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Cytosolic long dsRNA, among the most potent proinflammatory signals, is recognized by melanoma differentiationassociated protein 5 (MDA5). MDA5 binds dsRNA cooperatively forming helical filaments. ATP hydrolysis byMDA5 fulfills a proofreading function by promoting dissociation of shorter endogenous dsRNs from MDA5 while allowing longer viral dsRNAs to remain bound leading to activation of interferon-ß responses. Here, we show that adjacent MDA5 subunits in MDA5-dsRNA filaments hydrolyze ATP cooperatively, inducing cooperative filament disassembly. Consecutive rounds of ATP hydrolysis amplify the filament footprint, displacing tightly bound proteins from dsRNA. Our electron microscopy and biochemical assays show that LGP2 binds to dsRNA at internal binding sites through noncooperative ATP hydrolysis. Unlike MDA5, LGP2 has low nucleic acid selectivity and can hydrolyze GTP and CTP as well as ATP. Binding of LGP2 to dsRNA promotes nucleation of MDA5 filament assembly resulting in shorter filaments. Molecular modeling identifies an internally bound MDA5-LGP2-RNA complex, with the LGP2 C-terminal tail forming the key contacts with MDA5. These contacts are specifically required for NTP-dependent internal RNA binding. We conclude that NTPase-dependent binding of LGP2 to internal dsRNA sites complements NTPase-independent binding to dsRNA ends, via distinct binding modes, to increase the number and signaling output of MDA5-dsRNA complexes. [ABSTRACT FROM AUTHOR]

Radiographically assessed body composition (BC) variables, including muscle and adipose tissue, may serve as prognostic biomarkers in patients with metastatic renal cell carcinoma (mRCC). We examined associations between baseline BC variables and outcomes for 99 patients with mRCC receiving first-line ipilimumab/nivolumab. Low skeletal muscle index (SMI) and low subcutaneous adipose tissue index (SATI) were associated with significantly better progression-free survival. Introduction: Biomarkers are needed to identify patients with metastatic renal cell carcinoma (mRCC) most likely to benefit from immune checkpoint inhibitors. We examined associations between radiographically assessed body composition (BC) variables and body mass index (BMI) with clinical outcomes for patients with mRCC receiving first-line ipilimumab + nivolumab (ipi/nivo). Patients and Methods: We retrospectively reviewed all patients with mRCC treated with first-line ipi/nivo at one institution before June 1, 2021 with an analyzable baseline computed tomography (CT) scan. BC variables (skeletal muscle index [SMI], subcutaneous adipose tissue index [SATI], and visceral adipose tissue index [VATI]) were measured using baseline CT scans. Relationships between BC variables and clinical outcomes were examined using Cox proportional hazard regression models. Results: Ninety-nine patients were analyzed (74% male, 64% overweight/obese, 75% low SMI). Controlling for age, IMDC risk, and sex (for BMI analyses), high vs. low SMI (HR = 2.433, CI: 1.397-4.238, P = .0017), high vs. low SATI (HR = 1.641, CI: 1.023-2.632, P = .0398), and obese BMI (≥ 30 kg/m²) vs. normal/overweight BMI (< 30 kg/m²) (HR = 1.859, CI: 1.156-2.989, P = .0105) were significantly associated with progression-free survival (PFS). Median overall survival (OS) for low SMI patients was higher (42.74 months, CI: 26.84, NR) than median OS for high SMI patients (27.01 months, CI: 15.28, NR) (adjusted HR = 1.728, CI: 0.909-3.285, P = .0952). No BC variables were significantly associated with OS or objective response rate. Conclusions: Low SMI and low SATI were associated with significantly better PFS for patients with mRCC receiving first-line ipi/nivo. Radiographic BC variables may be useful prognostic biomarkers in this setting. [ABSTRACT FROM AUTHOR]

