Matching synchrosqueezing transform: A useful tool for characterizing signals with fast varying instantaneous frequency and application to machine fault diagnosis

NASA Astrophysics Data System (ADS)

Wang, Shibin; Chen, Xuefeng; Selesnick, Ivan W.; Guo, Yanjie; Tong, Chaowei; Zhang, Xingwu

2018-02-01

Synchrosqueezing transform (SST) can effectively improve the readability of the time-frequency (TF) representation (TFR) of nonstationary signals composed of multiple components with slow varying instantaneous frequency (IF). However, for signals composed of multiple components with fast varying IF, SST still suffers from TF blurs. In this paper, we introduce a time-frequency analysis (TFA) method called matching synchrosqueezing transform (MSST) that achieves a highly concentrated TF representation comparable to the standard TF reassignment methods (STFRM), even for signals with fast varying IF, and furthermore, MSST retains the reconstruction benefit of SST. MSST captures the philosophy of STFRM to simultaneously consider time and frequency variables, and incorporates three estimators (i.e., the IF estimator, the group delay estimator, and a chirp-rate estimator) into a comprehensive and accurate IF estimator. In this paper, we first introduce the motivation of MSST with three heuristic examples. Then we introduce a precise mathematical definition of a class of chirp-like intrinsic-mode-type functions that locally can be viewed as a sum of a reasonably small number of approximate chirp signals, and we prove that MSST does indeed succeed in estimating chirp-rate and IF of arbitrary functions in this class and succeed in decomposing these functions. Furthermore, we describe an efficient numerical algorithm for the practical implementation of the MSST, and we provide an adaptive IF extraction method for MSST reconstruction. Finally, we verify the effectiveness of the MSST in practical applications for machine fault diagnosis, including gearbox fault diagnosis for a wind turbine in variable speed conditions and rotor rub-impact fault diagnosis for a dual-rotor turbofan engine.

Time-frequency analysis of SEMG--with special consideration to the interelectrode spacing.

PubMed

Alemu, M; Kumar, Dinesh Kant; Bradley, Alan

2003-12-01

The surface electromyogram (SEMG) is a complex, nonstationary signal. The spectrum of the SEMG is dependent on the force of contraction being generated and other factors like muscle fatigue and interelectrode distance (IED). The spectrum of the signal is time variant. This paper reports the experimental research conducted to study the influence of force of muscle contraction and IED on the SEMG signal using time-frequency (T-F) analysis. Two T-F techniques have been used: Wigner-Ville distribution (WVD) and Choi-Williams distribution (CWD). The experiment was conducted with the help of ten healthy volunteers (five males and five females) who performed isometric elbow flexions of the active right arm at 20%, 50%, and 80% of their maximal voluntary contraction. The SEMG signal was recorded using surface electrodes placed at a distance of 18 and 36 mm over biceps brachii muscle. The results indicate that the two distributions were spread out across the frequency range at smaller IED. Further, regardless of the spacing, both distributions displayed increased spectral compression with time at higher contraction level.

ConceFT for Time-Varying Heart Rate Variability Analysis as a Measure of Noxious Stimulation During General Anesthesia.

PubMed

Lin, Yu-Ting; Wu, Hau-Tieng

2017-01-01

Heart rate variability (HRV) offers a noninvasive way to peek into the physiological status of the human body. When this physiological status is dynamic, traditional HRV indices calculated from power spectrum do not resolve the dynamic situation due to the issue of nonstationarity. Clinical anesthesia is a typically dynamic situation that calls for time-varying HRV analysis. Concentration of frequency and time (ConceFT) is a nonlinear time-frequency (TF) analysis generalizing the multitaper technique and the synchrosqueezing transform. The result is a sharp TF representation capturing the dynamics inside HRV. Companion indices of the commonly applied HRV indices, including time-varying low-frequency power (tvLF), time-varying high-frequency power, and time-varying low-high ratio, are considered as measures of noxious stimulation. To evaluate the feasibility of the proposed indices, we apply these indices to study two different types of noxious stimulation, the endotracheal intubation and surgical skin incision, under general anesthesia. The performance was compared with traditional HRV indices, the heart rate reading, and indices from electroencephalography. The results indicate that the tvLF index performs best and outperforms not only the traditional HRV index, but also the commonly used heart rate reading. With the help of ConceFT, the proposed HRV indices are potential to provide a better quantification of the dynamic change of the autonomic nerve system. Our proposed scheme of time-varying HRV analysis could contribute to the clinical assessment of analgesia under general anesthesia.

Source localization of non-stationary acoustic data using time-frequency analysis

NASA Astrophysics Data System (ADS)

Stoughton, Jack; Edmonson, William

2005-04-01

An improvement in temporal locality of the generalized cross-correlation (GCC) for angle of arrival (AOA) estimation can be achieved by employing 2-D cross-correlation of infrasonic sensor data transformed to its time-frequency (TF) representation. Intermediate to the AOA evaluation is the time delay between pairs of sensors. The signal class of interest includes far field sources which are partially coherent across the array, nonstationary, and wideband. In addition, signals can occur as multiple short bursts, for which TF representations may be more appropriate for time delay estimation. The GCC tends to smooth out such temporal energy bursts. Simulation and experimental results will demonstrate the improvement in using a TF-based GCC, using the Cohen class, over the classic GCC method. Comparative demonstration of the methods will be performed on data captured on an infrasonic sensor array located at NASA Langley Research Center (LaRC). The infrasonic data sources include Delta IV and Space Shuttle launches from Kennedy Space Center which belong to the stated signal class. Of interest is to apply this method to the AOA estimation of atmospheric turbulence. [Work supported by NASA LaRC Creativity and Innovation project: Infrasonic Detection of Clear Air Turbulence and Severe Storms.

Bearing fault diagnosis under unknown time-varying rotational speed conditions via multiple time-frequency curve extraction

NASA Astrophysics Data System (ADS)

Huang, Huan; Baddour, Natalie; Liang, Ming

2018-02-01

Under normal operating conditions, bearings often run under time-varying rotational speed conditions. Under such circumstances, the bearing vibrational signal is non-stationary, which renders ineffective the techniques used for bearing fault diagnosis under constant running conditions. One of the conventional methods of bearing fault diagnosis under time-varying speed conditions is resampling the non-stationary signal to a stationary signal via order tracking with the measured variable speed. With the resampled signal, the methods available for constant condition cases are thus applicable. However, the accuracy of the order tracking is often inadequate and the time-varying speed is sometimes not measurable. Thus, resampling-free methods are of interest for bearing fault diagnosis under time-varying rotational speed for use without tachometers. With the development of time-frequency analysis, the time-varying fault character manifests as curves in the time-frequency domain. By extracting the Instantaneous Fault Characteristic Frequency (IFCF) from the Time-Frequency Representation (TFR) and converting the IFCF, its harmonics, and the Instantaneous Shaft Rotational Frequency (ISRF) into straight lines, the bearing fault can be detected and diagnosed without resampling. However, so far, the extraction of the IFCF for bearing fault diagnosis is mostly based on the assumption that at each moment the IFCF has the highest amplitude in the TFR, which is not always true. Hence, a more reliable T-F curve extraction approach should be investigated. Moreover, if the T-F curves including the IFCF, its harmonic, and the ISRF can be all extracted from the TFR directly, no extra processing is needed for fault diagnosis. Therefore, this paper proposes an algorithm for multiple T-F curve extraction from the TFR based on a fast path optimization which is more reliable for T-F curve extraction. Then, a new procedure for bearing fault diagnosis under unknown time-varying speed conditions is developed based on the proposed algorithm and a new fault diagnosis strategy. The average curve-to-curve ratios are utilized to describe the relationship of the extracted curves and fault diagnosis can then be achieved by comparing the ratios to the fault characteristic coefficients. The effectiveness of the proposed method is validated by simulated and experimental signals.

Socioeconomic indicators and frequency of traditional food, junk food, and fruit and vegetable consumption amongst Inuit adults in the Canadian Arctic.

PubMed

Hopping, B N; Erber, E; Mead, E; Sheehy, T; Roache, C; Sharma, S

2010-10-01

Increasing consumption of non-nutrient-dense foods (NNDF), decreasing consumption of traditional foods (TF) and low consumption of fruit and vegetables (FV) may contribute to increasing chronic disease rates amongst Inuit. The present study aimed to assess the daily frequency and socioeconomic and demographic factors influencing consumption of TF, FV and NNDF amongst Inuit adults in Nunavut, Canada. Using a cross-sectional study design and random household sampling in three communities in Nunavut, a food frequency questionnaire developed for the population was used to assess frequency of NNDF, TF and FV consumption amongst Inuit adults. Socioeconomic status (SES) was assessed by education level, ownership of items in working condition, and whether or not people in the household were employed or on income support. Mean frequencies of daily consumption were compared across gender and age groups, and associations with socioeconomic indicators were analysed using logistic regression. Two hundred and eleven participants (36 men, 175 women; mean (standard deviation) ages 42.1 (15.0) and 42.2 (13.2) years, respectively; response rate 69-93%) completed the study. Mean frequencies of consumption for NNDF, TF and FV were 6.3, 1.9 and 1.6 times per day, respectively. On average, participants ≤50 years consumed NNDF (P=0.003) and FV (P=0.01) more frequently and TF (P=0.01) less frequently than participants >50 years. Education was positively associated with FV consumption and negatively associated with TF consumption. Households on income support were more likely to consume TF and NNDF. These results support the hypothesis that the nutrition transition taking place amongst Inuit in Nunavut results in elevated consumption of NNDF compared with TF and FV. © 2010 The Authors. Journal compilation © 2010 The British Dietetic Association Ltd.

Wigner-Ville distribution and Gabor transform in Doppler ultrasound signal processing.

PubMed

Ghofrani, S; Ayatollahi, A; Shamsollahi, M B

2003-01-01

Time-frequency distributions have been used extensively for nonstationary signal analysis, they describe how the frequency content of a signal is changing in time. The Wigner-Ville distribution (WVD) is the best known. The draw back of WVD is cross-term artifacts. An alternative to the WVD is Gabor transform (GT), a signal decomposition method, which displays the time-frequency energy of a signal on a joint t-f plane without generating considerable cross-terms. In this paper the WVD and GT of ultrasound echo signals are computed analytically.

Perceptual learning for speech in noise after application of binary time-frequency masks

PubMed Central

Ahmadi, Mahnaz; Gross, Vauna L.; Sinex, Donal G.

2013-01-01

Ideal time-frequency (TF) masks can reject noise and improve the recognition of speech-noise mixtures. An ideal TF mask is constructed with prior knowledge of the target speech signal. The intelligibility of a processed speech-noise mixture depends upon the threshold criterion used to define the TF mask. The study reported here assessed the effect of training on the recognition of speech in noise after processing by ideal TF masks that did not restore perfect speech intelligibility. Two groups of listeners with normal hearing listened to speech-noise mixtures processed by TF masks calculated with different threshold criteria. For each group, a threshold criterion that initially produced word recognition scores between 0.56–0.69 was chosen for training. Listeners practiced with one set of TF-masked sentences until their word recognition performance approached asymptote. Perceptual learning was quantified by comparing word-recognition scores in the first and last training sessions. Word recognition scores improved with practice for all listeners with the greatest improvement observed for the same materials used in training. PMID:23464038

Time-frequency approach to underdetermined blind source separation.

PubMed

Xie, Shengli; Yang, Liu; Yang, Jun-Mei; Zhou, Guoxu; Xiang, Yong

2012-02-01

This paper presents a new time-frequency (TF) underdetermined blind source separation approach based on Wigner-Ville distribution (WVD) and Khatri-Rao product to separate N non-stationary sources from M(M <; N) mixtures. First, an improved method is proposed for estimating the mixing matrix, where the negative value of the auto WVD of the sources is fully considered. Then after extracting all the auto-term TF points, the auto WVD value of the sources at every auto-term TF point can be found out exactly with the proposed approach no matter how many active sources there are as long as N ≤ 2M-1. Further discussion about the extraction of auto-term TF points is made and finally the numerical simulation results are presented to show the superiority of the proposed algorithm by comparing it with the existing ones.

A High-Spin Rate Measurement Method for Projectiles Using a Magnetoresistive Sensor Based on Time-Frequency Domain Analysis.

PubMed

Shang, Jianyu; Deng, Zhihong; Fu, Mengyin; Wang, Shunting

2016-06-16

Traditional artillery guidance can significantly improve the attack accuracy and overall combat efficiency of projectiles, which makes it more adaptable to the information warfare of the future. Obviously, the accurate measurement of artillery spin rate, which has long been regarded as a daunting task, is the basis of precise guidance and control. Magnetoresistive (MR) sensors can be applied to spin rate measurement, especially in the high-spin and high-g projectile launch environment. In this paper, based on the theory of a MR sensor measuring spin rate, the mathematical relationship model between the frequency of MR sensor output and projectile spin rate was established through a fundamental derivation. By analyzing the characteristics of MR sensor output whose frequency varies with time, this paper proposed the Chirp z-Transform (CZT) time-frequency (TF) domain analysis method based on the rolling window of a Blackman window function (BCZT) which can accurately extract the projectile spin rate. To put it into practice, BCZT was applied to measure the spin rate of 155 mm artillery projectile. After extracting the spin rate, the impact that launch rotational angular velocity and aspect angle have on the extraction accuracy of the spin rate was analyzed. Simulation results show that the BCZT TF domain analysis method can effectively and accurately measure the projectile spin rate, especially in a high-spin and high-g projectile launch environment.

EEG error potentials detection and classification using time-frequency features for robot reinforcement learning.

PubMed

Boubchir, Larbi; Touati, Youcef; Daachi, Boubaker; Chérif, Arab Ali

2015-08-01

In thought-based steering of robots, error potentials (ErrP) can appear when the action resulting from the brain-machine interface (BMI) classifier/controller does not correspond to the user's thought. Using the Steady State Visual Evoked Potentials (SSVEP) techniques, ErrP, which appear when a classification error occurs, are not easily recognizable by only examining the temporal or frequency characteristics of EEG signals. A supplementary classification process is therefore needed to identify them in order to stop the course of the action and back up to a recovery state. This paper presents a set of time-frequency (t-f) features for the detection and classification of EEG ErrP in extra-brain activities due to misclassification observed by a user exploiting non-invasive BMI and robot control in the task space. The proposed features are able to characterize and detect ErrP activities in the t-f domain. These features are derived from the information embedded in the t-f representation of EEG signals, and include the Instantaneous Frequency (IF), t-f information complexity, SVD information, energy concentration and sub-bands' energies. The experiment results on real EEG data show that the use of the proposed t-f features for detecting and classifying EEG ErrP achieved an overall classification accuracy up to 97% for 50 EEG segments using 2-class SVM classifier.

Wavelets and Affine Distributions: A Time-Frequency Perspective

DTIC Science & Technology

2005-01-07

Ville Distribution ( WVD ) • Prominent member of the AC: the WVD • Properties of the WVD : – Covariant to TF scaling and time shift (of course) – Covariant...QTFRs • Wigner - Ville distribution and affine smoothing • Doppler tolerance and hyperbolic impulses • Hyperbolic TF localization and Bertrand P0...satisfy hyperbolic TF localization property: • Not satisfied by WVD ! 25 – 49 –WAMA-04 Cargèse, France The Bertrand P0 distribution • The hyperbolic

Separable Processes Before, During, and After the N400 Elicited by Previously Inferred and New Information: Evidence from Time-Frequency Decompositions

PubMed Central

Steele, Vaughn R.; Bernat, Edward M.; van den Broek, Paul; Collins, Paul F.; Patrick, Christopher J.; Marsolek, Chad J.

2012-01-01

Successful comprehension during reading often requires inferring information not explicitly presented. This information is readily accessible when subsequently encountered, and a neural correlate of this is an attenuation of the N400 event-related potential (ERP). We used ERPs and time-frequency (TF) analysis to investigate neural correlates of processing inferred information after a causal coherence inference had been generated during text comprehension. Participants read short texts, some of which promoted inference generation. After each text, they performed lexical decisions to target words that were unrelated or inference-related to the preceding text. Consistent with previous findings, inference-related words elicited an attenuated N400 relative to unrelated words. TF analyses revealed unique contributions to the N400 from activity occurring at 1–6 Hz (theta) and 0–2 Hz (delta), supporting the view that multiple, sequential processes underlie the N400. PMID:23165117

Multichannel interictal spike activity detection using time-frequency entropy measure.

PubMed

Thanaraj, Palani; Parvathavarthini, B

2017-06-01

Localization of interictal spikes is an important clinical step in the pre-surgical assessment of pharmacoresistant epileptic patients. The manual selection of interictal spike periods is cumbersome and involves a considerable amount of analysis workload for the physician. The primary focus of this paper is to automate the detection of interictal spikes for clinical applications in epilepsy localization. The epilepsy localization procedure involves detection of spikes in a multichannel EEG epoch. Therefore, a multichannel Time-Frequency (T-F) entropy measure is proposed to extract features related to the interictal spike activity. Least squares support vector machine is used to train the proposed feature to classify the EEG epochs as either normal or interictal spike period. The proposed T-F entropy measure, when validated with epilepsy dataset of 15 patients, shows an interictal spike classification accuracy of 91.20%, sensitivity of 100% and specificity of 84.23%. Moreover, the area under the curve of Receiver Operating Characteristics plot of 0.9339 shows the superior classification performance of the proposed T-F entropy measure. The results of this paper show a good spike detection accuracy without any prior information about the spike morphology.

A High-Spin Rate Measurement Method for Projectiles Using a Magnetoresistive Sensor Based on Time-Frequency Domain Analysis

PubMed Central

Shang, Jianyu; Deng, Zhihong; Fu, Mengyin; Wang, Shunting

2016-01-01

Traditional artillery guidance can significantly improve the attack accuracy and overall combat efficiency of projectiles, which makes it more adaptable to the information warfare of the future. Obviously, the accurate measurement of artillery spin rate, which has long been regarded as a daunting task, is the basis of precise guidance and control. Magnetoresistive (MR) sensors can be applied to spin rate measurement, especially in the high-spin and high-g projectile launch environment. In this paper, based on the theory of a MR sensor measuring spin rate, the mathematical relationship model between the frequency of MR sensor output and projectile spin rate was established through a fundamental derivation. By analyzing the characteristics of MR sensor output whose frequency varies with time, this paper proposed the Chirp z-Transform (CZT) time-frequency (TF) domain analysis method based on the rolling window of a Blackman window function (BCZT) which can accurately extract the projectile spin rate. To put it into practice, BCZT was applied to measure the spin rate of 155 mm artillery projectile. After extracting the spin rate, the impact that launch rotational angular velocity and aspect angle have on the extraction accuracy of the spin rate was analyzed. Simulation results show that the BCZT TF domain analysis method can effectively and accurately measure the projectile spin rate, especially in a high-spin and high-g projectile launch environment. PMID:27322266

Evaluation of the importance of time-frequency contributions to speech intelligibility in noise

PubMed Central

Yu, Chengzhu; Wójcicki, Kamil K.; Loizou, Philipos C.; Hansen, John H. L.; Johnson, Michael T.

2014-01-01

Recent studies on binary masking techniques make the assumption that each time-frequency (T-F) unit contributes an equal amount to the overall intelligibility of speech. The present study demonstrated that the importance of each T-F unit to speech intelligibility varies in accordance with speech content. Specifically, T-F units are categorized into two classes, speech-present T-F units and speech-absent T-F units. Results indicate that the importance of each speech-present T-F unit to speech intelligibility is highly related to the loudness of its target component, while the importance of each speech-absent T-F unit varies according to the loudness of its masker component. Two types of mask errors are also considered, which include miss and false alarm errors. Consistent with previous work, false alarm errors are shown to be more harmful to speech intelligibility than miss errors when the mixture signal-to-noise ratio (SNR) is below 0 dB. However, the relative importance between the two types of error is conditioned on the SNR level of the input speech signal. Based on these observations, a mask-based objective measure, the loudness weighted hit-false, is proposed for predicting speech intelligibility. The proposed objective measure shows significantly higher correlation with intelligibility compared to two existing mask-based objective measures. PMID:24815280

What can time-frequency and phase coherence measures tell us about the genetic basis of P3 amplitude?

PubMed Central

McGue, Matt; Iacono, William G.

2017-01-01

In a recent comprehensive investigation, we largely failed to identify significant genetic markers associated with P3 amplitude or to corroborate previous associations between P3 and specific single nucleotide polymorphisms (SNPs) or genes. In the present study we extended this line of investigation to examine time-frequency (TF) activity and intertrial phase coherence (ITPC) in the P3 time window, both of which are associated with P3 amplitude. Previous genome-wide research has reported associations between P3-related theta and delta activity and individual genetic variants. A large, population-based sample of 4211 subjects, comprising male and female adolescent twins and their parents, was genotyped for 527,828 single nucleotide polymorphisms (SNPs), from which over six million SNPs were accurately imputed. Heritability estimates were greater for TF energy than ITPC, whether based on biometric models or the combined influence of all measured SNPs (derived from genome-wide complex trait analysis). The magnitude of overlap in the specific SNPs associated with delta energy and ITPC and P3 amplitude was significant. A genome-wide analysis of all SNPs, accompanied by an analysis of approximately 17,600 genes, indicated a region of chromosome 2 around TEKT4 that was significantly associated with theta ITPC. Analysis of candidate SNPs and genes previously reported to be associated with P3 or related phenotypes yielded one association surviving correction for multiple tests: between theta energy and CRHR1. However, we did not obtain significant associations for SNPs implicated in previous genome-wide studies of TF measures. Identifying specific genetic variants associated with P3 amplitude remains a challenge. PMID:27871913

Exploring lateral genetic transfer among microbial genomes using TF-IDF.

PubMed

Cong, Yingnan; Chan, Yao-Ban; Ragan, Mark A

2016-07-25

Many microbes can acquire genetic material from their environment and incorporate it into their genome, a process known as lateral genetic transfer (LGT). Computational approaches have been developed to detect genomic regions of lateral origin, but typically lack sensitivity, ability to distinguish donor from recipient, and scalability to very large datasets. To address these issues we have introduced an alignment-free method based on ideas from document analysis, term frequency-inverse document frequency (TF-IDF). Here we examine the performance of TF-IDF on three empirical datasets: 27 genomes of Escherichia coli and Shigella, 110 genomes of enteric bacteria, and 143 genomes across 12 bacterial and three archaeal phyla. We investigate the effect of k-mer size, gap size and delineation of groups on the inference of genomic regions of lateral origin, finding an interplay among these parameters and sequence divergence. Because TF-IDF identifies donor groups and delineates regions of lateral origin within recipient genomes, aggregating these regions by gene enables us to explore, for the first time, the mosaic nature of lateral genes including the multiplicity of biological sources, ancestry of transfer and over-writing by subsequent transfers. We carry out Gene Ontology enrichment tests to investigate which biological processes are potentially affected by LGT.

Signal analysis by means of time-frequency (Wigner-type) distributions -- Applications to sonar and radar echoes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaunaurd, G.; Strifors, H.C.

1996-09-01

Time series data have been traditionally analyzed in either the time or the frequency domains. For signals with a time-varying frequency content, the combined time-frequency (TF) representations, based on the Cohen class of (generalized) Wigner distributions (WD`s) offer a powerful analysis tool. Using them, it is possible to: (1) trace the time-evolution of the resonance features usually present in a standard sonar cross section (SCS), or in a radar cross section (RCS) and (2) extract target information that may be difficult to even notice in an ordinary SCS or RCS. After a brief review of the fundamental properties of themore » WD, the authors discuss ways to reduce or suppress the cross term interference that appears in the WD of multicomponent systems. These points are illustrated with a variety of three-dimensional (3-D) plots of Wigner and pseudo-Wigner distributions (PWD), in which the strength of the distribution is depicted as the height of a Wigner surface with height scales measured by various color shades or pseudocolors. The authors also review studies they have made of the echoes returned by conducting or dielectric targets in the atmosphere, when they are illuminated by broadband radar pings. A TF domain analysis of these impulse radar returns demonstrates their superior informative content. These plots allow the identification of targets in an easier and clearer fashion than by the conventional RCS of narrowband systems. The authors show computed and measured plots of WD and PWD of various types of aircraft to illustrate the classification advantages of the approach at any aspect angle. They also show analogous results for metallic objects buried underground, in dielectric media, at various depths.« less

Phonons in a magnetized Coulomb crystal of ions with polarizable electron background

NASA Astrophysics Data System (ADS)

Baiko, D. A.; Kozhberov, A. A.

2017-11-01

We have studied phonon modes of a body-centered cubic (bcc) Coulomb crystal of ions in the presence of a uniform magnetic field B taking into account the polarizability of the electron background (electron screening) described by the Thomas-Fermi formalism. For k ≫κTF (k and κTF are the phonon wavevector and Thomas-Fermi wavenumber, respectively), electron polarizability is not important. At k ≪κTF , the electron response results in a pronounced effect. One of the three available modes is acoustic. For orthogonal propagation ( k ⊥B ), its frequency Ω is independent of B and κTF . For k ∥B , Ω∝1 /κTF and is independent of B. Another mode is quadratic. Its frequency is ∝1 /(B κTF) for orthogonal propagation and ∝1 /B and independent of κTF for the parallel case. The third mode is optic with Ω≈ωB ( ωB is the ion cyclotron frequency). A general expression is derived for the dynamic matrix of a Coulomb crystal with a polarizable background and more than one ion in the primitive cell. It is employed for a study of a magnetized hexagonal close-packed Coulomb crystal. We have also presented an analysis of phonon polarization vectors in a magnetized bcc crystal with or without screening. The results obtained can be used for realistic calculations of electron-phonon scattering rates and electron thermal and electrical conductivities in neutron star crusts.

Transcription factor target site search and gene regulation in a background of unspecific binding sites.

PubMed

Hettich, J; Gebhardt, J C M

2018-06-02

Response time and transcription level are vital parameters of gene regulation. They depend on how fast transcription factors (TFs) find and how efficient they occupy their specific target sites. It is well known that target site search is accelerated by TF binding to and sliding along unspecific DNA and that unspecific associations alter the occupation frequency of a gene. However, whether target site search time and occupation frequency can be optimized simultaneously is mostly unclear. We developed a transparent and intuitively accessible state-based formalism to calculate search times to target sites on and occupation frequencies of promoters of arbitrary state structure. Our formalism is based on dissociation rate constants experimentally accessible in live cell experiments. To demonstrate our approach, we consider promoters activated by a single TF, by two coactivators or in the presence of a competitive inhibitor. We find that target site search time and promoter occupancy differentially vary with the unspecific dissociation rate constant. Both parameters can be harmonized by adjusting the specific dissociation rate constant of the TF. However, while measured DNA residence times of various eukaryotic TFs correspond to a fast search time, the occupation frequencies of target sites are generally low. Cells might tolerate low target site occupancies as they enable timely gene regulation in response to a changing environment. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Temperature and chain length dependence of ultrafast vibrational dynamics of thiocyanate in alkylimidazolium ionic liquids: A random walk on a rugged energy landscape.

PubMed

Brinzer, Thomas; Garrett-Roe, Sean

2017-11-21

Ultrafast two-dimensional infrared spectroscopy of a thiocyanate vibrational probe (SCN - ) was used to investigate local dynamics in alkylimidazolium bis-[trifluoromethylsulfonyl]imide ionic liquids ([Im n,1 ][Tf 2 N], n = 2, 4, 6) at temperatures from 5 to 80 °C. The rate of frequency fluctuations reported by SCN - increases with increasing temperature and decreasing alkyl chain length. Temperature-dependent correlation times scale proportionally to temperature-dependent bulk viscosities of each ionic liquid studied. A multimode Brownian oscillator model demonstrates that very low frequency (<10 cm -1 ) modes primarily drive the observed spectral diffusion and that these modes broaden and blue shift on average with increasing temperature. An Arrhenius analysis shows activation barriers for local motions around the probe between 5.5 and 6.5 kcal/mol that are very similar to those for translational diffusion of ions. [Im 6,1 ][Tf 2 N] shows an unexpected decrease in activation energy compared to [Im 4,1 ][Tf 2 N] that may be related to mesoscopically ordered polar and nonpolar domains. A model of dynamics on a rugged potential energy landscape provides a unifying description of the observed Arrhenius behavior and the Brownian oscillator model of the low frequency modes.

Pressure effect on spin-glass behavior in Ce0.9Er0.1Al2

NASA Astrophysics Data System (ADS)

Wakiya, Kazuhei; Hu, Guanghui; Fuseya, Ryohei; Ohashi, Masashi; Uehara, Masatomo; Umehara, Izuru

2018-05-01

The dc magnetization and ac susceptibility of the Laves phase compound Ce0.9Er0.1Al2 have been measured at ambient and high pressures up to 1.1 GPa. The ac susceptibility shows a peak at around Tf 2.5 K, and Tf shifts to higher temperatures with an increase in the measuring frequency. Below Tf, the zero-field-cooled (ZFC) and field-cooled (FC) dc magnetizations separate from each other. Furthermore, long-time magnetic relaxation behavior is observed. These results indicate that a spin-glass state is formed below Tf. We found that the Tf determined by dc magnetization measurement decreases with an increase in pressure.

Catalog of Simulation Models and Wargames Used for Unit and Leader Training. Second Edition.

DTIC Science & Technology

1987-01-01

College; two or three brigade level games per year at brigade groups. In past - have played corps level games at Canadian Forces Command and Staff College...dedicated PERQ microcomputer Data Output Analysis: 5 minutes (generation of killer/victim scoreboard) Frequency of use: 4 times per year Users: HEL...classification: UNCLASSIFIED Frequency of use: 3 plays per year . Users: Training Gps, TF HQ and Infantry Centre. (The p. settings are changed to suit each

Separable processes before, during, and after the N400 elicited by previously inferred and new information: evidence from time-frequency decompositions.

PubMed

Steele, Vaughn R; Bernat, Edward M; van den Broek, Paul; Collins, Paul F; Patrick, Christopher J; Marsolek, Chad J

2013-01-25

Successful comprehension during reading often requires inferring information not explicitly presented. This information is readily accessible when subsequently encountered, and a neural correlate of this is an attenuation of the N400 event-related potential (ERP). We used ERPs and time-frequency (TF) analysis to investigate neural correlates of processing inferred information after a causal coherence inference had been generated during text comprehension. Participants read short texts, some of which promoted inference generation. After each text, they performed lexical decisions to target words that were unrelated or inference-related to the preceding text. Consistent with previous findings, inference-related words elicited an attenuated N400 relative to unrelated words. TF analyses revealed unique contributions to the N400 from activity occurring at 1-6 Hz (theta) and 0-2 Hz (delta), supporting the view that multiple, sequential processes underlie the N400. Copyright © 2012 Elsevier B.V. All rights reserved.

Single Channel EEG Artifact Identification Using Two-Dimensional Multi-Resolution Analysis.

PubMed

Taherisadr, Mojtaba; Dehzangi, Omid; Parsaei, Hossein

2017-12-13

As a diagnostic monitoring approach, electroencephalogram (EEG) signals can be decoded by signal processing methodologies for various health monitoring purposes. However, EEG recordings are contaminated by other interferences, particularly facial and ocular artifacts generated by the user. This is specifically an issue during continuous EEG recording sessions, and is therefore a key step in using EEG signals for either physiological monitoring and diagnosis or brain-computer interface to identify such artifacts from useful EEG components. In this study, we aim to design a new generic framework in order to process and characterize EEG recording as a multi-component and non-stationary signal with the aim of localizing and identifying its component (e.g., artifact). In the proposed method, we gather three complementary algorithms together to enhance the efficiency of the system. Algorithms include time-frequency (TF) analysis and representation, two-dimensional multi-resolution analysis (2D MRA), and feature extraction and classification. Then, a combination of spectro-temporal and geometric features are extracted by combining key instantaneous TF space descriptors, which enables the system to characterize the non-stationarities in the EEG dynamics. We fit a curvelet transform (as a MRA method) to 2D TF representation of EEG segments to decompose the given space to various levels of resolution. Such a decomposition efficiently improves the analysis of the TF spaces with different characteristics (e.g., resolution). Our experimental results demonstrate that the combination of expansion to TF space, analysis using MRA, and extracting a set of suitable features and applying a proper predictive model is effective in enhancing the EEG artifact identification performance. We also compare the performance of the designed system with another common EEG signal processing technique-namely, 1D wavelet transform. Our experimental results reveal that the proposed method outperforms 1D wavelet.

Evidence for two transferrin loci in the Salmo trutta genome.

PubMed

Rozman, T; Dovc, P; Marić, S; Kokalj-Vokac, N; Erjavec-Skerget, A; Rab, P; Snoj, A

2008-12-01

To determine the organization of transferrin (TF) locus in the Salmo trutta genome, partial DNA and cDNA sequencing, fluorescent in situ hybridization (FISH) and Salmo salar BAC analysis were performed. TF expression levels and copy number prediction were assessed using real-time PCR. In addition to two previously reported DNA TF variant sequences of S. trutta and Salmo marmoratus (TF1), two novel variant sequences (TF2) were revealed in both species. Variant-specific sequence tags, characterizing two variants for each TF type (TF1 and TF2), were identified in genomic clones from each of the F1 hybrids between S. trutta and S. marmoratus. These clearly documented double heterozygote status at the TF loci. The real-time PCR data showed that each of the two TF types (TF1 and TF2) existed in one copy only and that the transcription of TF2 was considerably lower compared with TF1. Using FISH, hybridization signals were observed on two medium-sized acrocentric chromosomes of S. trutta karyotype. A TF type-specific PCR followed by a restriction analysis revealed the presence of two TF loci in the majority of analysed BAC clones. It was concluded that the TF gene is duplicated in the genome of S. trutta, and that the two TF loci are located adjacent to one another on the same chromosome. The differing transcription levels of TF1 and TF2 appear to depend on the corresponding promoter activity, which at least for TF2 seems to vary between different Salmo congeners.

tf_unet: Generic convolutional neural network U-Net implementation in Tensorflow

NASA Astrophysics Data System (ADS)

Akeret, Joel; Chang, Chihway; Lucchi, Aurelien; Refregier, Alexandre

2016-11-01

tf_unet mitigates radio frequency interference (RFI) signals in radio data using a special type of Convolutional Neural Network, the U-Net, that enables the classification of clean signal and RFI signatures in 2D time-ordered data acquired from a radio telescope. The code is not tied to a specific segmentation and can be used, for example, to detect radio frequency interference (RFI) in radio astronomy or galaxies and stars in widefield imaging data. This U-Net implementation can outperform classical RFI mitigation algorithms.

Vibrational spectra from atomic fluctuations in dynamics simulations. II. Solvent-induced frequency fluctuations at femtosecond time resolution

NASA Astrophysics Data System (ADS)

Schmitz, Matthias; Tavan, Paul

2004-12-01

The midinfrared (MIR) spectra of molecules in polar solvents exhibit inhomogeneously broadened bands whose spectral positions are shifted as compared to the gas phase. The shifts are caused by interactions with structured solvation shells and the broadenings by fluctuations of these interactions. The MIR spectra can be calculated from hybrid molecular dynamics (MD) simulations, which treat the solute molecule by density functional theory and the solvent by molecular mechanics by the so-called instantaneous normal mode analysis (INMA) or by Fourier transforming the time correlation function (FTTCF) of the molecular dipole moment. In Paper I of this work [M. Schmitz and P. Tavan, J. Chem. Phys. 121, 12233 (2004)] we explored an alternative method based on generalized virial (GV) frequencies noting, however, that GV systematically underestimates frequencies. As shown by us these artifacts are caused by solvent-induced fluctuations of the (i) equilibrium geometry, (ii) force constants, and (iii) normal mode directions as well as by (iv) diagonal and (v) off-diagonal anharmonicities. Here we now show, by analyzing the time scales of fluctuations and sample MD trajectories of formaldehyde in the gas phase and in water, that all these sources of computational artifacts can be made visible by a Fourier analysis of the normal coordinates. Correspondingly, the error sources (i) and (iii)-(v) can be removed by bandpass filtering, as long as the spectral signatures of the respective effects are well separated from the fundamental band. Furthermore, the artifacts arising from effect (ii) can be strongly diminished by a time-resolved version of the GV approach (TF-GV). The TF-GV method then yields for each mode j a trajectory of the vibrational frequency ωj(t|τ) at a time resolution τ>τj, which is only limited by the corresponding oscillation time τj=2π/ωj and, thus, is in the femtosecond range. A correlation analysis of these trajectories clearly separates the librational motions from the conformational dynamics of the solvation shells and yields the inhomogeneously broadened MIR spectra, if the theory of motional narrowing is properly included. The MIR spectrum of formaldehyde in solution obtained by TF-GV agrees very well with the FTTCF result, if one applies the so-called "harmonic approximation" quantum correction factor and a temperature scaling to the FTTCF intensities. Also for INMA an excellent agreement is achieved if one disregards a slight INMA overestimate of linewidths.

A Chrysodeixis chalcites Single-Nucleocapsid Nucleopolyhedrovirus Population from the Canary Islands Is Genotypically Structured To Maximize Survival

PubMed Central

Bernal, Alexandra; Simón, Oihane; Williams, Trevor; Muñoz, Delia

2013-01-01

A Chrysodeixis chalcites single-nucleocapsid nucleopolyhedrovirus wild-type isolate from the Canary Islands, Spain, named ChchSNPV-TF1 (ChchTF1-wt), appears to have great potential as the basis for a biological insecticide for control of the pest. An improved understanding of the genotypic structure of this wild-type strain population should facilitate the selection of genotypes for inclusion in a bioinsecticidal product. Eight genetically distinct genotypes were cloned in vitro: ChchTF1-A to ChchTF1-H. Quantitative real-time PCR (qPCR) analysis confirmed that ChchTF1-A accounted for 36% of the genotypes in the wild-type population. In bioassays, ChchTF1-wt occlusion bodies (OBs) were significantly more pathogenic than any of the component single-genotype OBs, indicating that genotype interactions were likely responsible for the pathogenicity phenotype of wild-type OBs. However, the wild-type population was slower killing and produced higher OB yields than any of the single genotypes alone. These results strongly suggested that the ChchTF1-wt population is structured to maximize its transmission efficiency. Experimental OB mixtures and cooccluded genotype mixtures containing the most abundant and the rarest genotypes, at frequencies similar to those at which they were isolated, revealed a mutualistic interaction that restored the pathogenicity of OBs. In OB and cooccluded mixtures containing only the most abundant genotypes, ChchTF1-ABC, OB pathogenicity was even greater than that of wild-type OBs. The ChchTF1-ABC cooccluded mixture killed larvae 33 h faster than the wild-type population and remained genotypically and biologically stable throughout five successive passages in vivo. In conclusion, the ChchTF1-ABC mixture shows great potential as the active ingredient of a bioinsecticide to control C. chalcites in the Canary Islands. PMID:24096419

Neuromuscular fatigue and recovery dynamics following prolonged continuous run at anaerobic threshold.

PubMed

Skof, B; Strojnik, V

2006-03-01

The aim of this study was to determine the influence of intensive aerobic running on some muscle contractile characteristics and the dynamics of their recovery during a 2 hour period afterwards. Seven well trained runners performed a 6 km run at anaerobic threshold (V(OBLA)). Knee torque during single twitch, low and high frequency electrical stimulation (ES), maximum voluntary knee extension, and muscle activation level test of the quadriceps femoris muscles were measured before and immediately after the run, and at several time points during a 120 minute interval that followed the run. After exercise, the mean (SE) maximum twitch torque (T(TW)) and torque at ES with 20 Hz (low frequency ES; T(F20)) dropped by 14.1 (5.1)% (p<0.05) and 20.6 (7.9)% (p<0.05) respectively, while torque at stimulation with 100 Hz (high frequency ES; T(F100)), maximum isometric knee extension torque (maximum voluntary contraction torque; T(MVC)), and activation level did not change significantly. Twitch contraction time was shortened by 8 (2)% (p<0.05). Ten minutes after the run, T(TW) was 40% higher than immediately after the run and 10% (p<0.05) higher than before the run. T(F20), T(F100), and T(MVC) remained lower for 60 minutes (p<0.05) than before the run. A 6 km continuous run at V(OBLA) caused peripheral fatigue by impairing excitation-contraction coupling. Twitch torque recovered very quickly. However, the process of torque restoration at maximum isometric knee extension torque and at high and low frequency ES took much longer.

Research on the Sensing Performance of the Tuning Fork-Probe as a Micro Interaction Sensor

PubMed Central

Gao, Fengli; Li, Xide

2015-01-01

The shear force position system has been widely used in scanning near-field optical microscopy (SNOM) and recently extended into the force sensing area. The dynamic properties of a tuning fork (TF), the core component of this system, directly determine the sensing performance of the shear positioning system. Here, we combine experimental results and finite element method (FEM) analysis to investigate the dynamic behavior of the TF probe assembled structure (TF-probe). Results from experiments under varying atmospheric pressures illustrate that the oscillation amplitude of the TF-probe is linearly related to the quality factor, suggesting that decreasing the pressure will dramatically increase the quality factor. The results from FEM analysis reveal the influences of various parameters on the resonant performance of the TF-probe. We compared numerical results of the frequency spectrum with the experimental data collected by our recently developed laser Doppler vibrometer system. Then, we investigated the parameters affecting spatial resolution of the SNOM and the dynamic response of the TF-probe under longitudinal and transverse interactions. It is found that the interactions in transverse direction is much more sensitive than that in the longitudinal direction. Finally, the TF-probe was used to measure the friction coefficient of a silica–silica interface. PMID:26404310

Research on aviation unsafe incidents classification with improved TF-IDF algorithm

NASA Astrophysics Data System (ADS)

Wang, Yanhua; Zhang, Zhiyuan; Huo, Weigang

2016-05-01

The text content of Aviation Safety Confidential Reports contains a large number of valuable information. Term frequency-inverse document frequency algorithm is commonly used in text analysis, but it does not take into account the sequential relationship of the words in the text and its role in semantic expression. According to the seven category labels of civil aviation unsafe incidents, aiming at solving the problems of TF-IDF algorithm, this paper improved TF-IDF algorithm based on co-occurrence network; established feature words extraction and words sequential relations for classified incidents. Aviation domain lexicon was used to improve the accuracy rate of classification. Feature words network model was designed for multi-documents unsafe incidents classification, and it was used in the experiment. Finally, the classification accuracy of improved algorithm was verified by the experiments.

Time-frequency vibration analysis for the detection of motor damages caused by bearing currents

NASA Astrophysics Data System (ADS)

Prudhom, Aurelien; Antonino-Daviu, Jose; Razik, Hubert; Climente-Alarcon, Vicente

2017-02-01

Motor failure due to bearing currents is an issue that has drawn an increasing industrial interest over recent years. Bearing currents usually appear in motors operated by variable frequency drives (VFD); these drives may lead to common voltage modes which cause currents induced in the motor shaft that are discharged through the bearings. The presence of these currents may lead to the motor bearing failure only few months after system startup. Vibration monitoring is one of the most common ways for detecting bearing damages caused by circulating currents; the evaluation of the amplitudes of well-known characteristic components in the vibration Fourier spectrum that are associated with race, ball or cage defects enables to evaluate the bearing condition and, hence, to identify an eventual damage due to bearing currents. However, the inherent constraints of the Fourier transform may complicate the detection of the progressive bearing degradation; for instance, in some cases, other frequency components may mask or be confused with bearing defect-related while, in other cases, the analysis may not be suitable due to the eventual non-stationary nature of the captured vibration signals. Moreover, the fact that this analysis implies to lose the time-dimension limits the amount of information obtained from this technique. This work proposes the use of time-frequency (T-F) transforms to analyse vibration data in motors affected by bearing currents. The experimental results obtained in real machines show that the vibration analysis via T-F tools may provide significant advantages for the detection of bearing current damages; among other, these techniques enable to visualise the progressive degradation of the bearing while providing an effective discrimination versus other components that are not related with the fault. Moreover, their application is valid regardless of the operation regime of the machine. Both factors confirm the robustness and reliability of these tools that may be an interesting alternative for detecting this type of failure in induction motors.

Toward an Improvement of the Analysis of Neural Coding.

PubMed

Alegre-Cortés, Javier; Soto-Sánchez, Cristina; Albarracín, Ana L; Farfán, Fernando D; Val-Calvo, Mikel; Ferrandez, José M; Fernandez, Eduardo

2017-01-01

Machine learning and artificial intelligence have strong roots on principles of neural computation. Some examples are the structure of the first perceptron, inspired in the retina, neuroprosthetics based on ganglion cell recordings or Hopfield networks. In addition, machine learning provides a powerful set of tools to analyze neural data, which has already proved its efficacy in so distant fields of research as speech recognition, behavioral states classification, or LFP recordings. However, despite the huge technological advances in neural data reduction of dimensionality, pattern selection, and clustering during the last years, there has not been a proportional development of the analytical tools used for Time-Frequency (T-F) analysis in neuroscience. Bearing this in mind, we introduce the convenience of using non-linear, non-stationary tools, EMD algorithms in particular, for the transformation of the oscillatory neural data (EEG, EMG, spike oscillations…) into the T-F domain prior to its analysis with machine learning tools. We support that to achieve meaningful conclusions, the transformed data we analyze has to be as faithful as possible to the original recording, so that the transformations forced into the data due to restrictions in the T-F computation are not extended to the results of the machine learning analysis. Moreover, bioinspired computation such as brain-machine interface may be enriched from a more precise definition of neuronal coding where non-linearities of the neuronal dynamics are considered.

High frequency dynamic engine simulation. [TF-30 engine

NASA Technical Reports Server (NTRS)

Schuerman, J. A.; Fischer, K. E.; Mclaughlin, P. W.

1977-01-01

A digital computer simulation of a mixed flow, twin spool turbofan engine was assembled to evaluate and improve the dynamic characteristics of the engine simulation to disturbance frequencies of at least 100 Hz. One dimensional forms of the dynamic mass, momentum and energy equations were used to model the engine. A TF30 engine was simulated so that dynamic characteristics could be evaluated against results obtained from testing of the TF30 engine at the NASA Lewis Research Center. Dynamic characteristics of the engine simulation were improved by modifying the compression system model. Modifications to the compression system model were established by investigating the influence of size and number of finite dynamic elements. Based on the results of this program, high frequency engine simulations using finite dynamic elements can be assembled so that the engine dynamic configuration is optimum with respect to dynamic characteristics and computer execution time. Resizing of the compression systems finite elements improved the dynamic characteristics of the engine simulation but showed that additional refinements are required to obtain close agreement simulation and actual engine dynamic characteristics.

An adaptation method to improve secret key rates of time-frequency QKD in atmospheric turbulence channels

NASA Astrophysics Data System (ADS)

Sun, Xiaole; Djordjevic, Ivan B.; Neifeld, Mark A.

2016-03-01

Free-space optical (FSO) channels can be characterized by random power fluctuations due to atmospheric turbulence, which is known as scintillation. Weak coherent source based FSO quantum key distribution (QKD) systems suffer from the scintillation effect because during the deep channel fading the expected detection rate drops, which then gives an eavesdropper opportunity to get additional information about protocol by performing photon number splitting (PNS) attack and blocking single-photon pulses without changing QBER. To overcome this problem, in this paper, we study a large-alphabet QKD protocol, which is achieved by using pulse-position modulation (PPM)-like approach that utilizes the time-frequency uncertainty relation of the weak coherent photon state, called here TF-PPM-QKD protocol. We first complete finite size analysis for TF-PPM-QKD protocol to give practical bounds against non-negligible statistical fluctuation due to finite resources in practical implementations. The impact of scintillation under strong atmospheric turbulence regime is studied then. To overcome the secure key rate performance degradation of TF-PPM-QKD caused by scintillation, we propose an adaptation method for compensating the scintillation impact. By changing source intensity according to the channel state information (CSI), obtained by classical channel, the adaptation method improves the performance of QKD system with respect to the secret key rate. The CSI of a time-varying channel can be predicted using stochastic models, such as autoregressive (AR) models. Based on the channel state predictions, we change the source intensity to the optimal value to achieve a higher secret key rate. We demonstrate that the improvement of the adaptation method is dependent on the prediction accuracy.

Quantitative and descriptive comparison of four acoustic analysis systems: vowel measurements.

PubMed

Burris, Carlyn; Vorperian, Houri K; Fourakis, Marios; Kent, Ray D; Bolt, Daniel M

2014-02-01

This study examines accuracy and comparability of 4 trademarked acoustic analysis software packages (AASPs): Praat, WaveSurfer, TF32, and CSL by using synthesized and natural vowels. Features of AASPs are also described. Synthesized and natural vowels were analyzed using each of the AASP's default settings to secure 9 acoustic measures: fundamental frequency (F0), formant frequencies (F1-F4), and formant bandwidths (B1-B4). The discrepancy between the software measured values and the input values (synthesized, previously reported, and manual measurements) was used to assess comparability and accuracy. Basic AASP features are described. Results indicate that Praat, WaveSurfer, and TF32 generate accurate and comparable F0 and F1-F4 data for synthesized vowels and adult male natural vowels. Results varied by vowel for women and children, with some serious errors. Bandwidth measurements by AASPs were highly inaccurate as compared with manual measurements and published data on formant bandwidths. Values of F0 and F1-F4 are generally consistent and fairly accurate for adult vowels and for some child vowels using the default settings in Praat, WaveSurfer, and TF32. Manipulation of default settings yields improved output values in TF32 and CSL. Caution is recommended especially before accepting F1-F4 results for children and B1-B4 results for all speakers.

Polymorphism, selection and tandem duplication of transferrin genes in Atlantic cod (Gadus morhua) - Conserved synteny between fish monolobal and tetrapod bilobal transferrin loci

PubMed Central

2011-01-01

Background The two homologous iron-binding lobes of transferrins are thought to have evolved by gene duplication of an ancestral monolobal form, but any conserved synteny between bilobal and monolobal transferrin loci remains unexplored. The important role played by transferrin in the resistance to invading pathogens makes this polymorphic gene a highly valuable candidate for studying adaptive divergence among local populations. Results The Atlantic cod genome was shown to harbour two tandem duplicated serum transferrin genes (Tf1, Tf2), a melanotransferrin gene (MTf), and a monolobal transferrin gene (Omp). Whereas Tf1 and Tf2 were differentially expressed in liver and brain, the Omp transcript was restricted to the otoliths. Fish, chicken and mammals showed highly conserved syntenic regions in which monolobal and bilobal transferrins reside, but contrasting with tetrapods, the fish transferrin genes are positioned on three different linkage groups. Sequence alignment of cod Tf1 cDNAs from Northeast (NE) and Northwest (NW) Atlantic populations revealed 22 single nucleotide polymorphisms (SNP) causing the replacement of 16 amino acids, including eight surface residues revealed by the modelled 3D-structures, that might influence the binding of pathogens for removal of iron. SNP analysis of a total of 375 individuals from 14 trans-Atlantic populations showed that the Tf1-NE variant was almost fixed in the Baltic cod and predominated in the other NE Atlantic populations, whereas the NW Atlantic populations were more heterozygous and showed high frequencies of the Tf-NW SNP alleles. Conclusions The highly conserved synteny between fish and tetrapod transferrin loci infers that the fusion of tandem duplicated Omp-like genes gave rise to the modern transferrins. The multiple nonsynonymous substitutions in cod Tf1 with putative structural effects, together with highly divergent allele frequencies among different cod populations, strongly suggest evidence for positive selection and local adaptation in trans-Atlantic cod populations. PMID:21612617

Polymorphism, selection and tandem duplication of transferrin genes in Atlantic cod (Gadus morhua)--conserved synteny between fish monolobal and tetrapod bilobal transferrin loci.

PubMed

Andersen, Øivind; De Rosa, Maria Cristina; Pirolli, Davide; Tooming-Klunderud, Ave; Petersen, Petra E; André, Carl

2011-05-25

The two homologous iron-binding lobes of transferrins are thought to have evolved by gene duplication of an ancestral monolobal form, but any conserved synteny between bilobal and monolobal transferrin loci remains unexplored. The important role played by transferrin in the resistance to invading pathogens makes this polymorphic gene a highly valuable candidate for studying adaptive divergence among local populations. The Atlantic cod genome was shown to harbour two tandem duplicated serum transferrin genes (Tf1, Tf2), a melanotransferrin gene (MTf), and a monolobal transferrin gene (Omp). Whereas Tf1 and Tf2 were differentially expressed in liver and brain, the Omp transcript was restricted to the otoliths. Fish, chicken and mammals showed highly conserved syntenic regions in which monolobal and bilobal transferrins reside, but contrasting with tetrapods, the fish transferrin genes are positioned on three different linkage groups. Sequence alignment of cod Tf1 cDNAs from Northeast (NE) and Northwest (NW) Atlantic populations revealed 22 single nucleotide polymorphisms (SNP) causing the replacement of 16 amino acids, including eight surface residues revealed by the modelled 3D-structures, that might influence the binding of pathogens for removal of iron. SNP analysis of a total of 375 individuals from 14 trans-Atlantic populations showed that the Tf1-NE variant was almost fixed in the Baltic cod and predominated in the other NE Atlantic populations, whereas the NW Atlantic populations were more heterozygous and showed high frequencies of the Tf-NW SNP alleles. The highly conserved synteny between fish and tetrapod transferrin loci infers that the fusion of tandem duplicated Omp-like genes gave rise to the modern transferrins. The multiple nonsynonymous substitutions in cod Tf1 with putative structural effects, together with highly divergent allele frequencies among different cod populations, strongly suggest evidence for positive selection and local adaptation in trans-Atlantic cod populations.

Extracting surface waves, hum and normal modes: time-scale phase-weighted stack and beyond

NASA Astrophysics Data System (ADS)

Ventosa, Sergi; Schimmel, Martin; Stutzmann, Eleonore

2017-10-01

Stacks of ambient noise correlations are routinely used to extract empirical Green's functions (EGFs) between station pairs. The time-frequency phase-weighted stack (tf-PWS) is a physically intuitive nonlinear denoising method that uses the phase coherence to improve EGF convergence when the performance of conventional linear averaging methods is not sufficient. The high computational cost of a continuous approach to the time-frequency transformation is currently a main limitation in ambient noise studies. We introduce the time-scale phase-weighted stack (ts-PWS) as an alternative extension of the phase-weighted stack that uses complex frames of wavelets to build a time-frequency representation that is much more efficient and fast to compute and that preserve the performance and flexibility of the tf-PWS. In addition, we propose two strategies: the unbiased phase coherence and the two-stage ts-PWS methods to further improve noise attenuation, quality of the extracted signals and convergence speed. We demonstrate that these approaches enable to extract minor- and major-arc Rayleigh waves (up to the sixth Rayleigh wave train) from many years of data from the GEOSCOPE global network. Finally we also show that fundamental spheroidal modes can be extracted from these EGF.

Externalizing psychopathology and gain-loss feedback in a simulated gambling task: dissociable components of brain response revealed by time-frequency analysis.

PubMed

Bernat, Edward M; Nelson, Lindsay D; Steele, Vaughn R; Gehring, William J; Patrick, Christopher J

2011-05-01

Externalizing is a broad construct that reflects propensity toward a variety of impulse control problems, including antisocial personality disorder and substance use disorders. Two event-related potential responses known to be reduced among individuals high in externalizing proneness are the P300, which reflects postperceptual processing of a stimulus, and the error-related negativity (ERN), which indexes performance monitoring based on endogenous representations. In the current study, the authors used a simulated gambling task to examine the relation between externalizing proneness and the feedback-related negativity (FRN), a brain response that indexes performance monitoring related to exogenous cues, which is thought to be highly related to the ERN. Time-frequency (TF) analysis was used to disentangle the FRN from the accompanying P300 response to feedback cues by parsing the overall feedback-locked potential into distinctive theta (4-7 Hz) and delta (<3 Hz) TF components. Whereas delta-P300 amplitude was reduced among individuals high in externalizing proneness, theta-FRN response was unrelated to externalizing. These findings suggest that in contrast with previously reported deficits in endogenously based performance monitoring (as indexed by the ERN), individuals prone to externalizing problems show intact monitoring of exogenous cues (as indexed by the FRN). The results also contribute to a growing body of evidence indicating that the P300 is attenuated across a broad range of task conditions in high-externalizing individuals.

Adaptive multimode signal reconstruction from time–frequency representations

PubMed Central

Meignen, Sylvain; Oberlin, Thomas; Depalle, Philippe; Flandrin, Patrick

2016-01-01

This paper discusses methods for the adaptive reconstruction of the modes of multicomponent AM–FM signals by their time–frequency (TF) representation derived from their short-time Fourier transform (STFT). The STFT of an AM–FM component or mode spreads the information relative to that mode in the TF plane around curves commonly called ridges. An alternative view is to consider a mode as a particular TF domain termed a basin of attraction. Here we discuss two new approaches to mode reconstruction. The first determines the ridge associated with a mode by considering the location where the direction of the reassignment vector sharply changes, the technique used to determine the basin of attraction being directly derived from that used for ridge extraction. A second uses the fact that the STFT of a signal is fully characterized by its zeros (and then the particular distribution of these zeros for Gaussian noise) to deduce an algorithm to compute the mode domains. For both techniques, mode reconstruction is then carried out by simply integrating the information inside these basins of attraction or domains. PMID:26953184

Phase Transitions of Triflate-Based Ionic Liquids under High Pressure.

PubMed

Faria, Luiz F O; Ribeiro, Mauro C C

2015-11-05

Raman spectroscopy has been used to study phase transitions of ionic liquids based on the triflate anion, [TfO](-), as a function of pressure or temperature. Raman spectra of ionic liquids containing the cations 1-butyl-3-methylimidazolium, [C4C1Im](+), 1-octyl-3-methylimidazolium, [C8C1Im](+), 1-butyl-2,3-dimethylimidazolium, [C4C1C1Im](+), and 1-butyl-1-methylpyrrolidinium, [C4C1Pyr](+), were compared. Vibrational frequencies and binding energy of ionic pairs were calculated by quantum chemistry methods. The ionic liquids [C4C1Im][TfO] and [C4C1Pyr][TfO] crystallize at 1.0 GPa when the pressure is increased in steps of ∼ 0.2 GPa from the atmospheric pressure, whereas [C8C1Im][TfO] and [C4C1C1Im][TfO] do not crystallize up to 2.3 GPa of applied pressure. The low-frequency range of the Raman spectrum of [C4C1Im][TfO] indicates that the system undergoes glass transition, rather than crystallization, when the pressure applied on the liquid has been increased above 2.0 GPa in a single step. Strong hysteresis of spectral features (frequency shift and bandwidth) of the high-pressure crystalline phase when the pressure was released stepwise back to the atmospheric pressure has been found .

Shear wave elastography using Wigner-Ville distribution: a simulated multilayer media study.

