When grassroots innovation movements encounter mainstream institutions: implications for models of inclusive innovation

Grassroots innovation movements (GIMs) can be regarded as initiators or advocates of alternative pathways of innovation. Sometimes these movements engage with more established science, technology and innovation (STI) institutions and development agencies in pursuit of their goals. In this paper, we argue that an important aspect to encounters between GIMs and mainstream STI institutions is the negotiation of different framings of grassroots innovation and development of policy models for inclusive innovation. These encounters can result in two different modes of engagement by GIMs; what we call insertion and mobilization. We illustrate and discuss these interrelated notions of framings and modes of engagement by drawing on three case studies of GIMs: the Social Technologies Network in Brazil, and the Honey Bee Network and People's Science Movements in India. The cases highlight that inclusion in the context of GIMs is not an unproblematic, smooth endeavour, and involves diverse interpretations and framings, which shape what and who gets included or excluded. Within the context of increasing policy interest, the analysis of encounters between GIMs and STI institutions can offer important lessons for the design of models of inclusive innovation and development

Laser fresnel distance measuring system and method

A method and system for determining range to a target are provided. A beam of electromagnetic energy is transmitted through an aperture in an opaque screen such that a portion of the beam passes through the aperture to generate a region of diffraction that varies as a function of distance from the aperture. An imaging system is focused on a target plane in the region of diffraction with the generated image being compared to known diffraction patterns. Each known diffraction pattern has a unique value associated therewith that is indicative of a distance from the aperture. A match between the generated image and at least one of the known diffraction patterns is indicative of a distance between the aperture and target plane

Leukocyte-specific protein 1 interacts with DC-SIGN and mediates transport of HIV to the proteasome in dendritic cells

Dendritic cells (DCs) capture and internalize human immunodeficiency virus (HIV)-1 through C-type lectins, including DC-SIGN. These cells mediate efficient infection of T cells by concentrating the delivery of virus through the infectious synapse, a process dependent on the cytoplasmic domain of DC-SIGN. Here, we identify a cellular protein that binds specifically to the cytoplasmic region of DC-SIGN and directs internalized virus to the proteasome. This cellular protein, leukocyte-specific protein 1 (LSP1), was defined biochemically by immunoprecipitation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. LSP1 is an F-actin binding protein involved in leukocyte motility and found on the cytoplasmic surface of the plasma membrane. LSP1 interacted specifically with DC-SIGN and other C-type lectins, but not the inactive mutant DC-SIGNΔ35, which lacks a cytoplasmic domain and shows altered virus transport in DCs. LSP1 diverts HIV-1 to the proteasome. Down-regulation of LSP1 with specific small interfering RNAs in human DCs enhanced HIV-1 transfer to T cells, and bone marrow DCs from lsp1−/− mice also showed an increase in transfer of HIV-1BaL to a human T cell line. Proteasome inhibitors increased retention of viral proteins in lsp1+/+ DCs, and substantial colocalization of virus to the proteasome was observed in wild-type compared with LSP1-deficient cells. Collectively, these data suggest that LSP1 protein facilitates virus transport into the proteasome after its interaction with DC-SIGN through its interaction with cytoskeletal proteins

Organ health and development in larval kingfish are unaffected by ocean acidification and warming

Anthropogenic CO₂ emissions are causing global ocean warming and ocean acidification. The early life stages of some marine fish are vulnerable to elevated ocean temperatures and CO₂ concentrations, with lowered survival and growth rates most frequently documented. Underlying these effects, damage to different organs has been found as a response to elevated CO₂ in larvae of several species of marine fish, yet the combined effects of acidification and warming on organ health are unknown. Yellowtail kingfish, Seriola lalandi, a circumglobal subtropical pelagic fish of high commercial and recreational value, were reared from fertilization under control (21 °C) and elevated (25 °C) temperature conditions fully crossed with control (500 µatm) and elevated (1,000 µatm) pCO₂ conditions. Larvae were sampled at 11 days and 21 days post hatch for histological analysis of the eye, gills, gut, liver, pancreas, kidney and liver. Previous work found elevated temperature, but not elevated CO₂, significantly reduced larval kingfish survival while increasing growth and developmental rate. The current histological analysis aimed to determine whether there were additional sublethal effects on organ condition and development and whether underlying organ damage could be responsible for the documented effects of temperature on survivorship. While damage to different organs was found in a number of larvae, these effects were not related to temperature and/or CO₂ treatment. We conclude that kingfish larvae are generally vulnerable during organogenesis of the digestive system in their early development, but that this will not be exacerbated by near-future ocean warming and acidification

