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Conventional cancer vaccines based on soluble vaccines and traditional adjuvants have produced suboptimal therapeutic efficacy in clinical trials. Thus, there is an urgent need for vaccine technologies that can generate potent T cell responses with strong anti-tumor efficacy. We have previously reported the development of synthetic high-density protein (sHDL) nanodiscs for efficient lymph node (LN)-targeted co-delivery of antigen peptides and CpG oligonucleotides (a Toll-like receptor-9 agonist). Here, we performed a comparative study in mice and non-human primates (NHPs) to identify an ideal vaccine platform for induction of CD8+ T cell responses. In particular, we compared the efficacy of CpG class B, CpG class C, and polyICLC (a synthetic double-stranded RNA analog, a TLR-3 agonist), each formulated with antigen-carrying sHDL nanodiscs. Here, we report that sHDL-Ag admixed with polyICLC elicited robust Ag-specific CD8+ T cell responses in mice, and when used in combination with α-PD-1 immune checkpoint inhibitor, sHDL-Ag + polyICLC eliminated large established (~100 mm 3 ) MC-38 tumors in mice. Moreover, sHDL-Gag + polyICLC induced robust Simian immunodeficiency virus Gag-specific, polyfunctional CD8+ T cell responses in rhesus macaques and could further amplify the efficacy of recombinant adenovirus-based vaccine. Notably, while both sHDL-Ag-CpG-B and sHDL-Ag-CpG-C generated strong Ag-specific CD8+ T cell responses in mice, their results were mixed in NHPs. Overall, sHDL combined with polyICLC offers a strong platform to induce CD8+ T cells for vaccine applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Approximately 40% of the U.S. adult population are obese. An issue associated with this trend is proper seat belt fit for obese occupants. This study extends previous research, in which few individuals with high BMI (> 40 kg/m 2 ) were included, by examining the relationship between participant and belt factors on belt fit for drivers with Class I-III obesity., Methods: Posture and belt fit of 52 men and women with BMI from 31 to 59 kg/m 2 (median 38 kg/m 2 ) were measured in a laboratory vehicle mockup. Five seat belt configurations were achieved by manipulating the belt anchorage locations. Body and belt landmark locations were recorded using a three-dimensional coordinate measuring machine., Results: Higher BMI was associated with a lap belt position further forward and higher relative to the pelvis. On average, the lap belt was positioned an additional 32 mm forward and 13 mm above the ASIS with each increasing level of obesity classification. Sex had a small effect after accounting for BMI and stature. The mean fore-aft location of the lap belt was 24 mm more forward for men vs. women and 12 mm higher for women vs. men at the same stature and BMI. On average, women used 50 mm more belt webbing in the lap and 92 mm more in the shoulder vs. men., Conclusions: The results suggest that increasing levels of obesity class effectively introduces slack in the seat belt system by routing the belt further away from the skeleton. Because the belt is designed to engage the pelvis during a frontal crash, belt placements that are higher and further forward may increase injury risk by allowing excursions or submarining. Unique to this cohort, sex had an important effect on belt fit measures after taking into account stature and BMI. The participant and belt factors considered explained only about 40% of the variance in belt fit. The remaining variance may be due to preference or exogenous body shape effects. Further research is needed to assess methods for enhanced seat belt fit for people with obesity, including addressing sex differences in belt routing.

Neutrophil extracellular traps (NETs) are decondensed chromatin networks released by neutrophils that can trap and kill pathogens but can also paradoxically promote biofilms. The mechanism of NET functions remains ambiguous, at least in part, due to their complex and variable compositions. To unravel the antimicrobial performance of NETs, a minimalistic NET-like synthetic structure, termed "microwebs," is produced by the sonochemical complexation of DNA and histone. The prepared microwebs have structural similarity to NETs at the nanometer to micrometer dimensions but with well-defined molecular compositions. Microwebs prepared with different DNA to histone ratios show that microwebs trap pathogenic Escherichia coli in a manner similar to NETs when the zeta potential of the microwebs is positive. The DNA nanofiber networks and the bactericidal histone constituting the microwebs inhibit the growth of E. coli. Moreover, microwebs work synergistically with colistin sulfate, a common and a last-resort antibiotic, by targeting the cell envelope of pathogenic bacteria. The synthesis of microwebs enables mechanistic studies not possible with NETs, and it opens new possibilities for constructing biomimetic bacterial microenvironments to better understand and predict physiological pathogen responses., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The self-assembly of nanoparticles (NPs) is essential for emerging dispersion-based energy-conscious technologies. Of particular interest are micro- and macro-scale self-organizing superstructures that can bridge 2D/3D processing scales. Here we report the spontaneous assembly of CdTe NPs within an aqueous microdroplet suspended in soybean oil. The gradual diffusion of the water into the surrounding medium results in shrinking of the microdroplet, and a concomitant formation of branched assemblies from CdTe NPs that evolve in size from ∼50 μm to ∼1000 μm. The fractal dimension of NP assemblies increases from ∼1.7 to ∼1.9 during the assembly process. We found that constituents of the soybean oil enter the aqueous solution across the microdroplet interface and affect NP assembly. The obtained NP dendrites can be further altered morphologically by illumination with light that results in the disassembly of the NP dendrites. The use of this microheterogeneous dispersion platform with partially soluble hydrophilic and hydrophobic solvents highlights the sensitivity of the NP assembly process to environment and presents an opportunity to explore droplet-confined NP assembly.

