Search

Immune checkpoint therapies, such as programmed cell death ligand 1 (PD-L1) blockade, have shown remarkable clinical benefit in many cancers by restoring the function of exhausted T cells. Hence, the identification of novel PD-L1 regulators and the development of their inhibition strategies have significant therapeutic advantages. Here, we conducted pooled shRNA screening to identify regulators of membrane PD-L1 levels in lung cancer cells targeting druggable genes and cancer drivers. We identified WNK lysine deficient protein kinase 3 (WNK3) as a novel positive regulator of PD-L1 expression. The kinase-dead WNK3 mutant failed to elevate PD-L1 levels, indicating the involvement of its kinase domain in this function. WNK3 perturbation increased cancer cell death in cancer cell–immune cell coculture conditions and boosted the secretion of cytokines and cytolytic enzymes, promoting antitumor activities in CD4+ and CD8+ T cells. WNK463, a pan-WNK inhibitor, enhanced CD8+ T-cell-mediated antitumor activity and suppressed tumor growth as a monotherapy as well as in combination with a low-dose anti-PD-1 antibody in the MC38 syngeneic mouse model. Furthermore, we demonstrated that the c-JUN N-terminal kinase (JNK)/c-JUN pathway underlies WNK3-mediated transcriptional regulation of PD-L1. Our findings highlight that WNK3 inhibition might serve as a potential therapeutic strategy for cancer immunotherapy through its concurrent impact on cancer cells and immune cells.

A steel slit damper has been used to enhance the seismic performance of structures with several advantages. The damper can be easily manufactured at a low cost. Furthermore, it can dissipate a significant amount of seismic energy through the stable hysteretic behavior of steel. This study presents a preliminary investigation of the development of a composite steel slit damper that can respond effectively at multiple levels of seismic loading. The performance of the prototype composite steel slit damper is investigated in both experimental and analytical ways. In the experiments, the specimen shows the stable hysteretic response with sufficient ductility, where the multi-phased response is observed in the incremental-amplitude cyclic loading case. Furthermore, a nonlinear numerical analysis that combines both kinematic hardening and isotropic hardening models can reliably describe such characteristics.

Conventional channel estimation schemes may require for the transmission of orthogonal pilot signal for each antenna in frequency-division duplex (FDD) transmission systems. It is of great concern to get channel information with an affordable signaling overhead in FDD massive multi-input multi-output (m-MIMO) transmission environments. The signaling overhead for the channel estimation can be reduced by exploiting the channel correlation matrix (CCM) of m-MIMO channel. When the m-MIMO channel is correlated in spatial domain, the channel information can be estimated with reduced pilot signaling overhead. However, the estimation performance may seriously be affected by the accuracy of CCM. In this paper, we investigate the effect of CCM accuracy on the m-MIMO channel estimation and verify it by computer simulation.

A common approach for dynamic analysis in current practice is based on a discrete time-integration scheme. This approach can be largely attributed to the absence of a true variational framework for initial value problems. To resolve this problem, a new stationary variational principle was recently established for single-degree-of-freedom oscillating systems using mixed variables, fractional derivatives and convolutions of convolutions. In this mixed convolved action, all the governing differential equations and initial conditions are recovered from the stationarity of a single functional action. Thus, the entire description of linear elastic dynamical systems is encapsulated. For its practical application to structural dynamics, this variational formalism is systemically extended to linear elastic multidegree- of-freedom systems in this study, and a corresponding weak form is numerically implemented via a quadratic temporal finite element method. The developed numerical method is symplectic and unconditionally stable with respect to a time step for the underlying conservative system. For the forced-damped vibration, a three-story shear building is used as an example to investigate the performance of the developed numerical method, which provides accurate results with good convergence characteristics.

The objective of this study is to apply a constitutive damage model for cyclic response of E-shaped dampers as well as metal and metallic plate dampers in order to be used in more broad areas such as material and component levels. The seismic isolation system used as sliding bearings and metallic dampers undergoes almost elastoplastic behavior due to seismic excitation. Accordingly, a two surface damage model is applied to understand inelastic behavior and to evaluate the potential damaged state of E-shaped dampers in the seismic isolation system. This damage model is originally formulated through a thermodynamic approach based on the entropy production equation. The cyclic damage model proposed in this study can be implemented into a user subroutine in the finite element (FE) software ABAQUS. Finally, the numerical results for E-shaped energy dissipation devices in the seismic isolation system are compared with the experimental test results so as to check the validity of the proposed model.

