A versatile optimization framework for porous electrode design.

Porous electrodes are performance-defining components in electrochemical devices, such as redox flow batteries, as they govern the electrochemical performance and pumping demands of the reactor. Yet, conventional porous electrodes used in redox flow batteries are not tailored to sustain convection-enhanced electrochemical reactions. Thus, there is a need for electrode optimization to enhance the system performance. In this work, we present an optimization framework to carry out the bottom-up design of porous electrodes by coupling a genetic algorithm with a pore network modeling framework. We introduce geometrical versatility by adding a pore merging and splitting function, study the impact of various optimization parameters, geometrical definitions, and objective functions, and incorporate conventional electrode and flow field designs. Moreover, we show the need for optimizing geometries for specific reactor architectures and operating conditions to design next-generation electrodes, by analyzing the genetic algorithm optimization for initial starting geometries with diverse morphologies (cubic and a tomography-extracted commercial electrode), flow field designs (flow-through and interdigitated), and redox chemistries (VO2+/VO2 + and TEMPO/TEMPO+). We found that for kinetically sluggish electrolytes with high ionic conductivity, electrodes with numerous small pores and high internal surface area provide enhanced performance, whereas for kinetically facile electrolytes with low ionic conductivity, low through-plane tortuosity and high hydraulic conductance are desired. The computational tool developed in this work can further expanded to the design of high-performance electrode materials for a broad range of operating conditions, electrolyte chemistries, reactor designs, and electrochemical technologies.

Prognostic value and therapeutic consequences of vascular invasion in non-small cell lung carcinoma.

The prognostic relevance of blood vessel invasion (BVI) in non-small cell lung carcinoma (NSCLC) remains controversial, as is the question of whether its finding should influence therapeutic decisions after an R0 resection. One hundred and twelve cases of NSCLC were included in the study. All had been treated by potentially curative surgical resection of the primary tumor and systematic lymphadenectomy. In all cases, lymphatic metastatic spread was at its earliest stage and only one regional lymph node was involved, 27.0+/-8.9 nodes per patient being examined histologically. Most of the cases were pT2 (75.9%) and pN1 (81.3%), and all were MX/M0 and R0. 62.5% were at stage IIB, 25.9% at stage IIIA, and 9.8% at stage IIA. BVI was found in 45.5% of the tumors (V1), and 18.8% exhibited both lymphatic invasion and BVI (L1V1). Local recurrence occurred in 10.7% of the patients, distant metastasis in 24.1%, and both forms of tumor progression simultaneously in a further 7.1%. Thus 31.2% of the patients developed distant metastases by hematogenous spread (to the brain, bones, lung, adrenal, and liver, in descending order of frequency), mostly within two years of surgery. Late metastasis is not typical of NSCLC. Adenocarcinomas showed a strong tendency to be associated with a poorer prognosis than squamous cell carcinomas, probably because of their more frequent involvement of blood vessels. Five-year survival (Kaplan-Meier method) was significantly lower in V1 cases (37.2%) than in V0 cases (56.0%; p = 0.0249). Adjuvant mediastinal radiation in node-positive cases of NSCLC may prevent local recurrence but is unlikely to influence the development of distant metastases. The histological detection of BVI is of prognostic relevance and should be considered for inclusion in the staging criteria and indications for adjuvant chemotherapy.

An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles.

Tumor-derived extracellular vesicles (TEV) "educate" healthy cells to promote metastases. We found that melanoma TEV downregulated type I interferon (IFN) receptor and expression of IFN-inducible cholesterol 25-hydroxylase (CH25H). CH25H produces 25-hydroxycholesterol, which inhibited TEV uptake. Low CH25H levels in leukocytes from melanoma patients correlated with poor prognosis. Mice incapable of downregulating the IFN receptor and Ch25h were resistant to TEV uptake, TEV-induced pre-metastatic niche, and melanoma lung metastases; however, ablation of Ch25h reversed these phenotypes. An anti-hypertensive drug, reserpine, suppressed TEV uptake and disrupted TEV-induced formation of the pre-metastatic niche and melanoma lung metastases. These results suggest the importance of CH25H in defense against education of normal cells by TEV and argue for the use of reserpine in adjuvant melanoma therapy.

Surgical resection and survival of patients with unsuspected single node positive lung cancer (NSCLC) invading the descending aorta.

BACKGROUND: Surgical treatment of non-small cell lung cancer (NSCLC) with aortic invasion is still debated. METHODS: Thirteen patients with locally advanced (T4) NSCLC and invasion of the descending aorta underwent pneumonectomy (n=9) or lobectomy (n=4) together with aorta en bloc resection and reconstruction (n=8) or subadventitial dissection (n=5), complete lymph node dissection, and had microscopic unsuspected node metastasis at N1 (n=5) and N2/3 (n=8) levels of whom 12 received radiation therapy. Clamp-and-sew was used to resect and reconstruct the aorta. RESULTS: Operative mortality and morbidity rate was 0% and 23%, respectively. Four patients died of systemic tumor relapse and 2 of local recurrence. Six patients were alive after a median follow-up of 40 months (range 15-125 months). Overall 5-year survival rate was 45%. Median survival time and 5-year survival rate of patients after aortic resection was 35 months and 67%, respectively, and was 17 months and 0%, respectively, after aortic subadventi-tial dissection (p=0.001). N1 and N2 nodal status adversely affected survival, but survival difference was not significant (N1 versus N2/3; 52% versus 39% at 5 years; p=0.998). CONCLUSIONS: Aortic resection with single station node positive T4 lung cancer can achieve long-term survival. The data indicate that aortic resection-reconstruction is associated with better outcome than subadventitial dissection.