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Nanoindentation analysis of αtricalcium phosphate-poly(lactide-co-glycolide) nanocomposite degradation.
The internal mechanical property characteristics as functions of position and degradation time of PLGA(50:50)-αTCP nanocomposites of varying ceramic-polymer ratios degraded in an aqueous medium have been assessed using depth-sensing nanoindentation. The addition of nanoparticulate αTCP increases the elastic modulus of undegraded specimens from 3.72 ± 0.12 GPa for pure PLGA(50:50) samples to 7.23 ± 0.16 GPa recorded for undegraded 40 wt.% TCP nanocomposites. Additionally αTCP incorporation decreases the viscoelastic loss tangent from 0.189 ± 0.040 measured for pure undegraded PLGA(50:50) to an average of 0.091 ± 0.006 for undegraded ceramic-polymer composites. No variation in viscosity for the composites with ceramic loading was evidenced. The stiffening effect of αTCP addition closely conforms to the lower Hashin-Shtrikman bounds demonstrating that an evenly dispersed nano-filler is the least amenable ceramic configuration to enhance the mechanical properties of PLGA-αTCP nanocomposites. The mechanical property evolution for all composite types in an aqueous degradation medium is dominated by material hydration which effects reduced material stiffness and increased specimen viscosity generating a core-periphery mechanical property distribution in terms of elastic modulus and viscoelastic phase angle. The mechanical property core-periphery structure correlates strongly with the core-periphery density structure characterized using X-ray microtomography. Hydrated regions exhibit significant reductions in elastic modulus and viscosity increases which are typical of elastomers.RCUKThis is the author's accepted manuscript and will be under embargo until the 2nd of June 2015. The final version is published by Elsevier in Materials Science and Engineering: C here: http://www.sciencedirect.com/science/article/pii/S0928493114003099
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X-ray microtomographic analysis of α-tricalcium phosphate- poly(lactic-co-glycolic) acid nanocomposite degradation
The degradation characteristics of αTCP-PLGA(50:50) nanocomposites containing varying ceramic weight loadings in an aqueous medium have been assessed using X-ray microtomography (XμT). Also measured were bulk density changes, pharmaceutic drug release and medium acidification for the degrading materials. Calcium phosphate addition to the polymer leads to increasing delays in the onset of degradation medium acidification and tetracycline release. Bulk density changes with time for all composite materials measured using a buoyancy method were well described during the initial degradation regime by a t1/2function. PLGA density evolution follows a linear function of time which indicates a differing water absorption process occurring in the pure polymer compared with the nanocomposites. Nanocomposite microtomographic analysis over the same period elucidated a core-periphery structure caused by water imbibition. Peripheral regions closest to the specimen surface exhibit reduced attenuation coefficients compared with the core which may be characteristic of a frontal system caused by a polymer phase transition. The front position and specimen swelling are adequately described by a t1/2and complementary error function respectively which if assessed under the assumption of a diffusion controlled process yields a diffusion coefficient of water in all nanocomposites at 37 °C of 4.8 × 10-14cm2s-1. Nevertheless, a t dependence is a necessary but not sufficient condition of a Fickian diffusion process. For all nanocomposite types both XμT data and bulk density measurements exhibited no variations with ceramic filler content
Advancing NLP with Cognitive Language Processing Signals
When we read, our brain processes language and generates cognitive processing
data such as gaze patterns and brain activity. These signals can be recorded
while reading. Cognitive language processing data such as eye-tracking features
have shown improvements on single NLP tasks. We analyze whether using such
human features can show consistent improvement across tasks and data sources.