A retrospective study compared the oncologic and functional outcomes of salvage cryotherapy (SCT) after primary radiotherapy (XRT-SCT) and cryotherapy (CRYO-SCT). Survival analysis showed no difference in biochemical progression-free survival between cohorts at 2 and 5 years, and comparable functional outcomes, supporting that SCT may be used to treat local prostate cancer recurrence after XRT or Cryotherapy. Introduction: Local prostate cancer recurrence following radiotherapy (XRT) or cryoablation (CRYO) may be addressed with salvage cryotherapy (SCT), although little is known about how the primary treatment modality affects SCT results. Oncologic and functional outcomes of patients who underwent SCT after primary XRT (XRT-SCT) or cryoablation (CRYO-SCT) were studied. Methods: Data was collected using the Duke Prostate Cancer database and the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression-free survival (BPFS). Urinary incontinence, rectourethral fistula, and erectile dysfunction were secondary outcomes. The Kaplan-Meier log-rank test and univariable/multivariable Cox proportional hazards (CPH) models were utilized to evaluate BPFS between groups. Results: 419 XRT-SCT and 63 CRYO-SCT patients met inclusion cr iter ia, that was reduced to 63 patients in each cohort after propensity matching. There was no difference in BPFS at 2 and 5 years both before (P = .5 and P = .7) and after matching (P = .6 and P = .3). On multivariable CPH, BPFS was comparable between treatment groups (CRYO-SCT, HR = 1.1, [0.2-2.2]). On the same analysis, BPFS was lower in D'Amico high-risk (HR 3.2, P < .01) and intermediate-risk (HR 1.95, P < .05) categories compared to low-risk. There was no significant difference in functional outcomes between cohorts. Conclusion: Following primary cryotherapy, salvage cryoablation provides comparable intermediate oncological outcomes and functional outcomes compared to primary radiotherapy. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: At present, there is no available method to study the in vivo microstructures of the airway wall (epithelium, smooth muscle, adventitia, basement membrane, glands, cartilage). Currently, we rely on ex vivo histologic evaluation of airway biopsies. To overcome this obstacle, we have developed an endoscopic ultrahigh-resolution diffractive optical coherence tomography (OCT) system, operating at a wavelength of 800 nm, to non-invasively study the in vivo microstructures of the airway wall. Prior to human study, validation of diffractive OCT's ability to quantitate airway microstructural components is required.Materials and Methods: To validate and demonstrate the accuracy of this OCT system, we used an ovine model to image small airways (∼ 2 mm in diameter). Histologic samples and correlated OCT images were matched. The cross-sectional area of the airway wall, lumen, and other microstructures were measured and compared.Results: A total of 27 sheep were studied from which we identified 39 paired OCT-histology airway images. We found strong correlations between the OCT and the histology measurements of the airway wall area and the microstructural area measurements of the epithelium, basement membrane, airway smooth muscle, glands, cartilage, and adventitia. The correlations ranged from r=0.61 (p<0.001) for the epithelium to r=0.86 (p<0.001) for the adventitia with the correlation between the OCT and the histology measurements for the entire airway wall of r=0.76 (p<0.001).Conclusion: Given the high degree of correlation, these data validate the ability to acquire and quantify in vivo microscopic level imaging with this newly developed 800nm ultra-high resolution diffractive OCT system. [ABSTRACT FROM AUTHOR]

• A new silica/phenolic pyramidal lattice reinforced silicone rubber based ablative material composite structure is proposed. • The lattice enhances the high-temperature stiffness of ablative materials dramatically. • Effects of geometrical parameters and heating rates are obtained. Besides aerodynamic heating, ablative materials are always exposed to aerodynamic pressure. This paper proposes an effective method to improve the high-temperature compressive performance of silicone rubber based ablative materials using silica/phenolic pyramidal lattice. Composite structures of silica/phenolic pyramidal lattice reinforced silicone rubber based ablative material were fabricated and tested with the high-temperature material testing machine. To determine the stiffness of lattice reinforced ablative materials at different temperatures, a theoretical model was developed and validated by comparison with experimental results. Results show that silica/phenolic pyramidal lattices can significantly improve the stiffness of ablative materials at high temperatures. The changes in the stiffness of ablative materials reinforced with silica/phenolic pyramidal lattices at high temperatures can be divided into four stages. The composite lattice has a reinforcing effect on the mechanical properties of ablative materials up to 1000 °C, with optimal enhancement observed at 681 °C. Furthermore, the effects of geometrical parameters of the lattice and heating rates on stiffness at high temperatures are also discussed. [ABSTRACT FROM AUTHOR]

