Can Weak Substitution be Rehabilitated?

This paper develops a graphical analysis and an analytical model that demonstrate how weak substitution can be used for non-market valuation. Both weak complementarity and weak substitution can be evaluated as restrictions that allow quantity or quality changes in non-market goods to be described as price changes that yield equivalent changes in individual well being. They are Hicksian equivalents in that the price changes yield the same utility changes as would the quantity or quality changes. After discussion of several potential applications of weak substitution, the paper develops the parallel between the restriction and recent strategies from modeling differentiated goods.

Targeting Nucleotide Biosynthesis: A Strategy for Improving the Oncolytic Potential of DNA Viruses

The rapid growth of tumors depends upon elevated levels of dNTPs, and while dNTP concentrations are tightly regulated in normal cells, this control is often lost in transformed cells. This feature of cancer cells has been used to advantage to develop oncolytic DNA viruses. DNA viruses employ many different mechanisms to increase dNTP levels in infected cells, because the low concentration of dNTPs found in non-cycling cells can inhibit virus replication. By disrupting the virus-encoded gene(s) that normally promote dNTP biosynthesis, one can assemble oncolytic versions of these agents that replicate selectively in cancer cells. This review covers the pathways involved in dNTP production, how they are dysregulated in cancer cells, and the various approaches that have been used to exploit this biology to improve the tumor specificity of oncolytic viruses. In particular, we compare and contrast the ways that the different types of oncolytic virus candidates can directly modulate these processes. We limit our review to the large DNA viruses that naturally encode homologs of the cellular enzymes that catalyze dNTP biogenesis. Lastly, we consider how this knowledge might guide future development of oncolytic viruses

Hyperspectral Imager for the Coastal Ocean (HICO): Overview, Operational Updates, and Coastal Ocean Applications

The Hyperspectral Imager for the Coastal Ocean (HICO) was built to measure inwater properties of complex coastal regions. HICO enables synoptic coverage; 100meter spatial resolution for sampling the variability and spatial irregularity of coastal waters; and high spectral resolution to untangle the signals from chlorophyll, colored dissolved organic matter, suspended sediments and varying bottom types. HICO was built by the Naval Research Laboratory, installed on the International Space Station (ISS) in September 2009, and operated for ONR for the first three years. In 2013, NASA assumed sponsorship of operations in order to leverage HICO's ability to address their Earth monitoring mission. This has opened up access of HICO data to the broad research community. Over 8000 images are now available on NASA's Ocean Color Website (http://oceancolor.gsfc.nasa.gov/cgi/browse.pl?sen=hi). Oregon State University's HICO website (http://hico.coas.oregonstate.edu) remains the portal for researchers to request new collections and access their requested data. We will present updates on HICO's calibration and improvements in geolocation and show examples of the use of HICO data to address issues in the coastal ocean and Great Lakes

Standardization of electroencephalography for multi-site, multi-platform and multi-investigator studies: Insights from the canadian biomarker integration network in depression

Subsequent to global initiatives in mapping the human brain and investigations of neurobiological markers for brain disorders, the number of multi-site studies involving the collection and sharing of large volumes of brain data, including electroencephalography (EEG), has been increasing. Among the complexities of conducting multi-site studies and increasing the shelf life of biological data beyond the original study are timely standardization and documentation of relevant study parameters. We presentthe insights gained and guidelines established within the EEG working group of the Canadian Biomarker Integration Network in Depression (CAN-BIND). CAN-BIND is a multi-site, multi-investigator, and multiproject network supported by the Ontario Brain Institute with access to Brain-CODE, an informatics platform that hosts a multitude of biological data across a growing list of brain pathologies. We describe our approaches and insights on documenting and standardizing parameters across the study design, data collection, monitoring, analysis, integration, knowledge-translation, and data archiving phases of CAN-BIND projects. We introduce a custom-built EEG toolbox to track data preprocessing with open-access for the scientific community. We also evaluate the impact of variation in equipment setup on the accuracy of acquired data. Collectively, this work is intended to inspire establishing comprehensive and standardized guidelines for multi-site studies

"They go for gender first"

