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 π 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 π 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 (69–85%). 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 poly­(amidoamine) dendrimers were encapsulated into poly­(ethylene glycol)-<i>b</i>-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 (69–85%). 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 – 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 cell’s 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

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