Organizing the innovation process : complementarities in innovation networking

This paper contributes to the developing literature on complementarities in organizational design. We test for the existence of complementarities in the use of external networking between stages of the innovation process in a sample of UK and German manufacturing plants. Our evidence suggests some differences between the UK and Germany in terms of the optimal combination of innovation activities in which to implement external networking. Broadly, there is more evidence of complementarities in the case of Germany, with the exception of the product engineering stage. By contrast, the UK exhibits generally strong evidence of substitutability in external networking in different stages, except between the identification of new products and product design and development stages. These findings suggest that previous studies indicating strong complementarity between internal and external knowledge sources have provided only part of the picture of the strategic dilemmas facing firms

Identification of T cell stimulatory epitopes from the 18 kDa protein of Mycobacterium leprae

We have used different mouse strains to examine in vivo and in vitro responses to the 18 kDa protein of Mycobacterium leprae, which appears to be strongly immunogenic in both mice and humans. B and T cell stimulatory epitopes recognised by different strains of mice have been mapped using overlapping peptides that span the entire 18 kDa protein. Previous work established that Immunization of mice with the 18 kDa protein results in specific antibody production to common B cell epitopes and immunization of mice with peptides containing these B cell epitopes resulted in the induction of specific IgG to only a limited subset of epitopes in each strain. Now we report that T cells purified from mice immunized with peptides that stimulate antibody production, proliferate in vitro when rechallenged. The proliferating T cells produce levels of IL-2 and IFN-γ, that indicate antigen-specific T helper type 1 cells are present in significant numbers. Thus, a comparison of in vivo and in vitro data suggests that T cells bearing the phenotype associated with potentially protective cell-mediated responses can be primed in vivo by epitopes on small peptides. Since T cells from both strains of mice are capable of responding to the immunogenic synthetic peptides in vitro, but give different responses to the same peptides in vivo, factors other than epltope structure appear to influence T cell subset activation. This may have important implications for diseases such as leprosy where a polarized T cell response appears to develop and for the development of synthetic subunit vaccine

Configuration development study of the X-24C hypersonic research airplane

Bottom line results were made of a three-phase study to determine the feasibility of designing, building, and operating, and maintaining an air-launched high performance aircraft capable of cruising at speeds up to Mach 8 for short durations. The results show that Lockalloy heat-sink structure affords the capability for a 'work-horse' vehicle which can serve as an excellent platform for this research. It was further concluded that the performance of a blended wing body configuration surpassed that of a lifting body design for typical X-24C missions. The cost of a two vehicle program, less engines, B-52 modification and contractor support after delivery, can be kept within $70M (in Jan. 1976 dollars)

Rapid, Heuristic Discovery and Design of Promoter Collections in Non-Model Microbes for Industrial Applications

This is the author accepted manusript. The final version is available from American Chemical Society via the DOI in this recordAccession Codes: The sequence data for the four Geobacillus spp. used in this study have been submitted to the NCBI Sequence Read Archive and are available under the accession number PRJNA521450.Well-characterized promoter collections for synthetic biology applications are not always available in industrially relevant hosts. We developed a broadly applicable method for promoter identification in atypical microbial hosts that requires no a priori understanding of cis-regulatory element structure. This novel approach combines bioinformatic filtering with rapid empirical characterization to expand the promoter toolkit and uses machine learning to improve the understanding of the relationship between DNA sequence and function. Here, we apply the method in Geobacillus thermoglucosidasius, a thermophilic organism with high potential as a synthetic biology chassis for industrial applications. Bioinformatic screening of G. kaustophilus, G. stearothermophilus, G. thermodenitrificans, and G. thermoglucosidasius resulted in the identification of 636 100 bp putative promoters, encompassing the genome-wide design space and lacking known transcription factor binding sites. Eighty of these sequences were characterized in vivo, and activities covered a 2-log range of predictable expression levels. Seven sequences were shown to function consistently regardless of the downstream coding sequence. Partition modeling identified sequence positions upstream of the canonical -35 and -10 consensus motifs that were predicted to strongly influence regulatory activity in Geobacillus, and artificial neural network and partial least squares regression models were derived to assess if there were a simple, forward, quantitative method for in silico prediction of promoter function. However, the models were insufficiently general to predict pre hoc promoter activity in vivo, most probably as a result of the relatively small size of the training data set compared to the size of the modeled design space

X-ray Fluorescence Analysis of Feldspars and Silicate Glass: Effects of Melting Time on Fused Bead Consistency and Volatilisation

Reproducible preparation of lithium tetraborate fused beads for XRF analysis of glass and mineral samples is of paramount importance for analytical repeatability. However, as with all glass melting processes, losses due to volatilisation must be taken into account and their effects are not negligible. Here the effects of fused bead melting time have been studied for four Certified Reference Materials (CRM’s: three feldspars, one silicate glass), in terms of their effects on analytical variability and volatilisation losses arising from fused bead preparation. At melting temperatures of 1065 °C, and for feldspar samples, fused bead melting times shorter than approximately 25 min generally gave rise to a greater deviation of the XRF-analysed composition from the certified composition. This variation might be due to incomplete fusion and/or fused bead inhomogeneity but further research is needed. In contrast, the shortest fused bead melting time for the silicate glass CRM gave an XRF-analysed composition closer to the certified values than longer melting times. This may suggest a faster rate of glass-in-glass dissolution and homogenization during fused bead preparation. For all samples, longer melting times gave rise to greater volatilisation losses (including sulphates and halides) during fusion. This was demonstrated by a linear relationship between SO3 mass loss and time1/2, as predicted by a simple diffusion-based model. Iodine volatilisation displays a more complex relationship, suggestive of diffusion plus additional mechanisms. This conclusion may have implications for vitrification of iodine-bearing radioactive wastes. Our research demonstrates that the nature of the sample material impacts on the most appropriate fusion times. For feldspars no less than ~25 min and no more than ~60 min of fusion at 1065 °C, using Li2B4O7 as the fusion medium and in the context of feldspar samples and the automatic fusion equipment used here, strikes an acceptable (albeit non-ideal) balance between the competing factors of fused bead quality, analytical consistency and mitigating volatilisation losses. Conversely, for the silicate glass sample, shorter fusion times of less than ~30 min under the same conditions provided more accurate analyses whilst limiting volatile losses

