Disruption of HOX activity leads to cell death that can be enhanced by the interference of iron uptake in malignant B cells.

The HOX genes encode a family of transcription factors that are dysregulated in several malignancies and have been implicated in oncogenesis and cancer cell survival. Disruption of HOX protein function using the peptide HXR9 has shown anti-tumor effects against melanoma, lung cancer and renal cancer. In this report, we evaluated the expression of all 39 HOX genes in a panel of six malignant B-cell lines, including multiple myeloma cells and found different levels of expression of HOX family members suggesting that they also have a role in malignant B-cell survival. We show that disrupting HOX function using the peptide HXR9 induces significant cytotoxicity in the entire panel of cell lines. Importantly, we found that the cytotoxic effects of HXR9 can be enhanced by combining it with ch128.1Av, an antibody-avidin fusion protein specific for the human transferrin receptor 1 (CD71). Iron starvation induced by the fusion protein contributes to the enhanced effect and involves, at least in part, the induction of a caspase-independent pathway. These results show the relevance of HOX proteins in malignant B-cell survival and suggest that our therapeutic strategy may be effective in the treatment of incurable B-cell malignancies such as multiple myeloma

Surveys as cultural artefacts : applying the international self-report delinquency study to Latin American adolescents

Survey instruments are often watermarked with the language, thought patterns, experience and expectations of their designers’ cultural world. This creates some evident challenges when using surveys in international research projects (for example, in finding equivalent terms in translation), but also some less evident ones deriving from potentially hidden local variations in social experience, values and cognition. Using examples from the International Self-Report Delinquency Study, this article identifies several potential challenges to measurement that arise when an instrument designed with the youth of industrialized democracies in mind is presented to adolescents in a Latin American country (Venezuela). Some strategies for addressing these challenges are outlined

Comparative study of the performance of three cross-flow ceramic membranes for water treatment

Several tests using water as effluent are used to analyse the performance of three types of microfiltration cross-flow ceramicmembranes. Two of these membranes are commercial (Atech and Membralox/US Filter) and the third one is experimental.The main differences between them lie in their chemical composition (different origin of raw materials) and in their manufacturingprocess. The results presented here show the dominant effect of the filtering and the gel layer. Both are formed during operationacting as equalising agent between the three membranes. The membranes tested have similar performances in cross-flowoperation, although permeability rates for the membrane Membralox/US Filter were about 15% higher. This increase might be due to the smoother surface formed by a second filtering ultrafiltration layer (0.01 ìm) of 10 ìm width, which probably contributes to a decrease in the thickness of the gel layer formed during operation. Using specific raw materials (non-industrial) as well as a second ultrafiltration layer improves the results in operation (performances and cleaning intervals). However, they are uneconomical because of the extra costs involved.In conclusion, low-cost membranes can achieve similar results to the commercial and more expensive ones opening up their application to new uses and emergent markets

Integrating Soluble Biomarkers and Imaging Technologies in the Identification of Vulnerable Atherosclerotic Patients

The clinical utility of a biomarker depends on its ability to identify high-risk individuals to optimally manage the patient. A new biomarker would be of clinical value if it is accurate and reliable, provides good sensitivity and specificity, and is available for widespread application. Data are accumulating on the potential clinical utility of integrating imaging technologies and circulating biomarkers for the identification of vulnerable (high-risk) cardiovascular patients. A multi-biomarker strategy consisting of markers of inflammation, hemostasis and thrombosis, proteolysis and oxidative stress, combined with new imaging modalities (optical coherence tomography, virtual histology plus IVUS, PET) can increase our ability to identify such thombosis-prone patients. In an ideal scenario, cardiovascular biomarkers and imaging combined will provide a better diagnostic tool to identify high-risk individuals and also more efficient methods for effective therapies to reduce such cardiovascular risk. However, additional studies are required in order to show that this approach can contribute to improved diagnostic and therapeutic of atherosclerotic disease

The IGN-E case: Integrating through a hidden ontology

National Geographic Institute of Spain (IGN-E) wanted to integrate its main information sources for building a common vocabulary reference and thus to manage the huge amount of information it held. The main problem of this integration is the great heterogeneity of data sources. The Ontology Engineering Group (OEG) is working with IGN-E to attain this objective in two phases: first, by creating automatically an ontology using the semantics of catalogues sections, and second, by discovering mappings automatically that can relate ontology concepts to database instances. So, these mappings are the instruments to break the syntactic, semantic and granularity heterogeneity gap. We have developed software for building a first ontology version and for discovering automatically mappings using techniques that take into account all types of heterogeneity. The ontology contains a set of extra-attributes which are identified in the building process. The ontology, called PhenomenOntology, will be reviewed by domain experts of IGN-E. The automatic mapping discovery will be also used for discovering new knowledge that will be added to the ontology. For increasing the usability and giving independence to different parts, the processes of each phase will be designed automatically and as upgradeable as possible