PubMed

Bidari, Pooya Sobhe; Alirezaie, Javad; Tavakkoli, Jahan

2016-08-01

Shear Wave Elastography (SWE) is a quantitative ultrasound-based imaging modality for distinguishing normal and abnormal tissue types by estimating the local viscoelastic properties of the tissue. These properties have been estimated in many studies by propagating ultrasound shear wave within the tissue and estimating parameters such as speed of wave. Vast majority of the proposed techniques are based on the cross-correlation of consecutive ultrasound images. In this study, we propose a new method of wave detection based on time-frequency (TF) analysis of the ultrasound signal. The proposed method is a modified version of the Wigner-Ville Distribution (WVD) technique. The TF components of the wave are detected in a propagating ultrasound wave within a simulated multilayer tissue and the local properties are estimated based on the detected waves. Image processing techniques such as Alternative Sequential Filters (ASF) and Circular Hough Transform (CHT) have been utilized to improve the estimation of TF components. This method has been applied to a simulated data from Wave3000™ software (CyberLogic Inc., New York, NY). This data simulates the propagation of an acoustic radiation force impulse within a two-layer tissue with slightly different viscoelastic properties between the layers. By analyzing the local TF components of the wave, we estimate the longitudinal and shear elasticities and viscosities of the media. This work shows that our proposed method is capable of distinguishing between different layers of a tissue.

Schizosaccharomyces pombe Retrotransposon Tf2 Mobilizes Primarily through Homologous cDNA Recombination

PubMed Central

Hoff, Eleanor F.; Levin, Henry L.; Boeke, Jef D.

1998-01-01

The Tf2 retrotransposon, found in the fission yeast Schizosaccharomyces pombe, is nearly identical to its sister element, Tf1, in its reverse transcriptase-RNase H and integrase domains but is very divergent in the gag domain, the protease, the 5′ untranslated region, and the U3 domain of the long terminal repeats. It has now been demonstrated that a neo-marked copy of Tf2 overexpressed from a heterologous promoter can mobilize into the S. pombe genome and produce true transposition events. However, the Tf2-neo mobilization frequency is 10- to 20-fold lower than that of Tf1-neo, and 70% of the Tf2-neo events are homologous recombination events generated independently of a functional Tf2 integrase. Thus, the Tf2 element is primarily dependent on homologous recombination with preexisting copies of Tf2 for its propagation. Finally, production of Tf2-neo proteins and cDNA was also analyzed; surprisingly, Tf2 was found to produce its reverse transcriptase as a single species in which it is fused to protease, unlike all other retroviruses and retrotransposons. PMID:9774697

The Islamic State Battle Plan: Press Release Natural Language Processing

DTIC Science & Technology

2016-06-01

Processing, text mining , corpus, generalized linear model, cascade, R Shiny, leaflet, data visualization 15. NUMBER OF PAGES 83 16. PRICE CODE...Terrorism and Responses to Terrorism TDM Term Document Matrix TF Term Frequency TF-IDF Term Frequency-Inverse Document Frequency tm text mining (R...package=leaflet. Feinerer I, Hornik K (2015) Text Mining Package “tm,” Version 0.6-2. (Jul 3) https://cran.r-project.org/web/packages/tm/tm.pdf

Transcriptome-wide profiling and expression analysis of transcription factor families in a liverwort, Marchantia polymorpha

PubMed Central

2013-01-01

Background Transcription factors (TFs) are vital elements that regulate transcription and the spatio-temporal expression of genes, thereby ensuring the accurate development and functioning of an organism. The identification of TF-encoding genes in a liverwort, Marchantia polymorpha, offers insights into TF organization in the members of the most basal lineages of land plants (embryophytes). Therefore, a comparison of Marchantia TF genes with other land plants (monocots, dicots, bryophytes) and algae (chlorophytes, rhodophytes) provides the most comprehensive view of the rates of expansion or contraction of TF genes in plant evolution. Results In this study, we report the identification of TF-encoding transcripts in M. polymorpha for the first time, as evidenced by deep RNA sequencing data. In total, 3,471 putative TF encoding transcripts, distributed in 80 families, were identified, representing 7.4% of the generated Marchantia gametophytic transcriptome dataset. Overall, TF basic functions and distribution across families appear to be conserved when compared to other plant species. However, it is of interest to observe the genesis of novel sequences in 24 TF families and the apparent termination of 2 TF families with the emergence of Marchantia. Out of 24 TF families, 6 are known to be associated with plant reproductive development processes. We also examined the expression pattern of these TF-encoding transcripts in six male and female developmental stages in vegetative and reproductive gametophytic tissues of Marchantia. Conclusions The analysis highlighted the importance of Marchantia, a model plant system, in an evolutionary context. The dataset generated here provides a scientific resource for TF gene discovery and other comparative evolutionary studies of land plants. PMID:24365221

Estimation of Theaflavins (TF) and Thearubigins (TR) Ratio in Black Tea Liquor Using Electronic Vision System

NASA Astrophysics Data System (ADS)

Akuli, Amitava; Pal, Abhra; Ghosh, Arunangshu; Bhattacharyya, Nabarun; Bandhopadhyya, Rajib; Tamuly, Pradip; Gogoi, Nagen

2011-09-01

Quality of black tea is generally assessed using organoleptic tests by professional tea tasters. They determine the quality of black tea based on its appearance (in dry condition and during liquor formation), aroma and taste. Variation in the above parameters is actually contributed by a number of chemical compounds like, Theaflavins (TF), Thearubigins (TR), Caffeine, Linalool, Geraniol etc. Among the above, TF and TR are the most important chemical compounds, which actually contribute to the formation of taste, colour and brightness in tea liquor. Estimation of TF and TR in black tea is generally done using a spectrophotometer instrument. But, the analysis technique undergoes a rigorous and time consuming effort for sample preparation; also the operation of costly spectrophotometer requires expert manpower. To overcome above problems an Electronic Vision System based on digital image processing technique has been developed. The system is faster, low cost, repeatable and can estimate the amount of TF and TR ratio for black tea liquor with accuracy. The data analysis is done using Principal Component Analysis (PCA), Multiple Linear Regression (MLR) and Multiple Discriminate Analysis (MDA). A correlation has been established between colour of tea liquor images and TF, TR ratio. This paper describes the newly developed E-Vision system, experimental methods, data analysis algorithms and finally, the performance of the E-Vision System as compared to the results of traditional spectrophotometer.

Word Frequency Analysis. MOS: 16P. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

8217 ALSC1 ALP ESECATE I API’LYI A-129 I AjI ~ AS-L-%/VIC I ATTAIN I1As~L2r v L% WORO FAeQUIEN#rM r Tf~16O RIATE 80142 131? PACE 3 I AV-@ ____ I...ENOJ 21..i~u. 191.4PME 21MAV UOi.~lO51’.iNEe;W~1CA2SP1tF4i H4PiI**IAPI C, 4DS-I*~4A5-II..... ROJOS 1.....9 PM4 21 MY §So.OOH 512 CH.PN~𔄁..IAR

Term frequency - function of document frequency: a new term weighting scheme for enterprise information retrieval

NASA Astrophysics Data System (ADS)

Zhang, Hui; Wang, Deqing; Wu, Wenjun; Hu, Hongping

2012-11-01

In today's business environment, enterprises are increasingly under pressure to process the vast amount of data produced everyday within enterprises. One method is to focus on the business intelligence (BI) applications and increasing the commercial added-value through such business analytics activities. Term weighting scheme, which has been used to convert the documents as vectors in the term space, is a vital task in enterprise Information Retrieval (IR), text categorisation, text analytics, etc. When determining term weight in a document, the traditional TF-IDF scheme sets weight value for the term considering only its occurrence frequency within the document and in the entire set of documents, which leads to some meaningful terms that cannot get the appropriate weight. In this article, we propose a new term weighting scheme called Term Frequency - Function of Document Frequency (TF-FDF) to address this issue. Instead of using monotonically decreasing function such as Inverse Document Frequency, FDF presents a convex function that dynamically adjusts weights according to the significance of the words in a document set. This function can be manually tuned based on the distribution of the most meaningful words which semantically represent the document set. Our experiments show that the TF-FDF can achieve higher value of Normalised Discounted Cumulative Gain in IR than that of TF-IDF and its variants, and improving the accuracy of relevance ranking of the IR results.

Qualitative and Quantitative Assays of Transposition and Homologous Recombination of the Retrotransposon Tf1 in Schizosaccharomyces pombe.

PubMed

Sangesland, Maya; Atwood-Moore, Angela; Rai, Sudhir K; Levin, Henry L

2016-01-01

Transposition and homologous recombination assays are valuable genetic tools to measure the production and integration of cDNA from the long terminal repeat (LTR) retrotransposon Tf1 in the fission yeast (Schizosaccharomyces pombe). Here we describe two genetic assays, one that measures the transposition activity of Tf1 by monitoring the mobility of a drug resistance marked Tf1 element expressed from a multi-copy plasmid and another assay that measures homologous recombination between Tf1 cDNA and the expression plasmid. While the transposition assay measures insertion of full-length Tf1 cDNA mediated by the transposon integrase, the homologous recombination assay measures levels of cDNA present in the nucleus and is independent of integrase activity. Combined, these assays can be used to systematically screen large collections of strains to identify mutations that specifically inhibit the integration step in the retroelement life cycle. Such mutations can be identified because they reduce transposition activity but nevertheless have wild-type frequencies of homologous recombination. Qualitative assays of yeast patches on agar plates detect large defects in integration and recombination, while the quantitative approach provides a precise method of determining integration and recombination frequencies.

Dynamic fiber Bragg grating strain sensor interrogation with real-time measurement

NASA Astrophysics Data System (ADS)

Park, Jinwoo; Kwon, Yong Seok; Ko, Myeong Ock; Jeon, Min Yong

2017-11-01

We demonstrate a 1550 nm band resonance Fourier-domain mode-locked (FDML) fiber laser with fiber Bragg grating (FBG) array. Using the FDML fiber laser, we successfully demonstrate real-time monitoring of dynamic FBG strain sensor interrogation for structural health monitoring. The resonance FDML fiber laser consists of six multiplexed FBGs, which are arranged in series with delay fiber lengths. It is operated by driving the fiber Fabry-Perot tunable filter (FFP-TF) with a sinusoidal waveform at a frequency corresponding to the round-trip time of the laser cavity. Each FBG forms a laser cavity independently in the FDML fiber laser because the light travels different length for each FBG. The very closely positioned two FBGs in a pair are operated simultaneously with a frequency in the FDML fiber laser. The spatial positions of the sensing pair can be distinguished from the variation of the applied frequency to the FFP-TF. One of the FBGs in the pair is used as a reference signal and the other one is fixed on the piezoelectric transducer stack to apply the dynamic strain. We successfully achieve real-time measurement of the abrupt change of the frequencies applied to the FBG without any signal processing delay. The real-time monitoring system is displayed simultaneously on the monitor for the variation of the two peaks, the modulation interval of the two peaks, and their fast Fourier transform spectrum. The frequency resolution of the dynamic variation could reach up to 0.5 Hz for 2 s integration time. It depends on the integration time to measure the dynamic variation. We believe that the real-time monitoring system will have a potential application for structural health monitoring.

Low noise erbium fiber fs frequency comb based on a tapered-fiber carbon nanotube design.

PubMed

Wu, Tsung-Han; Kieu, K; Peyghambarian, N; Jones, R J

2011-03-14

We report on a low noise all-fiber erbium fs frequency comb based on a simple and robust tapered-fiber carbon nanotube (tf-CNT) design. We mitigate dominant noise sources to show that the free-running linewidth of the carrier-envelope offset frequency (fceo) can be comparable to the best reported performance to date for fiber-based frequency combs. A free-running fceo linewidth of ~20 kHz is demonstrated, corresponding to an improvement of ~30 times over previous work based on a CNT mode-locked fiber laser [Opt. Express 18, 1667 (2010)]. We also demonstrate the use of an acousto-optic modulator external to the laser cavity to stabilize fceo, enabling a 300 kHz feedback control bandwidth. The offset frequency is phase-locked with an in-loop integrated phase noise of ~0.8 rad from 10Hz to 400kHz. We show a resolution-limited linewidth of ~1 Hz, demonstrating over 90% of the carrier power within the coherent fceo signal. The results demonstrate that the relatively simple tf-CNT fiber laser design can provide a compact, robust and high-performance fs frequency comb.

Cognitive fiber Bragg grating sensors system based on fiber Fabry-Perot tunable filter technology

NASA Astrophysics Data System (ADS)

Zhang, Hongtao; Wang, Pengfei; Zou, Jilin; Xie, Jing; Cui, Hong-Liang

2011-05-01

The wavelength demodulation based on a Fiber Fabry-Pérot Tunable Filter (FFP-TF) is a common method for multiplexing Fiber Bragg Grating (FBG) sensors. But this method cannot be used to detect high frequency signals due to the limitation by the highest scanning rate that the FFP-TF can achieve. To overcome this disadvantage, in this paper we present a scheme of cognitive sensors network based on FFP-TF technology. By perceiving the sensing environment, system can automatically switch into monitoring signals in two modes to obtain better measurement results: multi measurement points, low frequency (<1 KHz) signal, and few measurement points but high frequency (~50 KHz) signals. This cognitive sensors network can be realized in current technology and satisfy current most industrial requirements.

Overview of Research Activities on Time and Frequency at the National Institute of Information and Communications Technology

DTIC Science & Technology

2004-12-01

FREQUENCY TRANSFER ( TWSTFT ) TWSTFT network in the Asia-Pacific region has developed by the collaboration of NICT and major T&F institutes in the...region [7]. A multi-channel TWSTFT modem has been developed by NICT. The performance evaluation shows that it is capable of sub-nanosecond time...intercomparison of NICT modem TWSTFT , ATLANTIS modem TWSTFT , and GPS common view (CV) in the case of the NICT-TL link is shown in Figure 4, and the stability

Implement trigger for a NI data acquisition card PCI 5105 in the measurement studio development environment for a high speed demodulator based on fiber Fabry-Pérot tunable filter (FFP-TF)

NASA Astrophysics Data System (ADS)

Zhang, Hongtao; Yang, Shangming; Fan, Lingling; Wang, Pengfei; Zhao, Xilin; Wang, Zhenhua; Cui, Hong-Liang

2010-04-01

In this paper we report a scheme of low-cost, small-size differential electrical converter to change analog trigger signals into digital trigger signals. This converter successfully resolves the incompatibility between the digital trigger mode of NI (National Instruments) data acquisition card PCI 5105 in Measurement Studio development environment for a demodulator and the requirement from instability of spectra of fiber Bragg grating (FBG) sensors. The instability is caused by intrinsic drifts of FFP-TF inside this high speed demodulator. The obtained results of frequency response about the converter have clearly demonstrated that this method is effective when the frequency of trigger signal is less than 3,000 Hz. This converter can satisfy the current requirements of demodulator based on FFP-TF, since mostly actual working scanning frequency of FFP-TF is less than 1,000 Hz. This method may be recommended to resolve similar problems for other NI customers who have developed their data acquisition system based on Measurement Studio.

Experimental Analysis of Heat Transfer Characteristics and Pressure Drop through Screen Regenerative Heat Exchangers

DTIC Science & Technology

1993-12-01

of fluid T1 initial temperature of matrix and fluid Tf1 average inlet temperature after the step change Tii average inlet temperature before the step...respectively, of the regenerator. The horizontal distances shown with Tf1 , Tj, and T,2 illustrate the time interval for which the average values were...temperature was not a true step function, the investigator made an approximation. The approximation was based on an average temperature. Tf1 was the

Optimizing Vowel Formant Measurements in Four Acoustic Analysis Systems for Diverse Speaker Groups

PubMed Central

Derdemezis, Ekaterini; Kent, Ray D.; Fourakis, Marios; Reinicke, Emily L.; Bolt, Daniel M.

2016-01-01

Purpose This study systematically assessed the effects of select linear predictive coding (LPC) analysis parameter manipulations on vowel formant measurements for diverse speaker groups using 4 trademarked Speech Acoustic Analysis Software Packages (SAASPs): CSL, Praat, TF32, and WaveSurfer. Method Productions of 4 words containing the corner vowels were recorded from 4 speaker groups with typical development (male and female adults and male and female children) and 4 speaker groups with Down syndrome (male and female adults and male and female children). Formant frequencies were determined from manual measurements using a consensus analysis procedure to establish formant reference values, and from the 4 SAASPs (using both the default analysis parameters and with adjustments or manipulations to select parameters). Smaller differences between values obtained from the SAASPs and the consensus analysis implied more optimal analysis parameter settings. Results Manipulations of default analysis parameters in CSL, Praat, and TF32 yielded more accurate formant measurements, though the benefit was not uniform across speaker groups and formants. In WaveSurfer, manipulations did not improve formant measurements. Conclusions The effects of analysis parameter manipulations on accuracy of formant-frequency measurements varied by SAASP, speaker group, and formant. The information from this study helps to guide clinical and research applications of SAASPs. PMID:26501214

Properties of magnetized Coulomb crystals of ions with polarizable electron background

NASA Astrophysics Data System (ADS)

Kozhberov, A. A.

2018-06-01

We have studied phonon and thermodynamic properties of a body-centered cubic (bcc) Coulomb crystal of ions with weakly polarized electron background in a uniform magnetic field B. At B = 0, the difference between phonon moments calculated using the Thomas-Fermi (TF) and random phase approximations is always less than 1% and for description of phonon properties of a crystal, TF formalism was used. This formalism was successfully applied to investigate thermodynamic properties of magnetized Coulomb crystals. It was shown that the influence of the polarization of the electron background is significant only at κ TF a > 0.1 and T ≪ T p ( 1 + h2 ) - 1 / 2 , where κTF is the Thomas-Fermi wavenumber, a is the ion sphere radius, T p ≡ ℏ ω p is the ion plasma temperature, h ≡ ω B / ω p , ωB is the ion cyclotron frequency, and ωp is the ion plasma frequency.

An algorithm that improves speech intelligibility in noise for normal-hearing listeners.

PubMed

Kim, Gibak; Lu, Yang; Hu, Yi; Loizou, Philipos C

2009-09-01

Traditional noise-suppression algorithms have been shown to improve speech quality, but not speech intelligibility. Motivated by prior intelligibility studies of speech synthesized using the ideal binary mask, an algorithm is proposed that decomposes the input signal into time-frequency (T-F) units and makes binary decisions, based on a Bayesian classifier, as to whether each T-F unit is dominated by the target or the masker. Speech corrupted at low signal-to-noise ratio (SNR) levels (-5 and 0 dB) using different types of maskers is synthesized by this algorithm and presented to normal-hearing listeners for identification. Results indicated substantial improvements in intelligibility (over 60% points in -5 dB babble) over that attained by human listeners with unprocessed stimuli. The findings from this study suggest that algorithms that can estimate reliably the SNR in each T-F unit can improve speech intelligibility.

Design of distributed FBG vibration measuring system based on Fabry-Perot tunable filter

NASA Astrophysics Data System (ADS)

Zhang, Cheng; Miao, Changyun; Li, Hongqiang; Gao, Hua; Gan, Jingmeng

2011-11-01

A distributed optical fiber grating wavelength interrogator based on fiber Fabry Perot tunable filter(FFP-TF) was proposed, which could measure dynamic strain or vibration of multi-sensing fiber gratings in one optical fiber by time division way. The wavelength demodulated mathematical model was built, the formulas of system output voltage and sensitivity were deduced and the method of finding static operating point was determined. The wavelength drifting characteristic of FFP-TF was discussed when the center wavelength of FFP-TF was set on the static operating point. A wavelength locking method was proposed by introducing a high-frequency driving voltage signal. A demodulated system was established based on Labview and its demodulated wavelength dynamic range is 290pm in theory. In experiment, by digital filtering applied to the system output data, 100Hz and 250Hz vibration signals were measured. The experiment results proved the feasibility of the demodulated method.

Comparison of transfemoral transcatheter aortic valve replacement performed in the catheterization laboratory (minimalist approach) versus hybrid operating room (standard approach): outcomes and cost analysis.

PubMed

Babaliaros, Vasilis; Devireddy, Chandan; Lerakis, Stamatios; Leonardi, Robert; Iturra, Sebastian A; Mavromatis, Kreton; Leshnower, Bradley G; Guyton, Robert A; Kanitkar, Mihir; Keegan, Patricia; Simone, Amy; Stewart, James P; Ghasemzadeh, Nima; Block, Peter; Thourani, Vinod H

2014-08-01

The aim of this study was to compare transfemoral transcatheter aortic valve replacement (TF TAVR) performed in a catheterization laboratory (minimalist approach [MA]) with TF TAVR performed in a hybrid operating room (standard approach [SA]). A MA-TF TAVR can be performed without general anesthesia, transesophageal echocardiography, or a surgical hybrid room. The outcomes and cost of MA-TF TAVR compared with those of the SA have not been described. Patients who underwent elective, percutaneous TF TAVR using the Edwards Sapien valve (Edwards Lifesciences, Irvine, California) were studied. Baseline characteristics, outcomes, and hospital costs of MA-TF TAVR and SA-TF TAVR were compared. A total of 142 patients were studied (MA-TF TAVR, n = 70 and SA-TF TAVR, n = 72). There were no differences in baseline comorbidities (Society of Thoracic Surgeons score, 10.6 ± 4.3 vs. 11.4 ± 5.8; p = 0.35). All procedures in the MA-TF TAVR group were successful; 1 patient was intubated. Three patients in the SA-TF TAVR group had procedure-related death. Procedure room time (150 ± 48 min vs. 218 ± 56 min, p < 0.001), total intensive care unit time (22 h vs. 28 h, p < 0.001), length of stay from procedure to discharge (3 days vs. 5 days, p < 0.001), and cost ($45,485 ± 14,397 vs. $55,377 ± 22,587, p < 0.001) were significantly less in the MA-TF TAVR group. Mortality at 30 days was not significantly different in the MA-TF TAVR group (0 vs. 6%, p = 0.12) and 30-day stroke/transient ischemic attack was similar (4.3% vs. 1.4%, p = 0.35). Moderate or severe paravalvular leak and device success were similar in the MA-TF TAVR and SA-TF TAVR groups (3% vs. 5.8%, p = 0.4 and 90% vs. 88%, p = 0.79, respectively) at 30 days. At a median follow-up of 435 days, there was no significant difference in survival (MA-TF TAVR, 83% vs. SA-TF TAVR, 82%; p = 0.639). MA-TF TAVR can be performed with minimal morbidity and mortality and equivalent effectiveness compared with SA-TF TAVR. The shorter length of stay and lower resource use with MA-TF TAVR significantly lowers hospital costs. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Study on mitigation of pulsed heat load for ITER cryogenic system

NASA Astrophysics Data System (ADS)

Peng, N.; Xiong, L. Y.; Jiang, Y. C.; Tang, J. C.; Liu, L. Q.

2015-03-01

One of the key requirements for ITER cryogenic system is the mitigation of the pulsed heat load deposited in the magnet system due to magnetic field variation and pulsed DT neutron production. As one of the control strategies, bypass valves of Toroidal Field (TF) case helium loop would be adjusted to mitigate the pulsed heat load to the LHe plant. A quasi-3D time-dependent thermal-hydraulic analysis of the TF winding packs and TF case has been performed to study the behaviors of TF magnets during the reference plasma scenario with the pulses of 400 s burn and repetition time of 1800 s. The model is based on a 1D helium flow and quasi-3D solid heat conduction model. The whole TF magnet is simulated taking into account thermal conduction between winding pack and case which are cooled separately. The heat loads are given as input information, which include AC losses in the conductor, eddy current losses in the structure, thermal radiation, thermal conduction and nuclear heating. The simulation results indicate that the temperature variation of TF magnet stays within the allowable range when the smooth control strategy is active.

Improved axial point spread function in a two-frequency laser scanning confocal fluorescence microscope

NASA Astrophysics Data System (ADS)

Wu, Jheng-Syong; Chung, Yung-Chin; Chien, Jun-Jei; Chou, Chien

2018-01-01

A two-frequency laser scanning confocal fluorescence microscope (TF-LSCFM) based on intensity modulated fluorescence signal detection was proposed. The specimen-induced spherical aberration and scattering effect were suppressed intrinsically, and high image contrast was presented due to heterodyne interference. An improved axial point spread function in a TF-LSCFM compared with a conventional laser scanning confocal fluorescence microscope was demonstrated and discussed.

Tibiofemoral Compression Force Differences Using Laxity- and Force-Based Initial Graft Tensioning Techniques in the ACL-Reconstructed Knee

PubMed Central

Fleming, Braden C.; Brady, Mark F.; Bradley, Michael P.; Banerjee, Rahul; Hulstyn, Michael J.; Fadale, Paul D.

2008-01-01

Purpose To document the tibiofemoral (TF) compression forces produced during clinical initial graft tension protocols. Methods An image analysis system was used to track the position of the tibia relative to the femur in 11 cadaver knees. TF compression forces were quantified using thin-film pressure sensors. Prior to performing ACL reconstructions with patellar tendon grafts, measurements of TF compression force were obtained from the ACL-intact knee with knee flexion. ACL reconstructions were then performed using “force-based” and “laxity-based” graft tension approaches. Within each approach, high- and low-tension conditions were compared to the ACL-intact condition over the range of knee flexion angles. Results The TF compression forces for all initial graft tension conditions were significantly greater than that of the normal knee when the knee was in full extension (0°). The TF compression forces when using the laxity-based approach were greater than those produced with the force-based approach. However the laxity-based approach was necessary to restore normal laxity at the time of surgery. Conclusions The initial graft tension conditions produce different TF compressive force profiles at the time of surgery. A compromise must be made between restoring knee laxity or TF compressive forces when reconstructing the ACL with patellar tendon graft. Clinical Relevance The TF compression forces were greater in the ACL-reconstructed knee for all the initial graft tension conditions when compared to the ACL-intact knee, and that clinically relevant initial graft tension conditions produce different TF compressive forces. PMID:18760214

Preliminary Kalman Filter Design to Improve Air Combat Maneuvering Target Estimation for the F-4E/G Fire Control System.

DTIC Science & Technology

1985-12-01

ADDED TN~*************************** COMMON/AIR/RATE,PHI ,PHIDIT,PP-HI ,PITCH,PITCHD,PPITCHTRATE, 1 TURN,TURND,FPTURNTR1 ,TR2,TR3,TR4, TF1 ,TF2...READ(2,*)ALPHAE’ETA *C READ(2,*)TR1, TF1 !FORWARD ROLL START,STOP TIMES READ(2,*)TR1 , TF1 C READ(2,*)TR2,TF2 !REVERSE ROLL START,STOP TIMES READ(2... TF1 ,TR2, 1 TF2,TR3,TF3,TR4,TF4,HORT1 ,1ORT2,HORTGEIELTA C C INITIALIZE AIRCRAFT MODEL C IA IR=0 CALL AIR C C INITIALIZE RADAR MODEL -- C I RADAR=O CALL

Electrodeposition of Al in 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)amide and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide ionic liquids: in situ STM and EQCM studies.

PubMed

Moustafa, E M; El Abedin, S Zein; Shkurankov, A; Zschippang, E; Saad, A Y; Bund, A; Endres, F

2007-05-10

In the present paper, the electrodeposition of Al on flame-annealed Au(111) and polycrystalline Au substrates in two air- and water-stable ionic liquids namely, 1-butyl-1-methyl-pyrrolidinium bis(trifluoromethylsulfonyl)amide, [Py(1,4)]Tf(2)N, and 1-ethyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)amide, [EMIm]Tf(2)N, has been investigated by in situ scanning tunneling microscopy (STM), electrochemical quartz crystal microbalance (EQCM), and cyclic voltammetry. The cyclic voltammogram of aluminum deposition and stripping on Au(111) in the upper phase of the biphasic mixture of AlCl(3)/[EMIm]Tf(2)N at room temperature (25 degrees C) shows that the electrodeposition process is completely reversible as also evidenced by in situ STM and EQCM studies. Additionally, a cathodic peak at an electrode potential of about 0.55 V vs Al/Al(III) is correlated to the aluminum UPD process that was evidenced by in situ STM. A surface alloying of Al with Au at the early stage of deposition occurs. It has been found that the Au(111) surface is subject to a restructuring/reconstruction in the upper phase of the biphasic mixture of AlCl(3)/[Py(1,4)]Tf(2)N at room temperature (25 degrees C) and that the deposition is not fully reversible. Furthermore, the underpotential deposition of Al in [Py(1,4)]Tf(2)N is not as clear as in [EMIm]Tf(2)N. The frequency shift in the EQCM experiments in [Py(1,4)]Tf(2)N shows a surprising result as an increase in frequency and a decrease in damping with bulk aluminum deposition at potentials more negative than -1.8 V was observed at room temperature. However, at 100 degrees C there is a frequency decrease with ongoing Al deposition. At -2.0 V vs Al/Al(III), a bulk aluminum deposition sets in.

The Effects of Hydrogen-Like Impurity and Temperature on State Energies and Transition Frequency of Strong-Coupling Bound Polaron in an Asymmetric Gaussian Potential Quantum Well

NASA Astrophysics Data System (ADS)

Xiao, Jing-lin

2018-02-01

In the present work, we study the ground state energy, the first excited state energy and the transition frequency (TF) between the two states of the strong-coupling impurity bound polaron in an asymmetric Gaussian potential quantum well (AGPQW) by using the variational method of the Pekar type. By employing quantum statistics theory, the temperature effect on the state energies (SEs) and the TF are also calculated with a hydrogen-like impurity at the coordinate origin of the AGPQW. According to the obtained results, we found that the SEs and the TF are increasing functions of the temperature, whereas they are decreasing ones of the Coulombic impurity potential.

A Language-Independent Approach to Automatic Text Difficulty Assessment for Second-Language Learners

DTIC Science & Technology

2013-08-01

best-suited for regression. Our baseline uses z-normalized shallow length features and TF -LOG weighted vectors on bag-of-words for Arabic, Dari...length features and TF -LOG weighted vectors on bag-of-words for Arabic, Dari, English and Pashto. We compare Support Vector Machines and the Margin...football, whereas they are much less common in documents about opera). We used TF -LOG weighted word frequencies on bag-of-words for each document

Surface properties and exponential stress relaxations of mammalian meibum films.

PubMed

Eftimov, Petar; Yokoi, Norihiko; Tonchev, Vesselin; Nencheva, Yana; Georgiev, Georgi As

2017-03-01

The surface properties of meibomian secretion (MGS), the major constituent of the tear film (TF) lipid layer, are of key importance for TF stability. The interfacial properties of canine, cMGS, and feline, fMGS, meibum films were studied using a Langmuir surface balance. These species were selected because they have blinking frequency and TF stability similar to those of humans. The sample's performance during dynamic area changes was evaluated by surface pressure (π)-area (A) isocycles and the layer structure was monitored with Brewster angle microscopy. The films' dilatational rheology was probed via the stress-relaxation technique. The animal MGS showed similar behavior both between each other and with human MGS (studied previously). They form reversible, non-collapsible, multilayer thick films. The relaxations of canine, feline, and human MGS films were well described by double exponential decay reflecting the presence of two processes: (1) fast elastic process, with characteristic time τ < 10 s and (2) slow viscous process, with τ > 100 s-emphasizing the meibum layers viscoelasticity. The temperature decrease from 35 to 25 °C resulted in decreased thickness and lateral expansion of all MGS layers accompanied with increase of the π/A hysteresis and of the elastic process contribution to π relaxation transients. Thus, MGS films of mammals with similar blinking frequency and TF stability have similar surface properties and stress relaxations unaltered by the interspecies MGS compositional variations. Such knowledge may impact the selection of animal mimics of human MGS and on a better understanding of lipid classes' impact on meibum functionality.

Inhibition of liver metastases from neuraminidase-treated colon 26 cells by an anti-Thomsen-Friedenreich-specific monoclonal antibody.

PubMed

Shigeoka, H; Karsten, U; Okuno, K; Yasutomi, M

1999-01-01

Thomsen-Friedenreich antigen (TF; Galbeta1-3GalNAcalpha1-) is expressed on many human carcinomas. Evidence suggests that TF-carrying tumor cells specifically bind asialoglycoprotein receptors on hepatocytes resulting in metastasis formation in the liver. We used an animal model to examine the feasibility of preventing metastasis formation by an antibody to TF. Treatment of Colon 26 cells with neuraminidase led to the exposure of TF, and consequently to a higher frequency of liver metastases in syngeneic Balb/c mice. This could be prevented by an antibody to TF (A78-G/A7), but not by a control antibody. The results may open up a new strategy for the prophylaxis of metastatic spread to the liver.

High Throughput ELISAs to Measure a Unique Glycan on Transferrin in Cerebrospinal Fluid: A Possible Extension toward Alzheimer's Disease Biomarker Development

PubMed Central

Shirotani, Keiro; Futakawa, Satoshi; Nara, Kiyomitsu; Hoshi, Kyoka; Saito, Toshie; Tohyama, Yuriko; Kitazume, Shinobu; Yuasa, Tatsuhiko; Miyajima, Masakazu; Arai, Hajime; Kuno, Atsushi; Narimatsu, Hisashi; Hashimoto, Yasuhiro

2011-01-01

We have established high-throughput lectin-antibody ELISAs to measure different glycans on transferrin (Tf) in cerebrospinal fluid (CSF) using lectins and an anti-transferrin antibody (TfAb). Lectin blot and precipitation analysis of CSF revealed that PVL (Psathyrella velutina lectin) bound an unique N-acetylglucosamine-terminated N-glycans on “CSF-type” Tf whereas SSA (Sambucus sieboldiana agglutinin) bound α2,6-N-acetylneuraminic acid-terminated N-glycans on “serum-type” Tf. PVL-TfAb ELISA of 0.5 μL CSF samples detected “CSF-type” Tf but not “serum-type” Tf whereas SSA-TfAb ELISA detected “serum-type” Tf but not “CSF-type” Tf, demonstrating the specificity of the lectin-TfAb ELISAs. In idiopathic normal pressure hydrocephalus (iNPH), a senile dementia associated with ventriculomegaly, amounts of the SSA-reactive Tf were significantly higher than in non-iNPH patients, indicating that Tf glycan analysis by the high-throughput lectin-TfAb ELISAs could become practical diagnostic tools for iNPH. The lectin-antibody ELISAs of CSF proteins might be useful for diagnosis of the other neurological diseases. PMID:21876827

High Throughput ELISAs to Measure a Unique Glycan on Transferrin in Cerebrospinal Fluid: A Possible Extension toward Alzheimer's Disease Biomarker Development.

PubMed

Shirotani, Keiro; Futakawa, Satoshi; Nara, Kiyomitsu; Hoshi, Kyoka; Saito, Toshie; Tohyama, Yuriko; Kitazume, Shinobu; Yuasa, Tatsuhiko; Miyajima, Masakazu; Arai, Hajime; Kuno, Atsushi; Narimatsu, Hisashi; Hashimoto, Yasuhiro

2011-01-01

We have established high-throughput lectin-antibody ELISAs to measure different glycans on transferrin (Tf) in cerebrospinal fluid (CSF) using lectins and an anti-transferrin antibody (TfAb). Lectin blot and precipitation analysis of CSF revealed that PVL (Psathyrella velutina lectin) bound an unique N-acetylglucosamine-terminated N-glycans on "CSF-type" Tf whereas SSA (Sambucus sieboldiana agglutinin) bound α2,6-N-acetylneuraminic acid-terminated N-glycans on "serum-type" Tf. PVL-TfAb ELISA of 0.5 μL CSF samples detected "CSF-type" Tf but not "serum-type" Tf whereas SSA-TfAb ELISA detected "serum-type" Tf but not "CSF-type" Tf, demonstrating the specificity of the lectin-TfAb ELISAs. In idiopathic normal pressure hydrocephalus (iNPH), a senile dementia associated with ventriculomegaly, amounts of the SSA-reactive Tf were significantly higher than in non-iNPH patients, indicating that Tf glycan analysis by the high-throughput lectin-TfAb ELISAs could become practical diagnostic tools for iNPH. The lectin-antibody ELISAs of CSF proteins might be useful for diagnosis of the other neurological diseases.

Direct optical mapping of transcription factor binding sites on field-stretched λ-DNA in nanofluidic devices

PubMed Central

Sriram, K. K.; Yeh, Jia-Wei; Lin, Yii-Lih; Chang, Yi-Ren; Chou, Chia-Fu

2014-01-01

Mapping transcription factor (TF) binding sites along a DNA backbone is crucial in understanding the regulatory circuits that control cellular processes. Here, we deployed a method adopting bioconjugation, nanofluidic confinement and fluorescence single molecule imaging for direct mapping of TF (RNA polymerase) binding sites on field-stretched single DNA molecules. Using this method, we have mapped out five of the TF binding sites of E. coli RNA polymerase to bacteriophage λ-DNA, where two promoter sites and three pseudo-promoter sites are identified with the corresponding binding frequency of 45% and 30%, respectively. Our method is quick, robust and capable of resolving protein-binding locations with high accuracy (∼ 300 bp), making our system a complementary platform to the methods currently practiced. It is advantageous in parallel analysis and less prone to false positive results over other single molecule mapping techniques such as optical tweezers, atomic force microscopy and molecular combing, and could potentially be extended to general mapping of protein–DNA interaction sites. PMID:24753422

IRRA at TREC 2009: Index Term Weighting based on Divergence From Independence Model

DTIC Science & Technology

2009-11-01

weighting scheme ( Salton and Buckley, 1988), where TF stands for the term frequency and IDF stands for the inverse document frequency. In contrast to TF...IDF is a collection dependent factor, which identifies the terms that concentrates in a few documents of the collection. Salton and Buckley (1988...chapter 4, pages 35–56. Butterworths, Oxford, UK, 1981. G. Salton and C. Buckley. Term-weighting approaches in automatic text retrieval. In Information Processing and Management, pages 513–523, 1988. 15

Selected Economic Translations on Eastern Europe (166th in the series)

DTIC Science & Technology

1960-04-22

number of veins in ä cable can be unspooled and utilized in carriör-frequency fashion . It must also be taken into accounts that the switch-off. of...distortion), no longer be assured with the present methods of low-frequency’ technology but only, with TF systems with a higher number of channels...distance cables, which contain only TF quad- ruples lines, since the coaxial tube of 3-Vl2.7 millimeters is not fully utilised with a V 960 system. The

Genetic characteristic of swamp buffalo (Bubalus bubalis) from Pampangan, South Sumatra based on blood protein profile

NASA Astrophysics Data System (ADS)

Windusari, Yuanita; Hanum, Laila; Wahyudi, Rizki

2017-11-01

Swamp buffalo (Bubalus bubalis) is an endemic species and one of the genetic wealth of South Sumatra with a distribution area in the district of Pampangan (OganIlir and OganOganIlir). Suspected inbreeding causes decreased phenotypic properties. Inbreeding among various swamp buffalo is certainly not only lower the qualities but also genotypes and phenotypes. It is of interest to determine kinship variants swamp buffaloes from Pampangan through the analysis of a blood protein profile. Blood protein profile of four variants swamps buffalo was studied by using five electrophoresis system i.e. pre-albumin (Palb), albumin (Alb), ceruloplasmin (Cp), transferrin (Tf) and transferrin post (Ptf). In this paper, it is obtained that there was no significant differences among the four variants of the buffaloes were used as a sample. Prealbumin has two alleles (Palb1 and Palb2), albumin has three alleles (Alba, AlbB, AlbC), ceruloplasmin has one allele (BPA), post-transferrin has one allele (PTFA) with an allele frequency 1.0000 at any time transferrin has two alleles (TFA and TFB) with the allele frequency of 0.7500 and 1.0000. Characteristics prealbumin (Palb), albumin (Alb), ceruloplasmin (Cp), and post-transferrin (P-tf) is monomorphic, while transferrin is polymorphic average heterozygosity values all loci (H) 0.1286. Based on average heterozygosity, the swamp buffalo (Bubalusbubalis) from Pampangan has low genetic variation and closest genetic relationship.

Thermal analysis of the cryostat feed through for the ITER Tokamak TF feeder

NASA Astrophysics Data System (ADS)

Zhang, Shanwen; Song, Yuntao; Lu, Kun; Wang, Zhongwei; Zhang, Jianfeng; Qin, Yongfa

2017-04-01

In Tokamaks, the toroidal field (TF) coil feeder is an important component that is used to supply the cryogens and electrical power for the TF coils. As a part of the TF feeder, the cryostat-feed through (CFT) is subject to low temperatures of 9 and 80 K inside and room temperature of 300 K outside. Based on the features of the International Thermonuclear Experimental Reactor TF feeder, the thermal performance of the CFT under the nominal conditions is studied. Taking into account the conductive, convective and radiation heat transfer, the finite element model of the CFT is built. Transient thermal analysis is performed to determine the temperatures of the CFT on the 9th day of cooldown. The model is assessed by comparing the cooling curves of the CFT after 9 days. If the simulation and experimental results are the same, the finite element model can be considered as calibrated. The model predicts that the cooling time will be approximately 26 days and the temperature distribution and heat load of the main components are obtained when the CFT reaches thermal equilibrium. This study provides a valid quantitative characterization of the CFT design.

Low Multiplicity of HIV-1 Infection and No Vaccine Enhancement in VAX003 Injection Drug Users

PubMed Central

Sterrett, Sarah; Learn, Gerald H.; Edlefsen, Paul T.; Haynes, Barton F.; Hahn, Beatrice H.; Shaw, George M.; Bar, Katharine J.

2014-01-01

Background  We performed human immunodeficiency virus type 1 (HIV-1) transmitted/founder (T/F) virus analysis of the VAX003 vaccine efficacy trial participants to characterize the transmission bottleneck and test for vaccine-associated reduction or enhancement of infection in this injection drug user (IDU) cohort. Methods  We performed single genome sequencing of plasma vRNA from 50 subjects sampled in early HIV infection. Sequences were analyzed phylogenetically, T/F viruses enumerated, and a sieve analysis performed. Results  Eight of 19 (42%) placebo recipients were productively infected by more than 1 virus (range 1–5, median 1, mean 1.7). This frequency of multiple virus transmission was greater than reported for heterosexual cohorts (19%, P = .03) but not statistically different from vaccine recipients (22.6%, P > .05), where the range was 1–3, median 1, and mean 1.3 (P > .05 for all comparisons). An atypical sieve effect was detected in Env V2 but was not associated with reduction or enhancement of virus acquisition. Conclusions  The number of T/F viruses in IDUs was surprising low, with 95% of individuals infected by only 1–3 viruses. This finding suggests that a successful vaccine or other prevention modality generally needs to protect against only one or a few viruses regardless of risk behavior. T/F analysis identified an atypical genetic sieve in the V2 region of Envelope and found no evidence for vaccine-mediated enhancement in VAX003. PMID:25734126

Human operator identification model and related computer programs

NASA Technical Reports Server (NTRS)

Kessler, K. M.; Mohr, J. N.

1978-01-01

Four computer programs which provide computational assistance in the analysis of man/machine systems are reported. The programs are: (1) Modified Transfer Function Program (TF); (2) Time Varying Response Program (TVSR); (3) Optimal Simulation Program (TVOPT); and (4) Linear Identification Program (SCIDNT). The TV program converts the time domain state variable system representative to frequency domain transfer function system representation. The TVSR program computes time histories of the input/output responses of the human operator model. The TVOPT program is an optimal simulation program and is similar to TVSR in that it produces time histories of system states associated with an operator in the loop system. The differences between the two programs are presented. The SCIDNT program is an open loop identification code which operates on the simulated data from TVOPT (or TVSR) or real operator data from motion simulators.

A Method to Predict Compressor Stall in the TF34-100 Turbofan Engine Utilizing Real-Time Performance Data

DTIC Science & Technology

2015-06-01

A METHOD TO PREDICT COMPRESSOR STALL IN THE TF34-100 TURBOFAN ENGINE UTILIZING REAL-TIME PERFORMANCE...THE TF34-100 TURBOFAN ENGINE UTILIZING REAL-TIME PERFORMANCE DATA THESIS Presented to the Faculty Department of Systems Engineering and...036 A METHOD TO PREDICT COMPRESSOR STALL IN THE TF34-100 TURBOFAN ENGINE UTILIZING REAL-TIME PERFORMANCE DATA Shuxiang ‘Albert’ Li, BS

Transfer of radionuclides to plants of natural ecosystems at the Semipalatinsk Test Site.

PubMed

Larionova, N V; Lukashenko, S N; Kabdyrakova, A M; Kunduzbayeva, A Ye; Panitskiy, A V; Ivanova, A R

2018-06-01

A systematic study devoted to 137 Cs, 90 Sr, 241 Am, 239+240 Pu radionuclides in vegetation cover from several spots of the Semipalatinsk test site (STS) is summarised in this paper, highlighting the main findings obtained. The analysed spots are characterized by various types of radioactive contamination. Transfer factors (Tf) required for the quantitative description of the radionuclides transition from the soil to aboveground plant parts were determined, being found that, on average, the minimum Tf for all the radionuclides concerned were determined on the "Experimental Field" ground, followed by the determined ones in the "plumes" of radioactive fallout and in the conditionally "background" territories analysed. The highest transfer factors were characteristic of zones of radioactive streamflows and places of warfare radioactive agent (WRA) tests. On the other hand, ordering the radionuclide transferring factors in descending order, the following sequence was obtained: 90 Sr Tf > Cs Tf >  239+240 Pu Tf >  241 Am Tf, with the 90 Sr Tf, on the average, exceeding the 137 Cs Tf by 8 times and exceeding the 239+240 Pu Tf by up 16 times. 239+240 Pu Tf values were up to 3 times higher than the 241 Am Tf. The exception to the indicated radionuclide Tf descending order corresponded to places of WRA tests where Tf of radionuclides of interest by plants follows the sequence 90 Sr >  239+240 Pu >  137 Cs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Time and Frequency Activities at NICT, Japan

DTIC Science & Technology

2009-11-01

consistency and accuracy of our development. 4.2. TWSTFT [11] NICT and major T&F institutes in the Asia-Pacific region, such as NMIA in Australia, NTSC...in China, TL in Taipei, Taiwan, and KRISS in Korea are cooperatively constructing a TWSTFT network in this region. Time transfer is regularly...8 in 2009. A TWSTFT link between NICT and PTB has been established by using IS-4 satellite. The time transfer is performed hourly and the data

Rapid screening of transferrin-binders in the flowers of Bauhinia blakeana Dunn by on-line high-performance liquid chromatography-diode-array detector-electrospray ionization-ion-trap-time-of-flight-mass spectrometry-transferrin-fluorescence detection system.

PubMed

Liu, Meixian; Dong, Jing; Lin, Zongtao; Niu, Yanyan; Zhang, Xiaotian; Jiang, Haixiu; Guo, Ning; Li, Wei; Wang, Hong; Chen, Shizhong

2016-06-10

Transferrin (Transferrin, TRF, TF) has drawn increasing attention in cancer therapy due to its potential applications in drug delivery. TF receptor, highly expressed in tumor cells, recognizes and transports Fe(3+)-TF into cells to release iron into cytoplasm. Thus, discovering TF-binding compounds has become an active research area and is of great importance for target therapy. In this study, an on-line analysis method was established for screening TF-binding compounds from the flowers of Bauhinia blakeana Dunn using a high-performance liquid chromatography-diode-array detector-multi-stage mass spectrometry-transferrin-fluorescence detector (HPLC-DAD-MS(n)-TF-FLD) method. As a result, 33 of 80 identified or tentatively characterized compounds in the sample were TF-binding active. Twenty-five flavonol glycosides and eight phenolic acids were identified as TF-binders. Twelve of these active compounds together with six standard compounds were used to study the dose-response effects and structure-activity relationships of flavonoids and phenolic acids. The method was validated by vitexin with a good linearity in the range of concentrations used in the study. The limit of detection for vitexin was 0.1596 nmol. Our study indicated that the established method is simple, rapid and sensitive for screening TF-binding active compounds in the extract of Bauhinia blakeana Dunn, and therefore is important for discovering potential anti-cancer ingredients from complex samples for TF related drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

Expression of Tissue Factor in Epithelial Ovarian Carcinoma Is Involved in the Development of Venous Thromboembolism.

PubMed

Sakurai, Manabu; Matsumoto, Koji; Gosho, Masahiko; Sakata, Akiko; Hosokawa, Yoshihiko; Tenjimbayashi, Yuri; Katoh, Takashi; Shikama, Ayumi; Komiya, Haruna; Michikami, Hiroo; Tasaka, Nobutaka; Akiyama-Abe, Azusa; Nakao, Sari; Ochi, Hiroyuki; Onuki, Mamiko; Minaguchi, Takeo; Yoshikawa, Hiroyuki; Satoh, Toyomi

2017-01-01

Our 2007 study of 32 patients with ovarian cancer reported the possible involvement of tissue factor (TF) in the development of venous thromboembolism (VTE) before treatment, especially in clear cell carcinoma (CCC). This follow-up study further investigated this possibility in a larger cohort. We investigated the intensity of TF expression (ITFE) and other variables for associations with VTE using univariate and multivariate analyses in 128 patients with epithelial ovarian cancer initially treated between November 2004 and December 2010, none of whom had received neoadjuvant chemotherapy. Before starting treatment, all patients were ultrasonographically screened for VTE. The ITFE was graded based on immunostaining of surgical specimens. Histological types were serous carcinoma (n = 42), CCC (n = 12), endometrioid carcinoma (n = 15), mucinous carcinoma (n = 53), and undifferentiated carcinoma (n = 6). The prevalence of VTE was significantly higher in CCC (34%) than in non-CCC (17%, P = 0.03). As ITFE increased, the frequencies of CCC and VTE increased significantly (P < 0.001 and P = 0.014, respectively). Multivariate analysis identified TF expression and pretreatment dimerized plasmin fragment D level as significant independent risk factors for VTE development. These factors showed particularly strong impacts on advanced-stage disease (P = 0.021). The 2007 cohort was small, preventing multivariate analysis. This study of a larger cohort yielded stronger evidence that the development of VTE in epithelial ovarian cancer may involve TF expression in cancer tissues.

A new sample treatment for asialo-Tf determination with capillary electrophoresis: an added value to the analysis of CDT.

PubMed

Porpiglia, Nadia Maria; De Palo, Elio Franco; Savchuk, Sergey Alexandrovich; Appolonova, Svetlana Alexandrovna; Bortolotti, Federica; Tagliaro, Franco

2018-05-10

The non-glycosylated glycoform of transferrin (Tf), known as asialo-Tf, was not selected (in favor of disialo-Tf) as the measurand for the standardization of carbohydrate deficient transferrin (CDT) determination because of a lower diagnostic sensitivity provided with the currently available analytical procedures for sera. However, asialo-Tf could provide an additional value to disialo-Tf in the CDT analysis employed in forensic toxicology contexts. The present work aimed at developing an easy sample preparation based on PEG precipitation in order to improve the detectability of asialo-Tf in capillary electrophoresis (CE). Equal volumes (35 μL) of serum and of 30% PEG-8000 were mixed and briefly vortexed. After centrifugation, the supernatant was iron saturated with a ferric solution (1:1, v/v). The mixture was analyzed in CE for asialo-Tf and disialo-Tf determination. PEG-8000 precipitation allowed the improvement of the baseline in the electropherograms in terms of interferences reduction particularly in the asialo-Tf migration region. The detection of asialo-Tf was possible in 89% of samples with disialo-Tf above the cut-off limit, whereas only 16% of them showed asialo-Tf by employing the traditional sample preteatment. Asialo-Tf represents an additional value to disialo-Tf as a biomarker of alcohol abuse in forensic toxicology. Copyright © 2018. Published by Elsevier B.V.

Word Frequency Analysis. MOS: 33S. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

rts Wq -1A~ ttSttii AArjtr I TF1 P!16 1,1,1 PAGE 1 TV 1" r Y Nsv’r 1 1 - ? I l1 1 , .I I I o ’ , ’’II A T 1T1 1 1 1Ilr A-r P y? A T f TS...TIFl’nfl n ! ’ cVT AT (rhi I nrV I", I n I’I𔃿F𔃻 1 rnIbrrTnn 1 n 19 r (.T I 9 I 1 .. i’r"’r TF1 LIn’I~r I, ItiVsS En 1 OI1;VIa V Cn AV. f" I" I " c,’’’ 1

Frequency Modulation of Transcriptional Bursting Enables Sensitive and Rapid Gene Regulation.

PubMed

Li, Congxin; Cesbron, François; Oehler, Michael; Brunner, Michael; Höfer, Thomas

2018-04-25

Gene regulation is a complex non-equilibrium process. Here, we show that quantitating the temporal regulation of key gene states (transcriptionally inactive, active, and refractory) provides a parsimonious framework for analyzing gene regulation. Our theory makes two non-intuitive predictions. First, for transcription factors (TFs) that regulate transcription burst frequency, as opposed to amplitude or duration, weak TF binding is sufficient to elicit strong transcriptional responses. Second, refractoriness of a gene after a transcription burst enables rapid responses to stimuli. We validate both predictions experimentally by exploiting the natural, optogenetic-like responsiveness of the Neurospora GATA-type TF White Collar Complex (WCC) to blue light. Further, we demonstrate that differential regulation of WCC target genes is caused by different gene activation rates, not different TF occupancy, and that these rates are tuned by both the core promoter and the distance between TF-binding site and core promoter. In total, our work demonstrates the relevance of a kinetic, non-equilibrium framework for understanding transcriptional regulation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Stochastic modular analysis for gene circuits: interplay among retroactivity, nonlinearity, and stochasticity.

PubMed

Kim, Kyung Hyuk; Sauro, Herbert M

2015-01-01

This chapter introduces a computational analysis method for analyzing gene circuit dynamics in terms of modules while taking into account stochasticity, system nonlinearity, and retroactivity. (1) ANALOG ELECTRICAL CIRCUIT REPRESENTATION FOR GENE CIRCUITS: A connection between two gene circuit components is often mediated by a transcription factor (TF) and the connection signal is described by the TF concentration. The TF is sequestered to its specific binding site (promoter region) and regulates downstream transcription. This sequestration has been known to affect the dynamics of the TF by increasing its response time. The downstream effect-retroactivity-has been shown to be explicitly described in an electrical circuit representation, as an input capacitance increase. We provide a brief review on this topic. (2) MODULAR DESCRIPTION OF NOISE PROPAGATION: Gene circuit signals are noisy due to the random nature of biological reactions. The noisy fluctuations in TF concentrations affect downstream regulation. Thus, noise can propagate throughout the connected system components. This can cause different circuit components to behave in a statistically dependent manner, hampering a modular analysis. Here, we show that the modular analysis is still possible at the linear noise approximation level. (3) NOISE EFFECT ON MODULE INPUT-OUTPUT RESPONSE: We investigate how to deal with a module input-output response and its noise dependency. Noise-induced phenotypes are described as an interplay between system nonlinearity and signal noise. Lastly, we provide the comprehensive approach incorporating the above three analysis methods, which we call "stochastic modular analysis." This method can provide an analysis framework for gene circuit dynamics when the nontrivial effects of retroactivity, stochasticity, and nonlinearity need to be taken into account.

Magnetoelectric coupling characteristics in multiferroic heterostructures with different thickness of nanocrystalline soft magnetic alloy

NASA Astrophysics Data System (ADS)

Chen, Lei; Wang, Yao

2016-05-01

Magnetoelectric(ME) coupling characteristics in multiferroic heterostructures with different thickness of nanocrystalline soft magnetic alloy has been investigated at low frequency. The ME response with obvious hysteresis, self-biased and dual-peak phenomenon is observed for multiferroic heterostructures, which results from strong magnetic interactions between two ferromagnetic materials with different magnetic properties, magnetostrictions and optimum bias magnetic fields Hdc,opti. The proposed multiferroic heterostructures not only enhance ME coupling significantly, but also broaden dc magnetic bias operating range and overcomes the limitations of narrow bias range. By optimizing the thickness of nanocrystalline soft magnetic alloy Tf, a significantly zero-biased ME voltage coefficient(MEVC) of 14.8mV/Oe (185 mV/cmṡ Oe) at Tf = 0.09 mm can be obtained, which is about 10.8 times as large as that of traditional PZT/Terfenol-D composite with a weak ME coupling at zero bias Hdc,zero. Furthermore, when Tf increases from 0.03 mm to 0.18 mm, the maximum MEVC increases nearly linearly with the increased Tf at Hdc,opti. Additionally, the experimental results demonstrate the ME response for multiferroic heterostructures spreads over a wide magnetic dc bias operating range. The excellent ME performance provides a promising and practicable application for both highly sensitive magnetic field sensors without bias and ME energy harvesters.

Binaural segregation in multisource reverberant environments.

PubMed

Roman, Nicoleta; Srinivasan, Soundararajan; Wang, DeLiang

2006-12-01

In a natural environment, speech signals are degraded by both reverberation and concurrent noise sources. While human listening is robust under these conditions using only two ears, current two-microphone algorithms perform poorly. The psychological process of figure-ground segregation suggests that the target signal is perceived as a foreground while the remaining stimuli are perceived as a background. Accordingly, the goal is to estimate an ideal time-frequency (T-F) binary mask, which selects the target if it is stronger than the interference in a local T-F unit. In this paper, a binaural segregation system that extracts the reverberant target signal from multisource reverberant mixtures by utilizing only the location information of target source is proposed. The proposed system combines target cancellation through adaptive filtering and a binary decision rule to estimate the ideal T-F binary mask. The main observation in this work is that the target attenuation in a T-F unit resulting from adaptive filtering is correlated with the relative strength of target to mixture. A comprehensive evaluation shows that the proposed system results in large SNR gains. In addition, comparisons using SNR as well as automatic speech recognition measures show that this system outperforms standard two-microphone beamforming approaches and a recent binaural processor.

Mutation in Torenia fournieri Lind. UFO homolog confers loss of TfLFY interaction and results in a petal to sepal transformation.

PubMed

Sasaki, Katsutomo; Yamaguchi, Hiroyasu; Aida, Ryutaro; Shikata, Masahito; Abe, Tomoko; Ohtsubo, Norihiro

2012-09-01

We identified a Torenia fournieri Lind. mutant (no. 252) that exhibited a sepaloid phenotype in which the second whorls were changed to sepal-like organs. This mutant had no stamens, and the floral organs consisted of sepals and carpels. Although the expression of a torenia class B MADS-box gene, GLOBOSA (TfGLO), was abolished in the 252 mutant, no mutation of TfGLO was found. Among torenia homologs such as APETALA1 (AP1), LEAFY (LFY), and UNUSUAL FLORAL ORGANS (UFO), which regulate expression of class B genes in Arabidopsis, only accumulation of the TfUFO transcript was diminished in the 252 mutant. Furthermore, a missense mutation was found in the coding region of the mutant TfUFO. Intact TfUFO complemented the mutant phenotype whereas mutated TfUFO did not; in addition, the transgenic phenotype of TfUFO-knockdown torenias coincided with the mutant phenotype. Yeast two-hybrid analysis revealed that the mutated TfUFO lost its ability to interact with TfLFY protein. In situ hybridization analysis indicated that the transcripts of TfUFO and TfLFY were partially accumulated in the same region. These results clearly demonstrate that the defect in TfUFO caused the sepaloid phenotype in the 252 mutant due to the loss of interaction with TfLFY. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

The Model Analyst’s Toolkit: Scientific Model Development, Analysis, and Validation

DTIC Science & Technology

2013-11-20

Granger causality F-test validation 3.1.2. Dynamic time warping for uneven temporal relationships Many causal relationships are imperfectly...mapping for dynamic feedback models Granger causality and DTW can identify causal relationships and consider complex temporal factors. However, many ...variant of the tf-idf algorithm (Manning, Raghavan, Schutze et al., 2008), typically used in search engines, to “score” features. The (-log tf) in

Discovery and characterization of potential prognostic biomarkers for dengue hemorrhagic fever.