• Local damage and imperfection sensitivities of pyramidal core sandwich cylinders are systematically studied. • Failure modes and defect types are considered to discuss the effects on buckling and post-buckling behavior. • When the imperfection offset factor varies from 0 to 1, the ultimate loads of pyramidal core sandwich cylinders are hardly reduced. Local damage and imperfections may affect the loading capacity of truss core sandwich cylinders. This study develops a numerical model to investigate the effects of missing lattice struts, unbound nodes, openings, and eigenmode-shape imperfections on the buckling and post-buckling behavior of pyramidal core sandwich cylinders. Results from the numerical model show that the pyramidal core sandwich cylinder is sensitive to missing struts and unbound nodes when local buckling is the main failure model. Critical loads show a gradual decrease as the opening damage increases. Pyramidal core sandwich cylinders are not sensitive to eigenmode-shape imperfections compared to the equivalent single-walled shells. [ABSTRACT FROM AUTHOR]

Solid oxide fuel cell hybrid generation system is the best scheme for the load tracking of off-grid monitoring stations. But there are still potential problems that need to be addressed: preventing fuel starvation and ensuring thermal safety while meeting load tracking in hybrid power generation system. In order to solve these problems, a feasible hybrid power generation system structure scheme is proposed which combined SOFC subsystem and Li-ion battery subsystem. Then a model of the hybrid power generation system is built based on the proposed system structure. On this basis, an adaptive controller, include the adaptive energy management algorithm and current feedforward gas supply strategy, is applied to manage the power-sharing in this hybrid system as well as keep the system operating within the safety constraints. The constraints, including maintaining the bus voltage at the desired level, keeping SOFC operating temperature in safety, and mitigating fuel starvation are explicitly considered. The stability of the proposed energy management algorithm is analyzed. Finally, the developed control algorithm is applied to the hybrid power generation system model, the operation result proves the feasibility of the designed controller strategy for hybrid generation system and effectively prevent fuel starvation and ensure thermal safety. • SOFC and battery hybrid system is designed and simulated for an off-grid device. • SOFC subsystem model is verified by experimental data. • A novel adaptive controller is developed to ensure system safety operation. • Developed controller improves power-sharing between the battery and SOFC subsystem. [ABSTRACT FROM AUTHOR]

Energy absorption properties of cellular materials have gained increasing interest due to their superior performance and immense design space. This paper introduces a novel lattice material with a Butterfly configuration that has controllable multi-stage crushing behavior and high specific energy absorption capacity. A theoretical model is developed to predict the plateau stress, elastic modulus and critical strain of each stage, in order to obtain the multi-stage stress-strain curve. Compression experiments and the finite element modelling are also carried out to validate the theoretical model. Theoretical and experimental results show that the Butterfly lattice material has more than two crushing stages and a specific energy absorption property comparable to the traditional stretching-dominated lattice material. Finally, effects of topology configuration, cell number, and geometrical parameter on the energy absorption behavior are analyzed. It is found that the length of the vertical beam dramatically influences the plateau load and deformation behavior of each stage. [ABSTRACT FROM AUTHOR]

