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At least 1,387 records · Page 77

Propensity Score–Matched Analysis of Comprehensive Local Therapy for Oligometastatic Non-Small Cell Lung Cancer That Did Not Progress After Front-Line Chemotherapy

Purpose: To retrospectively analyze factors influencing survival in patients with non-small cell lung cancer presenting with ≤3 synchronous metastatic lesions. Methods and Materials: We identified 90 patients presenting between 1998 and 2012 with non-small cell lung cancer and ≤3 metastatic lesions who had received at least 2 cycles of chemotherapy followed by surgery or radiation therapy before disease progression. The median number of chemotherapy cycles before comprehensive local therapy (CLT) (including concurrent chemoradiation as first-line therapy) was 6. Factors potentially affecting overall (OS) or progression-free survival (PFS) were evaluated with Cox proportional hazards regression. Propensity score matching was used to assess the efficacy of CLT. Results: Median follow-up time was 46.6 months. Benefits in OS (27.1 vs 13.1 months) and PFS (11.3 months vs 8.0 months) were found with CLT, and the differences were statistically significant when propensity score matching was used (P ≤ .01). On adjusted analysis, CLT had a statistically significant benefit in terms of OS (hazard ratio, 0.37; 95% confidence interval, 0.20-0.70; P ≤ .01) but not PFS (P=.10). In an adjusted subgroup analysis of patients receiving CLT, favorable performance status (hazard ratio, 0.43; 95% confidence interval, 0.22-0.84; P=.01) was found to predict improved OS. Conclusions: Comprehensive local therapy was associated with improved OS in an adjusted analysis and seemed to favorably influence OS and PFS when factors such as N status, number of metastatic lesions, and disease sites were controlled for with propensity score–matched analysis. Patients with favorable performance status had improved outcomes with CLT. Ultimately, prospective, randomized trials are needed to provide definitive evidence as to the optimal treatment approach for this patient population.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Diagnosing and overcoming recombination and resistive losses in non-silicon solar cells using a silicon-inspired characterization platform

This project aimed to generate the characterization tools needed for accurate and systematic loss analysis in non-silicon photovoltaic solar cell technologies and, through the use of these tools and analysis techniques, contribute to the development of a novel class of hetero-contacts to II-VI absorbers, with the final goal of demonstrating record-breaking CdSeTe devices. CdSeTe solar cells provide a prime example of the potential impact of the techniques we proposed to develop and implement: record poly-CdSeTe cells have bandgap-voltage deficits (W oc ) of approximately 550 mV, as compared with below 400 mV for all other mature PV technologies. Similarly, these record CdSeTe devices have FFs below 80%, when other mature cells are near or above 85%. Frustratingly, a systematic identification of the origin of these sub-par performances—for example recombination or resistive losses—has been lacking, thus slowing down the development of these technologies. Similarly, it is often asserted that CdSeTe cells need a better back (hole) contact. Although most believe this is true, no one knew—at the start of this project—how high the V oc and FF could be for a given cell if it had a perfect back contact. Such characterization techniques and loss analysis methods exist and are routinely performed on c-Si solar cells (e.g. injection-dependent lifetime, Suns-V oc , transfer length method, etc). Over the years, they have been instrumental in the development of silicon devices that operate at 91% of their theoretical (Auger) limit. Lifetime testing, and the associated reconstruction of the implied-J-V curve, can moreover be performed at every cell-processing step, thus allowing a direct peek into the impact of that step on cell performance. Therefore, adapting these techniques and tools to non-Si devices would greatly improve their learning rate. In this project, we developed a Suns-ERE technique—the equipment, methodology, and know-how—to measure the implied-J-V curve, the pseudo-J-V curve, and the actual J-V curve of a thin-film solar cell, allowing an accurate assessment of the quality of the bulk material and its surface passivation, the selectivity of the contact, and its resistivity. We used this technique to show that the absorber of present CdSeTe solar cells is capable of achieving 1 V Voc,, that passivation layers exist (e.g., Al2O3) that can support such high voltages, and that the barrier is identifying contact layers that are both passivating and carrier-selective. The characterization platform created in this project and the understanding generated using it will accelerate the progress of non-silicon PV technologies. In particular, the project will contribute to CdSeTe solar cells with Voc > 1 V and cell efficiency > 24%. Such cells provide a pathway to module-level efficiencies >23%. As CdSeTe presently competes with silicon on module cost (in $\$ $/W) and yet has significantly more room for efficiency gains, the potential for LCOE reduction is particularly large. For example, CdTe modules with an efficiency of 21% would allow an LCOE below $\$ $0.04kWh -1 in average US climates.