PubMed

Poole-Smith, B Katherine; Gilbert, Alexa; Gonzalez, Andrea L; Beltran, Manuela; Tomashek, Kay M; Ward, Brian J; Hunsperger, Elizabeth A; Ndao, Momar

2014-12-01

Half a million patients are hospitalized with severe dengue every year, many of whom would die without timely, appropriate clinical intervention. The majority of dengue cases are uncomplicated; however, 2-5% progress to severe dengue. Severe dengue cases have been reported with increasing frequency over the last 30 years. To discover biomarkers for severe dengue, we used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to analyze dengue virus positive serum samples from the acute phase of infection. Using this method, 16 proteins were identified as candidate biomarkers for severe dengue. From these 16 biomarkers, three candidates were selected for confirmation by enzyme-linked immunosorbent assay and Western blot: vitronectin (Vtn, 55.1 kDa), hemopexin (Hx, 52.4 kDa), and serotransferrin (Tf, 79.2 kDa). Vitronectin, Hx, and Tf best differentiated between dengue and severe dengue. © The American Society of Tropical Medicine and Hygiene.

Discovery and Characterization of Potential Prognostic Biomarkers for Dengue Hemorrhagic Fever

PubMed Central

Poole-Smith, B. Katherine; Gilbert, Alexa; Gonzalez, Andrea L.; Beltran, Manuela; Tomashek, Kay M.; Ward, Brian J.; Hunsperger, Elizabeth A.; Ndao, Momar

2014-01-01

Half a million patients are hospitalized with severe dengue every year, many of whom would die without timely, appropriate clinical intervention. The majority of dengue cases are uncomplicated; however, 2–5% progress to severe dengue. Severe dengue cases have been reported with increasing frequency over the last 30 years. To discover biomarkers for severe dengue, we used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to analyze dengue virus positive serum samples from the acute phase of infection. Using this method, 16 proteins were identified as candidate biomarkers for severe dengue. From these 16 biomarkers, three candidates were selected for confirmation by enzyme-linked immunosorbent assay and Western blot: vitronectin (Vtn, 55.1 kDa), hemopexin (Hx, 52.4 kDa), and serotransferrin (Tf, 79.2 kDa). Vitronectin, Hx, and Tf best differentiated between dengue and severe dengue. PMID:25349378

An analysis of subunit exchange in the dimeric DNA-binding and DNA-bending protein, TF1.

PubMed

Andera, L; Schneider, G J; Geiduschek, E P

1994-01-01

TF1 is the Bacillus subtilis bacteriophage-encoded dimeric type II DNA-binding protein. This relative of the eubacterial HU proteins and of the Escherichia coli integration host factor binds preferentially to 5-(hydroxymethyluracil)-containing DNA. We have examined the dynamics of exchange of monomer subunits between molecules of dimeric TF1. The analysis takes advantage of the fact that replacement of phenylalanine with arginine at amino acid 61 in the beta-loop 'arm' of TF1 alters DNA-bending and -binding properties, generating DNA complexes with distinctively different mobilities in gel electrophoresis. New species of DNA-protein complexes were formed by mixtures of wild type and mutant TF1, reflecting the formation of heterodimeric TF1, and making the dynamics of monomer exchange between TF1 dimers accessible to a simple gel retardation analysis. Exchange was rapid at high protein concentrations, even at 0 degrees C, and is proposed to be capable of proceeding through an interaction of molecules of TF1 dimer rather than exclusively through dissociation into monomer subunits. Evidence suggesting that DNA-bound TF1 dimers do not exchange subunits readily is also presented.

Characterization of iron uptake from transferrin by murine endothelial cells.

PubMed

Hallmann, R; Savigni, D L; Morgan, E H; Baker, E

2000-01-01

Iron is required by the brain for normal function, however, the mechanisms by which it crosses the blood-brain barrier (BBB) are poorly understood. The uptake and efflux of transferrin (Tf) and Fe by murine brain-derived (bEND3) and lymph node-derived (m1END1) endothelial cell lines was compared. The effects of iron chelators, metabolic inhibitors and the cellular activators, lipopolysaccharide (LPS) and tumour necrosis factor-alpha (TNF-alpha), on Tf and Fe uptake were investigated. Cells were incubated with 59Fe-125I-Tf; Fe uptake was shown to increase linearly over time for both cell lines, while Tf uptake reached a plateau within 2 h. Both Tf and Fe uptake were saturable. bEND3 cells were shown to have half as many Tf receptors as m1END1 cells, but the mean cycling times of a Tf molecule were the same. Tf and Fe efflux from the cells were measured over time, revealing that after 2 h only 25% of the Tf but 80% of the Fe remained associated with the cells. Of 7 iron chelators, only deferriprone (L1) markedly decreased Tf uptake. However, Fe uptake was reduced by more than 50% by L1, pyridoxal isonicotinoyl hydrazone (PIH) and desferrithiocin (DFT). The cellular activators TNF-alpha or LPS had little effect on Tf turnover, but they accelerated Fe uptake in both endothelial cell types. Phenylarsenoxide (PhAsO) and N-ethyl maleimide (NEM), inhibitors of Tf endocytosis, reduced both Tf and Fe uptake in both cell lines, while bafilomycin A1, an inhibitor of endosomal acidification, reduced Fe uptake but did not affect Tf uptake. The results suggest that Tf and Fe uptake by both bEND3 and m1END1 is via receptor-mediated endocytosis with release of Fe from Tf within the cell and recycling of apo-Tf. On the basis of Tf- and Fe-metabolism both cell lines are similar and therefore well suited for use in in vitro models for Fe transport across the BBB.

Dynamic motif occupancy (DynaMO) analysis identifies transcription factors and their binding sites driving dynamic biological processes

PubMed Central

Kuang, Zheng; Ji, Zhicheng

2018-01-01

Abstract Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data. In the first step, DynaMO predicts TF binding sites with a random forests approach. Next and uniquely, DynaMO infers dynamic TF binding activities at predicted binding sites using their local chromatin profiles from multiple biological conditions. Another landmark of DynaMO is to identify key TFs in a dynamic process using a clustering and enrichment analysis of dynamic TF binding patterns. Application of DynaMO to the yeast ultradian cycle, mouse circadian clock and human neural differentiation exhibits its accuracy and versatility. We anticipate DynaMO will be generally useful for elucidating transcriptional programs in dynamic processes. PMID:29325176

Localization and Ballistic Diffusion for the Tempered Fractional Brownian-Langevin Motion

NASA Astrophysics Data System (ADS)

Chen, Yao; Wang, Xudong; Deng, Weihua

2017-10-01

This paper discusses the tempered fractional Brownian motion (tfBm), its ergodicity, and the derivation of the corresponding Fokker-Planck equation. Then we introduce the generalized Langevin equation with the tempered fractional Gaussian noise for a free particle, called tempered fractional Langevin equation (tfLe). While the tfBm displays localization diffusion for the long time limit and for the short time its mean squared displacement (MSD) has the asymptotic form t^{2H}, we show that the asymptotic form of the MSD of the tfLe transits from t^2 (ballistic diffusion for short time) to t^{2-2H}, and then to t^2 (again ballistic diffusion for long time). On the other hand, the overdamped tfLe has the transition of the diffusion type from t^{2-2H} to t^2 (ballistic diffusion). The tfLe with harmonic potential is also considered.

Does minimalist transfemoral transcatheter aortic valve replacement produce better survival in patients with severe chronic obstructive pulmonary disease?

PubMed

Condado, Jose F; Haider, Moosa N; Lerakis, Stamatios; Keegan, Patricia; Caughron, Hope; Thourani, Vinod H; Devireddy, Chandan; Leshnower, Bradley; Mavromatis, Kreton; Sarin, Eric L; Stewart, James; Guyton, Robert; Forcillo, Jessica; Patel, Ateet; Simone, Amy; Block, Peter C; Babaliaros, Vasilis

2017-03-01

To compare outcomes after minimalist and standard transfemoral transcatheter aortic valve replacement (TF-TAVR) in patients with severe chronic obstructive pulmonary disease (COPD). TF-TAVR is increasingly performed with conscious sedation and transthoracic echocardiography guidance (minimalist). The safety/efficacy of this technique in patients with severe COPD is unknown. We compared demographics, 30-day outcomes and 1-year survival of patients with severe COPD (FEV1% ≤50) who underwent minimalist vs. standard TF-TAVR between 2008 and 2015 at our institution. Of 88 patients with severe COPD, 46 underwent minimalist and 42 underwent standard TF-TAVR. There were no differences on baseline characteristics, except for more history of coronary artery bypass grafting (45.5% vs. 20.6%, P = 0.03) and less history of cerebrovascular disease (16.7% vs. 45.5%, P = 0.03) in the standard TF-TAVR. Seventeen minimalist TF-TAVR patients (41.0%) were transferred directly to the general medical ward with telemetry monitoring (without ICU stay); all standard TF-TAVR patients went to the ICU. Minimalist TF-TAVR patients had shorter procedure time (97 vs. 129 min, P < 0.001), ICU time (21.8 vs. 29.8 hr, P = 0.001) and length of stay (2 vs. 5 days, P = 0.001). There were no differences in procedure complications and 30-day mortality between groups. In our multivariate analysis, minimalist TF-TAVR (HR 0.28, 95%CI 0.08-0.97) and previous coronary revascularization (HR 0.24, 95%CI 0.09-0.65) were associated with increased 1-year survival. In contrast, moderate paravalvular leak (HR 7.73, 95%CI 1.94-30.84) was associated with decreased 1-year survival. In patients with severe COPD, Minimalist TF-TAVR results in less resource utilization and improved 1-year survival compared to standard approach. Our findings should be validated in a larger cohort of patients with severe COPD. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Mapping of the Pim-1 oncogene in mouse t-haplotypes and its use to define the relative map positions of the tcl loci t0(t6) and tw12 and the marker tf (tufted).

PubMed

Ark, B; Gummere, G; Bennett, D; Artzt, K

1991-06-01

Pim-1 is an oncogene activated in mouse T-cell lymphomas induced by Moloney and AKR mink cell focus (MCF) viruses. Pim-1 was previously mapped to chromosome 17 by somatic cell hybrids, and subsequently to the region between the hemoglobin alpha-chain pseudogene 4 (Hba-4ps) and the alpha-crystalline gene (Crya-1) by Southern blot analysis of DNA obtained from panels of recombinant inbred strains. We have now mapped Pim-1 more accurately in t-haplotypes by analysis of recombinant t-chromosomes. The recombinants were derived from Tts6tf/t12 parents backcrossed to + tf/ + tf, and scored for recombination between the loci of T and tf. For simplicity all t-complex lethal genes properly named tcl-tx are shortened to tx. The Pim-1 gene was localized 0.6 cM proximal to the tw12 lethal gene, thus placing the Pim-1 gene 5.2 cM distal to the H-2 region in t-haplotypes. Once mapped, the Pim-1 gene was used as a marker for further genetic analysis of t-haplotypes. tw12 is so close to tf that even with a large number of recombinants it was not possible to determine whether it is proximal or distal to tf. Southern blot analysis of DNA from T-tf recombinants with a separation of tw12 and tf indicated that tw12 is proximal to tf. The mapping of two allelic t-lethals, t0 and t6 with respect to tw12 and tf has also been a problem.(ABSTRACT TRUNCATED AT 250 WORDS)

"Hit-and-Run" transcription: de novo transcription initiated by a transient bZIP1 "hit" persists after the "run".

PubMed

Doidy, Joan; Li, Ying; Neymotin, Benjamin; Edwards, Molly B; Varala, Kranthi; Gresham, David; Coruzzi, Gloria M

2016-02-03

Dynamic transcriptional regulation is critical for an organism's response to environmental signals and yet remains elusive to capture. Such transcriptional regulation is mediated by master transcription factors (TF) that control large gene regulatory networks. Recently, we described a dynamic mode of TF regulation named "hit-and-run". This model proposes that master TF can interact transiently with a set of targets, but the transcription of these transient targets continues after the TF dissociation from the target promoter. However, experimental evidence validating active transcription of the transient TF-targets is still lacking. Here, we show that active transcription continues after transient TF-target interactions by tracking de novo synthesis of RNAs made in response to TF nuclear import. To do this, we introduced an affinity-labeled 4-thiouracil (4tU) nucleobase to specifically isolate newly synthesized transcripts following conditional TF nuclear import. Thus, we extended the TARGET system (Transient Assay Reporting Genome-wide Effects of Transcription factors) to include 4tU-labeling and named this new technology TARGET-tU. Our proof-of-principle example is the master TF Basic Leucine Zipper 1 (bZIP1), a central integrator of metabolic signaling in plants. Using TARGET-tU, we captured newly synthesized mRNAs made in response to bZIP1 nuclear import at a time when bZIP1 is no longer detectably bound to its target. Thus, the analysis of de novo transcripomics demonstrates that bZIP1 may act as a catalyst TF to initiate a transcriptional complex ("hit"), after which active transcription by RNA polymerase continues without the TF being bound to the gene promoter ("run"). Our findings provide experimental proof for active transcription of transient TF-targets supporting a "hit-and-run" mode of action. This dynamic regulatory model allows a master TF to catalytically propagate rapid and broad transcriptional responses to changes in environment. Thus, the functional read-out of de novo transcripts produced by transient TF-target interactions allowed us to capture new models for genome-wide transcriptional control.

Temporal transcriptional logic of dynamic regulatory networks underlying nitrogen signaling and use in plants.

PubMed

Varala, Kranthi; Marshall-Colón, Amy; Cirrone, Jacopo; Brooks, Matthew D; Pasquino, Angelo V; Léran, Sophie; Mittal, Shipra; Rock, Tara M; Edwards, Molly B; Kim, Grace J; Ruffel, Sandrine; McCombie, W Richard; Shasha, Dennis; Coruzzi, Gloria M

2018-06-19

This study exploits time, the relatively unexplored fourth dimension of gene regulatory networks (GRNs), to learn the temporal transcriptional logic underlying dynamic nitrogen (N) signaling in plants. Our "just-in-time" analysis of time-series transcriptome data uncovered a temporal cascade of cis elements underlying dynamic N signaling. To infer transcription factor (TF)-target edges in a GRN, we applied a time-based machine learning method to 2,174 dynamic N-responsive genes. We experimentally determined a network precision cutoff, using TF-regulated genome-wide targets of three TF hubs (CRF4, SNZ, and CDF1), used to "prune" the network to 155 TFs and 608 targets. This network precision was reconfirmed using genome-wide TF-target regulation data for four additional TFs (TGA1, HHO5/6, and PHL1) not used in network pruning. These higher-confidence edges in the GRN were further filtered by independent TF-target binding data, used to calculate a TF "N-specificity" index. This refined GRN identifies the temporal relationship of known/validated regulators of N signaling (NLP7/8, TGA1/4, NAC4, HRS1, and LBD37/38/39) and 146 additional regulators. Six TFs-CRF4, SNZ, CDF1, HHO5/6, and PHL1-validated herein regulate a significant number of genes in the dynamic N response, targeting 54% of N-uptake/assimilation pathway genes. Phenotypically, inducible overexpression of CRF4 in planta regulates genes resulting in altered biomass, root development, and 15 NO 3 - uptake, specifically under low-N conditions. This dynamic N-signaling GRN now provides the temporal "transcriptional logic" for 155 candidate TFs to improve nitrogen use efficiency with potential agricultural applications. Broadly, these time-based approaches can uncover the temporal transcriptional logic for any biological response system in biology, agriculture, or medicine. Copyright © 2018 the Author(s). Published by PNAS.

Comparison of Grouping Methods for Template Extraction from VA Medical Record Text.

PubMed

Redd, Andrew M; Gundlapalli, Adi V; Divita, Guy; Tran, Le-Thuy; Pettey, Warren B P; Samore, Matthew H

2017-01-01

We investigate options for grouping templates for the purpose of template identification and extraction from electronic medical records. We sampled a corpus of 1000 documents originating from Veterans Health Administration (VA) electronic medical record. We grouped documents through hashing and binning tokens (Hashed) as well as by the top 5% of tokens identified as important through the term frequency inverse document frequency metric (TF-IDF). We then compared the approaches on the number of groups with 3 or more and the resulting longest common subsequences (LCSs) common to all documents in the group. We found that the Hashed method had a higher success rate for finding LCSs, and longer LCSs than the TF-IDF method, however the TF-IDF approach found more groups than the Hashed and subsequently more long sequences, however the average length of LCSs were lower. In conclusion, each algorithm appears to have areas where it appears to be superior.

Tapered fiber based Brillouin random fiber laser and its application for linewidth measurement.

PubMed

Gao, Song; Zhang, Liang; Xu, Yanping; Lu, Ping; Chen, Liang; Bao, Xiaoyi

2016-12-12

A one-end pumping Brillouin random fiber laser (BRFL) based on a 5-km tapered fiber (TF) is demonstrated. The enhanced Rayleigh scattering and the increased power density from tapering in the TF provide good directionality and a high degree of coherent feedback. Both the transmitting and TF enhanced Rayleigh scattered pump lights formed effective bi-direction pumping for the Brillouin gain in the standing cavity configuration in the distributed way as the gain and random feedback in the same fiber. The linewidth of the laser shows ~1.17 kHz while the relative intensity noise (RIN) has been verified to be suppressed comparing with that of the two-end pumping of the standard single mode fiber (SMF). Furthermore, utilizing the proposed laser, a high-resolution (~kHz) linewidth measurement method is demonstrated without long delay fiber (>100km) and extra frequency shifter thanks to the acoustic frequency shift from fiber itself.

The relationship of fibroblast translocations to cell morphology and stress fibre density.

PubMed

Lewis, L; Verna, J M; Levinstone, D; Sher, S; Marek, L; Bell, E

1982-02-01

Translocation of human fibroblasts in culture was studied using techniques of time-lapse cinemicrography, indirect immunofluorescence, and computer analysis. An inverse relationship between the velocity of cells during the last hour of life and the density of stress fibers seen by immune staining was demonstrated. Translocating cells generally assumed one of two interconvertible morphologies: a triangular tailed shape or tailed fibroblast (TF), and a tailless form that resembled a half-moon, which we call a half-moon fibroblast (HMF). The tail of TFs formed only on regions of substrate that had been previously traversed by cells. The half-moon morphology developed either on previously used or on virgin substrate. Cells adopted the HMF rather than the TF morphology with a four-fold greater frequency. HMFs translocated slightly faster than TFs. The foregoing observation suggest that the fibroblast tail is not an organelle essential for translocation. Since our technique allowed us to distinguish between cells which were cycling and those which had left cycle, we compared their velocities and found them to be similar. Also the average velocities of cells of different population-doubling levels (10th, 30th, 40th) were approximately equal.

Image Quality and Diagnostic Performance of a Digital PET Prototype in Patients with Oncologic Diseases: Initial Experience and Comparison with Analog PET.

PubMed

Nguyen, Nghi C; Vercher-Conejero, Jose L; Sattar, Abdus; Miller, Michael A; Maniawski, Piotr J; Jordan, David W; Muzic, Raymond F; Su, Kuan-Hao; O'Donnell, James K; Faulhaber, Peter F

2015-09-01

We report our initial clinical experience for image quality and diagnostic performance of a digital PET prototype scanner with time-of-flight (DigitalTF), compared with an analog PET scanner with time-of-flight (GeminiTF PET/CT). Twenty-one oncologic patients, mean age 58 y, first underwent clinical (18)F-FDG PET/CT on the GeminiTF. The scanner table was then withdrawn while the patient remained on the table, and the DigitalTF was inserted between the GeminiTF PET and CT scanner. The patients were scanned for a second time using the same PET field of view with CT from the GeminiTF for attenuation correction. Two interpreters reviewed the 2 sets of PET/CT images for overall image quality, lesion conspicuity, and sharpness. They counted the number of suggestive (18)F-FDG-avid lesions and provided the TNM staging for the 5 patients referred for initial staging. Standardized uptake values (SUVs) and SUV gradients as a measure of lesion sharpness were obtained. The DigitalTF showed better image quality than the GeminiTF. In a side-by-side comparison using a 5-point scale, lesion conspicuity (4.3 ± 0.6), lesion sharpness (4.3 ± 0.6), and diagnostic confidence (3.4 ± 0.7) were better with DigitalTF than with GeminiTF (P < 0.01). In 52 representative lesions, the lesion maximum SUV was 36% higher with DigitalTF than with GeminiTF, lesion-to-blood-pool SUV ratio was 59% higher, and SUV gradient was 51% higher, with good correlation between the 2 scanners. Lesions less than 1.5 cm showed a greater increase in SUV from GeminiTF to DigitalTF than those lesions 1.5 cm or greater. In 5 of 21 patients, DigitalTF showed an additional 8 suggestive lesions that were not seen using GeminiTF. In the 15 restaging patients, the true-negative rate was 100% and true-positive rate was 78% for both scanners. In the 5 patients for initial staging, DigitalTF led to upstaging in 2 patients and showed the same staging in the other 3 patients, compared with GeminiTF. DigitalTF provides better image quality, diagnostic confidence, and accuracy than GeminiTF. DigitalTF may be the most beneficial in detecting small tumor lesions and disease staging. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Factors Associated with Clinician Participation in TF-CBT Post-workshop Training Components.

PubMed

Pemberton, Joy R; Conners-Burrow, Nicola A; Sigel, Benjamin A; Sievers, Chad M; Stokes, Lauren D; Kramer, Teresa L

2017-07-01

For proficiency in an evidence-based treatment (EBT), mental health professionals (MHPs) need training activities extending beyond a one-time workshop. Using data from 178 MHPs participating in a statewide TF-CBT dissemination project, we used five variables assessed at the workshop, via multiple and logistic regression, to predict participation in three post-workshop training components. Perceived in-workshop learning and client-treatment mismatch were predictive of consultation call participation and case presentation respectively. Attitudes toward EBTs were predictive of trauma assessment utilization, although only with non-call participants removed from analysis. Productivity requirements and confidence in TF-CBT skills were not associated with participation in post-workshop activities.

Regulation of tissue factor in NT2 germ cell tumor cells by cisplatin chemotherapy.

PubMed

Jacobsen, Christine; Oechsle, Karin; Hauschild, Jessica; Steinemann, Gustav; Spath, Brigitte; Bokemeyer, Carsten; Ruf, Wolfram; Honecker, Friedemann; Langer, Florian

2015-09-01

Patients with germ cell tumors (GCTs) receiving cisplatin-based chemotherapy are at increased risk of thrombosis, but the underlying cellular and molecular mechanisms remain obscure. To study baseline tissue factor (TF) expression by GCT cell lines and its modulation by cisplatin treatment. TF expression was assessed by single-stage clotting and thrombin generation assay, flow cytometry, ELISA, and Western blot analysis. Cell cycle analysis and detection of phosphatidylserine (PS) membrane exposure were carried out by flow cytometry. TF mRNA was analyzed by quantitative RT-PCR. Significant expression of TF-specific procoagulant activity (PCA) was detected on three non-seminoma (NT2, 2102Ep, NCCIT) and one seminoma cell line (TCam-2). Treatment with 0.4μM cisplatin (corresponding to the IC50) for 48hrs increased TF PCA on NT2 cells 3-fold, an effect that was largely independent of PS exposure and that could not be explained by translocation of active TF from intracellular storage pools. Cisplatin-induced TF PCA expression in NT2 cells did not occur before 12hrs, but was steady thereafter and accompanied by a 2-fold increase in total and surface-located TF antigen. Importantly, increased TF gene transcription or production and release of an intermediate factor were not involved in this process. Cell cycle analysis suggested that cisplatin-induced G2/M arrest resulted in an accumulation of procoagulant TF on the membrane surface of NT2 cells. In addition to induction of apoptosis/necrosis with PS-mediated activation of preformed TF, cisplatin may alter the procoagulant phenotype of GCT cells through an increase in total cellular TF antigen. Copyright © 2015 Elsevier Ltd. All rights reserved.

Identification of Tf1 integration events in S. pombe under nonselective conditions

PubMed Central

Cherry, Kristina E.; Hearn, Willis E.; Seshie, Osborne Y.; Singleton, Teresa L.; Singleton, Teresa L.

2014-01-01

Integration of retroviral elements into the host genome is a phenomena observed among many classes of retroviruses. Much information concerning integration of retroviral elements has been documented based on in vitro analysis or expression of selectable markers. To identify possible Tf1 integration events within silent regions of the S. pombe genome, we focused on performing an in vivo genome-wide analysis of Tf1 integration events from the nonselective phase of the retrotransposition assay. We analyzed 1000 individual colonies streaked from four independent Tf1 transposed patches under nonselection conditions. Our analysis detected a population of G418S/neo+ Tf1 integration events that would have been overlooked during the selective phase of the assay. Further RNA analysis from the G418S/neo+ clones revealed 50% of clones expressing the neo selectable marker. Our data reveals Tf1’s ability to insert within silent regions of S. pombe’s genome. PMID:24680781

Identification of Tf1 integration events in S. pombe under nonselective conditions.

PubMed

Cherry, Kristina E; Hearn, Willis E; Seshie, Osborne Y K; Singleton, Teresa L

2014-06-01

Integration of retroviral elements into the host genome is a phenomena observed among many classes of retroviruses. Much information concerning the integration of retroviral elements has been documented based on in vitro analysis or expression of selectable markers. To identify possible Tf1 integration events within silent regions of the Schizosaccharomyces pombe genome, we focused on performing an in vivo genome-wide analysis of Tf1 integration events from the nonselective phase of the retrotransposition assay. We analyzed 1000 individual colonies streaked from four independent Tf1 transposed patches under nonselection conditions. Our analysis detected a population of G418(S)/neo(+) Tf1 integration events that would have been overlooked during the selective phase of the assay. Further RNA analysis from the G418(S)/neo(+) clones revealed 50% of clones expressing the neo selectable marker. Our data reveals Tf1's ability to insert within silent regions of S. pombe's genome. Copyright © 2014 Elsevier B.V. All rights reserved.

Angiotensin II Type 1 Receptor Antagonism Attenuates Abnormalities in Dynamic Renal Blood Flow Autoregulation in Rats with Endotoxin-Induced Acute Kidney Injury.

PubMed

Nitescu, Nicoletta; DiBona, Gerald F; Grimberg, Elisabeth; Guron, Gregor

2010-01-01

The aim was to examine the role of angiotensin II type 1 receptors in dynamic autoregulation of renal blood flow (RBF) in endotoxemia. Experiments were performed on anesthetized rats 16 h after intraperitoneal lipopolysaccharide (LPS) or vehicle administration. After baseline measurements, groups Sham-Saline, LPS-Saline and LPS-Candesartan received isotonic saline or candesartan (10 μg kg(-1) i.v.). Data were collected during eight consecutive 20-min clearance periods (C1-8). Transfer function (TF) analysis in the frequency domain was used to examine dynamic autoregulation of RBF. Endotoxemic rats showed an approximate 50% reduction in glomerular filtration rate (GFR) and RBF (p < 0.05 vs. Sham-Saline). Candesartan significantly increased RBF (+40 ± 6% vs. baseline; p < 0.05) but did not significantly influence GFR. Endotoxemic animals showed a normal myogenic response but had elevated TF gain values in the frequency range of the tubuloglomerular feedback mechanism (TGF; 0.01-0.03 Hz) reflecting impaired autoregulation (periods C3-4, 2.2 ± 1.6 vs. -2.6 ± 0.6 dB, p < 0.05, and C7-8, -0.4 ± 1.3 vs. -4.0 ± 0.8 dB, p < 0.05; in groups LPS-Saline and Sham-Saline, respectively). Candesartan normalized TF gain in this frequency range (periods C7-8, -6.1 ± 2.3 dB in group LPS-Candesartan, p < 0.05 vs. LPS-Saline). Candesartan ameliorates the adverse effect of endotoxin on the TGF component of dynamic autoregulation of RBF. Copyright © 2010 S. Karger AG, Basel.

The Role of Eating Habits on the Iron Status of Pregnant Women.

PubMed

Bivolarska, Anelia V; Gatseva, Penka D; Maneva, Ana I

2016-01-01

This study highlights the relationship between some eating habits and iron status during pregnancy. The study included 219 healthy pregnant women aged 27.6 ± 5.7 years from southern Bulgaria. Subjects' iron status was assessed on the basis of the following iron indicators: hemoglobin (Hb), serum ferritin (SF), serum transferrin receptor (sTfR), and body iron index (mg/kg). Severe anemia among the women from southern Bulgaria was not observed. Advanced pregnancy and some eating habits are factors that deteriorate iron status. Women who had consumed fish at least 3 times a week had lower levels of sTfR (р = 0.008), higher levels of SF (р = 0.05), and lower levels of body iron (р = 0.018). Frequent legume consumption was related to increased levels of sTfR (р = 0.036). Pregnant women with a high frequency of coffee consumption had lower values of body iron (р < 0.0001). Women who had consumed cow's milk at least 3 times a week had lower levels of SF (р = 0.026) and body iron (р = 0.042). Regular consumption of fish and legumes, rarely drinking coffee, and milk consumption during the intervals between food intake are conditions for optimization of iron status during pregnancy.

Quantitative analysis of collagens and fibronectin expression in human right ventricular hypertrophy.

PubMed

Peters, T H; Sharma, H S; Yilmaz, E; Bogers, A J

1999-06-30

One of the main features in human tetralogy of Fallot (TF) is right ventricular hypertrophy (RVH) due to pressure (sub-pulmonary stenosis) and volume overload (ventricular septal defect). Currently, primary correction at a young age is the treatment of choice. To unravel the role of extracellular matrix in RVH, we examined myocardial expression of collagens and fibronectin in TF patients with primary correction (TF1, age 0.7 +/- 0.2 yr.), secondary surgery (TF2, age 36.9 +/- 4.6 yr), and in age-matched control patients. Sirius red staining quantified by video imaging showed significantly increased interstitial staining for collagens in both TF1 and TF2 groups as compared to respective controls. Fibronectin was expressed in extracellular spaces, perivascular regions, and in some cardiomyocytes. Quantitative analysis of fibronectin revealed increased expression in only TF1 group as compared to respective control. Our results indicate an increased amount of myocardial extracellular matrix deposition as a sign of fibrosis during RVH in patients with TF.

Ventricular Fibrillation and Tachycardia detection from surface ECG using time-frequency representation images as input dataset for machine learning.

PubMed

Mjahad, A; Rosado-Muñoz, A; Bataller-Mompeán, M; Francés-Víllora, J V; Guerrero-Martínez, J F

2017-04-01

To safely select the proper therapy for Ventricullar Fibrillation (VF) is essential to distinct it correctly from Ventricular Tachycardia (VT) and other rhythms. Provided that the required therapy would not be the same, an erroneous detection might lead to serious injuries to the patient or even cause Ventricular Fibrillation (VF). The main novelty of this paper is the use of time-frequency (t-f) representation images as the direct input to the classifier. We hypothesize that this method allow to improve classification results as it allows to eliminate the typical feature selection and extraction stage, and its corresponding loss of information. The standard AHA and MIT-BIH databases were used for evaluation and comparison with other authors. Previous to t-f Pseudo Wigner-Ville (PWV) calculation, only a basic preprocessing for denoising and signal alignment is necessary. In order to check the validity of the method independently of the classifier, four different classifiers are used: Logistic Regression with L2 Regularization (L2 RLR), Adaptive Neural Network Classifier (ANNC), Support Vector Machine (SSVM), and Bagging classifier (BAGG). The main classification results for VF detection (including flutter episodes) are 95.56% sensitivity and 98.8% specificity, 88.80% sensitivity and 99.5% specificity for ventricular tachycardia (VT), 98.98% sensitivity and 97.7% specificity for normal sinus, and 96.87% sensitivity and 99.55% specificity for other rhythms. Results shows that using t-f data representations to feed classifiers provide superior performance values than the feature selection strategies used in previous works. It opens the door to be used in any other detection applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Dynamic Transcription Factor Networks in Epithelial-Mesenchymal Transition in Breast Cancer Models

PubMed Central

Siletz, Anaar; Schnabel, Michael; Kniazeva, Ekaterina; Schumacher, Andrew J.; Shin, Seungjin; Jeruss, Jacqueline S.; Shea, Lonnie D.

2013-01-01

The epithelial-mesenchymal transition (EMT) is a complex change in cell differentiation that allows breast carcinoma cells to acquire invasive properties. EMT involves a cascade of regulatory changes that destabilize the epithelial phenotype and allow mesenchymal features to manifest. As transcription factors (TFs) are upstream effectors of the genome-wide expression changes that result in phenotypic change, understanding the sequential changes in TF activity during EMT provides rich information on the mechanism of this process. Because molecular interactions will vary as cells progress from an epithelial to a mesenchymal differentiation program, dynamic networks are needed to capture the changing context of molecular processes. In this study we applied an emerging high-throughput, dynamic TF activity array to define TF activity network changes in three cell-based models of EMT in breast cancer based on HMLE Twist ER and MCF-7 mammary epithelial cells. The TF array distinguished conserved from model-specific TF activity changes in the three models. Time-dependent data was used to identify pairs of TF activities with significant positive or negative correlation, indicative of interdependent TF activity throughout the six-day study period. Dynamic TF activity patterns were clustered into groups of TFs that change along a time course of gene expression changes and acquisition of invasive capacity. Time-dependent TF activity data was combined with prior knowledge of TF interactions to construct dynamic models of TF activity networks as epithelial cells acquire invasive characteristics. These analyses show EMT from a unique and targetable vantage and may ultimately contribute to diagnosis and therapy. PMID:23593114

Dynamic transcription factor networks in epithelial-mesenchymal transition in breast cancer models.

PubMed

Siletz, Anaar; Schnabel, Michael; Kniazeva, Ekaterina; Schumacher, Andrew J; Shin, Seungjin; Jeruss, Jacqueline S; Shea, Lonnie D

2013-01-01

The epithelial-mesenchymal transition (EMT) is a complex change in cell differentiation that allows breast carcinoma cells to acquire invasive properties. EMT involves a cascade of regulatory changes that destabilize the epithelial phenotype and allow mesenchymal features to manifest. As transcription factors (TFs) are upstream effectors of the genome-wide expression changes that result in phenotypic change, understanding the sequential changes in TF activity during EMT provides rich information on the mechanism of this process. Because molecular interactions will vary as cells progress from an epithelial to a mesenchymal differentiation program, dynamic networks are needed to capture the changing context of molecular processes. In this study we applied an emerging high-throughput, dynamic TF activity array to define TF activity network changes in three cell-based models of EMT in breast cancer based on HMLE Twist ER and MCF-7 mammary epithelial cells. The TF array distinguished conserved from model-specific TF activity changes in the three models. Time-dependent data was used to identify pairs of TF activities with significant positive or negative correlation, indicative of interdependent TF activity throughout the six-day study period. Dynamic TF activity patterns were clustered into groups of TFs that change along a time course of gene expression changes and acquisition of invasive capacity. Time-dependent TF activity data was combined with prior knowledge of TF interactions to construct dynamic models of TF activity networks as epithelial cells acquire invasive characteristics. These analyses show EMT from a unique and targetable vantage and may ultimately contribute to diagnosis and therapy.

Comparative Analysis of Ultrasonic Inspection Procedures for Kaman K747 Root End Fittings

DTIC Science & Technology

1989-04-01

I.CI- IA 4cz 4c-- a- LLJ 4A ccu I46 APPENDIX III. TRANSDUCER WEDGE ANGLE DATA RESULTS No Procedure, Gain = 70 dB 45.Degre Probe REF# TF1 TF2 TF3 TAl...Degree Probe REF # TF1 TF2 TF3 TAl TA2 TA3 BF1 BF2 BF3 BAl BA2 BA3 B5328 35 33 -. . . 31 - - - - - 38 38 B5102 38 - 31 .. - - 31 - - - B5298 40 42...50 No Procedure, Gain = 70 dB 50-Degree Probe REF # TF1 TF2 TF3 TAl TA2 TA3 BF1 BF2 BF3 BAl BA2 BA3 B5328 - . . . . 32 - 40 B5102 34 .- 30

DNA-bending properties of TF1.

PubMed

Schneider, G J; Sayre, M H; Geiduschek, E P

1991-10-05

Transcription factor 1 (TF1) is the Bacillus subtilis phage SPO1-encoded member of the family of DNA-binding proteins that includes Escherichia coli HU and integration host factor, IHF. A gel electrophoretic retardation method has been used to show that a TF1 dimer binding to one of its preferred sites in (5-hydroxymethyl)uracil (hmUra)-containing DNA sharply bends the latter. In fact, the DNA-bending properties of TF1 and E. coli IHF are indistinguishable. Substitutions at amino acid 61 in the DNA-binding "arm" of TF1 are known to affect DNA-binding affinity and site selectivity. Experiments described here show that these substitutions also affect DNA bending. The selectivity of TF1 binding is very greatly diminished and the affinity is reduced when hmUra is replaced in DNA by thymine (T). An extension of the gel retardation method that permits an analysis of DNA bending by non-specifically bound TF1 is proposed. Under the assumptions of this analysis, the reduced affinity of TF1 for T-containing DNA is shown to be associated with bending that is still sharp. The analysis of the TF1-DNA interaction has also been extended by hydroxyl radical (.OH) and methylation interference footprinting at two DNA sites. At each of these sites, and on each strand, TF1 strongly protects three segments of DNA from attack by OH. Patches of protected DNA are centered approximately ten base-pairs apart and fall on one side of the B-helix. Methylation in either the major or minor groove in the central ten base-pairs of the two TF1 binding sites quantitatively diminishes, but does not abolish, TF1 binding. We propose that multiple protein contacts allow DNA to wrap around the relatively small TF1 dimer, considerably deforming the DNA B-helix in the process.

Non-linear transfer characteristics of stimulation and recording hardware account for spurious low-frequency artifacts during amplitude modulated transcranial alternating current stimulation (AM-tACS).

PubMed

Kasten, Florian H; Negahbani, Ehsan; Fröhlich, Flavio; Herrmann, Christoph S

2018-05-31

Amplitude modulated transcranial alternating current stimulation (AM-tACS) has been recently proposed as a possible solution to overcome the pronounced stimulation artifact encountered when recording brain activity during tACS. In theory, AM-tACS does not entail power at its modulating frequency, thus avoiding the problem of spectral overlap between brain signal of interest and stimulation artifact. However, the current study demonstrates how weak non-linear transfer characteristics inherent to stimulation and recording hardware can reintroduce spurious artifacts at the modulation frequency. The input-output transfer functions (TFs) of different stimulation setups were measured. Setups included recordings of signal-generator and stimulator outputs and M/EEG phantom measurements. 6 th -degree polynomial regression models were fitted to model the input-output TFs of each setup. The resulting TF models were applied to digitally generated AM-tACS signals to predict the frequency of spurious artifacts in the spectrum. All four setups measured for the study exhibited low-frequency artifacts at the modulation frequency and its harmonics when recording AM-tACS. Fitted TF models showed non-linear contributions significantly different from zero (all p < .05) and successfully predicted the frequency of artifacts observed in AM-signal recordings. Results suggest that even weak non-linearities of stimulation and recording hardware can lead to spurious artifacts at the modulation frequency and its harmonics. These artifacts were substantially larger than alpha-oscillations of a human subject in the MEG. Findings emphasize the need for more linear stimulation devices for AM-tACS and careful analysis procedures, taking into account low-frequency artifacts to avoid confusion with effects of AM-tACS on the brain. Copyright © 2018 Elsevier Inc. All rights reserved.

Innu food consumption patterns: traditional food and body mass index.

PubMed

Atikessé, Laura; de Grosbois, Sylvie Boucher; St-Jean, Mélissa; Penashue, Basile Mashen; Benuen, Manipia

2010-01-01

Food consumption patterns of an Innu community were described and the benefits of traditional food (TF) were investigated in relation to body mass index (BMI). A cross-sectional study was conducted using food frequency and 24-hour recall questionnaires to evaluate consumption patterns (n=118) and to assess energy and nutrient intakes from TF and store-bought food (SBF) (n=161). Body mass index was calculated with a sub-sample of 45 participants. Mean yearly TF meal consumption was significantly related to age (p=0.05). Participants reporting high TF and low SBF consumption presented with a normal body weight (BMI=24.1) at the lower quartile and a slightly overweight status (BMI=25.8) at the median. Mean values for protein and carbohydrate intake were higher than the Dietary Reference Intakes, whereas dietary fibre intake was below these guidelines for both genders. Store-bought food provided higher levels of energy and nutrients, except for protein. Although Innu consume high amounts of TF and SBF, a lack of some essential nutrients was observed. Because TF intake was related to a tendency toward a lower BMI, a combined, targeted diet could be proposed. Health services could reinforce the importance of TF consumption and promote traditional dietary practices that offer advantages at many levels.

Restriction of Retrotransposon Mobilization in Schizosaccharomyces pombe by Transcriptional Silencing and Higher-Order Chromatin Organization

PubMed Central

Murton, Heather E.; Grady, Patrick J. R.; Chan, Tsun Ho; Cam, Hugh P.; Whitehall, Simon K.

2016-01-01

Uncontrolled propagation of retrotransposons is potentially detrimental to host genome integrity. Therefore, cells have evolved surveillance mechanisms to restrict the mobility of these elements. In Schizosaccharomyces pombe the Tf2 LTR retrotransposons are transcriptionally silenced and are also clustered in the nucleus into structures termed Tf bodies. Here we describe the impact of silencing and clustering on the mobility of an endogenous Tf2 element. Deletion of genes such as set1+ (histone H3 lysine 4 methyltransferase) or abp1+ (CENP-B homolog) that both alleviate silencing and clustering, result in a corresponding increase in mobilization. Furthermore, expression of constitutively active Sre1, a transcriptional activator of Tf2 elements, also alleviates clustering and induces mobilization. In contrast, clustering is not disrupted by loss of the HIRA histone chaperone, despite high levels of expression, and in this background, mobilization frequency is only marginally increased. Thus, mutations that compromise transcriptional silencing but not Tf bodies are insufficient to drive mobilization. Furthermore, analyses of mutant alleles that separate the transcriptional repression and clustering functions of Set1 are consistent with control of Tf2 propagation via a combination of silencing and spatial organization. Our results indicate that host surveillance mechanisms operate at multiple levels to restrict Tf2 retrotransposon mobilization. PMID:27343236

Dynamic motif occupancy (DynaMO) analysis identifies transcription factors and their binding sites driving dynamic biological processes.

PubMed

Kuang, Zheng; Ji, Zhicheng; Boeke, Jef D; Ji, Hongkai

2018-01-09

Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data. In the first step, DynaMO predicts TF binding sites with a random forests approach. Next and uniquely, DynaMO infers dynamic TF binding activities at predicted binding sites using their local chromatin profiles from multiple biological conditions. Another landmark of DynaMO is to identify key TFs in a dynamic process using a clustering and enrichment analysis of dynamic TF binding patterns. Application of DynaMO to the yeast ultradian cycle, mouse circadian clock and human neural differentiation exhibits its accuracy and versatility. We anticipate DynaMO will be generally useful for elucidating transcriptional programs in dynamic processes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Characterization of the interaction between diferric transferrin and transferrin receptor 2 by functional assays and atomic force microscopy*

PubMed Central

Ikuta, Katsuya; Yersin, Alexandre; Ikai, Atsushi; Aisen, Philip; Kohgo, Yutaka

2010-01-01

Transferrin receptor (TfR2), a homologue of classical transferrin receptor 1 (TfR1), is found in two isoforms, α and β. Like TfR1, TfR2α is a type II membrane protein, but the β form lacks transmembrane portions and therefore is likely to be an intracellular protein. To investigate the functional properties of TfR2α we expressed the protein with FLAG-tagging in transferrin receptor-deficient Chinese hamster ovary cells. The association constant for binding of diferric transferrin (Tf) to TfR2α is 5.6 × 106 M−1, which is about 50 times lower than that of TfR1, with correspondingly reduced rates of iron uptake. Evidence for Tf internalization and recycling via TfR2α without degradation, as in the TfR1 pathway, was also found. The interaction of TfR2α with Tf was further investigated using atomic force microscopy (AFM), a powerful tool for investigation of the interaction between ligand and receptor at the single molecule level on the living cell surface. Dynamic force microscopy reveals a difference in the interactions of Tf with TfR2α and TfR1, with Tf-TfR1 unbinding characterized by 2 energy barriers, while only one is present for Tf-TfR2. We speculate that this difference may reflect Tf binding to TfR2α by a single lobe, whereas two lobes of Tf participate in binding to TfR1. The difference in the binding properties of Tf to TfR1 and TfR2α may help account for the different physiological roles of the two receptors. PMID:20096706

Next generation phenotyping using narrative reports in a rare disease clinical data warehouse.

PubMed

Garcelon, Nicolas; Neuraz, Antoine; Salomon, Rémi; Bahi-Buisson, Nadia; Amiel, Jeanne; Picard, Capucine; Mahlaoui, Nizar; Benoit, Vincent; Burgun, Anita; Rance, Bastien

2018-05-31

Secondary use of data collected in Electronic Health Records opens perspectives for increasing our knowledge of rare diseases. The clinical data warehouse (named Dr. Warehouse) at the Necker-Enfants Malades Children's Hospital contains data collected during normal care for thousands of patients. Dr. Warehouse is oriented toward the exploration of clinical narratives. In this study, we present our method to find phenotypes associated with diseases of interest. We leveraged the frequency and TF-IDF to explore the association between clinical phenotypes and rare diseases. We applied our method in six use cases: phenotypes associated with the Rett, Lowe, Silver Russell, Bardet-Biedl syndromes, DOCK8 deficiency and Activated PI3-kinase Delta Syndrome (APDS). We asked domain experts to evaluate the relevance of the top-50 (for frequency and TF-IDF) phenotypes identified by Dr. Warehouse and computed the average precision and mean average precision. Experts concluded that between 16 and 39 phenotypes could be considered as relevant in the top-50 phenotypes ranked by descending frequency discovered by Dr. Warehouse (resp. between 11 and 41 for TF-IDF). Average precision ranges from 0.55 to 0.91 for frequency and 0.52 to 0.95 for TF-IDF. Mean average precision was 0.79. Our study suggests that phenotypes identified in clinical narratives stored in Electronic Health Record can provide rare disease specialists with candidate phenotypes that can be used in addition to the literature. Clinical Data Warehouses can be used to perform Next Generation Phenotyping, especially in the context of rare diseases. We have developed a method to detect phenotypes associated with a group of patients using medical concepts extracted from free-text clinical narratives.

[siRNA-mediated tissue factor knockdown in porcine neonatal islet cell clusters in vitro].

PubMed

Ji, Ming; Yi, Shounan; Yu, Deling; Wang, Wei

2011-12-01

To determine the genetic modification on neonatal porcine islet cell clusters (NICC) by small interfering RNA (siRNA)-mediated tissue factor (TF) knockdown in vitro. Porcine NICC were transfected with 5 pairs of designed siRNA respectively or in different combinations with lipofectamine 2000. Transfected NICC were analyzed for TF gene by real-time PCR to select the siRNA which worked best. Meanwhile, the viability of NICC after the TF siRNA transfection was examined by FACS. The efficiency of TF gene and protein suppression was measured by real-time PCR and and FACS respectively. Real-time PCR and FACS showed that a 60% reduction in the TF gene expression and a 50% reduction in the protien level of TF on NICC were achieved by transfecting 3 pairs of selected siRNA. The siRNA transfection had no significant effect on the viability of NICC which was analyzed by FACS. The expression of TF on porcine NICC is efficiently suppressed by 3 pairs of designed siRNA in vitro.

The microbial changes in subgingival plaques of orthodontic patients: a systematic review and meta-analysis of clinical trials.

PubMed

Guo, Runzhi; Lin, Yifan; Zheng, Yunfei; Li, Weiran

2017-06-02

Orthodontic treatment was found to have an impact on the quantity and constitution of subgingival microbiota. However, contradictory findings regarding the effects of fixed appliances on microbial changes were reported. The aim of this systematic review was to investigate the microbial changes in subgingival plaques of orthodontic patients. The PubMed, Cochrane Library, and EMBASE databases were searched up to November 20, 2016. Longitudinal studies observing microbial changes in subgingival plaques at different time points of orthodontic treatment are included. The methodological quality of the included studies was assessed by Methodological index for non-randomized studies (MINORS). The studies that reported the frequency of subgingival periodontopathogens were used for quantitative analysis. Other studies were analysed qualitatively to describe the microbial changes during orthodontic treatment. Thirteen studies were selected, including two controlled clinical trials, three cohort studies and eight self-controlled studies. Four periodontopathogens, including Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi) and Tannerella forsythia (Tf), were analysed. Following orthodontic appliance placement, the frequencies of Pg and Aa showed no significant change (P = 0.97 and P = 0.77), whereas the frequency of Tf significantly increased (P < 0.01) during short-term observation (0-3 months). The frequency of Pi showed a tooth-specific difference, as it presented no significant difference (P = 0.25) at the site of the first molar but was significantly increased (P = 0.01) at the incisor. During long-term observation (> = 6 months), two studies reported that the levels of subgingival periodontopathogens exhibited a transient increase but decreased to the pretreatment levels afterwards. After removal of the orthodontic appliance, the four periodontopathogens showed no significant difference compared with before removal. The levels of subgingival pathogens presented temporary increases after orthodontic appliance placement, and appeared to return to pretreatment levels several months later. This indicates that orthodontic treatment might not permanently induce periodontal disease by affecting the level of subgingival periodontal pathogen levels. Further studies of high methodological quality are required to provide more reliable evidence regarding this issue.

Fructose induces prothrombotic phenotype in human endothelial cells : A new role for "added sugar" in cardio-metabolic risk.

PubMed

Cirillo, Plinio; Pellegrino, Grazia; Conte, Stefano; Maresca, Fabio; Pacifico, Francesco; Leonardi, Antonio; Trimarco, Bruno

2015-11-01

Intake of large amounts of added sweeteners has been associated with the pathogenesis of cardiometabolic risk. Several studies have shown that fructose increases the cardiovascular risk by modulating endothelial dysfunction and promoting atherosclerosis. Recently, a potential role for fructose in cardiovascular thrombosis has been suggested but with controversial results. Tissue factor (TF) plays a pivotal role in the pathophysiology of cardiovascular thrombosis by triggering the formation of intracoronary thrombi following endothelial injury. This study investigates the effects of fructose, in a concentration range usually observed in the plasma of patients with increased cardiovascular risk, on TF in human umbilical endothelial cells (HUVECs). Cells were stimulated with increasing concentrations of fructose (0.25, 1 and 2.5 mM) and then processed to evaluate TF-mRNA levels by real-time PCR as well as TF expression/activity by FACS analysis and procoagulant activity. Finally, a potential molecular pathway involved in modulating this phenomenon was investigated. We demonstrate that fructose induces transcription of mRNA for TF. In addition, we show that this monosaccharide promotes surface expression of TF that is functionally active. Fructose effects on TF appear modulated by the oxygen free radicals through activation of the transcription factor NF-κB since superoxide dismutase and NF-κB inhibitors suppressed TF expression. Data of the present study, although in vitro, indicate that fructose, besides promoting atherosclerosis, induces a prothrombotic phenotype in HUVECs, thus indicating one the mechanism(s) by which this sweetener might increase cardiometabolic risk.

Super-Resolution of Multi-Pixel and Sub-Pixel Images for the SDI

DTIC Science & Technology

1993-06-08

where the phase of the transmitted signal is not needed. The Wigner - Ville distribution ( WVD ) of a real signal s(t), associated with the complex...B. Boashash, 0. P. Kenny and H. J. Whitehouse, "Radar imaging using the Wigner - Ville distribution ", in Real-Time Signal Processing, J. P. Letellier...analytic signal z(t), is a time- frequency distribution defined as-’- 00 W(tf) Z (~t + ) t- -)exp(-i2nft) . (45) Note that the WVD is the double Fourier

Carbohydrates and activity of natural and recombinant tissue factor.

PubMed

Krudysz-Amblo, Jolanta; Jennings, Mark E; Mann, Kenneth G; Butenas, Saulius

2010-01-29

The effect of glycosylation on tissue factor (TF) activity was evaluated, and site-specific glycosylation of full-length recombinant TF (rTF) and that of natural TF from human placenta (pTF) were studied by liquid chromatography-tandem mass spectrometry. The amidolytic activity of the TF.factor VIIa (FVIIa) complex toward a fluorogenic substrate showed that the catalytic efficiency (V(max)) of the complex increased in the order rTF(1-243) (Escherichia coli) < rTF(1-263) (Sf9 insect cells) < pTF for the glycosylated and deglycosylated forms. Substrate hydrolysis was unaltered by deglycosylation. In FXase, the K(m) of FX for rTF(1-263)-FVIIa remained unchanged after deglycosylation, whereas the k(cat) decreased slightly. A pronounced decrease, 4-fold, in k(cat) was observed for pTF.FVIIa upon deglycosylation, whereas the K(m) was minimally altered. The parameters of FX activation by both rTF(1-263D)-FVIIa and pTF(D)-FVIIa were identical and similar to those for rTF(1-243)-FVIIa. In conclusion, carbohydrates significantly influence the activity of TF proteins. Carbohydrate analysis revealed glycosylation on asparagines 11, 124, and 137 in both rTF(1-263) and pTF. The carbohydrates of rTF(1-263) contain high mannose, hybrid, and fucosylated glycans. Natural pTF contains no high mannose glycans but is modified with hybrid, highly fucosylated, and sialylated sugars.

Quantitative in vivo imaging of tissue factor expression in glioma using dynamic contrast-enhanced MRI derived parameters.

PubMed

Chen, Xiao; Xie, Tian; Fang, Jingqin; Xue, Wei; Tong, Haipeng; Kang, Houyi; Wang, Sumei; Yang, Yizeng; Xu, Minhui; Zhang, Weiguo

2017-08-01

Tissue Factor (TF) has been well established in angiogenesis, invasion, metastasis, and prognosis in glioma. A noninvasive assessment of TF expression status in glioma is therefore of obvious clinical relevance. Dynamic contrast-enhanced (DCE) MRI parameters have been used to evaluate microvascular characteristics and predict molecular expression status in tumors. Our aim is to investigate whether quantitative DCE-MRI parameters could assess TF expression in glioma. Thirty-two patients with histopathologically diagnosed supratentorial glioma who underwent DCE-MRI were retrospectively recruited. Extended Tofts linear model was used for DCE-MRI post-processing. Hot-spot, whole tumor cross-sectional approaches, and histogram were used for analysis of model based parameters. Four serial paraffin sections of each case were stained with TF, CD105, CD34 and α-Sooth Muscle Actin, respectively for evaluating the association of TF and microvascular properties. Pearson correlation was performed between percentage of TF expression area and DCE-MRI parameters, multiple microvascular indexes. Volume transfer constant (K trans ) hot-spot value best correlated with TF (r=0.886, p<0.001), followed by 90th percentile K trans value (r=0.801, p<0.001). Moreover, histogram analysis of K trans value demonstrated that weak TF expression was associated with less heterogeneous and positively skewed distribution. Finally, pathology analysis revealed TF was associated with glioma grade and significantly correlated with these two dynamic angiogenic indexes which could be used to explain the strong correlation between K trans and TF expression. Our results indicate that K trans may serve as a potential clinical imaging biomarker to predict TF expression status preoperatively in gliomas. Copyright © 2017 Elsevier B.V. All rights reserved.

Radiation hardness of lead glasses TF1 and TF101

NASA Astrophysics Data System (ADS)

Kobayashi, Masaaki; Prokoshkin, Yuri; Singovsky, Alexandre; Takamatsu, Kunio

1994-06-01

We have measured the radiation hardness of two types of lead glasses, TF1 and TF101, for low energy γ-rays from 60Co. TF101 containing cerium is a few tens times radiation harder than TF1 which contains no cerium. The radiation hardness, or the tolerable accumulated dose, of TF101 is 2 × 10 3 rad when the degradation of the transmittance is required to be less than 1% for the unit radiation length X0 = 2.8 cm. When the present result is compared with the work of Inyakin et al., the radiation hardness of TF101 glass should be similar for both γ-rays and for high energy hadrons.

Stepped care versus standard trauma-focused cognitive behavioral therapy for young children

PubMed Central

Salloum, Alison; Wang, Wei; Robst, John; Murphy, Tanya K.; Scheeringa, Michael S.; Cohen, Judith A.; Storch, Eric A.

2015-01-01

Background Compare the effectiveness and cost of stepped care trauma-focused cognitive behavioral therapy (SC-TF-CBT), a new service delivery method designed to address treatment barriers, to standard TF-CBT among young children who were experiencing posttraumatic stress symptoms (PTSS). Methods A total of 53 children (ages 3-7 years) who were experiencing PTSS were randomly assigned (2:1) to receive SC-TF-CBT or TF-CBT. Assessments by a blinded evaluator occurred at screening/baseline, after Step One for SC-TF-CBT, post-treatment, and 3-month follow-up. Trial registration: ClinicalTrials.gov: https://www.clinicaltrials.gov/ct2/show/NCT01603563 Results There were comparable improvements over time in PTSS and secondary outcomes in both conditions. Non-inferiority of SC-TF-CBT compared to TF-CBT was supported for the primary outcome of PTSS, and the secondary outcomes of severity and internalizing symptoms, but not for externalizing symptoms. There were no statistical differences in comparisons of changes over time from pre- to post-treatment and pre- to 3 month follow-up for PTSD diagnostic status, treatment response or remission. Parent satisfaction was high for both conditions. Costs were 51.3% lower for children in SC-TF-CBT compared to TF-CBT. Conclusions Although future research is needed, preliminary evidence suggests that SC-TF-CBT is comparable to TF-CBT, and delivery costs are significantly less than standard care. SC-TF-CBT may be a viable service delivery system to address treatment barriers. PMID:26443493

A Critical Policy Analysis of 'Teach for Bangladesh': A Travelling Policy Touches Down

ERIC Educational Resources Information Center

Adhikary, Rino Wiseman; Lingard, Bob

2018-01-01

This paper provides a critical policy analysis and network ethnography of "Teach for Bangladesh" ("TfB"). We demonstrate that TfB is a localised version of a global teacher education policy--"Teach for All/America" ("TfAll/A"). Santos, Boaventura De Sousa [2002. "The Processes of Globalisation."…

Identification of Human Lineage-Specific Transcriptional Coregulators Enabled by a Glossary of Binding Modules and Tunable Genomic Backgrounds.

