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As planners and engineers in large cities around the United States continue to seek solutions to transportation-related problems such as congestion, greenhouse gas emissions, and safe and efficient access to goods and services, light rail transit (LRT) systems have become an increasingly popular option. While LRT has the potential to address these issues, it also has the potential to create negative externalities. This study examines the effects that LRT has had on the single-family residence housing market in Charlotte-Mecklenburg, North Carolina, in both the announcement and operations phases. Using spatially explicit quasi-experimental econometric models, we found that the announcement of the LRT led to increases in price per square feet for properties as distance to LRT station decreases while the price per square foot of properties decreases as distance to LRT station decreases after the system began operations. These results indicate that while land speculation may have resulted from the announcement of the LRT system, homeowners living closest to the stations during operations may have viewed the LRT stations more as a nuisance than a benefit.

The dual-channel nearly perfect absorption is realized by the coupled modes of topological interface states (TIS) in the near-infrared range. An all-dielectric layered heterostructure composed of photonic crystals (PhC)/graphene/PhC/graphene/PhC on GaAs substrate is proposed to excite the TIS at the interface of adjacent PhC with opposite topological properties. Based on finite element method (FEM) and transfer matrix method (TMM), the dual-channel absorption can be modulated by the periodic number of middle PhC, Fermi level of graphene, and angle of incident light (TE and TM polarizations). Especially, by fine-tuning the Fermi level of graphene around 0.4 eV, the absorption of both channels can be switched rapidly and synchronously. This design is hopefully integrated into silicon-based chips to control light.

Introduction: Recently, liquid biopsy has begun to be adopted for treatment selection and drug-resistance assessment for cancers. However, currently liquid biopsy is mostly focused on analyzing cell-free DNA (cfDNA). Though analyzing RNA provides more accurate analysis for functional gene fusions, little is known about the stability and availability of cfRNA (cell free RNA). Here we report our one-tube robust cfTNA (cell free total nucleic acids) assay to analyze ctDNA and ctRNA simultaneously. Methods: We assessed Pillar’s cell free TNA panel performance on 2 confirmed fusion positive and 5 fusion negative samples that were serially diluted to obtain a total of 88 samples including replicates. An input of 10ng cfTNA was used for fusion positive samples with fusion frequency ranging from 0.2% to 20%. A range of 5 to 30ng input was used for fusion negative samples. The amount of input cfRNA was estimated as equal to the cfDNA input. Total nucleic acids were extracted and cfRNA was reverse transcribed. Amplicons targeted the specific breakpoints of 36 known fusion transcripts. Fusion positive samples were diluted for library prep to achieve fusion frequency of 0.5%, 1%, 4%, 5% and 20%. Novaseq was used for sequencing with an average depth of 200,000X and downsampled by 25%. Pillar Variant Analysis Toolkit (PiVAT®) was used to map and call fusions. Results: Among dilutions of >=4%, PiVAT achieved >=99% sensitivity and >=99.9% specificity in calling RNA fusions from 10ng input. Even at extremely low dilutions of = 50% sensitivity. Conclusion: Pillar’s cell free TNA panel offers a simple, rapid, and reliable workflow that enables detection of a broad range of clinically relevant gene fusions. Detection of fusion events in cell-free samples from noninvasive liquid biopsies represents an important step forward in cancer diagnosis and monitoring. Citation Format: Tejashree Modak, Jilong Li, Sean Polvino, Yue Ke, Zhaohui Wang, Alex V. Kotlar. Single tube PCR-based NGS assay for detection of multiple gene fusions from cell free total nucleic acid [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5996.

Introduction: MSI is caused by mutations in mismatch repair (MMR) genes that result in increased insertions and deletions within simple repeats in the genome. The MSI-High (MSI-H) phenotype is prevalent in Lynch Syndrome, caused by the inheritance of MMR loss-of-function alleles as well as in 15% of all colorectal cancers. Accurate, timely detection of MSI is important for predicting the efficacy of immunotherapies that take advantage of increased expression of neoantigens in MSI-H tumors. The Pillar oncoReveal MSI Panel is a targeted NGS assay comprised of a single-tube multiplex PCR-based chemistry and companion Pillar Variant Analysis Toolkit (PiVAT) software with MSIsensor-based detection of tumor MSI status. We report the accuracy of the PiVAT MSI module in detection of tumor MSI status without the need for a matched normal comparator. Methods: 56 pairs of clinical tumor and matched normal FFPE samples were analyzed using the oncoReveal MSI Panel. MSI status was verified by a standard MSI detection method. Illumina sequencing was performed using a PE2x150 protocol. PiVAT determines MSI status using MSIsensor. Call performance on Burrows-Wheeler Alignment (BWA) BAM files was compared with PiVAT’s paired-end assembled and filtered BAM files (PBAM). In both cases coverage normalization and FDR thresholds were set to 1. In a second experiment, 88 clinical normal tissue samples were combined with the matched tumor/normal samples and analyzed using the PiVAT MSI module’s unmatched calling protocol using a synthetic pooled normal. Results: MSI was first assessed in matched tumor/normal samples using MSIsensor. Preliminary analyses revealed a greater separation of MSI scores between MSI-positive and -negative tumors when MSIsensor was run on PBAM vs BWA-generated BAM files. Due to high individual variability at MS sites, MSI detection is difficult for tumor samples with no available matched normal tissue. Hierarchical clustering demonstrated that a subset of MS sites exhibited low variability between normal samples and showed large differences between MSI-H tumor, and MS stable (MSS) tumor and/or normal samples when compared to a pooled normal baseline. Analyses based on the full target set did not accurately detect differences between MSI-H and MSS tumor or normal samples in the pooled normal calling context. When using a clustered subset of sites, MSI-detection was comparable with the matched tumor/normal context. Conclusions: We developed a robust assay for MSI detection in multiple tumor types that encompasses library generation, data analysis, and diagnosis with 97% sensitivity and 100% specificity. We also demonstrate that accurate MSI-detection is possible in the absence of matched normal tissue, using a pooled normal reference and a curated target set. Citation Format: Jordan Aldersley, Michael Liu, Lixing Qi, Ye Jiao, Akuah Kontor, Yue Ke, Zhaohui Wang. Accurate detection of microsatellite instability (MSI) in matched and unmatched clinical tumor samples using the Pillar oncoReveal MSI panel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5694.

Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Since autophagy-related genes (ARGs) play a key role in the pathogenesis of many tumors, including ESCC, the purpose of this study is to establish an autophagy-related prognostic risk signature based on ARGs expression profile, and to provide a new method for improving prediction of clinical outcomes. We obtained the expression profiles of ESCC from public data (GSE53625) and extracted the portion of ARGs. Differential expression analysis and enrichment analysis were performed to confirm abnormal autophagy-related biological functions. Univariate and multivariate Cox regression analyses were performed on RNA microarray data (GSE53625) to construct a prognostic risk signature associated with autophagy. The performance of the model was evaluated by receiver operating characteristic (ROC) analysis, survival analysis and Brier score. The model was subjected to bootstrap internal validation. The potential molecular mechanism of gene signature was explored by gene set enrichment analysis (GSEA). Spearman correlation coefficient examined the correlation between risk score and immune status and ferroptosis. The expression levels of genes and proteins were validated by qRT-PCR and immunohistochemistry in ESCC cell lines and ESCC tissues. We constructed and validated an autophagy-related prognostic risk signature in 179 patients with ESCC. The long-term survival of patients in high-risk group was lower than that in low-risk group (log-rank, P value

Researches have indicated that the endocannabinoid system (ECS) plays a crucial role in pathophysiology of depressive disorder. However, both hypo- and hyperfunction of the ECS were reported in depressive patients or animal models of depression. We proposed that the dual functional changes of the ECS in depression might be due to its region-specific dysregulation. Therefore, we investigated the mRNA expression of genes coding for the components of the ECS in the key depression-associated brain regions of the mouse learned helplessness model of depression. We found that in the mPFC, mRNA of transient receptor potential vanilloid type 1 (TRPV1) was significantly decreased in learned helplessness-resilient mice, whereas diacylglycerol lipases-α (DAGL-α) was decreased in both learned helplessness and learned helplessness-resilient mice. In the hippocampus, a significant increase of DAGL-α was observed in learned helplessness-resilient mice. In the amygdala, G-protein-coupled receptor 55 (GPR55) and DAGL-α were significantly decreased in both learned helplessness and learned helplessness-resilient mice. Meanwhile, fatty acid amide hydrolase (FAAH) was significantly decreased only in learned helplessness-resilient mice. In the LHb, the GPR55 was significantly decreased in both learned helplessness and learned helplessness-resilient mice, whereas the DAGL-β and FAAH were significantly downregulated only in learned helplessness-resilient mice. Therefore, our study reveals novel implications of the ECS in the development of depression-like or depression-resilient behaviors and discloses a region-specific manner of the ECS dysregulation by learned helplessness stress, suggesting that brain region-specific strategy might be necessary for the ECS to be intervened for the precise treatment of depression.

Epileptic seizures are the manifestation of hypersynchronous and excessive neuronal excitation. While the glutamatergic and GABAergic neurons play major roles in shaping fast neuronal excitation/inhibition homeostasis, it is well illustrated that astrocytes profoundly regulate neuronal excitation by controlling glutamate, GABA, cannabinoids, adenosine, and concentration of K+ around neurons. However, little is known about whether microglia take part in the regulation of acute neuronal excitation and ongoing epileptic behaviors. We proposed that if microglia are innately ready to respond to epileptic overexcitation, depletion of microglia might alter neuronal excitability and severity of acute epileptic seizures. We found that microglia depletion by plx3397, an inhibitor of CSF1R, exacerbates seizure severity and excitotoxicity-induced neuronal degeneration, indicating that microglia are rapidly responsive to the change of excitation/inhibition homeostasis and participate in the protection of neurons from overexcitation.

Glutamatergic and GABAergic synaptic transmission controls excitation and inhibition of postsynaptic neurons, whereas activity of ion channels modulates neuronal intrinsic excitability. However, it is unclear how excessive neuronal excitation affects intrinsic inhibition to regain homeostatic stability under physiological or pathophysiological conditions. Here, we report that a seizure-like sustained depolarization can induce short-term inhibition of hippocampal CA3 neurons via a mechanism of membrane shunting. This depolarization-induced shunting inhibition (DShI) mediates a non-synaptic, but neuronal intrinsic, short-term plasticity that is able to suppress action potential generation and postsynaptic responses by activated ionotropic receptors. We demonstrate that the TRESK channel significantly contributes to DShI. Disruption of DShI by genetic knockout of TRESK exacerbates the sensitivity and severity of epileptic seizures of mice, whereas overexpression of TRESK attenuates seizures. In summary, these results uncover a type of homeostatic intrinsic plasticity and its underlying mechanism. TRESK might represent a therapeutic target for antiepileptic drugs.

