Sensitive detection of BRAF V600E mutation by Amplification Refractory Mutation System (ARMS)-PCR

BACKGROUND: BRAF mutations occur in approximately 8% of all human cancers and approach 50% in melanoma and papillary carcinoma of thyroid. These mutations provide potentially valuable diagnostic, prognostic and treatment response prediction markers. A sensitive, specific, low-cost assay to detect these mutations is needed. RESULTS: To detect BRAF V600E mutation in formalin-fixed, paraffin-embedded (FFPE) tissue, we developed a method using Amplification Refractory Mutation System (ARMS)-PCR. This method was designed to amplify three products in a single reaction tube: a 200 bp common product serving as an amplification control, a 144 bp BRAF V600E specific product, and a 97 bp wild-type (wt) specific product. The sensitivity of this method was determined to be as low as 0.5% for the BRAF V600E allele in a wild-type background. This method was successfully validated in 72 thyroid tumors. It detected V600E mutation in 22 out of 33 (67%) of the conventional papillary thyroid carcinoma (PTC), 8 out of 12 (75%) of the tall-cell variant of PTC, whereas none of the 10 follicular variant of PTC showed BRAF V600E mutation. In addition, none of the 14 follicular adenomas and 3 follicular carcinomas had BRAF V600E mutation. As a comparison method, direct dideoxy sequencing found only 27 out of 30 (90%) mutations detected by ARMS-PCR method, suggesting that this ARMS-PCR method has higher sensitivity. CONCLUSIONS: Our ARMS-PCR method provides a new tool for rapid detection of BRAF V600E mutation. Our results indicate that ARMS-PCR is more sensitive than automated dideoxy sequencing in detecting low BRAF V600E allele burdens in FFPE tumor specimen. The strategy of this ARMS-PCR design may be adapted for early detection of point mutations of a variety of biomarker genes

Spiking NeRF: Making Bio-inspired Neural Networks See through the Real World

Spiking neuron networks (SNNs) have been thriving on numerous tasks to leverage their promising energy efficiency and exploit their potentialities as biologically plausible intelligence. Meanwhile, the Neural Radiance Fields (NeRF) render high-quality 3D scenes with massive energy consumption, and few works delve into the energy-saving solution with a bio-inspired approach. In this paper, we propose spiking NeRF (SpikingNeRF), which aligns the radiance ray with the temporal dimension of SNN, to naturally accommodate the SNN to the reconstruction of Radiance Fields. Thus, the computation turns into a spike-based, multiplication-free manner, reducing the energy consumption. In SpikingNeRF, each sampled point on the ray is matched onto a particular time step, and represented in a hybrid manner where the voxel grids are maintained as well. Based on the voxel grids, sampled points are determined whether to be masked for better training and inference. However, this operation also incurs irregular temporal length. We propose the temporal condensing-and-padding (TCP) strategy to tackle the masked samples to maintain regular temporal length, i.e., regular tensors, for hardware-friendly computation. Extensive experiments on a variety of datasets demonstrate that our method reduces the $76.74\%$ energy consumption on average and obtains comparable synthesis quality with the ANN baseline

Research on Public Transit Network Hierarchy Based on Residential Transit Trip Distance

To the problem of being lack of transit network hierarchy theory, a research on public transit network hierarchy optimization based on residential transit trip distance is conducted. Firstly, the hierarchy standard of transit network is given, in addition, both simulating electron cloud model and Rayleigh distribution model are used to fit the residential transit trip distance. Secondly, from the view of balance between supply and demand, the hierarchy step of transit network based on residential transit trip distance is proposed. Then, models of transit’s supply turnover and demand turnover are developed. Finally, the method and models are applied into transit network optimization of Baoding, Hebei, China

Complete Genome Sequences of Four Toxigenic ;Clostridium difficile Clinical Isolates from Patients of the Lower Hudson Valley, New York, USA

Complete genome sequences of four toxigenic Clostridium difficile isolates from patients in the lower Hudson Valley, New York, USA, were achieved. These isolates represent four common sequence types (ST1, ST2, ST8, and ST42) belonging to two distinct phylogenetic clades. All isolates have a 4.0- to 4.2-Mb circular chromosome, and one carries a phage

An initial implementation of multiagent simulation of travel behavior for a medium-sized city in China

Since the traditional four-step model is so simple that it cannot solve complex modern transportation problems, microsimulation is gradually applied for transportation planning and some researches indicate that it is more compatible and realistic. In this paper, a framework of agent-based simulation of travel behavior is proposed, which is realized by MATSim, a simulation tool developed for large-scale agent-based simulation. MATSim is currently developed and some of its models are under training, so a detailed introduction of simulation structure and preparation of input data will be presented. In practice, the preparation process differs from one to another in different simulation projects because the available data for simulation is various. Thus, a simulation of travel behavior under a condition of limited available survey data will be studied based on MATSim; furthermore, a medium-sized city in China will be taken as an example to check whether agent-based simulation of travel behavior can be successfully applied in China

