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Abstract Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lung cancer still leads cancer mortality, and non-small-cell lung carcinoma patients with mutant EGFR cannot benefit from checkpoint inhibitors due to toxicity, relying only on palliative chemotherapy and the third-generation tyrosine kinase inhibitor (TKI) osimertinib. This new drug extends lifespan by 9-months vs. second-generation TKIs, but unfortunately, cancers relapse due to resistance mechanisms and the lack of antitumor immune responses. Here we explored the combination of osimertinib with anti-HER3 monoclonal antibodies and observed that the immune system contributed to eliminate tumor cells in mice and co-culture experiments using bone marrow-derived macrophages and human PBMCs. Osimertinib led to apoptosis of tumors but simultaneously, it triggered inositol-requiring-enzyme (IRE1α)-dependent HER3 upregulation, increased macrophage infiltration, and activated cGAS in cancer cells to produce cGAMP (detected by a lentivirally transduced STING activity biosensor), transactivating STING in macrophages. We sought to target osimertinib-induced HER3 upregulation with monoclonal antibodies, which engaged Fc receptor-dependent tumor elimination by macrophages, and STING agonists enhanced macrophage-mediated tumor elimination further. Thus, by engaging a tumor non-autonomous mechanism involving cGAS-STING and innate immunity, the combination of osimertinib and anti-HER3 antibodies could improve the limited therapeutic and stratification options for advanced stage lung cancer patients with mutant EGFR.

Lipoprotein lipase (LPL) and hepatic lipase (HL) enzyme activities were previously reported to be regulated during development, but the underlying molecular events are unknown. In addition, little is known about LPL evolution. We cloned and sequenced a complete mouse LPL cDNA. Comparison of sequences from mouse, human, bovine, and guinea pig cDNAs indicated that the rates of evolution of mouse, human, and bovine LPL are quite low, but guinea pig LPL has evolved several times faster than the others. 32P-Labeled mouse LPL and rat HL cDNAs were used to study lipase mRNA tissue distribution and developmental regulation in the rat. Northern gel analysis revealed the presence of a single 1.87 kb HL mRNA species in liver, but not in other tissues including adrenal and ovary. A single 4.0 kb LPL mRNA species was detected in epididymal fat, heart, psoas muscle, lactating mammary gland, adrenal, lung, and ovary, but not in adult kidney, liver, intestine, or brain. Quantitative slot-blot hybridization analysis demonstrated the following relative amounts of LPL mRNA in rat tissues: adipose, 100%; heart, 94%; adrenal, 6.6%; muscle, 3.8%; lung, 3.0%; kidney, 0%; adult liver, 0%. The same quantitative analysis was used to study lipase mRNA levels during development. There was little postnatal variation in LPL mRNA in adipose tissue; maximal levels were detected at the earliest time points studied for both inguinal and epididymal fat. In heart, however, LPL mRNA was detected at low levels 6 days before birth and increased 278-fold as the animals grew to adulthood.(ABSTRACT TRUNCATED AT 250 WORDS)

Despite the recent achievements in the stretchability of kirigami metallic glasses, relevant research is still mainly relying on the single-level kirigami structure. In our work, three different hierarchical levels of patterns were developed for kirigami metallic glass structures for both strip and square units. The degree of freedom that reflects the availability for morphing is shown to be a key factor affecting the mechanical response of the hierarchical metallic glasses. It is found that a high hierarchical order with a large degree of freedom leads to the high stretchability of kirigami metallic glasses. Kirigami metallic glasses, designed with square units, with a large degree of freedom show high stretchability compared to those designed with strip units, with a small degree of freedom, at the same hierarchical level. Our study, combining the degree of freedom in the hierarchical construction, highlights the potential for a multilevel architected structure as a programmable block for stretchable mechanical metamaterials.

