21 research outputs found
Development of Standard Criteria to Evaluate the Effectiveness of Helmets at Decreasing the Risk of Concussions
In many sports, such as American football, accumulations of mild traumatic brain injuries have been suggested as a possible link to neurodegeneration and future mental disorders. With head impacts occurring at all levels of competition and in different sports, it is critical to develop an accurate method for quantifying the effects of head impacts and determining the efficacy of helmets. This study examines the derivation of different dimensionless numbers and ascertains the critical factors needed to predict the effects of head impacts, specifically the resulting accelerations from an impact. Given a known force of impact, parameters such as peak translation acceleration and impact duration were collected for a total of 200 impacts at 10 locations around the head. These parameters were used in conjunction with dimensionless numbers to compare various helmet designs across sports. Five input and four output criteria, or Ļ variables, were derived using fundamental variables of total mass, width of neck, and the difference between muscle reaction time and the impact duration. By determining the coefficients of the governing equations for each output Ļ variable, the impulse of impacts had a consistent effect on helmet efficacy, while the masses and radii of helmets contained confounding variables that made it difficult to predict the effectiveness of attenuating the head accelerations
Tissue-Specific Genetic Control of Splicing: Implications for the Study of Complex Traits
Numerous genome-wide screens for polymorphisms that influence gene expression have provided key insights into the genetic control of transcription. Despite this work, the relevance of specific polymorphisms to in vivo expression and splicing remains unclear. We carried out the first genome-wide screen, to our knowledge, for SNPs that associate with alternative splicing and gene expression in human primary cells, evaluating 93 autopsy-collected cortical brain tissue samples with no defined neuropsychiatric condition and 80 peripheral blood mononucleated cell samples collected from living healthy donors. We identified 23 high confidence associations with total expression and 80 with alternative splicing as reflected by expression levels of specific exons. Fewer than 50% of the implicated SNPs however show effects in both tissue types, reflecting strong evidence for distinct genetic control of splicing and expression in the two tissue types. The data generated here also suggest the possibility that splicing effects may be responsible for up to 13 out of 84 reported genome-wide significant associations with human traits. These results emphasize the importance of establishing a database of polymorphisms affecting splicing and expression in primary tissue types and suggest that splicing effects may be of more phenotypic significance than overall gene expression changes
Temporal control over cellular targeting through hybridization of folate-targeted dendrimers and PEG-PLA nanoparticles
Polymeric nanoparticles (NPs) and dendrimers are two major classes of nanomaterials that have demonstrated great potential for targeted drug delivery. However, their targeting efficacy has not yet met clinical needs, largely because of a lack of control over their targeting kinetics, which often results in rapid clearance and off-target drug delivery. To address this issue, we have designed a novel hybrid NP (nanohybrid) platform that allows targeting kinetics to be effectively controlled through hybridization of targeted dendrimers with polymeric NPs. Folate (FA)-targeted generation 4 poly(amidoamine) dendrimers were encapsulated into poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-PLA) NPs using a double emulsion method, forming nanohybrids with a uniform size (100 nm in diameter) at high encapsulation efficiencies (69ā85%). Targeted dendrimers encapsulated within the NPs selectively interacted with FA receptor (FR)-overexpressing KB cells upon release in a temporally controlled manner. The targeting kinetics of the nanohybrids were modulated using three different molecular weights (MW) of the PLA block (23, 30, and 45 kDa). The release rates of the dendrimers from the nanohybrids were inversely proportional to the MW of the PLA block, which dictated their binding and internalization kinetics with KB cells. Our results provide evidence that selective cellular interactions can be kinetically controlled by the nanohybrid design, which can potentially enhance targeting efficacy of nanocarriers
Temporal Control over Cellular Targeting through Hybridization of Folate-targeted Dendrimers and PEG-PLA Nanoparticles
Polymeric nanoparticles (NPs) and dendrimers are two
major classes
of nanomaterials that have demonstrated great potential for targeted
drug delivery. However, their targeting efficacy has not yet met clinical
needs, largely because of a lack of control over their targeting kinetics,
which often results in rapid clearance and off-target drug delivery.
To address this issue, we have designed a novel hybrid NP (nanohybrid)
platform that allows targeting kinetics to be effectively controlled
through hybridization of targeted dendrimers with polymeric NPs. Folate
(FA)-targeted generation 4 polyĀ(amidoamine) dendrimers were encapsulated
into polyĀ(ethylene glycol)-<i>b</i>-polyĀ(d,l-lactide) (PEG-PLA) NPs using a double emulsion method, forming
nanohybrids with a uniform size (ā¼100 nm in diameter) at high
encapsulation efficiencies (69ā85%). Targeted dendrimers encapsulated
within the NPs selectively interacted with FA receptor (FR)-overexpressing
KB cells upon release in a temporally controlled manner. The targeting
kinetics of the nanohybrids were modulated using three different molecular
weights (MW) of the PLA block (23, 30, and 45 kDa). The release rates
of the dendrimers from the nanohybrids were inversely proportional
to the MW of the PLA block, which dictated their binding and internalization
kinetics with KB cells. Our results provide evidence that selective
cellular interactions can be kinetically controlled by the nanohybrid
design, which can potentially enhance targeting efficacy of nanocarriers
Improving Photovoltaics with High Luminescence Efficiency Quantum Dot Layers
A solar cell relies on its ability to turn photons into current. Because short wavelength photons
are typically absorbed near the top surface of a cell, the generated charge carriers recombine
before being collected. But when a layer of quantum dots (nanoscale semiconductor particles) is
placed on top of the cell, it absorbs short wavelength photons and emits them into the cell at
longer wavelengths, which enables more efficient carrier collection. However, the resulting
power conversion efficiency of the system depends critically on the quantum dot luminescence
efficiency ā the nature of this relationship was previously unknown. Our calculations suggest
that a quantum dot layer must have high luminescence efficiency (at least 80%) to improve the
current output of existing photovoltaic (PV) cells; otherwise, it may worsen the cellās efficiency.
Our quantum dot layer (using quantum dots with over 85% quantum yield) slightly reduced the
efficiency of our PV cells. We observed a decrease in short circuit current of a commercial-grade
cell from 0.1977 A to 0.1826 A, a 7.6% drop, suggesting that improved optical coupling from the
quantum dot emission into the solar cell is needed. With better optical coupling, we predict
current enhancements between ~6% and ~8% for a solar cell that already has an antireflection
coating. Such improvements could have important commercial impacts if the coating could be
deployed in a scalable fashion
Sensory Stimulation (Electro-Acupuncture) and Physical Exercise, Effects on Blood Pressure, and Nociception
Marked for death
SUMOylation of PML-RaR alpha oncoprotein has been linked to its arsenic-induced degradation and the therapeutic response in acute promyelocytic leukaemia. Two groups identify PML as an in vivo target of the RING finger ubiquitin E3 ligase RNF4, which specifically binds polysUMOylated PML and is essential for the arsenic-induced catabolism of both PML and PML -RaR alpha