An improvement in MATSim computing time for large-scale travel behaviour microsimulation

Abstract: Coupling activity-based models with dynamic traffic assignment appears to form a promising approach to investigating travel demand. However, such an integrated framework is generally time-consuming, especially for large-scale scenarios. This paper attempts to improve the performance of these kinds of integrated frameworks through some simple adjustments using MATSim as an example. We focus on two specific areas of the model—replanning and time stepping. In the first case we adjust the scoring system for agents to use in assessing their travel plans to include only agents with low plan scores, rather than selecting agents at random, as is the case in the current model. Secondly, we vary the model time step to account for network loading in the execution module of MATSim. The city of Baoding, China is used as a case study. The performance of the proposed methods was assessed through comparison between the improved and original MATSim, calibrated using Cadyts. The results suggest that the first solution can significantly decrease the computing time at the cost of slight increase of model error, but the second solution makes the improved MATSim outperform the original one, both in terms of computing time and model accuracy; Integrating all new proposed methods takes still less computing time and obtains relatively accurate outcomes, compared with those only incorporating one new method

Estrogen-Dependent Epigenetic Regulation of Soluble Epoxide Hydrolase via DNA Methylation

To elucidate molecular mechanisms responsible for the sexually dimorphic phenotype of soluble epoxide hydrolase (sEH) expression, we tested the hypothesis that female-specific down-regulation of sEH expression is driven by estrogen-dependent methylation of the Ephx2 gene. Mesenteric arteries isolated from male, female, ovariectomized female (OV), and OV with estrogen replacement (OVE) mice, as well as the human cell line (HEK293T) were used. Methylation-specific PCR and bisulfite genomic sequencing analysis indicate significant increases in DNA/CG methylation in vessels of female and OVE compared with those of male and OV mice. The same increase in CG methylation was also observed in male vessels incubated with a physiological concentration of 17beta-estradiol (17beta-E2) for 48 hours. All vessels that displayed increases in CG methylation were concomitantly associated with decreases in their Ephx2 mRNA and protein, suggesting a methylation-induced gene silencing. Transient transfection assays indicate that the activity of Ephx2 promoter-coding luciferase was significantly attenuated in HEK293T cells treated with 17beta-E2, which was prevented by additional treatment with an estrogen receptor antagonist (ICI). ChIP analysis indicates significantly reduced binding activities of transcription factors (including SP1, AP-1, and NF-kappaB with their binding elements located in the Ephx2 promoter) in vessels of female mice and human cells treated with 17beta-E2, responses that were prevented by ICI and Decitabine (DNA methyltransferase inhibitor), respectively. In conclusion, estrogen/estrogen receptor-dependent methylation of the promoter of Ephx2 gene silences sEH expression, which is involved in specific transcription factor-directed regulatory pathways

Impact of Transit Network Layout on Resident Mode Choice

This study reviews the impact of public transit network layout (TNL) on resident mode choice. The review of TNL as a factor uses variables divided into three groups: a variable set without considering the TNL, one considering TNL from the zone level, and one considering TNL from the individual level. Using Baoding’s travel survey data, a Multinomial Logit (MNL) model is used, and the parameter estimation result shows that TNL has significant effect on resident mode choice. Based on parameter estimation, the factors affecting mode choice are further screened. The screened variable set is regarded as the input data to the BP neural network’s training and forecasting. Both forecasting results indicate that introducing TNL can improve the performance of mode choice forecasting

Obeticholic acid and ferrostatin-1 differentially ameliorate non-alcoholic steatohepatitis in AMLN diet-fed ob/ob mice

Introduction: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common chronic liver diseases with limited treatment options.Methods: Ob/ob mice (6 weeks old) were fed with the Control diet or amylin liver NASH (AMLN) diet for 24 weeks to establish the NASH, the AMLN diet-fed mice were treated with obeticholic acid (OCA), ferrostatin-1 (Fer-1) or their combination for 7 weeks. Finally, various clinical profiles were assessed.Results: Our results indicate that Fer-1 exerts better effects on improving body weight, blood glucose levels, transaminase levels and insulin resistance than OCA. OCA has a profound effect on ameliorating lipid accumulation. OCA and Fer-1 differentially inhibit the activation of hepatic Kupffer cells and HSCs. The combination of OCA and Fer-1 significantly reduces inflammation and protects mice against liver oxidative stress. OCA and Fer-1 differentially reshape the intestinal microbiota and affect the hepatic lipidome.Discussion: Our study compares the effects of OCA, Fer-1 and their combination on various clinical profiles in NASH. These data demonstrate that different drug combinations results in different improvements, and these discoveries provide a reference for the use of the OCA, Fer-1 and their combination in the clinical treatment of NAFLD/NASH