In this study, a two surface plasticity model was developed and used to simulate the uniaxial ratchetting response of CS 1026 steel. Most cyclic plasticity models used in ratchetting simulations are Chaboche-type nonlinear kinematic hardening models, which deal with dynamic recovery terms considering the back stress tensor. This paper describes the ratchetting simulation of steel by the two surface model based on yield theory following both isotropic and kinematic hardening rules in order to obtain enhanced ratchetting response. The parameters used in the simulation were obtained from a parametric study and were determined from the initial range and stabilized range of CS 1026 steel. In addition, the two surface model was validated by comparing the results of a ratchetting simulation with experimentally determined maximum axial strain per cycle. The ratchetting responses obtained from the two surface model are an improved simulation results compared with results from bilinear and kinematic hardening models.

In this study, a cDNA microarray was developed from over 60,000 mRNA readings to analyze the expression profiles of transcriptomes of Haematococcus lacustris under astaxanthin-inducing culture conditions, high irradiance and nitrate starvation. Among 20,033 genes on the cDNA microarray, 2,675 genes exhibited a twofold or greater difference in expression. Of these, 1,333 genes were up-regulated and 1,342 genes were down-regulated. A significant decrease in the expression of chlorophyll biosynthesis and light harvesting complex (LHC) related genes were observed under astaxanthin inducing conditions (forming red cyst cells). On the other hand, respirationrelated genes, lipid metabolism-related genes and stress response-related genes were activated in the red cyst cells under stress conditions. These results enabled a better understanding of the cell responses during stress induction of H. lacustris such as photosynthesis, respiration, and some biopathways.

Experimental investigations on the atomization characteristics of twin-fluid water mist nozzle were conducted using particle image velocimetry (PIV) system and particle motion analysis system (PMAS). The twin-fluid water mist nozzles with swirlers designed two types of swirl angles such as 0°, 90° and three different size nozzle hole diameters such as 0.5mm, 1mm, 1.5mm were employed. The experiments were carried out by the injection pressure of water and air divided into 1bar, 2bar respectively. The droplet size of the spray was measured using PMAS. The velocity and turbulence intensity were measured using PIV. The velocity, turbulence intensity and SMD distributions of the sprays were measured along the centerline and radial direction. As the experimental results, swirl angle controlled to droplet sizes. It was found that SMD distribution decreases with the increase of swirl angle. The developed twin-fluid water mist nozzle was satisfied to the criteria of NFPA 750, Class 1. It was proven that the developed nozzle under low pressures could be applied to fire protection system.

The velocities, turbulence intensities, Reynolds shear stresses, and turbulent kinetic energies of the flow fields around two square cylinders in a tandem arrangement were investigated using particle image velocimetry (PIV). The experiments were made for the spacing between the two cylinders ranging from s/D = 0.5 to 10.0 and two Reynolds numbers of 5,300 and 16,000. The results showed that the flow patterns at s/D≤2.0 were drastically different from those at s/D≥2.5 for both Reynolds numbers. The sudden change in the flow patterns depended on the reattachment of the shear layer separated from the upstream cylinder.

Investigations on alternative material for bipolar plates of PEMFC (polymer electrolyte membrane fuel cell) are becoming a research hotspot for many fuel cell researchers. In this paper, LF11 Al alloy bipolar plates via a surface plasma Au plating preparation were applied as bipolar plates. Performances and duration times of PEMFC single cells using graphite; Au-coated LF11 Al bipolar (ALABP) and Au-coated 316L stainless steel plates were compared. It was shown that ALABP exhibited preferable properties. Based on the preparations illustrated above, a kilowatt class proton exchange membrane fuel cell stack consisting of 30 cells was successfully assembled. Pure hydrogen and air were used as the fuel and oxidant, respectively, in the stack. External humidification was employed and cycle cooling water was used to remove the heat from the reaction in order to maintain a constant temperature. A Nafion 1135 membrane and Johnson-Matthy platinum on carbon with a Pt loading of 0.4 mg/cm2 were adopted as the electrolyte and catalyst, respectively. The working temperature of the stack ranged from 25 to 100°C. The stack typically worked well under conditions in which the pressure ratio of H2/air was 0.2/0.22 MPa. The output power, current and voltage were 1–1.3 kW, 40–80 A, and 26–20 V, respectively. The normal current density of the electrode was 200–800 mA/cm2, and the energy efficiency of the stack was 51%.

Submicron-sized Li(Ni1/3Co1/3Mn1/3)O2 particles were prepared by spray pyrolysis. A polymeric precursor solution containing citric acid and ethylene glycol enabled the formation of submicron-sized Li(Ni1/3Co1/3Mn1/3)O2 spherical particles with narrow-sized distribution and non-aggregation characteristics in the spray pyrolysis. The mean sizes of the particles post-treated at temperatures of 800 and 900∘C were 380 and 770 nm. On the other hand, the Li(Ni1/3Co1/3Mn1/3)O2 particles obtained from the aqueous solution had irregular morphology and broad-sized distribution. The discharge capacity of the particles prepared from polymeric precursor solution decreased from 88 mAh/g to 135 mAh/g after 50 cycles. The particles prepared from polymeric precursor solution had high discharge capacity and good cyclic properties than those of the particles prepared from the aqueous solution.