PubMed

Mariani, Luca; Weinand, Kathryn; Vedenko, Anastasia; Barrera, Luis A; Bulyk, Martha L

2017-09-27

Transcription factors (TFs) control cellular processes by binding specific DNA motifs to modulate gene expression. Motif enrichment analysis of regulatory regions can identify direct and indirect TF binding sites. Here, we created a glossary of 108 non-redundant TF-8mer "modules" of shared specificity for 671 metazoan TFs from publicly available and new universal protein binding microarray data. Analysis of 239 ENCODE TF chromatin immunoprecipitation sequencing datasets and associated RNA sequencing profiles suggest the 8mer modules are more precise than position weight matrices in identifying indirect binding motifs and their associated tethering TFs. We also developed GENRE (genomically equivalent negative regions), a tunable tool for construction of matched genomic background sequences for analysis of regulatory regions. GENRE outperformed four state-of-the-art approaches to background sequence construction. We used our TF-8mer glossary and GENRE in the analysis of the indirect binding motifs for the co-occurrence of tethering factors, suggesting novel TF-TF interactions. We anticipate that these tools will aid in elucidating tissue-specific gene-regulatory programs. Copyright © 2017 Elsevier Inc. All rights reserved.

A multivariate time-frequency method to characterize the influence of respiration over heart period and arterial pressure

NASA Astrophysics Data System (ADS)

Orini, Michele; Bailón, Raquel; Laguna, Pablo; Mainardi, Luca T.; Barbieri, Riccardo

2012-12-01

Respiratory activity introduces oscillations both in arterial pressure and heart period, through mechanical and autonomic mechanisms. Respiration, arterial pressure, and heart period are, generally, non-stationary processes and the interactions between them are dynamic. In this study we present a methodology to robustly estimate the time course of cross spectral indices to characterize dynamic interactions between respiratory oscillations of heart period and blood pressure, as well as their interactions with respiratory activity. Time-frequency distributions belonging to Cohen's class are used to estimate time-frequency (TF) representations of coherence, partial coherence and phase difference. The characterization is based on the estimation of the time course of cross spectral indices estimated in specific TF regions around the respiratory frequency. We used this methodology to describe the interactions between respiration, heart period variability (HPV) and systolic arterial pressure variability (SAPV) during tilt table test with both spontaneous and controlled respiratory patterns. The effect of selective autonomic blockade was also studied. Results suggest the presence of common underling mechanisms of regulation between cardiovascular signals, whose interactions are time-varying. SAPV changes followed respiratory flow both in supine and standing positions and even after selective autonomic blockade. During head-up tilt, phase differences between respiration and SAPV increased. Phase differences between respiration and HPV were comparable to those between respiration and SAPV during supine position, and significantly increased during standing. As a result, respiratory oscillations in SAPV preceded respiratory oscillations in HPV during standing. Partial coherence was the most sensitive index to orthostatic stress. Phase difference estimates were consistent among spontaneous and controlled breathing patterns, whereas coherence was higher in spontaneous breathing. Parasympathetic blockade did not affect interactions between respiration and SAPV, reduced the coherence between SAPV and HPV and between respiration and HPV. Our results support the hypothesis that non-autonomic, possibly mechanically mediated, mechanisms also contributes to the respiratory oscillations in HPV. A small contribution of sympathetic activity on HPV-SAPV interactions around the respiratory frequency was also observed.

Demonstration of retrotransposition of the Tf1 element in fission yeast.

PubMed

Levin, H L; Boeke, J D

1992-03-01

Tf1, a retrotransposon from fission yeast, has LTRs and coding sequences resembling the protease, reverse transcriptase and integrase domains of retroviral pol genes. A unique aspect of Tf1 is that it contains a single open reading frame whereas other retroviruses and retrotransposons usually possess two or more open reading frames. To determine whether Tf1 can transpose, we overproduced Tf1 transcripts encoded by a plasmid copy of the element marked with a neo gene. Approximately 0.1-4.0% of the cell population acquired chromosomally inherited resistance to G418. DNA blot analysis demonstrated that such strains had acquired both Tf1 and neo specific sequences within a restriction fragment of the same size; the size of this restriction fragment varied between different isolates. Structural analysis of the cloned DNA flanking the Tf1-neo element of two transposition candidates with the same regions in the parent strain showed that the ability to grow on G418 was due to transposition of Tf1-neo and not other types of recombination events.

Effect of circulating tissue factor on hypercoagulability in type 2 diabetes mellitus studied by rheometry and dielectric blood coagulometry.

PubMed

Uchimura, Isao; Kaibara, Makoto; Nagasawa, Masayuki; Hayashi, Yoshihito

2016-01-01

Hypercoagulability in type 2 diabetes mellitus (T2DM) patients increases their risk of cardiovascular diseases. The aim of this work was to investigate the hypercoagulation mechanism in T2DM patients in terms of circulating tissue factor (TF). Whole blood coagulation tests by damped oscillation rheometry and dielectric blood coagulometry (DBCM) were performed. The average coagulation time was significantly shorter for T2DM patients than for healthy controls. In vitro addition of either anti-TF or anti-activated factor VII (FVIIa) antibody to hypercoagulable blood samples prolonged coagulation times for one group of patients, while coagulation times remained short for another group. The levels of circulating TF were estimated in the former group by measuring the coagulation times for blood samples from healthy subjects with addition of various concentrations of TF and comparing them with the coagulation times for the group. The results indicated that the levels of circulating TF were on the order of subpicomolar at most. Circulating TF is at least partially responsible for a hypercoagulable group of T2DM patients, while an abnormality in the intrinsic coagulation pathway probably occurs in the other group.

High-Resolution Global Analysis of the Influences of Bas1 and Ino4 Transcription Factors on Meiotic DNA Break Distributions in Saccharomyces cerevisiae

PubMed Central

Zhu, Xuan; Keeney, Scott

2015-01-01

Meiotic recombination initiates with DNA double-strand breaks (DSBs) made by Spo11. In Saccharomyces cerevisiae, many DSBs occur in “hotspots” coinciding with nucleosome-depleted gene promoters. Transcription factors (TFs) stimulate DSB formation in some hotspots, but TF roles are complex and variable between locations. Until now, available data for TF effects on global DSB patterns were of low spatial resolution and confined to a single TF. Here, we examine at high resolution the contributions of two TFs to genome-wide DSB distributions: Bas1, which was known to regulate DSB activity at some loci, and Ino4, for which some binding sites were known to be within strong DSB hotspots. We examined fine-scale DSB distributions in TF mutant strains by deep sequencing oligonucleotides that remain covalently bound to Spo11 as a byproduct of DSB formation, mapped Bas1 and Ino4 binding sites in meiotic cells, evaluated chromatin structure around DSB hotspots, and measured changes in global messenger RNA levels. Our findings show that binding of these TFs has essentially no predictive power for DSB hotspot activity and definitively support the hypothesis that TF control of DSB numbers is context dependent and frequently indirect. TFs often affected the fine-scale distributions of DSBs within hotspots, and when seen, these effects paralleled effects on local chromatin structure. In contrast, changes in DSB frequencies in hotspots did not correlate with quantitative measures of chromatin accessibility, histone H3 lysine 4 trimethylation, or transcript levels. We also ruled out hotspot competition as a major source of indirect TF effects on DSB distributions. Thus, counter to prevailing models, roles of these TFs on DSB hotspot strength cannot be simply explained via chromatin “openness,” histone modification, or compensatory interactions between adjacent hotspots. PMID:26245832

Ultrasound-Assisted Extraction of Cannabinoids from Cannabis Sativa L. Optimized by Response Surface Methodology.

PubMed

Agarwal, Charu; Máthé, Katalin; Hofmann, Tamás; Csóka, Levente

2018-03-01

Ultrasonication was used to extract bioactive compounds from Cannabis sativa L. such as polyphenols, flavonoids, and cannabinoids. The influence of 3 independent factors (time, input power, and methanol concentration) was evaluated on the extraction of total phenols (TPC), flavonoids (TF), ferric reducing ability of plasma (FRAP) and the overall yield. A face-centered central composite design was used for statistical modelling of the response data, followed by regression and analysis of variance in order to determine the significance of the model and factors. Both the solvent composition and the time significantly affected the extraction while the sonication power had no significant impact on the responses. The response predictions obtained at optimum extraction conditions of 15 min time, 130 W power, and 80% methanol were 314.822 mg GAE/g DW of TPC, 28.173 mg QE/g DW of TF, 18.79 mM AAE/g DW of FRAP, and 10.86% of yield. A good correlation was observed between the predicted and experimental values of the responses, which validated the mathematical model. On comparing the ultrasonic process with the control extraction, noticeably higher values were obtained for each of the responses. Additionally, ultrasound considerably improved the extraction of cannabinoids present in Cannabis. Low frequency ultrasound was employed to extract bioactive compounds from the inflorescence part of Cannabis. The responses evaluated were-total phenols, flavonoids, ferric reducing assay and yield. The solvent composition and time significantly influenced the extraction process. Appreciably higher extraction of cannabinoids was achieved on sonication against control. © 2018 Institute of Food Technologists®.

Transfemoral, transapical and transcatheter aortic valve implantation and surgical aortic valve replacement: a meta-analysis of direct and adjusted indirect comparisons of early and mid-term deaths.

PubMed

Ando, Tomo; Takagi, Hisato; Grines, Cindy L

2017-09-01

Clinical outcomes of transfemoral-transcatheter aortic valve implantation (TF-TAVI) versus surgical aortic valve replacement (SAVR) or transapical (TA)-TAVI are limited to a few randomized clinical trials (RCTs). Because previous meta-analyses only included a limited number of adjusted studies or several non-adjusted studies, our goal was to compare and summarize the outcomes of TF-TAVI vs SAVR and TF-TAVI vs TA-TAVI exclusively with the RCT and propensity-matched cohort studies with direct and adjusted indirect comparisons to reach more precise conclusions. We hypothesized that TF-TAVI would offer surgical candidates a better outcome compared with SAVR and TA-TAVI because of its potential for fewer myocardial injuries. A literature search was conducted through PUBMED and EMBASE through June 2016. Only RCTs and propensity-matched cohort studies were included. A direct meta-analysis of TF-TAVI vs SAVR, TA-TAVI vs SAVR and TF-TAVI vs TA-TAVI was conducted. Then, the effect size of an indirect meta-analysis was calculated from the direct meta-analysis. The effect sizes of direct and indirect meta-analyses were then combined. A random-effects model was used to calculate the hazards ratio and the odds ratio with 95% confidence intervals. Early (in-hospital or 30 days) and mid-term (≥1 year) all-cause mortality rates were assessed. Our search resulted in 4 RCTs (n = 2319) and 14 propensity-matched cohort (n = 7217) studies with 9536 patients of whom 3471, 1769 and 4296 received TF, TA and SAVR, respectively. Direct meta-analyses and combined direct and indirect meta-analyses of early and mid-term deaths with TF-TAVI and SAVR were similar. Early deaths with TF-TAVI vs TA-TAVI were comparable in direct meta-analyses (odds ratio 0.64, P = 0.35) and direct and indirect meta-analyses combined (odds ratio 0.73, P = 0.24). Mid-term deaths with TF-TAVI vs TA-TAVI were increased (hazard ratio 0.83, P = 0.07) in a direct meta-analysis and became significant after addition of the indirect meta-analysis (hazard ratio 0.78, 95% confidence interval 0.67-0.92, P = 0.003). In conclusion, TF-TAVI was associated with similar early and mid-term deaths compared with SAVR. The number of early deaths was not significantly different between TF-TAVI and TA-TAVI, whereas there were fewer mid-term deaths with TF-TAVI than with TA-TAVI. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Properties of a recombinant bovine tissue factor expressed by Silkworm pupae and its performance as an Owren-type prothrombin time reagent for warfarin monitoring.

PubMed

Okuda, Masahiro; Taniguchi, Tomokuni; Takamiya, Osamu

2012-09-01

Tissue factor (TF), or thromboplastin, is a glycoprotein that triggers the extrinsic coagulation pathway. In blood coagulation testing, TF has been used as a natural source for determining Quick prothrombin time (PT) or the Owren PT (OBT). Currently, natural sources are being replaced with recombinant proteins because of their uniform characteristics and the possibility of stable mass production of PT reagents. Because bovine spongiform encephalopathy (BSE)-infected cows are widespread in Japan, we prepared a recombinant bovine TF (rbTF) with a baculovirus expression system using silkworms. To overcome the limitations of natural TF, especially in bovine brain, we expressed a full-length rbTF protein in Silkworm pupae with a baculovirus expression system. Baculovirus inactivation and the presence of DNA fragments in the rbTF fraction were confirmed using Reed-Muench and polymerase chain reaction methods after inactivation with a detergent. The rbTF fraction prepared by an immobilized anti-Silkworm pupae fluid protein Sepharose 4B column was identified as a visible band on western blots with a polyclonal antibody against human TF with cross-reactivity with TFs. The inhibition of the polyclonal antibody against human TF by the clotting assay for PT was identified, and amidolytic biological activity through activated factor VII on S-2288 substrate was observed. In conclusion, the rbTF expressed by the baculovirus system using Silkworm pupae was uniformly specific for bovine TF. The OBT reagent incorporated by this rbTF was similar to those of commercial reagents. It also showed a suitable International Sensitivity Index and reproducibility precision, thereby allowing for diagnostic use. Copyright © 2012 Elsevier Ltd. All rights reserved.

Accelerated Seismic Release and Related Aspects of Seismicity Patterns on Earthquake Faults

NASA Astrophysics Data System (ADS)

Ben-Zion, Y.; Lyakhovsky, V.

2001-05-01

Observational studies indicate that large earthquakes are sometimes preceded by phases of accelerated seismic release (ASR) characterized by cumulative Benioff strain following a power law time-to-failure relation with a term (tf - t)m, where tf is the failure time of the large event and observed values of m are close to 0.3. We discuss properties of ASR and related aspects of seismicity patterns associated with several theoretical frameworks, with a focus on models of heterogeneous faults in continuum solids. Using stress and earthquake histories simulated by the model of Ben-Zion (1996) for a discrete fault with quenched heterogeneities in a 3D elastic half space, we show that large model earthquakes are associated with non-repeating cyclical establishment and destruction of long-range stress correlations, accompanied by non-stationary cumulative Benioff strain release. We then analyze results associated with a regional lithospheric model consisting of a seismogenic upper crust governed by the damage rheology of Lyakhovsky et al. (1997) over a viscoelastic substrate. We demonstrate analytically for a simplified 1D case that the employed damage rheology leads to a singular power law equation for strain proportional to (tf - t)-1/3, and a non-singular power law relation for cumulative Benioff strain proportional to (tf - t)1/3. A simple approximate generalization of the latter for regional cumulative Benioff strain is obtained by adding to the result a linear function of time representing a stationary background release. To go beyond the analytical expectations, we examine results generated by various realizations of the regional lithospheric model producing seismicity following the characteristic frequency-size statistics, Gutenberg-Richter power law distribution, and mode switching activity. We find that phases of ASR exist only when the seismicity preceding a given large event has broad frequency-size statistics. In such cases the simulated ASR phases can be fitted well by the singular analytical relation with m = -1/3, the non-singular equation with m = 0.2, and the generalized version of the latter including a linear term with m = 1/3. The obtained good fits with all three relations highlight the difficulty of deriving reliable information on functional forms and parameter values from such data sets. The activation process in the simulated ASR phases is found to be accommodated both by increasing rates of moderate events and increasing average event size, with the former starting a few years earlier than the latter. The lack of ASR in portions of the seismicity not having broad frequency-size statistics may explain why some large earthquakes are preceded by ASR and other are not.

Multiple linear regression to estimate time-frequency electrophysiological responses in single trials

PubMed Central

Hu, L.; Zhang, Z.G.; Mouraux, A.; Iannetti, G.D.

2015-01-01

Transient sensory, motor or cognitive event elicit not only phase-locked event-related potentials (ERPs) in the ongoing electroencephalogram (EEG), but also induce non-phase-locked modulations of ongoing EEG oscillations. These modulations can be detected when single-trial waveforms are analysed in the time-frequency domain, and consist in stimulus-induced decreases (event-related desynchronization, ERD) or increases (event-related synchronization, ERS) of synchrony in the activity of the underlying neuronal populations. ERD and ERS reflect changes in the parameters that control oscillations in neuronal networks and, depending on the frequency at which they occur, represent neuronal mechanisms involved in cortical activation, inhibition and binding. ERD and ERS are commonly estimated by averaging the time-frequency decomposition of single trials. However, their trial-to-trial variability that can reflect physiologically-important information is lost by across-trial averaging. Here, we aim to (1) develop novel approaches to explore single-trial parameters (including latency, frequency and magnitude) of ERP/ERD/ERS; (2) disclose the relationship between estimated single-trial parameters and other experimental factors (e.g., perceived intensity). We found that (1) stimulus-elicited ERP/ERD/ERS can be correctly separated using principal component analysis (PCA) decomposition with Varimax rotation on the single-trial time-frequency distributions; (2) time-frequency multiple linear regression with dispersion term (TF-MLRd) enhances the signal-to-noise ratio of ERP/ERD/ERS in single trials, and provides an unbiased estimation of their latency, frequency, and magnitude at single-trial level; (3) these estimates can be meaningfully correlated with each other and with other experimental factors at single-trial level (e.g., perceived stimulus intensity and ERP magnitude). The methods described in this article allow exploring fully non-phase-locked stimulus-induced cortical oscillations, obtaining single-trial estimate of response latency, frequency, and magnitude. This permits within-subject statistical comparisons, correlation with pre-stimulus features, and integration of simultaneously-recorded EEG and fMRI. PMID:25665966

Modulation of transferrin receptor mRNA by transferrin-gallium in human myeloid HL60 and lymphoid CCRF-CEM leukaemic cells.

PubMed Central

Ul-Haq, R; Chitambar, C R

1993-01-01

Gallium binds to the iron transport protein transferrin (Tf), is incorporated into cells through transferrin receptors (TfR) and inhibits iron-dependent DNA synthesis. Since cellular TfR expression is tightly regulated by the availability of iron, we investigated the effects of transferrin-gallium (Tf-Ga) on TfR mRNA levels in myeloid HL60 and lymphoid CCRF-CEM cells. In HL60 cells, Tf-Ga increased TfR mRNA levels in a dose-dependent fashion. This increase in TfR mRNA was blocked by Tf-Fe and by cycloheximide. Analysis of the rate of mRNA decay in the presence of actinomycin D revealed that the half-life of TfR mRNA was increased in HL60 cells incubated with Tf-Ga. The rate of transcription of TfR mRNA was not increased by Tf-Ga. In contrast with HL60 cells, CCRF-CEM cells displayed a decrease in the level of TfR mRNA after incubation with Tf-Ga. Tf-Ga inhibited iron uptake in both HL60 and CCRF-CEM cells but increased the level of TfR mRNA only in HL60 cells, suggesting that the Tf-Ga induction of TfR mRNA was not solely due to inhibition of cellular iron uptake. At growth-inhibitory concentrations, Tf-Ga increased the TfR mRNA level in HL60 cells but decreased it in CCRF-CEM cells. Our studies suggest that in HL60 cells, gallium regulates TfR expression at the post-transcriptional level by mechanisms which require de novo protein synthesis and involve interaction with iron. The divergent effects of Tf-Ga on TfR mRNA in myeloid HL60 and lymphoid CCRF-CEM cells suggest that differences exist in the regulation of TfR expression between these two cell types. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8379943

Task and spatial frequency modulations of object processing: an EEG study.

PubMed

Craddock, Matt; Martinovic, Jasna; Müller, Matthias M

2013-01-01

Visual object processing may follow a coarse-to-fine sequence imposed by fast processing of low spatial frequencies (LSF) and slow processing of high spatial frequencies (HSF). Objects can be categorized at varying levels of specificity: the superordinate (e.g. animal), the basic (e.g. dog), or the subordinate (e.g. Border Collie). We tested whether superordinate and more specific categorization depend on different spatial frequency ranges, and whether any such dependencies might be revealed by or influence signals recorded using EEG. We used event-related potentials (ERPs) and time-frequency (TF) analysis to examine the time course of object processing while participants performed either a grammatical gender-classification task (which generally forces basic-level categorization) or a living/non-living judgement (superordinate categorization) on everyday, real-life objects. Objects were filtered to contain only HSF or LSF. We found a greater positivity and greater negativity for HSF than for LSF pictures in the P1 and N1 respectively, but no effects of task on either component. A later, fronto-central negativity (N350) was more negative in the gender-classification task than the superordinate categorization task, which may indicate that this component relates to semantic or syntactic processing. We found no significant effects of task or spatial frequency on evoked or total gamma band responses. Our results demonstrate early differences in processing of HSF and LSF content that were not modulated by categorization task, with later responses reflecting such higher-level cognitive factors.

Trauma-focused cognitive behavioral therapy or eye movement desensitization and reprocessing: what works in children with posttraumatic stress symptoms? A randomized controlled trial.

PubMed

Diehle, Julia; Opmeer, Brent C; Boer, Frits; Mannarino, Anthony P; Lindauer, Ramón J L

2015-02-01

To prevent adverse long-term effects, children who suffer from posttraumatic stress symptoms (PTSS) need treatment. Trauma-focused cognitive behavioral therapy (TF-CBT) is an established treatment for children with PTSS. However, alternatives are important for non-responders or if TF-CBT trained therapists are unavailable. Eye movement desensitization and reprocessing (EMDR) is a promising treatment for which sound comparative evidence is lacking. The current randomized controlled trial investigates the effectiveness and efficiency of both treatments. Forty-eight children (8-18 years) were randomly assigned to eight sessions of TF-CBT or EMDR. The primary outcome was PTSS as measured with the Clinician-Administered PTSD Scale for Children and Adolescents (CAPS-CA). Secondary outcomes included parental report of child PTSD diagnosis status and questionnaires on comorbid problems. The Children's Revised Impact of Event Scale was administered during the course of treatment. TF-CBT and EMDR showed large reductions from pre- to post-treatment on the CAPS-CA (-20.2; 95% CI -12.2 to -28.1 and -20.9; 95% CI -32.7 to -9.1). The difference in reduction was small and not statistically significant (mean difference of 0.69, 95% CI -13.4 to 14.8). Treatment duration was not significantly shorter for EMDR (p = 0.09). Mixed model analysis of monitored PTSS during treatment showed a significant effect for time (p < 0.001) but not for treatment (p = 0.44) or the interaction of time by treatment (p = 0.74). Parents of children treated with TF-CBT reported a significant reduction of comorbid depressive and hyperactive symptoms. TF-CBT and EMDR are effective and efficient in reducing PTSS in children.

The impact of transfer from hemodialysis on peritoneal dialysis technique survival.

PubMed

Nessim, Sharon J; Bargman, Joanne M; Jassal, S Vanita; Oliver, Matthew J; Na, Yingbo; Perl, Jeffrey

2015-01-01

A significant proportion of peritoneal dialysis (PD) patients receive an initial period of hemodialysis (HD) before transitioning to PD ("PD-switch"). We sought to better understand the risks of PD technique failure (TF) and mortality for those patients compared with patients starting with PD as their first dialysis modality ("PD-first"). Using Canadian Organ Replacement Register data, we compared the risk of PD TF between PD-first and PD-switch patients within the first year after HD initiation. In a secondary analysis, the PD-switch patients were stratified into three groups based on timing of the switch from initial HD to PD as follows: 0 - 90 days, 91 - 180 days, and 181 - 365 days. Each group was compared with PD-first patients for risk of PD TF and death. Between 2001 and 2010, 9404 patients initiated PD as their first renal replacement therapy, and 3757 switched from HD to PD. After multivariable adjustment, the risk of PD TF was higher among PD-switch patients than among PD-first patients [adjusted hazard ratio (AHR): 1.37; 95% confidence interval (CI): 1.26 to 1.49], particularly within the first year after the switch from HD to PD (AHR: 1.51; 95% CI: 1.36 to 1.68). There was no association between time on HD within the first year and subsequent risk of PD TF. For all the stratified PD-switch groups, death rates were higher than those for PD-first patients. Compared with patients who start renal replacement therapy with PD, those who transfer from HD to PD within the first year on dialysis experience higher rates of PD TF and death, with the highest risk being observed in the initial year after the switch to PD. Copyright © 2015 International Society for Peritoneal Dialysis.

Theaflavins in black tea and catechins in green tea are equally effective antioxidants.

PubMed

Leung, L K; Su, Y; Chen, R; Zhang, Z; Huang, Y; Chen, Z Y

2001-09-01

Green tea catechins, including (-)-epicatechin (EC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG), are oxidized and dimerized during the manufacture of black tea and oolong tea to form orange-red pigments, theaflavins (TF), a mixture of theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin-3'-gallate (TF2B) and theaflavin-3,3'-digallate (TF3). The present study was designed to compare the antioxidant activities of individual TF with that of each catechin using human LDL oxidation as a model. All catechins and TF tested inhibited Cu(+2)-mediated LDL oxidation. Analysis of the thiobarbituric acid-reactive substances (TBARS) and conjugated dienes produced during LDL oxidation revealed that the antioxidant activity was in the order: TF3 > ECG > EGCG > or = TF2B > or = TF2A > TF1 > or = EC > EGC. Four TF derivatives also demonstrated a dose-dependent antioxidant activity in Cu(+2)-mediated LDL oxidation at concentrations of 5-40 micromol/L. These results demonstrate that the TF present in black tea possess at least the same antioxidant potency as catechins present in green tea, and that the conversion of catechins to TF during fermentation in making black tea does not alter significantly their free radical-scavenging activity.

Repressor- and Activator-Type Ethylene Response Factors Functioning in Jasmonate Signaling and Disease Resistance Identified via a Genome-Wide Screen of Arabidopsis Transcription Factor Gene Expression[w

PubMed Central

McGrath, Ken C.; Dombrecht, Bruno; Manners, John M.; Schenk, Peer M.; Edgar, Cameron I.; Maclean, Donald J.; Scheible, Wolf-Rüdiger; Udvardi, Michael K.; Kazan, Kemal

2005-01-01

To identify transcription factors (TFs) involved in jasmonate (JA) signaling and plant defense, we screened 1,534 Arabidopsis (Arabidopsis thaliana) TFs by real-time quantitative reverse transcription-PCR for their altered transcript at 6 h following either methyl JA treatment or inoculation with the incompatible pathogen Alternaria brassicicola. We identified 134 TFs that showed a significant change in expression, including many APETALA2/ethylene response factor (AP2/ERF), MYB, WRKY, and NAC TF genes with unknown functions. Twenty TF genes were induced by both the pathogen and methyl JA and these included 10 members of the AP2/ERF TF family, primarily from the B1a and B3 subclusters. Functional analysis of the B1a TF AtERF4 revealed that AtERF4 acts as a novel negative regulator of JA-responsive defense gene expression and resistance to the necrotrophic fungal pathogen Fusarium oxysporum and antagonizes JA inhibition of root elongation. In contrast, functional analysis of the B3 TF AtERF2 showed that AtERF2 is a positive regulator of JA-responsive defense genes and resistance to F. oxysporum and enhances JA inhibition of root elongation. Our results suggest that plants coordinately express multiple repressor- and activator-type AP2/ERFs during pathogen challenge to modulate defense gene expression and disease resistance. PMID:16183832

Coup-TF1 and Coup-TF2 control subtype and laminar identity of MGE-derived neocortical interneurons.

PubMed

Hu, Jia Sheng; Vogt, Daniel; Lindtner, Susan; Sandberg, Magnus; Silberberg, Shanni N; Rubenstein, John L R

2017-08-01

Distinct cortical interneuron (CIN) subtypes have unique circuit functions; dysfunction in specific subtypes is implicated in neuropsychiatric disorders. Somatostatin- and parvalbumin-expressing (SST + and PV + ) interneurons are the two major subtypes generated by medial ganglionic eminence (MGE) progenitors. Spatial and temporal mechanisms governing their cell-fate specification and differential integration into cortical layers are largely unknown. We provide evidence that Coup-TF1 and Coup-TF2 ( Nr2f1 and Nr2f2 ) transcription factor expression in an arc-shaped progenitor domain within the MGE promotes time-dependent survival of this neuroepithelium and the time-dependent specification of layer V SST + CINs. Coup-TF1 and Coup-TF2 autonomously repress PV + fate in MGE progenitors, in part through directly driving Sox6 expression. These results have identified, in mouse, a transcriptional pathway that controls SST-PV fate. © 2017. Published by The Company of Biologists Ltd.

TF34 convertible engine control system design

NASA Technical Reports Server (NTRS)

Gilmore, D. R., Jr.

1984-01-01

The characteristics of the TF34 convertible engine, capable of producing shaft power, thrust, or a combination of both, is investigated with respect to the control system design, development, bench testing, and the anticipated transient response during engine testing at NASA. The modifications to the prototype standard TF34-GE-400 turbofan, made primarily in the fan section, consist of the variable inlet guide vanes and variable exit guide vanes. The control system was designed using classical frequency domain techniques and was based on the anticipated convertible/VTOL airframe requirements. The engine has been run in the fan mode and in the shaft mode, exhibiting a response of 0.14 second to a 5-percent thrust change.

Fast Fourier Tranformation Algorithms: Experiments with Microcomputers.

DTIC Science & Technology

1986-07-01

is, functions a with a known, discrete Fourier transform A Such functions are given fn [I]. The functions, TF1 , TF2, and TF3, were used and are...the IBM PC, all with TF1 (Eq. 1). ’The compilers provided options to improve performance, as noted, for which a penalty in compiling time has to be...BASIC only. Series I In this series the procedures were as follows: (i) Calculate the input values for TF1 of ar and the modulus Iar (which is

Restraint stress enhances arterial thrombosis in vivo--role of the sympathetic nervous system.

PubMed

Stämpfli, Simon F; Camici, Giovanni G; Keller, Stephan; Rozenberg, Izabela; Arras, Margarete; Schuler, Beat; Gassmann, Max; Garcia, Irene; Lüscher, Thomas F; Tanner, Felix C

2014-01-01

Stress is known to correlate with the incidence of acute myocardial infarction. However, the molecular mechanisms underlying this correlation are not known. This study was designed to assess the effect of experimental stress on arterial thrombus formation, the key event in acute myocardial infarction. Mice exposed to 20 h of restraint stress displayed an increased arterial prothrombotic potential as assessed by photochemical injury-induced time to thrombotic occlusion. This increase was prevented by chemical sympathectomy performed through 6-hydroxydopamine (6-OHDA). Blood-born tissue factor (TF) activity was enhanced by stress and this increase could be prevented by 6-OHDA treatment. Vessel wall TF, platelet count, platelet aggregation, coagulation times (PT, aPTT), fibrinolytic system (t-PA and PAI-1) and tail bleeding time remained unaltered. Telemetric analysis revealed only minor hemodynamic changes throughout the stress protocol. Plasma catecholamines remained unaffected after restraint stress. Tumor necrosis factor alpha (TNF-α) plasma levels were unchanged and inhibition of TNF-α had no effect on stress-enhanced thrombosis. These results indicate that restraint stress enhances arterial thrombosis via the sympathetic nervous system. Blood-borne TF contributes, at least in part, to the observed effect whereas vessel wall TF, platelets, circulating coagulation factors, fibrinolysis and inflammation do not appear to play a role. These findings shed new light on the understanding of stress-induced cardiovascular events.

A Multidisciplinary Approach to Health Monitoring and Materials Damage Prognosis for Metallic Aerospace Systems

DTIC Science & Technology

2013-03-01

framework of orientation distribution functions and crack-induced texture o Quantify effects of temperature on damage behavior and damage monitoring...measurement model was obtained from hidden Markov modeling (HMM) of joint time-frequency (TF) features extracted from the PZT sensor signals using the...considered PZT sensor signals recorded from a bolted aluminum plate. About only 20% of the samples of a signal were first randomly selected as

Identification and expression of the WRKY transcription factors of Carica papaya in response to abiotic and biotic stresses.

PubMed

Pan, Lin-Jie; Jiang, Ling

2014-03-01

The WRKY transcription factor (TF) plays a very important role in the response of plants to various abiotic and biotic stresses. A local papaya database was built according to the GenBank expressed sequence tag database using the BioEdit software. Fifty-two coding sequences of Carica papaya WRKY TFs were predicted using the tBLASTn tool. The phylogenetic tree of the WRKY proteins was classified. The expression profiles of 13 selected C. papaya WRKY TF genes under stress induction were constructed by quantitative real-time polymerase chain reaction. The expression levels of these WRKY genes in response to 3 abiotic and 2 biotic stresses were evaluated. TF807.3 and TF72.14 are upregulated by low temperature; TF807.3, TF43.76, TF12.199 and TF12.62 are involved in the response to drought stress; TF9.35, TF18.51, TF72.14 and TF12.199 is involved in response to wound; TF12.199, TF807.3, TF21.156 and TF18.51 was induced by PRSV pathogen; TF72.14 and TF43.76 are upregulated by SA. The regulated expression levels of above eight genes normalized against housekeeping gene actin were significant at probability of 0.01 levels. These WRKY TFs could be related to corresponding stress resistance and selected as the candidate genes, especially, the two genes TF807.3 and TF12.199, which were regulated notably by four stresses respectively. This study may provide useful information and candidate genes for the development of transgenic stress tolerant papaya varieties.

A complex structure in the mRNA of Tf1 is recognized and cleaved to generate the primer of reverse transcription.

PubMed

Lin, J H; Levin, H L

1997-01-15

All retroviruses and LTR-containing retrotransposons are thought to require specific tRNA molecules to serve as primers of reverse transcription. An exception is the LTR-containing retrotransposon Tf1, isolated from Schizosaccharomyces pombe. Instead of requiring a tRNA, the reverse transcriptase of Tf1 uses the first 11 bases of the Tf1 transcript as the primer for reverse transcription. The primer is generated by a cleavage that occurs between bases 11 and 12 of the Tf1 mRNA. Sequence analysis of the 5' untranslated region of the Tf1 mRNA resulted in the identification of a region with the potential to form an RNA structure of 89 bases that included the primer binding site and the first 11 bases of the Tf1 mRNA. Systematic mutagenesis of this region revealed 34 single-point mutants in the structure that resulted in reduced transposition activity. The defects in transposition correlated with reduced level of Tf1 reverse transcripts as determined by DNA blot analysis. Evidence that the RNA structure did form in vivo included the result that strains with second site mutations that restored complementarity resulted in increased levels of reverse transcripts and Tf1 transposition. The majority of the mutants defective for reverse transcription were unable to cleave the Tf1 mRNA between bases 11 and 12. These data indicate that formation of an extensive RNA structure was required for the cleavage reaction that generated the primer for Tf1 reverse transcription.

Immunological and biochemical analysis of glycosylated surface antigens and lipophosphoglycan of Tritrichomonas foetus.

PubMed

Singh, B N; BonDurant, R H; Campero, C M; Corbeil, L B

2001-08-01

Immunoaffinity-purified TF1.17 adhesin antigen was compared biochemically and antigenically to Tritrichomonas foetus (TF) lipophosphoglycan (LPG) and a soluble glycosylated antigen (SGA) released from T. foetus and implicated in pathogenesis and immunity. The monoclonal antibodies (Mabs TF1.15 and TF1.17) specific for a glycosylated TF1.17 antigen were previously shown to prevent adhesion of the T. foetus parasites to bovine vaginal epithelial cells and to mediate killing by bovine complement. SGA was isolated from T. foetus-conditioned buffer and purified by octyl-Sepharose hydrophobic column chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of SGA showed a major SGA1 component (approximately 190 kDa) and a minor SGA2 component (50-70 kDa), which migrated close to TF-LPG and TF1.17. The carbohydrate and lipid compositional analyses of affinity-purified TF1.17 and SGA2 by high-performance liquid chromatography (HPLC) and gas-liquid chromatography revealed the presence of monosaccharides and fatty acids as found in TF-LPG. All antigens contained terminal fucose as determined by alpha-fucosidase digestion followed by HPLC. ELISA and western blots were used to further characterize these glycosylated antigens and to analyze their relationships. The Mabs TF1.15 and TF1.17 reacted very strongly to TF-LPG and SGA2. as well as TF1.17 antigen, indicating that these molecules share common epitopes. These Mabs did not react with the SGA1 component either in ELISA and western blot analyses. Also, the monosaccharide composition of SGA1 was very different from the other three antigen, suggesting SGA1 was different from LPG, SGA2 and TF1.17. Although LPG reacted with Mabs to native TF1.17 antigen, LPG did not induce an immune response in cattle with the same route and adjuvant used to produce strong antibody responses to the native antigen. The latter response suggests that the tightly bound peptide present in the immunoaffinity-purified antigen is necessary for induction of a response to (an) epitope(s) in TF-LPG and TF1.17. Furthermore, vaginal fluid from T. foetus-infected heifers and serum from a cow with a T. foetus-associated pyometra recognized both TF1.17 and TF-LPG in western blots. These results suggest that T. foetus LPG and SGA2 are related to TF1.17 antigen, which was previously shown to play an important role in the pathogenesis and host response in bovine trichomoniasis.

Effect of circulating tissue factor on hypercoagulability in type 2 diabetes mellitus studied by rheometry and dielectric blood coagulometry

PubMed Central

Uchimura, Isao; Kaibara, Makoto; Nagasawa, Masayuki; Hayashi, Yoshihito

2016-01-01

Background: Hypercoagulability in type 2 diabetes mellitus (T2DM) patients increases their risk of cardiovascular diseases. Objective: The aim of this work was to investigate the hypercoagulation mechanism in T2DM patients in terms of circulating tissue factor (TF). Methods: Whole blood coagulation tests by damped oscillation rheometry and dielectric blood coagulometry (DBCM) were performed. Results: The average coagulation time was significantly shorter for T2DM patients than for healthy controls. In vitro addition of either anti-TF or anti-activated factor VII (FVIIa) antibody to hypercoagulable blood samples prolonged coagulation times for one group of patients, while coagulation times remained short for another group. The levels of circulating TF were estimated in the former group by measuring the coagulation times for blood samples from healthy subjects with addition of various concentrations of TF and comparing them with the coagulation times for the group. The results indicated that the levels of circulating TF were on the order of subpicomolar at most. Conclusions: Circulating TF is at least partially responsible for a hypercoagulable group of T2DM patients, while an abnormality in the intrinsic coagulation pathway probably occurs in the other group. PMID:27858671

COUP-TF1 Modulates Thyroid Hormone Action in an Embryonic Stem-Cell Model of Cortical Pyramidal Neuronal Differentiation.

PubMed

Teng, Xiaochun; Liu, Yan-Yun; Teng, Weiping; Brent, Gregory A

2018-05-01

Thyroid hormone is critical for normal brain development and acts in a spatial and temporal specific pattern. Thyroid hormone excess, or deficiency, can lead to irreversible impairment of brain and sensory development. Chicken ovalbumin upstream-transcription factor 1 (COUP-TF1), expressed early in neuronal development, is essential to achieve normal brain structure. Thyroid hormone stimulation of gene expression is inversely correlated with the level of COUP-TF1 expression. An in vitro method of differentiating mouse embryonic stem (mES) cells into cortical neurons was utilized to study the influence of COUP-TF1 on thyroid hormone signaling in brain development. mES cells were cultured and differentiated in specific conditioned media, and a high percentage of nestin-positive progenitor neurons in the first stage, and cortical neurons in the second stage, was obtained with characteristic neuronal firing. The number of nestin-positive progenitors, as determined by fluorescence-activated cell sorting analysis, was significantly greater with triiodothyronine (T3) treatment compared to control (p < 0.05). T3 enhanced the expression of cortical neuron marker (Tbr1 and Rc3) mRNAs. After COUP-TF1 knockdown, the number of nestin-positive progenitors was reduced compared to control (p < 0.05), but the number increased with T3 treatment. The mRNA of cortical neuronal gene markers was measured after COUP-TF1 knockdown. In the presence of T3, the peak expression of neuron markers Emx1, Tbr1, Camkiv, and Rc3 mRNA was earlier, at day 18 of differentiation, compared to control cells, at day 22. Furthermore, after COUP-TF1 knockdown, T3 induction of Rc3 and Tbr1 mRNA was significantly enhanced compared to cells expressing COUP-TF1. These results indicate that COUP-TF1 plays an important role in modulating the timing and magnitude of T3-stimulated gene expression required for normal corticogenesis.

Molecular cloning and characterization of a C-type lectin in roughskin sculpin (Trachidermus fasciatus).

PubMed

Yu, Shanshan; Yang, Hui; Chai, Yingmei; Liu, Yingying; Zhang, Qiuxia; Ding, Xinbiao; Zhu, Qian

2013-02-01

C-type lectins, as the members of pattern-recognition receptors (PRRs), play significant roles in innate immunity responses through binding to the pathogen-associated molecular patterns (PAMPs) presented on surfaces of microorganisms. In our study, a C-type lectin gene (TfCTL1) was cloned from the roughskin sculpin using expression sequence tag (EST) and rapid amplification of cDNA ends (RACE) techniques. The full-length of TfCTL1 was 696 bp, consisting of a 95 bp 5' untranslated region (UTR), a 498 bp open reading frame (ORF) encoding a 165 amino acid protein, and a 103 bp 3' UTR with a polyadenylation signal sequence AATAAA and a poly(A) tail. The deduced amino acid sequence of TfCTL1 contained a signal peptide and a single carbohydrate recognition domain (CRD) which had four conserved disulfide-bonded cysteine residues (Cys(61)-Cys(158), Cys(134)-Cys(150)) and a Ca(2+)/carbohydrate-binding site (QPD motif). Results from the qRT-PCR indicated that TfCTL1 mRNA was predominately expressed in the liver. The temporal expression of TfCTL1 was obviously up-regulated in the skin, blood, spleen and heart in time dependent manners by lipopolysaccharide (LPS) challenge, whereas in the liver, TfCTL1 was initially down-regulated from 2 h to 48 h followed by an abrupt up-regulation at 72 h. Recombinant TfCTL1 CRD purified from Escherichia coli BL21 was able to agglutinate some Gram-positive bacteria, Gram-negative bacteria and a yeast in a Ca(2+)-dependent manner. Further analysis showed that TfCTL1 can bind to several kinds of microorganisms selectively in a Ca(2+)-independent manner. These results suggested that TfCTL1 might be involved in the innate response as a PRR. Copyright © 2012 Elsevier Ltd. All rights reserved.

The effects of small interfering RNA–targeting tissue factor on an in vitro model of neovascularization

PubMed Central

Peng, Wenyan; Yu, Ying; Li, Tiejun; Zhu, Yuanyuan

2013-01-01

Purpose Tissue factor (TF) plays an important role in neovascularization (NV). This study aimed to determine whether small interfering RNA–targeting TF (TF-siRNA) could knock down TF expression and inhibit cell proliferation, cell migration, and tube formation in an in vitro model of NV. Methods Lipopolysaccharide (LPS) was used to stimulate human umbilical vein endothelial cell (HUVEC) lines to express TF and mimic certain phenotypes of NV in vitro. HUVECs were transfected with TF-siRNAs and control siRNAs using LipofectamineTM 2000. The inhibitory effect of the siRNAs on the expression of TF mRNA and protein was evaluated by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) and western blot analysis. The effects on the cell viability, migration, and tube formation of siRNA-treated cells were examined by MTT assay, wound-healing assay, and Matrigel-induced capillary tube formation. Results Lipopolysaccharide treatment increased the expression of TF. TF-siRNAs effectively knocked down TF expression, with the most efficient TF-siRNA reducing 78.9% of TF expression. TF protein was also notably curtailed by TF-siRNA. The MTT and wound-healing assays showed that the TF-siRNA substantially inhibited the proliferation and migration of HUVECs. Tube formation was decreased by 47.4% and 59.4% in cells treated with the TF-siRNA and vascular endothelial growth factor–siRNA, respectively, compared with the blank control. Conclusions TF-siRNA can knockdown TF expression and inhibit cell proliferation, migration, and tube formation in vitro. TF-siRNA may provide a novel therapeutic candidate for NV-related diseases. PMID:23805036

JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles

PubMed Central

Mathelier, Anthony; Fornes, Oriol; Arenillas, David J.; Chen, Chih-yu; Denay, Grégoire; Lee, Jessica; Shi, Wenqiang; Shyr, Casper; Tan, Ge; Worsley-Hunt, Rebecca; Zhang, Allen W.; Parcy, François; Lenhard, Boris; Sandelin, Albin; Wasserman, Wyeth W.

2016-01-01

JASPAR (http://jaspar.genereg.net) is an open-access database storing curated, non-redundant transcription factor (TF) binding profiles representing transcription factor binding preferences as position frequency matrices for multiple species in six taxonomic groups. For this 2016 release, we expanded the JASPAR CORE collection with 494 new TF binding profiles (315 in vertebrates, 11 in nematodes, 3 in insects, 1 in fungi and 164 in plants) and updated 59 profiles (58 in vertebrates and 1 in fungi). The introduced profiles represent an 83% expansion and 10% update when compared to the previous release. We updated the structural annotation of the TF DNA binding domains (DBDs) following a published hierarchical structural classification. In addition, we introduced 130 transcription factor flexible models trained on ChIP-seq data for vertebrates, which capture dinucleotide dependencies within TF binding sites. This new JASPAR release is accompanied by a new web tool to infer JASPAR TF binding profiles recognized by a given TF protein sequence. Moreover, we provide the users with a Ruby module complementing the JASPAR API to ease programmatic access and use of the JASPAR collection of profiles. Finally, we provide the JASPAR2016 R/Bioconductor data package with the data of this release. PMID:26531826

[A study on the diagnostic value of tear film objective scatter index in dry eye].

PubMed

Su, Y D; Liang, Q F; Wang, N L; Antoine, Labbè

2017-09-11

Objective: To study the sensitivity and specificity of tear film objective scatter index to the diagnosis dry eye disease (DED). Methods: A prospective case-controlled study. Fifty-three patients with DED and 32 healthy age- and sex-matched control subjects were included from July to October 2016. All subjects underwent the examinations sequentially as follows: evaluation of ocular surface disease symptoms using the Ocular Surface Disease Index, optical quality detection, lipid layer thickness, tear film breakup time and SchirmerⅠtest. With Optical Quality Analysis SystemⅡ, the values of modulation transfer function cut off, basic objective scatter index (OSI) and total OSI were measured. To eliminate the influence of other refractive media, the tear film OSI (TF-OSI) was calculated, and the difference in TF-OSI between two groups was analyzed with the independent-samples t test. Spearman's correlation analysis was used to detect the correlation of each parameter in the DED group. With the receiver operating characteristic curve and the area under the curve (AUC), the specificity and sensitivity of TF-OSI and other parameters were described to differentiate DED from normal eyes. Results: In the dry eye group, the value of modulation transfer function cut off (32.07±11.95) was significantly lower than the normal group (39.38±9.44, t=- 3.096, P= 0.003) , and the mean value and dispersion of TF-OSI (0.50±0.43, 0.52±0.81) were higher than the normal group (0.21±0.16, 0.12±0.01) ( t= 4.300, P= 0.000, t= 3.546, P= 0.001) . The mean value of TF-OSI had a positive correlation with lipid layer thickness ( r= 0.365, P= 0.007) and dispersion of TF-OSI ( r= 0.581, P= 0.000), and a negative correlation with MTF cut off ( r=- 0.368, P= 0.007). To the diagnostic value of DED, the mean value of TF-OSI had a sensitivity of 0.736, a specificity of 0.762, and the AUC was 0.764. The dispersion of TF-OSI had a sensitivity of 0.811 and a specificity of 0.810, and the AUC was 0.900. Conclusion: In the DED group, the mean value and dispersion of TF-OSI were higher than the normal group. With its advantages, the TF-OSI may be a new method for the auxiliary diagnosis of dry eye. (Chin J Ophthalmol, 2017, 53: 668-674) .

Implement an adjustable delay time digital trigger for an NI data acquisition card in a high-speed demodulation system

NASA Astrophysics Data System (ADS)

Zhang, Hongtao; Fan, Lingling; Wang, Pengfei; Park, Seong-Wook

2012-06-01

A National Instruments (NI) DAQ card PCI 5105 is installed in a high-speed demodulation system based on Fiber Fabry-Pérot Tunable Filter. The instability of the spectra of Fiber Bragg Grating sensors caused by intrinsic drifts of FFP-TF needs an appropriate, flexible trigger. However, the driver of the DAQ card in the current development environment does not provide the functions of analog trigger but digital trigger type. Moreover, the high level of the trigger signal from the tuning voltage of FFP-TF is larger than the maximum input overload voltage of PCI 5105 card. To resolve this incompatibility, a novel converter to change an analog trigger signal into a digital trigger signal has been reported previously. However, the obvious delay time between input and output signals limits the function of demodulation system. Accordingly, we report an improved low-cost, small-size converter with an adjustable delay time. This new scheme can decline the delay time to or close to zero when the frequency of trigger signal is less than 3,000 Hz. This method might be employed to resolve similar problems or to be applied in semiconductor integrated circuits.

A novel alignment-free method for detection of lateral genetic transfer based on TF-IDF.

PubMed

Cong, Yingnan; Chan, Yao-Ban; Ragan, Mark A

2016-07-25

Lateral genetic transfer (LGT) plays an important role in the evolution of microbes. Existing computational methods for detecting genomic regions of putative lateral origin scale poorly to large data. Here, we propose a novel method based on TF-IDF (Term Frequency-Inverse Document Frequency) statistics to detect not only regions of lateral origin, but also their origin and direction of transfer, in sets of hierarchically structured nucleotide or protein sequences. This approach is based on the frequency distributions of k-mers in the sequences. If a set of contiguous k-mers appears sufficiently more frequently in another phyletic group than in its own, we infer that they have been transferred from the first group to the second. We performed rigorous tests of TF-IDF using simulated and empirical datasets. With the simulated data, we tested our method under different parameter settings for sequence length, substitution rate between and within groups and post-LGT, deletion rate, length of transferred region and k size, and found that we can detect LGT events with high precision and recall. Our method performs better than an established method, ALFY, which has high recall but low precision. Our method is efficient, with runtime increasing approximately linearly with sequence length.

Identification and positional distribution analysis of transcription factor binding sites for genes from the wheat fl-cDNA sequences.

PubMed

Chen, Zhen-Yong; Guo, Xiao-Jiang; Chen, Zhong-Xu; Chen, Wei-Ying; Wang, Ji-Rui

2017-06-01

The binding sites of transcription factors (TFs) in upstream DNA regions are called transcription factor binding sites (TFBSs). TFBSs are important elements for regulating gene expression. To date, there have been few studies on the profiles of TFBSs in plants. In total, 4,873 sequences with 5' upstream regions from 8530 wheat fl-cDNA sequences were used to predict TFBSs. We found 4572 TFBSs for the MADS TF family, which was twice as many as for bHLH (1951), B3 (1951), HB superfamily (1914), ERF (1820), and AP2/ERF (1725) TFs, and was approximately four times higher than the remaining TFBS types. The percentage of TFBSs and TF members showed a distinct distribution in different tissues. Overall, the distribution of TFBSs in the upstream regions of wheat fl-cDNA sequences had significant difference. Meanwhile, high frequencies of some types of TFBSs were found in specific regions in the upstream sequences. Both TFs and fl-cDNA with TFBSs predicted in the same tissues exhibited specific distribution preferences for regulating gene expression. The tissue-specific analysis of TFs and fl-cDNA with TFBSs provides useful information for functional research, and can be used to identify relationships between tissue-specific TFs and fl-cDNA with TFBSs. Moreover, the positional distribution of TFBSs indicates that some types of wheat TFBS have different positional distribution preferences in the upstream regions of genes.

Gonad Transcriptome Analysis of High-Temperature-Treated Females and High-Temperature-Induced Sex-Reversed Neomales in Nile Tilapia.

PubMed

Sun, Li Xue; Teng, Jian; Zhao, Yan; Li, Ning; Wang, Hui; Ji, Xiang Shan

2018-02-28

Nowadays, the molecular mechanisms governing TSD (temperature-dependent sex determination) or GSD + TE (genotypic sex determination + temperature effects) remain a mystery in fish. We developed three all-female families of Nile tilapia ( Oreochromis niloticus ), and the family with the highest male ratio after high-temperature treatment was used for transcriptome analysis. First, gonadal histology analysis indicated that the histological morphology of control females (CF) was not significantly different from that of high-temperature-treated females (TF) at various development stages. However, the high-temperature treatment caused a lag of spermatogenesis in high-temperature-induced neomales (IM). Next, we sequenced the transcriptome of CF, TF, and IM Nile tilapia. 79, 11,117, and 11,000 differentially expressed genes (DEGs) were detected in the CF-TF, CF-IM, and TF-IM comparisons, respectively, and 44 DEGs showed identical expression changes in the CF-TF and CF-IM comparisons. Principal component analysis (PCA) indicated that three individuals in CF and three individuals in TF formed a cluster, and three individuals in IM formed a distinct cluster, which confirmed that the gonad transcriptome profile of TF was similar to that of CF and different from that of IM. Finally, six sex-related genes were validated by qRT-PCR. This study identifies a number of genes that may be involved in GSD + TE, which will be useful for investigating the molecular mechanisms of TSD or GSD + TE in fish.

Structural, functional and evolutionary characterization of major drought transcription factors families in maize

NASA Astrophysics Data System (ADS)

Mittal, Shikha; Banduni, Pooja; Mallikarjuna, Mallana G.; Rao, Atmakuri R.; Jain, Prashant A.; Dash, Prasanta K.; Thirunavukkarasu, Nepolean

2018-05-01

Drought is one of the major threats to maize production. In order to improve the production and to breed tolerant hybrids, understanding the genes and regulatory mechanisms during drought stress is important. Transcription factors (TFs) play a major role in gene regulation and many TFs have been identified in response to drought stress. In our experiment, a set of 15 major TF families comprising 1436 genes was structurally and functionally characterized using in-silico tools and a gene expression assay. All 1436 genes were mapped on 10 chromosome of maize. The functional annotation indicated the involvement of these genes in ABA signaling, ROS scavenging, photosynthesis, stomatal regulation, and sucrose metabolism. Duplication was identified as the primary force in divergence and expansion of TF families. Phylogenetic relationship was developed individually for each TF family as well as combined TF families. Phylogenetic analysis grouped the TF family of genes into TF-specific and mixed groups. Phylogenetic analysis of genes belonging to various TF families suggested that the origin of TFs occurred in the lineage of maize evolution. Gene structure analysis revealed that more number of genes were intron-rich as compared to intronless genes. Drought-responsive CRE’s such as ABREA, ABREB, DRE1 and DRECRTCOREAT have been identified. Expression and interaction analyses identified leaf-specific bZIP TF, GRMZM2G140355, as a potential contributor toward drought tolerance in maize. We also analyzed protein-protein interaction network of 269 drought-responsive genes belonging to different drought-related TFs. The information generated on structural and functional characteristics, expression and interaction of the drought-related TF families will be useful to decipher the drought tolerance mechanisms and to derive drought-tolerant genotypes in maize.

Workload, Performance, and Reliability of Digital Computing Systems.

DTIC Science & Technology

1980-12-01

maximized is then P()(tf, ...... , ad .[[. P(ts) h( tf1 ),) (0 42.33) Note that this problem is equivalent to minimazing the function En Jn ,l~~f,) (-X) 1...have been observed at times tf1 , after observing the system since tsl. Take, for instance, the case of the distribution obtained from the simplified...represented by a set of pairs [ts,, tf1 ] i 1 ...... n the maximum likelihood values of a,y,P are these values that maximize the function p(n)( tf1 -ts 1 . . ts

Combined analysis of cortical (EEG) and nerve stump signals improves robotic hand control.

PubMed

Tombini, Mario; Rigosa, Jacopo; Zappasodi, Filippo; Porcaro, Camillo; Citi, Luca; Carpaneto, Jacopo; Rossini, Paolo Maria; Micera, Silvestro

2012-01-01

Interfacing an amputee's upper-extremity stump nerves to control a robotic hand requires training of the individual and algorithms to process interactions between cortical and peripheral signals. To evaluate for the first time whether EEG-driven analysis of peripheral neural signals as an amputee practices could improve the classification of motor commands. Four thin-film longitudinal intrafascicular electrodes (tf-LIFEs-4) were implanted in the median and ulnar nerves of the stump in the distal upper arm for 4 weeks. Artificial intelligence classifiers were implemented to analyze LIFE signals recorded while the participant tried to perform 3 different hand and finger movements as pictures representing these tasks were randomly presented on a screen. In the final week, the participant was trained to perform the same movements with a robotic hand prosthesis through modulation of tf-LIFE-4 signals. To improve the classification performance, an event-related desynchronization/synchronization (ERD/ERS) procedure was applied to EEG data to identify the exact timing of each motor command. Real-time control of neural (motor) output was achieved by the participant. By focusing electroneurographic (ENG) signal analysis in an EEG-driven time window, movement classification performance improved. After training, the participant regained normal modulation of background rhythms for movement preparation (α/β band desynchronization) in the sensorimotor area contralateral to the missing limb. Moreover, coherence analysis found a restored α band synchronization of Rolandic area with frontal and parietal ipsilateral regions, similar to that observed in the opposite hemisphere for movement of the intact hand. Of note, phantom limb pain (PLP) resolved for several months. Combining information from both cortical (EEG) and stump nerve (ENG) signals improved the classification performance compared with tf-LIFE signals processing alone; training led to cortical reorganization and mitigation of PLP.

Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

NASA Astrophysics Data System (ADS)

Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

2013-06-01

Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.

Metal retention in human transferrin: consequences of solvent composition in analytical sample preparation methods.

PubMed

Quarles, C Derrick; Randunu, K Manoj; Brumaghim, Julia L; Marcus, R Kenneth

2011-10-01

The analysis of metal-binding proteins requires careful sample manipulation to ensure that the metal-protein complex remains in its native state and the metal retention is preserved during sample preparation or analysis. Chemical analysis for the metal content in proteins typically involves some type of liquid chromatography/electrophoresis separation step coupled with an atomic (i.e., inductively coupled plasma-optical emission spectroscopy or -mass spectrometry) or molecular (i.e., electrospray ionization-mass spectrometry) analysis step that requires altered-solvent introduction techniques. UV-VIS absorbance is employed here to monitor the iron content in human holo-transferrin (Tf) under various solvent conditions, changing polarity, pH, ionic strength, and the ionic and hydrophobic environment of the protein. Iron loading percentages (i.e. 100% loading equates to 2 Fe(3+):1 Tf) were quantitatively determined to evaluate the effect of solvent composition on the retention of Fe(3+) in Tf. Maximum retention of Fe(3+) was found in buffered (20 mM Tris) solutions (96 ± 1%). Exposure to organic solvents and deionized H(2)O caused release of ~23-36% of the Fe(3+) from the binding pocket(s) at physiological pH (7.4). Salt concentrations similar to separation conditions used for ion exchange had little to no effect on Fe(3+) retention in holo-Tf. Unsurprisingly, changes in ionic strength caused by additions of guanidine HCl (0-10 M) to holo-Tf resulted in unfolding of the protein and loss of Fe(3+) from Tf; however, denaturing and metal loss was found not to be an instantaneous process for additions of 1-5 M guanidinium to Tf. In contrast, complete denaturing and loss of Fe(3+) was instantaneous with ≥6 M additions of guanidinium, and denaturing and loss of iron from Tf occurred in parallel proportions. Changes to the hydrophobicity of Tf (via addition of 0-14 M urea) had less effect on denaturing and release of Fe(3+) from the Tf binding pocket compared to changes in ionic strength. This journal is © The Royal Society of Chemistry 2011

Rapid freeze-drying cycle optimization using computer programs developed based on heat and mass transfer models and facilitated by tunable diode laser absorption spectroscopy (TDLAS).

