A Strategic Assessment of Needs and Opportunities for the Wider Adoption of Electric Vehicles in Indiana

INDOT plans to invest nearly $100 million to build a statewide electric vehicle (EV) charging network as part of the National Electric Vehicle Infrastructure Formula Program. SPR-4509 Phase-I identified energy EV charging deserts in Indiana for long-distance trips. SPR-4509 Phase-II further examines the charging stations\u27 impact on EV long-distance trips in Indiana. Using an agent-based simulation model, the number of charges, vehicle miles traveled, energy used during the trip, and energy used during charging were estimated for nine different cases. High EV daily charging demand areas in Indiana were shown in ArcGIS based on multiple scenarios of different charging station construction phases and EV market penetration rates. The study findings can inform the state’s EV charging plan development

A Strategic Assessment of Needs and Opportunities for the Wider Adoption of Electric Vehicles in Indiana [Phase 2]

SPR-4509 Phase IIThe primary objective of this study was to assess the challenges and opportunities associated with the provision of appropriate infrastructure to support electric vehicle (EV) operations and electrification across Indiana. A secondary objective of this study was to develop a strategic plan for the Indiana Department of Transportation (INDOT) that outlines new business opportunities for developing EV charging stations. To achieve these objectives, the project team assessed current and emerging trends in EV operations, particularly EV charging infrastructure and EV demand forecasting. They also examined opportunities for the strategic deployment of EV charging stations by identifying EV infrastructure deficit areas; investigated the impact of EV adoption on highway revenue and the feasibility of new revenue structures; and evaluated strategic partnerships and business models. The agent-based simulation model developed for future long distance EV trip scenarios enables INDOT to identify EV energy deficient areas for current and future energy charging demand scenarios, and it can support Indiana\u2019s strategic plans for EV charging infrastructure development. The results of the revenue impact analysis can inform INDOT\u2019s revenue model. The estimations of the recovery EV fee, the vehicle miles travelled (VMT) fee, and pay-as-you-charge fee that break-even the fuel tax revenue loss can be used by INDOT in pilot programs to capture users\u2019 perspectives and estimate appropriate fee rates and structures. The insights obtained from the stakeholder interviews can be used to enhance preparedness for increasing EV adoption rates across vehicle classes and to strengthen the engagement of different entities in the provision of charging infrastructure

Humanized Anti-hepatocyte Growth Factor Monoclonal Antibody (YYB-101) Inhibits Ovarian Cancer Progression

Current chemotherapy regimens have certain limitations in improving the survival rates of patients with advanced ovarian cancer. Hepatocyte growth factor (HGF) is important in ovarian cancer cell migration and invasion. This study assessed the effects of YYB-101, a humanized monoclonal anti-HGF antibody, on the growth and metastasis of ovarian cancer cells. YYB-101 suppressed the phosphorylation of the HGF receptor c-MET and inhibited the migration and invasion of SKOV3 and A2780 ovarian cancer cells. Moreover, the combination of YYB-101 and paclitaxel synergistically inhibited tumor growth in an in vivo ovarian cancer mouse xenograft model and significantly increased the overall survival (OS) rate compared with either paclitaxel or YYB-101 alone. Taken together, these findings suggest that YYB-101 has therapeutic potential in ovarian cancer when combined with conventional chemotherapy agents.1

Generation of homogeneous midbrain organoids with in vivo-like cellular composition facilitates neurotoxin-based Parkinson\u27s disease modeling

Recent studies have demonstrated the generation of midbrain-like organoids (MOs) from human pluripotent stem cells. However, the low efficiency of MO generation and the relatively immature and heterogeneous structures of the MOs hinder the translation of these organoids from the bench to the clinic. Here we describe the robust generation of MOs with homogeneous distribution of midbrain dopaminergic (mDA) neurons. Our MOs contain not only mDA neurons but also other neuronal subtypes as well as functional glial cells including astrocytes and oligodendrocytes. Furthermore, our MOs exhibit mDA neuron-specific cell death upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, indicating that MOs could be a proper human model system for studying the in vivo pathology of Parkinson\u27s disease (PD). Our optimized conditions for producing homogeneous and mature MOs might provide an advanced patient-specific platform for in vitro disease modeling as well as for drug screening for PD

Epigenetic inactivation of the NORE1 gene correlates with malignant progression of colorectal tumors