14 SOLAR ENERGY↗

Impact of Amorphous SiO{sub 2} Nanoparticles on a Living Organism: Morphological, Behavioral, and Molecular Biology Implications

It is generally accepted that silica (SiO{sub 2}) is not toxic. But the increasing use of silica nanoparticles (SiO{sub 2}NPs) in many different industrial fields has prompted the careful investigation of their toxicity in biological systems. In this report, we describe the effects elicited by SiO{sub 2}NPs on animal and cell physiology. Stable and monodisperse amorphous silica nanoparticles, 25 nM in diameter, were administered to living Hydra vulgaris (Cnidaria). The dose-related effects were defined by morphological and behavioral assays. The results revealed an all-or-nothing lethal toxicity with a rather high threshold (35 nM NPs) and a LT50 of 38 h. At sub lethal doses, the morphophysiological effects included: animal morphology alterations, paralysis of the gastric region, disorganization and depletion of tentacle specialized cells, increase of apoptotic and collapsed cells, and reduction of the epithelial cell proliferation rate. Transcriptome analysis (RNAseq) revealed 45 differentially expressed genes, mostly involved in stress response and cuticle renovation. Our results show that Hydra reacts to SiO{sub 2}NPs, is able to rebalance the animal homeostasis up to a relatively high doses of SiO{sub 2}NPs, and that the physiological modifications are transduced to gene expression modulation.

60 APPLIED LIFE SCIENCES↗

Global properties and bifurcation analysis of an HIV-1 infection model with two target cells

In this paper, the authors consider a four-compartmental HIV epidemiological model, which describes the interaction between HIV virus and two target cells, CD4 T cells and macrophages in vivo. It is proved that the bilinear incidence can cause the backward bifurcation, where a locally asymptotically stable disease-free equilibrium co-exists with a locally asymptotically stable endemic equilibrium when the basic reproduction number (R{sub 0}) is less than unity. It is shown that a sequence of Hopf bifurcations occur at the endemic equilibrium by choosing one parameter of the model as the bifurcation parameter. Meanwhile, the global asymptotic stabilities of the equilibria are established by constructing suitable Lyapunov functions under some conditions. Furthermore, the authors develop an extended model by incorporating with the intracellular delays and derive global asymptotic stability of the delayed model by constructing Lyapunov functions. Some numerical simulations for justifying the theoretical analysis results are also given.

60 APPLIED LIFE SCIENCES↗

Construction of a high-yield dengue virus by replacing nonstructural proteins 3–4B without increasing virulence

Highlights: • Dengue virus clinical isolate exhibits lower virus production in cultured cells. • The NS3-NS4B region of high-replicating laboratory strain enhances vRNA synthesis. • The replacement with the NS3-NS4B region of H241 does not increase virulence. Producing virus at high yield is critically important for development of whole virion inactivated vaccines or live attenuated vaccines. Most dengue virus (DENV) clinical isolates, however, replicate at low levels in cultured cells, which limits their use for vaccine development. The present study examined differences between low-replicating DENV clinical isolates and high-replicating laboratory strains with the aim of engineering high-yield DENV clinical isolates. Construction of a series of recombinant chimeric viruses derived from a high-replicating laboratory DENV type 4 (DENV-4) H241 strain and a clinical isolate revealed that the NS3-NS4B region of H241 conferred a replication advantage in cultured cells. Furthermore, northern blot analysis revealed that this advantage was due to more efficient synthesis of viral RNA. Importantly, replacement of the NS3-NS4B region of H241 did not increase virulence in mice, suggesting that viral production can be increased safely. This study provided information that will facilitate engineering of safe and high-yield viruses that can be used for vaccine development.