To investigate the effects of thanatos-associated protein 11 (THAP11) on the proliferation and apoptosis of esophageal cancer cell and the underlying mechanism. Methods: Expression of THAP11 in human esophageal epithelial cells (Het-1A) and esophageal cancer cells (Eca109, TE-1, Ec 9706) were detected by Western blotting. Esophageal cancer TE-1 cells were divided into 3 groups: a normal control (NC) group, a negative control (LV-NC) group and a THAP11 (LV-THAP11) group. Then the cell proliferation were detected by MTT assay, cell apoptosis were detected by flow cytometry, caspase-3 and caspase-9 levels were detected by caspases kits. Ubiquitination of p53 was determined in esophageal cancer TE-1 cells. Results: Expression of THAP11 was reduced in esophageal cancer cells compared with human esophageal epithelial cells (P0.05). After transfection with LV-THAP11 in TE-1 cells, cell viability was reduced (P0.05), while apoptosis rate and caspase-3 and caspase-9 levels were increased (P0.05), indicating that THAP11 inhibited growth of esophageal cancer cells. In addition, the THAP11 increased the levels of p53 (P0.05) and inhibited the ubiquitination of p53 regulated by MDM2. Conclusion: THAP11 may inhibit the proliferation of esophageal cancer cells by inhibiting ubiquitination of p53.目的：探讨死亡相关蛋白(thanatos-associated protein，THAP)11对食管癌细胞增殖和凋亡的影响及其潜在的机制。方法：采用蛋白质印迹法检测人食管上皮细胞Het-1A和人食管癌细胞(Eca109，TE-1和Ec 9706)中THAP11的表达。将食管癌TE-1细胞分为空白对照(NC)组、阴性对照(LV-LC)组、TRAP11(LV-TRAP11)组，按分组处理细胞后，采用MTT法检测细胞活力，流式细胞术检测细胞凋亡，caspases试剂盒检测caspase-3和caspase-9的活性。采用体外泛素化实验检测TE-1细胞的p53泛素化水平。结果：与Het-1A细胞相比，食管癌细胞中THAP11的表达显著下降(P0.05)。LV-THAP11转染食管癌细胞后，细胞活力降低(P0.05)，凋亡率升高(P0.05)，caspase-3和caspase-9活性升高(P0.05)。THAP11能够提高食管癌细胞中p53蛋白的表达(P0.05)。与LV-LC组相比，转染THAP11后食管癌细胞中p53的表达上调(P0.05)，MDM2调节的p53的泛素化也被抑制。结论：THAP11通过抑制p53的泛素化抑制食管癌细胞的增殖，促进食管癌细胞的凋亡。.

Platelets attribute to the hypercoagulation of blood and maintenance of the tumor vascular integrity, resulting in limited intratumoral perfusion of nanoparticle into solid tumors. To overcome these adversities, we herein present an antiplatelet strategy based on erythrocyte membrane-enveloped proteinic nanoparticles that biomimic nitric oxide synthase (NOS)with co-loading of l-Arginine (LA) and photosensitizer IR783 for local NO release and inhibition of the activation of tumor-associated platelets specifically, thereby enhancing vascular permeability and accumulation of the nanoparticles in tumors. A cRGD-immobolized membrane structure is constructed to actively target platelets and cancer cells respectively, through overexpressed integrin receptors such as integrin αIIbβ3 and αvβ3, accelerating the inhibition of platelet activation and endocytosis of nanoparticles by tumor cells. Bio-mimicking the arginine/NO pathway in vivo, synergistical delivery of LA and IR783 enables LA molecules readily oxidize to NO with O2 that is mediated by activated IR783, the resulted NO not only retards the activity of platelets to disrupt the vascular integrity of tumor but also enhances toxicity to cancer cells. In addition, NIR-controlled release localizes the NO spatiotemporally to tumor-associated platelets and prevents undesirable systemic bleeding substantially. The reduction of the hypercoagulable state is further demonstrated by the down-regulation of tissues factor (TF) expression in tumor cells. Our study describes a promising approach to combat cancer, which advances the biomimetic NOS system as the potent therapeutic forces toward clinic applications.

The 2007 Great Recession is widely considered the worst economic downturn in recent United States History. In Indiana, the unemployment rate reached 10.6%, and took nearly seven years to return to pre-recession levels. However, employment data from this period shows that the change in total employment at the county level ranged from -20% to +5%, indicating that while many counties suffered from high unemployment, other counties experienced gains in total employment. Various research efforts, including this project, have been undertaken to understand the local characteristics that influence the differing degrees to which regional/city economies were able to resist or cope with the effects of the recession. In the literature, this ability is referred to as regional economic resilience (RER). This research project’s primary objective is to develop a framework and tool that could be used by INDOT’s Asset Planning & Management Division and Indiana metropolitan planning organizations (MPOs) to evaluate the role of transportation accessibility in building RER of Indiana’s regions to economic shocks. The following tasks were undertaken: the development of a resilience index to inform stakeholders of the comparative RERs in Indiana; the estimation of an econometric model to evaluate the association between Indiana counties’ regional characteristics and the resilience index; the development of a framework in which results of previous tasks can be incorporated into transportation decision-making at the sketch level by MPOs, regional development organizations, and other similar agencies; and design of a tool to allow planners to examine the potential changes to RER due to policies or other exogenous shocks.