• The membrane-based liquid desiccant air dehumidification technology was reviewed. • The parallel-plate and hollow fiber membrane contactors with various flow arrangements were summarized. • The single stage and multiply stage membrane-based liquid desiccant air dehumidification systems were analyzed. • The development prospects of this novel technology were predicted. The membrane-based liquid desiccant air dehumidification method had been reviewed based on the momentum, thermal, and mass transports, the performance analysis, and the thermodynamics. The parallel-plate membrane dehumidifiers (PMC) and hollow fiber membrane dehumidifiers (HFMC) with the cross-flow, quasi-counter flow, and counter flow configurations were summarized. The adiabatic and internally-cooled membrane dehumidifiers were described. The single-stage and the multistage membrane-based liquid desiccant air dehumidification (M-LDAD) systems to enhance their performances were analyzed. The internally-cooled quasi-counter flow PMC of the side in and side out type and hexagonal type were the promising alternatives. The counter flow and cross-flow HFMC were suitable for the small and relatively large air flow rates, respectively. The inclined flow type should be avoided to prevent from the performance deterioration. The internally-cooled HFMC with the cooling coils inside the solution channels between the neighboring short sub-contactors might have better performances with at the expenses of increasing equipment and operating costs. Effects of the membrane deformations on the momentum, thermal, and mass transports both in the PMC and HFMC should be studied. The randomly distributions of the hollow fiber tubes should be avoided. The multistage M-LDAD systems based on the internally-cooled PMC and HFMC complementarily driven by the waste energy and renewable energy sources were the better choices in the practical application whose thermodynamic and dynamics should be investigated. [ABSTRACT FROM AUTHOR]

• The kilowatt scale SOFC stack of natural gas systems were operated for 250 h. • Data-driven approach—Elman neural network was used for fault prediction of SOFC system. • The faults of heat exchanger breakage and the SOFC stack voltage jitter inside the system were analyzed and handled. • Application background is household generation system. For the distributed household generation technology, the operation status identification and prediction of multiple startup and shutdown solid oxide fuel cell (SOFC) system are of great significance to the optimization of power generation efficiency and long-term operation. The existing SOFC system research focuses on traditional physical models rather than actual SOFC system, which makes the system research too idealized and ignores the actual problems, such as health state prediction, voltage fluctuation and failure analysis of key equipment such as heat exchanger. Therefore, based on the data-driven actual natural gas SOFC system, this paper builds Elman neural network state prediction model under the entire stage (including system start-stop, long-term operation, hot-standby) to predict the future voltage, and infers the potential fault information of the system from the residual voltage. On this basis, combined with the dynamic response of the system, the essential causes of voltage fluctuation and heat exchanger breakage of the actual SOFC system are found out. And the improvement scheme of the system is proposed. The results show that the typical faults of the SOFC system can be accurately identified by combining Elman neural network state prediction model with multivariable dynamic response analysis of SOFC system. [ABSTRACT FROM AUTHOR]

• Melatonin exhibits a therapeutic potential in influenza A H1N1 virus infection. • Melatonin elicits anti-inflammatory and immune modulatory effects. • The induction of IL-10 by melatonin occurs via the upregulation of IL-27 in DC. • Melatonin treatment exhibits a synergistic effect with an anti-viral drug. Influenza is an infectious disease caused by an RNA virus that affects birds and mammals. It is a leading cause of morbidity, mortality and economic loss worldwide. Under influenza A virus infection, an uncontrolled inflammatory response in the lungs frequently leads to severe pneumonia. The anti-inflammatory and immune modulatory effects of melatonin may provide a beneficial effect for this disease. In this study, we found that melatonin treatment significantly decreases the expression of TNF-α, IL-6 and IFN-γ, and increases the production of IL-10 and TGF-β. The induction of IL-10 by melatonin occurs via the upregulation of IL-27 expression in dendritic cells. Melatonin also significantly inhibits the production of TNF-α in CD8 T cells. Co-treatment of melatonin and ribavirin significantly increases the survival of virus-infected mice compared to ribavirin alone. Our study suggests that melatonin possesses a therapeutic potential in influenza-induced pneumonia as an adjuvant treatment with anti-viral drugs. [ABSTRACT FROM AUTHOR]

