134 research outputs found
Enhanced spatial state feedback for night vision goggle displays
A preliminary study was conducted to investigate the use of visual flow cues as an aid to ground and vertical drift awareness
during helicopter flight and targeting while using night vision goggles (NVG's). Three displays were compared: 1) NVG
display: simulated NVG image of cockpit and external environment; 2) Overlay display: NVG image with an overlay of a
flow cue field and a surrounding wire-frame globe; 3) Cut-out display: same as the Overlay display but with symbology
removed from the central region (leaving an unobscured 20 degree field-of-view of the NVG image). Three levels of contrast
were also compared using each display type. The visual scenery was displayed to subjects using a helmet-mounted virtual
reality device that had a 40 X 50 degree field-of-view liquid crystal displayCharles Stark Draper Laboratory under grant DL-H-496004
Acid-Labile Traceless Click Linker for Protein Transduction
Intracellular delivery of active proteins presents an interesting approach in research and therapy. We created a protein transduction shuttle based on a new traceless click linker that combines the advantages of click reactions with implementation of reversible pH-sensitive bonds. The azidomethyl-methylmaleic anhydride (AzMMMan) linker was found compatible with different click chemistries, demonstrated in bioreversible protein modification with dyes, polyethylene glycol, or a transduction carrier. Linkages were stable at physiological pH but reversible at the mild acidic pH of endosomes or lysosomes. We show that pH-reversible attachment of a defined endosome-destabilizing three-arm oligo(ethane amino)amide carrier generates an effective shuttle for protein delivery. The cargo protein nlsEGFP, when coupled via the traceless AzMMMan linker, experiences efficient cellular uptake and endosomal escape into the cytosol, followed by import into the nucleus. In contrast, irreversible linkage to the same shuttle hampers nuclear delivery of nlsEGFP which after uptake remains trapped in the cytosol. Successful intracellular delivery of bioactive ß-galactosidase as a model enzyme was also demonstrated using the pH-controlled shuttle system
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Characterization of aerosol growth events over Ellesmere Island during the summers of 2015 and 2016
The occurrence of frequent aerosol nucleation and growth events in the Arctic
during summertime may impact the region's climate through increasing the
number of cloud condensation nuclei in the Arctic atmosphere. Measurements of
aerosol size distributions and aerosol composition were taken during the
summers of 2015 and 2016 at Eureka and Alert on Ellesmere Island in Nunavut,
Canada. These results provide a better understanding of the frequency and
spatial extent of elevated Aitken mode aerosol concentrations as well as of
the composition and sources of aerosol mass during particle growth. Frequent
appearances of small particles followed by growth occurred throughout the
summer. These particle growth events were observed beginning in June with the
melting of the sea ice rather than with the polar sunrise, which strongly
suggests that influence from the marine boundary layer was the primary cause
of the events. Correlated particle growth events at the two sites, separated
by 480 km, indicate conditions existing over large scales play a key role in
determining the timing and the characteristics of the events.
In addition, aerosol mass spectrometry measurements were used to analyze the
size-resolved chemical composition of aerosols during two selected growth
events. It was found that particles with diameters between 50 and 80 nm
(physical diameter) during these growth events were predominately organic
with only a small sulfate contribution. The oxidation of the organics also
changed with particle size, with the fraction of organic acids increasing
with diameter from 80 to 400 nm.