Human serum albumin (HSA) plays a pivotal role in various physiological processes of humans, and is generally considered to be one of the early signs of many diseases. Although dysfunction of intracellular lysosome is accompanied in those diseases, the regulation mechanism of HSA in lysosomes still need to be explored. In this work, we report a novel near-infrared naphthalimide probe NI-1 that specifically detects HSA in intracellular lysosomes with the “turn-on” fluorescent sensing modes. In the cell, the N-containing malononitrile group of NI-1 could bind to the lysosome. Moreover, NI-1 can specifically enter the site II hydrophobic cavity of HSA in lysosome. Due to the binding force between NI-1 and HSA, strong steric hindrance and the hydrophobic pocket inside HSA inhibit the twisted internal charge transfer (TICT) effect in the probe itself. Therefore, NI-1 emits strong red fluorescence. More importantly, NI-1 can effectively localize bioimaging of exogenous and endogenous HSA in lysosome. In addition, the novel probe NI-1 achieved a much high selectivity for HSA over bovine serum albumin (BSA), and the interaction mechanism between probe NI-1 and HSA or BSA site II was explained for the first time through molecular docking methods. These results indicate that the probe NI-1 has great potential in exploring further function of HSA for pharmacy and medicine.

We herein designed a simple and feasible photoluminescence (PL) immunoassay for sensitive detection of p53 protein in biological fluid by using grapefruit peel-extracted carbon quantum dots (CQDs) as the signal-generation tags. CQDs were first synthesized on the basis of grapefruit peel as the carbon source via a typical hydrothermal method. Thereafter, the synthesized CQDs were encapsulated into silica nanoparticles (CQD-SiNP) for the signal enhancement. In the presence of p53, a sandwich-type immunoreaction was fulfilled on monoclonal anti-p53 capture antibody-coated microplate by using CQD-SiNP-labeled polyclonal anti-p53 secondary antibody. Relative to CQD-labeled strategy, use of CQD-SiNP could amplify the photoluminescence signal toward the same-concentration target p53. Under the optimum conditions, the photoluminescence intensity via the CQD-SiNP-labeled strategy exhibited high sensitivity, and allowed the detection of target p53 as low as a concentration of 2.7 pg mL−1. No interfering signals were acquired toward non-target analytes including biomarkers or enzymes in human serum. Below 15% of relative standard deviations (RSDs) were obtained for detection of p53 analyte in all cases. Additionally, CQD-SiNP-based photoluminescence immunoassays were utilized for the evaluation of real human serum samples, and received well-matched results with commercial enzyme-linked immunosorbent assay (ELISA) kit.

In US urban areas, traffic congestion remains a growing and costly problem. The Texas Transportation Institute estimated that in 2014 delays due to congestion caused an extra 7 billion extra hours in delay, leading to wasted fuel, increased environmental degradation, and high user costs. Previous studies have focused on the impacts to congestion via highway toll lanes and the income distributional effects of tolling. While tolling can be effective in reducing congestion levels, these tolls have been found to be at least as regressive as fuel taxes. Further, these studies do not investigate the impacts tolling has on rural households compared to urban households. This study presents a per-mile congestion tax as an alternative policy tool to congestion tolling. Using a Suits Index with the Oregon Households Activity Survey, we find a per-mile congestion charge to be progressive on income. This suggests that the administratively challenging toll revenue redistribution payments that would be necessary to make congestion tolling progressive would not be needed. At the same time, however, the Suits Index suggests that a per-mile congestion charge would be regressive with regards to rural households. Econometric models are estimated to further support and explain these outcomes. While rural households, in general, drive more during peak hours compared to urban households, we find that low-income rural households are less likely to drive during these periods than wealthier rural households.

Phosphorus (P) fertilizer has been widely applied to improve crop yields in the North China Plain; however, most of applied P fertilizer is disabled due to the strong sorption/fixing processes in the soil. This study evaluates the change characteristics of soil properties on different textural soils and their relationships with the P adsorption and desorption under long-term fertilization to do a favor to make strategies for improving the P availability of the soil. Five textural fluvo-aquic soils including gritty sand, silt sand, sandy loam, medium loam, and light clay were investigated in a 27-year (1990–2017) long-term fertilization experiment at Zhengzhou (Henan province) of China. Soil samples were collected in 1990, 1999, and 2017 at 0–20 cm to measure soil properties (i.e., soil mechanical composition) and P adsorption and desorption characteristics. The clay and silt contents decreased and sand content increased in the light clay soil with the cultivation years, the opposite situation for the gritty sand and silt sand soils. The contents of total P, Olsen–P, and organic matter (SOM) in the five textural soils were increased over time. There were stronger P absorption capacity and weaker desorption ability for the light clay soil relative to others, which was reflected in the largest P maximum buffer capacity (MBC) and the lowest β value; however, the P adsorption capacity tended to decrease over time for the light clay soil. Clay and silt fractions were positively correlated with MBC, while negatively correlated with β (P

