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Kerckhoffs R.C.P.,Institute of Engineering in Medicine | Kerckhoffs R.C.P.,University of California at San Diego | Omens J.H.,Institute of Engineering in Medicine | McCulloch A.D.,Institute of Engineering in Medicine | Mulligan L.J.,Medtronic Inc.
Circulation: Heart Failure | Year: 2010

Background-Heart failure (HF) in combination with mechanical dyssynchrony is associated with a high mortality rate. To quantify contractile dysfunction in patients with HF, investigators have proposed several indices of mechanical dyssynchrony, including percentile range of time to peak shortening (WTpeak), circumferential uniformity ratio estimate (CURE), and internal stretch fraction (ISF). The goal of this study was to compare the sensitivity of these indices to 4 major abnormalities responsible for cardiac dysfunction in dyssynchronous HF: dilation, negative inotropy, negative lusitropy, and dyssynchronous activation. Methods and Results-All combinations of these 4 major abnormalities were included in 3D computational models of ventricular electromechanics. Compared with a nonfailing heart model, ventricles were dilated, inotropy was reduced, twitch duration was prolonged, and activation sequence was changed from normal to left bundle branch block. In the nonfailing heart, CURE, ISF, and WTpeak were 0.97±0.004, 0.010±0.002, and 78±1 milliseconds, respectively. With dilation alone, CURE decreased 2.0±0.07%, ISF increased 58±47%, and WTpeak increased 31±3%. With dyssynchronous activation alone, CURE decreased 15±0.6%, ISF increased 14-fold (±3), and WTpeak increased 121±4%. With the combination of dilation and dyssynchronous activation, CURE decreased 23±0.8%, ISF increased 20-fold (±5), and WTpeak increased 147±5%. Conclusions-Dilation and left bundle branch block combined synergistically decreased regional cardiac function. CURE and ISF were sensitive to this combination, but WTpeak was not. CURE and ISF also reflected the relative nonuniform distribution of regional work better than WTpeak. These findings might explain why CURE and ISF are better predictors of reverse remodeling in cardiac resynchronization therapy. © 2010 American Heart Association, Inc.

Hwang M.T.,University of California at San Diego | Landon P.B.,University of California at San Diego | Lee J.,University of California at San Diego | Mo A.,University of California at San Diego | And 3 more authors.
Nanoscale | Year: 2015

DNA can be manipulated to design nano-machines through specific sequence recognition. We report a switchable DNA carrier for repeatable capture and release of a single stranded DNA. The activity of the carrier was regulated by the interactions among a double-stranded actuator, single stranded target, fuel, and anti-fuel DNA strands. Inosine was used to maintain a stable triple-stranded complex when the actuator's conformation was switched between open (capture) and closed (release) configurations. Time lapse fluorescence measurements show repeatable capture and release of target strands. TEM images also show visible capture of target DNA strands when gold nanoparticles were attached to the DNA carrier and the target DNA strand. The carrier activity was controlled by length of toeholds, number of mismatches, and inosine substitutions. Significantly, unlike in previously published work that reported the devices functioned only when there is a perfect match between the interacting DNA strands, the present device works only when there are mismatches in the fuel strand and the best performance is achieved for 1-3 mismatches. The device was used to successfully capture and release gold nanoparticles when linked to the target single-stranded DNA. In general, this type of devices can be used for transport and delivery of theranostic molecules. © The Royal Society of Chemistry 2015.

Wei C.-S.,Institute for Neural Computation | Wei C.-S.,Institute of Engineering in Medicine | Wei C.-S.,University of California at San Diego | Lin Y.-P.,Institute for Neural Computation | And 3 more authors.
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2016

Recent developments of brain-computer interfaces (BCIs) for driving lapse detection based on electroencephalogram (EEG) have made much progress. This study aims to leverage these new developments and explore the use of robust principal component analysis (RPCA) to extract informative EEG features associated with neurocognitive lapses. Study results showed that the RPCA decomposition could separate lapse-related EEG dynamics from the task-irrelevant spontaneous background activity, leading to more robust neural correlates of neurocognitive lapse as compared to the original EEG signals. This study will shed light on the development of a robust lapse-detection BCI system in real-world environments. © Springer International Publishing Switzerland 2016.

Mo A.H.,Materials Science and Engineering Program | Landon P.B.,Institute of Engineering in Medicine | Gomez K.S.,Institute of Engineering in Medicine | Gomez K.S.,University of Sonora | And 12 more authors.
Nanoscale | Year: 2016

Composite colloidal structures with multi-functional properties have wide applications in targeted delivery of therapeutics and imaging contrast molecules and high-throughput molecular bio-sensing. We have constructed a multifunctional composite magnetic nanobowl using the bottom-up approach on an asymmetric silica/polystyrene Janus template consisting of a silica shell around a partially exposed polystyrene core. The nanobowl consists of a silica bowl and a gold exterior shell with iron oxide magnetic nanoparticles sandwiched between the silica and gold shells. The nanobowls were characterized by electron microscopy, atomic force microscopy, magnetometry, vis-NIR and FTIR spectroscopy. Magnetically vectored transport of these nanobowls was ascertained by time-lapsed imaging of their flow in fluid through a porous hydrogel under a defined magnetic field. These magnetically-responsive nanobowls show distinct surface enhanced Raman spectroscopy (SERS) imaging capability. The PEGylated magnetically-responsive nanobowls show size-dependent cellular uptake in vitro. © 2016 The Royal Society of Chemistry.

Mazor R.,Institute of Engineering in Medicine | Alsaigh T.,Institute of Engineering in Medicine | Shaked H.,University of California at San Diego | Altshuler A.E.,Institute of Engineering in Medicine | And 6 more authors.
Journal of Biological Chemistry | Year: 2013

Matrix metalloproteinase-1 (MMP-1) is a collagenase that is highly active in extracellular matrix and vascular remodeling, angiogenesis, and tumor progression. Vascular endothelial growth factor receptor-2 (VEGFR2), the main receptor for VEGF-A, is expressed on endothelial cells and promotes cell survival, proliferation, and other functions. Although MMP-1 and VEGFR2 co-exist in many normal and pathophysiological conditions, the effect of MMP-1 on cellular VEGFR2 that can promote the above processes is unknown. In this study we test the hypothesis that stimulation of endothelial cells with MMP-1 increases their levels of VEGFR2. The increased VEGFR2 is then available to bind VEGF-A, resulting in increased response. Indeed we found that endothelial cells incubated with active MMP-1 had higher mRNA and protein levels of VEGFR2. Furthermore, VEGF-A-dependent phosphorylation of intracellular signaling molecules and endothelial proliferation were elevated after MMP-1 treatment. MMP-1 caused activation of the nuclear factor-κB (NF-κB) pathway (p65/RelA) in endothelial cells, and this response was dependent upon activation of protease activated receptor-1 (PAR-1). Chromatin immunoprecipitation was used to confirm NF-κB-mediated active transcription of the VEGFR2 (KDR) gene. Elevation in VEGFR2 after MMP-1 stimulation was inhibited by PAR-1 knockdown and NF-κB specific inhibition. We conclude that MMP-1 promotes VEGFR2 expression and proliferation of endothelial cells through stimulation of PAR-1 and activation of NF-κB. These results suggest a mechanism by which MMP-1 may prime or sensitize endothelial cell functions. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

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