Chronology of the site of Grotte du Renne, Arcy-sur-Cure, France: implications for Neanderthal symbolic behaviour

Higham et al (2010) published a large series of new dates from the key French Palaeolithic site of the Grotte du Renne at Arcy-sur-Cure. The site is important because it is one of only two sites in Europe in which Châtelperronian lithic remains co-occur with Neanderthal human remains. A large series of dates from the Mousterian, Châtelperronian, Aurignacian and Gravettian levels of the site was obtained. The 14C results showed great variability, which Higham et al (2010) interpreted as most likely to be due to mixing of archaeological material in the site. In contrast, Caron et al (2011) suggested that the site stratigraphy is well preserved and that the problem with the variability in the radiocarbon ages was due to unremoved contamination in the dated bone. In this paper we address their critique of the original Higham et al (2010) paper

Elucidating the mechanism and active site of the cyclohexanol dehydrogenation on copper-based catalysts: A density functional theory study

Abstract The dehydrogenation of cyclohexanol to cyclohexanone is very important in the manufacture of nylon. Copper-based catalysts are the most popular catalysts for this reaction, and on these catalysts the reaction mechanism and active site are in debate. In order to elucidate the mechanism and active site of the cyclohexanol dehydrogenation on copper-based catalysts, density functional theory with dispersion corrections were performed on up to six facets of copper in two different oxidation states: monovalent copper and metallic copper. By calculating the surface energies of these facets, Cu(111) and Cu2O(111) were found to be the most stable facets for metallic copper and for monovalent copper, respectively. On these two facets, all the possible elementary steps in the dehydrogenation pathway of cyclohexanol were calculated, including the adsorption, dehydrogenation, hydrogen coupling and desorption. Two different reaction pathways for dehydrogenation were considered on both surfaces. It was revealed that the dehydrogenation mechanisms are different on these two surfaces: on Cu(111) the hydrogen belonging to the hydroxyl is removed first, then the hydrogen belonging to the carbon is subtracted, while on Cu2O(111) the hydrogen belonging to the carbon is removed followed by the subtraction of the hydrogen in the hydroxyl group. Furthermore, by comparing the energy profiles of these two surfaces, Cu2O(111) was found to be more active for cyclohexanol dehydrogenation than Cu(111). In addition, we found that the coordinatively unsaturated copper sites on Cu2O(111) are the reaction sites for all the steps. Therefore, the coordinatively unsaturated copper site on Cu2O(111) is likely to be the active site for cyclohexanol dehydrogenation on the copper-based catalysts.

A potentiometric biosensor for rapid on-site disease diagnostics

Quantitative point-of-care (POC) devices are the next generation for serological disease diagnosis. Whilst pathogen serology is typically performed by centralized laboratories using Enzyme-Linked ImmunoSorbent Assay (ELISA), faster on-site diagnosis would infer improved disease management and treatment decisions. Using the model pathogen Bovine Herpes Virus-1 (BHV-1) this study employs an extended-gate field-effect transistor (FET) for direct potentiometric serological diagnosis. BHV-1 is a major viral pathogen of Bovine Respiratory Disease (BRD), the leading cause of economic loss ($2 billion annually in the US only) to the cattle and dairy industry. To demonstrate the sensor capabilities as a diagnostic tool, BHV-1 viral protein gE was expressed and immobilized on the sensor surface to serve as a capture antigen for a BHV-1-specific antibody (anti-gE), produced in cattle in response to viral infection. The gE-coated immunosensor was shown to be highly sensitive and selective to anti-gE present in commercially available anti-BHV-1 antiserum and in real serum samples from cattle with results being in excellent agreement with Surface Plasmon Resonance (SPR) and ELISA. The FET sensor is significantly faster than ELISA (<10 min), a crucial factor for successful disease intervention. This sensor technology is versatile, amenable to multiplexing, easily integrated to POC devices, and has the potential to impact a wide range of human and animal diseases.

A two-site, population-based study of barriers to cataract surgery in rural china.