Renewable energy in fisheries and aquaculture: Case studies from the United States

Fisheries and aquaculture are highly reliant on fossil fuels and must transition to renewable energy to reduce carbon emissions and meet global planetary heath goals. Here, we assessed total and renewable energy use in farmed catfish and wild-caught salmon, two of the largest seafood sectors in the United States (U.S.). Interviews were used to explore participants’ views of key barriers and opportunities to replace fossil fuel use. Modeled scenarios were used to assess changes in grid source energy and electricity costs for the farmed catfish sector using the U.S. EIA National Energy Modeling System. We found that renewable energy makes up 5% of direct energy use in catfish aquaculture in Mississippi and Alabama. Catfish industry interviewees indicate that cheap electricity costs and diurnal energy use are barriers to onsite implementation of renewables. Projected renewable energy use for the catfish sector could be as high as 41% of total direct energy use in 2050 under modeled scenarios, which would result in 86% lower CO2 emissions but 34% higher electricity costs. For wild-capture pink salmon from Prince William Sound, Alaska (AK) and sockeye salmon from Bristol Bay, AK, renewable energy makes up 2% and 0% of direct energy use, respectively. Wild-caught salmon industry interviewees identified the short duration of the fishing season as a barrier for onsite renewable energy, though there is a desire for more regional renewable energy technologies to lower electricity costs and increase reliability. Proposed renewable energy projects at utilities in fish processing towns in AK would only make modest improvements in the share of direct energy from renewables due to fuel use by fishing vessels. This is the first study to characterize current and potential renewable energy use among parts of the fisheries and aquaculture sectors in the U.S. We found that energy needs for fisheries and aquaculture are influenced by their often-remote location, production methods, and seasonal energy demands, which require context-specific solutions. There is the need for federal and state policies and incentives to shift energy sources used in these sectors to meet national and international climate change goals while supporting food security.publishedVersio

Alkane-modified short polyethyleneimine for siRNA delivery

RNA interference (RNAi) is a highly specific gene-silencing mechanism triggered by small interfering RNA (siRNA). Effective intracellular delivery requires the development of potent siRNA carriers. Here, we describe the synthesis and screening of a series of siRNA delivery materials. Short polyethyleneimine (PEI, Mw 600) was selected as a cationic backbone to which lipid tails were conjugated at various levels of saturation. In solution these polymer–lipid hybrids self-assemble to form nanoparticles capable of complexing siRNA. The complexes silence genes specifically and with low cytotoxicity. The efficiency of gene knockdown increased as the number of lipid tails conjugated to the PEI backbone increased. This is explained by reducing the binding affinity between the siRNA strands to the complex, thereby enabling siRNA release after cellular internalization. These results highlight the importance of complexation strength when designing siRNA delivery materials.Misrock FoundationAmerican Society for Engineering Education. National Defense Science and Engineering Graduate FellowshipNational Institutes of Health (U.S) (Grant EB000244)National Cancer Institute (U.S.) (MIT-Harvard Center of Cancer Nanotechnology Excellence. Grant CA151884)National Science Foundation (U.S.)Massachusetts Institute of Technology (Presidential Fellowships

Longitudinal cohort of HIV-negative transgender women of colour in New York City: protocol for the TURNNT ('Trying to Understand Relationships, Networks and Neighbourhoods among Transgender women of colour') study.

IntroductionIn the USA, transgender women are among the most vulnerable to HIV. In particular, transgender women of colour face high rates of infection and low uptake of important HIV prevention tools, including pre-exposure prophylaxis (PrEP). This paper describes the design, sampling methods, data collection and analyses of the TURNNT ('Trying to Understand Relationships, Networks and Neighbourhoods among Transgender women of colour') study. In collaboration with communities of transgender women of colour, TURNNT aims to explore the complex social and environmental (ie, neighbourhood) structures that affect HIV prevention and other aspects of health in order to identify avenues for intervention.Methods and analysesTURNNT is a prospective cohort study, which will recruit 300 transgender women of colour (150 Black/African American, 100 Latina and 50 Asian/Pacific Islander participants) in New York City. There will be three waves of data collection separated by 6 months. At each wave, participants will provide information on their relationships, social and sexual networks, and neighbourhoods. Global position system technology will be used to generate individual daily path areas in order to estimate neighbourhood-level exposures. Multivariate analyses will be conducted to assess cross-sectional and longitudinal, independent and synergistic associations of personal relationships (notably individual social capital), social and sexual networks, and neighbourhood factors (notably neighbourhood-level social cohesion) with PrEP uptake and discontinuation.Ethics and disseminationThe TURNNT protocol was approved by the Columbia University Institutional Review Board (reference no. AAAS8164). This study will provide novel insights into the relationship, network and neighbourhood factors that influence HIV prevention behaviours among transgender women of colour and facilitate exploration of this population's health and well-being more broadly. Through community-based dissemination events and consultation with policy makers, this foundational work will be used to guide the development and implementation of future interventions with and for transgender women of colour