Nanoporous silica-based protocells at multiple scales for designs of life and nanomedicine.

Various protocell models have been constructed de novo with the bottom-up approach. Here we describe a silica-based protocell composed of a nanoporous amorphous silica core encapsulated within a lipid bilayer built by self-assembly that provides for independent definition of cell interior and the surface membrane. In this review, we will first describe the essential features of this architecture and then summarize the current development of silica-based protocells at both micro- and nanoscale with diverse functionalities. As the structure of the silica is relatively static, silica-core protocells do not have the ability to change shape, but their interior structure provides a highly crowded and, in some cases, authentic scaffold upon which biomolecular components and systems could be reconstituted. In basic research, the larger protocells based on precise silica replicas of cells could be developed into geometrically realistic bioreactor platforms to enable cellular functions like coupled biochemical reactions, while in translational research smaller protocells based on mesoporous silica nanoparticles are being developed for targeted nanomedicine. Ultimately we see two different motivations for protocell research and development: (1) to emulate life in order to understand it; and (2) to use biomimicry to engineer desired cellular interactions

The Effects of Product Liability Exemption in the Presence of the FDA

In the United States, drugs are jointly regulated by the US Food and Drug Administration, which oversees premarket clinical trials designed to ensure drug safety and efficacy, and the liability system, which allows patients to sue manufacturers for unsafe drugs. In this paper, we examine the potential welfare effects of this dual system aimed at ensuring the safety of medical products, and conclude that product liability exemptions for FDA regulated activities could raise economic efficiency. We show that while reductions in liability, such those associated with pre-emption, may lower welfare in the absence of the FDA, they may raise welfare in its presence. In the presence of the FDA, product liability may reduce efficiency by raising prices without pushing firms, who are already bound by the agency’s requirements, to invest further in product safety. We consider as a case study the National Vaccine Injury Compensation Program, which sharply reduced vaccine manufacturer’s liability in 1988. We find evidence that the program reduced prices without affecting vaccine safety, suggesting that liability reductions can enhance economic efficiency in the presence of the FDA.

Can Preschoolers be Health Messengers to Promote Breast Health among Chinese Americans?

Women’s limited knowledge about breast cancer screening (BCS), combined with differences in Eastern and Western disease prevention concepts, may contribute to late-stage breast cancer diagnosis among minorities. Children can be conduits of knowledge transfer to adults. This pilot study tested the use of a culturally-tailored theatrical preschool performance in increasing Chinese American women’s knowledge of BCS guidelines. Chinese preschool children relayed BCS guidelines through a culturally-tailored theatrical performance. Data were collected from 177 Chinese American women (84% foreign-born) who completed pre- and post-performance surveys. Findings suggested that promoting BCS guidelines through a culturally-tailored preschool theatrical performance significantly increased participants’ knowledge of the guidelines. Interventions involving young children as change agents to deliver simple health messages such as BCS guidelines are feasible and promising to increase knowledge and desired behavioral change within the target population. Further empirical investigations are warranted in larger randomized controlled trials

Mouse cytomegalovirus-experienced ILC1s acquire a memory response dependent on the viral glycoprotein m12.

Innate lymphoid cells (ILCs) are tissue-resident sentinels that are essential for early host protection from pathogens at initial sites of infection. However, whether pathogen-derived antigens directly modulate the responses of tissue-resident ILCs has remained unclear. In the present study, it was found that liver-resident type 1 ILCs (ILC1s) expanded locally and persisted after the resolution of infection with mouse cytomegalovirus (MCMV). ILC1s acquired stable transcriptional, epigenetic and phenotypic changes a month after the resolution of MCMV infection, and showed an enhanced protective effector response to secondary challenge with MCMV consistent with a memory lymphocyte response. Memory ILC1 responses were dependent on the MCMV-encoded glycoprotein m12, and were independent of bystander activation by proinflammatory cytokines after heterologous infection. Thus, liver ILC1s acquire adaptive features in an MCMV-specific manner

High-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines.

