Time-dependent Plot Research Articles

The m5 C methyltransferase NSUN2 promotes codon-dependent oncogenic translation by stabilising tRNA in anaplastic thyroid cancer.

Translation dysregulation plays a crucial role in tumourigenesis and cancer progression. Oncogenic translation relies on the stability and availability of tRNAs for protein synthesis, making them potential targets for cancer therapy. This study performed immunohistochemistry analysis to assess NSUN2 levels in thyroid cancer. Furthermore, to elucidate the impact of NSUN2 on anaplastic thyroid cancer (ATC) malignancy, phenotypic assays were conducted. Drug inhibition and time-dependent plots were employed to analyse drug resistance. Liquid chromatography-mass spectrometry and bisulphite sequencing were used to investigate the m5 C methylation of tRNA at both global and single-base levels. Puromycin intake and high-frequency codon reporter assays verified the protein translation level. By combining mRNA and ribosome profiling, a series of downstream proteins and codon usage bias were identified. The acquired data were further validated by tRNA sequencing. This study observed that the tRNA m5 C methyltransferase NSUN2 was up-regulated in ATC and is associated with dedifferentiation. Furthermore, NSUN2 knockdown repressed ATC formation, proliferation, invasion and migration both in vivo and in vitro. Moreover, NSUN2 repression enhanced the sensitivity of ATC to genotoxic drugs. Mechanically, NSUN2 catalyses tRNA structure-related m5 C modification, stabilising tRNA that maintains homeostasis and rapidly transports amino acids, particularly leucine. This stable tRNA has a substantially increased efficiency necessary to support a pro-cancer translation program including c-Myc, BCL2, RAB31, JUNB and TRAF2. Additionally, the NSUN2-mediated variations in m5C levels and different tRNA Leu iso-decoder families, partially contribute to a codon-dependent translation bias. Surprisingly, targeting NSUN2 disrupted the c-Myc to NSUN2 cycle in ATC. This research revealed that a pro-tumour m5C methyltransferase, dynamic tRNA stability regulation and downstream oncogenes, c-Myc, elicits a codon-dependent oncogenic translation network that enhances ATC growth and formation. Furthermore, it provides new opportunities for targeting translation reprogramming in cancer cells.

A cosmic-ray database update: CRDB v4.1

The cosmic-ray database, CRDB, has been gathering cosmic-ray data for the community since 2013. We present a new release, CRDB v4.1, providing many new quantities and data sets, with several improvements made on the code and web interface, and with new visualisation tools. CRDB relies on the MySQL database management system, jquery and table-sorter libraries for queries and sorting, and PHP web pages and AJAX protocol for displays. A REST interface enables user queries from command line or scripts. A new (pip-installable) CRDB python library is developed and extensive jupyter notebook examples are provided. This release contains cosmic-ray dipole anisotropy data, high-energy p¯/p\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\bar{p}/p$$\\end{document} upper limits, some unpublished LEE and AESOP lepton time series, many more ultra-high energy data, and a few missing old data sets. It also includes high-precision data from the last three years, in particular the hundreds of thousands AMS-02 and PAMELA data time series (time-dependent plots are now enabled). All these data are shown in a gallery of plots, which can be easily reproduced from the public notebook examples. CRDB contains 316,126 data points from 504 publications, in 4111 sub-experiments from 131 experiments.

A Distinctive Pattern for Substituent Effects on Transition Metal Centers: Enhanced Electron-Donating Capacity of Cationic Palladium Species

A Distinctive Pattern for Substituent Effects on Transition Metal Centers: Enhanced Electron-Donating Capacity of Cationic Palladium Species

Electrical impedance tomography detects changes in ventilation after airway clearance in spinal muscular atrophy type I