The use of statistical models for analyzing traffic safety (crash) data has been well-established. However, time series techniques have traditionally been underrepresented in the corresponding literature, due to challenges in data collection, along with a limited knowledge of proper methodology. In recent years, new types of high-resolution traffic safety data, especially in measuring driver behavior, have made time series modeling techniques an increasingly salient topic of study. Yet there remains a dearth of information to guide analysts in their use. This paper provides an overview of the state of the art in using time series models in traffic safety research, and discusses some of the fundamental techniques and considerations in classic time series modeling. It also presents ongoing and future opportunities for expanding the use of time series models, and explores newer modeling techniques, including computational intelligence models, which hold promise in effectively handling ever-larger data sets. The information contained herein is meant to guide safety researchers in understanding this broad area of transportation data analysis, and provide a framework for understanding safety trends that can influence policy-making.

Introduction Health problems such as obesity and related illnesses have been attributed to the lack of both spatial and economic access to healthy food. Even though access to healthy food in urban areas has been widely studied, access to healthy food in rural areas has not received much attention to date. Rural residents usually face similar accessibility challenges as urban populations but at a greater magnitude. The lack of access to reliable transportation in rural areas acts as a barrier to accessing healthy food, especially for individuals that might not have access to an automobile. Methodology This paper uses a cost-based accessibility measure and estimates spatial econometric models to identify the differences between healthy food accessibility in rural and urban areas considering multiple transportation modes available in those areas. Furthermore, the paper explores the relationship between healthy food accessibility and the characteristics of the built environment that can be used to advise planning decisions and policy. Four study areas in Indiana were selected to demonstrate the study methodology. Results Both the location of healthy food providers and infrastructure that allows access by different modes are spatially clustered. Urban area residents incur a lower average cost to reach healthy food, especially when driving and walking are considered, compared to rural areas. The spatial models' results suggested that built environment characteristics, especially land-use characteristics, influence the cost to reach healthy food providers in urban areas, regardless of the mode. Conclusions The solution to facilitate access to healthy food providers is not a one-size-fits-all approach. However, transportation innovations such as mobile markets, ridesharing, drone delivery, and autonomous delivery services can serve to bring closer healthy food to the population that cannot access it by their current means. This paper's methodology involves publicly available data that allow for easy replication by any planning agency.

Purpose To evaluate the survival benefit of radiotherapy (RT) in esophageal cancer (EC) patients aged ≥ 80. Materials and Methods Records for all EC patients aged ≥ 65 years were extracted from the Surveillance, Epidemiology, and End Results database. Chi-square test compared the characteristic and treatment between patients aged ≥ 80 with those aged 65–79. Focusing on patients aged ≥ 80, we employed multivariable logistic regression to identify the association between selection of RT and patients’ characteristics. Survival curve was employed to visualize the survival rate and multivariable Cox proportional hazard model was established to quantify the effect of RT on overall survival (OS) and cancer special survival (CSS). Results Patients aged ≥ 80 were more likely to be white male and have localized EC (all P < 0.001). Selection of RT in patients aged ≥ 80 were associated with cancer histology (P < 0.001), grade (P = 0.024) and stage (P < 0.001). RT significantly improved the OS (hazard ratio(HR) = 0.717) and CSS (HR = 0.722) (all P < 0.001). Further stratified analysis found the improvement were only significant in the localized (OS HR = 0.662; CSS HR=0.652) and regional stage patients (OS HR = 0.571; CSS HR = 0.581) (all P < 0.001). Conclusions Our study suggested EC patients aged ≥ 80 benefit from RT only if the cancer is in localized/regional stage.

In this letter, a method to realize topological rainbow trapping is presented, which is composed of gradual trivial-nontrivial-trivial heterostructures based on two-dimensional photonic crystals with C-4 symmetry. In the proposed sandwiched structure, the two coupled topological edge states with different frequencies are separated and trapped in different positions, due to group velocity of near to zero. We have achieved the dual-mode of topological rainbow in one structure, and the dual-mode of topological rainbow under one mode excitation is also realized by using a simple bend design. The immunity to defects is also investigated and it is found our slowing light system has strong robustness. Finite element method simulation results verify our idea, and our work opens up a new approach for frequency routing of topological photonic states.

Crop nitrogen nutrition is an important indicator for evaluating crop growth. Rapid and non-destructive estimation of nitrogen accumulation in wheat leaves is of great significance for crop nitrogen fertilizer management. Based on field test data from multiple wheat varieties for different locations, years, nitrogen levels, and growth periods, the relationship between 11 canopy hyperspectral parameters and nitrogen accumulation in wheat plants was studied. According to the results of correlation and regression analysis, the flowering period of wheat was selected as the most suitable growth period for crop growth evaluation (the average R2 was 0.732, and the root mean square error (RMSE) was 0.354). A new vegetation index, NDchI*DDN (referred to as the nitrogen accumulation vegetation index, abbreviated as NAVI), was constructed based on the pairwise combination of traditional vegetation index products. This parameter had a high correlation with plant nitrogen accumulation (R2 = 0.856), and the root mean square error (RMSE) was 0.296. Tested by independent experimental data, the fitting degree of the plant nitrogen accumulation inversion model established with NAVI as the variable was R2 = 0.861, the relative error RE = 9.3%, RMSE = 0.398, and the prediction accuracy was significantly higher than other models. Therefore, construction of a NAVI-based plant nitrogen accumulation monitoring model gave ideal test results, which could reduce the limitations of experimental conditions and is expected to provide new important technical support for precise fertilization.