PubMed

Kuu, Wei Y; Nail, Steven L

2009-09-01

Computer programs in FORTRAN were developed to rapidly determine the optimal shelf temperature, T(f), and chamber pressure, P(c), to achieve the shortest primary drying time. The constraint for the optimization is to ensure that the product temperature profile, T(b), is below the target temperature, T(target). Five percent mannitol was chosen as the model formulation. After obtaining the optimal sets of T(f) and P(c), each cycle was assigned with a cycle rank number in terms of the length of drying time. Further optimization was achieved by dividing the drying time into a series of ramping steps for T(f), in a cascading manner (termed the cascading T(f) cycle), to further shorten the cycle time. For the purpose of demonstrating the validity of the optimized T(f) and P(c), four cycles with different predicted lengths of drying time, along with the cascading T(f) cycle, were chosen for experimental cycle runs. Tunable diode laser absorption spectroscopy (TDLAS) was used to continuously measure the sublimation rate. As predicted, maximum product temperatures were controlled slightly below the target temperature of -25 degrees C, and the cascading T(f)-ramping cycle is the most efficient cycle design. In addition, the experimental cycle rank order closely matches with that determined by modeling.

Diversification of transcription factor-DNA interactions and the evolution of gene regulatory networks.

PubMed

Rogers, Julia M; Bulyk, Martha L

2018-04-25

Sequence-specific transcription factors (TFs) bind short DNA sequences in the genome to regulate the expression of target genes. In the last decade, numerous technical advances have enabled the determination of the DNA-binding specificities of many of these factors. Large-scale screens of many TFs enabled the creation of databases of TF DNA-binding specificities, typically represented as position weight matrices (PWMs). Although great progress has been made in determining and predicting binding specificities systematically, there are still many surprises to be found when studying a particular TF's interactions with DNA in detail. Paralogous TFs' binding specificities can differ in subtle ways, in a manner that is not immediately apparent from looking at their PWMs. These differences affect gene regulatory outputs and enable TFs to rewire transcriptional networks over evolutionary time. This review discusses recent observations made in the study of TF-DNA interactions that highlight the importance of continued in-depth analysis of TF-DNA interactions and their inherent complexity. This article is categorized under: Biological Mechanisms > Regulatory Biology. © 2018 Wiley Periodicals, Inc.

[Effect of Leonurus Heterophyllus Sweet on tissue factor transcription and expression in human umbilical vein endothelial cells in vitro].

PubMed

Zheng, Lian; Fang, Chi-hua

2007-06-01

To investigate the effect of Leonurus Heterophyllus Sweet, (LHS) on tissue factor (TF) transcription and expression induced by thrombin in human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with different concentrations of LHS and the TF mRNA expression was detected by reverse transcript-polymerase chain reaction (RT-PCR). LHS treatment of HUVECs at different concentrations and for different times resulted in significant differences in TF expression (Plt;0.01). The transcription of TF in LHS-treated cells was significantly different from that of the blank control group (Plt;0.01). LHS can decrease the expression of TF and intervene with TF transcription in HUVECs in vitro.

Single molecule tracking of Ace1p in Saccharomyces cerevisiae defines a characteristic residence time for non-specific interactions of transcription factors with chromatin

PubMed Central

Ball, David A.; Mehta, Gunjan D.; Salomon-Kent, Ronit; Mazza, Davide; Morisaki, Tatsuya; Mueller, Florian; McNally, James G.; Karpova, Tatiana S.

2016-01-01

In vivo single molecule tracking has recently developed into a powerful technique for measuring and understanding the transient interactions of transcription factors (TF) with their chromatin response elements. However, this method still lacks a solid foundation for distinguishing between specific and non-specific interactions. To address this issue, we took advantage of the power of molecular genetics of yeast. Yeast TF Ace1p has only five specific sites in the genome and thus serves as a benchmark to distinguish specific from non-specific binding. Here, we show that the estimated residence time of the short-residence molecules is essentially the same for Hht1p, Ace1p and Hsf1p, equaling 0.12–0.32 s. These three DNA-binding proteins are very different in their structure, function and intracellular concentration. This suggests that (i) short-residence molecules are bound to DNA non-specifically, and (ii) that non-specific binding shares common characteristics between vastly different DNA-bound proteins and thus may have a common underlying mechanism. We develop new and robust procedure for evaluation of adverse effects of labeling, and new quantitative analysis procedures that significantly improve residence time measurements by accounting for fluorophore blinking. Our results provide a framework for the reliable performance and analysis of single molecule TF experiments in yeast. PMID:27566148

Mass spectrometric studies of 1-ethyl-3-methylimidazolium and 1-propyl-2,3-dimethylimidazolium bis(trifluoromethyl)-sulfonylimides.

PubMed

Chilingarov, Norbert S; Medvedev, Artem A; Deyko, Grigoriy S; Kustov, Leonid M; Chernikova, Elena A; Glukhov, Lev M; Markov, Vitaliy Yu; Ioffe, Il'ya N; Senyavin, Vladimir M; Polyakova, Marina V; Sidorov, Lev N

2015-07-15

Ionic liquids ([Cat(+)][An(-)]) were believed to decompose before reaching vaporization temperatures, but recently some of them have been shown to vaporize congruently. Low-temperature vaporization of ionic substances is an intriguing phenomenon, so the vapor-phase composition and reactions of ionic liquids deserve more extensive study. Evaporation of two ionic liquids, [C2MIM(+)][Tf2 N(-)] and [C3MMIM(+)][Tf2N(-)], was studied by means of Knudsen effusion mass spectrometry. These liquids were also characterized using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, UV/Vis, IR, NMR spectroscopy, and elemental analysis. The vaporization enthalpies of (118 ± 3) and (124 ± 2) kJ·mol(-1) were determined for [C2MIM(+)][Tf2N(-)] and [C3MMIM(+)][Tf2N(-)], respectively. The corresponding equations for their saturated vapor pressures are: ln(p{[C2MIM(+)][Tf2N(-)]}/Pa) = -(14213 ± 325)/(T/K) + (26.57 ± 1.04), ln(p{[C2MMIM(+)][Tf2N(-)]}/Pa) = -(14868 ± 221)/(T/K) + (27.19 ± 0.60). The MALDI studies (positive and negative ion modes) enabled detection of monomeric [Cat(+)] and [An(-)] ions, the cluster ions {[Cat(+)]2 [An(-)]}(+) and {[Cat(+)][An(-)]2}(-), and some complex anions {2[An(-)] + Na(+)}(-), {2[An(-)] + K(+)}(-), {2[An(-)] + Cu(+)}(-) and {3[An(-)] + Ca(2+)}(-). Knudsen effusion mass spectrometry proved to be a valuable method to study the thermodynamics of ionic liquids. The saturated vapor pressure and vaporization enthalpy of [C3MMIM(+)][Tf2N(-)] were accurately determined for the first time. MALDI is also capable of providing indirect information on hydrogen bonding. Copyright © 2015 John Wiley & Sons, Ltd.

JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles.

PubMed

Mathelier, Anthony; Fornes, Oriol; Arenillas, David J; Chen, Chih-Yu; Denay, Grégoire; Lee, Jessica; Shi, Wenqiang; Shyr, Casper; Tan, Ge; Worsley-Hunt, Rebecca; Zhang, Allen W; Parcy, François; Lenhard, Boris; Sandelin, Albin; Wasserman, Wyeth W

2016-01-04

JASPAR (http://jaspar.genereg.net) is an open-access database storing curated, non-redundant transcription factor (TF) binding profiles representing transcription factor binding preferences as position frequency matrices for multiple species in six taxonomic groups. For this 2016 release, we expanded the JASPAR CORE collection with 494 new TF binding profiles (315 in vertebrates, 11 in nematodes, 3 in insects, 1 in fungi and 164 in plants) and updated 59 profiles (58 in vertebrates and 1 in fungi). The introduced profiles represent an 83% expansion and 10% update when compared to the previous release. We updated the structural annotation of the TF DNA binding domains (DBDs) following a published hierarchical structural classification. In addition, we introduced 130 transcription factor flexible models trained on ChIP-seq data for vertebrates, which capture dinucleotide dependencies within TF binding sites. This new JASPAR release is accompanied by a new web tool to infer JASPAR TF binding profiles recognized by a given TF protein sequence. Moreover, we provide the users with a Ruby module complementing the JASPAR API to ease programmatic access and use of the JASPAR collection of profiles. Finally, we provide the JASPAR2016 R/Bioconductor data package with the data of this release. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Lead suppresses chimeric human transferrin gene expression in transgenic mouse liver.

PubMed

Adrian, G S; Rivera, E V; Adrian, E K; Lu, Y; Buchanan, J; Herbert, D C; Weaker, F J; Walter, C A; Bowman, B H

1993-01-01

The major iron-transport protein in serum is transferrin (TF) which also has the capacity to transport other metals. This report presents evidence that synthesis of human TF can be regulated by the metal lead. Transgenic mice carrying chimeric human TF-chloramphenicol acetyl transferase (CAT) genes received lead or sodium salts by intraperitoneal injections or in drinking water. Transgene expression in liver was suppressed 31 to 50% by the lead treatment. Lead regulates human TF transgenes at the mRNA level since liver CAT enzyme activity, CAT protein, and TF-CAT mRNA levels were all suppressed. The dosages of lead did not alter synthesis of the other liver proteins, mouse TF and albumin, as measured by Northern blot analysis of total liver RNA and rocket immunoelectrophoresis of mouse sera. Moderate levels of lead exposure were sufficient to evoke the human TF transgene response; blood lead levels in mice that received lead acetate in drinking water ranged from 30 micrograms/dl to 56 micrograms/dl. In addition to suppressing expression of TF-CAT genes in transgenic mice, lead also suppressed synthesis of TF protein in cultured human hepatoma HepG2 cells. The regulation of human TF apparently differs from the regulation of mouse TF which is unresponsive to lead exposure.

Structural basis for receptor recognition by New World hemorrhagic fever arenaviruses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abraham, Jonathan; Corbett, Kevin D.; Farzan, Michael

New World hemorrhagic fever arenaviruses are rodent-borne agents that cause severe human disease. The GP1 subunit of the surface glycoprotein mediates cell attachment through transferrin receptor 1 (TfR1). We report the structure of Machupo virus (MACV) GP1 bound with human TfR1. Atomic details of the GP1-TfR1 interface clarify the importance of TfR1 residues implicated in New World arenavirus host specificity. Analysis of sequence variation among New World arenavirus GP1s and their host-species receptors, in light of the molecular structure, indicates determinants of viral zoonotic transmission. Infectivities of pseudoviruses in cells expressing mutated TfR1 confirm that contacts at the tip ofmore » the TfR1 apical domain determine the capacity of human TfR1 to mediate infection by particular New World arenaviruses. We propose that New World arenaviruses that are pathogenic to humans fortuitously acquired affinity for human TfR1 during adaptation to TfR1 of their natural hosts.« less

Design, synthesis, nuclear localization, and biological activity of a fluorescent duocarmycin analog, HxTfA.

PubMed

Kiakos, Konstantinos; Englinger, Bernhard; Yanow, Stephanie K; Wernitznig, Debora; Jakupec, Michael A; Berger, Walter; Keppler, Bernhard K; Hartley, John A; Lee, Moses; Patil, Pravin C

2018-05-01

HxTfA 4 is a fluorescent analog of a potent cytotoxic and antimalarial agent, TfA 3, which is currently being investigated for the development of an antimalarial vaccine, PlasProtect®. HxTfA contains a p-anisylbenzimidazole or Hx moiety, which is endowed with a blue emission upon excitation at 318 nm; thus enabling it to be used as a surrogate for probing the cellular fate of TfA using confocal microscopy, and addressing the question of nuclear localization. HxTfA exhibits similar selectivity to TfA for A-tract sequences of DNA, alkylating adenine-N3, albeit at 10-fold higher concentrations. It also possesses in vitro cytotoxicity against A549 human lung carcinoma cells and Plasmodium falciparum. Confocal microscopy studies showed for the first time that HxTfA, and by inference TfA, entered A549 cells and localized in the nucleus to exert its biological activity. At biologically relevant concentrations, HxTfA elicits DNA damage response as evidenced by a marked increase in the levels of γH2AX observed by confocal microscopy and immunoblotting studies, and ultimately induces apoptosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

"Hit-and-Run" leaves its mark: catalyst transcription factors and chromatin modification.

PubMed

Varala, Kranthi; Li, Ying; Marshall-Colón, Amy; Para, Alessia; Coruzzi, Gloria M

2015-08-01

Understanding how transcription factor (TF) binding is related to gene regulation is a moving target. We recently uncovered genome-wide evidence for a "Hit-and-Run" model of transcription. In this model, a master TF "hits" a target promoter to initiate a rapid response to a signal. As the "hit" is transient, the model invokes recruitment of partner TFs to sustain transcription over time. Following the "run", the master TF "hits" other targets to propagate the response genome-wide. As such, a TF may act as a "catalyst" to mount a broad and acute response in cells that first sense the signal, while the recruited TF partners promote long-term adaptive behavior in the whole organism. This "Hit-and-Run" model likely has broad relevance, as TF perturbation studies across eukaryotes show small overlaps between TF-regulated and TF-bound genes, implicating transient TF-target binding. Here, we explore this "Hit-and-Run" model to suggest molecular mechanisms and its biological relevance. © 2015 The Authors. Bioessays published by WILEY Periodicals, Inc.

Cyclic fatigue analysis of twisted file rotary NiTi instruments used in reciprocating motion.

PubMed

Gambarini, G; Gergi, R; Naaman, A; Osta, N; Al Sudani, D

2012-09-01

To evaluate the cyclic fatigue fracture resistance of engine-driven twisted file (TF) instruments under reciprocating movement. A sample of 30 size 25, 0.08 taper NiTi TF instruments was tested in a simulated canal with 60˚ angle of curvature and a 3 mm radius. During mechanical testing, different movement kinematics were used at a constant speed, which resulted in three experimental groups (each group n = 10). The instruments from the first group (G1) were rotated until fracture occurred. The instruments in the second (G2) and third group (G3) were driven under reciprocating movement with different angles of reciprocation. The time of fracture for each instrument was measured, and statistical analysis was performed using one-way analysis of variance followed by Tukey's Honestly Significant Different test. Reciprocating movement resulted in a significantly longer cyclic fatigue life (P < 0.0001) when compared with continuous rotation. No difference was found between reciprocation 150° clockwise/30° counterclockwise (CW/CCW) and 30° CW/150° CCW. The reciprocating movement was associated with an extended cyclic fatigue life of the TF size 0.25, 0.08 taper instruments in comparison with conventional rotation. © 2012 International Endodontic Journal.

Hemoglobin enhances tissue factor expression on human malignant cells.

PubMed

Siddiqui, F A; Amirkhosravi, A; Amaya, M; Meyer, T; Biggerstaff, J; Desai, H; Francis, J L

2001-04-01

Tissue Factor (TF) is a transmembrane glycoprotein that complexes with factor VII/activated factor VII to initiate blood coagulation. TF may be expressed on the surface of various cells including monocytes and endothelial cells. Over-expression of TF in human tumor cell lines promotes metastasis. We recently showed that hemoglobin (Hb) forms a specific complex with TF purified from human malignant melanoma cells and enhances its procoagulant activity (PCA). To further study this interaction, we examined the effect of Hb on the expression of TF on human malignant (TF+) cells and KG1 myeloid leukemia (TF-) cells. Human melanoma A375 and J82 bladder carcinoma cells, which express TF at moderate and relatively high levels, respectively, were incubated with varying concentrations (0-1.5 mg/ml) of Hb. After washing, cells were analyzed for Hb binding and TF expression using flow cytometry and confocal microscopy. Hb bound to the cells in a concentration-dependent manner, and increased both TF expression and PCA. The human A375 malignant melanoma cells incubated with Hb (1 mg/ml) expressed up to six times more TF antigen than cells without Hb. This increase in TF expression and PCA of intact cells incubated with Hb was significantly inhibited by cycloheximide at a concentration of 10 microg/ml (P < 0.01). An increase in total cellular TF antigen content was demonstrated by specific immunoassay. In contrast, Hb (5 mg/ml) did not induce TF expression and PCA on KG1 cells as determined by flow cytometry and TF (FXAA) activity. We conclude that Hb specifically binds to TF-bearing malignant cells and increases their PCA. This effect seems to be at least partly due to de novo synthesis of TF and increased surface expression. However, the exact mechanism by which Hb binds and upregulates TF expression remains to be determined.

A Follow-Up Study from a Multisite, Randomized Controlled Trial for Traumatized Children Receiving TF-CBT.

PubMed

Jensen, Tine K; Holt, Tonje; Ormhaug, Silje M

2017-11-01

Trauma-focused cognitive behavioral therapy (TF-CBT) is the treatment of choice for traumatized youth, however, follow-up studies are scarce, and treatment effects for co-occurring depression show mixed findings. The aims of this study were to examine whether treatment effects of TF-CBT are maintained at 18 month follow-up and whether degree of co-occurring depression influences treatment effects. As rapid improvement in psychological functioning is warranted for youth, we also investigated whether the symptom trajectory was different for TF-CBT compared to therapy as usual (TAU). The sample consisted of 156 youth (M age = 15.05, 79.50% girls) randomly assigned to TF-CBT or TAU. The youth were assessed for posttraumatic stress symptoms (PTSS), depression, anxiety and general mental health symptoms. Mixed effects analyses followed the symptom courses over 5 time points. Youth receiving TF-CBT maintained their symptom improvement at 18 months follow-up with scores below clinical cut-of on all symptom measures. The most depressed youth had also a significant decline in symptoms that were maintained at follow-up. Symptom trajectories differed as the TF-CBT group reported a more rapid symptom reduction compared to the TAU condition. In the TAU condition, participants received 1.5 times the number of treatment sessions compared to the TF-CBT participants. After 18 months the groups were significantly different on general mental health symptoms only. In conclusion, youth receiving TF-CBT experienced more efficient improvement in trauma related symptoms than youth receiving TAU and these improvements were maintained after 18 months. Also youth experiencing serious co-occurring depression benefitted from TF-CBT.

Effect of Thawing Time, Cooling Rate and Boron Nutrition on Freezing Point of the Primordial Shoot in Norway Spruce Buds

PubMed Central

RÄISÄNEN, MIKKO; REPO, TAPANI; LEHTO, TARJA

2006-01-01

• Background Effects of cooling rates on bud frost hardiness have been studied but there is little information on bud responses to thawing. Since the cell wall pore size has been found to increase with boron (B) deficiency, B deficiency may affect the supercooling ability of buds in winter. • Methods The effects of duration of thawing time and rate of cooling on bud frost hardiness of Norway spruce (Picea abies) were studied in a B fertilization trial in February 2003 and March 2005. Frost hardiness of apical buds was determined by differential thermal analysis (DTA) and visual scoring of damage. • Key Results In 2003, the freezing point of primordial shoots of buds (Tf), i.e. the low-temperature exotherm (LTE), was, on average, −39 °C when buds were thawed for less than 3 h and the Tf increased to −21 °C after 18 h of thawing. During the first 4 h of thawing, the rate of dehardening was 6 °C h−1. In 2005, buds dehardened linearly from −39 °C to −35 °C at a rate of 0·7 °C h−1. In 2003, different cooling rates of 1–5 °C h−1 had a minor effect on Tf but in 2005 with slow cooling rates Tf decreased. In both samplings, at cooling rates of 2 and 1 °C h−1, Tf was slightly higher in B-fertilized than in non-fertilized trees. By contrast, at very short thawing times in 2003, Tf was somewhat lower in B-fertilized trees. • Conclusions There was little evidence of reduced frost hardiness in trees with low B status. This study showed that buds deharden rapidly when exposed to above-freezing temperatures in winter, but if cooled again they reharden more slowly. According to this study, rapid dehardening of buds has to be taken into account in assessments of frost hardiness. PMID:16464880

TF1, the bacteriophage SPO1-encoded type II DNA-binding protein, is essential for viral multiplication.

PubMed

Sayre, M H; Geiduschek, E P

1988-09-01

The lytic Bacillus subtilis bacteriophage SPO1 encodes an abundant, 99-amino-acid type II DNA-binding protein, transcription factor 1 (TF1). TF1 is special in this family of procaryotic chromatin-forming proteins in its preference for hydroxymethyluracil-containing DNA, such as SPO1 DNA, and in binding with high affinity to specific sites in the SPO1 chromosome. We constructed recessive null alleles of the TF1 gene and introduced them into SPO1 chromosomes. Segregation analysis with partially diploid phage heterozygous for TF1 showed that phage bearing only these null alleles was inviable. Deletion of the nine C-proximal amino acids of TF1 prohibited phage multiplication in vivo and abolished its site-specific DNA-binding activity in vitro.

Nifedipine Increases Iron Content in WKPT-0293 Cl.2 Cells via Up-Regulating Iron Influx Proteins

PubMed Central

Yu, Shuang-Shuang; Jiang, Li-Rong; Ling, Yan; Qian, Zhong-Ming; Zhou, Yu-Fu; Li, Juan; Ke, Ya

2017-01-01

Nifedipine was reported to enhance urinary iron excretion in iron overloaded mice. However, it remains unknown how nifedipine stimulates urinary iron excretion in the kidney. We speculated that nifedipine might inhibit the TfR1/ DMT1 (transferrin receptor 1/divalent metal transporter1)-mediated iron uptake by proximal tubule cells in addition to blocking L-type Ca2+ channels, leading to an increase in iron in lumen-fluid and then urinary iron excretion. To test this hypothesis, we investigated the effects of nifedipine on iron content and expression of TfR1, DMT1 and ferroportin1 (Fpn1) in WKPT-0293 Cl.2 cells of the S1 segment of the proximal tubule in rats, using a graphite furnace atomic absorption spectrophotometer and Western blot analysis, respectively. We demonstrated for the first time that nifedipine significantly enhanced iron content as well as TfR1 and DMT1 expression and had no effect on Fpn1 levels in the cells. We also found that ferric ammonium citrate decreased TfR1 levels, increased Fpn1 expression and had no effect on DMT1 content, while co-treatment with nifedipine and FAC increase TfR1 and DMT1 expression and also had no effect on Fpn1 levels. These findings suggest that the nifedipine-induced increase in cell iron may mainly be due to the corresponding increase in TfR1 and DMT1 expression and also imply that the effects of nifedipine on iron transport in proximal tubule cells can not explain the increase in urinary iron excretion. PMID:28243203

Impact of Orbit Position Errors on Future Satellite Gravity Models

NASA Astrophysics Data System (ADS)

Encarnacao, J.; Ditmar, P.; Klees, R.

2015-12-01

We present the results of a study of the impact of orbit positioning noise (OPN) caused by incomplete knowledge of the Earth's gravity field on gravity models estimated from satellite gravity data. The OPN is simulated as the difference between two sets of orbits integrated on the basis of different static gravity field models. The OPN is propagated into ll-SST data, here computed as averaged inter-satellite accelerations projected onto the Line of Sight (LoS) vector between the two satellites. We consider the cartwheel formation (CF), pendulum formation (PF), and trailing formation (TF) as they produce a different dominant orientation of the LoS vector. Given the polar orbits of the formations, the LoS vector is mainly aligned with the North-South direction in the TF, with the East-West direction in the PF (i.e. no along-track offset), and contains a radial component in the CF. An analytical analysis predicts that the CF suffers from a very high sensitivity to the OPN. This is a fundamental characteristic of this formation, which results from the amplification of this noise by diagonal components of the gravity gradient tensor (defined in the local frame) during the propagation into satellite gravity data. In contrast, the OPN in the data from PF and TF is only scaled by off-diagonal gravity gradient components, which are much smaller than the diagonal tensor components. A numerical analysis shows that the effect of the OPN is similar in the data collected by the TF and the PF. The amplification of the OPN errors for the CF leads to errors in the gravity model that are three orders of magnitude larger than those in case of the PF. This means that any implementation of the CF will most likely produce data with relatively low quality since this error dominates the error budget, especially at low frequencies. This is particularly critical for future gravimetric missions that will be equipped with highly accurate ranging sensors.

Cross-correlation analysis between Chinese TF contracts and treasury ETF based on high-frequency data

NASA Astrophysics Data System (ADS)

Zhou, Yu; Chen, Shi

2016-02-01

In this paper, we investigate the high-frequency cross-correlation relationship between Chinese treasury futures contracts and treasury ETF. We analyze the logarithmic return of these two price series, from which we can conclude that both return series are not normally distributed and the futures markets have greater volatility. We find significant cross-correlation between these two series. We further confirm the relationship using the DCCA coefficient and the DMCA coefficient. We quantify the long-range cross-correlation with DCCA method, and we further show that the relationship is multifractal. An arbitrage algorithm based on DFA regression with stable return is proposed in the last part.

Quantitative Evaluation of 2 Scatter-Correction Techniques for 18F-FDG Brain PET/MRI in Regard to MR-Based Attenuation Correction.

PubMed

Teuho, Jarmo; Saunavaara, Virva; Tolvanen, Tuula; Tuokkola, Terhi; Karlsson, Antti; Tuisku, Jouni; Teräs, Mika

2017-10-01

In PET, corrections for photon scatter and attenuation are essential for visual and quantitative consistency. MR attenuation correction (MRAC) is generally conducted by image segmentation and assignment of discrete attenuation coefficients, which offer limited accuracy compared with CT attenuation correction. Potential inaccuracies in MRAC may affect scatter correction, because the attenuation image (μ-map) is used in single scatter simulation (SSS) to calculate the scatter estimate. We assessed the impact of MRAC to scatter correction using 2 scatter-correction techniques and 3 μ-maps for MRAC. Methods: The tail-fitted SSS (TF-SSS) and a Monte Carlo-based single scatter simulation (MC-SSS) algorithm implementations on the Philips Ingenuity TF PET/MR were used with 1 CT-based and 2 MR-based μ-maps. Data from 7 subjects were used in the clinical evaluation, and a phantom study using an anatomic brain phantom was conducted. Scatter-correction sinograms were evaluated for each scatter correction method and μ-map. Absolute image quantification was investigated with the phantom data. Quantitative assessment of PET images was performed by volume-of-interest and ratio image analysis. Results: MRAC did not result in large differences in scatter algorithm performance, especially with TF-SSS. Scatter sinograms and scatter fractions did not reveal large differences regardless of the μ-map used. TF-SSS showed slightly higher absolute quantification. The differences in volume-of-interest analysis between TF-SSS and MC-SSS were 3% at maximum in the phantom and 4% in the patient study. Both algorithms showed excellent correlation with each other with no visual differences between PET images. MC-SSS showed a slight dependency on the μ-map used, with a difference of 2% on average and 4% at maximum when a μ-map without bone was used. Conclusion: The effect of different MR-based μ-maps on the performance of scatter correction was minimal in non-time-of-flight 18 F-FDG PET/MR brain imaging. The SSS algorithm was not affected significantly by MRAC. The performance of the MC-SSS algorithm is comparable but not superior to TF-SSS, warranting further investigations of algorithm optimization and performance with different radiotracers and time-of-flight imaging. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Cyclic fatigue resistance of R-Pilot, WaveOne Gold Glider, and ProGlider glide path instruments.

PubMed

Keskin, Cangül; İnan, Uğur; Demiral, Murat; Keleş, Ali

2018-02-17

The aim of the present study was to compare the cyclic fatigue resistance of R-Pilot (VDW; Munich, Germany) with ProGlider (Denstply Sirona; Ballaigues, Switzerland) and WaveOne Gold Glider (Denstply Sirona; Ballaigues, Switzerland) glide path instruments. R-Pilot, ProGlider, and WaveOne Gold Glider instruments were collected (n = 15) and tested in a dynamic cyclic fatigue test device, which has an artificial canal with 60° angle of curvature and a 5-mm radius of curvature. All instruments were operated until fracture occurred, and both time to fracture (TF) and the lengths of the fractured fragments were recorded. Mean and standard deviations of TF and fragment length were calculated for each reciprocating system. TF data and fractured fragment length data were subjected to one-way ANOVA and post-hoc Tukey tests (P < 0.05). Also a Weibull analysis was performed on TF data. The cyclic fatigue resistance values of the WaveOne Gold Glider and R-Pilot were significantly higher than those of the ProGlider (P < 0.05), with no significant difference between them (P > 0.05). Weibull analysis revealed that WaveOne Gold Glider showed the highest predicted TF value for 99% survival rate, which was followed by R-Pilot and ProGlider. Regarding the length of the fractured tips, there were no significant differences among the instruments (P > 0.05). The reciprocating WaveOne Gold Glider and R-Pilot instruments had significantly higher cyclic fatigue resistance than rotary ProGlider instruments. This study reported that novel reciprocating glide path instruments exhibited higher cyclic fatigue resistance than rotating glide path instrument.

Controls on Patterns of Repeated Fault Rupture: Examples From the Denali and Bear River Faults

NASA Astrophysics Data System (ADS)

Schwartz, D. P.; Hecker, S.

2013-12-01

A requirement for estimating seismic hazards is assigning magnitudes to earthquake sources. This relies on anticipating rupture length and slip along faults. Fundamental questions include whether lengths of past surface ruptures can be reasonably determined from fault zone characteristics and whether the variability in length and slip during repeated faulting can be constrained. To address these issues, we look at rupture characteristics and their possible controls from examples in very different tectonic settings: the high slip rate (≥15 mm/yr) Denali fault system, Alaska, and the recently activated Bear River normal fault, Wyoming-Utah. The 2002 rupture of the central Denali fault (CDF) is associated with two noteworthy geometric features. First, rupture initiated where the Susitna Glacier thrust fault (SG) intersects the CDF at depth, near the apex of a structurally complex restraining bend along the Denali. Paleoseismic data show that for the past 700 years the timing of large surface ruptures on the Denali fault west of the 2002 rupture has been distinct from those along the CDF. For the past ~6ka the frequency of SG to Denali ruptures has been ~1:12, indicating that this complexity of the 2002 rupture has not been common. Second, rupture propagated off of one strike-slip fault (CDF) onto another (the Totschunda fault, TF), an occurrence that seldom has been observed. LiDAR mapping of the intersection shows direct connectivity of the two faults--the CDF simply branches into both the TF and the eastern Denali fault (EDF). Differences in the timing of earthquakes during the past 700-800 years at sites surrounding this intersection, and estimates of accumulated slip from slip rates, indicate that for the 2002 rupture sufficient strain had accumulated on the TF to favor its failure. In contrast, the penultimate CDF rupture, with the same slip distribution as in 2002, appears to have stopped at or near the branch point, implying that neither the TF nor the EDF was stressed sufficiently to fail at that time. The Bear River fault zone (BRFZ) is a young normal fault along the eastern margin of basin-range extension that appears to have reactivated a ramp in the Laramide-age Darby-Hogsback thrust. The entire Cenozoic history of the BRFZ may consist of only two surface-rupturing events in the late Holocene (one at ~5 ka and the most recent at ~2.5 ka). The 40-km-long fault comprises synthetic and antithetic scarps extending across a zone up to 5 km wide. Remote sensing, including airborne LiDAR, and field studies show that, despite the complexity, the pattern of faulting was similar (in location and amount) for each of the two events and, at the south end, was strongly influenced by the east-west-trending Uinta Arch. Pre-existing structure clearly has exerted a first-order control on moment release on this immature fault. As shown by these examples, data on timing of surface ruptures, coseismic slip, slip rate, and fault geometry can provide a basis to constrain lengths of past and future earthquake ruptures, including possible alternative rupture scenarios. The difficult question for hazard analysis is whether the available data capture the full range of behavior and with what relative frequency do the alternatives occur?

Efficacy of Twisted File Adaptive, Reciproc and ProTaper Universal Retreatment instruments for root-canal-filling removal: A cone-beam computed tomography study.

PubMed

Akbulut, Makbule Bilge; Akman, Melek; Terlemez, Arslan; Magat, Guldane; Sener, Sevgi; Shetty, Heeresh

2016-01-01

The aim of this study was to evaluate the efficacy of Twisted File (TF) Adaptive, Reciproc, and ProTaper Universal Retreatment (UR) System instruments for removing root-canal-filling. Sixty single rooted teeth were decoronated, instrumented and obturated. Preoperative CBCT scans were taken and the teeth were retreated with TF Adaptive, Reciproc, ProTaper UR, or hand files (n=15). Then, the teeth were rescanned, and the percentage volume of the residual root-canal-filling material was established. The total time for retreatment was recorded, and the data was statistically analyzed. The statistical ranking of the residual filling material volume was as follows: hand file=TF Adaptive>ProTaper UR=Reciproc. The ProTaper UR and Reciproc systems required shorter periods of time for retreatment. Root canal filling was more efficiently removed by using Reciproc and ProTaper UR instruments than TF Adaptive instruments and hand files. The TF Adaptive system was advantageous over hand files with regard to operating time.

p53 determines prognostic significance of the carbohydrate stem cell marker TF1 (CD176) in ovarian cancer.

PubMed

Heublein, Sabine; Page, Sabina K; Mayr, Doris; Ditsch, Nina; Jeschke, Udo

2016-06-01

The oncofoetal Thomsen-Friedenreich (TF1, CD176) epitope is a carbohydrate cancer stem cell (CSC) antigen, and TF1-mediated cancer progression can be widely reversed by anti-TF1 antibodies. Particularly, CSC-like cells are regarded to be tumorigenic and chemoresistant. Aberrant p53 is probably the factor most closely associated with chemoresistance and tumour aggressiveness in ovarian tumours. We thus questioned whether TF1 in combination with p53 or as a single marker may be related to clinico-pathological features and survival of ovarian cancer patients. Both markers were quantified in ovarian cancer tissue (n = 151) by immunohistochemistry. p53 staining was subdivided into three subgroups [n (completely negative) = 57, n (moderately stained) = 28, n (overexpressing) = 66]. TF1 was scored as positive (n = 30) versus negative (n = 121). Only in those cancers classified with moderate p53 staining-and thus most likely displaying with wild-type TP53-TF1 positivity turned out to be a predictor for shortened overall survival (univariate: p < 0.001, multivariate: p = 0.001). By screening 17 different protein markers for correlation with TF1, only mucin-1 emerged as a potential TF1 carrier protein. It is hypothesized that TF1 may confer tumour-promoting features, especially in a TP53 wild-type genetic background. In addition, TF1 is an attractive immunotherapeutic target. Whether those cases classified as TF1 positive and at the same time as moderately stained for p53 might particularly benefit from a future anti-TF1 antibody treatment or from TF1 vaccination therapy remains to be determined.

An efficient method to transcription factor binding sites imputation via simultaneous completion of multiple matrices with positional consistency.

PubMed

Guo, Wei-Li; Huang, De-Shuang

2017-08-22

Transcription factors (TFs) are DNA-binding proteins that have a central role in regulating gene expression. Identification of DNA-binding sites of TFs is a key task in understanding transcriptional regulation, cellular processes and disease. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) enables genome-wide identification of in vivo TF binding sites. However, it is still difficult to map every TF in every cell line owing to cost and biological material availability, which poses an enormous obstacle for integrated analysis of gene regulation. To address this problem, we propose a novel computational approach, TFBSImpute, for predicting additional TF binding profiles by leveraging information from available ChIP-seq TF binding data. TFBSImpute fuses the dataset to a 3-mode tensor and imputes missing TF binding signals via simultaneous completion of multiple TF binding matrices with positional consistency. We show that signals predicted by our method achieve overall similarity with experimental data and that TFBSImpute significantly outperforms baseline approaches, by assessing the performance of imputation methods against observed ChIP-seq TF binding profiles. Besides, motif analysis shows that TFBSImpute preforms better in capturing binding motifs enriched in observed data compared with baselines, indicating that the higher performance of TFBSImpute is not simply due to averaging related samples. We anticipate that our approach will constitute a useful complement to experimental mapping of TF binding, which is beneficial for further study of regulation mechanisms and disease.

Robust Inference of Genetic Exchange Communities from Microbial Genomes Using TF-IDF.

PubMed

Cong, Yingnan; Chan, Yao-Ban; Phillips, Charles A; Langston, Michael A; Ragan, Mark A

2017-01-01

Bacteria and archaea can exchange genetic material across lineages through processes of lateral genetic transfer (LGT). Collectively, these exchange relationships can be modeled as a network and analyzed using concepts from graph theory. In particular, densely connected regions within an LGT network have been defined as genetic exchange communities (GECs). However, it has been problematic to construct networks in which edges solely represent LGT. Here we apply term frequency-inverse document frequency (TF-IDF), an alignment-free method originating from document analysis, to infer regions of lateral origin in bacterial genomes. We examine four empirical datasets of different size (number of genomes) and phyletic breadth, varying a key parameter (word length k ) within bounds established in previous work. We map the inferred lateral regions to genes in recipient genomes, and construct networks in which the nodes are groups of genomes, and the edges natively represent LGT. We then extract maximum and maximal cliques (i.e., GECs) from these graphs, and identify nodes that belong to GECs across a wide range of k . Most surviving lateral transfer has happened within these GECs. Using Gene Ontology enrichment tests we demonstrate that biological processes associated with metabolism, regulation and transport are often over-represented among the genes affected by LGT within these communities. These enrichments are largely robust to change of k .

Gonad Transcriptome Analysis of High-Temperature-Treated Females and High-Temperature-Induced Sex-Reversed Neomales in Nile Tilapia

PubMed Central

Sun, Li Xue; Teng, Jian; Zhao, Yan; Li, Ning; Wang, Hui

2018-01-01

Background: Nowadays, the molecular mechanisms governing TSD (temperature-dependent sex determination) or GSD + TE (genotypic sex determination + temperature effects) remain a mystery in fish. Methods: We developed three all-female families of Nile tilapia (Oreochromis niloticus), and the family with the highest male ratio after high-temperature treatment was used for transcriptome analysis. Results: First, gonadal histology analysis indicated that the histological morphology of control females (CF) was not significantly different from that of high-temperature-treated females (TF) at various development stages. However, the high-temperature treatment caused a lag of spermatogenesis in high-temperature-induced neomales (IM). Next, we sequenced the transcriptome of CF, TF, and IM Nile tilapia. 79, 11,117, and 11,000 differentially expressed genes (DEGs) were detected in the CF–TF, CF–IM, and TF–IM comparisons, respectively, and 44 DEGs showed identical expression changes in the CF–TF and CF–IM comparisons. Principal component analysis (PCA) indicated that three individuals in CF and three individuals in TF formed a cluster, and three individuals in IM formed a distinct cluster, which confirmed that the gonad transcriptome profile of TF was similar to that of CF and different from that of IM. Finally, six sex-related genes were validated by qRT-PCR. Conclusions: This study identifies a number of genes that may be involved in GSD + TE, which will be useful for investigating the molecular mechanisms of TSD or GSD + TE in fish. PMID:29495590

ROBNCA: robust network component analysis for recovering transcription factor activities.

PubMed

Noor, Amina; Ahmad, Aitzaz; Serpedin, Erchin; Nounou, Mohamed; Nounou, Hazem

2013-10-01

Network component analysis (NCA) is an efficient method of reconstructing the transcription factor activity (TFA), which makes use of the gene expression data and prior information available about transcription factor (TF)-gene regulations. Most of the contemporary algorithms either exhibit the drawback of inconsistency and poor reliability, or suffer from prohibitive computational complexity. In addition, the existing algorithms do not possess the ability to counteract the presence of outliers in the microarray data. Hence, robust and computationally efficient algorithms are needed to enable practical applications. We propose ROBust Network Component Analysis (ROBNCA), a novel iterative algorithm that explicitly models the possible outliers in the microarray data. An attractive feature of the ROBNCA algorithm is the derivation of a closed form solution for estimating the connectivity matrix, which was not available in prior contributions. The ROBNCA algorithm is compared with FastNCA and the non-iterative NCA (NI-NCA). ROBNCA estimates the TF activity profiles as well as the TF-gene control strength matrix with a much higher degree of accuracy than FastNCA and NI-NCA, irrespective of varying noise, correlation and/or amount of outliers in case of synthetic data. The ROBNCA algorithm is also tested on Saccharomyces cerevisiae data and Escherichia coli data, and it is observed to outperform the existing algorithms. The run time of the ROBNCA algorithm is comparable with that of FastNCA, and is hundreds of times faster than NI-NCA. The ROBNCA software is available at http://people.tamu.edu/∼amina/ROBNCA

Single Pulse Electrical Stimulation to identify epileptogenic cortex: Clinical information obtained from early evoked responses.

PubMed

Mouthaan, B E; van 't Klooster, M A; Keizer, D; Hebbink, G J; Leijten, F S S; Ferrier, C H; van Putten, M J A M; Zijlmans, M; Huiskamp, G J M

2016-02-01

Single Pulse Electrical Stimulation (SPES) probes epileptogenic cortex during electrocorticography. Two SPES responses are described: pathological delayed responses (DR, >100 ms) associated with the seizure onset zone (SOZ) and physiological early responses (ER, <100 ms) that map cortical connectivity. We analyzed properties of ERs, including frequencies >80 Hz, in the SOZ and seizure propagation areas. We used data from 12 refractory epilepsy patients. SPES consisted of 10 pulses of 1 ms, 4-8 mA and 5s interval on adjacent electrodes pairs. Data were available at 2048 samples/s for six and 512 samples/s (22 bits) for eight patients and analyzed in the time-frequency (TF) and time-domain (TD). Electrodes with ERs were stronger associated with SOZ than non-SOZ electrodes. ERs with frequency content >80 Hz exist and are specific for SOZ channels. ERs evoked by stimulation of seizure onset electrodes were associated with electrodes involved in seizure propagation. Analysis of ERs can reveal aspects of pathology, manifested by association with seizure propagation and areas with high ER numbers that coincide with the SOZ. Not only DRs, but also ERs could have clinical value for mapping epileptogenic cortex and help to unravel aspects of the epileptic network. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

High-throughput sequencing of retrotransposon integration provides a saturated profile of target activity in Schizosaccharomyces pombe.

PubMed

Guo, Yabin; Levin, Henry L

2010-02-01

The biological impact of transposons on the physiology of the host depends greatly on the frequency and position of integration. Previous studies of Tf1, a long terminal repeat retrotransposon in Schizosaccharomyces pombe, showed that integration occurs at the promoters of RNA polymerase II (Pol II) transcribed genes. To determine whether specific promoters are preferred targets of integration, we sequenced large numbers of insertions using high-throughput pyrosequencing. In four independent experiments we identified a total of 73,125 independent integration events. These data provided strong support for the conclusion that Pol II promoters are the targets of Tf1 integration. The size and number of the integration experiments resulted in reproducible measures of integration for each intergenic region and ORF in the S. pombe genome. The reproducibility of the integration activity from experiment to experiment demonstrates that we have saturated the full set of insertion sites that are actively targeted by Tf1. We found Tf1 integration was highly biased in favor of a specific set of Pol II promoters. The overwhelming majority (76%) of the insertions were distributed in intergenic sequences that contained 31% of the promoters of S. pombe. Interestingly, there was no correlation between the amount of integration at these promoters and their level of transcription. Instead, we found Tf1 had a strong preference for promoters that are induced by conditions of stress. This targeting of stress response genes coupled with the ability of Tf1 to regulate the expression of adjacent genes suggests Tf1 may improve the survival of S. pombe when cells are exposed to environmental stress.

High-throughput sequencing of retrotransposon integration provides a saturated profile of target activity in Schizosaccharomyces pombe

PubMed Central

Guo, Yabin; Levin, Henry L.

2010-01-01

The biological impact of transposons on the physiology of the host depends greatly on the frequency and position of integration. Previous studies of Tf1, a long terminal repeat retrotransposon in Schizosaccharomyces pombe, showed that integration occurs at the promoters of RNA polymerase II (Pol II) transcribed genes. To determine whether specific promoters are preferred targets of integration, we sequenced large numbers of insertions using high-throughput pyrosequencing. In four independent experiments we identified a total of 73,125 independent integration events. These data provided strong support for the conclusion that Pol II promoters are the targets of Tf1 integration. The size and number of the integration experiments resulted in reproducible measures of integration for each intergenic region and ORF in the S. pombe genome. The reproducibility of the integration activity from experiment to experiment demonstrates that we have saturated the full set of insertion sites that are actively targeted by Tf1. We found Tf1 integration was highly biased in favor of a specific set of Pol II promoters. The overwhelming majority (76%) of the insertions were distributed in intergenic sequences that contained 31% of the promoters of S. pombe. Interestingly, there was no correlation between the amount of integration at these promoters and their level of transcription. Instead, we found Tf1 had a strong preference for promoters that are induced by conditions of stress. This targeting of stress response genes coupled with the ability of Tf1 to regulate the expression of adjacent genes suggests Tf1 may improve the survival of S. pombe when cells are exposed to environmental stress. PMID:20040583

Characterization of early and late endocytic compartments of the transferrin cycle. Transferrin receptor antibody blocks erythroid differentiation by trapping the receptor in the early endosome.

PubMed

Killisch, I; Steinlein, P; Römisch, K; Hollinshead, R; Beug, H; Griffiths, G

1992-09-01

We describe a detailed morphological characterization of the endocytic pathway in differentiating chicken erythroblasts transformed by a temperature-sensitive mutant of avian erythroblastosis virus (AEV). These cells express high levels of transferrin receptors (TfR) when induced to differentiate at 42 degrees C. Biochemical analysis showed that most (approximately 90%) of the internalized 125I-Tf recycled within approximately 30 min while a smaller fraction of 125I-Tf required up to 2 h for recycling. By immunocytochemistry, the bulk of Tf and TfR was localized at the plasma membrane and in tubuloreticular early endosomes. This structure contained coated buds that labelled with an antibody specific for the clathrin light chain. Decreasing amounts of both Tf and TfR were detected in two distal compartments, spherical endosome vesicles resembling multivesicular bodies and the prelysosomal compartment (PLC) enriched in cation-independent mannose 6-phosphate receptor. As shown by fluorescent (FITC-Tf) labelling of living cells, the movement of Tf/TfR complex into these late structures was accompanied by a significant drop in pH from about 6, the value displayed by early endosomes, to values below pH 5.0. Since no detectable 125I-Tf degradation was observed during a 4 h period we believe that the Tf/TfR detected in these late endocytic structures avoids degradation and recycles back to the cell surface. The addition of an anti-TfR monoclonal antibody to the culture medium of these cells blocks their differentiation. Under this condition the antibody-TfR complex was trapped in an early endosome compartment that enlarged to more than twice its normal size. However, this condition did not affect the transport kinetics of horseradish peroxidase from the medium to the PLC.

Nerves and Tissue Repair.

DTIC Science & Technology

1992-05-21

complete dependence on nerves. Organ culture of sciatic nerves, combined with an assay for axolotl transferrin developed earlier, allows quantitative study...axonal release of various unknown proteins. Combining this approach with the ELISA for quantitative measurement of axolotl transferrin developed with...light microscope autoradiographic analysis following binding of radiolabelled Tf. Studies of Tf synthesis will employ cDNA probes for axolotl Tf mRNA

The Development of Protein Microarrays and Their Applications in DNA-Protein and Protein-Protein Interaction Analyses of Arabidopsis Transcription Factors

PubMed Central

Gong, Wei; He, Kun; Covington, Mike; Dinesh-Kumar, S. P.; Snyder, Michael; Harmer, Stacey L.; Zhu, Yu-Xian; Deng, Xing Wang

2009-01-01

We used our collection of Arabidopsis transcription factor (TF) ORFeome clones to construct protein microarrays containing as many as 802 TF proteins. These protein microarrays were used for both protein-DNA and protein-protein interaction analyses. For protein-DNA interaction studies, we examined AP2/ERF family TFs and their cognate cis-elements. By careful comparison of the DNA-binding specificity of 13 TFs on the protein microarray with previous non-microarray data, we showed that protein microarrays provide an efficient and high throughput tool for genome-wide analysis of TF-DNA interactions. This microarray protein-DNA interaction analysis allowed us to derive a comprehensive view of DNA-binding profiles of AP2/ERF family proteins in Arabidopsis. It also revealed four TFs that bound the EE (evening element) and had the expected phased gene expression under clock-regulation, thus providing a basis for further functional analysis of their roles in clock regulation of gene expression. We also developed procedures for detecting protein interactions using this TF protein microarray and discovered four novel partners that interact with HY5, which can be validated by yeast two-hybrid assays. Thus, plant TF protein microarrays offer an attractive high-throughput alternative to traditional techniques for TF functional characterization on a global scale. PMID:19802365

Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer

PubMed Central

Uno, K; Homma, S; Satoh, T; Nakanishi, K; Abe, D; Matsumoto, K; Oki, A; Tsunoda, H; Yamaguchi, I; Nagasawa, T; Yoshikawa, H; Aonuma, K

2007-01-01

Ovarian cancer, and clear cell carcinoma in particular, reportedly increases the risk of venous thromboembolism (VTE). However, the mechanisms remain unclear. Tissue factor (TF) supposedly represents a major factor in the procoagulant activities of cancer cells. The present study examined the involvement of TF expression in VTE for patients with ovarian cancer. Subjects comprised 32 consecutive patients (mean age 49.8 years) with histologically confirmed ovarian cancer. Presence of VTE was examined using a combination of clinical features, D-dimer levels and venous ultrasonography. Immunohistochemical analysis was used to evaluate TF expression into 4 degrees. Venous thromboembolism was identified in 10 of the 32 patients (31%), including five of the 11 patients with clear cell carcinoma. Tissue factor expression was detected in cancer tissues from 24 patients and displayed significant correlations with VTE development (P=0.0003), D-dimer concentration (P=0.003) and clear cell carcinoma (P<0.05). Multivariate analysis identified TF expression as an independent predictive factor of VTE development (P<0.05). Tissue factor (TF) expression is a possible determinant of VTE development in ovarian cancer. In particular, clear cell carcinoma may produce excessive levels of TF and is more likely to develop VTE. PMID:17211468

Navigating the Functional Landscape of Transcription Factors via Non-Negative Tensor Factorization Analysis of MEDLINE Abstracts

PubMed Central

Roy, Sujoy; Yun, Daqing; Madahian, Behrouz; Berry, Michael W.; Deng, Lih-Yuan; Goldowitz, Daniel; Homayouni, Ramin

2017-01-01

In this study, we developed and evaluated a novel text-mining approach, using non-negative tensor factorization (NTF), to simultaneously extract and functionally annotate transcriptional modules consisting of sets of genes, transcription factors (TFs), and terms from MEDLINE abstracts. A sparse 3-mode term × gene × TF tensor was constructed that contained weighted frequencies of 106,895 terms in 26,781 abstracts shared among 7,695 genes and 994 TFs. The tensor was decomposed into sub-tensors using non-negative tensor factorization (NTF) across 16 different approximation ranks. Dominant entries of each of 2,861 sub-tensors were extracted to form term–gene–TF annotated transcriptional modules (ATMs). More than 94% of the ATMs were found to be enriched in at least one KEGG pathway or GO category, suggesting that the ATMs are functionally relevant. One advantage of this method is that it can discover potentially new gene–TF associations from the literature. Using a set of microarray and ChIP-Seq datasets as gold standard, we show that the precision of our method for predicting gene–TF associations is significantly higher than chance. In addition, we demonstrate that the terms in each ATM can be used to suggest new GO classifications to genes and TFs. Taken together, our results indicate that NTF is useful for simultaneous extraction and functional annotation of transcriptional regulatory networks from unstructured text, as well as for literature based discovery. A web tool called Transcriptional Regulatory Modules Extracted from Literature (TREMEL), available at http://binf1.memphis.edu/tremel, was built to enable browsing and searching of ATMs. PMID:28894735

Copper sulfide nanoparticle-based localized drug delivery system as an effective cancer synergistic treatment and theranostic platform.

PubMed

Hou, Lin; Shan, Xiaoning; Hao, Lisha; Feng, Qianhua; Zhang, Zhenzhong

2017-05-01

Localized cancer treatment with combination therapy has attracted increasing attention for effective inhibition of tumor growth. In this work, we introduced diffusion molecular retention (DMR) tumor targeting effect, a new strategy that employed transferrin (Tf) modified hollow mesoporous CuS nanoparticles (HMCuS NPs) to undergo extensive diffuse through the interstitium and tumor retention after a peritumoral (PT) injection. Herein, HMCuS NPs with strong near-infrared (NIR) absorption and photothermal conversion efficiency could serve as not only a drug carrier but also a powerful contrast agent for photoacoustic imaging to guide chemo-phototherapy. The iron-dependent artesunate (AS), which possessed profound cytotoxicity against tumor cell, was used as model drug. As a result, this AS loaded Tf-HMCuS NPs (AS/Tf-HMCuS NPs) system could specially target to tumor cells and synchronously deliver AS as well as irons into tumor to achieve enhanced antitumor activity. It was found that AS/Tf-HMCuS NPs was taken up by MCF-7 cells via Tf-mediated endocytosis, and could effectively convert NIR light into heat for photothermal therapy as well as generated high levels of reactive oxygen species (ROS) for photodynamic therapy. In addition, in vivo antitumor efficacy studies showed that tumor-bearing mice treated with AS/Tf-HMCuS NPs through peritumoral (PT) injection under NIR laser irradiation displayed the strongest inhibition rate of about 74.8%, even with the reduced frequency of administration. Furthermore, to demonstrate DMR, the optical imaging, photoacoustic tomography and immunofluorescence after PT injection were adopted to track the behavior of AS/Tf-HMCuS NPs in vivo. The results exhibited that Tf-HMCuS NPs prolonged the local accumulation and retention together with slow vascular uptake and extensive interstitial diffusion, which was consistent with the biodistribution studies of AS/Tf-HMCuS NPs. Therefore, the approach of localized delivery through DMR combined with multi-mechanism therapy may be a promising method for cancer treatment. In recent years, localized cancer treatment using different biomaterials has attracted increasing attention for effective inhibition of tumor growth. However, it is still challenging for this kind of system to achieve a high drug loading, overcome biological barriers from the site of injection to the site of action, and combine synergetic therapy with diagnosis without adversely affecting the formation process. This study provides a localized diffusion molecular retention (DMR) tumor targeting drug delivery system based on hollow mesoporous copper sulfide nanoparticles (HMCuS NPs) entrapment of anticancer drug for the first time, which can achieve high drug loading, improve local drug accumulation and retention, accomplish synergistic combination of chemo-phototherapy, and finally enhance antitumor effect. In addition, HMCuS NPs also possesses the property suitable for photoacoustic imaging, which could offer us a theranostic platform. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII.

PubMed

Ollivier, V; Bentolila, S; Chabbat, J; Hakim, J; de Prost, D

1998-04-15

The transmembrane protein tissue factor (TF) is the cell surface receptor for coagulation factor VII (FVII) and activated factor VII (FVIIa). Recently, TF has been identified as a regulator of angiogenesis, tumor growth, and metastasis. This study was designed to link the binding of FVII(a) to its receptor, TF, with the subsequent triggering of angiogenesis through vascular endothelial growth factor (VEGF) production by human lung fibroblasts. We report that incubation of fibroblasts, which express constitutive surface TF, with FVII(a) induces VEGF synthesis. FVII(a)-induced VEGF secretion, assessed by a specific enzyme-linked immunosorbent assay, was time- and concentration-dependent. VEGF secretion was maximal after 24 hours of incubation of the cells with 100 nmol/L FVII(a) and represented a threefold induction of the basal VEGF level. Reverse transcriptase-polymerase chain reaction analysis of VEGF detected three mRNA species of 180, 312, and 384 bp corresponding, respectively, to VEGF121, VEGF165, and VEGF189. A 2.5- to 3.5-fold increase was observed for the 180- and 312-bp transcripts at 12 and 24 hours, respectively. FVII(a)-dependent VEGF production was inhibited by a pool of antibodies against TF, pointing to the involvement of this receptor. On specific active-site inhibition with dansyl-glutamyl-glycinyl-arginyl chloromethyl ketone, FVIIa lost 70% of its capacity to elicit VEGF production. Consistent with this, the native form (zymogen) of FVII only had a 1.8-fold stimulating effect. Protein tyrosine kinase and protein kinase C are involved in signal transduction leading to VEGF production, as shown by the inhibitory effects of genistein and GF 109203X. The results of this study indicate that TF is essential for VIIa-induced VEGF production by human fibroblasts and that its role is mainly linked to the proteolytic activity of the TF-VIIa complex.

Social Relationships of Dually Diagnosed Homeless Adults Following Enrollment in Housing First or Traditional Treatment Services

PubMed Central

Henwood, Benjamin F.; Stefancic, Ana; Petering, Robin; Schreiber, Sarah; Abrams, Courtney; Padgett, Deborah K.

2015-01-01

Objective Strong and effective social support is a critical element of mental health recovery, yet social support is often lacking for adults experiencing homelessness. This study examines differences in the social networks of participants newly enrolled in programs that use either a Housing First (HF) approach (i.e., provides immediate access to permanent housing with ongoing consumer-driven support services) or a treatment first (TF) approach (i.e., traditional clinician-driven staircse model that requires temporary or transitional housing and treatment placements before accessing permanent housing). Method We use a mixed-methods social network analysis approach to assess group differences of 75 individuals based on program type (HF or TF) and program retention. Results Quantitative results show that compared with TF, HF participants have a greater proportion of staff members in their network. TF participants are more likely than HF participants to maintain mixed-quality relationships (i.e., relationships with elements of support and conflict). As compared with participants who remain in a program, those who disengage from programs have a greater proportion of mixed relationships and relationships that grow distant. Qualitative analyses suggest that HF participants regard housing as providing a stable foundation from which to reconnect or restore broken relationships. However, HF participants are guarded about close relationships for fear of being exploited due to their newly acquired apartments. TF participants report that they are less inclined to develop new relationships with peers or staff members due to the time-limited nature of the TF programs. Conclusions These findings suggest that HF participants are not more socially isolated than those in traditional care. Implications for practice, policy and future research are discussed. PMID:26635919

Time-dependent changes in the growth of ultrathin ionic liquid films on Ag(111).

PubMed

Lexow, Matthias; Talwar, Timo; Heller, Bettina S J; May, Benjamin; Bhuin, Radha G; Maier, Florian; Steinrück, Hans-Peter

2018-05-09

Various amounts of the ionic liquids (ILs) [C1C1Im][Tf2N] and [C8C1Im][Tf2N] were deposited in vacuo by physical vapour deposition (PVD) on single crystalline Ag(111) at room temperature and subsequently monitored by angle-resolved X-ray photoelectron spectroscopy (ARXPS) as a function of time. For very low coverages of up to one closed molecular layer, an initial wetting layer was rapidly formed for both ILs. Deposition of higher amounts of [C1C1Im][Tf2N] revealed an initial three-dimensional film morphology. On the time scale of hours, characteristic changes of the XPS signals were observed. These are interpreted as island spreading and a transformation towards a nearly two dimensional [C1C1Im][Tf2N] film as the final state. In contrast, a film morphology close to 2D was found from the very beginning for [C8C1Im][Tf2N] deposited on Ag(111) demonstrating the influence of the alkyl chain length on the growth kinetics. These studies also highlight the suitability of time-resolved ARXPS for the investigation of IL/solid interfaces, which play a crucial role in IL thin film applications such as in catalysis, sensor, lubrication, and coating technologies.