Organic aerosol (OA) is a major constituent of ultrafine particulate matter (PM0. 1). Recent epidemiological studies have identified associations between PM0. 1 OA and premature mortality and low birth weight. In this study, the source-oriented UCD/CIT model was used to simulate the concentrations and sources of primary organic aerosols (POA) and secondary organic aerosols (SOA) in PM0. 1 in California for a 9-year (2000–2008) modeling period with 4 km horizontal resolution to provide more insights about PM0. 1 OA for health effect studies. As a related quality control, predicted monthly average concentrations of fine particulate matter (PM2. 5) total organic carbon at six major urban sites had mean fractional bias of −0.31 to 0.19 and mean fractional errors of 0.4 to 0.59. The predicted ratio of PM2. 5 SOA ∕ OA was lower than estimates derived from chemical mass balance (CMB) calculations by a factor of 2–3, which suggests the potential effects of processes such as POA volatility, additional SOA formation mechanism, and missing sources. OA in PM0. 1, the focus size fraction of this study, is dominated by POA. Wood smoke is found to be the single biggest source of PM0. 1 OA in winter in California, while meat cooking, mobile emissions (gasoline and diesel engines), and other anthropogenic sources (mainly solvent usage and waste disposal) are the most important sources in summer. Biogenic emissions are predicted to be the largest PM0. 1 SOA source, followed by mobile sources and other anthropogenic sources, but these rankings are sensitive to the SOA model used in the calculation. Air pollution control programs aiming to reduce the PM0. 1 OA concentrations should consider controlling solvent usage, waste disposal, and mobile emissions in California, but these findings should be revisited after the latest science is incorporated into the SOA exposure calculations. The spatial distributions of SOA associated with different sources are not sensitive to the choice of SOA model, although the absolute amount of SOA can change significantly. Therefore, the spatial distributions of PM0. 1 POA and SOA over the 9-year study period provide useful information for epidemiological studies to further investigate the associations with health outcomes.

The source-oriented Weather Research and Forecasting chemistry model (SOWC) was modified to include warm cloud processes and was applied to investigate how aerosol mixing states influence fog formation and optical properties in the atmosphere. SOWC tracks a 6-D chemical variable (X, Z, Y, size bins, source types, species) through an explicit simulation of atmospheric chemistry and physics. A source-oriented cloud condensation nuclei module was implemented into the SOWC model to simulate warm clouds using the modified two-moment Purdue Lin microphysics scheme. The Goddard shortwave and long-wave radiation schemes were modified to interact with source-oriented aerosols and cloud droplets so that aerosol direct and indirect effects could be studied. The enhanced SOWC model was applied to study a fog event that occurred on 17 January 2011, in the Central Valley of California. Tule fog occurred because an atmospheric river effectively advected high moisture into the Central Valley and nighttime drainage flow brought cold air from mountains into the valley. The SOWC model produced reasonable liquid water path, spatial distribution and duration of fog events. The inclusion of aerosol–radiation interaction only slightly modified simulation results since cloud optical thickness dominated the radiation budget in fog events. The source-oriented mixture representation of particles reduced cloud droplet number relative to the internal mixture approach that artificially coats hydrophobic particles with hygroscopic components. The fraction of aerosols activating into cloud condensation nuclei (CCN) at a supersaturation of 0.5 % in the Central Valley decreased from 94 % in the internal mixture model to 80 % in the source-oriented model. This increased surface energy flux by 3–5 W m−2 and surface temperature by as much as 0.25 K in the daytime.

Copper-metallized gallium nitride (GaN) high-electron-mobility transistors (HEMTs) using a Ti/Pt/Ti diffusion barrier layer are fabricated and characterized for Ka-band applications. With a thick copper metallization layer of 6.8 μm adopted, the device exhibited a high output power density of 8.2 W/mm and a power-added efficiency (PAE) of 26% at 38 GHz. Such superior performance is mainly attributed to the substantial reduction of the source and drain resistance of the device. In addition to improvement in the Radio Frequency (RF) performance, the successful integration of the thick copper metallization in the device technology further reduces the manufacturing cost, making it extremely promising for future fifth-generation mobile communication system applications at millimeter-wave frequencies.

Motivated by numerous applications, active research is being conducted worldwide to explore the terahertz (THz) region of the electromagnetic spectrum. Waveguides are key components for the generation, propagation, and utilization of THz waves. This paper addresses two types of commonly-used waveguides in their simplest implementation: the single-wire and hollow metallic waveguides. Research on these two types of waveguides has appeared rather separately in literature. Yet they are based on a common formalism. This suggests a treatment on the same theoretical footing for an examination of their basic properties in terms of the field behavior, power flow, dispersion relation, and attenuation rate. Here, we present a comparative study on their similarities, differences, and relative merits, along with physical interpretations.

