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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.

The effect of global climate change on the annual average concentration of fine particulate matter (PM2.5) in California was studied using a climate-air quality modeling system composed of global through regional models. Output from the NCAR/DOE Parallel Climate Model (PCM) generated under the "business as usual" global emissions scenario was downscaled using the Weather Research and Forecasting (WRF) model followed by air quality simulations using the UCD/CIT airshed model. The system represents major atmospheric processes acting on gas and particle phase species including meteorological effects on emissions, advection, dispersion, chemical reaction rates, gas-particle conversion, and dry/wet deposition. The air quality simulations were carried out for the entire state of California with a resolution of 8-km for the years 2000–2006 (present climate with present emissions) and 2047–2053 (future climate with present emissions). Each of these 7-year analysis periods was analyzed using a total of 1008 simulated days to span a climatologically relevant time period with a practical computational burden. The 7-year windows were chosen to properly account for annual variability with the added benefit that the air quality predictions under the present climate could be compared to actual measurements. The climate-air quality modeling system successfully predicted the spatial pattern of present climate PM2.5 concentrations in California but the absolute magnitude of the annual average PM2.5 concentrations were under-predicted by ~4–39% in the major air basins. The majority of this under-prediction was caused by excess ventilation predicted by PCM-WRF that should be present to the same degree in the current and future time periods so that the net bias introduced into the comparison is minimized. Surface temperature, relative humidity (RH), rain rate, and wind speed were predicted to increase in the future climate while the ultra violet (UV) radiation was predicted to decrease in major urban areas in the San Joaquin Valley (SJV) and South Coast Air Basin (SoCAB). These changes lead to a predicted decrease in PM2.5 mass concentrations of ~0.3–0.7 μg m−3 in the southern portion of the SJV and ~0.3–1.1 μg m−3 along coastal regions of California including the heavily populated San Francisco Bay Area and the SoCAB surrounding Los Angeles. Annual average PM2.5 concentrations were predicted to increase at certain locations within the SJV and the Sacramento Valley (SV) due to the effects of climate change, but a corresponding analysis of the annual variability showed that these predictions are not statistically significant (i.e. the choice of a different 7-year period could produce a different outcome for these regions). Overall, virtually no region in California outside of coastal + central Los Angeles, and a small region around the port of Oakland in the San Francisco Bay Area experienced a statistically significant change in annual average PM2.5 concentrations due to the effects of climate change in the present~study. The present study employs the highest spatial resolution (8 km) and the longest analysis windows (7 years) of any climate-air quality analysis conducted for California to date, but the results still have some degree of uncertainty. Most significantly, GCM calculations have inherent uncertainty that is not fully represented in the current study since a single GCM was used as the starting point for all calculations. The PCM results used in the current study predicted greater wintertime increases in air temperature over the Pacific Ocean than over land, further motivating comparison to other GCM results. Ensembles of GCM results are usually employed to build confidence in climate calculations. The current results provide a first data-point for the climate-air quality analysis that simultaneously employ the fine spatial resolution and long time scales needed to capture the behavior of climate-PM2.5 interactions in California. Future downscaling studies should follow up with a full ensemble of GCMs as their starting point, and include aerosol feedback effects on local meteorology.

Metallic glasses (MGs), a new class of advanced structural materials with extraordinary mechanical properties, such as high strength approaching the theoretical value and an elastic limit several times larger than the conventional metals, are being used to develop cellular structures with excellent mechanical-energy-dissipation performance. In this paper, the research progress on the development of MG structures for energy-dissipation applications is reviewed, including MG foams, MG honeycombs, cellular MGs with macroscopic cellular structures, microscopic MG lattice structures and kirigami MG structures. MG structures not only have high plastic energy absorption capacity superior to conventional cellular metals, but also demonstrate great potential for storing the elastic energy during cyclic loading. The deformation behavior as well as the mechanisms for the excellent energy-dissipation performance of varying kinds MG structures is compared and discussed. Suggestions on the future development/optimization of MG structures for enhanced energy-dissipation performance are proposed, which can be helpful for exploring the widespread structural-application of MGs.

