Stable sample delivery in a viscous medium via a polyimide-based single-channel microfluidic chip for serial crystallography
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The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue to impact the lives and health of people across the world for the foreseeable future. The rollout of vaccines has provided highly anticipated relief, but effective therapeutics are required to further reduce the risk and severity of infections. Monoclonal antibodies have been shown to be effective as therapeutics for SARS-CoV-2, but as new variants of concern (VoC) continue to emerge, their utility and use have waned due to limited or no efficacy against these variants. Furthermore, cumbersome systemic administration limits easy and broad access to such drugs. As well, concentrations of systemically administered antibodies in the mucosal epithelium, a primary site of initial infection, are dependent on neonatal Fc receptor mediated transport and require high drug concentrations. To reduce the viral load more effectively in the lung, we developed an inhalable formulation of a SARS-CoV-2 neutralizing antibody binding to a conserved epitope on the Spike protein, ensuring pan-neutralizing properties. Administration of this antibody via a vibrating mesh nebulization device retained antibody integrity and resulted in effective distribution of the antibody in the upper and lower respiratory tract of non-human primates (NHP). In comparison with intravenous administration, significantly higher antibody concentrations can be obtained in the lung, resulting in highly effective reduction in viral load post SARS-CoV-2 challenge. This approach may reduce the barriers of access and uptake of antibody therapeutics in real-world clinical settings and provide a more effective blueprint for targeting existing and potentially emerging respiratory tract viruses.
Introduction: Natural and biocompatible clay nanotubes are among the best inorganic materials for drug nanoformulations. These halloysite tubes with SiO 2 on the outermost surface have diameter of ca. 50 nm, length around 1 micrometer and may be loaded with drugs at 10-30 wt. %. Narrow tube openings allow for controllable sustained drug release for hours, days or even weeks. Areas covered: Physical-chemical properties of these nanotubes are described followed by examples of drug-loading capabilities, release characteristics, and control of duration of release through the end tube capping with polymers. Development of halloysite-polymer composites such as tissue scaffolds and bone cement/dentist resin formulations with enhanced mechanical properties and extension of the drug release to 2-3 weeks are described. Examples of the compression properties of halloysite in tablets and capsules are also shown. Expert opinion: Here, we expect that clay nanotubes will be used primarily for non-injectable drug formulations, such as topical and oral dosage forms, cosmetics, as well as for composite materials with enhanced therapeutic effects. These include tissue scaffolds, bone cement and dentist resins with sustained release of antimicrobial and cell growth-promoting medicines (including proteins and DNA) as well as other formulations such as compounds for antiseptic treatment of hospitals.
This group of data models include the 2024 NETL models for the NETL Coal Baseline Lifecycle Model in both open LCA and Excel, in addition to basin and transportation inventory data files in Excel supporting the overall model.
Space conditioning represents nearly 50% of average residential household energy consumption, highlighting the need to identify alternative cost-effective, energy-efficient cooling and heating strategies. As homes are better built, there is an increasing need for strategies that are particularly well suited for high performance, low load homes. ARBI researchers worked with two test homes in hot-dry climates to evaluate the in-situ performance of air-to-water heat pump (AWHP) systems, an energy efficient space conditioning solution designed to cost-effectively provide comfort in homes with efficient, safe, and durable operation. Two monitoring projects of test houses in hot-dry climates were initiated in 2010 to test this system. Both systems were fully instrumented and have been monitored over one year to capture complete performance data over the cooling and heating seasons. Results are used to quantify energy savings, cost-effectiveness, and system performance using different operating modes and strategies. A calibrated TRNSYS model was developed and used to evaluate performance in various climate regions. This strategy is most effective in tight, insulated homes with high levels of thermal mass (i.e. exposed slab floors).
Space conditioning represents nearly 50% of average residential household energy consumption, highlighting the need to identify alternative cost-effective, energy-efficient cooling and heating strategies. As homes are better built, there is an increasing need for strategies that are particularly well suited for high performance, low load homes. ARBI researchers worked with two test homes in hot-dry climates to evaluate the in-situ performance of air-to-water heat pump (AWHP) systems, an energy efficient space conditioning solution designed to cost-effectively provide comfort in homes with efficient, safe, and durable operation. Two monitoring projects of test houses in hot-dry climates were initiated in 2010 to test this system. Both systems were fully instrumented and have been monitored over one year to capture complete performance data over the cooling and heating seasons. Results are used to quantify energy savings, cost-effectiveness, and system performance using different operating modes and strategies. A calibrated TRNSYS model was developed and used to evaluate performance in various climate regions. This strategy is most effective in tight, insulated homes with high levels of thermal mass (i.e. exposed slab floors).
As a corporate workforce grows, managers need more information close at hand to make decisions for the company. As every scientist knows, we can’t judge, let alone improve, something that can’t be measured. Thus, firms that are committed to constant improvement generate reports on various business metrics in order to make informed decisions. Sandia National Labs is no exception. Enterprise business intelligence (BI) is very important to keep such a large organization on the right track, as it signals any adjustments that may be required to stay the course. Like teams in other fields, Sandia’s HR Reporting wants to provide the most valuable Workforce BI possible, and it is considering a change in reporting paradigm to achieve that.