By introducing a sub-terawatt (TW) laser pulse into a high-density gas target, the self-focusing effect and the self-modulation instability can greatly enhance the laser peak power to a level capable of driving the laser wakefield acceleration (LWFA) of electrons. A particle-in-cell model has been developed to study the scheme in which 1030-nm pulses produced from a diode-pumped laser system are introduced into a gas cell with a flat-top density profile, allowing the LWFA to be operated at high frequencies. Because 1030-nm lasers are typically produced with a long duration >200 fs, a spectral broadening technique can be applied to reduce the pulse duration, from which a greater ponderomotive force is acquired to drive LWFA. To understand the dependence of LWFA performance on the driving pulse duration, selected durations, ranging from 200 fs to 10 fs, are assigned for 0.5-TW, 1030-nm pulses in a series of simulations. Results show that a duration around 50 fs can provide the optimal LWFA results, as a compromise between the weak ponderomotive force available from a long pulse >100 fs and the depletion effect which can rapidly diminish a short pulse 2 μm represents a viable route to realize the LWFA with a low laser peak power; in this way, an appropriately selected target density which allows the laser peak power PL ∼ 1.25Pcr of self-focusing critical power is favourable for realizing an efficient LWFA process.

For the first time, a ~ decadal (9 years from 2000 to 2008) air quality model simulation with 4 km horizontal resolution over populated regions and daily time resolution has been conducted for California to provide air quality data for health effect studies. Model predictions are compared to measurements to evaluate the accuracy of the simulation with an emphasis on spatial and temporal variations that could be used in epidemiology studies. Better model performance is found at longer averaging times, suggesting that model results with averaging times ≥ 1 month should be the first to be considered in epidemiological studies. The UCD/CIT model predicts spatial and temporal variations in the concentrations of O3, PM2.5, elemental carbon (EC), organic carbon (OC), nitrate, and ammonium that meet standard modeling performance criteria when compared to monthly-averaged measurements. Predicted sulfate concentrations do not meet target performance metrics due to missing sulfur sources in the emissions. Predicted seasonal and annual variations of PM2.5, EC, OC, nitrate, and ammonium have mean fractional biases that meet the model performance criteria in 95, 100, 71, 73, and 92% of the simulated months, respectively. The base data set provides an improvement for predicted population exposure to PM concentrations in California compared to exposures estimated by central site monitors operated 1 day out of every 3 days at a few urban locations. Uncertainties in the model predictions arise from several issues. Incomplete understanding of secondary organic aerosol formation mechanisms leads to OC bias in the model results in summertime but does not affect OC predictions in winter when concentrations are typically highest. The CO and NO (species dominated by mobile emissions) results reveal temporal and spatial uncertainties associated with the mobile emissions generated by the EMFAC 2007 model. The WRF model tends to overpredict wind speed during stagnation events, leading to underpredictions of high PM concentrations, usually in winter months. The WRF model also generally underpredicts relative humidity, resulting in less particulate nitrate formation, especially during winter months. These limitations must be recognized when using data in health studies. All model results included in the current manuscript can be downloaded free of charge at http://faculty.engineering.ucdavis.edu/kleeman/ .

The use of Polyvinylidene Fluoride (PVDF) based piezoelectric nanofibers for sensing and actuation has been reported widely in the past. However, in most cases, PVDF piezoelectric nanofiber mats have been used for sensing applications. This work fundamentally characterizes a single electrospun PVDF nanofiber and demonstrates its application as a sensing element for nanoelectromechanical sensors (NEMS). PVDF nanofiber mats were spun by far field electrospinning (FFES) process and complete material characterization was conducted by means of scanning electron microscope (SEM) imaging, Raman Spectroscopy and FTIR spectroscopy. An optimized recipe was developed for spinning a single suspended nanofiber on a specially designed MEMS substrate which allows the nano-mechanical and electrical characterization of a single PVDF nanofiber. Electrical characterization is conducted using a single suspended nanofiber to determine the piezoelectric coefficient (d33) of the nanofiber to be -58.77 pm/V. Also the mechanical characterization conducted using a nanoindenter revealed a Young’s Modulus and hardness of 2.2 GPa and 0.1 GPa respectively. Finally, an application that utilizes the single PVDF nanofiber as a sensing element to form a NEMS flow sensor is demonstrated. The single nanofiber flow sensor is tested in presence of various oscillatory flow conditions.