Head and neck squamous cell carcinoma (HNSCC) is a common cancer diagnosis worldwide. Despite advances in treatment, HNSCC has very poor survival outcomes, emphasizing an ongoing need for development of improved therapeutic options. The distinct tumor characteristics of human papillomavirus (HPV)-positive vs. HPV-negative disease necessitate development of treatment strategies tailored to tumor HPV-status. High-throughput robotic screening of 1,433 biologically and pharmacologically relevant compounds at a single dose (4 μM) was carried out against 6 HPV-positive and 20 HPV-negative HNSCC cell lines for preliminary identification of therapeutically relevant compounds. Statistical analysis was further carried out to differentiate compounds with preferential activity against cell lines stratified by the HPV-status. These analyses yielded 57 compounds with higher activity in HPV-negative cell lines, and 34 with higher-activity in HPV-positive ones. Multi-point dose-response curves were generated for six of these compounds (Ryuvidine, MK-1775, SNS-032, Flavopiridol, AZD-7762 and ARP-101), confirming Ryuvidine to have preferential potency against HPV-negative cell lines, and MK-1775 to have preferential potency against HPV-positive cell lines. These data comprise a valuable resource for further investigation of compounds with therapeutic potential in the HNSCC

Enabling and scaling biomolecular simulations of 100 million atoms on petascale machines with a multicore-optimized message-driven runtime

A 100-million-atom biomolecular simulation with NAMD is one of the three benchmarks for the NSF-funded sustainable petascale machine. Simulating this large molecular system on a petascale machine presents great challenges, including handling I/O, large memory footprint and getting good strong-scaling results. In this paper, we present parallel I/O techniques to enable the simula-tion. A new SMP model is designed to efficiently utilize ubiquitous wide multicore clusters by extending the CHARM++ asynchronous message-driven runtime. We exploit node-aware techniques to op-timize both the application and the underlying SMP runtime. Hi-erarchical load balancing is further exploited to scale NAMD to the full Jaguar PF Cray XT5 (224,076 cores) at Oak Ridge Na-tional Laboratory, both with and without PME full electrostatics, achieving 93 % parallel efficiency (vs 6720 cores) at 9 ms per step for a simple cutoff calculation. Excellent scaling is also obtained on 65,536 cores of the Intrepid Blue Gene/P at Argonne National Laboratory. 1

Rice consumption and risk of cardiovascular disease: results from a pooled analysis of 3 U.S. cohorts1234

Background: Health concerns have been raised about rice consumption, which may significantly contribute to arsenic exposure. However, little is known regarding whether habitual rice consumption is associated with cardiovascular disease (CVD) risk. Objective: We examined prospectively the association of white rice and brown rice consumption with CVD risk. Design: We followed a total of 207,556 women and men [73,228 women from the Nurses’ Health Study (1984–2010), 92,158 women from the Nurses’ Health Study II (1991–2011), and 42,170 men from the Health Professionals Follow-Up Study (1986–2010)] who were free of CVD and cancer at baseline. Validated semiquantitative food-frequency questionnaires were used to assess consumption of white rice, brown rice, and other food items. Fatal and nonfatal CVD (coronary artery disease and stroke) was confirmed by medical records or self-reports. Results: During 4,393,130 person-years of follow-up, 12,391 cases of CVD were identified. After adjustment for major CVD risk factors, including demographics, lifestyle, and other dietary intakes, rice consumption was not associated with CVD risk. The multivariable-adjuted HR of developing CVD comparing ≥5 servings/wk with <1 serving/wk was 0.98 (95% CI: 0.84, 1.14) for white rice, 1.01 (0.79, 1.28) for brown rice, and 0.99 (0.90, 1.08) for total rice. To minimize the potential impact of racial difference in rice consumption, we restricted the analyses to whites only and obtained similar results: the HRs of CVD for ≥5 servings/wk compared with <1 serving/wk were 1.04 (95% CI: 0.88, 1.22) for white rice and 1.01 (0.78, 1.31) for brown rice. Conclusions: Greater habitual consumption of white rice or brown rice is not associated with CVD risk. These findings suggest that rice consumption may not pose a significant CVD risk among the U.S. population when consumed at current amounts. More prospective studies are needed to explore these associations in other populations