub regions as tiers of economic governance, before examining the lessons to be learnt from the experiences of the existing city regions in the North East of England. It argues that while contemporary plans to develop Local Enterprise Partnerships (LEPs) can be usefully considered within the context of the emerging city regional developments under the previous Labour Governments, a number of important challenges remain, particularly in relation to ensuring accountable structures of governance, a range of appropriate functions, adequate funding, and comprehensive coverage across a variety of sub-regional contexts. While the proposals of the new Government create the necessary ‘space’ to develop sub-regional bodies and offer genuine opportunities for both city and county LEPs, the scale of the sub-regional challenge should not be underestimated, particularly given the context of economic recession and major reductions in the public sector

Clarifying misconceptions of extinction risk assessment with the IUCN Red List

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.The identification of species at risk of extinction is a central goal of conservation. As the use of data compiled for IUCN Red List assessments expands, a number of misconceptions regarding the purpose, application and use of the IUCN Red List categories and criteria have arisen. We outline five such classes of misconception; the most consequential drive proposals for adapted versions of the criteria, rendering assessments among species incomparable. A key challenge for the future will be to recognize the point where understanding has developed so markedly that it is time for the next generation of the Red List criteria. We do not believe we are there yet but, recognizing the need for scrutiny and continued development of Red Listing, conclude by suggesting areas where additional research could be valuable in improving the understanding of extinction risk among species

Assessing the cost of global biodiversity and conservation knowledge

Knowledge products comprise assessments of authoritative information supported by stan-dards, governance, quality control, data, tools, and capacity building mechanisms. Considerable resources are dedicated to developing and maintaining knowledge productsfor biodiversity conservation, and they are widely used to inform policy and advise decisionmakers and practitioners. However, the financial cost of delivering this information is largelyundocumented. We evaluated the costs and funding sources for developing and maintain-ing four global biodiversity and conservation knowledge products: The IUCN Red List ofThreatened Species, the IUCN Red List of Ecosystems, Protected Planet, and the WorldDatabase of Key Biodiversity Areas. These are secondary data sets, built on primary datacollected by extensive networks of expert contributors worldwide. We estimate that US$160million (range: US$116–204 million), plus 293 person-years of volunteer time (range: 278–308 person-years) valued at US$14 million (range US$12–16 million), were invested inthese four knowledge products between 1979 and 2013. More than half of this financingwas provided through philanthropy, and nearly three-quarters was spent on personnelcosts. The estimated annual cost of maintaining data and platforms for three of these knowl-edge products (excluding the IUCN Red List of Ecosystems for which annual costs were notpossible to estimate for 2013) is US$6.5 million in total (range: US$6.2–6.7 million). We esti-mated that an additional US$114 million will be needed to reach pre-defined baselines ofdata coverage for all the four knowledge products, and that once achieved, annual mainte-nance costs will be approximately US$12 million. These costs are much lower than those tomaintain many other, similarly important, global knowledge products. Ensuring that biodi-versity and conservation knowledge products are sufficiently up to date, comprehensiveand accurate is fundamental to inform decision-making for biodiversity conservation andsustainable development. Thus, the development and implementation of plans for sustain-able long-term financing for them is critical

Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al

In the dedicated pursuit of dedicated capital: restoring an indigenous investment ethic to British capitalism

Tony Blair’s landslide electoral victory on May 1 (New Labour Day?) presents the party in power with a rare, perhaps even unprecedented, opportunity to revitalise and modernise Britain’s ailing and antiquated manufacturing economy.* If it is to do so, it must remain true to its long-standing (indeed, historic) commitment to restore an indigenous investment ethic to British capitalism. In this paper we argue that this in turn requires that the party reject the very neo-liberal orthodoxies which it offered to the electorate as evidence of its competence, moderation and ‘modernisation’, which is has internalised, and which it apparently now views as circumscribing the parameters of the politically and economically possible