The effect of mechanical insufflation-exsufflation (MIE) for airway clearance in patients with spinal muscular atrophy type I (SMA‐I) on the distribution of ventilation in the lung is unknown, as is the duration of its beneficial effects. A pilot study to investigate the feasibility of using three dimensional (3-D) electrical impedance tomography (EIT) images to estimate lung volumes pre- and post-MIE for assessing the effectiveness of mechanical insufflation-exsufflation (MIE) was conducted in 6 pediatric patients with SMA‐I in the neuromuscular clinic at Children's Hospital Colorado. EIT data were collected before, during, and after the MIE procedure on two rows of 16 electrodes placed around the chest. Lung volumes were computed from the images and compared before, during, and after the MIE procedure to assess the ability of EIT to estimate changes in lung volume during insufflation and exsufflation. Images of pulsatile pulmonary perfusion were computed in subjects able to perform breath-holding. In four of the six subjects, lung volumes during tidal breathing increased after MIE (average change from pre to post MIE was 58.8±55.1 mL). The time-dependent plots of lung volume computed from the EIT data clearly show when the MIE device insufflates and exsufflates air and the rest periods between mechanical coughs. Images of pulmonary pulsatile perfusion were computed from data collected during breathing pauses. The results suggest that EIT holds promise for estimating lung volumes and ventilation/perfusion mismatch, both of which are useful for assessing the effectiveness of MIE in clearing mucus plugs.

Monitoring Growth and Antibiotic Susceptibility of Escherichia coli with Photoluminescence Emitting Semiconductor Biochips

Growth and antibiotic sensitivity of Escherichia coli were evaluated with an innovative method based on photocorrosion of biofunctionalized GaAs/AlGaAs quantum well (QW) biochips. The formation of surface oxides and dissolution of a limited thickness GaAs cap material results in the appearance of a characteristic maximum in a time-dependent plot of the photoluminescence (PL) emitting biochip. A position of the PL maximum depends on the electrostatic interaction between bacteria and the biochip surface, and it becomes delayed with increasing concentration of bacteria growing on the biochip surface. We demonstrate detection of the bacteria reaction to antibiotics within less than 3 hours.

Dual-porosity poroviscoelasticity and quantitative hydromechanical characterization of the brain tissue with experimental hydrocephalus data

Hydromechanical brain models often involve constitutive relations which must account for soft tissue deformation and creep, together with the interstitial fluid movement and exchange through capillaries. The interaction of rather unknown mechanisms which produce, absorb, and circulate the cerebrospinal fluid within the central nervous system can further add to their complexity. Once proper models for these phenomena or processes are selected, estimation of the associated parameters could be even more challenging.This paper presents the results of a consistent, coupled poroviscoelastic modeling and characterization of the brain tissue as a dual-porosity system. The model draws from Biot׳s theory of poroviscoelasticity, and adopts the generalized Kelvin׳s rheological description of the viscoelastic tissue behavior. While the interstitial space serves as the primary porosity through which the bulk flow of the interstitial fluid occurs, a secondary porosity network comprising the capillaries and venous system allows for its partial absorption into the blood. The correspondence principle is used in deriving a time-dependent analytical solution to the proposed model. It allows for identical poroelastic formulation of the original poroviscoelastic problem in the Laplace transform space.Hydrocephalus generally refers to a class of medical conditions which share the ventricles enlargement as a common feature. A set of published data from induced hydrocephalus and follow-up perfusion of cats׳ brains is used for quantitative characterization of the proposed model. A selected portion of these data including the ventricular volume and rate of fluid absorption from the perfused brain, together with the forward model solution, is utilized via an inverse problem technique to find proper estimations of the model parameters. Results show significant improvement in model predictions of the experimental data.The convoluted and coupled solution results are presented through the time-dependent plots of the ventricular volume undergoing the perfusion experiment. The plots demonstrate the intricate interplay of viscous and poroelastic diffusive time scales, and their competition in reaching the steady state response of the system.