60 APPLIED LIFE SCIENCES↗

Technical Analysis of Installed Micro-Combined Heat and Power Fuel-Cell System

Combined heat and power fuel cell systems (CHP-FCSs) provide consistent electrical power and hot water with greater efficiency and lower emissions than alternative sources. These systems can be used either as baseload, grid-connected, or as off-the-grid power sources. This report presents a technical analysis of 5 kWe CHP-FCSs installed in different locations in the U.S. At some sites as many as five 5 kWe system is used to provide up to 25kWe of power. Systems in this power range are considered “micro”-CHP-FCS. To better assess performance of micro-CHP-FCS and understand their benefits, the U.S. Department of Energy worked with ClearEdge Power to install fifteen 5-kWe PBI high temperature PEM fuel cells (CE5 models) in the commercial markets of California and Oregon. Pacific Northwest National Laboratory evaluated these systems in terms of their economics, operations, and technical performance. These units were monitored from September 2011 until June 2013. During this time, about 190,000 hours of data were collected and more than 17 billion data points were analyzed. Beginning in July 2013, ten of these systems were gradually replaced with ungraded systems (M5 models) containing phosphoric acid fuel cell technology. The new units were monitored until June 2014 until they went offline because ClearEdge was bought by Doosan at the time and the new manufacturer did not continue to support data collection and maintenance of these units. During these two phases, data was collected at once per second and data analysis techniques were applied to understand behavior of these systems. The results of this analysis indicate that systems installed in the second phase of this demonstration performed much better in terms of availability, consistency in generation, and reliability. The average net electrical power output increased from 4.1 to 4.9 kWe, net heat recovery from 4.7 to 5.4 kWth, and system availability improved from 94% to 95%. The average net system electric efficiency, average net heat recovery efficiency, and overall net efficiency of the system increased respectively from 33% to 36%, from 38% to 41%, and from 71% to 76%. The temperature of water sent to sit however reduced by about 16% from 51⁰C to 43 ⁰C. This was a control strategy and the temperature can be controlled depending on building heat demands. More importantly, the number of shutdowns and maintenance events required to keep the systems running at the manufacturer’s rated performance specifications were substantially reduced by about 76% (for 8 to 10 units running over a one-year period). From July 2012 to June 2013, there were eight CE5 units in operation and a total of 134 scheduled and unscheduled shutdowns took place. From July 2013 to June 2014, between two to ten units were in operation and only 32 shutdowns were reported (all unscheduled). In summary, the number of shutdowns reduced from 10 shutdowns per month on average for eight CE5units to an average of 2.7 shutdowns per month for M5 units (between two to ten units).

combined heat and power↗

SwinCell: a 3D transformer and flow-based framework for improved cell segmentation

Segmentation of three-dimensional (3D) cellular images is fundamental for studying and understanding cell structure and function. However, 3D cellular segmentation is challenging, particularly for dense cells and tissues. This challenge arises mainly from the complex contextual information within 3D images, anisotropic properties, and the sensitivity to internal cellular structures, which often lead to incorrect segmentation. In this work, we introduce SwinCell, a 3D transformer-based framework that leverages Swin-transformer to predict flow and differentiate individual cell instances. We demonstrate SwinCell’s utility in the segmentation of nuclei, colon tissue cells, and densely cultured cells. SwinCell strikes a balance between maintaining detailed local feature recognition and understanding broader contextual information. Through extensive testing with both public and in-house 3D cell imaging datasets, SwinCell shows utility in segmenting dense cells, making it a valuable tool for 3D segmentation in cellular analysis that could expedite research in cell biology and tissue engineering.