Road user charges (RUCs) in the form of per mile charges have been suggested as an alternative to fuel taxes to help keep up with the costs of maintaining and expanding public road systems. The success of a RUC in providing for the long term stability of highway finance depends partly on how drivers respond to changes in the tax structure and also other determinants of driving behavior. Region specific characteristics, such as public transit accessibility and biking infrastructure, may also affect vehicle miles traveled (VMT) demand. This paper uses econometric techniques to examine the determinants of VMT using data from the Oregon Household Activities Survey (OHAS). We use standard OLS regression to examine the impact of urban density, household income, fuel cost, transit mileage, household location, and additional household characteristics on VMT. Preliminary results show that statewide Oregon demand for VMT is positively and significantly impacted by household income. Statewide, fuel price, transit use and population density are all found to be statistically significant and negatively related to household VMT. However, at the regional level some of these variables lose significance. Holding all factors constant, household VMT is found to differ by region as well as by population density.

Background Hydroxychloroquine exhibits synergistic anticancer properties as an adjuvant. However, the role and molecular mechanisms underlying of HCQ as monotherapy for lung adenocarcinoma (LUAD) have yet to be elucidated. Methods We assessed the antitumor effects of HCQ in LUAD cells through a series of in vitro and in vivo assays. GEO database and R packages were used to predict molecular mechanisms of HCQ in the treatment of lung adenocarcinoma, followed by verification of gene expression and subcellular localization via immunoblotting, immunofluorescent and immunohistochemistry assays. Results We showed the phenotypic effects that HCQ inhibited cell growth, induced apoptosis and cell cycle arrest at G1/S transition in A549 and PC-9 cells, which was associated with inhibition of CDK2, CDK4, CyclinD1 and CyclinE, but up-regulation of p21 and p27Kip1. Bioinformatic analysis predicted that 63 targets related to HCQ and LUAD were mainly enriched in JAK-STAT and FoxO pathways. Then, we observed that HCQ decreased the phosphorylation of STAT3, but increased the expression of FoxO3a and its accumulation in the nucleus. The specific STAT3 inhibitor cryptotanshinon augmented the HCQ-induced upregulation and nuclear translocation of FoxO3a. In addition, HCQ increased the expression of p27Kip1, which was impaired by FoxO3a blockade with siRNA. Finally, ablation of p27Kip1 expression abrogated the cytotoxicity of HCQ. More importantly, similar results were further confirmed in vivo. Conclusions Taken together, this study suggests that STAT3/FoxO3a/p27Kip1 signaling pathway is involved in the anticancer effects of HCQ, and provides preliminary evidence for therapeutic prospects of HCQ alone in LUAD.

The morbidity and mortality of hepatocellular carcinoma (HCC) are growing yearly. Several reports emphasize the importance of long non-coding RNAs (lncRNAs) in HCC. This paper provides a molecular mechanism for the function of GAS6-AS2 in HCC. The expressions of GAS6-AS2, miR-493-5p and OTUB1 were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration, and invasion were measured by cell counting kit-8 (CCK-8), flow cytometry and transwell assay, respectively. The interaction of miR-493-5p and GAS6-AS2 or OTU domain-containing Ubiquitin Aldehyde-binding Protein 1 (OTUB1) was analyzed by starBase v2.0 and verified by luciferase reporter assay. The protein level of OTUB1 as well as PI3K, p-PI3K, AKT, p-AKT, FoxO3a, p-FoxO3a and β-actin protein levels were distinguished by western blot. GAS6-AS2 was up-regulated in HCC tissues and cells. GAS6-AS2 knockdown inhibited proliferation, migration, and invasion but promoted apoptosis. MiR-493-5p, a target of GAS6-AS2, was down-regulated in HCC tissues and cells. Inhibition of miR-493-5p reversed the effects of GAS6-AS2 knockdown on HCC cells. OTUB1, a target of miR-493-5p, was up-regulated in HCC cells and its expression was modulated by miR-493-5p. Overexpression of OTUB1 recovered the positive effects of miR-493-5p enrichment or GAS6-AS2 knockdown on HCC cells. GAS6-AS2 knockdown impeded the activation of PI3K/AKT/FoxO3a signaling pathway, while this activation was reversed by miR-493-5p inhibition or OTUB1 overexpression. In conclusion, GAS6-AS2 knockdown suppressed proliferation, migration, and invasion but promoted apoptosis of HCC cells by impeding PI3K/AKT/FoxO3a signaling pathway through regulating the GAS6-AS2/miR-493-5p/OTUB1 axis.