The improvement of flame-retardant properties of polyamide 6 (PA6) was achieved by using reduced graphene oxide decorated with halloysite nanotubes (HNTs-d-rGO) hybrid composite as the additive in PA6 matrix. The intimate integration of reduced graphene oxide (rGO) and halloysite nanotubes (HNTs) through a three-step chemical functionalization, enabled the combination of their unique physical and chemical characteristics together. The nanostructure of HNTs-d-rGO was determined by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). A morphological study revealed that HNTs-d-rGO was dispersed uniformly in PA6 matrix. From the results of cone calorimetry measurements, the fire retardant properties of PA6 were further improved with the addition of HNTs-d-rGO when compared with that of either HNTs, or GO, or a mixture of HNTs and GO (HNTs-m-GO) used in PA6 matrix. The results indicate clearly that higher flame-retardant activity of the integrated HNTs-d-rGO nanostructures than that of the simple mixture verifies the importance of the intimate integration between HNTs and rGO, which ascribe to the combination of the stable silica layer created by HNT and the barrier effect of rGO.

A source-oriented version of the Weather Research and Forecasting model with chemistry (SOWC, hereinafter) was developed. SOWC separately tracks primary particles with different hygroscopic properties rather than instantaneously combining them into an internal mixture. This approach avoids artificially mixing light absorbing black + brown carbon particles with materials such as sulfate that would encourage the formation of additional coatings. Source-oriented particles undergo coagulation and gas-particle conversion, but these processes are considered in a dynamic framework that realistically "ages" primary particles over hours and days in the atmosphere. SOWC more realistically predicts radiative feedbacks from anthropogenic aerosols compared to models that make internal mixing or other artificial mixing assumptions. A three-week stagnation episode (15 December 2000 to 6 January 2001) in the San Joaquin Valley (SJV) during the California Regional PM10 / PM2.5 Air Quality Study (CRPAQS) was chosen for the initial application of the new modeling system. Primary particles emitted from diesel engines, wood smoke, high-sulfur fuel combustion, food cooking, and other anthropogenic sources were tracked separately throughout the simulation as they aged in the atmosphere. Differences were identified between predictions from the source oriented vs. the internally mixed representation of particles with meteorological feedbacks in WRF/Chem for a number of meteorological parameters: aerosol extinction coefficients, downward shortwave flux, planetary boundary layer depth, and primary and secondary particulate matter concentrations. Comparisons with observations show that SOWC predicts particle scattering coefficients more accurately than the internally mixed model. Downward shortwave radiation predicted by SOWC is enhanced by ~1% at ground level chiefly because diesel engine particles in the source-oriented mixture are not artificially coated with material that increases their absorption efficiency. The extinction coefficient predicted by SOWC is reduced by an average of 0.012 km−1 (4.8%) in the SJV with a maximum reduction of ~0.2 km−1. Planetary boundary layer (PBL) height is increased by an average of 5.2 m (1.5%) with a~maximum of ~100 m in the SJV. Particulate matter concentrations predicted by SOWC are 2.23 μg m−3 (3.8%) lower than the average by the internally mixed version of the same model in the SJV because increased solar radiation at the ground increases atmospheric mixing. The changes in predicted meteorological parameters and particle concentrations identified in the current study stem from the mixing state of black carbon. The source-oriented model representation with realistic aging processes predicts that hydrophobic diesel engine particles remain largely uncoated over the +7 day simulation period, while the internal mixture model representation predicts significant accumulation of secondary nitrate and water on diesel engine particles. Similar results will likely be found in any air pollution stagnation episode that is characterized by significant particulate nitrate production. Future work should consider episodes where coatings are predominantly sulfate and/or secondary organic aerosol.

Full biodegradable poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) composite films were prepared with 5~40 wt% green tea polyphenol (TP) as toughener. The effects of mixing TP on mechanical properties, thermal properties and hydrophilic-hydrophobic properties of composite films were investigated. Tension test results show that the incorporation of TP in the PHBV matrix can enhance the toughness of the composite films. Differential scanning calorimetric (DSC) studies show that there is a single glass transition temperature and the lower melting point temperature. Fourier transform infrared (FT-IR) results confirm that the intermolecular hydrogen bonding interactions in composite films. Contact angle measurements show that the hydrophilicity of TP/PHBV composite films can be controlled through adjusting the composition of TP.