59 BASIC BIOLOGICAL SCIENCES↗

Mouse osteoblastic cell line (MC3T3-E1) expresses extracellular calcium (Ca2+o)-sensing receptor and its agonists stimulate chemotaxis and proliferation of MC3T3-E1 cells

The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and kidney. Osteoblasts appear at sites of osteoclastic bone resorption during bone remodeling in the "reversal" phase following osteoclastic resorption and preceding bone formation. Bone resorption produces substantial local increases in Ca2+o that could provide a signal for osteoblasts in the vicinity, leading us to determine whether such osteoblasts express the CaR. In this study, we used the mouse osteoblastic, clonal cell line MC3T3-E1. Both immunocytochemistry and Western blot analysis, using an antiserum specific for the CaR, detected CaR protein in MC3T3-E1 cells. We also identified CaR transcripts in MC3T3-E1 cells by Northern analysis using a CaR-specific riboprobe and by reverse transcription-polymerase chain reaction with CaR-specific primers, followed by nucleotide sequencing of the amplified products. Exposure of MC3T3-E1 cells to high Ca2+o (up to 4.8 mM) or the polycationic CaR agonists, neomycin and gadolinium (Gd3+), stimulated both chemotaxis and DNA synthesis in MC3T3-E1 cells. Therefore, taken together, our data strongly suggest that the osteoblastic cell line MC3T3-E1 possesses both CaR protein and mRNA very similar, if not identical, to those in parathyroid and kidney. Furthermore, the CaR in these osteoblasts could play a key role in regulating bone turnover by stimulating the proliferation and migration of such cells to sites of bone resorption as a result of local release of Ca2+o.

Non-NASA Center↗

Combined Theoretical and Experimental Analysis of Processes Determining Cathode Performance in Solid Oxide Fuel Cells

Solid oxide fuel cells (SOFC) are under intensive investigation since the 1980’s as these devices open the way for ecologically clean direct conversion of the chemical energy into electricity, avoiding the efficiency limitation by Carnot’s cycle for thermochemical conversion. However, the practical development of SOFC faces a number of unresolved fundamental problems, in particular concerning the kinetics of the electrode reactions, especially oxygen reduction reaction. We review recent experimental and theoretical achievements in the current understanding of the cathode performance by exploring and comparing mostly three materials: (La,Sr)MnO3 (LSM), (La,Sr)(Co,Fe)O3 (LSCF) and (Ba,Sr)(Co,Fe)O3 (BSCF). Special attention is paid to a critical evaluation of advantages and disadvantages of BSCF, which shows the best cathode kinetics known so far for oxides. We demonstrate that it is the combined experimental and theoretical analysis of all major elementary steps of the oxygen reduction reaction which allows us to predict the rate determining steps for a given material under specific operational conditions and thus control and improve SOFC performance.

Environmental Molecular Sciences Laboratory↗

Palmer Station, Antarctica: A Ground-Based Spaceflight Analog Suitable for Validation of Biomedical Countermeasures for Deep Space Missions