Optimized Flow Cytometry to Measure Anti-ABO Immunoglobulin G

Background: An accurate measurement of ABO antibody levels before and after ABO-incompatible organ transplantations is critical. We verified several assay steps of a previously reported protocol using flow cytometry, improved its shortcomings, and developed a more optimized protocol, which we named Flow ABO Ab, for the anti-ABO immunoglobulin G (IgG). Methods: Fixed red blood cells (RBCs) were sensitized with dithiothreitol-treated sera at 4°C. Residual hemagglutination and hemolysis were monitored on a time-dependent plot. Only singlet RBCs were analyzed, excluding RBC agglutinates, to obtain mean fluorescence intensity (MFI) ratios. Results: The sensitivity for anti-ABO IgG was compared between Flow ABO Ab and the column agglutination technique (CAT) in 34 sera diluted to have borderline reactivity of anti-ABO IgG. Flow ABO Ab yielded a positivity rate of 68% (23/34), whereas CAT yielded 50% (17/34) (P = .18). The CAT titer was highly correlated with the mean fluorescence intensity (MFI) ratio of Flow ABO Ab (r = 0.843, P<.001) in 17 undiluted sera. Using Flow ABO Ab, all group A (30 [100%]) and group B (30 [100%]) healthy individuals tested positive for anti-B and anti-A, respectively. Conclusions: Our protocol markedly improved on the previously reported protocol and provided its analytical performance to be comparable to that of CAT, suggesting its potential as an additional effective tool for the measurement of anti-ABO IgG. Further studies are needed to clarify the target MFI ratio for transplantation and whether Flow ABO Ab is preferable to CAT for a correlation with a clinical outcome.

Real-time analysis of intracellular glucose and calcium in pancreatic beta cells by fluorescence microscopy

Glucose is the physiological stimulus for insulin secretion in pancreatic beta cells. The uptake and phosphorylation of glucose initiate and control downstream pathways, resulting in insulin secretion. However, the temporal coordination of these events in beta cells is not fully understood. The recent development of the FLII12Pglu-700μ-δ6 glucose nanosensor facilitates real-time analysis of intracellular glucose within a broad concentration range. Using this fluorescence-based technique, we show the shift in intracellular glucose concentration upon external supply and removal in primary mouse beta cells with high resolution. Glucose influx, efflux, and metabolism rates were calculated from the time-dependent plots. Comparison of insulin-producing cells with different expression levels of glucose transporters and phosphorylating enzymes showed that a high glucose influx rate correlated with GLUT2 expression, but was largely also sustainable by high GLUT1 expression. In contrast, in cells not expressing the glucose sensor enzyme glucokinase glucose metabolism was slow. We found no evidence of oscillations of the intracellular glucose concentration in beta cells. Concomitant real-time analysis of glucose and calcium dynamics using FLII12Pglu-700μ-δ6 and fura-2-acetoxymethyl-ester determined a glucose threshold of 4mM for the [Ca2+]i increase in beta cells. Indeed, a glucose concentration of 7mM had to be reached to evoke large amplitude [Ca2+]i oscillations. The KATP channel closing agent glibenclamide was not able to induce large amplitude [Ca2+]i oscillations in the absence of glucose. Our findings suggest that glucose has to reach a threshold to evoke the [Ca2+]i increase and subsequently initiate [Ca2+]i oscillations in a KATP channel independent manner.

Radiation oxidation of polypropylene: A solid-state 13C NMR study using selective isotopic labeling

Polypropylene samples, in which the three different carbon atoms along the chain were selectively labeled with carbon-13, were subjected to radiation under inert and air atmospheres, and to post-irradiation exposure in air at various temperatures. By using solid-state 13C NMR measurements at room temperature, we have been able to identify and quantify the oxidation products. The isotopic labeling provides insight into chemical reaction mechanisms, since oxidation products can be traced back to their positions of origin on the macromolecule. The major products include peroxides and alcohols, both formed at tertiary carbon sites along the chain. Other products include methyl ketones, acids, esters, peresters, and hemiketals formed from reaction at the tertiary carbon, together with in-chain ketones and esters from reaction at the secondary chain carbon. No evidence is found of products arising from reactions at the methyl side chain. Significant temperature-dependent differences are apparent; for example much higher yields of chain-end methyl ketones, which are the indicator product of chain scission, are generated for both elevated temperature irradiation and for post-irradiation treatment at elevated temperatures. Time-dependent plots of yields of the various oxidation products have been obtained under a wide range of conditions, including the post-irradiation oxidation of a sample at room temperature in air that has been monitored for 2 years. Radiation-oxidation products of polypropylene are contrasted to products measured for 13C-labeled polyethylene in an earlier investigation: the peroxides formed in irradiated polypropylene are remarkably longer lived, the non-peroxidic products are significantly different, and the overall ratios of oxidation products in polypropylene change relatively little as a function of the extent of oxidation.

