The Synthesis and Initial Evaluation of MerTK Targeted PET Agents

MerTK (Mer tyrosine kinase), a receptor tyrosine kinase, is ectopically or aberrantly expressed in numerous human hematologic and solid malignancies. Although a variety of MerTK targeting therapies are being developed to enhance outcomes for patients with various cancers, the sensitivity of tumors to MerTK suppression may not be uniform due to the heterogeneity of solid tumors and different tumor stages. In this report, we develop a series of radiolabeled agents as potential MerTK PET (positron emission tomography) agents. In our initial in vivo evaluation, [18F]-MerTK-6 showed prominent uptake rate (4.79 ± 0.24%ID/g) in B16F10 tumor-bearing mice. The tumor to muscle ratio reached 1.86 and 3.09 at 0.5 and 2 h post-injection, respectively. In summary, [18F]-MerTK-6 is a promising PET agent for MerTK imaging and is worth further evaluation in future studies

Development of a novel embryonic germline gene-related prognostic model of lung adenocarcinoma

Background Emerging evidence implicates the correlation of embryonic germline genes with the tumor progress and patient’s outcome. However, the prognostic value of these genes in lung adenocarcinoma (LUAD) has not been fully studied. Here we systematically evaluated this issue, and constructed a novel signature and a nomogram associated with embryonic germline genes for predicting the outcomes of lung adenocarcinoma. Methods The LUAD cohorts retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were used as training set and testing set, respectively. The embryonic germline genes were downloaded from the website https://venn.lodder.dev. Then, the differentially expressed embryonic germline genes (DEGGs) between the tumor and normal samples were identified by limma package. The functional enrichment and pathway analyses were also performed by clusterProfiler package. The prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO)-Cox regression method. Survival and Receiver Operating Characteristic (ROC) analyses were performed to validate the model using training set and four testing GEO datasets. Finally, a prognostic nomogram based on the signature genes was constructed using multivariate regression method. Results Among the identified 269 DEGGs, 249 were up-regulated and 20 were down-regulated. GO and KEGG analyses revealed that these DEGGs were mainly enriched in the process of cell proliferation and DNA damage repair. Then, 103 DEGGs with prognostic value were identified by univariate Cox regression and further filtered by LASSO method. The resulting sixteen DEGGs were included in step multivariate Cox regression and an eleven embryonic germline gene related signature (EGRS) was constructed. The model could robustly stratify the LUAD patients into high-risk and low-risk groups in both training and testing sets, and low-risk patients had much better outcomes. The multi-ROC analysis also showed that the EGRS model had the best predictive efficacy compared with other common clinicopathological factors. The EGRS model also showed robust predictive ability in four independent external datasets, and the area under curve (AUC) was 0.726 (GSE30219), 0.764 (GSE50081), 0.657 (GSE37745) and 0.668 (GSE72094). More importantly, the expression level of some genes in EGRS has a significant correlation with the progression of LUAD clinicopathology, suggesting these genes might play an important role in the progression of LUAD. Finally, based on EGRS genes, we built and calibrated a nomogram for conveniently evaluating patients’ outcomes

Investigation and Optimization of Fast Cold Start of 18650 Lithium-Ion Cell by Heating Film-Based Heating Method

In this paper, based on the multi-scale multi-domain (MSMD) battery modeling approach, the NTGK model was used to model the 18650 cylindrical lithium-ion single battery on the electrochemical sub-scale. The model was successful, as it was able to fit the experimental voltage and temperature of the battery at different temperatures. Lithium-ion battery discharge capacity and energy output can be improved during cold starting by preheating and insulation, as demonstrated by a comparison of the impacts of heat transfer coefficient and preheating duration at −20 °C ambient temperature. For the traditional heating method, the heating model of heating film (HF) and liquid-cooled plate (LCP) is constructed in this paper, and the heating performance of both is compared by Fluent. Analysis of the energy balance of Li-ion battery at low temperatures has been presented, showing that Li-ion battery requires a suitable start-up temperature to maximize energy output. Taking care of the problem of excessive temperature difference inside the battery due to excessive heating power, we investigated the effects of axial thermal conductivity, heating power, and heating area on the heating uniformity of the battery in this paper. Finally, a multi-stage stepped power (MSP) heating method was proposed to improve the temperature control accuracy of HF. A level orthogonal test L16(43) without interaction was designed to determine the degree of influence of each parameter on the temperature control performance and the optimal level combination, revealing that the optimized maximum temperature and temperature control rate were reduced by 4.09% and 40.53%, respectively, when compared to direct heating