We present an extensive investigation of the benefits and limitations of using
cognitive processing data for NLP. Specifically, we use gaze and EEG features
to augment models of named entity recognition, relation classification, and
sentiment analysis. These methods significantly outperform the baselines and
show the potential and current limitations of employing human language
processing data for NLP
Decoding EEG brain activity for multi-modal natural language processing
Until recently, human behavioral data from reading has mainly been of
interest to researchers to understand human cognition. However, these human
language processing signals can also be beneficial in machine learning-based
natural language processing tasks. Using EEG brain activity to this purpose is
largely unexplored as of yet. In this paper, we present the first large-scale
study of systematically analyzing the potential of EEG brain activity data for
improving natural language processing tasks, with a special focus on which
features of the signal are most beneficial. We present a multi-modal machine
learning architecture that learns jointly from textual input as well as from
EEG features. We find that filtering the EEG signals into frequency bands is
more beneficial than using the broadband signal. Moreover, for a range of word
embedding types, EEG data improves binary and ternary sentiment classification
and outperforms multiple baselines. For more complex tasks such as relation
detection, further research is needed. Finally, EEG data shows to be
particularly promising when limited training data is available
Fish oil omega-3 fatty acids partially prevent lipid-induced insulin resistance in human skeletal muscle without limiting acylcarnitine accumulation
This is the author accepted manuscript. The final version is available from Portland Press via the DOI in this record Acylcarnitine accumulation in skeletal muscle and plasma has been observed in numerous models of mitochondrial lipid overload and insulin resistance. Fish oil n3PUFA (omega-3 polyunsaturated fatty acids) are thought to protect against lipid-induced insulin resistance. The present study tested the hypothesis that the addition of n3PUFA to an intravenous lipid emulsion would limit muscle acylcarnitine accumulation and reduce the inhibitory effect of lipid overload on insulin action. On three occasions, six healthy young men underwent a 6-h euglycaemic-hyperinsulinaemic clamp accompanied by intravenous infusion of saline (Control), 10% Intralipid® [n6PUFA (omega-6 polyunsaturated fatty acids)] or 10% Intralipid®+10% Omegaven® (2:1; n3PUFA). The decline in insulin-stimulated whole-body glucose infusion rate, muscle PDCa (pyruvate dehydrogenase complex activation) and glycogen storage associated with n6PUFA compared with Control was prevented with n3PUFA. Muscle acetyl-CoA accumulation was greater following n6PUFA compared with Control and n3PUFA, suggesting that mitochondrial lipid overload was responsible for the lower insulin action observed. Despite these favourable metabolic effects of n3PUFA, accumulation of total muscle acylcarnitine was not attenuated when compared with n6PUFA. These findings demonstrate that n3PUFA exert beneficial effects on insulin-stimulated skeletal muscle glucose storage and oxidation independently of total acylcarnitine accumulation, which does not always reflect mitochondrial lipid overload.This research study was funded by The Royal Society [Grant RG100575]
Probing the Heterogeneity of Protein Kinase Activation in Cells by Super-Resolution Microscopy
Heterogeneity of mitogen-activated protein kinase (MAPK) activation in genetically identical cells, which occurs in response to epidermal growth factor receptor (EGFR) signaling, remains poorly understood. MAPK cascades integrate signals emanating from different EGFR spatial locations, including the plasma membrane and endocytic compartment. We previously hypothesized that in EGF-stimulated cells the MAPK phosphorylation (pMAPK) level and activity are largely determined by the spatial organization of the EGFR clusters within the cell. For experimental testing of this hypothesis, we used super-resolution microscopy to define EGFR clusters by receptor numbers (N) and average intra-cluster distances (d). From this data, we predicted the extent of pMAPK with 85% accuracy on a cell-to-cell basis with control data returning 54% accuracy (P50nm were most predictive for pMAPK level in cells. Electron microscopy revealed that these large clusters were primarily localized to the limiting membrane of multivesicular bodies (MVB). Many tighter packed dimers/multimers (d<50nm) were found on intraluminal vesicles within MVBs, where they were unlikely to activate MAPK because of the physical separation. Our results suggest that cell-to-cell differences in N and d contain crucial information to predict EGFR-activated cellular pMAPK levels and explain pMAPK heterogeneity in isogenic cells
Immunosuppression and the Risk of Post-Transplant Malignancy Among Cadaveric First Kidney Transplant Recipients
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73619/1/j.1600-6135.2003.00274.x.pd
Medical student case presentation performance and perception when using mobile learning technology in the emergency department
Hand-held mobile learning technology provides opportunities for clinically relevant self-instructional modules to augment traditional bedside teaching. Using this technology as a teaching tool has not been well studied. We sought to evaluate medical students&rsquo; case presentation performance and perception when viewing short, just-in-time mobile learning videos using the iPod touch prior to patient encounters.Twenty-two fourth-year medical students were randomized to receive or not to receive instruction by video, using the iPod Touch, prior to patient encounters. After seeing a patient, they presented the case to their faculty, who completed a standard data collection sheet. Students were surveyed on their perceived confidence and effectiveness after using these videos.Twenty-two students completed a total of 67 patient encounters. There was a statistically significant improvement in presentations when the videos were viewed for the first time (p = 0.032). There was no difference when the presentations were summed for the entire rotation (p = 0.671). The reliable (alpha = 0.97) survey indicated that the videos were a useful teaching tool and gave students more confidence in their presentations.Medical student patient presentations were improved with the use of mobile instructional videos following first time use, suggesting mobile learning videos may be useful in medical student education. If direct bedside teaching is unavailable, just-in-time iPod touch videos can be an alternative instructional strategy to improve first-time patient presentations by medical students
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