Objective: To review the recent advances in available technologies for imaging COPD and present the novel optical coherence tomography (OCT) airway imaging technology.Materials and Methods: This is an unstructured review of published evidence of available pulmonary imaging technologies along with a demonstration of state-of-the-art OCT imaging technology of in vivo human and animal airways.Results: Advanced imaging techniques such as Magnetic Resonance (MR) imaging using hyperoloarized noble gases, micro-Computed Tomography (micro-CT), and OCT aim to further our understanding of COPD. Lung densitometry can aid in identifying an exacerbation prone phenotype which may have implications for targeting specific therapies to these individuals. MR ventilation scans have the ability to provide a functional and regional distribution of airflow obstruction offering insight into the airway and parenchymal changes induced by COPD. Micro-CT gives a near microscopic view of the terminal bronchioles and alveoli permitting study of the microarchitecture of the lung ex vivo. Optical coherence tomography can visualize the microstructure of the airway walls (epithelium, smooth muscle, blood vessels, cartilage) permitting real time in vivo as well as longitudinal evaluation of airway changes in patients with COPD.Conclusion: Advanced imaging techniques play a vital role in expanding our current understanding of COPD. [ABSTRACT FROM AUTHOR]

Abstract Solid oxide fuel cell is a device that can convert chemical energy directly into electricity. Its advantages, such as high efficiency, low emission, quiet operation, fuel flexibility, bring about the broad application prospect. However, it is difficult to obtain the temperature distribution in the existing planar cross flow solid oxide fuel cell through the experiment. In this paper, a control orient two-dimensional differential equation model is established for a planar cross flow solid oxide fuel cell based on the finite node method, and an iterative algorithm for calculating the real time voltage of the fuel cell is proposed for the model. Based on the model, the temperature distribution of the fuel cell in the test and system configuration is simulated. The simulation results show that the model can reflect the thermoelectric characteristics of the planar cross flow solid oxide fuel cell, especially the temperature distribution of the fuel cell. The SOFC temperature distribution modeling in this paper is helpful for the development of temperature distribution observers and design related control methods in later studies. [ABSTRACT FROM AUTHOR]

Abstract The dynamic recrystallization (DRX) behavior of magnesium alloy AZ31B with large initial grain size was investigated. Two methods were applied to establish the DRX kinetics model. One is based on the values of DRX volume fraction evaluated by true stress-strain curves (Model 1). The other is based on the values of DRX volume fraction evaluated using optical micrographs (Model 2). It is found that the predicted DRX volume fraction by Model 1 is significantly larger than that by Model 2. It indicates that the value of DRX volume fraction (X drx) cannot be calculated by the true stress-strain curves for the magnesium alloy AZ31B with large initial grain size. To understand the phenomenon, the reason was analyzed and discussed. We found that the main reason can be attributed to the strong fine-grain strengthening (FGS) effect of magnesium alloy AZ31B. For the studied material, the flow behavior will be mainly affected by two factors during DRX: 1) the decrease of average dislocation density which gives rise to the decrease of flow stress; 2) the decrease of average grain size which results in the increase of flow stress. The latter causes that the DRX volume fraction evaluated by the true stress-strain curves is obviously larger than the real one. The research results will be good references for the evaluation of DRX volume fraction of other FGS materials with large initial grain sizes. Graphical Abstract Unlabelled Image Highlights • The DRX behavior of magnesium alloy AZ31B with large initial grain size is investigated. • The DRX faction evaluated by true stress-strain curve is obviously larger than real one. • The DRX faction cannot be evaluated by true stress-strain curve due to fine-grain strengthening effect [ABSTRACT FROM AUTHOR]

This paper presented a three dimensional deformation and full-field temperature measurement method for continuous wave laser irradiated structures over a range extending from the room temperature to the melting point. The deformation was measured by the three dimensional digital image correlation technique. The speckle pattern was made on the specimen surface by the high temperature glue with a maximum service temperature of 1700 °C. A bandpass filter and a blue light source were used to eliminate the effect of thermal radiation from the laser irradiated region. The accuracy of present method was validated by the coordinate measurement machine and the laser Doppler vibrometer. According to the relationship between the gray value of images and the temperature, the full-field temperature distribution were measured by the colorimetry temperature measurement method. Finally, parameters that affect the response of laser irradiated thin plates, including laser power, high-speed airflow, plate thickness and material properties are investigated. [ABSTRACT FROM AUTHOR]