<p>Abstract</p> <p>Background</p> <p>NORE1 (RASSF5) is a newly described member of the RASSF family with Ras effector function. <it>NORE1 </it>expression is frequently inactivated by aberrant promoter hypermethylation in many human cancers, suggesting that NORE1 might be a putative tumor suppressor. However, expression and mutation status of <it>NORE1 </it>and its implication in colorectal tumorigenesis has not been evaluated.</p> <p>Methods</p> <p>Expression, mutation, and methylation status of <it>NORE1A </it>and <it>NORE1B </it>in 10 cancer cell lines and 80 primary tumors were characterized by quantitative PCR, SSCP, and bisulfite DNA sequencing analyses. Effect of NORE1A and NORE1B expression on tumor cell growth was evaluated using cell number counting, flow cytometry, and colony formation assays.</p> <p>Results</p> <p>Expression of <it>NORE1A </it>and <it>NORE1B </it>transcript was easily detectable in all normal colonic epithelial tissues, but substantially decreased in 7 (70%) and 4 (40%) of 10 cancer cell lines and 31 (38.8%) and 25 (31.3%) of 80 primary carcinoma tissues, respectively. Moreover, 46 (57.6%) and 38 (47.5%) of 80 matched tissue sets exhibited tumor-specific reduction of <it>NORE1A </it>and <it>NORE1B</it>, respectively. Abnormal reduction of <it>NORE1 </it>was more commonly observed in advanced stage and high grade tumors compared to early and low grade tumors. While somatic mutations of the gene were not identified, its expression was re-activated in all low expressor cells after treatment with the demethylating agent 5-aza-dC. Bisulfite DNA sequencing analysis of 31 CpG sites within the promoter region demonstrated that abnormal reduction of <it>NORE1A </it>is tightly associated with promoter CpG sites hypermethylation. Moreover, transient expression and siRNA-mediated knockdown assays revealed that both NORE1A and NORE1B decrease cellular growth and colony forming ability of tumor cells and enhance tumor cell response to apoptotic stress.</p> <p><b>Conclusion</b></p> <p>Our data indicate that epigenetic inactivation of <it>NORE1 </it>due to aberrant promoter hypermethylation is a frequent event in colorectal tumorigenesis and might be implicated in the malignant progression of colorectal tumors.</p

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Three-Dimensionally Printed Expandable Structural Electronics Via Multi-Material Printing Room-Temperature-Vulcanizing (RTV) Silicone/Silver Flake Composite and RTV

Three-dimensional (3D) printing has various applications in many fields, such as soft electronics, robotic systems, biomedical implants, and the recycling of thermoplastic composite materials. Three-dimensional printing, which was only previously available for prototyping, is currently evolving into a technology that can be utilized by integrating various materials into customized structures in a single step. Owing to the aforementioned advantages, multi-functional 3D objects or multi-material-designed 3D patterns can be fabricated. In this study, we designed and fabricated 3D-printed expandable structural electronics in a substrateless auxetic pattern that can be adapted to multi-dimensional deformation. The printability and electrical conductivity of a stretchable conductor (Ag-RTV composite) were optimized by incorporating a lubricant. The Ag-RTV and RTV were printed in the form of conducting voxels and frame voxels through multi-nozzle printing and were arranged in a negative Poisson’s ratio pattern with a missing rib structure, to realize an expandable passive component. In addition, the expandable structural electronics were embedded in a soft actuator via one-step printing, confirming the possibility of fabricating stable interconnections in expanding deformation via a missing rib pattern

Two Types of Diurnal Variations in Heavy Rainfall during July over Korea

© 2021, The Author(s).This study examined the characteristics of the diurnal variations of heavy rainfall (⩾110 mm in 12 hours) in Korea and the related atmospheric circulation for July from 1980–2020. During the analysis period, two dominant pattens of diurnal variation of the heavy rainfall emerged: all-day heavy rainfall (AD) and morning only heavy rainfall (MO) types. For the AD-type, the heavy rainfall is caused by abundant moisture content in conjunction with active convection in the morning (0000–1200, LST; LST = UTC + 9) and the afternoon hours (1200–2400 LST). These systems are related to the enhanced moisture inflow and upward motion induced by the strengthening of the western North Pacific subtropical high and upper-tropospheric jet. For the MO-type, heavy rainfall occurs mostly in the morning hours; the associated atmospheric patterns are similar to the climatology. We find that the atmospheric pattern related to severe heavy rainfalls in 2020 corresponds to a typical AD-type and resembles the 1991 heavy-rainfall system in its overall synoptic/mesoscale circulations. The present results imply that extremely heavy rainfall episodes in Korea during the 2020 summer may occur again in the future associated with the recurring atmospheric phenomenon related to the heavy rainfall.11Nsciescopu

Sikyungbanha-Tang Suppressing Acute Lung Injury in Mice Is Related to the Activation of Nrf2 and TNFAIP3

Sikyungbanha-Tang (SKBHT) is a Chinese traditional medicine popularly prescribed to patients with respiratory inflammatory symptoms in Korea. Although the Korea Food and Drug Administration approved SKBHT as a therapeutics for relieving the symptoms, experimental evidence for SKBHT suppressing inflammation is scarce. Here, we presented evidence that SKBHT can suppress inflammation in an acute lung injury (ALI) mouse model and explored the possible underlying mechanisms of SKBHT’s anti-inflammatory activity. Single intratracheal (i.t.) injection of SKBHT (1 mg/kg or 10 mg/kg body weight) into mouse lungs decreased prototypic features of lung inflammation found in ALI, such as a high level of proinflammatory cytokines, neutrophil infiltration, and the formation of hyaline membrane, which were induced by a single i.t. LPS (2 mg/kg body weight). When added to a murine macrophage RAW 264.7 cells, SKBHT activated an anti-inflammatory factor Nrf2, increasing the expression of genes regulated by Nrf2. SKBHT suppressed the ubiquitination of Nrf2, suggesting that SKBHT increases the level of and thus activates Nrf2 by blunting the ubiquitin-dependent degradation of Nrf2. SKBHT induced the expression of tumor necrosis factor α-induced protein 3 (TNFAIP3), an ubiquitin-modulating protein that suppresses various cellular signals to NF-κB. Concordantly, SKBHT suppressed NF-κB activity and the expression of inflammatory cytokine genes regulated by NF-κB. Given that Nrf2 and TNFAIP3 are involved in regulating inflammation, our results suggest that SKBHT suppresses inflammation in the lung, the effect of which is related to SKBHT activating Nrf2 and TNFAIP3