The growth events at Eureka were observed most often when the temperature
inversion between the sea and the measurement site (at 610 m a.s.l.) was
non-existent or weak, presumably creating conditions with low aerosol
condensation sink and allowing fresh marine emissions to be mixed upward to
the observatory's altitude. While the nature of the gaseous precursors
responsible for the growth events is still poorly understood, oxidation of
dimethyl sulfide alone to produce particle-phase sulfate or
methanesulfonic acid was inconsistent with the measured aerosol composition,
suggesting the importance of other gas-phase organic compounds condensing for
particle growth.</p
Neuropilin-1 antagonism in human carcinoma cells inhibits migration and enhances chemosensitivity
BACKGROUND: Neuropilin-1 (NRP1) is a non-tyrosine kinase receptor for vascular endothelial growth factor (VEGF) recently implicated in tumour functions.METHODS: In this study we used a specific antagonist of VEGF binding to the NRP1 b1 domain, EG3287, to investigate the functional roles of NRP1 in human carcinoma cell lines, non-small-cell lung A549, kidney ACHN, and prostate DU145 cells expressing NRP1, and the underlying mechanisms involved.RESULTS: EG3287 potently displaced the specific binding of VEGF to NRP1 in carcinoma cell lines and significantly inhibited the migration of A549 and ACHN cells. Neuropilin-1 downregulation by siRNA also decreased cell migration. EG3287 reduced the adhesion of A549 and ACHN cells to extracellular matrix (ECM), and enhanced the anti-adhesive effects of a beta 1-integrin function-blocking antibody. EG3287 increased the cytotoxic effects of the chemotherapeutic agents 5-FU, paclitaxel, or cisplatin on A549 and DU145 cells, through inhibition of integrin-dependent cell interaction with the ECM.CONCLUSIONS: These findings indicate that NRP1 is important for tumour cell migration and adhesion, and that NRP1 antagonism enhances chemosensitivity, at least in part, by interfering with integrin-dependent survival pathways. A major implication of this study is that therapeutic strategies targeting NRP1 in tumour cells may be particularly useful in combination with other drugs for combating tumour survival, growth, and metastatic spread independently of an antiangiogenic effect of blocking NRP1. British Journal of Cancer (2010) 102, 541-552. doi:10.1038/sj.bjc.6605539 www.bjcancer.com Published online 19 January 2010 (C) 2010 Cancer Research U
"Nanohybrids" based on pH-responsive hydrogels and inorganic nanoparticles for drug delivery and sensor applications.
Allyl-PEG capped inorganic NPs, including magnetic iron oxide (IONPs), fluorescent CdSe/ZnS quantum dots (QDs), and metallic gold (AuNPs of 5 and 10 nm) both individually and in combination, were covalently attached to pH-responsive poly(2-vinylpyridine-co-divinylbenzene) nanogels via a facile and robust one-step surfactant-free emulsion polymerization procedure. Control of the NPs associated to the nanogels was achieved by the late injection of the NPs to the polymerization solution at a stage when just polymeric radicals were present. Remarkably, by varying the total amount of NPs injected, the swelling behavior could be affected. Furthermore, the magnetic response as well as the optical features of the nanogels containing either IONPs or QDs could be modified. In addition, a radical quenching in case of gold nanoparticles was observed, thus affecting the final nanogel geometry
AP-1 Is a Component of the Transcriptional Network Regulated by GSK-3 in Quiescent Cells
The protein kinase GSK-3 is constitutively active in quiescent cells in the absence of growth factor signaling. Previously, we identified a set of genes that required GSK-3 to maintain their repression during quiescence. Computational analysis of the upstream sequences of these genes predicted transcription factor binding sites for CREB, NFκB and AP-1. In our previous work, contributions of CREB and NFκB were examined. In the current study, the AP-1 component of the signaling network in quiescent cells was explored.Using chromatin immunoprecipitation analysis, two AP-1 family members, c-Jun and JunD, bound to predicted upstream regulatory sequences in 8 of the 12 GSK-3-regulated genes. c-Jun was phosphorylated on threonine 239 by GSK-3 in quiescent cells, consistent with previous studies demonstrating inhibition of c-Jun by GSK-3. Inhibition of GSK-3 attenuated this phosphorylation, resulting in the stabilization of c-Jun. The association of c-Jun with its target sequences was increased by growth factor stimulation as well as by direct GSK-3 inhibition. The physiological role for c-Jun was also confirmed by siRNA inhibition of gene induction.These results indicate that inhibition of c-Jun by GSK-3 contributes to the repression of growth factor-inducible genes in quiescent cells. Together, AP-1, CREB and NFκB form an integrated transcriptional network that is largely responsible for maintaining repression of target genes downstream of GSK-3 signaling
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