Astronauts are known to exhibit a variety of immunological alterations during spaceflight including changes in leukocyte distribution and plasma cytokine concentrations, a reduction in T-cell function, and subclinical reactivation of latent herpesviruses. These alterations are most likely due to mission-associated stressors including circadian misalignment, microgravity, isolation, altered nutrition, and increased exposure to cosmic radiation. Some of these stressors may also occur in terrestrial situations. This study sought to determine if crewmembers performing overwinter deployment at Palmer Station, Antarctica displayed similar immune alterations. The larger goal was to validate a ground analog suitable for the evaluation of countermeasures designed to protect astronauts during future deep space missions. For this pilot study, plasma, saliva, hair, and health surveys were collected from Palmer Station, Antarctica winterover participants at baseline, and at five overwinter timepoints. Twenty-six subjects consented to participate over the course of two seasons. Initial sample processing was performed at Palmer, and eventually stabilized samples were returned to the Johnson Space Center for analysis. A white blood cell differential was performed (real time) using a fingerstick blood sample to determine alterations in basic leukocyte subsets throughout the winterover. Plasma and saliva samples were analyzed for 30 and 13 cytokines, respectively. Saliva was analyzed for cortisol concentration and three latent herpesviruses (DNA by qPCR), EBV, HSV1, and VZV. Hair samples were analyzed for several hormones, as a measure of stress over prolonged periods of time. Voluntary surveys related to general health and adverse clinical events were distributed to participants. It is noteworthy that due to logistical constraints due to COVID-19, the baseline samples for each season were collected in Punta Arenas, Chile, after long international travel and during isolation. Therefore, the palmer pre mission samples may not reflect a true normal ‘baseline’. Minimal alterations were observed in leukocyte distribution during overwinter. The mean percentage of monocyte concentration elevated at one timepoint. Plasma G-CSF, IL1RA, MCP-1, MIP-1β, TNFα and VEGF were decreased during at least one overwinter timepoint, whereas RANTES was significantly increased. No statistically significant changes were observed in mean saliva cytokine concentrations. Salivary cortisol was substantially elevated throughout the entire winterover compared to baseline. Compared to shedding levels observed in healthy controls (23%), the percentage of participants who shed EBV was higher throughout all winterover timepoints (52-60%). Five subjects shed HSV1 during at least one timepoint throughout the season compared to no subjects shedding during pre-deployment. Finally, VZV reactivation, common in astronauts but exceptionally rare in ground-based stress analogs, was observed in one subject during pre-deployment and a different subject at WO2 and WO3. These pilot data, somewhat influenced by the COVID-19 situation, do suggest that participants at Palmer Station do undergo immunological alterations similar to, but likely in reduced magnitude, as those observed in astronauts. We suggest that overwinter at Palmer Station may be suitable test analog for spaceflight biomedical countermeasures designed to mitigate clinical risks for deep space missions.

Space↗

High-Throughput Directed Evolution of Marine Microalgae and Phototrophic Consortia for Improved Biomass Yields (Final Report)