Biohydrogen production from diary processing wastewater by anaerobic biofilm reactors

Fermentative hydrogen production was studied in packed bed batch reactors to assess the influence of environmental factors over yield hydrogen production from dairy wastewater. Dried stems of Opuntia imbricata were used as substratum adding a pretreated mixed culture for biofilm formation. Experimental results showed that, yield hydrogen production was significantly affected by initial COD concentration, temperature and dairy wastewater pH. Maximum yield obtained was 12.73 mM H2/g CODc when initial COD concentration was 21.1 g COD, dairy wastewater pH with no adjustment (11.32) and room temperature of 16 ± 3°C. Methane production was completely inhibit at an initial pH of 4 at all temperature studied (final pH 4.06), meanwhile, with an initial pH of 11.32, with exception for 16°C, methanogenic activity was not completely inhibit when final pH was over 5, showing an increase in methane production of 0.35 to 0.75 g CH4/l for 35 to 55°C.Key words: Biofilm, dairy wastewater, hydrogen, Opuntia imbricat

Geant4-GATE Simulation of a Large Plastic Scintillator for Muon Radiography

Envisaging the possibility of using large-area plastic scintillator slabs as robust detectors for high spatial resolution muon radiography, and prior to prototype development, we study expected basic performance by Monte Carlo simulation. We present preliminary results for a scalable square footprint detector unit of similar to 1 m(2), defining a representative simulation model volume of 50 cm x 50 cm, with reflective surfaces and a light readout by direct coupling of 4 small PMTs (in a square arrangement) at one face of the scintillator slab. Light detection efficiency is calculated for several light collection configurations, considering different values of surface roughness, reflectivity, optical coupling index and scintillator thickness. Values maximizing photon detection have been identified. The light response function of 2.5-3.5 cm diameter PMTs for the proposed configuration has been determined. A detector intrinsic spatial resolution of the order of 1 cm is estimated for muon interactions at the center region of the detector module, using a simple centroid positioning algorithm (Anger logic)

“You and your laws and us with our laws” : a murderer’s stories navigate conflicting normative domains

Employing Labov’s structural model of stories and Schönbach’s typology of accounts, we examine an interview with a murderer in Venezuela and compare two stories that were narrated within it: one about the murder and one about his family life. While most of the first story accounted for the murder by calling on values and norms that attach to the criminal subculture, it also evaluated the crime from the perspective of a conventional framework that recognized the importance of family. The second story was set within that same family framework, revealing a conflict between different normative demands made on the murderer. He resolved it by finally giving primacy to his subcultural values and identity

Evidence for global cooling in the Late Cretaceous

PublishedArticleThe Late Cretaceous ‘greenhouse’ world witnessed a transition from one of the warmest climates of the past 140 million years to cooler conditions, yet still without significant continental ice. Low-latitude sea surface temperature (SST) records are a vital piece of evidence required to unravel the cause of Late Cretaceous cooling, but high-quality data remain illusive. Here, using an organic geochemical palaeothermometer (TEX86), we present a record of SSTs for the Campanian–Maastrichtian interval (~83–66 Ma) from hemipelagic sediments deposited on the western North Atlantic shelf. Our record reveals that the North Atlantic at 35 °N was relatively warm in the earliest Campanian, with maximum SSTs of ~35 °C, but experienced significant cooling (~7 °C) after this to <~28 °C during the Maastrichtian. The overall stratigraphic trend is remarkably similar to records of high-latitude SSTs and bottom-water temperatures, suggesting that the cooling pattern was global rather than regional and, therefore, driven predominantly by declining atmospheric pCO2 levels.We gratefully acknowledge funding from the German Science Foundation (DFG Research Stipend Li 2177/1-1 to C.L.), a Royal Society (UK) URF (S.A.R.), a NERC (UK) grant (J.A.L.), a NERC (UK) studentship (K.L.), The Curry Fund of UCL (C.L.), the Cushman Foundation for Foraminiferal Research (J.M. Resig Fellowship to F.F.) and the Spanish Ministerio de Ciencia e Innovación project CGL2011-22912, co-financed by the European Regional Development Fund (I.P.-R., J.A.A., J.A.L.). We thank T. Dunkley-Jones and J. Young for assistance in collecting the samples and S. Schouten for providing TEX86L data from Demerara Rise. This paper is dedicated to Ernie Russell, who sadly died after submission of the manuscript