Multicomponent <i>cis</i>- and <i>trans</i>-Aziridinatons in the Syntheses of All Four Stereoisomers of Sphinganine

All four stereoisomers of sphinganine can be synthesized by a multicomponent aziridination of an aldehyde, an amine and an α-diazo carbonyl compound mediated by a BOROX catalyst with high asymmetric induction (≥96% ee). The threo isomers are available from ring-opening of <i>cis</i>-aziridines by an oxygen nucleophile with inversion at the C-3 position and the erythro-isomers are likewise available from <i>trans</i>-aziridines

Numerical Simulations for Indirect and Direct Cooling of 54 V LiFePO₄ Battery Pack

In this study, three-dimensional thermal simulations for a 54 V Lithium-ion battery pack composed of 18 LiFePO4 pouch battery cells connected in series were conducted using a multi-scale electrochemical-thermal-fluid model. An equivalent circuit model (ECM) is used as a subscale electrochemical model at each cell node of the battery, which is then combined with the macro-scale thermal and fluid equations to construct a model of the battery and battery pack. With the model, the cooling effects of indirect cooling and direct cooling battery thermal management systems (BTMS) on the battery pack under rapid discharging conditions are explored. It is found that when the battery pack is discharged at 2C, indirect cooling of the bottom plate can effectively dissipate heat and control the temperature of the battery pack. Under the 10C discharging condition, the maximum temperature of the battery pack will exceed 100 °C, and the temperature uniformity will be very poor when using indirect cooling of the bottom plate for the battery pack. Direct air cooling is also unable to meet the cooling requirements of the battery pack at a 10C discharging rate. The possible reason is that the convective heat transfer coefficient of direct air cooling is small, which makes it difficult to meet the heat dissipation requirements at the 10C condition. When single-phase direct cooling with fluorinated liquid is used, the maximum temperature of the battery pack under the 10C discharging condition can be controlled at about 65 °C. Compared with air direct cooling, the pressure drop of fluorinated liquid single-phase direct cooling is smaller, and the obtained battery pack temperature uniformity is better. From the detailed study of fluorinated liquid single-phase direct cooling, it is concluded that increasing the coolant flow rate and reducing the cell spacing in the battery pack can achieve a better cooling effect. Finally, a new cooling method, two-phase immersion cooling, is investigated for cooling the battery pack. The maximum temperature of the battery pack discharged at a 10C rate can be controlled below 35 °C, and good temperature uniformity of the battery pack is also achieved at the same time. This study focuses on fluorinated liquid immersion cooling using numerical simulations, showing that it is a promising cooling method for lithium-ion battery packs and deserves further study. This paper will provide a reference for the design and selection of BTMS for electric vehicles

Three-Dimensional Thermal Simulations of 18650 Lithium-Ion Batteries Cooled by Different Schemes under High Rate Discharging and External Shorting Conditions

