PAR2 modulators derived from GB88

PAR2 antagonists have potential for treating inflammatory, respiratory, gastrointestinal, neurological, and metabolic disorders, but few antagonists are known. Derivatives of GB88 (3) suggest that all four of its components bind at distinct PAR2 sites with the isoxazole, cyclohexylalanine, and isoleucine determining affinity and selectivity, while the C-terminal substituent determines agonist/antagonist function. Here we report structurally similar PAR2 ligands with opposing functions (agonist vs antagonist) upon binding to PAR2. A biased ligand AY117 (65) was found to antagonize calcium release induced by PAR2 agonists trypsin and hexapeptide 2f-LIGRLO-NH2 (IC50 2.2 and 0.7 mu M, HT29 cells), but it was a selective PAR2 agonist in inhibiting cAMP stimulation and activating ERK1/2 phosphorylation. It showed antiinflammatory properties both in vitro and in vivo

Depuranat project: sustainable management of wastewater in rural areas

The Urban Wastewater Directive is aiming to implement adequate treatments of collected wastewater before 31 December 2005 in small communities with a population until 2000 equivalentinhabitant. Within the framework of the DEPURANAT project, co-financed by the European Interregional Cooperation Programme (Interreg IIIB Atlantic Arc), several Natural Reclamation Systems (NRS) based upon no-conventional technologies of wastewater treatment, have been studied from different points of view in rural areas: their effectiveness for producing regenerated wastewater of acceptable quality for several reuse options and vegetal biomass for different purposes, their environmental integration or their potential of implementation. Most of these treatment plants achieved high mean removal efficiencies: TSS (73–96%); BOD5 (74–94%); COD (53–90%); E. coli (2–3 log units); Enterococci (1.5–4 log units). The environmental impact of the systems was determined using an adapted life cycle assessment methodology and the economic analysis of the systems was focused on analysing the financial indicators, empirical cost functions, and the potential market for these technologies. Furthermore, maps of potential implementation of these systems and a support tool for deciding upon the installation of conventional or NRS were designed with the aim of promoting them.Communitary Interreg III-B Atlantic Area of EuropeDEPURANAT consortiu

Spatial Guilds in the Serengeti Food Web Revealed by a Bayesian Group Model

Food webs, networks of feeding relationships among organisms, provide fundamental insights into mechanisms that determine ecosystem stability and persistence. Despite long-standing interest in the compartmental structure of food webs, past network analyses of food webs have been constrained by a standard definition of compartments, or modules, that requires many links within compartments and few links between them. Empirical analyses have been further limited by low-resolution data for primary producers. In this paper, we present a Bayesian computational method for identifying group structure in food webs using a flexible definition of a group that can describe both functional roles and standard compartments. The Serengeti ecosystem provides an opportunity to examine structure in a newly compiled food web that includes species-level resolution among plants, allowing us to address whether groups in the food web correspond to tightly-connected compartments or functional groups, and whether network structure reflects spatial or trophic organization, or a combination of the two. We have compiled the major mammalian and plant components of the Serengeti food web from published literature, and we infer its group structure using our method. We find that network structure corresponds to spatially distinct plant groups coupled at higher trophic levels by groups of herbivores, which are in turn coupled by carnivore groups. Thus the group structure of the Serengeti web represents a mixture of trophic guild structure and spatial patterns, in contrast to the standard compartments typically identified in ecological networks. From data consisting only of nodes and links, the group structure that emerges supports recent ideas on spatial coupling and energy channels in ecosystems that have been proposed as important for persistence.Comment: 28 pages, 6 figures (+ 3 supporting), 2 tables (+ 4 supporting

The challenges of long-term invasive mammal management: lessons from the UK

We consider the motivations, strategies, and costs involved in invasive mammal management undertaken in the UK. Widespread established invasive mammals require long‐term management to limit damage or spread, but ongoing management is costly and complex. Long‐term management is most effective where it is applied at a landscape scale, but this requires overarching co‐ordination between multiple stakeholders. Five challenges for successful long‐term management of invasive mammal species are identified as follows: defining landscape‐scale strategies, management co‐ordination, stakeholder and community engagement, sustainable funding, and evidence requirements. We make recommendations on the supportive infrastructure needed for effective landscape‐scale management of invasive mammals to fulfil long‐term conservation aims, as follows. 1. There is a need for evidence‐based Invasive Species Action Plans to provide strategy for the long‐term ongoing management of prioritised species at appropriate scales. 2. Where possible, multispecies approaches to invasive species management should be adopted. 3. Trusted leadership should be identified to take ownership of Action Plans and provide an overarching co‐ordination to bring individuals, organisations, and funders together. 4. Support for a centralised hub for training, data, and knowledge flows will greatly improve scientific outcomes through a searchable evidence base, and via best practice and knowledge sharing

Changing presentation of prostate cancer in a UK population--10 year trends in prostate cancer risk profiles in the East of England.