Primary project achievements include using selective pressures (O 2 , light, temperature) and developing culturing regimes for the diatom Nitzschia inconspicua str. hildebrandi to attain enrichments with an ~90% increase in areal biomass productivity relative to the parental strain under pond-mimicking conditions with high O 2 stress in laboratory bioreactors. The resulting strain (GAI-337) was tested further for dilution time, culture density, CO 2 supplementation, pH, temperature, and dissolved O 2 concentration under outdoor pond-mimicking conditions to improve areal productivities. These experiments yielded an optimum harvest and dilution time just after sunset, ~0.45 g AFDW L -1 initial culture density for maximal productivities, no requirement for CO 2 supplementation or pH control, maximal performance under a diel temperature curve going from 24 °C at night to 36 °C during the day, and benefits from some O 2 removal from the culture by bubbling with air. Using pond-mimicking laboratory bioreactors, N. inconspicua GAI-337 achieved ~42 g AFDW m -2 d -1 . Nutrient limitation experiments resulted in a biomass composition that equated to ~160 Gallons of Gasoline Equivalent energy per ton AFDW, highlighting the potential of GAI-337 as a promising renewable fuel feedstock strain. Genome resequencing has revealed genome alterations potentially contributing to the improved growth of GAI-337 in the laboratory. Based on the comparative analyses of the GAI-337 and GAI-229 (reference) strains, we identified 144 single nucleotide substitutions that resulted in amino acid change, 7 single nucleotide substitutions that resulted in protein truncation; 5 deletions; and 1 frameshift mutation. From the mutations that potentially affect expression of functionally annotated genes, particular interest was noted for an interferon-induced 6-16 family protein that may be involved in the host immune response against microbe invasion; the chaperone protein DnaK, which may function to protect the folding of proteins within the cell; and SPRY domain protein that is found in many eukaryotic proteins important in cell signaling pathways. Transcriptome analysis revealed over 1000 genes with increased transcript levels. Many of these and many of the genes with mutations are not yet functionally annotated and an increased bioinformatics effort is necessary to more completely analyze the Nitzschia inconspicua genome. Adaptive laboratory evolution (ALE) was performed for over 300 days using consecutive 0.5°C temperature increases in a constant temperature incubator to attain greater thermal tolerance in Nitzschia inconspicua. The adapted strain was able to grow at a constant temperature of 37.5°C; whereas this constant temperature was lethal to the parental control, which had an upper temperature boundary of 35.5°C prior to adaptive evolution. Several high-temperature clonal isolates were obtained from the evolved population following ALE, and increased temperature tolerance was observed in clonal adapted cultures. The final temperature adaptation was maintained through cryopreservation and was observed in multiple clonal isolates, including multiple clonal isolates with significantly increased cell size, indicating the potential occurrence of a sexual cycle during the clonal isolation process. A survey of Nannochloropsis strains was conducted for tolerances to high pH and high bicarbonate media. Nannochloropsis granulata showed promising growth in diel bioreactors and was successfully grown at the GAI Kauai farm site in long-term growth campaigns. Co-culturing using Nitzschia inconspicua, Nannochloropsis and a cyanobacterium were assembled in the laboratory to determine if productivity synergies could be attained. Although all strains grew well in the laboratory high-bicarbonate media individually, the cyanobacterium quickly outgrew the other strains in the laboratory consortium pushing the co-culture away from a diverse (and potentially synergistic assemblage) phototroph culture towards a monoculture dominated by the cyanobacterium. Several outdoor growth campaigns were conducted, with productivities ranging between 10-20 g/m 2 /d of biomass. The best performing strain in the laboratory (GAI-337) did not outperform reference strains at the Kauai farm under the conditions used. Addition growth campaigns are necessary under conditions that result in higher biomass (>20 g/m 2 /d) and that attain higher O 2 levels are likely necessary. Initial data indicate that the thermally adapted strain did slightly better than the control strain at higher temperatures; however, additional campaigns are necessary to establish statistical significance. In summary, Nitzschia inconspicua is able to attain exemplary biomass and lipid yields in the laboratory bioreactors. Strain evolution to both O 2 and temperature resulted in targeted strain improvements. Additional outdoor campaigns are necessary to determine if laboratory improvements translate to the field.

09 BIOMASS FUELS↗

Evolutionary Diversification of Host-Targeted Bartonella Effectors Proteins Derived from a Conserved FicTA Toxin-Antitoxin Module

Proteins containing a FIC domain catalyze AMPylation and other post-translational modifications (PTMs). In bacteria, they are typically part of FicTA toxin-antitoxin modules that control conserved biochemical processes such as topoisomerase activity, but they have also repeatedly diversified into host-targeted virulence factors. Among these, Bartonella effector proteins (Beps) comprise a particularly diverse ensemble of FIC domains that subvert various host cellular functions. However, no comprehensive comparative analysis has been performed to infer molecular mechanisms underlying the biochemical and functional diversification of FIC domains in the vast Bep family. Here, we used X-ray crystallography, structural modelling, and phylogenetic analyses to unravel the expansion and diversification of Bep repertoires that evolved in parallel in three Bartonella lineages from a single ancestral FicTA toxin-antitoxin module. Our analysis is based on 99 non-redundant Bep sequences and nine crystal structures. Inferred from the conservation of the FIC signature motif that comprises the catalytic histidine and residues involved in substrate binding, about half of them represent AMP transferases. A quarter of Beps show a glutamate in a strategic position in the putative substrate binding pocket that would interfere with triphosphate-nucleotide binding but may allow binding of an AMPylated target for deAMPylation or another substrate to catalyze a distinct PTM. The β-hairpin flap that registers the modifiable target segment to the active site exhibits remarkable structural variability. The corresponding sequences form few well-defined groups that may recognize distinct target proteins. The binding of Beps to promiscuous FicA antitoxins is well conserved, indicating a role of the antitoxin to inhibit enzymatic activity or to serve as a chaperone for the FIC domain before translocation of the Bep into host cells. Taken together, our analysis indicates a remarkable functional plasticity of Beps that is mostly brought about by structural changes in the substrate pocket and the target dock. These findings may guide future structure–function analyses of the highly versatile FIC domains.