PURPOSE: China has among the lowest cataract surgical rates in Asia. This study was conducted to identify barriers to cataract surgery in rural China. METHODS: All subjects having undergone cataract surgery and persons with presenting visual acuity <or=6/60 (in Yangjiang) or <or=6/18 (in Handan) in >or=1 eye due to nonsurgically treated cataract were identified in two population-based studies in southern (Yangjiang) and northern (Handan) China. The subjects were administered a questionnaire assessing attitudes in four areas constituting potential barriers to surgery: knowledge about cataract, perceptions of local surgical quality, transportation and cost, and available resources. RESULTS: Interviews were completed on 71% to 86% of eligible subjects in both sites. Interviewed subjects did not differ significantly from nonrespondents with regard to age, sex, and presenting acuity in the better-seeing eye. A total of 214 (80.4%) nonsurgical and 131 (76.6%) surgical participants were interviewed, with a mean age of 71.8 +/- 8.0 and 73.7 +/- 7.4 years, respectively (P > 0.1). Among the nonsurgical subjects, 67.8% were blind (presenting vision, <or=6/60) in >or=1 eye due to cataract, whereas among the surgical participants, 25.2% remained blind in the eye that had undergone surgical removal of the cataract. In a multivariate analysis adjusted for age, sex, and site, increased knowledge and higher estimates of the quality of surgery were associated with having had surgery, whereas cost and transportation scores were not. CONCLUSIONS: Lack of knowledge about cataract and concerns about the quality of local services appear to be the principal barriers to cataract surgery in rural China.

Probing a 3,4'-bis-guanidinium diaryl derivative as an allosteric inhibitor of the Ras pathway

Mutations in the Ras-pathway occur in 40–45% of colorectal cancer patients and these are refractory to treatment with anti-EGFR-targeted therapies. With this in mind, we have studied novel guanidinium- based compounds with demonstrated ability to inhibit protein kinases. We have performed docking stud- ies with several proteins involved in the Ras-pathway and evaluated 3,40-bis-guanidinium derivatives as inhibitors of B-Raf. Compound 3, the most potent in this series, demonstrated strong cytotoxicity in WTB-Raf colorectal cancer cells and also cells with V600EB-Raf mutations. Cell death was induced by apop- tosis, detected by cleavage of PARP. Compound 3 also potently inhibited ERK1/2 signalling, inhibited EGFR activation, as well as Src, STAT3 and AKT phosphorylation. Mechanistically, compound 3 did not inhibit ATP binding to B-Raf, but direct assay of B-Raf activity was inhibited in vitro. Summarizing, we have identified a novel B-Raf type-III inhibitor that exhibits potent cellular cytotoxicity

A Molecular Mechanism for Sequential Activation of a G Protein-Coupled Receptor

Ligands targeting G protein-coupled receptors (GPCRs) are currently classified as either orthosteric, allosteric, or dualsteric/bitopic. Here, we introduce a new pharmacological concept for GPCR functional modulation: sequential receptor activation. A hallmark feature of this is a stepwise ligand binding mode with transient activation of a first receptor site followed by sustained activation of a second topographically distinct site. We identify 4-CMTB (2-(4-chlorophenyl)-3-methyl-N-(thiazol-2-yl)butanamide), previously classified as a pure allosteric agonist of the free fatty acid receptor 2, as the first sequential activator and corroborate its two-step activation in living cells by tracking integrated responses with innovative label-free biosensors that visualize multiple signaling inputs in real time. We validate this unique pharmacology with traditional cellular readouts, including mutational and pharmacological perturbations along with computational methods, and propose a kinetic model applicable to the analysis of sequential receptor activation. We envision this form of dynamic agonism as a common principle of nature to spatiotemporally encode cellular information.

Continuing the fight in reducing the risk of surgical site infections in the perioperative environment

Assessing risk has become part of the process of supporting patients andmaintaining safety in the healthcare setting. The risk of healthcare associatedinfections (HCAIs) has long been well documented and surgical site infection (SSI)is recognised as one of the most prevalent (Tanner & Khan 2008, Wilson 2013a).

Project Management within an Urban Site Context: Issues considering External Stakeholders

Large construction projects create numerous hazards, making it one of the most dangerous industries in which to work. This element of risk increases in urban areas and can have a negative impact on the external stakeholders associated with the project, along with their surrounding environments. The aim of this paper is to identify and document, in an urban context, the numerous issues encountered by on-site project managers from external stakeholders and how they affect a construction project. In addressing this aim, the core objective is to identify what issues are involved in the management of these stakeholders. In order to meet this requirement, a qualitative methodology encompassing an informative literature review followed by five individual case study interviews. The data gathered is assessed qualitatively using mind mapping software. A number of issues are identified which have an impact on the external stakeholders involved, and also how they affected proceedings on site. Collectively the most commonly occurring issues are environmental, legal, health and safety and communication issues. These ranged from road closures and traffic disruption to noise, dust and vibrations from site works. It is anticipated that the results of this study will assist and aid project managers in identifying issues considering external stakeholders, particularly on urban construction projects. A wide range of issues can develop depending on the complexity and nature of each project, but this research will illustrate and reinforce to project managers, that identifying issues early, effective communication and appropriate liaising can be used to manage the issues considering external stakeholders.