PurposeTo evaluate the survival benefit of combining radiotherapy with surgery in locally advanced esophageal squamous cell carcinoma (ESCC) patients aged over 65.MethodsUsing the SEER database, we selected patients age >= 65 years that were diagnosed as locally advanced ESCC during 2004-2013. Cancer-specific survival (CSS) was examined using the Kaplan-Meier analysis and compared by the log-rank test. Univariable and multivariable Cox proportional hazard models were established to identify possible prognostic factors.ResultsA total of 972 cases were included in the study. For surgical patients aged 65-79 years, 74 patients (32.9%) were treated by surgery alone and 122 patients (54.2%) had received additional neoadjuvant radiotherapy (NRT). NRT+surgery was associated with improved CSS comparing with surgery alone (HR, 0.58; 95%CI, 0.39 to 0.85; P=0.005). In subgroup analysis, NRT was associated with improved CSS for patients aged 65-74 years (2-year CSS 56.6% versus 39.6%, P=0.026). No significant differences of progonosis was observed for different treatment groups in 75-79 years patients (P=0.972).ConclusionsIn this SEER-based study, the addition of neoadjuvant radiotherapy before surgery was associated with improved CSS for locally advanced ESCC patients aged 65 to 74 years.

Preservation and maintenance activities protect pavements and bridges, extending the life of these assets and guarantee the safety of users. Because rebuilding a road in poor condition can cost ten times as much as work needed to keep the road in good condition, these activities also represent significant savings to taxpayers. In addition to these benefits, preservation activities can also have wider economic benefits in the form of reduced user costs related to vehicle operation, travel time, and safety. This project aims to develop sketch planning tools for assessing the economic development impacts of pavement and bridge preservation projects to meet the needs of INDOT’s Division of Asset Planning and Management. To accomplish these objectives, the following tasks were undertaken: a literature review, an evaluation of existing tools that could address some aspect of the study topic or be used as guidance for the development of the project tools, the development of the tool, and the preparation of guidance materials and documentation.

Although mitochondrial metabolism has recently gained attention as a promising therapeutic strategy in cancer, little is known on the impact of mitochondrial respiration inhibition on oral tongue squamous cell carcinoma (OTSCC). Using in vitro and in vivo OTSCC models, our work demonstrates that inducing mitochondrial dysfunction by anti-malarial drug artesunate is effective in targeting OTSCC stem-cell like and bulk cells. Artesunate inhibits anchorage-independent colony formation, proliferation and survival in all tested OTSCC cell lines although with varying efficacy. Artesunate displays preferential anti-OTSCC activity by sparing normal cells. Mechanism analysis indicates that artesunate inhibits mitochondrial respiration via suppressing mitochondrial complex I and II but not IV or V, resulting in oxidative stress and damage. Interestingly, OTSCC cells that are more sensitive to artesunate have higher level of basal mitochondrial respiration and reversed respiratory capacity compared to those with less sensitivity to artesunate, suggesting the varying dependence on mitochondrial respiration among OTSCC cell lines. In addition, artesunate induces oxidative stress and damage in cells with low sensitivity to a less extent than in those with high sensitivity. We confirm that mitochondrial respiration inhibition is required for the action of artesunate in OTSCC. Mitochondrial dysfunction by artesunate further activates AMPK and suppresses Akt/mTOR. Importantly, the in vitro observations are reproducible in vivo OTSCC xenograft mouse model. Our findings provide pre-clinical evidence on the efficacy of artesunate and emphasize the therapeutic value of targeting mitochondrial respiration in OTSCC.

Although heparin-based nanoparticles are widely used to treat cancer, the knowledge on the effect of heparin derivative and heparin-based nanoparticles on cancer-associated thrombosis is still lacking. To address this issue, the heparin derivatives including amphiphilic heparin-deoxycholic acid (DOCA) polymer with non-sensitive (Hep-DOCA) and redox-sensitive properties (Hep-ss-DOCA) are synthesized, and paclitaxel (PTX) is encapsulated in heparin-based micelles to fabricate nanoparticles. The chemical structure of synthesized polymer, the size, morphology and stability of nanoparticles and redox-sensitivity of nanoparticles are analyzed. And the effect of heparin-deoxycholic acid polymer and PTX loaded nanoparticles on cancer-associated thrombosis are investigated both in vitro and in vivo. It is found that redox-sensitive PTX/nanoparticles is effectively in reducing thrombosis for cancer mice. This result is mainly attributed to down-regulation for coagulation after apoptosis of cancer cell. This work not only clarifies the effect of heparin-based nanoparticles on blood hypercoagulation but provides basic principles to inhibit cancer-associated thrombosis.

Aluminum-catalyzed silicon nanopyramids grown using low-pressure chemical vapor deposition (LPCVD) are presented as an approach to silicon surface texturing. The nanopyramids are grown by vapor-liquid-solid growth using aluminum thin films on silicon. Silicon nanowires with hexagonal cross sections are formed at a growth temperature of 650 degrees C; as the temperature is increased to 700 degrees C, the wires become pyramid-shaped with triangular cross-sections. The silicon nanopyramids are single crystal and grow in the direction with (112) facets, as confirmed by transmission electron microscopy. Pyramid tapering increases with increasing growth temperatures and the pyramid arrays grown at 700 C show refiectivities between 4 and 6% between 400 nm and 800 nm and appear black to the eye. Based on these results, aluminum-catalyzed nanopyramids present themselves as a plausible alternative to etch-based silicon surface textures. (C) 2016 Elsevier B.V. All rights reserved.