The goal of this proposal is to demonstrate that colocalization of protein subunit antigens and adjuvants on nanolipoprotein particles (NLPs) can increase the protective efficacy of subunit antigens from Burkholderia spp. and Francisella tularensis against an aerosol challenge. In the third quarter of the third year, F344 rats vaccinated with adjuvanted NLP formulations were challenged with F. tularensis SCHU S4 at Battelle. Preliminary data indicate that up to 65% of females vaccinated intranasally with an NLP-based formulation survived this challenge, compared to only 20% survival of naïve animals. In addition, NLPs were successfully formulated with Burkholderia protein antigens. IACUC approval for immunological assessments in BALB/c mice was received and we anticipate that these assessments will begin by March 2015, pending ACURO approval.
The goal of this proposal is to demonstrate that colocalization of protein subunit antigens and adjuvants on nanolipoprotein particles (NLPs) can increase the protective efficacy of subunit antigens from Burkholderia spp. and Francisella tularensis against an aerosol challenge. In the second quarter of the third year, LLNL finalized all immunological assessments of NLP vaccine formulations in the F344 model. Battelle has immunized rats with three unique NLP formulations by either intramuscular or intranasal administration. All inoculations have been completed, and protective efficacy against an aerosolized challenge will begin at the end of October, 2014.
The purpose of this project was for Seeo to deliver the first ever large-scale or grid-scale prototype of a new class of advanced lithium-ion rechargeable batteries. The technology combines unprecedented energy density, lifetime, safety, and cost. The goal was to demonstrate Seeo’s entirely new class of lithium-based batteries based on Seeo’s proprietary nanostructured polymer electrolyte. This technology can enable the widespread deployment in Smart Grid applications and was demonstrated through the development and testing of a 10 kilowatt-hour (kWh) prototype battery system. This development effort, supported by the United States Department of Energy (DOE) enabled Seeo to pursue and validate the transformational performance advantages of its technology for use in grid-tied energy storage applications. The focus of this project and Seeo’s goal as demonstrated through the efforts made under this project is to address the utility market needs for energy storage systems applications, especially for residential and commercial customers tied to solar photovoltaic installations. In addition to grid energy storage opportunities Seeo’s technology has been tested with automotive drive cycles and is seen as equally applicable for battery packs for electric vehicles. The goals of the project were outlined and achieved through a series of specific tasks, which encompassed materials development, scaling up of cells, demonstrating the performance of the cells, designing, building and demonstrating a pack prototype, and providing an economic and environmental assessment. Nearly all of the tasks were achieved over the duration of the program, with only the full demonstration of the battery system and a complete economic and environmental analysis not able to be fully completed. A timeline over the duration of the program is shown in figure 1.
Space conditioning represents nearly 50% of average residential household energy consumption, highlighting the need to identify alternative cost-effective, energy-efficient cooling and heating strategies. As homes are better built, there is an increasing need for strategies that are particularly well suited for high performance, low load homes. ARBI researchers worked with two test homes in hot-dry climates to evaluate the in-situ performance of air-to-water heat pump systems, an energy efficient space conditioning solution designed to cost-effectively provide comfort in homes with efficient, safe, and durable operation. Two monitoring projects of test houses in hot-dry climates were initiated in 2010 to test this system. Both systems were fully instrumented and have been monitored over one year to capture complete performance data over the cooling and heating seasons. Results are used to quantify energy savings, cost-effectiveness, and system performance using different operating modes and strategies. A calibrated TRNSYS model was developed and used to evaluate performance in various climate regions. This strategy is most effective in tight, insulated homes with high levels of thermal mass (i.e. exposed slab floors).
The objective for the experimental effort was to provide validation for the electrostatic aerosol transport models for particle size and deposition rate and to determine the feasibility of an electrostatic spray process in delivering non-corrosive decontaminants to complex interior spaces, such as an aircraft. The project utilized ITW (Illinois Tool Works) rotary atomizing induction charged nozzle to disperse small, charged droplets of liquid decontaminants uniformly through a contaminated space. Particle size and deposition studies were conducted prior to the feasibility study where the ITW nozzle was optimized and characterized for two decontaminants: EasyDeconTM200 (DF-200) and Steriplex® SD. In addition to the validation studies, two feasibility studies were conducted with anthrax simulant (B. atrophaeus) and sarin simulant (diphenol chlorophosphate, DPCP). Running parameters for the two studies varied according to the starting contaminant challenges (1.0 x 108 CFU/m 2 for B. atrophaeus and 1.0 g/m 2 for DPCP), the amount of decontaminant deposition, and, finally, decontaminant to agent contact time. Results for the DPCP study confirm that our spray method met and exceeded the threshold criteria of <10 mg/m 2 , postdecontamination, for Teflon and aluminum coupons. Results from this study also showed that polycarbonate and rubber coupons can be reduced by <98% and <92%, respectively. Results for the B. atrophaeus study presented a slightly different challenge due to coupon size, however, increasing the size of the coupon confirmed that it is possible for our spray method to meet the threshold criteria of <100 CFU/m 2 . In addition, a computational model was developed in ANSYS Fluent to solve for the air flow, space charge, electric field, and droplet motion involved in electrostatic aerosol transport. Comparison of the model to experiments resulted in good agreement in deposition pattern and total mass deposited on surfaces. Finally, as a consequence of this project, the methodology used for decontamination could be used to improve future contamination scenarios by eliminating or reducing contaminant hazards, thereby allowing equipment and/or facilities, previously unusable, to be reclaimed rather than discarded, resulting in an overall cost savings to the customer.