Fission yeast retrotransposon Tf1 integration is targeted to 5' ends of open reading frames.

PubMed

Behrens, R; Hayles, J; Nurse, P

2000-12-01

Target site selection of transposable elements is usually not random but involves some specificity for a DNA sequence or a DNA binding host factor. We have investigated the target site selection of the long terminal repeat-containing retrotransposon Tf1 from the fission yeast Schizosaccharomyces pombe. By monitoring induced transposition events we found that Tf1 integration sites were distributed throughout the genome. Mapping these insertions revealed that Tf1 did not integrate into open reading frames, but occurred preferentially in longer intergenic regions with integration biased towards a region 100-420 bp upstream of the translation start site. Northern blot analysis showed that transcription of genes adjacent to Tf1 insertions was not significantly changed.

The self primer of the long terminal repeat retrotransposon Tf1 is not removed during reverse transcription.

PubMed

Atwood-Moore, Angela; Yan, Kenneth; Judson, Robert L; Levin, Henry L

2006-08-01

The long terminal repeat retrotransposon Tf1 of Schizosaccharomyces pombe uses a unique mechanism of self priming to initiate reverse transcription. Instead of using a tRNA, Tf1 primes minus-strand synthesis with an 11-nucleotide RNA removed from the 5' end of its own transcript. We tested whether the self primer of Tf1 was similar to tRNA primers in being removed from the cDNA by RNase H. Our analysis of Tf1 cDNA extracted from virus-like particles revealed the surprising observation that the dominant species of cDNA retained the self primer. This suggests that integration of the cDNA relies on mechanisms other than reverse transcription to remove the primer.

Fission yeast retrotransposon Tf1 integration is targeted to 5′ ends of open reading frames

PubMed Central

Behrens, Ralf; Hayles, Jacky; Nurse, Paul

2000-01-01

Target site selection of transposable elements is usually not random but involves some specificity for a DNA sequence or a DNA binding host factor. We have investigated the target site selection of the long terminal repeat-containing retrotransposon Tf1 from the fission yeast Schizosaccharomyces pombe. By monitoring induced transposition events we found that Tf1 integration sites were distributed throughout the genome. Mapping these insertions revealed that Tf1 did not integrate into open reading frames, but occurred preferentially in longer intergenic regions with integration biased towards a region 100–420 bp upstream of the translation start site. Northern blot analysis showed that transcription of genes adjacent to Tf1 insertions was not significantly changed. PMID:11095681

[Trigger factor dependent refolding of bacterial luciferases in Escherichia coli cells: kinetics, efficiency and effect of the bichaperone system, DnaKJE-ClpB].

PubMed

Mel'kina, O E; Gorianin, I I; Manukhov, I V; Zavil'gel'skiĭ, G B

2013-01-01

Here were determined the basic parameters of the Tigger Factor (TF) -dependent refolding of thermal inactivated bacterial luciferases. The TF-dependent refolding is less efficient and requires more time than DnaKJE-dependent refolding. The increase in the intracellular concentration of TF leads to an apparent decrease in the level of the thermal inactivated bacterial luciferase refolding. For thermolabile luciferases, the level of TF-dependent refolding is significantly higher, than for thermostable luciferases: 30-40%--for the thermolabile Aliivibrio fischeri and Photobacterium leiognathi luciferases, and 10 and 0.5% for the thermostable Vibrio harveyi and Photorhabdus luminescens luciferases, respectively. The negative effect of the ClpB protein on the TF-dependent refolding was shown: in Escherichia coli clpB::kan TF-dependent refolding is more efficient than in the E. coli clpB+.

Integrating Natural Language Processing and Machine Learning Algorithms to Categorize Oncologic Response in Radiology Reports.

PubMed

Chen, Po-Hao; Zafar, Hanna; Galperin-Aizenberg, Maya; Cook, Tessa

2018-04-01

A significant volume of medical data remains unstructured. Natural language processing (NLP) and machine learning (ML) techniques have shown to successfully extract insights from radiology reports. However, the codependent effects of NLP and ML in this context have not been well-studied. Between April 1, 2015 and November 1, 2016, 9418 cross-sectional abdomen/pelvis CT and MR examinations containing our internal structured reporting element for cancer were separated into four categories: Progression, Stable Disease, Improvement, or No Cancer. We combined each of three NLP techniques with five ML algorithms to predict the assigned label using the unstructured report text and compared the performance of each combination. The three NLP algorithms included term frequency-inverse document frequency (TF-IDF), term frequency weighting (TF), and 16-bit feature hashing. The ML algorithms included logistic regression (LR), random decision forest (RDF), one-vs-all support vector machine (SVM), one-vs-all Bayes point machine (BPM), and fully connected neural network (NN). The best-performing NLP model consisted of tokenized unigrams and bigrams with TF-IDF. Increasing N-gram length yielded little to no added benefit for most ML algorithms. With all parameters optimized, SVM had the best performance on the test dataset, with 90.6 average accuracy and F score of 0.813. The interplay between ML and NLP algorithms and their effect on interpretation accuracy is complex. The best accuracy is achieved when both algorithms are optimized concurrently.

Ionic liquid-in-oil microemulsions composed of double chain surface active ionic liquid as a surfactant: temperature dependent solvent and rotational relaxation dynamics of coumarin-153 in [Py][TF2N]/[C4mim][AOT]/benzene microemulsions.

PubMed

Rao, Vishal Govind; Mandal, Sarthak; Ghosh, Surajit; Banerjee, Chiranjib; Sarkar, Nilmoni

2012-07-19

In the recent past, nonaqueous microemulsions containing ionic liquids (ILs) have been utilized for performing chemical reactions, preparation of nanomaterials, and synthesis of nanostructured polymers and in drug delivery systems. The most promising fact about IL-in-oil microemulsions is their high thermal stability compared to that of aqueous microemulsions. In our earlier publication (Rao, V. G.; Ghosh, S.; Ghatak, C.; Mandal, S.; Brahmachari, U.; Sarkar, N. J. Phys. Chem. B 2012, 116, 2850-2855), we presented for the first time the possibility of creating huge number of IL-in-oil microemulsions, just by replacing the inorganic cation, Na(+), of NaAOT by any organic cation and using different ionic liquids as the polar core. In this manuscript we are interested in exploring the effect of temperature on such systems. We have characterized the phase diagram of the [Py][TF2N]/[C4mim][AOT]/benzene ternary system at 298 K. We have shown that in the experimental temperature range employed in this study, the microemulsions remain stable and a slight decrease in the size of the microemulsions is observed with increasing temperature. We have reported the detailed study of solvent and rotational relaxation of coumarin 153 (C-153) in neat IL, N-methyl-N-propylpyrrolidinium bis((trifluoromethyl)sulfonyl)imide ([Py][TF2N]), and in [Py][TF2N]/[C4mim][AOT]/benzene microemulsions using steady state and picosecond time-resolved spectroscopy. We have monitored the effect of (i) varying the [Py][TF2N]/[C4mim][AOT] molar ratio (R value) and (ii) temperature on solvent and rotational relaxation of C-153. The features observed in absorption and emission spectra clearly indicate that (i) the probe molecules reside at the polar interfacial region of the [Py][TF2N]/[C4mim][AOT]/benzene microemulsions and (ii) with increasing R value the probe molecules move toward the polar IL-pool of the microemulsion. We have shown that the increase in solvation time on going from neat [Py][TF2N] to [Py][TF2N]-containing microemulsions is very small compared to the increase in solvation time on going from pure water to water-containing microemulsions. The average solvation time decreases with increasing R values at 298 K, but it shows only a small R dependence compared to microemulsions containing solvents capable of forming hydrogen bonds. We have also shown that the temperature has substantial effect on the solvent and rotational relaxation of C-153 in neat [Py][TF2N] compared to that of [Py][TF2N]/[C4mim][AOT]/benzene microemulsions at R = 0.69.

ECCM Scheme against Interrupted Sampling Repeater Jammer Based on Parameter-Adjusted Waveform Design

PubMed Central

Wei, Zhenhua; Peng, Bo; Shen, Rui

2018-01-01

Interrupted sampling repeater jamming (ISRJ) is an effective way of deceiving coherent radar sensors, especially for linear frequency modulated (LFM) radar. In this paper, for a simplified scenario with a single jammer, we propose a dynamic electronic counter-counter measure (ECCM) scheme based on jammer parameter estimation and transmitted signal design. Firstly, the LFM waveform is transmitted to estimate the main jamming parameters by investigating the discontinuousness of the ISRJ’s time-frequency (TF) characteristics. Then, a parameter-adjusted intra-pulse frequency coded signal, whose ISRJ signal after matched filtering only forms a single false target, is designed adaptively according to the estimated parameters, i.e., sampling interval, sampling duration and repeater times. Ultimately, for typical jamming scenes with different jamming signal ratio (JSR) and duty cycle, we propose two particular ISRJ suppression approaches. Simulation results validate the effective performance of the proposed scheme for countering the ISRJ, and the trade-off relationship between the two approaches is demonstrated. PMID:29642508

Rotational diffusion of nondipolar and charged solutes in alkyl-substituted imidazolium triflimides: effect of C2 methylation on solute rotation.

PubMed

Prabhu, Sugosh R; Dutt, G B

2014-08-07

Rotational diffusion of a nondipolar solute 2,5-dimethyl-1,4-dioxo-3,6-diphenylpyrrolo[3,4-c]pyrrole (DMDPP) and a charged solute rhodamine 110 (R110) has been investigated in 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([BMIM][Tf2N]) and 1-butyl-2,3-dimethylimidazolium bis(trifluoromethylsulfonyl)imide ([BMMIM][Tf2N]) to understand the influence of the C2 methylation on solute rotation. The measured reorientation times of the nondipolar solute DMDPP are similar in both the ionic liquids and follow Stokes-Einstein-Debye hydrodynamic theory with slip hydrodynamics. In contrast, rotational diffusion of the charged solute R110 in [BMIM][Tf2N] obeys stick hydrodynamics due to specific interactions with the anion of the ionic liquid. Nevertheless, the intriguing result of this study is that the reorientation times of R110 in [BMMIM][Tf2N] deviate significantly from the predictions of stick hydrodynamics, especially at ambient temperatures. The solute-solvent boundary condition parameter Cobs, which is defined as the ratio of the measured reorientation time to the one calculated using the SED theory with stick boundary condition, for R110 is lower by a factor of 2 in [BMMIM][Tf2N] compared to [BMIM][Tf2N] at 298 K. Upon increasing the temperature, Cobs gradually increases and eventually matches with that obtained in [BMIM][Tf2N] at 348 K. It has been well established that methylation of the C2 position in [BMMIM][Tf2N] switches off the main hydrogen-bonding interaction between the anion and the cation, but increases the Coulombic interactions. As a consequence of the enhanced interionic interactions between the cation and anion of the ionic liquid, specific interactions between R110 and [Tf2N] diminish leading to the faster rotation of the solute. However, such an influence is not apparent in case of DMDPP as it does not experience specific interactions with either the cation or the anion of these ionic liquids.

Genome-Wide Analysis of Androgen Receptor Targets Reveals COUP-TF1 as a Novel Player in Human Prostate Cancer

PubMed Central

Perets, Ruth; Kaplan, Tommy; Stein, Ilan; Hidas, Guy; Tayeb, Shay; Avraham, Eti; Ben-Neriah, Yinon; Simon, Itamar; Pikarsky, Eli

2012-01-01

Androgen activity plays a key role in prostate cancer progression. Androgen receptor (AR) is the main mediator of androgen activity in the prostate, through its ability to act as a transcription mediator. Here we performed a genome-wide analysis of human AR binding to promoters in the presence of an agonist or antagonist in an androgen dependent prostate cancer cell line. Many of the AR bound promoters are bound in all examined conditions while others are bound only in the presence of an agonist or antagonist. Several motifs are enriched in AR bound promoters, including the AR Response Element (ARE) half-site and recognition elements for the transcription factors OCT1 and SOX9. This suggests that these 3 factors could define a module of co-operating transcription factors in the prostate. Interestingly, AR bound promoters are preferentially located in AT rich genomic regions. Analysis of mRNA expression identified chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1) as a direct AR target gene that is downregulated upon binding by the agonist liganded AR. COUP-TF1 immunostaining revealed nucleolar localization of COUP-TF1 in epithelium of human androgen dependent prostate cancer, but not in adjacent benign prostate epithelium. Stromal cells both in human and mouse prostate show nuclear COUP-TF1 staining. We further show that there is an inverse correlation between COUP-TF1 expression in prostate stromal cells and the rising levels of androgen with advancing puberty. This study extends the pool of recognized putative AR targets and identifies a negatively regulated target of AR – COUP-TF1 – which could possibly play a role in human prostate cancer. PMID:23056316

Genome-wide analysis of androgen receptor targets reveals COUP-TF1 as a novel player in human prostate cancer.

PubMed

Perets, Ruth; Kaplan, Tommy; Stein, Ilan; Hidas, Guy; Tayeb, Shay; Avraham, Eti; Ben-Neriah, Yinon; Simon, Itamar; Pikarsky, Eli

2012-01-01

Androgen activity plays a key role in prostate cancer progression. Androgen receptor (AR) is the main mediator of androgen activity in the prostate, through its ability to act as a transcription mediator. Here we performed a genome-wide analysis of human AR binding to promoters in the presence of an agonist or antagonist in an androgen dependent prostate cancer cell line. Many of the AR bound promoters are bound in all examined conditions while others are bound only in the presence of an agonist or antagonist. Several motifs are enriched in AR bound promoters, including the AR Response Element (ARE) half-site and recognition elements for the transcription factors OCT1 and SOX9. This suggests that these 3 factors could define a module of co-operating transcription factors in the prostate. Interestingly, AR bound promoters are preferentially located in AT rich genomic regions. Analysis of mRNA expression identified chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1) as a direct AR target gene that is downregulated upon binding by the agonist liganded AR. COUP-TF1 immunostaining revealed nucleolar localization of COUP-TF1 in epithelium of human androgen dependent prostate cancer, but not in adjacent benign prostate epithelium. Stromal cells both in human and mouse prostate show nuclear COUP-TF1 staining. We further show that there is an inverse correlation between COUP-TF1 expression in prostate stromal cells and the rising levels of androgen with advancing puberty. This study extends the pool of recognized putative AR targets and identifies a negatively regulated target of AR - COUP-TF1 - which could possibly play a role in human prostate cancer.

A microfluidic method for synthesis of transferrin-lipid nanoparticles loaded with siRNA LOR-1284 for therapy of acute myeloid leukemia

PubMed Central

Yang, Zhaogang; Yu, Bo; Zhu, Jing; Huang, Xiaomeng; Xie, Jing; Xu, Songlin; Yang, Xiaojuan; Wang, Xinmei; Yung, Bryant C.; Lee, L. James; Lee, Robert J.; Teng, Lesheng

2015-01-01

siRNA LOR-1284 targets the R2 subunit of ribonucleotide reductase (RRM2) and has shown promise in cancer therapy. In this study, transferrin (Tf) conjugated lipid nanoparticles (Tf-NP-LOR-1284) were synthesized by microfluidic hydrodynamic focusing (MHF) and evaluated for targeted delivery of LOR-1284 siRNA to acute myeloid leukemia (AML) cells. In vitro study showed that Tf-NP-LOR-1284 can protect LOR-1284 from serum nuclease degradation. Selective uptake of Tf-NP-LOR-1284 was observed in MV4–11 cells. In addition, qRT-PCR and Western blot results revealed that Tf-NP-LOR-1284 was more effective than free LOR-1284 in reducing the R2 mRNA and protein levels. Tf-NP-LOR-1284 showed prolonged circulation time and increased AUC after i.v. administration relative to free LOR-1284. Furthermore, Tf-NP-LOR-1284 facilitated increased accumulation at the tumor site along with decreased R2 mRNA and protein expression in a murine xenograft model. These results suggest that Tf-conjugated NPs prepared by MHF provide a suitable platform for efficient and specific thereapeutic delivery of LOR-1284 to AML. PMID:25003978

Pediatric tinea faciei in southern Spain: a 30-year survey.

PubMed

del Boz, Javier; Crespo, Vicente; de Troya, Magdalena

2012-01-01

Tinea faciei (TF) is a common clinical form of tinea in children that is frequently misdiagnosed and treated with corticosteroids. No large case series of TF focusing on children have been published. The aim of this study was to analyze the main epidemiologic, clinical, and microbiologic features of TF in children over a period of 30 years and compare these features with those of other tineas. We undertook a retrospective study of 818 cases of tinea in children at a referral hospital in southern Spain, diagnosed between 1977 and 2006, concentrating for this study on TF. Of the 73 cases of TF diagnosed, 50.7% were in girls. Most children (46.6%) were 4 to 9 years old. At the time of diagnosis, 29.2% of the cases had been treated with topical steroids. The most frequently isolated dermatophyte was Trichophyton mentagrophytes, which was isolated significantly more frequently in TF than in the other tineas. Cases of TF in children were not extremely unusual, emphasizing that TF must be considered in children with inflammatory facial eruptions. This consideration and the more-frequent use of mycologic tests can help achieve the correct diagnosis, when present. © 2011 Wiley Periodicals, Inc.

Thiophenone Attenuates Enteropathogenic Escherichia coli O103:H2 Virulence by Interfering with AI-2 Signaling.

PubMed

Witsø, Ingun Lund; Valen Rukke, Håkon; Benneche, Tore; Aamdal Scheie, Anne

2016-01-01

Interference with bacterial quorum sensing communication provides an anti-virulence strategy to control pathogenic bacteria. Here, using the Enteropathogenic E. coli (EPEC) O103:H2, we showed for the first time that thiophenone TF101 reduced expression of lsrB; the gene encoding the AI-2 receptor. Combined results of transcriptional and phenotypic analyses suggested that TF101 interfere with AI-2 signalling, possibly by competing with AI-2 for binding to LsrB. This is supported by in silico docking prediction of thiophenone TF101 in the LsrB pocket. Transcriptional analyses furthermore showed that thiophenone TF101 interfered with expression of the virulence genes eae and fimH. In addition, TF101 reduced AI-2 induced E. coli adhesion to colorectal adenocarcinoma cells. TF101, on the other hand, did not affect epinephrine or norepinephrine enhanced E. coli adhesion. Overall, our results showed that thiophenone TF101 interfered with virulence expression in E. coli O103:H2, suggestedly by interfering with AI-2 mediated quorum sensing. We thus conclude that thiophenone TF101 might represent a promising future anti-virulence agent in the fight against pathogenic E. coli.

Thiophenone Attenuates Enteropathogenic Escherichia coli O103:H2 Virulence by Interfering with AI-2 Signaling

PubMed Central

Valen Rukke, Håkon; Benneche, Tore; Aamdal Scheie, Anne

2016-01-01

Interference with bacterial quorum sensing communication provides an anti-virulence strategy to control pathogenic bacteria. Here, using the Enteropathogenic E. coli (EPEC) O103:H2, we showed for the first time that thiophenone TF101 reduced expression of lsrB; the gene encoding the AI-2 receptor. Combined results of transcriptional and phenotypic analyses suggested that TF101 interfere with AI-2 signalling, possibly by competing with AI-2 for binding to LsrB. This is supported by in silico docking prediction of thiophenone TF101 in the LsrB pocket. Transcriptional analyses furthermore showed that thiophenone TF101 interfered with expression of the virulence genes eae and fimH. In addition, TF101 reduced AI-2 induced E. coli adhesion to colorectal adenocarcinoma cells. TF101, on the other hand, did not affect epinephrine or norepinephrine enhanced E. coli adhesion. Overall, our results showed that thiophenone TF101 interfered with virulence expression in E. coli O103:H2, suggestedly by interfering with AI-2 mediated quorum sensing. We thus conclude that thiophenone TF101 might represent a promising future anti-virulence agent in the fight against pathogenic E. coli. PMID:27309855

Continuous versus bolus tube feeds: Does the modality affect glycemic variability, tube feeding volume, caloric intake, or insulin utilization?

PubMed

Evans, David C; Forbes, Rachel; Jones, Christian; Cotterman, Robert; Njoku, Chinedu; Thongrong, Cattleya; Tulman, David; Bergese, Sergio D; Thomas, Sheela; Papadimos, Thomas J; Stawicki, Stanislaw P

2016-01-01

Enteral nutrition (EN) is very important to optimizing outcomes in critical illness. Debate exists regarding the best strategy for enteral tube feeding (TF), with concerns that bolus TF (BTF) may increase glycemic variability (GV) but result in fewer nutritional interruptions than continuous TF (CTF). This study examines if there is a difference in GV, insulin usage, TF volume, and caloric delivery among intensive care patients receiving BTF versus CTF. We hypothesize that there are no significant differences between CTF and BTF when comparing the above parameters. Prospective, randomized pilot study of critically ill adult patients undergoing percutaneous endoscopic gastrostomy (PEG) placement for EN was performed between March 1, 2012 and May 15, 2014. Patients were randomized to BTF or CTF. Glucose values, insulin use, TF volume, and calories administered were recorded. Data were organized into 12-h epochs for statistical analyses and GV determination. In addition, time to ≥80% nutritional delivery goal, demographics, Acute Physiology and Chronic Health Evaluation II scores, and TF interruptions were examined. When performing BTF versus CTF assessments, continuous parameters were compared using Mann-Whitney U-test or repeated measures t-test, as appropriate. Categorical data were analyzed using Fisher's exact test. No significant demographic or physiologic differences between the CTF (n = 24) and BTF (n = 26) groups were seen. The immediate post-PEG 12-h epoch showed significantly lower GV and median TF volume for patients in the CTF group. All subsequent epochs (up to 18 days post-PEG) showed no differences in GV, insulin use, TF volume, or caloric intake. Insulin use for both groups increased when comparing the first 24 h post-PEG values to measurements from day 8. There were no differences in TF interruptions, time to ≥80% nutritional delivery goal, or hypoglycemic episodes. This study demonstrated no clinically relevant differences in GV, insulin use, TF volume or caloric intake between BTF and CTF groups. Despite some shortcomings, our data suggest that providers should not feel limited to BTF or CTF because of concerns for GV, time to goal nutrition, insulin use, or caloric intake, and should consider other factors such as resource utilization, ease of administration, and/or institutional/patient characteristics.

Tissue distribution and metabolism of triadimefon and triadimenol enantiomers in Chinese lizards (Eremias argus).

PubMed

Li, Jitong; Wang, Yinghuan; Li, Wei; Xu, Peng; Guo, Baoyuan; Li, Jianzhong; Wang, Huili

2017-08-01

Triadimefon (TF, S-(+)-TF, R-(-)-TF) and its metabolite triadimenol (TN, TN-A1, A2 and TN-B1, B2) are two systemic fungicides and both of them are chiral pharmaceuticals which are widely used in agricultural industry. Many researches focused on the toxicity effects of triadimefon on mammals, while the ecotoxicological data of tiradimefon on reptiles is limited. In order to understand the toxicity mechanism of triadimefon in reptiles, the current study administrated S-(+)-TF or R-(-)-TF traidimefon (50mg/kg bw ) to Chinese lizards (Eremias argus) respectively, the absorption, distribution of triadimefon and the formation of triadimenol were analysed at different sampling times. The metabolic pathways were demonstrated through relative gene expression using quantitative real-time PCR reaction. During the experiment time, triadimefon was quickly peaked to the maximum concentration within 12h in liver, brain, kidney, and plasma, eliminated slowly. The biotransformation in kidney was the lowest and fat possessed the worst degradation ability among others. The metabolite, triadimenol was detected in blood in 2h and reached to a plateau at about 12h in most organs (fat excepted), while the process of metabolism is stereoselective. The mainly metabolite in R-(-)-TF treated group was TN-B1, and TN-A2 in S-(+)-TF group which showed the selective metabolism to other species caused by environmental conditions, differences in the animal models and concentration of TF. The related gene expression of cyp1a1, cyp3a1 and hsd11β mRNA level in lizards showed different metabolic pathways in the liver and brain. Both P450s enzymes and 11β-hydroxysteroid dehydrogenase participated in metabolic reaction in liver, while no 11β-hydroxysteroid dehydrogenase pathway observed in brain. This diversity in liver and brain may cause different degradation rate and ecotoxicological effect in different organs. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparing the dynamic performance of wastewater treatment systems: A metafrontier Malmquist productivity index approach.

PubMed

Molinos-Senante, María; Hernández-Sancho, Francesc; Sala-Garrido, Ramón

2015-09-15

The assessment of productivity change of wastewater treatment plants (WWTPs) is essential to improve the performance over time of the facilities evaluated. This study assessed and compared the productivity growth of WWTPs operating with non-homogeneous technologies. The metafrontier Malmquist productivity index (MMPI) was computed for a sample of 99 WWTPs encompassing 4 alternative technologies: activated sludge (AS), aerated lagoon (AL), trickling filter (TF) and rotating biological contactor (BD). The results indicated that, on average, WWTPs with AS and BD exhibited better performance over time than WWTPs with AL and TF. The MMPI indicates that, over the period 2007-2009, the productivity rose by 0.9% and 0.3% for AS and BD technologies, respectively, whilst for the AL and TF processes, the productivity decreased by 0.5% and 2.2%, respectively. The decomposition of the MMPI into efficiency change (EC) and technical change (TC) illustrated that EC was a positive driver of productivity change for WWTPs that use AS, whilst TC contributed positively to the productivity growth of WWTPs using AL and BD. Several policy implications to help managers make informed decisions were drawn from our empirical analysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Midfrontal Theta and Posterior Parietal Alpha Band Oscillations Support Conflict Resolution in a Masked Affective Priming Task.

PubMed

Jiang, Jun; Bailey, Kira; Xiao, Xiao

2018-01-01

Past attempts to characterize the neural mechanisms of affective priming have conceptualized it in terms of classic cognitive conflict, but have not examined the neural oscillatory mechanisms of subliminal affective priming. Using behavioral and electroencephalogram (EEG) time frequency (TF) analysis, the current study examines the oscillatory dynamics of unconsciously triggered conflict in an emotional facial expressions version of the masked affective priming task. The results demonstrate that the power dynamics of conflict are characterized by increased midfrontal theta activity and suppressed parieto-occipital alpha activity. Across-subject and within-trial correlation analyses further confirmed this pattern. Phase synchrony and Granger causality analyses (GCAs) revealed that the fronto-parietal network was involved in unconscious conflict detection and resolution. Our findings support a response conflict account of affective priming, and reveal the role of the fronto-parietal network in unconscious conflict control.

Investigating the interaction of anticancer drug temsirolimus with human transferrin: Molecular docking and spectroscopic approach.

PubMed

Shamsi, Anas; Ahmed, Azaj; Khan, Mohd Shahnawaz; Husain, Fohad Mabood; Amani, Samreen; Bano, Bilqees

2018-05-16

In our present study, binding between an important anti renal cancer drug temsirolimus and human transferrin (hTF) was investigated employing spectroscopic and molecular docking approach. In the presence of temsirolimus, hyper chromaticity is observed in hTF in UV spectroscopy suggestive of complex formation between hTF and temsirolimus. Fluorescence spectroscopy revealed the occurrence of quenching in hTF in the presence of temsirolimus implying complex formation taking place between hTF and temsirolimus. Further, the mode of interaction between hTF and temsirolimus was revealed to be static by fluorescence quenching analysis at 3 different temperatures. Binding constant values obtained employing fluorescence spectroscopy depicts strong interaction between hTF and temsirolimus; temsirolimus binds to hTF at 298 K with a binding constant of .32 × 10 4  M -1 implying the strength of this interaction. The negative Gibbs free energy obtained through quenching experiments is evident of the fact that the binding is spontaneous. CD spectra of hTF also showed a downward shift in the presence of temsirolimus as compared with free hTF implying complex formation between hTF and temsirolimus. Molecular docking was performed with a view to find out which residues are key players in this interaction. The importance of our study stems from the fact it will provide an insight into binding pattern of commonly administered renal cancer drug with an important protein that plays a pivotal role in many physiological processes. Copyright © 2018 John Wiley & Sons, Ltd.

Selective tissue factor/factor VIIa Inhibitor, ER-410660, and its prodrug, E5539, have anti-venous and anti-arterial thrombotic effects with a low risk of bleeding.

PubMed

Nagakura, Tadashi; Tabata, Kimiyo; Kira, Kazunobu; Hirota, Shinsuke; Clark, Richard; Matsuura, Fumiyoshi; Hiyoshi, Hironobu

2013-08-01

Many anticoagulant drugs target factors common to both the intrinsic and extrinsic coagulation pathways, which may lead to bleeding complications. Since the tissue factor (TF)/factor VIIa complex is associated with thrombosis onset and specifically activates the extrinsic coagulation pathway, compounds that inhibit this complex may provide therapeutic and/or prophylactic benefits with a decreased risk of bleeding. The in vitro enzyme profile and anticoagulation selectivity of the TF/VIIa complex inhibitor, ER-410660, and its prodrug E5539 were assessed using enzyme inhibitory and plasma clotting assays. In vivo effects of ER-410660 and E5539 were determined using a TF-induced, thrombin generation rhesus monkey model; a stasis-induced, venous thrombosis rat model; a photochemically induced, arterial thrombosis rat model; and a rat tail-cut bleeding model. ER-410660 selectively prolonged prothrombin time, but had a less potent anticoagulant effect on the intrinsic pathway. It also exhibited a dose-dependent inhibitory effect on thrombin generation caused by TF-injection in the rhesus monkey model. ER-410660 also reduced venous thrombus weights in the TF-administered, stasis-induced, venous thrombosis rat model and prolonged the occlusion time induced by arterial thrombus formation after vascular injury. The compound was capable of doubling the total bleeding time in the rat tail-cut model, albeit with a considerably higher dose compared to the effective dose in the venous and arterial thrombosis models. Moreover, E5539, an orally available ER-410660 prodrug, reduced the thrombin-anti-thrombin complex levels, induced by TF-injection, in a dose-dependent manner. Selective TF/VIIa inhibitors have potential as novel anticoagulants with a lower propensity for enhancing bleeding. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparison of cleaning efficiency and deformation characteristics of Twisted File and ProTaper rotary instruments

PubMed Central

Li, Hang; Zhang, Chenzheng; Li, Qing; Wang, Changning; Song, Yaling

2014-01-01

Objective: The objective of the following study is to compare the cleaning efficiency and deformation characteristics of Twisted File (TF) and ProTaper (PT) nickel-titanium rotary instruments in root canal preparation. Materials and Methods: A total of 52 canals from 26 extracted maxillary first molars were randomly assigned into two groups of each including 13 mesiobuccal and 12 distobuccal (DB) canals. Two DB canals were as blank controls. After preparation with TF and PT, we recorded the preparation time and evaluate the amounts of debris and smear layer at apical, middle and coronal canals under scanning electron microscopy (SEM). Three cross-sections of canals at 3 mm, 5 mm and 7 mm from the apex foramens were scanned before and after preparation under micro-computed tomography. Changes of the cross-section area (CSA) at the three levels were calculated with Photoshop CS4. File deformation was also investigated under SEM. Two groups were statistically compared with Mann-Whitney test and independent sample t-test. Results: Less debris and smear layer were found in coronal regions of canals prepared with TF (P = 0.006, P = 0.001, respectively). TF group displayed more CSA change than PT group (P = 0.045) at cross-sections of 5 mm from the apex foramens and took significantly less preparation time than PT group did (P = 9.06 × 10−28). All five TF files without obvious micro-cracks and two out of 25 PT files with many micro-cracks showed visible unwound deformation. Conclusion: Neither TF nor PT achieves complete cleanliness of canal walls. Their deformation features might indicate different fracture resistance. TF single-file technique would substantially shorten the time of root canal preparation. PMID:24966769

The long terminal repeat-containing retrotransposon Tf1 possesses amino acids in gag that regulate nuclear localization and particle formation.

PubMed

Kim, Min-Kyung; Claiborn, Kathryn C; Levin, Henry L

2005-08-01

Tf1 is a long terminal repeat-containing retrotransposon of Schizosaccharomyces pombe that is studied to further our understanding of retrovirus propagation. One important application is to examine Tf1 as a model for how human immunodeficiency virus type 1 proteins enter the nucleus. The accumulation of Tf1 Gag in the nucleus requires an N-terminal nuclear localization signal (NLS) and the nuclear pore factor Nup124p. Here, we report that NLS activity is regulated by adjacent residues. Five mutant transposons were made, each with sequential tracts of four amino acids in Gag replaced by alanines. All five versions of Tf1 transposed with frequencies that were significantly lower than that of the wild type. Although all five made normal amounts of Gag, two of the mutations did not make cDNA, indicating that Gag contributed to reverse transcription. The localization of the Gag in the nucleus was significantly reduced by mutations A1, A2, and A3. These results identified residues in Gag that contribute to the function of the NLS. The Gags of A4 and A5 localized within the nucleus but exhibited severe defects in the formation of virus-like particles. Of particular interest was that the mutations in Gag-A4 and Gag-A5 caused their nuclear localization to become independent of Nup124p. These results suggested that Nup124p was only required for import of Tf1 Gag because of its extensive multimerization.

Hardware Model of a Shipboard Generator

DTIC Science & Technology

2009-05-19

controller output PM motor power RM motor resistance Td derivative time constant Tf1 fuel valve time constant Tg1 governor time constant Tg2 governor...in speed, sending a response signal to the fuel valve that regulates gas turbine power. At this point, there is an inherent variation between the...basic response analysis [5]. 29 Electrical Power Rotor Inertia Amplifiers Fuel Valve Turbine Dynamics Rotational Friction and Windage

Association study between four polymorphisms in the HFE, TF and TFR genes and Parkinson's disease in southern Italy.

PubMed

Greco, Valentina; De Marco, Elvira Valeria; Rocca, Francesca Emanuela; Annesi, Ferdinanda; Civitelli, Donatella; Provenzano, Giovanni; Tarantino, Patrizia; Scornaienchi, Vittorio; Pucci, Franco; Salsone, Maria; Novellino, Fabiana; Morelli, Maurizio; Paglionico, Sandra; Gambardella, Antonio; Quattrone, Aldo; Annesi, Grazia

2011-06-01

Iron overload may lead to neurodegenerative disorders such as Parkinson's disease (PD) and alterations of iron-related genes might be involved in the pathogenesis of this disease. The gene of haemochromatosis (HFE) encodes the HFE protein which interacts with the transferrin receptor (TFR), lowering its affinity for iron-bound transferrin (TF). We examined four known polymorphisms, C282Y and H63D in the HFE gene, G258S in the TF gene and S82G in the TFR gene, in 181 sporadic PD patients and 180 controls from Southern Italy to investigate their possible role in susceptibility to PD. No significant differences were found in genotype and allele frequencies between PD and controls for all the polymorphisms studied, suggesting that these variants do not contribute significantly to the risk of PD.

CAP waveform estimation from the measured electrical bioimpedance values: Patient's heart rate variability analysis.

PubMed

Krivoshei, A; Uuetoa, H; Min, M; Annus, P; Uuetoa, T; Lamp, J

2015-08-01

The paper presents analysis of the generic transfer function (TF) between Electrical Bioimpedance (EBI) measured non-invasively on the wrist and Central Aortic Pressure (CAP) invasively measured at the aortic root. Influence of the Heart Rate (HR) variations on the generic TF and on reconstructed CAP waveforms is investigated. The HR variation analysis is provided on a single patient data to exclude inter-patient influences at the current research stage. A new approach for the generic TF estimating from a data ensemble is presented as well. Moreover, an influence of the cardiac period beginning point selection is analyzed and empirically optimal solution for its selection is proposed.

Integrative Analysis of Transcription Factor Combinatorial Interactions Using a Bayesian Tensor Factorization Approach

PubMed Central

Ye, Yusen; Gao, Lin; Zhang, Shihua

2017-01-01

Transcription factors play a key role in transcriptional regulation of genes and determination of cellular identity through combinatorial interactions. However, current studies about combinatorial regulation is deficient due to lack of experimental data in the same cellular environment and extensive existence of data noise. Here, we adopt a Bayesian CANDECOMP/PARAFAC (CP) factorization approach (BCPF) to integrate multiple datasets in a network paradigm for determining precise TF interaction landscapes. In our first application, we apply BCPF to integrate three networks built based on diverse datasets of multiple cell lines from ENCODE respectively to predict a global and precise TF interaction network. This network gives 38 novel TF interactions with distinct biological functions. In our second application, we apply BCPF to seven types of cell type TF regulatory networks and predict seven cell lineage TF interaction networks, respectively. By further exploring the dynamics and modularity of them, we find cell lineage-specific hub TFs participate in cell type or lineage-specific regulation by interacting with non-specific TFs. Furthermore, we illustrate the biological function of hub TFs by taking those of cancer lineage and blood lineage as examples. Taken together, our integrative analysis can reveal more precise and extensive description about human TF combinatorial interactions. PMID:29033978

Integrative Analysis of Transcription Factor Combinatorial Interactions Using a Bayesian Tensor Factorization Approach.

PubMed

Ye, Yusen; Gao, Lin; Zhang, Shihua

2017-01-01

Transcription factors play a key role in transcriptional regulation of genes and determination of cellular identity through combinatorial interactions. However, current studies about combinatorial regulation is deficient due to lack of experimental data in the same cellular environment and extensive existence of data noise. Here, we adopt a Bayesian CANDECOMP/PARAFAC (CP) factorization approach (BCPF) to integrate multiple datasets in a network paradigm for determining precise TF interaction landscapes. In our first application, we apply BCPF to integrate three networks built based on diverse datasets of multiple cell lines from ENCODE respectively to predict a global and precise TF interaction network. This network gives 38 novel TF interactions with distinct biological functions. In our second application, we apply BCPF to seven types of cell type TF regulatory networks and predict seven cell lineage TF interaction networks, respectively. By further exploring the dynamics and modularity of them, we find cell lineage-specific hub TFs participate in cell type or lineage-specific regulation by interacting with non-specific TFs. Furthermore, we illustrate the biological function of hub TFs by taking those of cancer lineage and blood lineage as examples. Taken together, our integrative analysis can reveal more precise and extensive description about human TF combinatorial interactions.

Inhibition effects of total flavonoids from Scutellaria barbata D. Don on human breast carcinoma bone metastasis via downregulating PTHrP pathway

PubMed Central

Liu, Huihui; Guo, Shanyu

2018-01-01

It is abundantly clear that tumor-derived parathyroid hormone-related protein (PTHrP), receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) are central contributors in promoting osteolytic process of breast carcinoma bone metastasis. Forcusing on this molecular basis, the study was undertaken to explore the inhibition effects of total flavonoids from Scutellaria barbata D. Don (TF-SB) on human breast carcinoma bone metastasis. MDA-MB-231 cells and nude mouse models of breast cancer bone metastasis were given TF-SB in different concentrations. The proliferation, migration and invasion potentials of MDA-MB-231 cells were respectively tested. The effects of TF-SB on tumor weights and bone destruction were investigated. The mRNA and protein expression of PTHrP, OPG and RANKL were assessed by qPCR and western blot analysis. In vitro, TF-SB inhibited the proliferation, migration and invasion of MDA-MB-231 cells in a dose-dependent manner. In vivo, TF-SB prevented bone metastasis of breast cancer by decreasing the number of osteoclast cells per field in a dose-dependent manner, but not affecting tumor growth or mouse survival. Molecular analysis revealed that TF-SB controled the secretion of osteolysis-related factors PTHrP and its downstream RANKL/OPG. Together, by controlling the expression of PTHrP and its downstream OPG/RANKL, TF-SB has significant inhibition effects on breast cancer bone metastasis, which indicates a new therapeutic method. PMID:29512770

Mimvec: a deep learning approach for analyzing the human phenome.

PubMed

Gan, Mingxin; Li, Wenran; Zeng, Wanwen; Wang, Xiaojian; Jiang, Rui

2017-09-21

The human phenome has been widely used with a variety of genomic data sources in the inference of disease genes. However, most existing methods thus far derive phenotype similarity based on the analysis of biomedical databases by using the traditional term frequency-inverse document frequency (TF-IDF) formulation. This framework, though intuitive, not only ignores semantic relationships between words but also tends to produce high-dimensional vectors, and hence lacks the ability to precisely capture intrinsic semantic characteristics of biomedical documents. To overcome these limitations, we propose a framework called mimvec to analyze the human phenome by making use of the state-of-the-art deep learning technique in natural language processing. We converted 24,061 records in the Online Mendelian Inheritance in Man (OMIM) database to low-dimensional vectors using our method. We demonstrated that the vector presentation not only effectively enabled classification of phenotype records against gene ones, but also succeeded in discriminating diseases of different inheritance styles and different mechanisms. We further derived pairwise phenotype similarities between 7988 human inherited diseases using their vector presentations. With a joint analysis of this phenome with multiple genomic data, we showed that phenotype overlap indeed implied genotype overlap. We finally used the derived phenotype similarities with genomic data to prioritize candidate genes and demonstrated advantages of this method over existing ones. Our method is capable of not only capturing semantic relationships between words in biomedical records but also alleviating the dimensional disaster accompanying the traditional TF-IDF framework. With the approaching of precision medicine, there will be abundant electronic records of medicine and health awaiting for deep analysis, and we expect to see a wide spectrum of applications borrowing the idea of our method in the near future.

Prosthetic Aortic Valve Fixation Study: 48 Replacement Valves Analyzed Using Digital Pressure Mapping.

PubMed

Lee, Candice Y; Wong, Joshua K; Ross, Ronald E; Liu, David C; Khabbaz, Kamal R; Martellaro, Angelo J; Gorea, Heather R; Sauer, Jude S; Knight, Peter A

Prostheses attachment is critical in aortic valve replacement surgery, yet reliable prosthetic security remains a challenge. Accurate techniques to analyze prosthetic fixation pressures may enable the use of fewer sutures while reducing the risk of paravalvular leaks (PVL). Customized digital thin film pressure transducers were sutured between aortic annulus models and 21-mm bioprosthetic valves with 15 × 4-mm, 12 × 4-mm, or 9 × 6-mm-wide pledgeted mattress sutures. Simulating open and minimally invasive access, 4 surgeons, blinded to data acquisition, each secured 12 valves using manual knot-tying (hand-tied [HT] or knot-pusher [KP]) or automated titanium fasteners (TFs). Real-time pressure measurements and times were recorded. Two-dimensional (2D) and 3D pressure maps were generated for all valves. Pressures less than 80 mm Hg were considered at risk for PVL. Pressures under each knot (intrasuture) fell less than 80 mm Hg for 12 of 144 manual knots (5/144 HT, 7/144 KP) versus 0 of 288 TF (P < 0.001). Pressures outside adjacent sutures (extrasuture) were less than 80 mm Hg in 10 of 60 HT, zero of 60 KP, and zero of 120 TF sites for 15 × 4-mm valves; 17 of 48 HT, 25 of 48 KP, and 12 of 96 TF for 12 × 4-mm valves; and 15 of 36 HT, 17 of 36 KP, and 9 and 72 TF for 9 × 6-mm valves; P < 0.001 all manual versus TF. Annular areas with pressures less than 80 mm Hg ranged from 0% of the sewing-ring area (all open TF) to 31% (12 × 4 mm, KP). The average time per manual knot, 46 seconds (HT, 31 seconds; KP, 61 seconds), was greater than TF, 14 seconds (P < 0.005). Reduced operative times and PVL risk would fortify the advantages of surgical aortic valve replacement. This research encourages continued exploration of technical factors in optimizing prosthetic valve security.

The Self Primer of the Long Terminal Repeat Retrotransposon Tf1 Is Not Removed during Reverse Transcription

PubMed Central

Atwood-Moore, Angela; Yan, Kenneth; Judson, Robert L.; Levin, Henry L.

2006-01-01

The long terminal repeat retrotransposon Tf1 of Schizosaccharomyces pombe uses a unique mechanism of self priming to initiate reverse transcription. Instead of using a tRNA, Tf1 primes minus-strand synthesis with an 11-nucleotide RNA removed from the 5′ end of its own transcript. We tested whether the self primer of Tf1 was similar to tRNA primers in being removed from the cDNA by RNase H. Our analysis of Tf1 cDNA extracted from virus-like particles revealed the surprising observation that the dominant species of cDNA retained the self primer. This suggests that integration of the cDNA relies on mechanisms other than reverse transcription to remove the primer. PMID:16873283

Systematic Analysis of Zn2Cys6 Transcription Factors Required for Development and Pathogenicity by High-Throughput Gene Knockout in the Rice Blast Fungus

PubMed Central

Huang, Pengyun; Lin, Fucheng

2014-01-01

Because of great challenges and workload in deleting genes on a large scale, the functions of most genes in pathogenic fungi are still unclear. In this study, we developed a high-throughput gene knockout system using a novel yeast-Escherichia-Agrobacterium shuttle vector, pKO1B, in the rice blast fungus Magnaporthe oryzae. Using this method, we deleted 104 fungal-specific Zn2Cys6 transcription factor (TF) genes in M. oryzae. We then analyzed the phenotypes of these mutants with regard to growth, asexual and infection-related development, pathogenesis, and 9 abiotic stresses. The resulting data provide new insights into how this rice pathogen of global significance regulates important traits in the infection cycle through Zn2Cys6TF genes. A large variation in biological functions of Zn2Cys6TF genes was observed under the conditions tested. Sixty-one of 104 Zn2Cys6 TF genes were found to be required for fungal development. In-depth analysis of TF genes revealed that TF genes involved in pathogenicity frequently tend to function in multiple development stages, and disclosed many highly conserved but unidentified functional TF genes of importance in the fungal kingdom. We further found that the virulence-required TF genes GPF1 and CNF2 have similar regulation mechanisms in the gene expression involved in pathogenicity. These experimental validations clearly demonstrated the value of a high-throughput gene knockout system in understanding the biological functions of genes on a genome scale in fungi, and provided a solid foundation for elucidating the gene expression network that regulates the development and pathogenicity of M. oryzae. PMID:25299517

Computer Modeling and Optimization of OBOGS with Contaminants

DTIC Science & Technology

1986-10-10

OBOGS model can be ucd to optimize and design OBOGS systems with respect to system parameters such as cycle time and bed and valve dimensions. 3. C N I...6,172) TP 172 FORMLATC FINAL OBSERVATION TIME (SEC’,T40,F.4,/) READ *, TF1 IF(TFl.LT.EPSI) GOTO 10 TF=TF 1 COTO 10 175 WRITE(6,177) TCYC 177 FORMAT...225,235,207 207 IF(N-10) 336,246,255 209 WRITE(6,210) DBYIN 210 FORMAT(’ BY-PASS VALVE DIAMETER (IN)’,T40,FS.4,/) READ -,DBYIN1 IFCDBYIN1.LT.EPSI

Single molecule tracking of Ace1p in Saccharomyces cerevisiae defines a characteristic residence time for non-specific interactions of transcription factors with chromatin.

PubMed

Ball, David A; Mehta, Gunjan D; Salomon-Kent, Ronit; Mazza, Davide; Morisaki, Tatsuya; Mueller, Florian; McNally, James G; Karpova, Tatiana S

2016-12-01

In vivo single molecule tracking has recently developed into a powerful technique for measuring and understanding the transient interactions of transcription factors (TF) with their chromatin response elements. However, this method still lacks a solid foundation for distinguishing between specific and non-specific interactions. To address this issue, we took advantage of the power of molecular genetics of yeast. Yeast TF Ace1p has only five specific sites in the genome and thus serves as a benchmark to distinguish specific from non-specific binding. Here, we show that the estimated residence time of the short-residence molecules is essentially the same for Hht1p, Ace1p and Hsf1p, equaling 0.12-0.32 s. These three DNA-binding proteins are very different in their structure, function and intracellular concentration. This suggests that (i) short-residence molecules are bound to DNA non-specifically, and (ii) that non-specific binding shares common characteristics between vastly different DNA-bound proteins and thus may have a common underlying mechanism. We develop new and robust procedure for evaluation of adverse effects of labeling, and new quantitative analysis procedures that significantly improve residence time measurements by accounting for fluorophore blinking. Our results provide a framework for the reliable performance and analysis of single molecule TF experiments in yeast. Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Evaluation of the root canal shaping ability of two rotary nickel-titanium systems.

PubMed

Al-Manei, K K; Al-Hadlaq, S M S

2014-10-01

The aim was to investigate the canal shaping abilities of the twisted file (TF) and GT series X file (GTX) systems. Sixty mesial root canals of mandibular molars with curvatures of 15-50° were divided randomly into two groups of 30 canals each. The teeth were sectioned horizontally at 3, 6 and 9 mm from the apex. Root canals were prepared with TF and GTX files, respectively, and the shaping abilities of the systems were evaluated at three levels (coronal, middle and apical) based on the comparison of pre- and post-instrumentation photographs using AutoCAD software. Preparation time was also assessed. Data from the two groups were compared statistically using the Student's t-test. There was no significant difference between the rotary systems in terms of change in root canal cross-sectional area, root canal transportation, centring ability or minimum dentine thickness. Remaining dentine thickness at the coronal and middle levels was similar in the TF and GTX groups, but GTX instruments left significantly less dentine than TF instruments on the mesial aspects of root canals at the apical level. Root canal preparation with TF instruments required significantly less time than with GTX instruments. The TF and GTX NiTi rotary instruments showed similar shaping abilities, but root canal preparation was more rapid with the TF than with the GTX system. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Non-Stationarity in the “Resting Brain’s” Modular Architecture

PubMed Central

Jones, David T.; Vemuri, Prashanthi; Murphy, Matthew C.; Gunter, Jeffrey L.; Senjem, Matthew L.; Machulda, Mary M.; Przybelski, Scott A.; Gregg, Brian E.; Kantarci, Kejal; Knopman, David S.; Boeve, Bradley F.; Petersen, Ronald C.; Jack, Clifford R.

2012-01-01

Task-free functional magnetic resonance imaging (TF-fMRI) has great potential for advancing the understanding and treatment of neurologic illness. However, as with all measures of neural activity, variability is a hallmark of intrinsic connectivity networks (ICNs) identified by TF-fMRI. This variability has hampered efforts to define a robust metric of connectivity suitable as a biomarker for neurologic illness. We hypothesized that some of this variability rather than representing noise in the measurement process, is related to a fundamental feature of connectivity within ICNs, which is their non-stationary nature. To test this hypothesis, we used a large (n = 892) population-based sample of older subjects to construct a well characterized atlas of 68 functional regions, which were categorized based on independent component analysis network of origin, anatomical locations, and a functional meta-analysis. These regions were then used to construct dynamic graphical representations of brain connectivity within a sliding time window for each subject. This allowed us to demonstrate the non-stationary nature of the brain’s modular organization and assign each region to a “meta-modular” group. Using this grouping, we then compared dwell time in strong sub-network configurations of the default mode network (DMN) between 28 subjects with Alzheimer’s dementia and 56 cognitively normal elderly subjects matched 1∶2 on age, gender, and education. We found that differences in connectivity we and others have previously observed in Alzheimer’s disease can be explained by differences in dwell time in DMN sub-network configurations, rather than steady state connectivity magnitude. DMN dwell time in specific modular configurations may also underlie the TF-fMRI findings that have been described in mild cognitive impairment and cognitively normal subjects who are at risk for Alzheimer’s dementia. PMID:22761880

Indications, usage, and dosage of the transfer factor.

PubMed

Berrón-Pérez, Renato; Chávez-Sánchez, Raúl; Estrada-García, Iris; Espinosa-Padilla, Sara; Cortez-Gómez, Rudyard; Serrano-Miranda, Ernestina; Ondarza-Aguilera, Rodolfo; Pérez-Tapia, Mayra; Pineda Olvera, Benjamín; Jiménez-Martínez, María del Carmen; Portugués, Abraham; Rodríguez, Azucena; Cano, Laura; Pacheco, Pedro Urcino; Barrientos, Javier; Chacón, Rommel; Serafín, Jeannet; Mendez, Patricia; Monges, Abelardo; Cervantes, Edgar; Estrada-Parra, Sergio

2007-01-01

The transfer factor (TF) was described in 1955 by S. Lawrence. In 1992 Kirkpatrick characterized the specific TF at molecular level. The TF is constituted by a group of numerous molecules, of low molecular weight, from 1.0 to 6.0 kDa. The 5 kDa fraction corresponds to the TF specific to antigens. There are a number of publications about the clinical indications of the TF for diverse diseases, in particular those where the cellular immune response is compromised or in those where there is a deficient regulation of the immune response. In this article we present our clinical and basic experiences, especially regarding the indications, usage and dosage of the TF. Our group demonstrated that the TF increases the expression of IFN-gamma and RANTES, while decreases the expression of osteopontine. Using animal models we have worked with M. tuberculosis, and with a model of glioma with good therapeutic results. In the clinical setting we have worked with herpes zoster, herpes simplex type I, herpetic keratitis, atopic dermatitis, osteosarcoma, tuberculosis, asthma, post-herpetic neuritis, anergic coccidioidomycosis, leishmaniasis, toxoplasmosis, mucocutaneous candidiasis, pediatric infections produced by diverse pathogen germs, sinusitis, pharyngitis, and otits media. All of these diseases were studied through protocols which main goals were to study the therapeutic effects of the TF, and to establish in a systematic way diverse dosage schema and time for treatment to guide the prescription of the TF.

Tannase-mediated biotransformation assisted separation and purification of theaflavin and epigallocatechin by high speed counter current chromatography and preparative high performance liquid chromatography: A comparative study.

PubMed

Xia, Guobin; Lin, Chunfang; Liu, Songbai

2016-09-01

A large scale isolation and purification of theaflavin (TF) and epigallocatechin (EGC) has been successfully developed by tannase-mediated biotransformation combining high-speed countercurrent chromatography. After tannase hydrolysis of a commercially available theaflavins extract (TE), the content of TF and EGC in tannase-mediated biotransformation product (TBP) achieved approximately 3 times enrichment. SEM studies revealed smooth tannase biotransformation and the possibility of recovery of the tannase. A single 1.5 hours' HSCCC separation for TF and EGC employing a two-phase solvent system could simultaneously produce 180.8 mg of 97.3% purity TF and 87.5 mg of 97.3% purity EGC. However, a preparative HPLC separation of maximum injection volume containing 120 mg TBP prepared 11.2 mg TF of 94.9% purity and 7.7 mg EGC of 89.9% purity. HSCCC separation demonstrated significant advantages over Prep HPLC in terms of sample loading size, separation time, environmental friendly solvent systems, and the production. © 2016 Wiley Periodicals, Inc.

Serum transferrin receptor status of healthy adult Arabs.

PubMed

Knox-Macaulay, Huxley; Gravell, David; Elender, Frances

2007-01-01

Several studies have provided reference ranges for the concentration of serum transferrin receptor (sTfR) in various white populations, but there is a dearth of relevant reference sTfR data in non-whites. The aim of this investigation was to establish sTfR reference ranges and mean values for a healthy non-white Arab population that could be used also for Arabs worldwide. sTfR and serum ferritin concentrations were estimated by immunoassays and blood counts were determined by conventional methods. Analysis of the data of 114 volunteer Arab blood donors (91 male, 23 female) revealed a higher mean sTfR concentration in males of 22.6+/-8.1 nmol/L (range 10.9-38.7 nmol/L) compared to that in females of 18.7+/-4.4 nmol/L (range 10.7-25.8 nmol/L, p=0.001). There was no significant correlation of sTfR concentration with age, serum ferritin level, or blood haemoglobin level, but a strong inverse correlation was demonstrated with mean cell volume and mean cell haemoglobin of red cells. Iron-replete volunteer subjects with alpha-thalassaemia trait appear to have relatively high mean sTfR concentration. We recommend the use of gender-dependent sTfR reference values for Arabs.

A fast complex domain-matching pursuit algorithm and its application to deep-water gas reservoir detection

NASA Astrophysics Data System (ADS)

Zeng, Jing; Huang, Handong; Li, Huijie; Miao, Yuxin; Wen, Junxiang; Zhou, Fei

2017-12-01

The main emphasis of exploration and development is shifting from simple structural reservoirs to complex reservoirs, which all have the characteristics of complex structure, thin reservoir thickness and large buried depth. Faced with these complex geological features, hydrocarbon detection technology is a direct indication of changes in hydrocarbon reservoirs and a good approach for delimiting the distribution of underground reservoirs. It is common to utilize the time-frequency (TF) features of seismic data in detecting hydrocarbon reservoirs. Therefore, we research the complex domain-matching pursuit (CDMP) method and propose some improvements. First is the introduction of a scale parameter, which corrects the defect that atomic waveforms only change with the frequency parameter. Its introduction not only decomposes seismic signal with high accuracy and high efficiency but also reduces iterations. We also integrate jumping search with ergodic search to improve computational efficiency while maintaining the reasonable accuracy. Then we combine the improved CDMP with the Wigner-Ville distribution to obtain a high-resolution TF spectrum. A one-dimensional modeling experiment has proved the validity of our method. Basing on the low-frequency domain reflection coefficient in fluid-saturated porous media, we finally get an approximation formula for the mobility attributes of reservoir fluid. This approximation formula is used as a hydrocarbon identification factor to predict deep-water gas-bearing sand of the M oil field in the South China Sea. The results are consistent with the actual well test results and our method can help inform the future exploration of deep-water gas reservoirs.

Hierarchical Rhetorical Sentence Categorization for Scientific Papers

NASA Astrophysics Data System (ADS)

Rachman, G. H.; Khodra, M. L.; Widyantoro, D. H.

2018-03-01

Important information in scientific papers can be composed of rhetorical sentences that is structured from certain categories. To get this information, text categorization should be conducted. Actually, some works in this task have been completed by employing word frequency, semantic similarity words, hierarchical classification, and the others. Therefore, this paper aims to present the rhetorical sentence categorization from scientific paper by employing TF-IDF and Word2Vec to capture word frequency and semantic similarity words and employing hierarchical classification. Every experiment is tested in two classifiers, namely Naïve Bayes and SVM Linear. This paper shows that hierarchical classifier is better than flat classifier employing either TF-IDF or Word2Vec, although it increases only almost 2% from 27.82% when using flat classifier until 29.61% when using hierarchical classifier. It shows also different learning model for child-category can be built by hierarchical classifier.

Robust Inference of Genetic Exchange Communities from Microbial Genomes Using TF-IDF

PubMed Central

Cong, Yingnan; Chan, Yao-ban; Phillips, Charles A.; Langston, Michael A.; Ragan, Mark A.