There have been many recent media reports about the online harassment of women journalists working in technology, particularly the video gaming industry. However, little research has focused on this aspect, by looking at specific occupations, or analysing the implications for women and society. This paper is a feminist study of the experiences of sexist abuse of a sample of women journalists writing about technology. It is a commentary on the results of a questionnaire-based study of 102 women (and their approximately 300 comments) that work in what has emerged as one of the frontlines of the struggle for gender equality. The research looks at the extent of the abuse, the harm it causes and how women are reacting to it. Most of the participants have experienced abuse, many have changed their working practices and some have disguised their identity to avoid it. An examination of their comments suggests that sexist abuse is now often normalised, alongside a new kind of "invisible" feminism. It also reveals a mood of defiance and an appetite for radical change to address the problems of exclusion and loss of identity. Overall, results indicate that the abuse is damaging women’s lives and impacting journalism and society in a negative way

In Vivo Response to Methotrexate Forecasts Outcome of Acute Lymphoblastic Leukemia and Has a Distinct Gene Expression Profile

William Evans and colleagues investigate the genomic determinants of methotrexate resistance and interpatient differences in methotrexate response in patients newly diagnosed with childhood acute lymphoblastic leukemia

Glycan shifting on hepatitis C virus (HCV) E2 glycoprotein is a mechanism for escape from broadly neutralizing antibodies

Hepatitis C virus (HCV) infection is a major cause of liver disease and hepatocellular carcinoma. Glycan shielding has been proposed to be a mechanism by which HCV masks broadly neutralizing epitopes on its viral glycoproteins. However, the role of altered glycosylation in HCV resistance to broadly neutralizing antibodies is not fully understood. Here, we have generated potent HCV neutralizing antibodies hu5B3.v3 and MRCT10.v362 that, similar to the previously described AP33 and HCV1, bind to a highly conserved linear epitope on E2. We utilize a combination of in vitro resistance selections using the cell culture infectious HCV and structural analyses to identify mechanisms of HCV resistance to hu5B3.v3 and MRCT10.v362. Ultra deep sequencing from in vitro HCV resistance selection studies identified resistance mutations at asparagine N417 (N417S, N417T and N417G) as early as 5 days post treatment. Comparison of the glycosylation status of soluble versions of the E2 glycoprotein containing the respective resistance mutations revealed a glycosylation shift from N417 to N415 in the N417S and N417T E2 proteins. The N417G E2 variant was glycosylated neither at residue 415 nor at residue 417 and remained sensitive to MRCT10.v362. Structural analyses of the E2 epitope bound to hu5B3.v3 Fab and MRCT10.v362 Fab using X-ray crystallography confirmed that residue N415 is buried within the antibody–peptide interface. Thus, in addition to previously described mutations at N415 that abrogate the β-hairpin structure of this E2 linear epitope, we identify a second escape mechanism, termed glycan shifting, that decreases the efficacy of broadly neutralizing HCV antibodies

The need to promote behaviour change at the cultural level: one factor explaining the limited impact of the MEMA kwa Vijana adolescent sexual health intervention in rural Tanzania. A process evaluation

Background - Few of the many behavioral sexual health interventions in Africa have been rigorously evaluated. Where biological outcomes have been measured, improvements have rarely been found. One of the most rigorous trials was of the multi-component MEMA kwa Vijana adolescent sexual health programme, which showed improvements in knowledge and reported attitudes and behaviour, but none in biological outcomes. This paper attempts to explain these outcomes by reviewing the process evaluation findings, particularly in terms of contextual factors. Methods - A large-scale, primarily qualitative process evaluation based mainly on participant observation identified the principal contextual barriers and facilitators of behavioural change. Results - The contextual barriers involved four interrelated socio-structural factors: culture (i.e. shared practices and systems of belief), economic circumstances, social status, and gender. At an individual level they appeared to operate through the constructs of the theories underlying MEMA kwa Vijana - Social Cognitive Theory and the Theory of Reasoned Action – but the intervention was unable to substantially modify these individual-level constructs, apart from knowledge. Conclusion - The process evaluation suggests that one important reason for this failure is that the intervention did not operate sufficiently at a structural level, particularly in regard to culture. Recently most structural interventions have focused on gender or/and economics. Complementing these with a cultural approach could address the belief systems that justify and perpetuate gender and economic inequalities, as well as other barriers to behaviour change