In this work, three-dimensional thermal simulations of single 18650 lithium-ion battery cell and 75 V lithium-ion battery pack composed of 21 18650 battery cells are performed based on a multi-scale multi-domain (MSMD) battery modeling approach. Different cooling approaches’ effects on 18650 lithium-ion battery and battery pack thermal management under fast discharging and external shorting conditions are investigated and compared. It is found that for the natural convection, forced air cooling, and/or mini-channel liquid cooling approaches, the temperature of battery cell easily exceeds 40 °C under 3C rate discharging condition. While under external shorting condition, the temperature of cell rises sharply and reaches the 80 °C in a short period of time, which can trigger thermal runaway and may even lead to catastrophic battery fire. On the other hand, when the cooling method is single-phase direct cooling with FC-72 as coolant or two-phase immersed cooling by HFE-7000, the cell temperature is effectively limited to a tolerable level under both high C rate discharging and external shorting conditions. In addition, two-phase immersed cooling scheme is found to lead to better temperature uniformity according to the 75 V battery pack simulations

Optical properties of Er, Yb co-doped YAG transparent ceramics

The transparent polycrystalline erbium and ytterbium co-doped yttrium aluminum garnet (Er, Yb:YAG) ceramics with various Yb contents from 5% to 25% were prepared by the solid-state reaction and the vacuum-sintering technique. The in-line transmittances of the mirror-polished ceramics exceed 80% from the visible band to the infrared band. The samples are very compact with few pores. The average grain size of the Er,Yb:YAG ceramic is about 15 mu m. The upconversion luminescence spectra, infrared luminescence spectra and luminescence decay curves of the ceramics were observed and discussed. For 1%Er doped YAG ceramic, the best ion ratio of Yb(3+) and Er(3+) is around 15:1. (C) 2010 Elsevier Ltd and Techna Group S.r.l. All rights reserved

Three-Dimensional Modeling for the Internal Shorting Caused Thermal Runaway Process in 20Ah Lithium-Ion Battery

Better understanding of how internal short circuit causes thermal runaway will benefit the engineering for safer lithium-ion batteries. In this study, three-dimensional (3D) numerical simulations of a 20Ah lithium battery under internal shorting condition are performed. The effects of internal short circuit area, resistance, penetration depth, convective heat transfer coefficient and internal short circuit position, on the thermal runaway are investigated with the simulations in this work. This study demonstrates that the average cell temperature is only weakly affected by the internal short circuit area, penetration depth, and position. On the other hand, the internal short circuit resistance and the convective heat transfer coefficient have large impacts on the thermal runaway propagation in the lithium-ion battery. A high convective heat transfer coefficient can effectively suppress the thermal runaway propagation. However, such a high convective heat transfer coefficient is hard to achieve at the cell surface

Multicomponent Catalytic Asymmetric Synthesis of <i>trans</i>-Aziridines

A multicomponent <i>trans</i>-aziridination of aldehydes, amines, and diazo compounds with BOROX catalysts is developed. The optimal protocol is slightly different for aryl aldehydes than for aliphatic aldehydes. The key to the success with aryl aldehydes was allowing the catalyst, aldehyde, and amine to react for 20 min before addition of the diazo compound. A variety of 11 different electron-poor and electron-rich aryl aldehydes were screened to give <i>trans</i>-aziridines in 73–90% yield with 82–99% ee and <i>trans</i>/<i>cis</i> selectivities of 19:1 to >99:1. The optimal protocol for the <i>trans</i>-aziridination of aliphatic aldehydes did not require prereaction of the catalyst, aldehyde, and amine, and instead, the diazo compound could be added directly. The scope of the reaction is limited to unbranched aliphatic aldehydes and was tolerant of a number of functional groups including ethers, esters, epoxides, carbamates, and phthalimides. A total of 10 aliphatic aldehydes were examined and found to give <i>trans</i>-aziridines in 60–88% yield with 60–98% ee and <i>trans</i>/<i>cis</i> selectivities of 6:1 to >99:1. Alkenyl aldehydes did not react, but an alkynyl aldehyde gave a 71% yield and 95% ee of an aziridine that was found to be the <i>cis</i>- and not the <i>trans</i>-diastereomer. The aryl and aliphatic aldehydes both gave the <i>trans</i>-aziridines with the same absolute configuration with the same catalyst; however, in those cases where <i>cis</i>-aziridines were formed, the configuration was opposite for those formed from aryl versus aliphatic aldehydes