In the present work, we report the magneto-caloric effect (MCE) of a binary Gd50Co50 amorphous alloy near the freezing temperature of water. The Curie temperature of Gd50Co50 amorphous ribbons is about 267.5 K, which is very close to room temperature. The peak value of the magnetic entropy change (-ΔSmpeak) and the resulting adiabatic temperature rise (ΔTad.) of the Gd50Co50 amorphous ribbons is much higher than that of any other amorphous alloys previously reported with a Tc near room temperature. On the other hand, although the -ΔSmpeak of Gd50Co50 amorphous ribbons is not as high as those of crystalline alloys near room temperature, its refrigeration capacity (RC) is still much larger than the RC values of these crystalline alloys. The binary Gd50Co50 amorphous alloy provides a basic alloy for developing high performance multi-component amorphous alloys near room temperature.

Standing Alfvén waves of 1.1 mHz (~15 min in period) were observed by the Cluster satellites in the mid-tail during 06:00-07:00 UT on 8 August 2003. Pulsations with the same frequency were also observed at several ground stations near Cluster's footpoint. The standing wave properties were determined from the electric and magnetic field measurements of Cluster. Data from the ground magnetometers indicated a latitudinal amplitude and phase structure consistent with the driven field line resonance (FLR) at 1.1 mHz. Simultaneously, quasi-periodic oscillations at different frequencies were observed in the post-midnight/early morning sector by GOES 12 (l0≈8.7), Polar (l0≈11-14) and Geotail (l0≈9.8). The 8 August 2003 event yields rare and interesting datasets. It provides, for the first time, coordinated in situ and ground-based observations of a very low frequency FLR in the mid-tail on stretched field lines.

In this paper, we present in-situ observations of processes occurring at the magnetopause and vicinity, including surface waves, oscillatory magnetospheric field lines, and flux transfer events, and coordinated observations at geosynchronous orbit by the GOES spacecraft, and on the ground by CANOPUS and 210° Magnetic Meridian (210MM) magnetometer arrays. On 7 February 2002, during a high-speed solar wind stream, the Polar spacecraft was skimming the magnetopause in a post-noon meridian plane for ~3h. During this interval, it made two short excursions and a few partial crossings into the magnetosheath and observed quasi-periodic cold ion bursts in the region adjacent to the magnetopause current layer. The multiple magnetopause crossings, as well as the velocity of the cold ion bursts, indicate that the magnetopause was oscillating with an ~6-min period. Simultaneous observations of Pc5 waves at geosynchronous orbit by the GOES spacecraft and on the ground by the CANOPUS magnetometer array reveal that these magnetospheric pulsations were forced oscillations of magnetic field lines directly driven by the magnetopause oscillations. The magnetospheric pulsations occurred only in a limited longitudinal region in the post-noon dayside sector, and were not a global phenomenon, as one would expect for global field line resonance. Thus, the magnetopause oscillations at the source were also limited to a localized region spanning ~4h in local time. These observations suggest that it is unlikely that the Kelvin-Helmholz instability and/or fluctuations in the solar wind dynamic pressure were the direct driving mechanisms for the observed boundary oscillations. Instead, the likely mechanism for the localized boundary oscillations was pulsed reconnection at the magnetopause occurring along the X-line extending over the same 4-h region. The Pc5 band pressure fluctuations commonly seen in high-speed solar wind streams may modulate the reconnection rate as an indirect cause of the observed Pc5 pulsations. During the same interval, two flux transfer events were also observed in the magnetosphere near the oscillating magnetopause. Their ground signatures were identified in the CANOPUS data. The time delays of the FTE signatures from the Polar spacecraft to the ground stations enable us to estimate that the longitudinal extent of the reconnection X-line at the magnetopause was ~43° or ~5.2 RE. The coordinated in-situ and ground-based observations suggest that FTEs are produced by transient reconnection taking place along a single extended X-line at the magnetopause, as suggested in the models by Scholer (1988) and Southwood et al. (1988). The observations from this study suggest that the reconnection occurred in two different forms simultaneously in the same general region at the dayside magnetopause: 1) continuous reconnection with a pulsed reconnection rate, and 2) transient reconnection as flux transfer events. Key words. Magnetospheric physics (Magnetopause, cusp and boundary layers; Magnetosphere-ionosphere interactions; MHD waves and instabilities)

A charge sheet model is proposed to study the space charge effect and uniformity of charge separation of an electron pulse train in a drift space. An analytical formula is derived for the charge density limit as a function of gap spacing, injecting energy and pulse separation. To consider the relativistic effects, the theoretical results are verified by numerical solutions up to 80 MeV. This model can be applied to the design of Smith-Purcell radiation, multiple-pulse electron beam for time resolved electron microscopy, and to free electron laser.