LiCo0.8Ni0.2O2 powders were prepared by molten salt synthesis method using a 0.59LiNO3-0.41LiOH melt. The physico-chemical properties of the HT-LiCo0.8Ni0.2O2 powders were investigated by powder X-ray diffraction method, field emission scanning electron microscopy, cyclic voltammetry, and charge-discharge cycling. Uniform size nanocrystalline powder (~40 nm) could be obtained at temperature ranges of 280-480 °C. These nanocrystalline powders showed poor electrochemical properties because of presence of the low temperature phase. Pure single-phase HT-LiCo0.8Ni0.2O2 powder could be obtained at 580 °C. Charge-discharge measurements indicated that this exhibited a good capacity and cyclability without further heat treatment at higher temperatures.

A small proportion of cancer cells have stem-cell-like properties, are resistant to standard therapy and are associated with a poor prognosis. The metabolism of such drug-resistant cells differs from that of nearby non-resistant cells. In this study, the metabolism of drug-resistant lung adenocarcinoma cells was investigated. The expression of genes associated with oxidative phosphorylation in the mitochondrial membrane was negatively correlated with the prognosis of lung adenocarcinoma. Because the mitochondrial membrane potential (MMP) reflects the functional status of mitochondria and metastasis is the principal cause of death due to cancer, the relationship between MMP and metastasis was evaluated. Cells with a higher MMP exhibited greater migration and invasion than those with a lower MMP. Cells that survived treatment with cisplatin, a standard chemotherapeutic drug for lung adenocarcinoma, exhibited increased MMP and enhanced migration and invasion compared with parental cells. Consistent with these findings, inhibition of mitochondrial activity significantly impeded the migration and invasion of cisplatin-resistant cells. RNA-sequencing analysis indicated that the expression of mitochondrial complex genes was upregulated in cisplatin-resistant cells. These results suggested that drug-resistant cells have a greater MMP and that inhibition of mitochondrial activity could be used to prevent metastasis of drug-resistant lung adenocarcinoma cells.

Using 2.5-dinitrophenol as an optical indicator, the pKa of cacodylic acid were spectrophotometrically determined at elevated temperatures under saturation vapor pressures. The result is pKa = -26.41 + 1296/T + 4.973 InT whereT is in Kelvin. In a similar way, the pKa ofp-nitrophenol were obtained up to 200‡C giving pKa = -24.82 + 2135/T + 4.353 InT From these results, several thermodynamic functions of cacodylic acid andp- nitrophenol were calculated.

La1−xSrxMnO3 powders were prepared by auto-ignited combustion of poly(ethylene glycol) (PEG)–metal–nitrate gel precursors. The thermal behaviour of the precursors strongly depends on the ratio of PEG to metal nitrate, which is closely related to the ratio of fuel to oxidizer. The burning behaviour in a furnace was successfully explained by valence concepts normally encountered in propellant chemistry. The formation of a pure perovskite phase was significantly influenced by the homogeneity of the gel precursor. Perovskite structured oxides were formed through two different paths, one of which was direct formation from the burning of a gel precursor and the other was a subsequent structural evolution by heat treatment after burning. The formation procedure of the perovskite and the morphology of powders could be explained in terms of the burning behaviour of the precursor and the role of organic residue.

Using the temperature dependence of pKa for acetic acid, the pKa for 2,5-dinitrophenol have been spectrophotometrically determined in acetate buffer at elevated temperatures under the saturation vapor pressures. For 2,5-dinitrophenol $$pK_a = - 33.206 + 2106.7/T + 5.495\ln T$$ where T is in Kelvin. Similarly, pKa values of propionic acid were obtained at temperatures from 25°C to 175°C producing $$pK_a = - 43.703 + 2128.6/T + 7.2686\ln T$$ From this result, several thermodynamic functions of propionic acid were calculated and compared with those obtained from emf measurement.

A new method of measuring the pH of high-temperature aqueous solutions using optical indicators was developed. The absorbance spectrum of acridine changes as a function of pH, allowing its use as an optical indicator for pH. The pKa of acridine were experimentally determined in KOH-AcOH pH-buffer solutions at temperatures from 5 to 250°C at vaporsaturated pressures: $$pKa = 5.62 + 1158{\text{ }}/{\text{ }}T{\text{ - }}0.7168{\text{ }}lnT$$ where T is in Kelvin. The technique is demonstrated by experimentally determining the pKa of benzoic acid at temperatures up to 250°C where the result was $$pKa{\text{ }}(benzoic{\text{ }}acid) = {\text{ - }}60.67 + 3069{\text{ }}/{\text{ }}T{\text{ }} + {\text{ }}9.5542{\text{ }}lnT$$