BACKGROUND: Prostate cancer incidence is rising in the United Kingdom but there is little data on whether the disease profile is changing. To address this, we interrogated a regional cancer registry for temporal changes in presenting disease characteristics. METHODS: Prostate cancers diagnosed from 2000 to 2010 in the Anglian Cancer Network (n=21,044) were analysed. Risk groups (localised disease) were assigned based on NICE criteria. Age standardised incidence rates (IRs) were compared between 2000-2005 and 2006-2010 and plotted for yearly trends. RESULTS: Over the decade, overall IR increased significantly (P<0.00001), whereas metastasis rates fell (P<0.0007). For localised disease, IR across all risk groups also increased but at different rates (P<0.00001). The most striking change was a three-fold increase in intermediate-risk cancers. Increased IR was evident across all PSA and stage ranges but with no upward PSA or stage shift. In contrast, IR of histological diagnosis of low-grade cancers fell over the decade, whereas intermediate and high-grade diagnosis increased significantly (P<0.00001). CONCLUSION: This study suggests evidence of a significant upward migration in intermediate and high-grade histological diagnosis over the decade. This is most likely to be due to a change in histological reporting of diagnostic prostate biopsies. On the basis of this data, increasing proportions of newly diagnosed cancers will be considered eligible for radical treatment, which will have an impact on health resource planning and provision

Evaluation of Commercial Probiotic Products

Although there is a vast number of probiotic products commercially available due to their acceptability and increasing usage, their quality control has continuously been a major concern. This study aimed to assess some commercially available probiotics on the UK market for content in relation to their label claim. Seven products were used for the study. The bacteria content were isolated, identified and enumerated on selective media. The results revealed that all products evaluated contained viable probiotic bacteria but only three out of the seven products (43%) contained the claimed culture concentration or more. None of the multispecies product contained all the labelled probiotic bacteria. Misidentification of some species occurred. The results concurred with previous studies and showed that quality issues with commercial probiotics remain. Since probiotic activity is linked with probiotic concentration and is strain specific, the need exist for a global comprehensive legislation to control the quality of probiotics whose market is gaining huge momentum

Z-Pinch Generated X-Rays in Static-Wall Hohlraum Geometry Demonstrate Potential for Indirect-Drive ICF Studies

Hohlraums of full ignition scale (6-mm diameter by 7-mm length) have been heated by x-rays from a z-pinch target on Z to a variety of temperatures and pulse shapes which can be used to simulate the early phases of the National Ignition Facility (NIF) temperature drive. The pulse shape is varied by changing the on-axis target of the z pinch in a static-wall-hohlraum geometry. A 2-{micro}m-thick walled Cu cylindrical target of 8-mm diameter filled with 10 mg/cm{sup 3} CH, for example, produces foot-pulse conditions of {minus}85 eV for a duration of {approximately} 10 ns, while a solid cylindrical target of 5-mm diameter and 14-mg/cm{sup 3} CH generates first-step-pulse conditions of {approximately} 122 eV for a duration of a few ns. Alternatively, reducing the hohlraum size (to 4-mm diameter by 4-mm length) with the latter target has increased the peak temperature to {approximately} 150 eV, which is characteristic of a second-step-pulse temperature. In general, the temperature T of these x-ray driven hohlraums is in agreement with the Planckian relation (T-(P/A){sup 1/4}). P is the measured x-ray input power and A is the surface area of the hohlraum. Fully-integrated 2-D radiation-hydrodynamic simulations of the z pinch and subsequent hohlraum heating show plasma densities within the useful volume of the hohlraums to be on the order of air or less

Compact Wire Array Sources: Power Scaling and Implosion Physics.

A series of ten shots were performed on the Saturn generator in short pulse mode in order to study planar and small-diameter cylindrical tungsten wire arrays at {approx}5 MA current levels and 50-60 ns implosion times as candidates for compact z-pinch radiation sources. A new vacuum hohlraum configuration has been proposed in which multiple z pinches are driven in parallel by a pulsed power generator. Each pinch resides in a separate return current cage, serving also as a primary hohlraum. A collection of such radiation sources surround a compact secondary hohlraum, which may potentially provide an attractive Planckian radiation source or house an inertial confinement fusion fuel capsule. Prior to studying this concept experimentally or numerically, advanced compact wire array loads must be developed and their scaling behavior understood. The 2008 Saturn planar array experiments extend the data set presented in Ref. [1], which studied planar arrays at {approx}3 MA, 100 ns in Saturn long pulse mode. Planar wire array power and yield scaling studies now include current levels directly applicable to multi-pinch experiments that could be performed on the 25 MA Z machine. A maximum total x-ray power of 15 TW (250 kJ in the main pulse, 330 kJ total yield) was observed with a 12-mm-wide planar array at 5.3 MA, 52 ns. The full data set indicates power scaling that is sub-quadratic with load current, while total and main pulse yields are closer to quadratic; these trends are similar to observations of compact cylindrical tungsten arrays on Z. We continue the investigation of energy coupling in these short pulse Saturn experiments using zero-dimensional-type implosion modeling and pinhole imaging, indicating 16 cm/?s implosion velocity in a 12-mm-wide array. The same phenomena of significant trailing mass and evidence for resistive heating are observed at 5 MA as at 3 MA. 17 kJ of Al K-shell radiation was obtained in one Al planar array fielded at 5.5 MA, 57 ns and we compare this to cylindrical array results in the context of a K-shell yield scaling model. We have also performed an initial study of compact 3 mm diameter cylindrical wire arrays, which are alternate candidates for a multi-pinch vacuum hohlraum concept. These massive 3.4 and 6 mg/cm loads may have been impacted by opacity, producing a maximum x-ray power of 7 TW at 4.5 MA, 45 ns. Future research directions in compact x-ray sources are discussed