Monitoring of iodinated X-ray contrast media in surface water

A monitoring programme was carried out in order to determine iodinated X-ray contrast media (ICM) in the River Danube and to investigate the raw water quality for drinking water production at Langenau waterworks. The study revealed that the maximum concentrations of ICM (over 500 ng l −1 for diatrizoic acid and iopamidol) were found in 2 h-composite samples taken from the downstream of the Ulm/Neu-Ulm metropolitan area. By means of a concentration profile over one month the highest ICM concentrations were observed on weekdays. The extended data evaluation with principal component analysis shows that the upstream and downstream samples had different pattern of variations in ICM concentration and also demonstrates a clear change in ICM composition by the discharge of municipal wastewater. In addition to load profiles of ICM, time-dependent plots of principal component 1 exhibited peaks, indicating a short-term discharge of ICM between the two sampling sites. In conclusion, a point source for ICM contamination between the sampling sites in Ulm upstream and Leipheim downstream seems to be the reasonable explanation for peak ICM concentrations. Due to the observed high variations of ICM concentrations in river, the evaluation of natural waters by means of a single analysis is not representative.

Modeling and Analysis of an Airport Departure Process

This paper develops and implements an analytical queueing model for an aircraft departure process. The model is formulated using data collected at LaGuardia Airport in June 1994. Departure demand is represented by a nonhomogeneous Poisson process, and service times are modeled as appropriate mixtures of exponential stages. Transient analysis of the resulting Markovian system is performed to produce a time-dependent plot of anticipated departure delay. The model and analytical results yield useful insights for airport capacity estimation and departure delay prediction. ROWING congestion at major U.S. airports has created a need for better understanding of factors that can lead to aircraft departure delays. This article presents an analytical queueing model that captures key variables in the aircraft de- parture process and offers an approach toward airport capacity estimation and departure delay prediction. The model is de- veloped and demonstrated using data collected from New York City' s LaGuardia Airport (LGA) during a single week in June 1994. LGA was selected because the airport has characteristics common to many U.S. facilities, including the frequent occur- rence of signie cant departure delays. Like many airports, LGA is cone gured with two intersecting runways. Normal operating procedures assign a primary de- parture runway, which can be viewed as the single server in a queueing system. Several dee nitions are useful in formulating an appropriate queueing model. Departure is synonymous with service completion, which occurs when an aircraft completes takeoff and clears the runway environment sufe ciently for an- other aircraft to be granted takeoff clearance. Service demand occurs when an aircraft enters the departure queue after leav- ing a passenger gate (pushback) and taxiing to the runway. Departure delay is the difference between service demand time and the initiation of service (clearance for takeoff ). Roll-out time is the total time between pushback and takeoff clearance (sum of taxi time and departure delay ). Initial analysis of the LGA activity data reveals that roll-out time varies greatly with time of day, primarily because of time- dependent variation in the frequency of scheduled pushbacks. The queueing model is consequently designed to capture var- iability in pushback rates and runway service time to produce a time-dependent plot of expected roll-out time. While this type of transient analysis has been explored for some aspects of airport operation, the departure process has received rela- tively little attention. There are various published investiga- tions of airport arrival (landing) processes. 1 › 6

Interstellar deuterium chemistry

An interstellar reaction scheme of the type described by E. Iglesias ( Astrophys. J. 218, 697 (1977)) has been extended to include deuterium chemistry and also isomeric forms of some molecules. The role of isomeric forms of the intermediates CNH 2 and HCNH+ in the production of interstellar HCN and HNC is considered. The lowest triplet states of these ions probably play an important part in determining the proportions of HCN and HNC produced. The results of numerical integration of the 108 coupled kinetic equations involved in the extended scheme are presented as time-dependent plots of concentrations of the different chemical species. Calculated concentrations at a molecular cloud age of 10 Ma (1 Ma — 10 6 years) are within the experimental uncertainties for 11 of the 14 species for which suitable observational data are available. Predicted values of HX /DX ratios fall into three broad groups around 10 2 , 10 3 and the accepted cosmic H /D ratio, 10 5 , and observations are broadly in agreement. Some reported enrichments that are higher than the predicted figures may arise from the use of data for optically thick molecular lines. Some previously unpublished observations of DNC and HN 13 C illustrate doubts associated with optically thick lines.