The goal of this proposal is to demonstrate that co-localization of protein subunit antigens and adjuvants on nanolipoprotein particles (NLPs) can increase the protective efficacy of recombinant subunit antigens from Burkholderia spp. and Francisella tularensis against an aerosol challenge. NLPs are are biocompatible, high-density lipoprotein mimetics that are amenable to the incorporation of multiple, chemically-disparate adjuvant and antigen molecules. We hypothesize that the ability to co-localize optimized adjuvant formulations with subunit antigens within a single particle will enhance the stimulation and activation of key immune effector cells, increasing the protective efficacy of subunit antigen-based vaccines. While Burkholderia spp. and F. tularensis subunit antigens are the focus of this proposal, we anticipate that this approach is applicable to a wide range of DOD-relevant biothreat agents. The F344 rat aerosol challenge model for F. tularensis has been successfully established at Battelle under this contract, and Year 3 efficacy studies performed at Battelle demonstrated that an NLP vaccine formulation was able to enhance survival of female F344 rats relative to naïve animals. In addition, Year 3 focused on the incorporation of multiple Burkholderia antigens (both polysaccharides and proteins) onto adjuvanted NLPs, with immunological analysis poised to begin in the next quarter.
The NorthernSTAR BA partnership investigated a new model to deploy building science-guided performance solutions to homeowners.
The I-710 and CA-60 highways are key transportation corridors in the Southern California region that are heavily used on a daily basis by heavy duty drayage trucks that transport the cargo from the ports to the inland transportation terminals. These terminals, which include store/warehouses, inland-railways, are anywhere from 5 to 50 miles in distance from the ports. The concentrated operation of these drayage vehicles in these corridors has had and will continue to have a significant impact on the air quality in this region whereby significantly impacting the quality of life in the communities surrounding these corridors. To reduce these negative impacts it is critical that zero and near-zero emission technologies be developed and deployed in the region. A potential local market size of up to 46,000 trucks exists in the South Coast Air Basin, based on near- dock drayage trucks and trucks operating on the I-710 freeway. The South Coast Air Quality Management District (SCAQMD), California Air Resources Board (CARB) and Southern California Association of Governments (SCAG) — the agencies responsible for preparing the State Implementation Plan required under the federal Clean Air Act — have stated that to attain federal air quality standards the region will need to transition to broad use of zero and near zero emission energy sources in cars, trucks and other equipment (Southern California Association of Governments et al, 2011). SCAQMD partnered with Volvo Trucks to develop, build and demonstrate a prototype Class 8 heavy-duty plug-in hybrid drayage truck with significantly reduced emissions and fuel use. Volvo’s approach leveraged the group’s global knowledge and experience in designing and deploying electromobility products. The proprietary hybrid driveline selected for this proof of concept was integrated with multiple enhancements to the complete vehicle in order to maximize the emission and energy impact of electrification. A detailed review of all technologies included in the demonstrator is presented in this report. The project was completed in July 2015 with a final demonstration of the concept vehicle on a simulated drayage route around Volvo’s North American headquarters in Greensboro, NC. The route included all traffic conditions typical of drayage operation in Southern California as well as geofences defined to showcase the zero emission capabilities of the truck. The demonstrator successfully completed four consecutive trips with a gross combined vehicle weight of 44,000 lb., covering approximately 2 miles out of a total distance of 9 miles per trip in the Zero Emission (ZE) geofence. This vehicle is expected to use approximately 30% less fuel than a typical drayage truck in daily operation, and it is designed to allow full electric operation whenever operating in a marine terminal in the ports of Los Angeles / Long Beach. A paper study on the feasibility of expanding the capabilities of the plug-in hybrid concept developed as part of this project was also delivered as an addendum to the regular progress reports.
To meet the needs of public and private stakeholders involved in the development, construction, and operation of hydrogen fueling stations needed to support the widespread roll-out of hydrogen fuel cell electric vehicles, this work presents publicly available station templates and analyses. These ‘Reference Stations’ help reduce the cost and speed the deployment of hydrogen stations by providing a common baseline with which to start a design, enable quick assessment of potential sites for a hydrogen station, identify contributors to poor economics, and suggest areas of research. This work presents layouts, bills of materials, piping and instrumentation diagrams, and detailed analyses of five new station designs. In the near term, delivered hydrogen results in a lower cost of hydrogen compared to on-site production via steam methane reforming or electrolysis, although the on-site production methods have other advantages. Modular station concepts including on-site production can reduce lot sizes from conventional assemble-on-site stations.