Oregon Senate Bill 810 created a program that allows drivers to pay a flat-mileage road user charge (RUC) of 1.5 cents per mile rather than the 30 cents per gallon state fuel tax. Major concerns about the adoption of this RUC are that it could increase costs for rural households relative to urban households and that the costs would fall disproportionately on lower-income groups. Further, it has been suggested that significant differences in the impact of the RUC could arise from locational distinctions beyond the urban–rural split alone. Earlier studies analyzed the regional impacts of an RUC only at the statewide level or only with the use of a broad urban–rural distinction. The newly available Oregon Households Activity Survey (OHAS) data provide detailed household location information, which permits impacts to be assessed with regional and geographic definitions relevant to policy makers in Oregon. Results with the use of OHAS data showed that, on average, statewide households would pay 5 cents more daily under the RUC than they did under the fuel tax because the 1.5 cents per mile RUC actually will produce more gross revenue than the fuel tax. However, the price increase in rural regions will be less than the statewide average, whereas more urban regions will pay slightly more than the statewide average. Further, the distributional impact of the flat 1.5 cents RUC on all households in the OHAS data set differed, depending on the region of the state examined.

Introduction: SLIMamp technology allows multiplex-PCR of tiled amplicons in a single tube, which enables targeting of large exons for NGS analysis with a streamlined process. Copy number variants (CNVs) are DNA segments that are present with variation in the number of copies compared to a normal genome. CNVs have a high prevalence in the pathogenesis of cancer and their characterization is important to acquire a more comprehensive picture of the mutations present in a patient sample. Pillar developed a proprietary CNV algorithm and combined it with SLIMamp to develop an integrated multi-cancer plus CNV detection NGS panel which identifies CNVs in the ERBB2, EGFR, MET, and MYC genes. Methods: To assess the ability of the ONCO/Reveal Multi-Cancer with CNV Panel to detect ERBB2 CNV compared to DISH (dual in situ hybridization), libraries were created from 44 well-characterized FFPE breast cancer samples plus 3 Genome in a Bottle (GIAB) samples. 23 tumor samples had known ERBB2 amplification (20 with matched normal tissue), 21 were known non-amplified tumors, and 3 GIAB samples were used as negative controls. Libraries were sequenced on an Illumina MiSeq and data was analyzed by the Pillar Variant Analysis Toolkit (PiVAT). The previous DISH results were not known to Pillar. Results were provided to an independent collaborator who unblinded the study and compared the NGS results to DISH. Results: Overall the assay performed well with a mapping rate of 99.4% ± 2.1%, on-target rate of 99.1% ± 0.4%, and coverage uniformity >0.2x mean coverage of 93.5% ± 4.1%. With respect to CNV calling, the assay and software detected 100% (21/21) of ERBB2 amplification negative samples as confirmed by DISH. For amplification positive samples, the NGS assay detected 100% (23/23) of positive samples. The software correctly identified 91% (21/23) of amplification positive samples. The two samples that were not called by PiVAT had normalized genes counts of 1.2 and 1.4, and also had the lowest DISH scores. All samples with a normalized gene count >1.5 were correctly called by PiVAT. The NGS assay was able to accurately call CNV independent of tumor cellularity with tumor content of 20%-90% not impacting the CNV call. Conclusions: The ONCO/Reveal Multi-Cancer with CNV Panel is a robust assay for the detection of CNVs, SNVs, and Indels of interest across multiple solid tumor cancer types. The workflow is streamlined, with same day loading of finished libraries when starting from as little as 5ng of isolated input DNA. The assay and software demonstrate detection of low CNV with the recommended cutoff set at 1.5. With further optimization of the calling algorithm accurate calling of even lower CNVs may be possible. The detection and identification of CNVs along with other mutations gives a more comprehensive overview of the mutations present in a sample, supporting better clinical management of patients. Citation Format: Nicholas Lodato, Zonghan Liu, Akuah Kontor, Xiaoxi Wu, Lukas Hillmer, Sean Polvino, Yue Ke, Erin Petrilli, Adam Labonte, Geoffrey Richman, Zhaohui Wang. Development and characterization an NGS multi-cancer panel plus CNV detection; a single-tube, multiplex-PCR based NGS Assay with 309 tiled amplicons [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5899.

Aims RING1 and YY1-binding protein (RYBP) is an epigenetic regulator and plays crucial roles in embryonic development. The anti-tumor effect of RYBP has been reported in several cancers recently, but the role of RYBP in esophageal squamous cell carcinoma (ESCC) has not been fully elucidated. The present study aimed to investigate the biological function and the underlying molecular mechanisms of RYBP in ESCC. Materials and methods We detected the expression of RYBP in ESCC tissue microarrays (TMA) by immunohistochemistry. Cell proliferation was assessed by CCK8 and colony formation assays. Cell cycle was analyzed by flow cytometry. Gene expression was determined by transcriptome arrays, quantitative real-time PCR (qRT-PCR) and Western blot. Four-week-old male nude mice were used to evaluate the effect of RYBP in ESCC growth. Key findings We found that RYBP was downregulated in ESCC compared with adjacent normal tissues. A high level of RYBP expression predicted a better outcome of ESCC patients. Furthermore, overexpression of RYBP inhibited ESCC growth both in vitro and in vivo. Transcriptome arrays and functional studies showed that RYBP decreased the expression of genes related to cell cycles, especially CDC6 and CDC45, which were essential to initiate the DNA replication and G1-S transition. Significance Taken together, our study suggests that RYBP suppresses ESCC proliferation by downregulating CDC6 and CDC45, thus inhibiting the G1-S transition.