Selective formation of amorphous, nematic (N), and beta phases in poly(9,9-di-n-octy1-2,7-fluorene) (PFO) films was achieved through judicious choice of process parameters. Phase structure and film morphology were carefully examined by means of X-ray diffraction as well as electron microscopy.

Structural evolution and its effect on the optical absorption behavior of poly(2,5,2',5'-tetrahexyloxy-8,7'-dicyano-di-p-phenylenevinylene) (DH-CNPPV) upon short term isothermal heat treatment at evaluated temperatures were studied. Results indicated that Kinetic preference for mesomorphic order in bulk DH-CNPPV, with the isotropizavicinity of 210 degree C.

Quasi-phase matched direct laser acceleration (DLA) of electrons can be realized with guided, radially polarized laser pulses in density-modulated plasma waveguides. A particle-in-cell model has been developed to describe the interactions among the laser field, injected electrons, and the background plasma in the DLA process. Simulations have been conducted to study the scheme in which seed electron bunches with moderate energies are injected into a plasma waveguide and the DLA is performed by use of relatively low-power (0.5-2 TW) laser pulses. Selected bunch injection delays with respect to the laser pulse, bunch lengths, and bunch transverse sizes have been studied in a series of simulations of DLA in a plasma waveguide. The results show that the injection delay is important for controlling the final transverse properties of short electron bunches, but it also affects the final energy gain. With a long injected bunch length, the enhanced ion-focusing force helps to collimate the electrons and a relatively small final emittance can be obtained. DLA efficiency is reduced when a bunch with a greater transverse size is injected; in addition, microbunching is clearly observed due to the focusing and defocusing of electrons by the radially directed Lorentz force. DLA should be performed with a moderate laser power to maintain favorable bunch transverse properties, while the waveguide length can be extended to obtain a higher maximum energy gain, with the commensurate increase of laser pulse duration and energy. [ABSTRACT FROM AUTHOR]

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-drGO 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 (HNTsm- 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. [ABSTRACT FROM AUTHOR]

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 gasparticle 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 5.2m (1.5 %) with a maximum of ~100m in the SJV. Particulate matter concentrations predicted by SOWC are 2.23 μgm-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. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) is known as a main problem in diabetic disorders. Some animal models for research in IR have been mentioned. Each model shows merit with some disadvantages. Thus, a new animal model for IR is required. The present study used zymosan, a mixture of cell-wall particles from the yeast named Saccharomyces cerevisiae , to establish a new model of IR in mice. Also, we compared the difference of this model with fructose-rich chow-induced model and found some merits of this model. Moreover, we identified that this model induced by zymosan is reversible and IR can be reversed gradually after termination of treatment. Taken together, we suggest zymosan as a useful agent to induce IR through inflammatory pathway in mice. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Specific antibodies are essential in the study of receptor protein. Gene matching shows that Nischarin (NISCH) is a mouse homologue of human imidazoline receptor antisera-selective (IRAS) protein, a viable candidate for imidazoline I-1 receptor. However, selectivity of this antibody against imidazoline I-2 or imidazoline I-3 receptors remained obscure. At first, an intracerebroventricular (ICV) injection of anti-NISCH antibody blocked the blood pressure lowering action of rilmenidine (I-1 receptor agonist) in spontaneous hypertensive rat (SHR). However, the same injection of anti-NISCH antibody showed no effect in SHR treated with clonidine (α 2 agonist). In order to clarify the selectivity of anti-NISCH antibody for each subtype of imidazoline receptors, this anti-NISCH antibody was subjected to the lysate of organs isolated from Wistar rats including cortex, hippocampus, cerebellum, and brain stem as central nervous tissues, and heart, liver, pancreas, skeletal muscle, kidney, prostate, and bladder as peripheral tissues. The results show that anti-NISCH antibody positively reacted with all tissues including heart, pancreas, skeletal muscle, kidney and bladder by Western blot analysis. Also, the blotting spots for anti-NISCH antibody show a concentration-dependent manner. Moreover, anti-NISCH antibody blocked the action of glucose uptake induced by 2-BFI (I-2 receptor agonist) in L6 cells. Taken together, the obtained data suggest that anti-NISCH antibody can be used not only for imidazoline I-1 receptor but also for I-2 and I-3 subtypes in immunoassays. [ABSTRACT FROM AUTHOR]