59 BASIC BIOLOGICAL SCIENCES↗

Analysis of the interaction of an electron beam with a solar cell. I. II

The short-circuit current generated by the electron beam of a scanning electron microscope when it impinges on the N-P junction of a solar cell is known to be dependent on the configuration used to investigate the cell's response, and the situation for one specific configuration is analyzed. This configuration is the case in which the highly collimated electron beam strikes the edge of a planar junction a variable distance away from the edge of the depletion layer. An earlier treatment is generalized to encompass the ohmic contact at the back surface. The analysis employing Fourier and Wiener-Hopf techniques shows that it is impractical to determine the bulk diffusion length of a solar cell by a SEM used in the studied configuration unless the ohmic contact is partially removed.

Von Roos, O.↗

State of the States: Fuel Cells in America 2015

This December 2015 report, the sixth in a series, provides a comprehensive analysis of state activities supporting fuel cell and hydrogen technology, profiles of leading states, and a catalog of recent installations, policies, funding, and deployments around the country.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Japan's participation in space station design: Feasibility study of GaAs solar cells for space station applications

The report gives the results of feasibility studies and a cost analysis done on GaAs solar battery cells for space stations. The studies and their results are as follows: (1) Cell size - The 2 x 4 cm cell size was found superior to the 4 x 4 cm cell; (2) Manufacturing technology - Overall, LPE crystal growth was found more suitable than MO-CVD. Current technology for post-growth processes and applying large-area cover glass can be used with few or no modifications; (3) Cell assemblies - Tests for mechanical and thermal stresses encountered from assembly through operation are recommended; (4) Procuring materials - Steps should be taken to avoid sharp price increases due to a speculative gallium market. There are no problems with arsenic materials; (5) Production facilities - The capital investment needed remains to be determined, but a working area of 4000 m2 will be required; (6) Cell costs to be determined; (7) Cell development-supply plan - Two-year lead time will be needed to develop the necessary technology and prepare for production.

Source record↗

Load transfer in the stiffener-to-skin joints of a pressurized fuselage

Structural analyses are developed to determine the linear elastic and the geometrically nonlinear elastic response of an internally pressurized, orthogonally stiffened, composite material cylindrical shell. The configuration is a long circular cylindrical shell stiffened on the inside by a regular arrangement of identical stringers and identical rings. Periodicity permits the analysis of a unit cell model consisting of a portion of the shell wall centered over one stringer-ring joint. The stringer-ring-shell joint is modeled in an idealized manner; the stiffeners are mathematically permitted to pass through one another without contact, but do interact indirectly through their mutual contact with the shell at the joint. Discrete beams models of the stiffeners include a stringer with a symmetrical cross section and a ring with either a symmetrical or an asymmetrical open section. Mathematical formulations presented for the linear response include the effect of transverse shear deformations and the effect of warping of the ring's cross section due to torsion. These effects are important when the ring has an asymmetrical cross section because the loss of symmetry in the problem results in torsion and out-of-plane bending of the ring, and a concomitant rotation of the joint at the stiffener intersection about the circumferential axis. Data from a composite material crown panel typical of a large transport fuselage structure are used for two numerical examples. Although the inclusion of geometric nonlinearity reduces the 'pillowing' of the shell, it is found that bending is localized to a narrow region near the stiffener. Including warping deformation of the ring into the analysis changes the sense of the joint rotation. Transverse shear deformation models result in increased joint flexibility.

