Passive vapor generation systems combining interfacial solar heating and vaporization enthalpy recycling enable high-efficient low-cost desalination.
Vapor condensation is routinely used as an effective means of transferring heat or separating fluids. Dropwise condensation, where discrete droplets form on the condenser surface, offers a potential improvement in heat transfer of up to an order of magnitude compared to filmwise condensation, where a liquid film covers the surface. Low surface tension fluid condensates such as hydrocarbons pose a unique challenge since typical hydrophobic condenser coatings used to promote dropwise condensation of water often do not repel fluids with lower surface tensions. Recent work has shown that lubricant infused surfaces (LIS) can promote droplet formation of hydrocarbons. In this work, we confirm the effectiveness of LIS in promoting dropwise condensation by providing experimental measurements of heat transfer performance during hydrocarbon condensation on a LIS, which enhances heat transfer by ≈450% compared to an uncoated surface. We also explored improvement through removal of noncondensable gases and highlighted a failure mechanism whereby shedding droplets depleted the lubricant over time. Enhanced condensation heat transfer for low surface tension fluids on LIS presents the opportunity for significant energy savings in natural gas processing as well as improvements in thermal management, heating and cooling, and power generation.
The treatment landscape for metastatic renal cell carcinoma (mRCC) and urothelial carcinoma (mUC) has evolved rapidly in recent years with the approval of several checkpoint inhibitors. Despite these advances, survival rates for metastatic disease remain poor, and additional strategies will be needed to improve the efficacy of checkpoint inhibitors. Combining anti-VEGF/VEGFR agents with checkpoint inhibitors has emerged as a potential strategy to advance the immunotherapy paradigm, because VEGF inhibitors have immunomodulatory potential. Cabozantinib is a tyrosine kinase inhibitor (TKI) whose targets include MET, AXL, and VEGFR2. Cabozantinib has a unique immunomodulatory profile and has demonstrated clinical efficacy as a monotherapy in mRCC and mUC, making it a potentially suitable partner for checkpoint inhibitor therapy. In this review, we summarize the current status of immunotherapy for mRCC and mUC and discuss the development of immunotherapy-TKI combinations, with a focus on cabozantinib. We discuss the rationale for such combinations based on our growing understanding of the tumor microenvironment, and we review in detail the preclinical and clinical studies supporting their use.
Purpose: Programmed death-ligand 1 (PD-L1) status by IHC is prognostic in metastatic renal cell carcinoma (mRCC), and its role as a potential predictive biomarker is under investigation. Using tumor tissue from the METEOR (NCT01865747) and CABOSUN (NCT01835158) clinical trials, we explored whether PD-L1 expression and the extent of the immune cell infiltrate can serve as prognostic and/or predictive biomarkers for cabozantinib and other targeted agents.Experimental Design: IHC double staining for PD-L1 and CD45/CD163 (immune cell markers) was performed on tumor tissue from METEOR (n ¼ 306) and CABOSUN (n ¼ 110) clinical trials. Immune cell density and MET expression levels were also analyzed. Our primary aim was to correlate progression-free survival (PFS) by independent central review with PD-L1 status in patients treated with cabozantinib, everolimus (METEOR), or sunitinib (CABOSUN). Overall survival (OS) was also interrogated.Results: Tumor cell (TC) PD-L1 expression (!1% cutoff) was detected in 29% and 23% of tumors from patients in the METEOR and CABOSUN trials, respectively. On univariate analysis, patients with PD-L1-positive TC had poorer PFS and OS than patients with PD-L1-negative TC on both trials, independent of therapy. On multivariable analysis and when combining the two trials, the association between TC PD-L1 expression and OS was statistically significant for all patients (P ¼ 0.034) and for patients treated with cabozantinib only (P ¼ 0.038). Cabozantinib was associated with improved PFS (HR < 0.70) and OS (HR < 0.85) compared with everolimus and sunitinib irrespective of PD-L1 expression.Conclusions: Higher PD-L1 expression results in worse clinical outcomes in mRCC treated with targeted therapy. Furthermore, PD-L1 expression is not predictive of response to cabozantinib therapy.