A highly efficient, carbon-free rice husk ash (RHA) has been successfully used as a catalyst in oxalic acid (OA) decomposition by combining with ozonation at pH 3. The catalyst was characterized using various analytical techniques. X-ray fluorescence (XRF) analysis showed that RHA catalyst contains SiO2as a major constituent and MgO, P2O5, SO3, K2O, CaO, MnO2, Fe2O3, CuO, ZnO as minor constituents. X-ray diffraction (XRD) and EDX analysis consistently confirmed the presence of silica as a major constituent. Cold field scanning electron microscopic (FESEM) analysis revealed nonuniform particle size and the presence of external pores on the catalyst surface. Elemental analysis (EA) indicated that RHA contains negligible percentage of carbon content. Oxalic acid degradation as well as its TOC removal was studied at various physicochemical conditions. Adsorption and ozonation processes are not effective for oxalic acid and its TOC removal. The addition of RHA catalyst in the ozonation process caused 76.2% OA decomposition and 75% TOC removal in 60 min. Also, 0.25 g/L RHA dosage was found to be optimum for effective removal of oxalic acid. The efficiencies of RHA was compared with other commercially available catalysts, and the order was found to be RHA TiO2-P25 > FeOOH > SiO2> Al2O3> ZnO. Oxalic acid decomposition was enhanced by increasing inlet gaseous ozone concentration from 40 to 120 mg/L. The catalytic ozonation process is more pronounced than the ozonation process alone at pH 3, 7, and 10. It is concluded that RHA is an efficient green catalyst for oxalic acid removal. [ABSTRACT FROM AUTHOR]

Phase behavior and morphological features of regioregular, n-type semiconducting poly(4-alkyl-2,6-quinoline)s were examined in detail via a combination of thermal, microscopic, and diffraction methods. Two members (P4OQ and P4DQ, with n-octyl and n-decyl substitutions, respectively) in this series were selected as representatives. Results indicate the dominance of lamellar mesophase throughout the experimentally accessed temperature range (from ambient to above 300 °C), with lamellar spacing well-correlated with side-chain length and temperature. Optical textures observed via polarized light microscopy reveal clear domain-wall features in P4OQ but more solid-like characteristics for P4DQ; improved lamellar order was also observed for P4DQ as compared to P4OQ. These signify stronger tendency toward supramolecular self-assembly with increasing side-chain length. A model of molecular arrangement in the lamellar mesophase in which the free volume is identified as the gap between tips of extended (and interdigitated) side chains and the backbone of the neighboring chain is proposed to account for the observed variation of layer spacing with side-chain length and temperature. The presence of nanodomains (similar to those previously reported for p-type conjugated polymers) is also identified in the present n-type series, implying general existence of this inherent morphological heterogeneity in semiconducting hairy-rod polymers. This means that molecular aggregation is determined solely by ground-state intermolecular forces; differences in carrier transport characteristics are irrelevant during morphological development. Origins of these nanodomains are discussed in terms of backbone folding (via inherent chemical defects or elastic bending) as well as fringed-micelle aggregates. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that solution-cast films of conjugated polymers with grafted alkyl side chains comprise clearly identifiable domains ca. 10 nm in size upon solvent evaporation. Here we show that these nanodomains indeed serve as basic units for morphological development in poly(9,9-di-n-octyl-2,7-fluorene) (PFO) films during cold crystallization. Results of our microscopic and diffraction observations indicate that the cold crystallization process involves intradomain nucleation and growth, followed by nanodomain alignment and coalescence into fibrils in the sub-micrometer length scale via thermally activated adjustment of nanodomain orientation. An analogy with oriented aggregation (or oriented attachment−coalescence) behavior of nanocrystals of metal oxides is drawn; the relevance to recently proposed models of polymer crystallization via primary nucleation induced at the growth front is addressed. [ABSTRACT FROM AUTHOR]