The National Highway Traffic Safety Administration (NHTSA) recently published a Request for Comments regarding a potential upgrade to the US New Car Assessment Program (US NCAP) - a star-rating program pertaining to vehicle crashworthiness. Therein, NHTSA (a) cited two metrics for assessing head risk: Head Injury Criterion (HIC15) and Brain Injury Criterion (BrIC), and (b) proposed to conduct risk assessment via its risk curves for those metrics, but did not prescribe a specific method for applying them. Recent studies, however, have indicated that the NHTSA risk curves for BrIC significantly overstate field-based head injury rates. Therefore, in the present three-part study, a new set of BrIC-based risk curves was derived, an overarching head risk equation involving risk curves for both BrIC and HIC15 was assessed, and some additional candidatepredictor- variable assessments were conducted. Part 1 pertained to the derivation. Specifically, data were pooled from various sources: Navy volunteers, amateur boxers, professional football players, simple-fall subjects, and racecar drivers. In total, there were 4,501 cases, with brain injury reported in 63. Injury outcomes were approximated on the Abbreviated Injury Scale (AIS). The statistical analysis was conducted subject to ordinal logistic regression analysis (OLR), such that the various levels of brain injury were cast as a function of BrIC. The resulting risk curves, with Goodman Kruksal Gamma=0.83, were significantly different than those from NHTSA. Part 2 pertained to the assessment relative to field data. Two perspectives were considered: "aggregate" (ΔV=0-56 km/h) and "point" (high-speed, regulatory focus). For the aggregate perspective, the new risk curves for BrIC were applied in field models pertaining to belted, mid-size, adult drivers in 11-1 o'clock, full-engagement frontal crashes in the National Automotive Sampling System (NASS, 1993-2014 calendar years). For the point perspective, BrIC data from tests were used. The assessments were conducted for minor, moderate, and serious injury levels for both Newer Vehicles (airbag-fitted) and Older Vehicles (not airbag-fitted). Curve-based injury rates and NASS-based injury rates were compared via average percent difference (AvgPctDiff). The new risk curves demonstrated significantly better fidelity than those from NHTSA. For example, for the aggregate perspective (n=12 assessments), the results were as follows: AvgPctDiff (present risk curves) = +67 versus AvgPctDiff (NHTSA risk curves) = +9378. Part 2 also contained a more comprehensive assessment. Specifically, BrIC-based risk curves were used to estimate brain-related injury probabilities, HIC15-based risk curves from NHTSA were used to estimate bone/other injury probabilities, and the maximum of the two resulting probabilities was used to represent the attendant headinjury probabilities. (Those HIC15-based risk curves yielded AvgPctDiff=+85 for that application.) Subject to the resulting 21 assessments, similar results were observed: AvgPctDiff (present risk curves) = +42 versus AvgPctDiff (NHTSA risk curves) = +5783. Therefore, based on the results from Part 2, if the existing BrIC metric is to be applied by NHTSA in vehicle assessment, we recommend that the corresponding risk curves derived in the present study be considered. Part 3 pertained to the assessment of various other candidate brain-injury metrics. Specifically, Parts 1 and 2 were revisited for HIC15, translation acceleration (TA), rotational acceleration (RA), rotational velocity (RV), and a different rotational brain injury criterion from NHTSA (BRIC). The rank-ordered results for the 21 assessments for each metric were as follows: RA, HIC15, BRIC, TA, BrIC, and RV. Therefore, of the six studied sets of OLR-based risk curves, the set for rotational acceleration demonstrated the best performance relative to NASS.

This paper describes a simple technique for patterning channels on elastomeric substrates, at two distinct scales of depth, through the use of controlled fracture. Control of channel depth is achieved by the careful use of different layers of PDMS, where the thickness and material properties of each layer, as well as the position of the layers relative to one another, dictate the depth of the channels formed. The system created in this work consists of a single 'deep' channel, whose width can be adjusted between the micron- and the nano-scale by the controlled application or removal of a uniaxial strain, and an array of 'shallow' nano-scale channels oriented perpendicular to the 'deep' channel. The utility of this system is demonstrated through the successful capture and linearization of DNA from a dilute solution by executing a two-step 'concentrate-then-linearize' procedure. When the 'deep' channel is in its open state and a voltage is applied across the channel network, an overlapping electric double layer forms within the 'shallow' channel array. This overlapping electric double layer was used to prevent passage of DNA into the 'shallow' channels when the DNA molecules migrate into the junctional region by electrophoresis. Release of the applied strain then allows the 'deep' channel to return to its closed state, reducing the cross-sectional area of this channel from the micro- to the nano-scale. The resulting hydrodynamic flow and nano-confinement effects then combine to efficiently uncoil and trap the DNA in its linearized form. By adopting this strategy, we were able to overcome the entropic barriers associated with capturing and linearizing DNA derived from a dilute solution.