Practice Options from Beyond Our Pages focuses on identifying, critiquing, and placing into context research studies published in other journals that have the potential to change our clinical practices. It is written by Allergy-Immunology Fellows partnered with faculty members, and does not require an invitation for submission. This feature is coordinated by Editorial Board members
Micro-Raman thermography is one of the most popular techniques for measuring local temperature rise in gallium nitride (GaN) high electron mobility transistors (HEMTs) with high spatial and temporal resolution. However, accurate temperature measurements based on changes in the Stokes peak positions of the GaN epitaxial layers requires properly accounting for the stress and/or strain induced by the inverse piezoelectric effect. It is common practice to use the pinched OFF state as the unpowered reference for temperature measurements because the vertical electric field in the GaN buffer that induces inverse piezoelectric stress/strain is relatively independent of the gate bias. Although this approach has yielded temperature measurements that agree with those derived from the Stokes/anti-Stokes ratio and thermal models, there has been significant difficulty in quantifying the mechanical state of the GaN buffer in the pinched OFF state from changes in the Raman spectra. In this paper, we review the experimental technique of micro-Raman thermography and derive expressions for the detailed dependence of the Raman peak positions on strain, stress, and electric field components in wurtzite GaN. We also use a combination of semiconductor device modeling and electro-mechanical modeling to predict the stress and strain induced by the inverse piezoelectric effect. Based on the insights gained from our electromechanical model and the best values of material properties in the literature, we analyze changes in the E2 high and A1 (LO) Raman peaks and demonstrate that there are major quantitative discrepancies between measured and modeled values of inverse piezoelectric stress and strain. We examine many of the hypotheses offered in the literature for these discrepancies but conclude that 2 none of them satisfactorily resolves these discrepancies. Further research is needed to determine whether the electric field along the -axis could be affecting the phonon frequencies apart from the inverse piezoelectric effect in wurtzite GaN, which has been predicted theoretically in zinc blende gallium arsenide (GaAs).
<b><i>Introduction:</i></b> Cabozantinib, an inhibitor of MET, AXL, and VEGF receptors, significantly improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with previously treated advanced hepatocellular carcinoma (HCC). In this exploratory analysis, outcomes were evaluated according to plasma biomarker levels. <b><i>Methods:</i></b> Baseline plasma levels were evaluated for MET, AXL, VEGFR2, HGF, GAS6, VEGF-A, PlGF, IL-8, EPO, ANG2, IGF-1, VEGF-C, and c-KIT for 674/707 randomized patients; and Week 4 levels were evaluated for MET, AXL, VEGFR2, HGF, GAS6, VEGF-A, PlGF, IL-8, and EPO for 614 patients. OS and PFS were analyzed by baseline levels as dichotomized or continuous variables and by on-treatment changes at Week 4 as continuous variables; biomarkers were considered potentially prognostic if <i>p</i> < 0.05 and predictive if <i>p</i> < 0.05 for the interaction between treatment and the biomarker. Multivariable analyses adjusting for clinical covariates were also performed. <b><i>Results:</i></b> In the placebo group, high levels of MET, HGF, GAS6, IL-8, and ANG2 and low levels of IGF-1 were associated with shorter OS in univariate and multivariable analyses; these associations were also observed for MET, IL-8, and ANG2 in the cabozantinib group. Hazard ratios for OS and PFS favored cabozantinib over the placebo at low and high baseline levels for all biomarkers. No baseline biomarkers were predictive of a treatment benefit. Cabozantinib promoted pharmacodynamic changes in several biomarkers, including increases in VEGF-A, PlGF, AXL, and GAS6 levels and decreases in VEGFR2 and HGF levels; these changes were not associated with OS or PFS. <b><i>Conclusion:</i></b> Cabozantinib improved OS and PFS versus placebo at high and low baseline concentrations for all biomarkers analyzed. Low baseline levels of MET, HGF, GAS6, IL-8, and ANG2 and high levels of IGF-1 were identified as potential favorable prognostic biomarkers for survival in previously treated advanced HCC. Although cabozantinib promoted pharmacodynamic changes in several biomarkers, these changes were not associated with survival.
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