Summary.  A study of male sterility over a period of three consecutive years on a conifer species endemic to Taiwan, Taiwania cryptomerioides Hayata (Taxodiaceae), was done for this article. With the aids of fluorescence and electron microscopic observations, the ontogenic processes in the fertile and sterile microsporangia are compared, using samples collected from Chitou Experimental Forest and Yeou-Shoei-Keng Clonal Orchard of the National Taiwan University, Nantou, Taiwan. The development of male strobili occurred from August to the end of March. Microsporogenesis starts with the formation of the archesporium and ends with the maturation of 2-celled pollen grains within the dehiscing microsporangium. Before meiosis, there was no significant difference in ultrastructure between the fertile and sterile microsporangia. Asynchronous pollen development with various tetrad forms may occur in the same microsporangium of either fertile or sterile strobili. However, a callose wall was observable in the fertile dyad and tetrad, but not in the sterile one. After dissolution of the callose wall, the fertile microspores were released into the locule, while some sterile microspores still retained as tetrads or dyads with intertwining of exine walls in the proximal faces. As a result, there was no well developed lamellated endexine and no granulate ectexine or intine in the sterile microspores. Eventually, the intracellular structures in sterile microspores were dramatically collapsed before anthesis. The present study shows that the abortion in pollen development is possibly attributed to the absence of the callose wall. The importance of this structure to the male sterility of T. cryptomerioides is discussed. [ABSTRACT FROM AUTHOR]

Here we report the phase behavior of poly(9,9-di-n-hexyl-2,7-fluorene) (PFH), which previously received little attention as compared to its homologues poly(9,9-di-n-octyl-2,7-fluorene) (PFO) and poly(9,9-di-(2‘-ethylhexyl)-2,7-fluorene) (PFEH). By means of differential scanning calorimetry, X-ray diffraction, and electron microscopy, we show that there exist four different phases in PFH. The as-cast film is mainly composed of a mesomorphic β phase with layer spacing of ca. 1.4 nm. This β phase is inherently metastable and, upon heating above 175 °C, transforms into a crystalline (α) form that melts into a nematic (N) liquid above 250 °C. Upon stepwise cooling, the nematic melt crystallizes into the α phase first, followed by solid−solid transformation into another crystalline (α‘) form. Unit cell structure of the α form is monoclinic whereas that of the α‘ form is triclinic, but departures from strict orthogonality are slight (by ca. 6°). These observations not only support our previous assignment of two crystalline forms (both orthorhombic in structure) in PFO but also provide insights to the crystalline nature of the polyfluorene series. [ABSTRACT FROM AUTHOR]

To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C – containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51±5.3% (s.e.) and the 5-year event-free survival 50±4.8%; for APL, these were 100%, 86±7.0, and 75±9.8%. For the whole group, the 5-year survival was 57±4.7% and the 5-year event-free survival 54±4.4%. The AML-97A regimen was well tolerated.Leukemia (2006) 20, 136–141. doi:10.1038/sj.leu.2403979; published online 10 November 2005 [ABSTRACT FROM AUTHOR]

We investigate, for two water models displaying a liquid-liquid critical point, the relation between changes in dynamic and thermodynamic anomalies arising from the presence of the liquid- liquid critical point. We find a correlation between the dynamic crossover and the locus of specific heat maxima CPmax ("Widom line") emanating from the critical point. Our findings are consistent with a possible relation between the previously hypothesized liquid-liquid phase transition and the transition in the dynamics recently observed in neutron scattering experiments on confined water. More generally, we argue that this connection between CPmax and dynamic crossover is not limited to the case of water, a hydrogen bond network-forming liquid, but is a more general feature of crossing the Widom line. Specifically, we also study the Jagla potential, a spherically symmetric two-stale potential known to possess a liquid-liquid critical point in which the competition between two liquid structures is generated by repulsive and attractive ramp interactions. [ABSTRACT FROM AUTHOR]

Elevated temperature true stress – strain curves have been determined for the isothermal deformation of a TC6 titanium alloy using hot compression testing in the deformation temperature range 800 – 1040°C, strain rate range 0.001 – 50 s-1 and reduction in height of 30 – 50%. The experimental results show that the flow stress of TC6 titanium alloy is strongly dependent on process parameters, especially on the deformation temperature and strain rate. The peak stress and steady stress of such an alloy have the same characterisation, which increases with higher strain rate and lower deformation temperature. During isothermal forging, microstructural characterisation, including volume fraction, grain size, and grain pattern of prior α phase, varies with different temperatures, height reductions, and strain rates. [ABSTRACT FROM AUTHOR]