Anticancer, Biophysical and Computational Investigations of Half-Sandwich Ruthenium(II) Thiosemicarbazone Complexes: The Effect of Arene \u3ci\u3eVersus\u3c/i\u3e Thiacrown Face-Cap

A series of half-sandwich ruthenium complexes, two containing an arene face-cap and the other a thiacrown ether face-cap were synthesized to investigate the necessity of the arene for anticancer activity in this class of compounds. The complexes are formulated as [(h6-p-cymene)Ru(dmabTSC)Cl]PF6, [(h6-benzene)Ru(dmabTSC)Cl]PF6 (arene complexes), and [([9]aneS3(dmabTSC)Cl]PF6 (dmabTSC = dimethylaminobenzaldehye thiosemicarbazone). It was observed that none of the complexes showed good anticancer activity in vitro against HCT-116 and Caco-2 (colon adenocarcinoma) cells. All three complexes can bind strongly to calf-thymus DNA with binding constants on the order of 105 M-1. In addition they all bind strongly to human serum albumin with binding constants between 105 and 106 M-1. There appears to be a single binding site on the protein for these complexes. A computational investigation of these complexes and their hydrolysis products was carried out by molecular docking with DNA and topoisomerase II. From this analysis it is noted that the type of face-capping ligand had different effects on the two macromolecules. It is therefore noted that the knowledge gained from this study will be useful in identifying the type of complexes in this class that show useful metallodrug potential

Synthesis, Characterisation, and Preliminary Anti-Cancer Photodynamic Therapeutic \u3ci\u3eIn Vitro\u3c/i\u3e Studies of Mixed-Metal Binuclear Ruthenium(II)-Vanadium(IV) Complexes

We report the synthesis and characterisation of mixed-metal binuclear ruthenium(II)-vanadium(IV) complexes, which were used as potential photodynamic therapeutic agents for melanoma cell growth inhibition. The novel complexes, [Ru(pbt)2(phen2DTT)](PF6)2•1.5H2O 1 (where phen2DTT = 1,4-bis(1,10-phenanthrolin-5-ylsulfanyl)butane-2,3-diol and pbt = 2-(2\u27-pyridyl)benzothiazole) and [Ru(pbt)2(tpphz)](PF6)2•3H2O 2 (where tpphz = tetrapyrido[3,2-a:2′,3′-c:3″,2″-h:2‴,3‴-j]phenazine) were synthesised and characterised. Compound 1 was reacted with [VO(sal-L-tryp)(H2O)] (where sal-L-tryp = N-salicylidene-L-tryptophanate) to produce [Ru(pbt)2(phen2DTT)VO(sal-L-tryp)](PF6)2•5H2O 4; while [VO(sal-L-tryp)(H2O)] was reacted with compound 2 to produce [Ru(pbt)2(tpphz)VO(sal-L-tryp)](PF6)2•6H2O 3. All complexes were characterised by elemental analysis, HRMS, ESI MS, UV-visible absorption, ESR spectroscopy, and cyclic voltammetry, where appropriate. In vitro cell toxicity studies (with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay) via dark and light reaction conditions were carried out with sodium diaqua-4,4\u27,4”,4”\u27tetrasulfophthalocyaninecobaltate(II) (Na4[Co(tspc)(H2O)2]), [VO(sal-L-tryp)(phen)]•H2O, and the chloride salts of complexes 3 and 4. Such studies involved A431, human epidermoid carcinoma cells; human amelanotic malignant melanoma cells; and HFF, non-cancerous human skin fibroblast cells. Both chloride salts of complexes 3 and 4 were found to be more toxic to melanoma cells than to non-cancerous fibroblast cells, and preferentially led to apoptosis of the melanoma cells over non-cancerous skin cells. The anti-cancer property of the chloride salts of complexes 3 and 4 was further enhanced when treated cells were exposed to light, while no such effect was observed on non-cancerous skin fibroblast cells. ESR and 51V NMR spectroscopic studies were also used to assess the stability of the chloride salts of complexes 3 and 4 in aqueous media at pH 7.19. This research illustrates the potential for using mixed-metal binuclear ruthenium(II)-vanadium(IV) complexes fighting skin cancer

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

Association of bradykinin receptor 2 (BDKRB2) variants with physical performance and muscle mass : findings from the LACE sarcopenia trial

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