Abstract A new function of filled sandwich panel with truss core, superior high-power laser resistance, is reported. When filled with carbon powder-reinforced silicone resin composite, which is an ablative material, the panel exhibits superior high-power laser resistance to monolithic plate with equal areal density. This paper revealed the detailed mechanisms and reproduced the process with numerical simulation. FIIR, SEM-EDS, and TG/DSC analyses on the virgin filler material and ablation residues are conducted to investigate the thermo-physicochemical process of the filler material during the laser ablation. Considering pyrolysis, oxidation, and phase change in the laser ablation process, a 3D numerical model is developed by using the finite element method. The temperature field and ablation morphology obtained from the numerical model agree with those from the experiment. The ablation evolution process, pyrolysis effect, and laser resistance mechanism of the filled sandwich panels with truss cores are evaluated based on the present model. [ABSTRACT FROM AUTHOR]

We reported a new function of sandwich panels with truss cores, i.e., superior performance under intense local heat flux induced by continuous wave laser. To further enhance the laser resistance, lightweight ablative material and thermal insulation material are filled in the sandwich panel respectively. A dimensional analysis is developed to find core filler materials with appropriate properties. Experiments show that sandwich panels filled with the compound of silicone resin and carbon powder, a typical ablative material, and porous ceramic, a typical thermal insulation material significantly improve the local heat flux resistance compared with monolithic plates and unfilled sandwich panels. The full-field temperature history and dynamic damage evolution of the back surface are recorded and compared, and the failure time to reach the melting point is prolonged in the following order: monolithic plate, unfilled sandwich panel, sandwich panel filled with ceramic, sandwich panel filled with the compound of silicone resin and carbon powder. Considering the lightweight design requirement of such structures, resistance in relation to specific weight is also evaluated and discussed. [ABSTRACT FROM AUTHOR]

The motion of coalescence-induced condensate droplets on superhydrophobic surface (SHS) has attracted increasing attention in energy-related applications. Previous researches were focused on regularly rough surfaces. Here a new approach, a mesoscale lattice Boltzmann method (LBM), is proposed and used to model the dynamic behavior of coalescence-induced droplet jumping on SHS with randomly distributed rough structures. A Fast Fourier Transformation (FFT) method is used to generate non-Gaussian randomly distributed rough surfaces with the skewness ( S k), kurtosis ( K ) and root mean square ( R q) obtained from real surfaces. Three typical spreading states of coalesced droplets are observed through LBM modeling on various rough surfaces, which are found to significantly influence the jumping ability of coalesced droplet. The coalesced droplets spreading in Cassie state or in composite state will jump off the rough surfaces, while the ones spreading in Wenzel state would eventually remain on the rough surfaces. It is demonstrated that the rough surfaces with smaller S ks, larger R qs and a K at 3.0 are beneficial to coalescence-induced droplet jumping. The new approach gives more detailed insights into the design of SHS. [ABSTRACT FROM AUTHOR]

The dynamic recrystallization (DRX) behavior of 42CrMo steel was studied by hot compressive tests and cellular automaton (CA) simulation. The experimental results showed that initial grain size besides deformation parameters has an obvious influence on dynamic recrystallization (DRX) behavior. It is found that the initial grain size not only influences the number of DRX nucleation site, but also the work-hardening (WH) coefficient, dynamic recovery (DRV) coefficient, DRX nucleation rate and grain boundary (GB) mobility. Moreover, the relationships between the WH coefficient, DRV coefficient, DRX nucleation rate, GB mobility and initial grain size can be well described by the power function. Based on the findings, the traditional CA model was extended to describe the effect of initial grain size on DRX behavior. The comparison between experimental and simulated results showed that the microstructural evolution of 42CrMo steel with different initial grain sizes during hot deformation can be accurately simulated by the extended CA model. [ABSTRACT FROM AUTHOR]