Flip chip package is the most important technology in IC package in terms of scale, velocity and cost in the development of semiconductor technology and the innovation of computer product. It has the advantage of low cost, low interface and small volume in IC package. This paper describes the analysis package of the solder ball and microchip for mold flow simulation (3D, midplane) and experiment. The numerical simulation of mold filling process is based on the concept of control volume finite element method. The injection point uses the corner, 1/4 side and central injection location. The injection process uses different parameters (mold temperature, injection temperature, injection pressure and injection time). For processing situation, the best result is from central injection, then 1/4 side injection and then corner injection. The results also show that the filling situation for 3D numerical simulation is closer to experiment. [ABSTRACT FROM AUTHOR]

Using three different quasielastic neutron spectrometers with widely different resolutions, we have been able to study the microscopic translational and rotational dynamics of water, in a mesoporos silica matrix MCM-48-S, from T=300 K to 220 K, with a single consistent model. We formulated our fitting routine using the relaxing cage model. Thus, from the fit of the experimental data, we extracted the fraction of water bound to the surface of the pore, the characteristic relaxation times of the long-time translational and rotational decays, the stretch exponent describing the shape of the relaxation processes, and the power exponent determining the Q-dependence of the translational relaxation time. A tremendous slowing down of the rotational relaxation time, as compared to the translational one, has been observed. [ABSTRACT FROM AUTHOR]

Buildings are responsible for a major share of global final energy consumption and carbon dioxide (CO _2 ) emissions. An analysis of the worldwide observed drivers of demand can highlight the policy actions most suited to drive the decarbonization of the building sector. To contribute to such an analysis, we carry out a mapping of the literature on determinants of energy demand and CO _2 emissions from buildings. The work includes a list and classification of relevant studies in an on-line geographical map, a description of trends and gaps, and a narrative review. We identify 4080 articles in the Scopus and the Web of Science databases, of which 712 are relevant after screening at the title and abstract level, and 376 are included for data extraction. The literature base mostly addresses electricity and water use, in North America and Europe (57% of the literature) and Asia (27%). Econometric modeling approaches using panel data to calculate demand elasticities, dominate. These findings highlight gaps in terms of the studied variables (only 5% focus on CO _2 emissions while a mere 1% have a lifecycle perspective), geographical scope (only 5% of the articles focus on Africa, 7% on Latin America and the Caribbean, and 5% on Oceania), and methodological approach (only 5% use qualitative methods). We confirm that worldwide, income, energy price and outdoor temperature are unequivocal drivers of buildings energy demand and CO _2 emissions, followed by other indicators of scale such as population or heated floor area. Our analysis makes it clear that decoupling from rising wealth levels has not been observed. This will continue to challenge reductions in energy use and CO _2 emissions from buildings in line with climate targets. Macroeconomic policies focusing on the impacts of income, energy price, population and growing floor area are needed in combination with technical policy to reduce the impact of outdoor climate.

Formulation of targets and establishing which factors in different contexts will achieve these targets are critical to successful decarbonization of the building sector. To contribute to this, we have performed an evidence map of roadmaps for zero and low energy and carbon buildings (ZLECB) worldwide, including a list and classification of documents in an on-line geographical map, a description of gaps, and a narrative review of the knowledge gluts. We have retrieved 1219 scientific documents from Scopus, extracted metadata from 274 documents, and identified 117 roadmaps, policies or plans from 27 countries worldwide. We find that there is a coverage bias towards more developed regions. The identified scientific studies are mostly recommendations to policy makers, different types of case studies, and demonstration projects. The geographical inequalities found in the coverage of the scientific literature are even more extreme in the coverage of the roadmaps. These underexplored world regions represent an area for further investigation and increased research/policy attention. Our review of the more substantial amount of literature and roadmaps for developed regions shows differences in target metrics and enforcement mechanisms but that all regions dedicate some efforts at national and local levels. Roadmaps generally focus more on new and public buildings than existing buildings, despite the fact that the latter are naturally larger in number and total floor area, and perform less energy efficiently. A combination of efficiency, technical upgrades, and renewable generation is generally proposed in the roadmaps, with behavioral measures only reflected in the use of information and communication technologies, and minimal focus being placed on lifecycle perspectives. We conclude that insufficient progress is being made in the implementation of ZLECB. More work is needed to couple the existing climate goals, with realistic, enforceable policies to make the carbon savings a reality for different contexts and stakeholders worldwide.