Johnson, Eric R.↗

Understanding Subsidies to Achieve Diesel Powertrain Financial Parity for Heavy-Duty Fuel Cell Electric Vehicles

The development of a long-term sustainable hydrogen energy economy for commercial vehicle transportation will need to overcome key critical technical and logistics considerations in the near term. As compared to zero-emission powertrains, fossil-fuel-based powertrains provide mission flexibility and high uptime at a comparatively low total cost of ownership (TCO). While the incumbent carbon-intensive powertrains suffer from poor efficiency and are not sustainable to support global climate change initiatives in transportation decarbonization, techno-economic challenges continue to create complex barriers to the large-scale displacement of these with highly electrified powertrains architectures. Here, this article specifically addresses opportunities that well-targeted subsidies would afford in achieving fuel cell electric powertrain financial parity with diesel powertrains in heavy-duty trucks (HDTs). It shows that a rigorous assessment of system TCO factors will be critical in designing a viable subsidy strategy. Based on powertrain component and fuel price points, subsidy variations (for both capital expenses and operating fuel expenses) are assessed and quantified to determine where and how much subsidies should be leveraged to accelerate achieving diesel system financial parity. It shows that subsidies on hydrogen fuel expenses (and associated constituents) will play an important role in achieving this goal while subsidies on capital expenses (the more typical subsidy formulation) may not always be the preferred subsidy strategy. The results provide subsidy agencies with clear guidance and a database approach to characterize and implement viable HDT hydrogen powertrain system subsidy strategies. The approach may be readily tailored for other applications and system architectures.

33 ADVANCED PROPULSION SYSTEMS↗

How do deer respiratory epithelial cells weather the initial storm of SARS-CoV-2 WA1/2020 strain?

The potential infectivity of severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) in animals raises a public health and economic concern, particularly the high susceptibility of white-tailed deer (WTD) to SARS-CoV-2. The disparity in the disease outcome between humans and WTD is very intriguing, as the latter are often asymptomatic, subclinical carriers of SARS-CoV-2. To date, no studies have evaluated the innate immune factors responsible for the contrasting SARS-CoV-2-associated disease outcomes in these mammalian species. A comparative transcriptomic analysis in primary respiratory epithelial cells of human (HRECs) and WTD (Deer-RECs) infected with the SARS-CoV-2 WA1/2020 strain was assessed throughout 48 h post inoculation (hpi). Both HRECs and Deer-RECs were susceptible to virus infection, with significantly ( P < 0.001) lower virus replication in Deer-RECs. The number of differentially expressed genes (DEG) gradually increased in Deer-RECs but decreased in HRECs throughout the infection. The ingenuity pathway analysis of DEGs further identified that genes commonly altered during SARS-CoV-2 infection mainly belong to cytokine and chemokine response pathways mediated via interleukin-17 (IL-17) and nuclear factor-κB (NF-κB) signaling pathways. Inhibition of the NF-κB signaling in the Deer-RECs pathway was predicted as early as 6 hpi. The findings from this study could explain the lack of clinical signs reported in WTD in response to SARS-CoV-2 infection as opposed to the severe clinical outcomes reported in humans. IMPORTANCE. This study demonstrated that human and white-tailed deer primary respiratory epithelial cells are susceptible to the SARS-CoV-2 WA1/2020 strain infection. However, the comparative transcriptomic analysis revealed that deer cells could limit viral replication without causing hypercytokinemia by downregulating IL-17 and NF-κB signaling pathways. Identifying differentially expressed genes in human and deer cells that modulate key innate immunity pathways during the early infection will lead to developing targeted therapies toward preventing or mitigating the “cytokine storm” often associated with severe cases of coronavirus disease 19 (COVID-19). Moreover, results from this study will aid in identifying novel prognostic biomarkers in predicting SARS-CoV-2 adaption and transmission in deer and associated cervids.

60 APPLIED LIFE SCIENCES↗