2017-01-01

Bacteria and archaea can exchange genetic material across lineages through processes of lateral genetic transfer (LGT). Collectively, these exchange relationships can be modeled as a network and analyzed using concepts from graph theory. In particular, densely connected regions within an LGT network have been defined as genetic exchange communities (GECs). However, it has been problematic to construct networks in which edges solely represent LGT. Here we apply term frequency-inverse document frequency (TF-IDF), an alignment-free method originating from document analysis, to infer regions of lateral origin in bacterial genomes. We examine four empirical datasets of different size (number of genomes) and phyletic breadth, varying a key parameter (word length k) within bounds established in previous work. We map the inferred lateral regions to genes in recipient genomes, and construct networks in which the nodes are groups of genomes, and the edges natively represent LGT. We then extract maximum and maximal cliques (i.e., GECs) from these graphs, and identify nodes that belong to GECs across a wide range of k. Most surviving lateral transfer has happened within these GECs. Using Gene Ontology enrichment tests we demonstrate that biological processes associated with metabolism, regulation and transport are often over-represented among the genes affected by LGT within these communities. These enrichments are largely robust to change of k. PMID:28154557

Decreasing TfR1 expression reverses anemia and hepcidin suppression in β-thalassemic mice

PubMed Central

Li, Huihui; Choesang, Tenzin; Bao, Weili; Chen, Huiyong; Feola, Maria; Garcia-Santos, Daniel; Li, Jie; Sun, Shuming; Follenzi, Antonia; Pham, Petra; Liu, Jing; Zhang, Jinghua; Ponka, Prem; An, Xiuli; Mohandas, Narla; Fleming, Robert E.; Rivella, Stefano; Li, Guiyuan

2017-01-01

Iron availability for erythropoiesis and its dysregulation in β-thalassemia are incompletely understood. We previously demonstrated that exogenous apotransferrin leads to more effective erythropoiesis, decreasing erythroferrone (ERFE) and derepressing hepcidin in β-thalassemic mice. Transferrin-bound iron binding to transferrin receptor 1 (TfR1) is essential for cellular iron delivery during erythropoiesis. We hypothesize that apotransferrin’s effect is mediated via decreased TfR1 expression and evaluate TfR1 expression in β-thalassemic mice in vivo and in vitro with and without added apotransferrin. Our findings demonstrate that β-thalassemic erythroid precursors overexpress TfR1, an effect that can be reversed by the administration of exogenous apotransferrin. In vitro experiments demonstrate that apotransferrin inhibits TfR1 expression independent of erythropoietin- and iron-related signaling, decreases TfR1 partitioning to reticulocytes during enucleation, and enhances enucleation of defective β-thalassemic erythroid precursors. These findings strongly suggest that overexpressed TfR1 may play a regulatory role contributing to iron overload and anemia in β-thalassemic mice. To evaluate further, we crossed TfR1+/− mice, themselves exhibiting iron-restricted erythropoiesis with increased hepcidin, with β-thalassemic mice. Resultant double-heterozygote mice demonstrate long-term improvement in ineffective erythropoiesis, hepcidin derepression, and increased erythroid enucleation in relation to β-thalassemic mice. Our data demonstrate for the first time that TfR1+/− haploinsufficiency reverses iron overload specifically in β-thalassemic erythroid precursors. Taken together, decreasing TfR1 expression during β-thalassemic erythropoiesis, either directly via induced haploinsufficiency or via exogenous apotransferrin, decreases ineffective erythropoiesis and provides an endogenous mechanism to upregulate hepcidin, leading to sustained iron-restricted erythropoiesis and preventing systemic iron overload in β-thalassemic mice. PMID:28151426

A microfluidic method to synthesize transferrin-lipid nanoparticles loaded with siRNA LOR-1284 for therapy of acute myeloid leukemia

NASA Astrophysics Data System (ADS)

Yang, Zhaogang; Yu, Bo; Zhu, Jing; Huang, Xiaomeng; Xie, Jing; Xu, Songlin; Yang, Xiaojuan; Wang, Xinmei; Yung, Bryant C.; Lee, L. James; Lee, Robert J.; Teng, Lesheng

2014-07-01

The siRNA LOR-1284 targets the R2 subunit of ribonucleotide reductase (RRM2) and has shown promise in cancer therapy. In this study, transferrin (Tf) conjugated lipid nanoparticles (Tf-NP-LOR-1284) were synthesized by microfluidic hydrodynamic focusing (MHF) and evaluated for the targeted delivery of LOR-1284 siRNA into acute myeloid leukemia (AML) cells. The in vitro study showed that Tf-NP-LOR-1284 can protect LOR-1284 from serum nuclease degradation. Selective uptake of Tf-NP-LOR-1284 was observed in MV4-11 cells. In addition, qRT-PCR and Western blot results revealed that Tf-NP-LOR-1284 was more effective than the free LOR-1284 in reducing the R2 mRNA and protein levels. The Tf-NP-LOR-1284 showed prolonged circulation time and increased AUC after i.v. administration relative to the free LOR-1284. Furthermore, Tf-NP-LOR-1284 facilitated increased accumulation at the tumor site along with the decreased R2 mRNA and protein expression in a murine xenograft model. These results suggest that Tf-conjugated NPs prepared by MHF provide a suitable platform for efficient and specific therapeutic delivery of LOR-1284 into AML cells.

Expression of the Thomsen-Friedenreich (TF) tumor antigen in human abort placentas.

PubMed

Richter, D U; Jeschke, U; Bergemann, C; Makovitzky, J; Lüthen, F; Karsten, U; Briese, V

2005-01-01

The Thomsen-Friedenreich antigen (TF), or more precisely epitope, has been known as a pancarcinoma antigen. It consists of galactose-beta1-3-N-acetylgalactose. We have already described the expression of TF in the normal placenta. TF is expressed by the syncytium and by extravillous trophoblast cells. In this study, we investigated the expression of TF in the abort placenta. Frozen samples of human abort placentas (12 placentas), obtained from the first and second trimesters of pregnancy and, for comparison, samples of normal placentas (17 placentas) from the first, second and third trimesters of pregnancy, were used. Expression of TF was investigated by immunohistochemical methods. For identification of TF-positive cells in abort placentas, immunofluorescence methods were used. Evaluation of simple and double immunofluorescence was performed on a laser scanning microscope. Furthermore, we isolated trophoblast cells from first and third trimester placentas and evaluated cytokeratin 7 and Muc1 expression by immunofluorescence methods. We observed expression of TF antigen in the syncytiotrophoblasts layer of the placenta in all three trimesters of pregnancy in normal and abort placentas evaluated by immunohistochemical methods. There was no expression of TF antigen in the decidua of abort placentas. Immunofluorescence double staining of TF antigen and cytokeratin 7 showed reduced expression of both antigens in the abort decidua and co-expression of both antigens in the syncytiotrophoblast layer of normal and abort placentas. TF expression in the syncytiotrophoblast was reduced in abort placentas. In the isolated trophoblast cells, no TF expression was found, however, Muc1 expression was visualized. Expression of TF antigen was reduced in the first and second trimester abort decidua compared to the normal decidua during the same time of pregnancy. TF antigen was restricted to the syncytiotrophoblast and extravillous trophoblast cells in the decidua. Abort placentas expressed TF antigen on the syncytiotrophoblast layer, but with lower intensity compared to normal placentas. We found a significantly reduced co-expression of TF antigen and cytokeratin 7 in the decidua of abort placentas. These data suggested a reduction of extravillous trophoblast cells in the decidua of abort placentas. In addition, we found higher numbers of CD45-positive cells in the abort decidua compared to normal placentas.

MicroRNA Expression Analysis in Serum of Patients with Congenital Hemochromatosis and Age-Related Macular Degeneration (AMD)

PubMed Central

Szemraj, Maciej; Oszajca, Katarzyna; Szemraj, Janusz; Jurowski, Piotr

2017-01-01

Background Congenital hemochromatosis is a disorder caused by mutations of genes involved in iron metabolism, leading to increased levels of iron concentration in tissues and serum. High concentrations of iron can lead to the development of AMD. The aim of this study was to analyze circulating miRNAs in the serum of congenital hemochromatosis patients with AMD and their correlation with the expression of genes involved in iron metabolism. Material/Methods Peripheral blood monolayer cells and serum were obtained from patients with congenital hemochromatosis, congenital hemochromatosis and AMD, AMD patients without congenital hemochromatosis, and healthy controls. Serum miRNAs expressions were analyzed by RT-PCR (qRT-PCR) using TaqMan MicroRNA probes, and proteins levels were measured by ELSA kits. Gene polymorphisms in TF and TFRC genes were determined using the TaqMan discrimination assay. Results Statistical analysis of the miRNAs expressions selected for further study the miR-31, miR-133a, miR-141, miR-145, miR-149, and miR-182, which are involved in the posttranscriptional expression of iron-related genes: TF, TFRI, DMT1, FTL, and FPN1. It was discovered that the observed changes in the expressions of the miRNAs was correlated with the level of protein in the serum of the analyzed genes. There were no statistically significant differences in the distribution of genotype and allele frequencies in TF and TFRC genes between analyzed groups of patients. Conclusions The differences studied in the miRNA serum profile, in conjunction with the changes in the analyzed protein levels, may be useful in the early detection of congenital hemochromatosis in patients who may develop AMD disease. PMID:28827515

Dynamic properties of cluster glass in La0.25Ca0.75MnO3 nanoparticles

NASA Astrophysics Data System (ADS)

Huang, X. H.; Ding, J. F.; Jiang, Z. L.; Yin, Y. W.; Yu, Q. X.; Li, X. G.

2009-10-01

The dynamic magnetic properties of cluster glass in La0.25Ca0.75MnO3 nanoparticles with average particle size range from 40 to 1000 nm have been investigated by measuring the frequency and dc magnetic field (H) dependencies of the ac susceptibility. The frequency-dependent Tf, the freezing temperature of the ferromagnetic clusters determined by the peak in the real part of the ac susceptibility χ' versus T curve with H =0, is fit to a power law. The relaxation time constant τ0 decreases as the particle size increases from 40 to 350 nm, which indicates the decrease in the size of the clusters at the surface of the nanoparticle. The relationship between H and Tf(H) deviates from the De Almeida-Thouless-type phase boundary at relatively high fields for the samples with size range from 40 to 350 nm. Moreover, for the samples with particle sizes of 40 and 100 nm, τ0 increases with increasing H, which indicates the increasing cluster size and may be ascribed to the competition between the influence of H and the local anisotropy field in the shell spins. All these results may give rise to a new insight into the behaviors of the cluster glass state in the nanosized antiferromagnetic charge-ordered perovskite manganites.

Theaflavin-3,3'-digallate, a component of black tea: an inducer of oxidative stress and apoptosis.

PubMed

Schuck, Alyssa G; Ausubel, Miriam B; Zuckerbraun, Harriet L; Babich, Harvey

2008-04-01

Treatment of human oral squamous carcinoma HSC-2 cells and normal GN46 fibroblasts with theaflavin-3,3'-digallate (TF-3), a polyphenol in black tea, showed a concentration and time dependent inhibition of growth, with the tumor cells more sensitive than the fibroblasts. In buffer and in cell culture medium, TF-3 generated reactive oxygen species, with lower levels detected in buffer amended with catalase and superoxide dismutase, indicating the generation of hydrogen peroxide and superoxide, respectively, and suggesting that TF-3 may be an inducer of oxidative stress. The toxicity of TF-3 was decreased in the presence of catalase, pyruvate, and divalent cobalt, all scavengers of reactive oxygen species, but was potentiated in the presence of diethyldithiocarbamate, an inhibitor of superoxide dismutase. The intracellular level of glutathione in HSC-2 cells was lessened after a 4-h exposure to 250 and 500 microM TF-3. However, for GN46 fibroblasts, a 4-h exposure to 250 microM TF-3 stimulated, but to 500 microM TF-3 lessened, intracellular glutathione. Treatment of the cells with the glutathione depleters, 1,3-bis(2-chloroethyl)-N-nitrosourea, 1-chloro-2,4-dinitrobenzene, and d,l-buthionine-[S,R]-sulfoximine potentiated the toxicity of TF-3. Induction of apoptotic cell death in HSC-2 cells treated with TF-3 was noted by apoptotic cell morphologies, by TUNEL staining, by PARP cleavage, and by elevated activity of caspase-3. Apoptosis was not noted in GN46 fibroblasts treated with TF-3.

Evaluation of recombinant MGL_1304 produced by Pichia pastoris for clinical application to sweat allergy.

PubMed

Kan, Takanobu; Hiragun, Takaaki; Ishii, Kaori; Hiragun, Makiko; Yanase, Yuhki; Tanaka, Akio; Hide, Michihiro

2015-07-01

We previously identified MGL_1304 secreted by Malassezia globosa as a sweat antigen for patients with atopic dermatitis (AD) and cholinergic urticaria (ChU). However, purifying native MGL_1304 from human sweat or culture supernatant of M. globosa (sup-MGL_1304) is costly and time-consuming. Moreover, recombinant MGL_1304 expressed by using Escherichia coli (TF-rMGL_1304) needs a large chaperon protein and lacks the original glycosylation of yeasts. Thus, we generated a recombinant MGL_1304 by Pichia pastoris (P-rMGL_1304) and investigated its characteristic features. Recombinant MGL_1304 proteins expressed by E. coli and P. pastoris were generated. Properties of these recombinants and native antigens were compared by western blot analysis, histamine release tests (HRT) of patients with AD and ChU, and β-hexosaminidase release tests with RBL-48 cells. P-rMGL_1304-specific IgE in sera of patients with AD were measured by sandwich ELISA. Western blot analysis revealed that IgE of patients with AD bound to all MGL_1304 recombinants and native antigens. The histamine releasing ability of P-rMGL_1304 was 100 times higher than that of TF-rMGL_1304, and was comparable to that of sup-MGL_1304. Degranulation rates of RBL-48 cells, sensitized with sera of patients with AD in response to the stimulation of P-rMGL_1304, were comparable to those of sup-MGL_1304, whereas those of TF-rMGL_1304 were relatively weak. The levels of P-rMGL_1304-specific IgE in sera of patients with AD were correlated with their disease severities. P-rMGL_1304 has an antigenicity comparable to the native antigen, and is more useful than TF-rMGL_1304, especially in HRT and degranulation assay of RBL-48 cells. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Photoaffinity labeling of the TF1-ATPase from the thermophilic bacterium PS3 with 3'-O-(4-benzoyl)benzoyl ADP.

PubMed

Bar-Zvi, D; Yoshida, M; Shavit, N

1985-05-31

3'-O-(4-Benzoyl)benzoyl ADP (BzADP) was used as a photoaffinity label for covalent binding of adenine nucleotide analogs to the nucleotide binding site(s) of the thermophilic bacterium PS3 ATPase (TF1). As with the CF1-ATPase (Bar-Zvi, D. and Shavit, N. (1984) Biochim. Biophys. Acta 765, 340-356) noncovalently bound BzADP is a reversible inhibitor of the TF1-ATPase. BzADP changes the kinetics of ATP hydrolysis from noncooperative to cooperative in the same way as ADP does, but, in contrast to the effect on the CF1-ATPase, it has no effect on the Vmax. In the absence of Mg2+ 1 mol BzADP binds noncovalently to TF1, while with Mg2+ 3 mol are bound. Photoactivation of BzADP results in the covalent binding of the analog to the nucleotide binding site(s) on TF1 and correlates with the inactivation of the ATPase. Complete inactivation of the TF1-ATPase occurs after covalent binding of 2 mol BzADP/mol TF1. Photoinactivation of TF1 by BzADP is prevented if excess of either ADP or ATP is present during irradiation. Analysis by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate of the Bz[3H]ADP-labeled TF1-ATPase shows that all the radioactivity is incorporated into the beta subunit.

Identification of Unequally Represented Founder Viruses Among Tissues in Very Early SIV Rectal Transmission

PubMed Central

Chen, Jian; Ren, Yanqin; Daharsh, Lance; Liu, Lu; Kang, Guobin; Li, Qingsheng; Wei, Qiang; Wan, Yanmin; Xu, Jianqing

2018-01-01

Characterizing the transmitted/founder (T/F) viruses of multi-variant SIV infection may shed new light on the understanding of mucosal transmission. We intrarectally inoculated six Chinese rhesus macaques with a single high dose of SIVmac251 (3.1 × 104 TCID50) and obtained 985 full-length env sequences from multiple tissues at 6 and 10 days post-infection by single genome amplification (SGA). All 6 monkeys were infected with a range of 2 to 8 T/F viruses and the dominant variants from the inoculum were still dominant in different tissues from each monkey. Interestingly, our data showed that a cluster of rare T/F viruses was unequally represented in different tissues. This cluster of rare T/F viruses phylogenetically related to the non-dominant SIV variants in the inoculum and was not detected in any rectum tissues, but could be identified in the descending colon, jejunum, spleen, or plasma. In 2 out of 6 macaques, identical SIVmac251 variants belonging to this cluster were detected simultaneously in descending colon/jejunum and the inoculum. We also demonstrated that the average CG dinucleotide frequency of these rare T/F viruses found in tissues, as well as non-dominant variants in the inoculum, was significantly higher than the dominant T/F viruses in tissues and the inoculum. Collectively, these findings suggest that descending colon/jejunum might be more susceptible than rectum to SIV in the very early phase of infection. And host CG suppression, which was previously shown to inhibit HIV replication in vitro, may also contribute to the bottleneck selection during in vivo transmission. PMID:29651274

Accelerated Seismic Release and Related Aspects of Seismicity Patterns on Earthquake Faults

NASA Astrophysics Data System (ADS)

Ben-Zion, Y.; Lyakhovsky, V.

Observational studies indicate that large earthquakes are sometimes preceded by phases of accelerated seismic release (ASR) characterized by cumulative Benioff strain following a power law time-to-failure relation with a term (tf-t)m, where tf is the failure time of the large event and observed values of m are close to 0.3. We discuss properties of ASR and related aspects of seismicity patterns associated with several theoretical frameworks. The subcritical crack growth approach developed to describe deformation on a crack prior to the occurrence of dynamic rupture predicts great variability and low asymptotic values of the exponent m that are not compatible with observed ASR phases. Statistical physics studies assuming that system-size failures in a deforming region correspond to critical phase transitions predict establishment of long-range correlations of dynamic variables and power-law statistics before large events. Using stress and earthquake histories simulated by the model of Ben-Zion (1996) for a discrete fault with quenched heterogeneities in a 3-D elastic half space, we show that large model earthquakes are associated with nonrepeating cyclical establishment and destruction of long-range stress correlations, accompanied by nonstationary cumulative Benioff strain release. We then analyze results associated with a regional lithospheric model consisting of a seismogenic upper crust governed by the damage rheology of Lyakhovskyet al. (1997) over a viscoelastic substrate. We demonstrate analytically for a simplified 1-D case that the employed damage rheology leads to a singular power-law equation for strain proportional to (tf-t)-1/3, and a nonsingular power-law relation for cumulative Benioff strain proportional to (tf-t)1/3. A simple approximate generalization of the latter for regional cumulative Benioff strain is obtained by adding to the result a linear function of time representing a stationary background release. To go beyond the analytical expectations, we examine results generated by various realizations of the regional lithospheric model producing seismicity following the characteristic frequency-size statistics, Gutenberg-Richter power-law distribution, and mode switching activity. We find that phases of ASR exist only when the seismicity preceding a given large event has broad frequency-size statistics. In such cases the simulated ASR phases can be fitted well by the singular analytical relation with m = -1/3, the nonsingular equation with m = 0.2, and the generalized version of the latter including a linear term with m = 1/3. The obtained good fits with all three relations highlight the difficulty of deriving reliable information on functional forms and parameter values from such data sets. The activation process in the simulated ASR phases is found to be accommodated both by increasing rates of moderate events and increasing average event size, with the former starting a few years earlier than the latter. The lack of ASR in portions of the seismicity not having broad frequency-size statistics may explain why some large earthquakes are preceded by ASR and other are not. The results suggest that observations of moderate and large events contain two complementary end-member predictive signals on the time of future large earthquakes. In portions of seismicity following the characteristic earthquake distribution, such information exists directly in the associated quasi-periodic temporal distribution of large events. In portions of seismicity having broad frequency-size statistics with random or clustered temporal distribution of large events, the ASR phases have predictive information. The extent to which natural seismicity may be understood in terms of these end-member cases remains to be clarified. Continuing studies of evolving stress and other dynamic variables in model calculations combined with advanced analyses of simulated and observed seismicity patterns may lead to improvements in existing forecasting strategies.

The nuclear orphan receptors COUP-TF and ARP-1 positively regulate the trout estrogen receptor gene through enhancing autoregulation.

PubMed Central

Lazennec, G; Kern, L; Valotaire, Y; Salbert, G

1997-01-01

The rainbow trout estrogen receptor (rtER) is a positively autoregulated gene in liver cells. In a previous report, we showed that upregulation is mediated by an estrogen response element (ERE) located in the proximal promoter of the gene and that a half binding site for nuclear receptors (5'-TGACCT-3') located 15 bp upstream of the ERE is involved in the magnitude of the estrogen response. We now report that the human orphan receptor COUP-TF and a COUP-TF-like protein from trout liver are able to bind to the consensus half-site. When cotransfected with the rtER gene proximal promoter, COUP-TF had no regulatory functions on its own. Interestingly, COUP-TF enhanced rtER transactivation properties in the presence of estradiol in a dose-dependent manner when cotransfected with the rtER gene promoter. Unliganded retinoid receptor heterodimers had the same helper function as COUP-TF in the presence of estradiol but were switched to repressors when the ligand all-trans-retinoic acid was added. Mutation of the consensus half-site only slightly reduced COUP-TF helper function, suggesting that it actually results from a complex mechanism that probably involves both DNA binding of COUP-TF to the promoter and protein-protein interaction with another transcription factor bound to the promoter. Nevertheless, a DNA-binding-defective mutant of COUP-TF was also defective in ER helper function. Competition footprinting analysis suggested that COUP-TF actually establishes contacts with the consensus upstream half-site and the downstream ERE half-site that would form a DR-24-like response element. Interaction of COUP-TF with the DR-24 element was confirmed in footprinting assays by using nuclear extracts from Saccharomyces cerevisiae expressing COUP-TF. Finally, interaction of COUP-TF with mutants of the rtER gene promoter showed that COUP-TF recognizes the ERE when the upstream half-site is mutated. These data show that COUP-TF may activate transcription through interaction with other nuclear receptors. This cross-talk between liganded nuclear receptors and orphan receptors is likely to modulate the spectrum of action of a particular ligand-receptor complex and may participate in the cell-type specificity of the ligand effect. PMID:9271383

On the connection between inherent DNA flexure and preferred binding of hydroxymethyluracil-containing DNA by the type II DNA-binding protein TF1.

PubMed

Grove, A; Galeone, A; Mayol, L; Geiduschek, E P

1996-07-12

TF1 is a member of the family of type II DNA-binding proteins, which also includes the bacterial HU proteins and the Escherichia coli integration host factor (IHF). Distinctive to TF1, which is encoded by the Bacillus subtilis bacteriophage SPO1, is its preferential binding to DNA in which thymine is replaced by 5-hydroxymethyluracil (hmU), as it is in the phage genome. TF1 binds to preferred sites within the phage genome and generates pronounced DNA bending. The extent to which DNA flexibility contributes to the sequence-specific binding of TF1, and the connection between hmU preference and DNA flexibility has been examined. Model flexible sites, consisting of consecutive mismatches, increase the affinity of thymine-containing DNA for TF1. In particular, tandem mismatches separated by nine base-pairs generate an increase, by orders of magnitude, in the affinity of TF1 for T-containing DNA with the sequence of a preferred TF1 binding site, and fully match the affinity of TF1 for this cognate site in hmU-containing DNA (Kd approximately 3 nM). Other placements of loops generate suboptimal binding. This is consistent with a significant contribution of site-specific DNA flexibility to complex formation. Analysis of complexes with hmU-DNA of decreasing length shows that a major part of the binding affinity is generated within a central 19 bp segment (delta G0 = 41.7 kJ mol-1) with more-distal DNA contributing modestly to the affinity (delta delta G = -0.42 kJ mol-1 bp-1 on increasing duplex length to 37 bp). However, a previously characterised thermostable and more tightly binding mutant TF1, TF1(E15G/T32I), derives most of its extra affinity from interaction with flanking DNA. We propose that inherent but sequence-dependent deformability of hmU-containing DNA underlies the preferential binding of TF1 and that TF1-induced DNA bendings is a result of distortions at two distinct sites separated by 9 bp of duplex DNA.

Effects of mutations at amino acid 61 in the arm of TF1 on its DNA-binding properties.

PubMed

Sayre, M H; Geiduschek, E P

1990-12-20

Transcription factor 1 (TF1) is the Bacillus subtilis phage SPO1-encoded member of the family of bacterial DNA-binding proteins that includes Escherichia coli HU and integration host factor (IHF). We have initiated a mutational analysis of the TF1 molecule to understand better its unique DNA-binding properties and to investigate its physiological function. We report here the consequences of mutating the putative DNA-binding "arms" of TF1. At position 61 in its primary sequence, TF1 contains a Phe residue in place of the Arg residue found in all other known members of the HU family. Substituting polar, uncharged residues for Phe61 substantially reduced the DNA-binding affinity and site-selectivity of TF1 in vitro, whereas the substitution of Tyr had no effect. Substituting Trp or Arg for Phe61 had little effect on the affinity of TF1 for SPO1 DNA, but altered the electrophoretic mobilities of protein-DNA complexes in non-denaturing gels. The Arg61 substitution increased the affinity of the protein for non-specific sites on thymine-containing DNA, thus reducing the natural preference of TF1 for (5-hydroxymethyluracil)-containing DNA. The Phe61-to-Arg mutation was also correlated with decreased phage yield and aberrant regulation of viral protein synthesis in vivo.

A single-nucleotide polymorphism in transferrin is associated with soluble transferrin receptor in Chinese adolescents.

PubMed

Piao, Wei; Wang, Li; Zhang, Ting; Wang, Zhen; Shangguan, Shaofang; Sun, Jing; Huo, Junsheng

2017-01-01

Associations between genetic variants in the hepcidin regulation pathway and iron status have been reported in previous studies. Most of these studies were conducted in populations of European descent and relatively few studies have been conducted in Chinese populations. In this study, we evaluated associations between single-nucleotide polymorphisms (SNPs) in the hepcidin regulation pathway, serum ferritin (SF) and soluble transferrin receptor (sTfR) in Chinese adolescents. In total, 692 students from rural boarding schools were selected from six cities in China. The participants were divided into case and control groups according to criteria for SF and sTfR. Furthermore, 33 SNPs in TMPRSS6, TF, TFR2, BMP2, BMP4, HJV, CYBRD1, HFE, IL6, PCSK7, HAMP, KIAA1468, and SRPRB were selected. Associations between the genetic variants and SF or sTfR were detected. For SF, rs4820268 in TMPRSS6 was associated with an SF <25 ng/mL status. Carriers of the G/G genotype of rs4820268 exhibited significantly lower SF levels than A allele carriers did (p=0.047). For sTfR, rs1880669 in TF, rs4901474 in BMP4, and rs7536827 in HJV were significantly associated with an sTfR >=4.4 mg/L status. However, in general linear model analysis, after adjustment for age, sex, and location, only rs1880669 exhibited a stable association with higher sTfR levels (p=0.032). We found rs4820268, in TMPRSS6 that was associated with a low SF level, as previously reported, and a new association between 1880669 in TF and sTfR.

The Application of a Homologous Recombination Assay Revealed Amino Acid Residues in an LTR-Retrotransposon That Were Critical for Integration

PubMed Central

Atwood, Angela; Choi, Jeannie; Levin, Henry L.

1998-01-01

Retroviruses and their relatives, the LTR-retrotransposons, possess an integrase protein (IN) that is required for the insertion of reverse transcripts into the genome of host cells. Schizosaccharomyces pombe is the host of Tf1, an LTR-retrotransposon with integration activity that can be studied by using techniques of yeast genetics. In this study, we sought to identify amino acid substitutions in Tf1 that specifically affected the integration step of transposition. In addition to seeking amino acid substitutions in IN, we also explored the possibility that other Tf1 proteins contributed to integration. By comparing the results of genetic assays that monitored both transposition and reverse transcription, we were able to seek point mutations throughout Tf1 that blocked transposition but not the synthesis of reverse transcripts. These mutant versions of Tf1 were candidates of elements that possessed defects in the integration step of transposition. Five mutations in Tf1 that resulted in low levels of integration were found to be located in the IN protein: two substitutions in the N-terminal Zn domain, two in the catalytic core, and one in the C-terminal domain. These results suggested that each of the three IN domains was required for Tf1 transposition. The potential role of these five amino acid residues in the function of IN is discussed. Two of the mutations that reduced integration mapped to the RNase H (RH) domain of Tf1 reverse transcriptase. The Tf1 elements with the RH mutations produced high levels of reverse transcripts, as determined by recombination and DNA blot analysis. These results indicated that the RH of Tf1 possesses a function critical for transposition that is independent of the accumulation of reverse transcripts. PMID:9445033

From data repositories to submission portals: rethinking the role of domain-specific databases in CollecTF.

PubMed

Kılıç, Sefa; Sagitova, Dinara M; Wolfish, Shoshannah; Bely, Benoit; Courtot, Mélanie; Ciufo, Stacy; Tatusova, Tatiana; O'Donovan, Claire; Chibucos, Marcus C; Martin, Maria J; Erill, Ivan

2016-01-01

Domain-specific databases are essential resources for the biomedical community, leveraging expert knowledge to curate published literature and provide access to referenced data and knowledge. The limited scope of these databases, however, poses important challenges on their infrastructure, visibility, funding and usefulness to the broader scientific community. CollecTF is a community-oriented database documenting experimentally validated transcription factor (TF)-binding sites in the Bacteria domain. In its quest to become a community resource for the annotation of transcriptional regulatory elements in bacterial genomes, CollecTF aims to move away from the conventional data-repository paradigm of domain-specific databases. Through the adoption of well-established ontologies, identifiers and collaborations, CollecTF has progressively become also a portal for the annotation and submission of information on transcriptional regulatory elements to major biological sequence resources (RefSeq, UniProtKB and the Gene Ontology Consortium). This fundamental change in database conception capitalizes on the domain-specific knowledge of contributing communities to provide high-quality annotations, while leveraging the availability of stable information hubs to promote long-term access and provide high-visibility to the data. As a submission portal, CollecTF generates TF-binding site information through direct annotation of RefSeq genome records, definition of TF-based regulatory networks in UniProtKB entries and submission of functional annotations to the Gene Ontology. As a database, CollecTF provides enhanced search and browsing, targeted data exports, binding motif analysis tools and integration with motif discovery and search platforms. This innovative approach will allow CollecTF to focus its limited resources on the generation of high-quality information and the provision of specialized access to the data.Database URL: http://www.collectf.org/. © The Author(s) 2016. Published by Oxford University Press.

Overexpression of OsTF1L, a rice HD-Zip transcription factor, promotes lignin biosynthesis and stomatal closure that improves drought tolerance.

PubMed

Bang, Seung Woon; Lee, Dong-Keun; Jung, Harin; Chung, Pil Joong; Kim, Youn Shic; Choi, Yang Do; Suh, Joo-Won; Kim, Ju-Kon

2018-05-21

Drought stress seriously impacts on plant development and productivity. Improvement of drought tolerance without yield penalty is a great challenge in crop biotechnology. Here, we report that the rice (Oryza sativa) homeodomain-leucine zipper transcription factor gene, OsTF1L (Oryza sativa transcription factor 1-like), is a key regulator of drought tolerance mechanisms. Overexpression of the OsTF1L in rice significantly increased drought tolerance at the vegetative stages of growth and promoted both effective photosynthesis and a reduction in the water loss rate under drought conditions. Importantly, the OsTF1L overexpressing plants showed a higher drought tolerance at the reproductive stage of growth with a higher grain yield than non-transgenic controls under field-drought conditions. Genome-wide analysis of OsTF1L overexpression plants revealed up-regulation of drought-inducible, stomatal movement and lignin biosynthetic genes. Overexpression of OsTF1L promoted accumulation of lignin in shoots, whereas the RNAi lines showed opposite patterns of lignin accumulation. OsTF1L is mainly expressed in outer cell layers including the epidermis, and the vasculature of the shoots, which coincides with areas of lignification. In addition, OsTF1L overexpression enhances stomatal closure under drought conditions resulted in drought tolerance. More importantly, OsTF1L directly bound to the promoters of lignin biosynthesis and drought-related genes involving poxN/PRX38, Nodulin protein, DHHC4, CASPL5B1 and AAA-type ATPase. Collectively, our results provide a new insight into the role of OsTF1L in enhancing drought tolerance through lignin biosynthesis and stomatal closure in rice. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Improvement of COBRA-TF for modeling of PWR cold- and hot-legs during reactor transients

NASA Astrophysics Data System (ADS)

Salko, Robert K.

COBRA-TF is a two-phase, three-field (liquid, vapor, droplets) thermal-hydraulic modeling tool that has been developed by the Pacific Northwest Laboratory under sponsorship of the NRC. The code was developed for Light Water Reactor analysis starting in the 1980s; however, its development has continued to this current time. COBRA-TF still finds wide-spread use throughout the nuclear engineering field, including nuclear-power vendors, academia, and research institutions. It has been proposed that extension of the COBRA-TF code-modeling region from vessel-only components to Pressurized Water Reactor (PWR) coolant-line regions can lead to improved Loss-of-Coolant Accident (LOCA) analysis. Improved modeling is anticipated due to COBRA-TF's capability to independently model the entrained-droplet flow-field behavior, which has been observed to impact delivery to the core region[1]. Because COBRA-TF was originally developed for vertically-dominated, in-vessel, sub-channel flow, extension of the COBRA-TF modeling region to the horizontal-pipe geometries of the coolant-lines required several code modifications, including: • Inclusion of the stratified flow regime into the COBRA-TF flow regime map, along with associated interfacial drag, wall drag and interfacial heat transfer correlations, • Inclusion of a horizontal-stratification force between adjacent mesh cells having unequal levels of stratified flow, and • Generation of a new code-input interface for the modeling of coolant-lines. The sheer number of COBRA-TF modifications that were required to complete this work turned this project into a code-development project as much as it was a study of thermal-hydraulics in reactor coolant-lines. The means for achieving these tasks shifted along the way, ultimately leading the development of a separate, nearly completely independent one-dimensional, two-phase-flow modeling code geared toward reactor coolant-line analysis. This developed code has been named CLAP, for Coolant-Line-Analysis Package. Versions were created that were both coupled to COBRA-TF and standalone, with the most recent version being a standalone code. This code performs a separate, simplified, 1-D solution of the conservation equations while making special considerations for coolant-line geometry and flow phenomena. The end of this project saw a functional code package that demonstrates a stable numerical solution and that has gone through a series of Validation and Verification tests using the Two-Phase Testing Facility (TPTF) experimental data[2]. The results indicate that CLAP is under-performing RELAP5-MOD3 in predicting the experimental void of the TPTF facility in some cases. There is no apparent pattern, however, to point to a consistent type of case that the code fails to predict properly (e.g., low-flow, high-flow, discharging to full vessel, or discharging to empty vessel). Pressure-profile predictions are sometimes unrealistic, which indicates that there may be a problem with test-case boundary conditions or with the coupling of continuity and momentum equations in the solution algorithm. The code does predict the flow regime correctly for all cases with the stratification-force model off. Turning the stratification model on can cause the low-flow case void profiles to over-react to the force and the flow regime to transition out of stratified flow. The code would benefit from an increased amount of Validation & Verification testing. The development of CLAP was significant, as it is a cleanly written, logical representation of the reactor coolant-line geometry. It is stable and capable of modeling basic flow physics in the reactor coolant-line. Code development and debugging required the temporary removal of the energy equation and mass-transfer terms in governing equations. The reintroduction of these terms will allow future coupling to RELAP and re-coupling with COBRA-TF. Adding in more applicable entrainment and de-entrainment models would allow the capture of more advanced physics in the coolant-line that can be expected during Loss-of-Coolant Accident. One of the package's benefits is its ability to be used as a platform for future coolant-line model development and implementation, including capturing of the important de-entrainment behavior in reactor hot-legs (steam-binding effect) and flow convection in the upper-plenum region of the vessel.

Carbohydrate antigens in nipple aspirate fluid predict the presence of atypia and cancer in women requiring diagnostic breast biopsy.

PubMed

Deutscher, Susan L; Dickerson, Marie; Gui, Gerald; Newton, Jessica; Holm, Jeffrey E; Vogeltanz-Holm, Nancy; Kliethermes, Beth; Hewett, John E; Kumar, Senthil R; Quinn, Thomas P; Sauter, Edward R

2010-10-01

The goal of this prospective study was to determine (a) concentrations of the carbohydrate biomarkers Thomsen Friedenreich (TF) antigen and its precursor, Tn antigen, in nipple discharge (ND) collected from women requiring biopsy because of a suspicious breast lesion; and (b) if concentration levels predicted pathologic diagnosis. Adult women requiring biopsy to exclude breast cancer were enrolled and ND obtained. The samples from 124 women were analyzed using an anti-TF and anti-Tn monoclonal antibodies in direct immunoassay. The highest median concentration in ND for TF and Tn was in women with ductal carcinoma in situ (DCIS). TF was higher in women with 1) cancer (DCIS or invasive) vs. either no cancer (atypia or benign pathology, p = .048), or benign pathology (p = .018); and 2) abnormal (atypia or cancer) versus benign pathology (p = .016); and was more predictive of atypia or cancer in post- compared to premenopausal women. Tn was not predictive of disease. High TF concentration and age were independent predictors of disease, correctly classifying either cancer or abnormal vs. benign pathology 83% of the time in postmenopausal women. TF concentrations in ND were higher in women with precancer and cancer compared to women with benign disease, and TF was an independent predictor of breast atypia and cancer. TF may prove useful in early breast cancer detection.

Positive Feedback Loops for Factor V and Factor VII Activation Supply Sensitivity to Local Surface Tissue Factor Density During Blood Coagulation

PubMed Central

Balandina, A.N.; Shibeko, A.M.; Kireev, D.A.; Novikova, A.A.; Shmirev, I.I.; Panteleev, M.A.; Ataullakhanov, F.I.

2011-01-01

Blood coagulation is triggered not only by surface tissue factor (TF) density but also by surface TF distribution. We investigated recognition of surface TF distribution patterns during blood coagulation and identified the underlying molecular mechanisms. For these investigations, we employed 1), an in vitro reaction-diffusion experimental model of coagulation; and 2), numerical simulations using a mathematical model of coagulation in a three-dimensional space. When TF was uniformly immobilized over the activating surface, the clotting initiation time in normal plasma increased from 4 min to >120 min, with a decrease in TF density from 100 to 0.7 pmol/m2. In contrast, surface-immobilized fibroblasts initiated clotting within 3–7 min, independently of fibroblast quantity and despite a change in average surface TF density from 0.5 to 130 pmol/m2. Experiments using factor V-, VII-, and VIII-deficient plasma and computer simulations demonstrated that different responses to these two TF distributions are caused by two positive feedback loops in the blood coagulation network: activation of the TF–VII complex by factor Xa, and activation of factor V by thrombin. This finding suggests a new role for these reactions: to supply sensitivity to local TF density during blood coagulation. PMID:22004734

Significant and serious dehydration does not affect skeletal muscle cramp threshold frequency.

PubMed

Braulick, Kyle W; Miller, Kevin C; Albrecht, Jay M; Tucker, Jared M; Deal, James E

2013-07-01

Many clinicians believe that exercise-associated muscle cramps (EAMC) occur because of dehydration. Experimental research supporting this theory is lacking. Mild hypohydration (3% body mass loss) does not alter threshold frequency (TF), a measure of cramp susceptibility, when fatigue and exercise intensity are controlled. No experimental research has examined TF following significant (3-5% body mass loss) or serious hypohydration (>5% body mass loss). Determine if significant or serious hypohydration, with moderate electrolyte losses, decreases TF. A prepost experimental design was used. Dominant limb flexor hallucis brevis cramp TF, cramp electromyography (EMG) amplitude and cramp intensity were measured in 10 euhydrated, unacclimated men (age=24±4 years, height=184.2±4.8 cm, mass=84.8±11.4 kg). Subjects alternated exercising with their non-dominant limb or upper body on a cycle ergometer every 15 min at a moderate intensity until 5% body mass loss or volitional exhaustion (3.8±0.8 h; 39.1±1.5°C; humidity 18.4±3%). Cramp variables were reassessed posthypohydration. Subjects were well hydrated at the study's onset (urine specific gravity=1.005±0.002). They lost 4.7±0.5% of their body mass (3.9±0.5 litres of fluid), 4.0±1.5 g of Na(+) and 0.6±0.1 g K(+) via exercise-induced sweating. Significant (n=5) or serious hypohydration (n=5) did not alter cramp TF (euhydrated=15±5 Hz, hypohydrated=13±6 Hz; F1,9=3.0, p=0.12), cramp intensity (euhydrated= 94.2±41%, hypohydrated=115.9±73%; F1,9=1.9, p=0.2) or cramp EMG amplitude (euhydrated=0.18±0.06 µV, hypohydrated= 0.18±0.09 µV; F1,9=0.1, p=0.79). Significant and serious hypohydration with moderate electrolyte losses does not alter cramp susceptibility when fatigue and exercise intensity are controlled. Neuromuscular control may be more important in the onset of muscle cramps than dehydration or electrolyte losses.

Application of NASTRAN to TFTR toroidal field coil structures

NASA Technical Reports Server (NTRS)

Chen, S. J.; Lee, E.

1978-01-01

The primary applied loads on the TF coils were electromagnetic and thermal. The complex structure and the tremendous applied loads necessitated computer type of solutions for the design problems. In the early stage of the TF coil design, many simplified finite element models were developed for the purpose of investigating the effects of material properties, supporting schemes, and coil case material on the stress levels in the case and in the copper coil. In the more sophisticated models that followed the parametric and scoping studies, the isoparametric elements, such as QUAD4, HEX8, and HEXA, were used. The analysis results from using these finite element models and the NASTRAN system were considered accurate enough to provide timely design information.

On the coordination of Zn2+ ion in Tf2N- based ionic liquids: structural and dynamic properties depending on the nature of the organic cation.

PubMed

Sessa, Francesco; Migliorati, Valentina; Serva, Alessandra; Lapi, Andrea; Aquilanti, Giuliana; Mancini, Giordano; D'Angelo, Paola

2018-01-24

A synergic approach combining molecular dynamics (MD) simulations and X-ray absorption spectroscopy has been used to investigate diluted solutions of zinc bis(trifluoromethanesulfonyl)imide (Zn(Tf 2 N) 2 ) in Tf 2 N - based ionic liquids (ILs) having different organic cations, namely the 1-butyl-3-methylimidazolium ([C 4 (mim)] + ), 1,8-bis(3-methylimidazolium-1-yl)octane ([C 8 (mim) 2 ] 2+ ), N,N,N-trimethyl-N-(2-hydroxyethyl)ammonium ([Choline] + ) and butyltrimethylammonium ([BTMA] + ) ions. All of the ILs tend to dissolve the Zn(Tf 2 N) 2 species giving rise to a different structural arrangement around the Zn 2+ as compared to that of the salt crystallographic structure. A quantitative analysis of the Zn K-edge extended X-ray absorption fine structure (EXAFS) spectra of the solutions has been carried out based on the microscopic description of the systems derived from the MD simulations. A very good agreement between theoretical and experimental EXAFS signals has been obtained, allowing us to assess the reliability of the MD structural results for all the investigated solutions. The Zn 2+ ion has been shown to be coordinated by six oxygen atoms of the Tf 2 N - anions arranged in an octahedral geometry in all the Tf 2 N - based ILs, regardless of the organic cation of the IL solvent. However, the nature of the organic cation has a small influence on the overall spatial arrangement of the Tf 2 N - anions in the Zn 2+ first solvation shell: two different Zn-Tf 2 N complexes are found in solution, a 5-fold one, with one bidentate and four monodentate Tf 2 N - anions, and a 6-fold one with only monodentate ligands, with the ratio between the two species being slightly dependent on the IL cation. The IL ion three-dimensional arrangements in the different IL solutions were also investigated by carrying out a thorough analysis of the MD simulations, highlighting similarities and differences between imidazolium and ammonium based IL systems.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peter H. Titus and Ali Zolfaghari

A critical design feature of any tokamak is the space taken up by the inner leg of the toroidal field (TF) coil. The radial build needed for the TF inner leg, along with shield thickness , size of the central solenoid and plasma minor radius set the major radius of the machine. The cost of the tokamak core roughly scales with the cube of the major radius. Small reductions in the TF build can have a big impact on the overall cost of the reactor. The cross section of the TF inner leg must structurally support the centering force andmore » that portion of the vertical separating force that is not supported by the outer structures. In this paper, the TF inner leg equatorial plane cross sections are considered. Out-of- Plane (OOP) forces must also be supported, but these are largest away from the equatorial plane, in the inner upper and lower corners and outboard sections of the TF coil. OOP forces are taken by structures that are not closely coupled with the radial build of the central column at the equatorial plane. The "Vertical Access AT Pilot Plant" currently under consideration at PPPL is used as a starting point for the structural, field and current requirements. Other TF structural concepts are considered. Most are drawn from existing designs such as ITER's circular conduits in radial plates bearing on a heavy nose section, and TPX's square conduits in a case, Each of these concepts can rely on full wedging, or partial wedging. Vaulted TF coils are considered as are those with some component of bucking against a central solenoid or bucking post. With the expectation that the pilot plant will be a steady state machine, a static stress criteria is used for all the concepts. The coils are assumed to be superconducting, with the superconductor not contributing to the structural strength. Limit analysis is employed to assess the degree of conservatism in the static criteria as it is applied to a linear elastic stress analysis. TF concepts, and in particular the PPPL AT PILOT plate concept are evaluated based on amount of space needed for structure and the amount of space left for superconductor.« less

Supramolecular assemblies of tetrafluoroterephthalic acid and N-heterocycles via various strong hydrogen bonds and weak Csbnd H⋯F interactions: Synthons cooperation, robust motifs and structural diversity

NASA Astrophysics Data System (ADS)

Hu, Yanjing; Hu, Hanbin; Li, Yingying; Chen, Ruixin; Yang, Yu; Wang, Lei

2016-10-01

A series of organic solid states including three salts, two co-crystals, and three hydrates based on tetrafluoroterephthalic acid (H2tfBDC) and N-bearing ligands (2,4-(1H,3H)-pyrimidine dione (PID), 2,4-dihydroxy-6-methyl pyrimidine (DHMPI), 2-amino-4,6-dimethyl pyrimidine (ADMPI), 2-amino-4,6-dimenthoxy pyrimidine (ADMOPI), 5,6-dimenthyl benzimidazole (DMBI), 2-aminobenzimidazole (ABI), 3,5-dimethyl pyrazole (DMP), and 3-cyanopyridine (3-CNpy)), namely, [(PID)2·(H2tfBDC)] (1), [(DHMPI)2·(H2tfBDC)] (2), [(H-ADMPI+)2·(tfBDC2-)·2(H2O)] (3), [(H-ADMOPI+)2·(tfBDC2-)·(H2O)] (4), [(H-DMBI+)2·(tfBDC2-)·2(H2O)] (5), [(H-ABI+)2·(tfBDC2-)] (6), [(H-DMP+)·(HtfBDC-)] (7), and [(H-3-CNpy+)·(HtfBDC-)] (8), were synthesized by solvent evaporation method. Crystal structures analyses show that the F atom of the H2tfBDC participates in multiple Csbnd H⋯F hydrogen bond formations, producing different supramolecular synthons. The weak hydrogen bonding Csbnd H⋯F and Nsbnd H⋯F play an important part in constructing the diversity structures 2-8, except in crystal 1. In complexes 1-3, they present the same synthon R22(8) with different N-heterocyclic compounds, which may show the strategy in constructing the supramolecular. Meanwhile, the complex 3 exhibits a 2D layer, and the independent molecules of water exist in the adjacent layers. In complexes 4 and 5, the water molecules connect the neighboring layers to form 3D network by strong Osbnd H⋯O hydrogen bonding. These crystals 1-8 were fully characterized by single-crystal X-ray crystallography, elemental analysis, infrared spectroscopy (IR), and thermogravimetric analysis (TGA).

“Hit‐and‐Run” leaves its mark: Catalyst transcription factors and chromatin modification

PubMed Central

Varala, Kranthi; Li, Ying; Marshall‐Colón, Amy; Para, Alessia

2015-01-01

Understanding how transcription factor (TF) binding is related to gene regulation is a moving target. We recently uncovered genome‐wide evidence for a “Hit‐and‐Run” model of transcription. In this model, a master TF “hits” a target promoter to initiate a rapid response to a signal. As the “hit” is transient, the model invokes recruitment of partner TFs to sustain transcription over time. Following the “run”, the master TF “hits” other targets to propagate the response genome‐wide. As such, a TF may act as a “catalyst” to mount a broad and acute response in cells that first sense the signal, while the recruited TF partners promote long‐term adaptive behavior in the whole organism. This “Hit‐and‐Run” model likely has broad relevance, as TF perturbation studies across eukaryotes show small overlaps between TF‐regulated and TF‐bound genes, implicating transient TF‐target binding. Here, we explore this “Hit‐and‐Run” model to suggest molecular mechanisms and its biological relevance. PMID:26108710

Temporal multiplexing to simulate multifocal intraocular lenses: theoretical considerations

PubMed Central

Akondi, Vyas; Dorronsoro, Carlos; Gambra, Enrique; Marcos, Susana

2017-01-01

Fast tunable lenses allow an effective design of a portable simultaneous vision simulator (SimVis) of multifocal corrections. A novel method of evaluating the temporal profile of a tunable lens in simulating different multifocal intraocular lenses (M-IOLs) is presented. The proposed method involves the characteristic fitting of the through-focus (TF) optical quality of the multifocal component of a given M-IOL to a linear combination of TF optical quality of monofocal lenses viable with a tunable lens. Three different types of M-IOL designs are tested, namely: segmented refractive, diffractive and refractive extended depth of focus. The metric used for the optical evaluation of the temporal profile is the visual Strehl (VS) ratio. It is shown that the time profiles generated with the VS ratio as a metric in SimVis resulted in TF VS ratio and TF simulated images that closely matched the TF VS ratio and TF simulated images predicted with the M-IOL. The effects of temporal sampling, varying pupil size, monochromatic aberrations, longitudinal chromatic aberrations and temporal dynamics on SimVis are discussed. PMID:28717577

[Alteration of Microparticle Levels in Early Complications During Hematopoietic Stem Cell Transplantation].

PubMed

Zhou, Li-Li; Han, Yue; Zhu, Qian; Zhao, Shi-Xiang; Wang, Qian; Zhu, Ming-Qing; Dai, Lan; Shen, Wen-Hong; Wu, De-Pei

2015-12-01

To investigate the alteration of microparticles (MP) in the recipients following hematopoietic stem cell transplantation (HSCT) and its significance, and to search the early diagnostic indicators of thrombotic complications after transplantation. According to the occurrence of transplantation-associated complications, 94 allo-HSCT patients were divided into 4 groups: thrombotic group (VOD n = 7, TMA n = 2), acute graft-versus-host disease (aGVHD) group (n = 27), infection group (n = 41) and non-complication group (n = 17). Alterations of serum concentration of tissue factor positive microparticles (TF(+) MP) and endothelial microparticles (EMP) were analyzed by flow cytometry during the process of conditioning treatment and the early stage after transplantation. The relation of these 2 kinds of MP with complications was analysed. (1) The levels of TF(+) MP and EMP of patients undogoing allo-HSCT before conditioning treatment were obviously higher than those in normal controls, and showed some elevation during different times, but there was no significant statistical difference. Although the levels of TF(+) MP and EMP at the end of conditioning treatment were some higher than those before conditioning treatment, but there was no statistical difference between them. (2)The levels of TF(+) MP and EMP in thrombotic group were obviously higher than those in aGVHD group and infection group (P < 0.05). (3)The levels of TF(+) MP and EMP in thrombotic group at different times were significant differences from those in other groups (P < 0.05), and the levels of TF(+) MP and EMP were no significant difference from those in non-complication group. The increase of the TF(+) MP and EMP levels may be associated with occurrence of thrombosis after transplantation, indicating occurrence of the thrombotic complications, like hepatic vein occulusive disease (HVOD). The dynamically monitoring levels of TF(+) MP and EMP contributes to early discovery of thrombotic complications.

Central blood pressure in children and adolescents: non-invasive development and testing of novel transfer functions.

PubMed

Cai, T Y; Qasem, A; Ayer, J G; Butlin, M; O'Meagher, S; Melki, C; Marks, G B; Avolio, A; Celermajer, D S; Skilton, M R

2017-12-01

Central blood pressure can be estimated from peripheral pulses in adults using generalised transfer functions (TF). We sought to create and test age-specific non-invasively developed TFs in children, with comparison to a pre-existing adult TF. We studied healthy children from two sites at two time points, 8 and 14 years of age, split by site into development and validation groups. Radial and carotid pressure waveforms were obtained by applanation tonometry. Central systolic pressure was derived from carotid waveforms calibrated to brachial mean and diastolic pressures. Age-specific TFs created in the development groups (n=50) were tested in the validation groups aged 8 (n=137) and 14 years (n=85). At 8 years of age, the age-specific TF estimated 82, 99 and 100% of central systolic pressure values within 5, 10 and 15 mm Hg of their measured values, respectively. This TF overestimated central systolic pressure by 2.2 (s.d. 3.7) mm Hg, compared to being underestimated by 5.6 (s.d. 3.9) mm Hg with the adult TF. At 14 years of age, the age-specific TF estimated 60, 87 and 95% of values within 5, 10 and 15 mm Hg of their measured values, respectively. This TF underestimated central systolic pressure by 0.5 (s.d. 6.7) mm Hg, while the adult TF underestimated it by 6.8 (s.d. 6.0) mm Hg. In conclusion, age-specific TFs more accurately predict central systolic pressure measured at the carotid artery in children than an existing adult TF.

Computational Identification of Diverse Mechanisms Underlying Transcription Factor-DNA Occupancy

PubMed Central

Cheng, Qiong; Kazemian, Majid; Pham, Hannah; Blatti, Charles; Celniker, Susan E.; Wolfe, Scot A.; Brodsky, Michael H.; Sinha, Saurabh

2013-01-01

ChIP-based genome-wide assays of transcription factor (TF) occupancy have emerged as a powerful, high-throughput method to understand transcriptional regulation, especially on a global scale. This has led to great interest in the underlying biochemical mechanisms that direct TF-DNA binding, with the ultimate goal of computationally predicting a TF's occupancy profile in any cellular condition. In this study, we examined the influence of various potential determinants of TF-DNA binding on a much larger scale than previously undertaken. We used a thermodynamics-based model of TF-DNA binding, called “STAP,” to analyze 45 TF-ChIP data sets from Drosophila embryonic development. We built a cross-validation framework that compares a baseline model, based on the ChIP'ed (“primary”) TF's motif, to more complex models where binding by secondary TFs is hypothesized to influence the primary TF's occupancy. Candidates interacting TFs were chosen based on RNA-SEQ expression data from the time point of the ChIP experiment. We found widespread evidence of both cooperative and antagonistic effects by secondary TFs, and explicitly quantified these effects. We were able to identify multiple classes of interactions, including (1) long-range interactions between primary and secondary motifs (separated by ≤150 bp), suggestive of indirect effects such as chromatin remodeling, (2) short-range interactions with specific inter-site spacing biases, suggestive of direct physical interactions, and (3) overlapping binding sites suggesting competitive binding. Furthermore, by factoring out the previously reported strong correlation between TF occupancy and DNA accessibility, we were able to categorize the effects into those that are likely to be mediated by the secondary TF's effect on local accessibility and those that utilize accessibility-independent mechanisms. Finally, we conducted in vitro pull-down assays to test model-based predictions of short-range cooperative interactions, and found that seven of the eight TF pairs tested physically interact and that some of these interactions mediate cooperative binding to DNA. PMID:23935523

Twenty-four hour intraocular pressure monitoring with the SENSIMED Triggerfish contact lens: effect of body posture during sleep.

PubMed

Beltran-Agulló, Laura; Buys, Yvonne M; Jahan, Farzana; Shapiro, Colin M; Flanagan, John G; Cheng, Jason; Trope, Graham E

2017-10-01

To determine the difference in relative intraocular pressure (IOP) measured by the SENSIMED Triggerfish (TF) contact lens in flat compared with 30° head-up sleeping positions in patients with progressive primary open-angle glaucoma or normotensive glaucoma, based on recent or recurrent disc haemorrhage. Prospective, randomised, cross-over, open-label comparative study. IOP was monitored for 24 hours using TF on two separate sessions. Patients were randomly assigned to sleep flat one night and 30° head-up the other. Outputs in arbitrary units were obtained. Sleep and wake periods were defined as 22:00-6:00 and 8:00-22:00, respectively. Mean TF values during sleep and wake periods and wake-sleep and sleep-wake slopes were calculated for each session. TF output signals were compared between positions. Twelve subjects completed the study. Significant mean positive slopes were noted during the sleep period for both positions (p<0.01). No significant differences in the TF mean values were observed between positions (p=0.51). Six (54%) subjects had mean TF values significantly higher during the flat supine session, while four (36%) subjects had higher values during the head-up session. A significant increase in Goldmann IOP (p=0.001) and TF (p=0.02) measurements were observed after 24 hours of TF wear ('drift phenomenon'). Sleep position affects IOP as measured by TF in some patients with progressive glaucoma. The upward drift in TF output detected in >50% of the subjects requires further investigation to establish whether the increased output values over time are an artefact induced by the TF or a real change in IOP. NCT01351779. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

New method for determining free core nutation parameters, considering geophysical effects

NASA Astrophysics Data System (ADS)

Vondrák, J.; Ron, C.

2017-08-01

Context. In addition to the torques exerted by the Moon, Sun, and planets, changes of precession-nutation are known to be caused also by geophysical excitations. Recently studies suggest that geomagnetic jerks (GMJ) might be associated with sudden changes of phase and amplitude of free core nutation. We showed that using atmospheric and oceanic excitations with those by GMJ improves substantially the agreement with observed celestial pole offsets. Aims: Traditionally, the period Tf and quality factor Qf of the free core nutation (FCN) are derived from VLBI-based celestial pole offsets (CPO). Either direct analysis of the observed CPO, or indirect method using resonant effects of nutation terms with frequencies close to FCN, are used. The latter method is usually preferred, since it yields more accurate results. Our aim is to combine both approaches to better derive FCN parameters. Methods: We numerically integrated the part of CPO that is due to geophysical excitations for different combinations of Tf, Qf, using Brzeziński's broadband Liouville equations (Brzeziński 1994, Manuscripta geodaetica, 19, 157), and compared the results with the observed values of CPO. The values yielding the best fit were then estimated. The observed CPO, however, must be corrected for the change of nutation that is caused by the Tf, Qf values different from those used to calculate IAU 2000 model of nutation. To this end, we have used the Mathews-Herring-Buffet transfer function and applied it to the five most affected terms of nutation (with periods 365.26, 182.62, 121.75, 27.55 and 13.66 days). Results: The results, based on the CPO data in the interval 1986.0—2016.0 and excitations with three different models, are presented. We demonstrate that better results are obtained if the influence of additional excitations at GMJ epochs is added to excitations by the atmosphere and oceans. Our preferred values are Tf = 430.28 ± 0.04 mean solar days and Qf = 19 500 ± 200.

Carryover of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) from soil to plant and distribution to the different plant compartments studied in cultures of carrots (Daucus carota ssp. Sativus), potatoes (Solanum tuberosum), and cucumbers (Cucumis Sativus).