Interpersonal synchrony is a crucial construct in understanding social interactions, which has been used in clinical studies to measure the quality of the therapeutic alliance. However, there is a lack of studies investigating the correlation between synchrony expressed on different levels: behavioural and neurophysiological. Furthermore, there are no studies that examine how the implementation of psychodramatic role-playing techniques, when individuals adopt the persona of a different character, may influence intrinsic biobehavioural synchrony between two parties. The present study, therefore, aims to uncover the relationship between behavioural and brain-to-brain synchrony across different role-playing techniques and elucidate the impact of these synchronies on participants’ levels of anxiety and empathy. By using functional near-infrared imaging and behavioural coding in a dyadic role-playing paradigm (n = 41 dyads), the study found correlations between behavioural and brain-to-brain synchrony during naturalistic conversations, but not during role-play, implying a qualitative change in interpersonal synchrony when implementing role-playing techniques. Additionally, the study noted significant contributions of both behavioural and brain-to-brain synchrony as well as peripheral factors such as dyadic sex make-up and role immersion in predicting dyadic anxiety and empathy changes. Findings call for future studies to consider role-playing scenarios as a qualitatively different form of social interaction.

Compared to conventional thermal imprinting using a flat mold, roll-to-roll (R2R) thermal imprinting using a roller mold is a high-speed, high through-put process. In an R2R thermal imprinting process, however, the contact duration between a mold and a thermoplastic substrate is extremely short. This results in insufficient heating and pressing, leading to low fidelity of the imprinted microstructures. We have developed an R2R thermal imprinting system, which allows us to extend the contact duration between the mold and substrate. This system consists of two continuous, seamless belts that are made of metal foil. Each belt is driven by an individual hot roller; at least one belt is used as an imprinting mold, another as a carrier belt. A thermoplastic film to be imprinted is sandwiched between the two belts that provide preheating, heating and pressing, holding, and cooling for demolding during imprinting, leading to extended mold-substrate contact duration and enhanced heat transfer from the belt mold to the polymer film. R2R thermal imprinting has been performed successfully and promising results have been demonstrated. [ABSTRACT FROM AUTHOR]

The nearby radio galaxy M87 is a very high-energy (VHE) gamma-ray emitter established by observations with ground-based gamma-ray detectors. Here we report the long-term monitoring of M87 from 2021 to 2024 with the Large High Altitude Air Shower Observatory (LHAASO). M87 has been detected by LHAASO with a statistical significance ∼ 9 σ . The observed energy spectrum extends to 20 TeV, with a possible hardening at ∼20 TeV and then a clear softening at higher energies. Assuming that the intrinsic spectrum is described by a single power law up to 20 TeV, a tight upper bound on the extragalactic background light intensity is obtained. A strong VHE flare lasting 8 days, with a rise time of ${\tau }_{r}^{\mathrm{rise}}=1.05\pm 0.49$ days and decay time of ${\tau }_{d}^{\mathrm{decay}}=2.17\pm 0.58$ days, was found in early 2022. A possible GeV flare is seen also in Fermi Large Area Telescope data during the VHE flare period. The variability time as short as 1 day seen in the LHAASO data suggests a compact emission region with a size of ∼3 × 10 ^15 δ cm ( δ being the Doppler factor of the emitting region), corresponding to a few Schwarzschild radii of the central supermassive black hole in M87. The continuous monitoring of the source reveals a duty cycle of ∼1% for VHE flares with a flux above 10 ^−11 erg cm ^−2 s ^−1 .

The first source catalog of the Large High Altitude Air Shower Observatory (LHAASO) reported the detection of a very high energy gamma-ray source, 1LHAASO J1219+2915. This Letter presents a further detailed study of the spectral and temporal behavior of this pointlike source. The best-fit position of the TeV source (R.A. = 185.°05 ± 0.°04, decl. = 29.°25 ± 0.°03) is compatible with NGC 4278 within ∼0.°03. Variation analysis shows an indication of variability on a timescale of a few months in the TeV band, which is consistent with low-frequency observations. Based on these observations, we report the detection of TeV γ -ray emissions from this low-luminosity active galactic nucleus. The observation by LHAASO's Water Cherenkov Detector Array during the active period has a significance level of 8.8 σ with a best-fit photon spectral index Γ = 2.56 ± 0.14 and a flux f _1–10 TeV = (7.0 ± 1.1 _sta ± 0.35 _syst ) × 10 ^−13 photons cm ^−2 s ^−1 , or approximately 5% of the Crab Nebula. The discovery of VHE gamma-ray emission from NGC 4278 indicates that compact, weak radio jets can efficiently accelerate particles and emit TeV photons.