PubMed

Lechner, Mareike; Knapp, Holger

2011-10-26

A vegetation study was carried out to investigate the carryover of Perfluorooctanoic Acid (PFOA) and Perfluorooctane Sulfonate (PFOS) from soil mixed with contaminated sewage sludge to potato, carrot, and cucumber plants. Analysis was done by liquid-extraction using acetonitrile with dispersive SPE cleanup and subsequent HPLC-MS/MS. In order to assess the transfer potential from soil, transfer factors (TF) were calculated for the different plant compartments: TF = [PFC](plant (wet substance))/[PFC](soil (dry weight)). The highest TF were found for the vegetative plant compartments with average values for PFOS below those for PFOA: cucumber, 0.17 (PFOS), 0.88 (PFOA); potato, 0.36 (PFOS), 0.40 (PFOA); carrot, 0.38 (PFOS), 0.53 (PFOA). Transfer of PFOA and PFOS into potato peelings (average values of TF: PFOA 0.03, PFOS 0.04) exceeded the carryover to the peeled tubers (PFOA 0.01, PFOS < 0.01). In carrots, this difference did not occur (average values of TF: PFOA 0.04, PFOS 0.04). Transfer of PFOS into the unpeeled cucumbers was low and comparable to that of peeled potatoes (TF < 0.01). For PFOA, it was higher (TF: 0.03).

Nup124p Is a Nuclear Pore Factor of Schizosaccharomyces pombe That Is Important for Nuclear Import and Activity of Retrotransposon Tf1

PubMed Central

Balasundaram, David; Benedik, Michael J.; Morphew, Mary; Dang, Van-Dinh; Levin, Henry L.

1999-01-01

The long terminal repeat (LTR)-containing retrotransposon Tf1 propagates within the fission yeast Schizosaccharomyces pombe as the result of several mechanisms that are typical of both retrotransposons and retroviruses. To identify host factors that contribute to the transposition process, we mutagenized cultures of S. pombe and screened them for strains that were unable to support Tf1 transposition. One such strain contained a mutation in a gene we named nup124. The product of this gene contains 11 FXFG repeats and is a component of the nuclear pore complex. In addition to the reduced levels of Tf1 transposition, the nup124-1 allele caused a significant reduction in the nuclear localization of Tf1 Gag. Surprisingly, the mutation in nup124-1 did not cause any reduction in the growth rate, the nuclear localization of specific nuclear localization signal-containing proteins, or the cytoplasmic localization of poly(A) mRNA. A two-hybrid analysis and an in vitro precipitation assay both identified an interaction between Tf1 Gag and the N terminus of Nup124p. These results provide evidence for an unusual mechanism of nuclear import that relies on a direct interaction between a nuclear pore factor and Tf1 Gag. PMID:10409764

Nup124p is a nuclear pore factor of Schizosaccharomyces pombe that is important for nuclear import and activity of retrotransposon Tf1.

PubMed

Balasundaram, D; Benedik, M J; Morphew, M; Dang, V D; Levin, H L

1999-08-01

The long terminal repeat (LTR)-containing retrotransposon Tf1 propagates within the fission yeast Schizosaccharomyces pombe as the result of several mechanisms that are typical of both retrotransposons and retroviruses. To identify host factors that contribute to the transposition process, we mutagenized cultures of S. pombe and screened them for strains that were unable to support Tf1 transposition. One such strain contained a mutation in a gene we named nup124. The product of this gene contains 11 FXFG repeats and is a component of the nuclear pore complex. In addition to the reduced levels of Tf1 transposition, the nup124-1 allele caused a significant reduction in the nuclear localization of Tf1 Gag. Surprisingly, the mutation in nup124-1 did not cause any reduction in the growth rate, the nuclear localization of specific nuclear localization signal-containing proteins, or the cytoplasmic localization of poly(A) mRNA. A two-hybrid analysis and an in vitro precipitation assay both identified an interaction between Tf1 Gag and the N terminus of Nup124p. These results provide evidence for an unusual mechanism of nuclear import that relies on a direct interaction between a nuclear pore factor and Tf1 Gag.

JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework.

PubMed

Khan, Aziz; Fornes, Oriol; Stigliani, Arnaud; Gheorghe, Marius; Castro-Mondragon, Jaime A; van der Lee, Robin; Bessy, Adrien; Chèneby, Jeanne; Kulkarni, Shubhada R; Tan, Ge; Baranasic, Damir; Arenillas, David J; Sandelin, Albin; Vandepoele, Klaas; Lenhard, Boris; Ballester, Benoît; Wasserman, Wyeth W; Parcy, François; Mathelier, Anthony

2018-01-04

JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) and TF flexible models (TFFMs) for TFs across multiple species in six taxonomic groups. In the 2018 release of JASPAR, the CORE collection has been expanded with 322 new PFMs (60 for vertebrates and 262 for plants) and 33 PFMs were updated (24 for vertebrates, 8 for plants and 1 for insects). These new profiles represent a 30% expansion compared to the 2016 release. In addition, we have introduced 316 TFFMs (95 for vertebrates, 218 for plants and 3 for insects). This release incorporates clusters of similar PFMs in each taxon and each TF class per taxon. The JASPAR 2018 CORE vertebrate collection of PFMs was used to predict TF-binding sites in the human genome. The predictions are made available to the scientific community through a UCSC Genome Browser track data hub. Finally, this update comes with a new web framework with an interactive and responsive user-interface, along with new features. All the underlying data can be retrieved programmatically using a RESTful API and through the JASPAR 2018 R/Bioconductor package. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Prophylactic stretching does not reduce cramp susceptibility.

PubMed

Miller, Kevin C; Harsen, James D; Long, Blaine C

2018-03-01

Some clinicians advocate stretching to prevent muscle cramps. It is unknown whether static or proprioceptive neuromuscular facilitation (PNF) stretching increases cramp threshold frequency (TF c ), a quantitative measure of cramp susceptibility. Fifteen individuals completed this randomized, counterbalanced, cross-over study. We measured passive hallux range of motion (ROM) and then performed 3 minutes of either static stretching, PNF stretching (hold-relax-with agonist contraction), or no stretching. ROM was reassessed and TF c was measured. PNF stretching increased hallux extension (pre-PNF 81 ± 11°, post-PNF 90 ± 10°; P < 0.05) but not hallux flexion (pre-PNF 40 ± 7°, post-PNF 40 ± 7°; P > 0.05). Static stretching increased hallux extension (pre-static 80 ± 11°, post-static 88 ± 9°; P < 0.05) but not hallux flexion (pre-static 38 ± 9°, post-static 39 ± 8°; P > 0.05). No ROM changes occurred with no stretching (P > 0.05). TF c was unaffected by stretching (no stretching 18 ± 7 Hz, PNF 16 ± 4 Hz, static 16 ± 5 Hz; P = 0.37). Static and PNF stretching increased hallux extension, but neither increased TF c . Acute stretching may not prevent muscle cramping. Muscle Nerve 57: 473-477, 2018. © 2017 Wiley Periodicals, Inc.

JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework

PubMed Central

Fornes, Oriol; Stigliani, Arnaud; Gheorghe, Marius; Castro-Mondragon, Jaime A; Bessy, Adrien; Chèneby, Jeanne; Kulkarni, Shubhada R; Tan, Ge; Baranasic, Damir; Arenillas, David J; Vandepoele, Klaas; Parcy, François

2018-01-01

Abstract JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) and TF flexible models (TFFMs) for TFs across multiple species in six taxonomic groups. In the 2018 release of JASPAR, the CORE collection has been expanded with 322 new PFMs (60 for vertebrates and 262 for plants) and 33 PFMs were updated (24 for vertebrates, 8 for plants and 1 for insects). These new profiles represent a 30% expansion compared to the 2016 release. In addition, we have introduced 316 TFFMs (95 for vertebrates, 218 for plants and 3 for insects). This release incorporates clusters of similar PFMs in each taxon and each TF class per taxon. The JASPAR 2018 CORE vertebrate collection of PFMs was used to predict TF-binding sites in the human genome. The predictions are made available to the scientific community through a UCSC Genome Browser track data hub. Finally, this update comes with a new web framework with an interactive and responsive user-interface, along with new features. All the underlying data can be retrieved programmatically using a RESTful API and through the JASPAR 2018 R/Bioconductor package. PMID:29140473

Cyclic fatigue resistance of 3 different nickel-titanium reciprocating instruments in artificial canals.

PubMed

Higuera, Oscar; Plotino, Gianluca; Tocci, Luigi; Carrillo, Gabriela; Gambarini, Gianluca; Jaramillo, David E

2015-06-01

The purpose of this study was to evaluate the cyclic fatigue resistance of 3 different nickel-titanium reciprocating instruments. A total of 45 nickel-titanium instruments were tested and divided into 3 experimental groups (n = 15): group 1, WaveOne Primary instruments; group 2, Reciproc R25 instruments; and group 3, Twisted File (TF) Adaptive M-L1 instruments. The instruments were then subjected to cyclic fatigue test on a static model consisting of a metal block with a simulated canal with 60° angle of curvature and a 5-mm radius of curvature. WaveOne Primary, Reciproc R25, and TF Adaptive instruments were activated by using their proprietary movements, WaveOne ALL, Reciproc ALL, and TF Adaptive, respectively. All instruments were activated until fracture occurred, and the time to fracture was recorded visually for each file with a 1/100-second chronometer. Mean number of cycles to failure and standard deviations were calculated for each group, and data were statistically analyzed (P < .05). Instruments were also observed through scanning electron microscopy to evaluate type of fracture. Cyclic fatigue resistance of Reciproc R25 and TF Adaptive M-L1 was significantly higher than that of WaveOne Primary (P = .009 and P = .002, respectively). The results showed no statistically significant difference between TF Adaptive M-L1 and Reciproc R25 (P = .686). Analysis of the fractured portion under scanning electron microscopy indicated that all instruments showed morphologic characteristics of ductile fracture that were due to accumulation of metal fatigue. No statistically significant differences were found between the instruments tested except for WaveOne Primary, which showed the lowest resistance to cyclic fatigue. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Flow field and oscillatory shear stress in a tuning-fork-shaped model of the average human carotid bifurcation.

PubMed

Ding, Z; Wang, K; Li, J; Cong, X

2001-12-01

The oscillatory shear index (OSI) was developed based on the hypothesis that intimal hyperplasia was correlated with oscillatory shear stresses. However, the validity of the OSI was in question since the correlation between intimal thickness and the OSI at the side walls of the sinus in the Y-shaped model of the average human carotid bifurcation (Y-AHCB) was weak. The objectives of this paper are to examine whether the reason for the weak correlation lies in the deviation in geometry of Y-AHCB from real human carotid bifurcation, and whether this correlation is clearly improved in the tuning-fork-shaped model of the average human carotid bifurcation (TF-AHCB). The geometry of the TF-AHCB model was based on observation and statistical analysis of specimens from 74 cadavers. The flow fields in both models were studied and compared by using flow visualization methods under steady flow conditions and by using laser Doppler anemometer (LDA) under pulsatile flow conditions. The TF-shaped geometry leads to a more complex flow field than the Y-shaped geometry. This added complexity includes strengthened helical movements in the sinus, new flow separation zone, and directional changes in the secondary flow patterns. The results show that the OSI-values at the side walls of the sinus in the TF-shaped model were more than two times as large as those in the Y-shaped model. This study confirmed the stronger correlation between the OSI and intimal thickness in the tuning-fork geometry of human carotid bifurcation, and the TF-AHCB model is a significant improvement over the traditional Y-shaped model.

Guidance and Control Design Considerations for Low-Altitude and Terminal-Area Flight

DTIC Science & Technology

1978-04-01

MEAN TIME BETWEEN DEFECTS MEAN TIME BETWEEN UNDETECTED FAILURES 1 BASIC SYSTEM 49. S hrs 8, 213 hrs 2 DUPLEX TFC/ APFD 51.0 hrs 14. 981 hrs 3 2...MOTION SENSORS Figure 6 TF System 2 AERIAL RADAR TX/RX R.P SERVOS STRAP DOWN INS «EL.VG hi I 1 -i «JNAV/WASS I J TF/ APFD COMPUTER

PET Imaging of Tissue Factor in Pancreatic Cancer Using 64Cu-Labeled Active Site-Inhibited Factor VII.

PubMed

Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Lotte K; Jensen, Mette M; El Ali, Henrik H; Madsen, Jacob; Wiinberg, Bo; Petersen, Lars C; Kjaer, Andreas

2016-07-01

Tissue factor (TF) is the main initiator of the extrinsic coagulation cascade. However, TF also plays an important role in cancer. TF expression has been reported in 53%-89% of all pancreatic adenocarcinomas, and the expression level of TF has in clinical studies correlated with advanced stage, increased microvessel density, metastasis, and poor overall survival. Imaging of TF expression is of clinical relevance as a prognostic biomarker and as a companion diagnostic for TF-directed therapies currently under clinical development. Factor VII (FVII) is the natural ligand to TF. The purpose of this study was to investigate the possibility of using active site-inhibited FVII (FVIIai) labeled with (64)Cu for PET imaging of TF expression. FVIIai was conjugated to 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) and labeled with (64)Cu ((64)Cu-NOTA-FVIIai). Longitudinal in vivo PET imaging was performed at 1, 4, 15, and 36 h after injection of (64)Cu-NOTA-FVIIai in mice with pancreatic adenocarcinomas (BxPC-3). The specificity of TF imaging with (64)Cu-NOTA-FVIIai was investigated in subcutaneous pancreatic tumor models with different levels of TF expression and in a competition experiment. In addition, imaging of orthotopic pancreatic tumors was performed using (64)Cu-NOTA-FVIIai and PET/MRI. In vivo imaging data were supported by ex vivo biodistribution, flow cytometry, and immunohistochemistry. Longitudinal PET imaging with (64)Cu-NOTA-FVIIai showed a tumor uptake of 2.3 ± 0.2, 3.7 ± 0.3, 3.4 ± 0.3, and 2.4 ± 0.3 percentage injected dose per gram at 1, 4, 15, and 36 h after injection, respectively. An increase in tumor-to-normal-tissue contrast was observed over the imaging time course. Competition with unlabeled FVIIai significantly (P < 0.001) reduced the tumor uptake. The tumor uptake observed in models with different TF expression levels was significantly different from each other (P < 0.001) and was in agreement with the TF level evaluated by TF immunohistochemistry staining. Orthotopic tumors were clearly visible on the PET/MR images, and the uptake of (64)Cu-NOTA-FVIIai was colocalized with viable tumor tissue. (64)Cu-NOTA-FVIIai is well suited for PET imaging of tumor TF expression, and imaging is capable of distinguishing the TF expression level of various pancreatic tumor models. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

A Decision Criteria to Select an Associative-Memory Organization That Minimizes the Execution Time of a Mix of Associative-Search Operations

DTIC Science & Technology

1993-06-01

s )) = Op (C(s), db(s))" (26) Equation (27) defines OP. Brt(JxBR’T()-,BR as the complement of Op,. Op,(C(s), db(s)) = 0p,(C(s), db(s))’" (27) The...9.5 tf=13.0 t= 11.0 tf= 12.8 128 words tr-13.5 tf=16.9 t,=14.3 t(=17.3 t,=16.5 tf=22.0 Op,,(C(s), db( s )), Op .<(C(s), db( s )), Op ,(C(s), db( s )), Op >(C...OP.(C(s), db( s )), Op •(C(s), db( s )), Op <(C(s), db( s )), Op >(C(s), db( s )), Op .(C(s), db( s

The retrotransposon Tf1 assembles virus-like particles that contain excess Gag relative to integrase because of a regulated degradation process.

PubMed

Atwood, A; Lin, J H; Levin, H L

1996-01-01

The retrotransposon Tf1, isolated from Schizosaccharomyces pombe, contains a single open reading frame with sequences encoding Gag, protease, reverse transcriptase, and integrase (IN). Tf1 has previously been shown to possess significant transposition activity. Although Tf1 proteins do assemble into virus-like particles, the assembly does not require readthrough of a translational reading frame shift or stop codon, common mechanisms used by retroelements to express Gag in molar excess of the polymerase proteins. This study was designed to determine if Tf1 particles contain equal amounts of Gag and polymerase proteins or whether they contain the typical molar excess of Gag. After using two separate methods to calibrate the strength of our antibodies, we found that both S. pombe extracts and partially purified Tf1 particles contained a 26-fold molar excess of Gag relative to IN. Knowing that Gag and IN are derived from the same Tf1 primary translation product, we concluded that the excess Gag most likely resulted from specific degradation of IN. We obtained evidence of regulated IN degradation in comparisons of Tf1 protein extracted from log-phase cells and that extracted from stationary-phase cells. The log-phase cells contained equal molar amounts of Gag and IN, whereas cells approaching stationary phase rapidly degraded IN, leaving an excess of Gag. Analysis of the reverse transcripts indicated that the bulk of reverse transcription occurred within the particles that possess a molar excess of Gag.

An Improved Method for Measuring Chromatin-binding Dynamics Using Time-dependent Formaldehyde Crosslinking

PubMed Central

Hoffman, Elizabeth A.; Zaidi, Hussain; Shetty, Savera J.; Bekiranov, Stefan; Auble, David T.

2018-01-01

Formaldehyde crosslinking is widely used in combination with chromatin immunoprecipitation (ChIP) to measure the locations along DNA and relative levels of transcription factor (TF)-DNA interactions in vivo. However, the measurements that are typically made do not provide unambiguous information about the dynamic properties of these interactions. We have developed a method to estimate binding kinetic parameters from time-dependent formaldehyde crosslinking data, called crosslinking kinetics (CLK) analysis. Cultures of yeast cells are crosslinked with formaldehyde for various periods of time, yielding the relative ChIP signal at particular loci. We fit the data using the mass-action CLK model to extract kinetic parameters of the TF-chromatin interaction, including the on- and off-rates and crosslinking rate. From the on- and off-rate we obtain the occupancy and residence time. The following protocol is the second iteration of this method, CLKv2, updated with improved crosslinking and quenching conditions, more information about crosslinking rates, and systematic procedures for modeling the observed kinetic regimes. CLKv2 analysis has been applied to investigate the binding behavior of the TATA-binding protein (TBP), and a selected subset of other TFs. The protocol was developed using yeast cells, but may be applicable to cells from other organisms as well. PMID:29682595

Characterization of individual straight and kinked boron carbide nanowires

NASA Astrophysics Data System (ADS)

Cui, Zhiguang

Boron carbides represent a class of ceramic materials with p-type semiconductor natures, complex structures and a wide homogeneous range of carbon compositions. Bulk boron carbides have long been projected as promising high temperature thermoelectric materials, but with limited performance. Bringing the bulk boron carbides to low dimensions (e.g., nanowires) is believed to be an option to enhance their thermoelectric performance because of the quantum size effects. However, the fundamental studies on the microstructure-thermal property relation of boron carbide nanowires are elusive. In this dissertation work, systematic structural characterization and thermal conductivity measurement of individual straight and kinked boron carbide nanowires were carried out to establish the true structure-thermal transport relation. In addition, a preliminary Raman spectroscopy study on identifying the defects in individual boron carbide nanowires was conducted. After the synthesis of single crystalline boron carbide nanowires, straight nanowires accompanied by the kinked ones were observed. Detailed structures of straight boron carbide nanowires have been reported, but not the kinked ones. After carefully examining tens of kinked nanowires utilizing Transmission Electron Microscopy (TEM), it was found that they could be categorized into five cases depending on the stacking faults orientations in the two arms of the kink: TF-TF, AF-TF, AF-AF, TF-IF and AF-IF kinks, in which TF, AF and IF denotes transverse faults (preferred growth direction perpendicular to the stacking fault planes), axial faults (preferred growth direction in parallel with the stacking fault planes) and inclined faults (preferred growth direction neither perpendicular to nor in parallel with the stacking fault planes). Simple structure models describing the characteristics of TF-TF, AF-TF, AF-AF kinked nanowires are constructed in SolidWorks, which help to differentiate the kinked nanowires viewed from the zone axes where stacking faults are invisible. In collaboration with the experts in the field of thermal property characterization of one dimensional nanostructures, thermal conductivities of over 60 nanowires including both straight and kinked ones have been measured in the temperature range of 20 - 420 K and the parameters (i.e., carbon contents, diameters, stacking faults densities/orientations and kinks) affecting the phonon transport were explored. The results disclose strong carbon content and diameter dependence of thermal conductivities of boron carbide nanowires, which decreases as lowering the carbon content and diameter. Stacking fault orientations do modulate the phonon transport (kappaTF < kappa AF), while stacking fault densities seems to only have obvious effects on phonon transport when meeting certain threshold ( 39%). The most interesting discovery is significant reduction of thermal conductivity (15% - 40%) in kinked boron carbide nanowires due to phonon mode conversions and scattering at the kink site. Last but not least, micro-Raman spectroscopy study on individual boron carbide nanowires has been performed for the first time, to the best of our knowledge. Based on the preliminary data, it is found that the stacking fault orientations have no apparent effect on the Raman scattering, but the stacking fault densities do. In addition, up as the size going down to nanoscale, some Raman modes are inactive while some new ones show up, which is largely ascribed to the quantum confinement effects. One more important finding is that the carbon content also plays important role in the Raman scattering of boron carbide nanowires in the low frequency region (< 600 cm-1), which mainly comes from the 3-atom chains (C-B-C or C-B-B).

Trauma-focused CBT for youth with complex trauma

PubMed Central

Mannarino, Anthony P.; Kliethermes, Matthew; Murray, Laura A.

2013-01-01

Objectives Many youth develop complex trauma, which includes regulation problems in the domains of affect, attachment, behavior, biology, cognition, and perception. Therapists often request strategies for using evidence-based treatments (EBTs) for this population. This article describes practical strategies for applying Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) for youth with complex trauma. Methods TF-CBT treatment phases are described and modifications of timing, proportionality and application are described for youth with complex trauma. Practical applications include a) dedicating proportionally more of the model to the TF-CBT coping skills phase; b) implementing the TF-CBT Safety component early and often as needed throughout treatment; c) titrating gradual exposure more slowly as needed by individual youth; d) incorporating unifying trauma themes throughout treatment; and e) when indicated, extending the TF-CBT treatment consolidation and closure phase to include traumatic grief components and to generalize ongoing safety and trust. Results Recent data from youth with complex trauma support the use of the above TF-CBT strategies to successfully treat these youth. Conclusions The above practical strategies can be incorporated into TF-CBT to effectively treat youth with complex trauma. Practice implications Practical strategies include providing a longer coping skills phase which incorporates safety and appropriate gradual exposure; including relevant unifying themes; and allowing for an adequate treatment closure phase to enhance ongoing trust and safety. Through these strategies therapists can successfully apply TF-CBT for youth with complex trauma. PMID:22749612

Synthesis, X-ray crystallography characterization, vibrational spectroscopic, molecular electrostatic potential maps, thermodynamic properties studies of N,N'-di(p-thiazole)formamidine.

PubMed

Rofouei, M K; Fereyduni, E; Sohrabi, N; Shamsipur, M; Attar Gharamaleki, J; Sundaraganesan, N

2011-01-01

In this work, we will report a combined experimental and theoretical study on molecular and vibrational structure of N,N'-di(p-thiazole)formamidine (DpTF). DpTF has been synthesized and characterized by elemental analysis, FT-IR, FT-Raman, 1H NMR, 13C NMR spectroscopy and X-ray single crystal diffraction. The FT-IR and FT-Raman spectra of DpTF were recorded in the solid phase. The optimized geometry was calculated by HF and B3LYP methods using 6-31G(d) basis set. The FT-IR and FT-Raman spectra of DpTF was calculated at the HF/B3LYP/6-31G(d) level and were interpreted in terms of potential energy distribution (PED) analysis. The scaled theoretical wavenumber showed very good agreement with the experimental values. A detailed interpretation of the infrared and Raman spectra of DpTF was reported. On the basis of vibrational analyses, the thermodynamic properties of the title compound at different temperatures have been calculated, revealing the correlations between Cp,m°, Sm°, Hm° and temperatures. Furthermore, molecular electrostatic potential maps (MESP) and total dipole moment properties of the compound have been calculated. Copyright © 2010 Elsevier B.V. All rights reserved.

Micelle assisted thin-film solid phase microextraction: a new approach for determination of quaternary ammonium compounds in environmental samples.

PubMed

Boyacı, Ezel; Pawliszyn, Janusz

2014-09-16

Determination of quaternary ammonium compounds (QACs) often is considered to be a challenging undertaking owing to secondary interactions of the analytes' permanently charged quaternary ammonium head or hydrophobic tail with the utilized labware. Here, for the first time, a micelle assisted thin-film solid phase microextraction (TF-SPME) using a zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) as a matrix modifier is introduced as a novel approach for in-laboratory sample preparation of the challenging compounds. The proposed micelle assisted TF-SPME method offers suppression/enhancement free electrospray ionization of analytes in mass spectrometric detection, minimal interaction of the micelles with the TF-SPME coating, and chromatographic stationary phase and analysis free of secondary interactions. Moreover, it was found that the matrix modifier has multiple functions; when its concentration is found below the critical micelle concentration (CMC), the matrix modifier primarily acts as a surface deactivator; above its CMC, it acts as a stabilizer for QACs. Additionally, shorter equilibrium extraction times in the presence of the modifier demonstrated that micelles also assist in the transfer of analytes from the bulk of the sample to the surface of the coating. The developed micelle assisted TF-SPME protocol using the 96-blade system requires only 30 min of extraction and 15 min of desorption. Together with a conditioning step (15 min), the entire method is 60 min; considering the advantage of using the 96-blade system, if all the blades in the brush are used, the sample preparation time per sample is 0.63 min. Moreover, the recoveries for all analytes with the developed method were found to range within 80.2-97.3%; as such, this method can be considered an open bed solid phase extraction. The proposed method was successfully validated using real samples.

UniNE at TREC 2008: Fact and Opinion Retrieval in the Blogsphere

DTIC Science & Technology

2008-11-01

where (1 ) ( / ) j j ij i j t q j ij i n df k tf Score D Q qtf df K tf K k b b l avdl ∈  − + ⋅ = ⋅ ⋅   +  = ⋅ − + ⋅ ∑ (1) in which the...the document score was evaluated as: ( , ) j i j ij t q Score D Q qtf w ∈ = ⋅∑ (2) where qtfj denotes the frequency of term tj in query Q, and...query submitted [8], [9]. To combine two or more single runs, we applied the Z- Score operator [10] defined as: jj k k jj j RSV Mean Z Score RSV

Asymmetry of the three catalytic sites on beta subunits of TF1 from a thermophilic Bacillus strain PS3.

PubMed

Hisabori, T; Kobayashi, H; Kaibara, C; Yoshida, M

1994-03-01

F1-ATPase isolated from plasma membrane of a thermophilic Bacillus strain PS3 (TF1) has very little or no endogenously bound adenine nucleotides. However, it can bind one ADP per mol of the enzyme on one of three beta subunits to form a stable TF1.ADP complex when incubated with a high concentration of ADP [Yoshida, M. & Allison, W.S. (1986) J. Biol. Chem. 261, 5714-5721]. The same TF1.ADP complex was recovered after filling all ADP binding sites with [3H]ADP and repeated gel filtration. Direct binding assay revealed that the TF1.ADP complex had lost the highest affinity site for TNP-ADP. When a substoichiometric amount of TNP-ATP was added, the complex hydrolyzed TNP-ATP slowly (single site hydrolysis), like native TF1. However, this hydrolysis was not promoted by chase-addition of excess ATP. The optimal pH of the ATPase activity of TF1 or the TF1.ADP complex measured with a short reaction period, 6.5, was lower than the reported value, 9.0, under the steady-state condition. Although the bound ADP was released from the complex only when the enzyme underwent multiple catalytic turnover, the rate of this release was much slower than the turnover. These results suggest that when one ADP binds to a site on one of the beta subunits and stays there for a long time, the enzyme will change form and the bound ADP will become a special species which is not able to be directly involved in the enzyme catalysis. This binding site for ADP appears to be the first site responsible for the single-site catalysis reaction observed for native TF1.

Clinician Documentation on Receipt of Trauma-Focused Evidence-Based Psychotherapies in a VA PTSD Clinic.

PubMed

Lu, Mary W; Plagge, Jane M; Marsiglio, Mary C; Dobscha, Steven K

2016-01-01

The U.S. Department of Veterans Affairs (VA) is implementing two trauma-focused, evidence-based psychotherapies (TF-EBPs) for posttraumatic stress disorder (PTSD): cognitive processing therapy and prolonged exposure therapy (PE). Veterans with PTSD often do not receive these treatments, and little is known about the reasons veterans may not receive TF-EBPs. The aim of this qualitative study was to summarize clinician-reported reasons in medical records for nonreceipt of TF-EBPs. All veterans (N = 63) identified through PTSD screening who were newly engaged in mental health care and received individual evaluations in a PTSD specialty clinic in fiscal year 2008 were included in the sample. Content analysis of electronic medical records revealed multiple potential reasons for nonreceipt of TF-EBPs including referral to other PTSD treatments, other clinical priorities, poor engagement in care, practical barriers, negative beliefs, and receipt of care in other settings. Eight veterans (13%) initiated TF-EBPs. Further interventions to promote engagement in PTSD treatment are warranted.

Retrotransposon Tf1 is targeted to pol II promoters by transcription activators

PubMed Central

Leem, Young-Eun; Ripmaster, Tracy; Kelly, Felice; Ebina, Hirotaka; Heincelman, Marc; Zhang, Ke; Grewal, Shiv I. S.; Hoffman, Charles S.; Levin, Henry L.

2008-01-01

SUMMARY The LTR-retrotransposon Tf1 preserves the coding capacity of its host Schizosaccharomyces pombe by integrating upstream of open reading frames (ORFs). To determine which features of the target sites were recognized by the transposon, we introduced plasmids containing candidate insertion sites into S. pombe and mapped the positions of integration. We found that Tf1 was targeted specifically to the promoters of pol II transcribed genes. A detailed analysis of integration in plasmids that contained either ade6 or fbp1 revealed insertions occurred in the promoters at positions where transcription factors bound. Further experiments revealed that the activator Atf1p and its binding site were required for directing integration to the promoter of fbp1. An interaction between Tf1 integrase and Atf1p was observed indicating that integration at fbp1 was mediated by the activator bound to its promoter. Surprisingly we found Tf1 contained sequences that activated transcription and these substituted for elements of the ade6 promoter disrupted by integration. PMID:18406330

Retrotransposon Tf1 is targeted to Pol II promoters by transcription activators.

PubMed

Leem, Young-Eun; Ripmaster, Tracy L; Kelly, Felice D; Ebina, Hirotaka; Heincelman, Marc E; Zhang, Ke; Grewal, Shiv I S; Hoffman, Charles S; Levin, Henry L

2008-04-11

The LTR-retrotransposon Tf1 preserves the coding capacity of its host Schizosaccharomyces pombe by integrating upstream of open reading frames (ORFs). To determine which features of the target sites were recognized by the transposon, we introduced plasmids containing candidate insertion sites into S. pombe and mapped the positions of integration. We found that Tf1 was targeted specifically to the promoters of Pol II-transcribed genes. A detailed analysis of integration in plasmids that contained either ade6 or fbp1 revealed insertions occurred in the promoters at positions where transcription factors bound. Further experiments revealed that the activator Atf1p and its binding site were required for directing integration to the promoter of fbp1. An interaction between Tf1 integrase and Atf1p was observed, indicating that integration at fbp1 was mediated by the activator bound to its promoter. Surprisingly, we found Tf1 contained sequences that activated transcription, and these substituted for elements of the ade6 promoter disrupted by integration.

PLGA-encapsulated tea polyphenols enhance the chemotherapeutic efficacy of cisplatin against human cancer cells and mice bearing Ehrlich ascites carcinoma

PubMed Central

Singh, Madhulika; Bhatnagar, Priyanka; Mishra, Sanjay; Kumar, Pradeep; Shukla, Yogeshwer; Gupta, Kailash Chand

2015-01-01

The clinical success of the applicability of tea polyphenols awaits efficient systemic delivery and bioavailability. Herein, following the concept of nanochemoprevention, which uses nanotechnology for enhancing the efficacy of chemotherapeutic drugs, we employed tea polyphenols, namely theaflavin (TF) and epigallocatechin-3-gallate (EGCG) encapsulated in a biodegradable nanoparticulate formulation based on poly(lactide-co-glycolide) (PLGA) with approximately 26% and 18% encapsulation efficiency, respectively. It was observed that TF/EGCG encapsulated PLGA nanoparticles (NPs) offered an up to ~7-fold dose advantage when compared with bulk TF/EGCG in terms of exerting its antiproliferative effects and also enhanced the anticancer potential of cisplatin (CDDP) in A549 (lung carcinoma), HeLa (cervical carcinoma), and THP-1 (acute monocytic leukemia) cells. Cell cycle analysis revealed that TF/EGCG-NPs were more efficient than bulk TF/EGCG in sensitizing A549 cells to CDDP-induced apoptosis, with a dose advantage of up to 20-fold. Further, TF/EGCG-NPs, alone or in combination with CDDP, were more effective in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase-9, and vascular endothelial growth factor, involved in cell proliferation, metastasis, and angiogenesis, respectively. EGCG and TF-NPs were also found to be more effective than bulk TF/EGCG in inducing the cleavage of caspase-3 and caspase-9 and Bax/Bcl2 ratio in favor of apoptosis. Further, in vivo evaluation of these NPs in combination with CDDP showed an increase in life span (P<0.05) in mice bearing Ehrlich’s ascites carcinoma cells, with apparent regression of tumor volume in comparison with mice treated with bulk doses with CDDP. These results indicate that EGCG and TF-NPs have superior cancer chemosensitization activity when compared with bulk TF/EGCG. PMID:26586942

Finding biomarkers in non-model species: literature mining of transcription factors involved in bovine embryo development

PubMed Central

2012-01-01

Background Since processes in well-known model organisms have specific features different from those in Bos taurus, the organism under study, a good way to describe gene regulation in ruminant embryos would be a species-specific consideration of closely related species to cattle, sheep and pig. However, as highlighted by a recent report, gene dictionaries in pig are smaller than in cattle, bringing a risk to reduce the gene resources to be mined (and so for sheep dictionaries). Bioinformatics approaches that allow an integration of available information on gene function in model organisms, taking into account their specificity, are thus needed. Besides these closely related and biologically relevant species, there is indeed much more knowledge of (i) trophoblast proliferation and differentiation or (ii) embryogenesis in human and mouse species, which provides opportunities for reconstructing proliferation and/or differentiation processes in other mammalian embryos, including ruminants. The necessary knowledge can be obtained partly from (i) stem cell or cancer research to supply useful information on molecular agents or molecular interactions at work in cell proliferation and (ii) mouse embryogenesis to supply useful information on embryo differentiation. However, the total number of publications for all these topics and species is great and their manual processing would be tedious and time consuming. This is why we used text mining for automated text analysis and automated knowledge extraction. To evaluate the quality of this “mining”, we took advantage of studies that reported gene expression profiles during the elongation of bovine embryos and defined a list of transcription factors (or TF, n = 64) that we used as biological “gold standard”. When successful, the “mining” approach would identify them all, as well as novel ones. Methods To gain knowledge on molecular-genetic regulations in a non model organism, we offer an approach based on literature-mining and score arrangement of data from model organisms. This approach was applied to identify novel transcription factors during bovine blastocyst elongation, a process that is not observed in rodents and primates. As a result, searching through human and mouse corpuses, we identified numerous bovine homologs, among which 11 to 14% of transcription factors including the gold standard TF as well as novel TF potentially important to gene regulation in ruminant embryo development. The scripts of the workflow are written in Perl and available on demand. They require data input coming from all various databases for any kind of biological issue once the data has been prepared according to keywords for the studied topic and species; we can provide data sample to illustrate the use and functionality of the workflow. Results To do so, we created a workflow that allowed the pipeline processing of literature data and biological data, extracted from Web of Science (WoS) or PubMed but also from Gene Expression Omnibus (GEO), Gene Ontology (GO), Uniprot, HomoloGene, TcoF-DB and TFe (TF encyclopedia). First, the human and mouse homologs of the bovine proteins were selected, filtered by text corpora and arranged by score functions. The score functions were based on the gene name frequencies in corpora. Then, transcription factors were identified using TcoF-DB and double-checked using TFe to characterise TF groups and families. Thus, among a search space of 18,670 bovine homologs, 489 were identified as transcription factors. Among them, 243 were absent from the high-throughput data available at the time of the study. They thus stand so far for putative TF acting during bovine embryo elongation, but might be retrieved from a recent RNA sequencing dataset (Mamo et al. , 2012). Beyond the 246 TF that appeared expressed in bovine elongating tissues, we restricted our interpretation to those occurring within a list of 50 top-ranked genes. Among the transcription factors identified therein, half belonged to the gold standard (ASCL2, c-FOS, ETS2, GATA3, HAND1) and half did not (ESR1, HES1, ID2, NANOG, PHB2, TP53, STAT3). Conclusions A workflow providing search for transcription factors acting in bovine elongation was developed. The model assumed that proteins sharing the same protein domains in closely related species had the same protein functionalities, even if they were differently regulated among species or involved in somewhat different pathways. Under this assumption, we merged the information on different mammalian species from different databases (literature and biology) and proposed 489 TF as potential participants of embryo proliferation and differentiation, with (i) a recall of 95% with regard to a biological gold standard defined in 2011 and (ii) an extension of more than 3 times the gold standard of TF detected so far in elongating tissues. The working capacity of the workflow was supported by the manual expertise of the biologists on the results. The workflow can serve as a new kind of bioinformatics tool to work on fused data sources and can thus be useful in studies of a wide range of biological processes. PMID:22931563

Identification of transcription factors potential related to brown planthopper resistance in rice via microarray expression profiling

PubMed Central

2012-01-01

Background Brown planthopper (BPH), Nilaparvata lugens Stål, is one of the most destructive insect pests of rice. The molecular responses of plants to sucking insects resemble responses to pathogen infection. However, the molecular mechanism of BPH-resistance in rice remains unclear. Transcription factors (TF) are up-stream regulators of various genes that bind to specific DNA sequences, thereby controlling the transcription from DNA to mRNA. They are key regulators for transcriptional expression in biological processes, and are probably involved in the BPH-induced pathways in resistant rice varieties. Results We conducted a microarray experiment to analyze TF genes related to BPH resistance in a Sri Lankan rice cultivar, Rathu Heenati (RHT). We compared the expression profiles of TF genes in RHT with those of the susceptible rice cultivar Taichun Native 1 (TN1). We detected 2038 TF genes showing differential expression signals between the two rice varieties. Of these, 442 TF genes were probably related to BPH-induced resistance in RHT and TN1, and 229 may be related to constitutive resistance only in RHT. These genes showed a fold change (FC) of more than 2.0 (P<0.05). Among the 442 TF genes related to BPH-induced resistance, most of them were readily induced in TN1 than in RHT by BPH feeding, for instance, 154 TF genes were up-regulated in TN1, but only 31 TF genes were up-regulated in RHT at 24 hours after BPH infestation; 2–4 times more TF genes were induced in TN1 than in RHT by BPH. At an FC threshold of >10, there were 37 induced TF genes and 26 constitutive resistance TF genes. Of these, 13 were probably involved in BPH-induced resistance, and 8 in constitutive resistance to BPH in RHT. Conclusions We explored the molecular mechanism of resistance to BPH in rice by comparing expressions of TF genes between RHT and TN1. We speculate that the level of gene repression, especially for early TF genes, plays an important role in the defense response. The fundamental point of the resistance strategy is that plants protect themselves by reducing their metabolic level to inhibit feeding by BPH and prevent damage from water and nutrient loss. We have selected 21 TF genes related to BPH resistance for further analyses to understand the molecular responses to BPH feeding in rice. PMID:23228240

Identification of transcription factors potential related to brown planthopper resistance in rice via microarray expression profiling.

PubMed

Wang, Yubing; Guo, Huimin; Li, Haichao; Zhang, Hao; Miao, Xuexia

2012-12-10

Brown planthopper (BPH), Nilaparvata lugens Stål, is one of the most destructive insect pests of rice. The molecular responses of plants to sucking insects resemble responses to pathogen infection. However, the molecular mechanism of BPH-resistance in rice remains unclear. Transcription factors (TF) are up-stream regulators of various genes that bind to specific DNA sequences, thereby controlling the transcription from DNA to mRNA. They are key regulators for transcriptional expression in biological processes, and are probably involved in the BPH-induced pathways in resistant rice varieties. We conducted a microarray experiment to analyze TF genes related to BPH resistance in a Sri Lankan rice cultivar, Rathu Heenati (RHT). We compared the expression profiles of TF genes in RHT with those of the susceptible rice cultivar Taichun Native 1 (TN1). We detected 2038 TF genes showing differential expression signals between the two rice varieties. Of these, 442 TF genes were probably related to BPH-induced resistance in RHT and TN1, and 229 may be related to constitutive resistance only in RHT. These genes showed a fold change (FC) of more than 2.0 (P<0.05). Among the 442 TF genes related to BPH-induced resistance, most of them were readily induced in TN1 than in RHT by BPH feeding, for instance, 154 TF genes were up-regulated in TN1, but only 31 TF genes were up-regulated in RHT at 24 hours after BPH infestation; 2-4 times more TF genes were induced in TN1 than in RHT by BPH. At an FC threshold of >10, there were 37 induced TF genes and 26 constitutive resistance TF genes. Of these, 13 were probably involved in BPH-induced resistance, and 8 in constitutive resistance to BPH in RHT. We explored the molecular mechanism of resistance to BPH in rice by comparing expressions of TF genes between RHT and TN1. We speculate that the level of gene repression, especially for early TF genes, plays an important role in the defense response. The fundamental point of the resistance strategy is that plants protect themselves by reducing their metabolic level to inhibit feeding by BPH and prevent damage from water and nutrient loss. We have selected 21 TF genes related to BPH resistance for further analyses to understand the molecular responses to BPH feeding in rice.

Studies on the binding of fulvic acid with transferrin by spectroscopic analysis

NASA Astrophysics Data System (ADS)

Zhang, Xiu-feng; Yang, Guang; Dong, Yu; Zhao, Yan-qin; Sun, Xiao-ran; Chen, Lei; Chen, Hong-bo

2015-02-01

Transferrin has shown potential in the delivery of anticancer drugs into primarily proliferating cancer cells that over-express transferrin receptors. Fulvic acid has a wide range of biological and pharmacological activities which caused widespread concerns, the interaction of fulvic acid with human serum transferrin (Tf) has great significance for gaining a deeper insight about anticancer activities of fulvic acid. In this study, the mechanism of interaction between fulvic acid and Tf, has been investigated by using fluorescence quenching, thermodynamics, synchronous fluorescence and circular dichroism (CD) under physiological condition. Our results have shown that fulvic acid binds to Tf and form a new complex, and the calculated apparent association constants are 5.04 × 108 M-1, 5.48 × 107 M-1, 7.38 × 106 M-1 from the fluorescence quenching at 288 K, 298 K, and 310 K. The thermodynamic parameters indicate that hydrogen bonding and weak van der Waals are involved in the interaction between fulvic acid and Tf. The binding of fulvic acid to Tf causes the α-helix structure content of the protein to reduce, and resulting that peptide chains of Tf become more stretched. Our results have indicated a mechanism of the interaction between fulvic acid and Tf, which may provide information for possible design of methods to deliver drug molecules via transferrin to target tissues and cells effectively.

Substance P - Neurokinin-1 Receptor Interaction Upregulates Monocyte Tissue Factor

PubMed Central

Khan, Mohammad M; Douglas, Steven D; Benton, Tami D

2011-01-01

Monocytes play an important role in hemostasis. In this study, the prothrombotic effects of the neuropeptide substance P (SP) on human monocytes through neurokinin-1 receptor (NK1-R) were characterized. SP upregulated monocyte tissue factor (TF), the major coagulation cascade stimulator, in a concentration and time dependent manner. Specific inhibition of NK1-R completely blocked TF expression. Monocytes stimulated by SP released cytokines and chemokines. When monocytes were stimulated with cytokines or chemokines, TF was expressed by the cytokines (GM-CSF, IFN-γ and TNF-α). Cytokines may play a major role in the mechanism of SP induced monocyte TF expression. NK1-R antagonists (NK1-RA) may have a role in developing novel therapeutic approaches to patients vulnerable to vaso-occlusive disorders. PMID:22115773

Localised transmission hotspots of a typhoid fever outbreak in the Democratic Republic of Congo.

PubMed

Ali, Engy; Bergh, Rafael Van Den; D'hondt, Rob; Kuma-Kuma, Donat; Weggheleire, Anja De; Baudot, Yves; Lambert, Vincent; Hunter, Paul; Zachariah, Rony; Maes, Peter

2017-01-01

In a semi-urban setting in the Democratic Republic of Congo, this study aims to understand the dynamic of a typhoid fever (TF) outbreak and to assess: a) the existence of hot spots for TF transmission and b) the difference between typhoid cases identified within those hot spots and the general population in relation to socio-demographic characteristics, sanitation practice, and sources of drinking water. This was a retrospective analysis of TF outbreaks in 2011 in Kikwit, DRC using microbiological analysis of water sources and a structured interview questionnaire. There were a total of 1430 reported TF cases. The outbreak's epidemic curve shows earliest and highest peak attack rates (AR) in three military camps located in Kikwit (Ebeya 3.2%; Ngubu 3.0%; and Nsinga 2.2%) compared to an average peak AR of 0.6% in other affected areas. A total 320 cases from the military camps and the high burden health areas were interviewed. Typhoid cases in the military camps shared a latrine with more than one family (P<0.02). All tap water sources in both the military camps and general population were found to be highly contaminated with faecal coliforms. The role of military camps in Kikwit as early hotspots of TF transmission was likely associated with lower sanitary and hygiene conditions. The proximity of camps to the general population might have been responsible for disseminating TF to the general population. Mapping of cases during an outbreak could be crucial to identify hot spots for transmission and institute corrective measures.

Localised transmission hotspots of a typhoid fever outbreak in the Democratic Republic of Congo

PubMed Central

Ali, Engy; Bergh, Rafael Van Den; D’hondt, Rob; Kuma-Kuma, Donat; Weggheleire, Anja De; Baudot, Yves; Lambert, Vincent; Hunter, Paul; Zachariah, Rony; Maes, Peter

2017-01-01

Introduction In a semi-urban setting in the Democratic Republic of Congo, this study aims to understand the dynamic of a typhoid fever (TF) outbreak and to assess: a) the existence of hot spots for TF transmission and b) the difference between typhoid cases identified within those hot spots and the general population in relation to socio-demographic characteristics, sanitation practice, and sources of drinking water. Methods This was a retrospective analysis of TF outbreaks in 2011 in Kikwit, DRC using microbiological analysis of water sources and a structured interview questionnaire. Results There were a total of 1430 reported TF cases. The outbreak’s epidemic curve shows earliest and highest peak attack rates (AR) in three military camps located in Kikwit (Ebeya 3.2%; Ngubu 3.0%; and Nsinga 2.2%) compared to an average peak AR of 0.6% in other affected areas. A total 320 cases from the military camps and the high burden health areas were interviewed. Typhoid cases in the military camps shared a latrine with more than one family (P<0.02). All tap water sources in both the military camps and general population were found to be highly contaminated with faecal coliforms. Conclusion The role of military camps in Kikwit as early hotspots of TF transmission was likely associated with lower sanitary and hygiene conditions. The proximity of camps to the general population might have been responsible for disseminating TF to the general population. Mapping of cases during an outbreak could be crucial to identify hot spots for transmission and institute corrective measures. PMID:29541325

Comparison of the shaping ability of GT® Series X, Twisted Files and AlphaKite rotary nickel-titanium systems in simulated canals

PubMed Central

2013-01-01

Background Efforts to improve the performance of rotary NiTi instruments by enhancing the properties of NiTi alloy, or their manufacturing processes rather than changes in instrument geometries have been reported. The aim of this study was to compare in-vitro the shaping ability of three different rotary nickel-titanium instruments produced by different manufacturing methods. Methods Thirty simulated root canals with a curvature of 35˚ in resin blocks were prepared with three different rotary NiTi systems: AK- AlphaKite (Gebr. Brasseler, Germany), GTX- GT® Series X (Dentsply, Germany) and TF- Twisted Files (SybronEndo, USA). The canals were prepared according to the manufacturers’ instructions. Pre- and post-instrumentation images were recorded and assessment of canal curvature modifications was carried out with an image analysis program (GSA, Germany). The preparation time and incidence of procedural errors were recorded. Instruments were evaluated under a microscope with 15 × magnifications (Carl Zeiss OPMI Pro Ergo, Germany) for signs of deformation. The Data were statistically analyzed using SPSS (Wilcoxon and Mann–Whitney U-tests, at a confidence interval of 95%). Results Less canal transportation was produced by TF apically, although the difference among the groups was not statistically significant. GTX removed the greatest amount of resin from the middle and coronal parts of the canal and the difference among the groups was statistically significant (p < 0.05). The shortest preparation time was registered with TF (444 s) and the longest with GTX (714 s), the difference among the groups was statistically significant (p < 0.05). During the preparation of the canals no instrument fractured. Eleven instruments of TF and one of AK were deformed. Conclusion Under the conditions of this study, all rotary NiTi instruments maintained the working length and prepared a well-shaped root canal. The least canal transportation was produced by AK. GTX displayed the greatest cutting efficiency. TF prepared the canals faster than the other two systems. PMID:24341354

The Transfer Function Model (TFM) as a Tool for Simulating Gravity Wave Phenomena in the Mesosphere

NASA Astrophysics Data System (ADS)

Porter, H.; Mayr, H.; Moore, J.; Wilson, S.; Armaly, A.

2008-12-01

The Transfer Function Model (TFM) is semi-analytical and linear, and it is designed to describe the acoustic gravity waves (GW) propagating over the globe and from the ground to 600 km under the influence of vertical temperature variations. Wave interactions with the flow are not accounted for. With an expansion in terms of frequency-dependent spherical harmonics, the time consuming vertical integration of the conservation equations is reduced to computing the transfer function (TF). (The applied lower and upper boundary conditions assure that spurious wave reflections will not occur.) The TF describes the dynamical properties of the medium divorced from the complexities of the temporal and horizontal variations of the excitation source. Given the TF, the atmospheric response to a chosen source is then obtained in short order to simulate the GW propagating through the atmosphere over the globe. In the past, this model has been applied to study auroral processes, which produce distinct wave phenomena such as: (1) standing lamb modes that propagate horizontally in the viscous medium of the thermosphere, (2) waves generated in the auroral oval that experience geometric amplification propagating to the pole where constructive interference generates secondary waves that propagate equatorward, (3) ducted modes propagating through the middle atmosphere that leak back into the thermosphere, and (4) GWs reflected from the Earth's surface that reach the thermosphere in a narrow propagation cone. Well-defined spectral features characterize these wave modes in the TF to provide analytical understanding. We propose the TFM as a tool for simulating GW in the mesosphere and in particular the features observed in Polar Mesospheric Clouds (PMC). With present-day computers, it takes less than one hour to compute the TF, so that there is virtually no practical limitation on the source configurations that can be applied and tested in the lower atmosphere. And there is no limitation on the temporal and spatial resolutions the model simulations can provide. We shall discuss the concept and organization of the TFM and present samples of GW simulations that illustrate the capabilities of the model and its user interface. We shall discuss in particular the waves that leak into the mesopause from the thermosphere above and propagate into the region from tropospheric weather systems below.

Word Frequency Analysis. MOS: 62E. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

j., JtU I J ’I JT S EiM. ’J~VERSA. 5 *J (Jtl~iL I ’JSJP 1 J LUSE t J &USED 5 1 .3 u51’G 3 J .3 UTZLI ATEICN 2 J & VALVE 1 0 J3 EVISUAL I .3 fVj5JLY 2...ECOVERY I 7TI;1Irk 9 REVI1VE I RECTLY 2 PEO 4 i:’ 1 R.EC13CED ? Rr.~vl I IlFr~k 44 RcFFZ(E: ; I Ff ," TF1 ’. I 1 !E* ST EPS 4 1 RELL..SSD 7 PkLIF I RELI~E t

Transactions of the Army Conference on Applied Mathematics and Computing (1st) Held at Washington, DC on 9-11 May 1983

DTIC Science & Technology

1984-02-01

I . . . . . . An Introduction to Geometric Programming Patrick D. Allen and David W. Baker . . . . . . , . . . . . . . Space and Time...Zarwyn, US-Army Electronics R & D Comhiand GEOMETRIC PROGRAMING SPACE AND TIFFE ANALYSIS IN DYNAMIC PROGRAMING ALGORITHMS Renne..tf Stizti, AkeanXa...physical and parameter space can be connected by asymptotic matching. The purpose of the asymptotic analysis is to define the simplest problems

ImmunoPET imaging of tissue factor expression in pancreatic cancer with 89Zr-Df-ALT-836.

PubMed

Hernandez, Reinier; England, Christopher G; Yang, Yunan; Valdovinos, Hector F; Liu, Bai; Wong, Hing C; Barnhart, Todd E; Cai, Weibo

2017-10-28

Overexpression of tissue factor (TF) has been associated with increased tumor growth, tumor angiogenesis, and metastatic potential in many malignancies, including pancreatic cancer. Additionally, high TF expression was shown to strongly correlate with poor prognoses and decreased survival in pancreatic cancer patients. Herein, we exploited the potential targeting of TF for positron emission tomography (PET) imaging of pancreatic cancer. The TF-targeted tracer was developed through radiolabeling of the anti-human TF monoclonal antibody (ALT-836) with 89 Zr. The tracer was characterized by fluorescence microscopy and flow cytometry assays in BXPC-3 and PANC-1 cells, two pancreatic cancer cell lines with high and low TF expression levels, respectively. Non-invasive PET scans were acquired in tumor-bearing mice injected with 89 Zr-Df-ALT-836. Additionally, ex vivo biodistribution, blocking, and histological studies were performed to establish the affinity and specificity of 89 Zr-Df-ALT-836 for TF in vivo. 89 Zr-labeling of Df-ALT-836 was achieved in high yield and good specific activity. Flow cytometry and microscopy studies revealed no detectable difference in TF-binding affinity between ALT-836 and Df-ALT-836 in vitro. Longitudinal PET scans unveiled a lasting and prominent 89 Zr-Df-ALT-836 uptake in BXPC-3 tumors (peak at 31.5±6.0%ID/g at 48h post-injection; n=3), which was significantly abrogated (2.3±0.5%ID/g at 48h post-injection; n=3) when mice were pre-injected with a blocking dose (50mg/kg) of unlabeled ALT-836. Ex vivo biodistribution data confirmed the accuracy of the PET results, and histological analysis correlated high tumor uptake with in situ TF expression. Taken together, these results attest to the excellent affinity and TF-specificity of 89 Zr-Df-ALT-836. With elevated, persistent, and specific accumulation in TF-positive BXPC-3 tumors, PET imaging using 89 Zr-Df-ALT-836 promises to open new avenues for improving future diagnosis, stratification, and treatment response assessment in pancreatic cancer patients. Copyright © 2017 Elsevier B.V. All rights reserved.

The Transferrin Receptor: A Potential Molecular Imaging Marker for Human Cancer1

PubMed Central

Högemann-Savellano, Dagmar; Bos, Erik; Blondet, Cyrille; Sato, Fuminori; Abe, Tatsuya; Josephson, Lee; Weissleder, Ralph; Gaudet, Justin; Sgroi, Dennis; Peters, Peter J.; Basilion, James P.

2003-01-01

Abstract Noninvasive imaging of differences between the molecular properties of cancer and normal tissue has the potential to enhance the detection of tumors. Because overexpression of endogenous transferrin receptor (TfR) has been qualitatively described for various cancers and is presumably due to malignant transformation of cells, TfR may represent a suitable target for application of molecular imaging technologies to increase detection of smaller tumors. In the work reported here, investigation into the biology of this receptor using electron microscopy has demonstrated that iron oxide particles targeted to TfR are internalized and accumulate in lysosomal vesicles within cells. Biochemical analysis of the interaction of imaging probes with cells overexpressing the TfR demonstrated that the extent of accumulation, and therefore probe efficacy, is dependent on the nature of the chemical cross-link between transferrin and the iron oxide particle. These data were utilized to design and synthesize an improved imaging probe. Experiments demonstrate that the novel magnetic resonance imaging (MRI) probe is sensitive enough to detect small differences in endogenous TfR expression in human cancer cell lines. Quantitative measurement of TfR overexpression in a panel of 27 human breast cancer patients demonstrated that 74% of patient cancer tissues overexpressed the TfR and that the sensitivity of the new imaging agent was suitable to detect TfR overexpression in greater than 40% of these cases. Based on a biochemical and cell biological approach, these studies have resulted in the synthesis and development of an improved MRI probe with the best in vitro and in vivo imaging properties reported to date. PMID:14965443

The construction of a novel kind of non-viral gene delivery vector based on protein as core backbone.

PubMed

Li, D; Kong, Y; Yu, H; Lehtinen, A; Huang, H; Shen, F; Min, L; Zhou, J; Tang, G; Wang, Q

2008-04-01

A novel kind of non-viral gene delivery vector based on transferrin (Tf) as the core component was constructed with high transfection efficiency and low toxicity. The synthesis vector of Tf-PEI600 was confirmed by different physicochemical methods, including (1)H nuclear magnetic resonance, gel permeation chromatography, X-ray and thermogravimetric analysis. The cytotoxicity and gene delivery efficiency of the synthesized vector were verified by in vitro experiments. The agarose gel electrophoresis assay indicated that the novel copolymer Tf-PEI600 could efficiently condense plasmid DNA and the condensed nanoparticles exhibited a spherical shape. As the weight ratio of Tf-PEI600 to DNA reached 15.0, the particle size (about 200 nm) and the zeta potential (about 20 mV) of the nanoparticles became optimal for gene delivery. The methylthiazolyl tetrazolium (MTT) assay showed the cytotoxicity of Tf-PEI600 to be similar to that of PEI600 and much lower than that of PEI25kDa. In gene-delivery experiments with COS-7 cells and HepG2 cells, the Tf-PEI600 showed about a 30- to 53-fold higher efficiency than PEI600 and nearly equal to that of PEI25kDa. These data suggest that Tf-PEI600, with the advantages of low toxicity and high gene-delivery efficiency, might have great prospects in the practice of gene delivery. The core-shell structure of Tf-PEI600 also provided a novel strategy for the construction of non-viral gene delivery vectors.

Dietary exposure to the endocrine disruptor tolylfluanid promotes global metabolic dysfunction in male mice.

PubMed

Regnier, Shane M; Kirkley, Andrew G; Ye, Honggang; El-Hashani, Essam; Zhang, Xiaojie; Neel, Brian A; Kamau, Wakanene; Thomas, Celeste C; Williams, Ayanna K; Hayes, Emily T; Massad, Nicole L; Johnson, Daniel N; Huang, Lei; Zhang, Chunling; Sargis, Robert M

2015-03-01

Environmental endocrine disruptors are implicated as putative contributors to the burgeoning metabolic disease epidemic. Tolylfluanid (TF) is a commonly detected fungicide in Europe, and previous in vitro and ex vivo work has identified it as a potent endocrine disruptor with the capacity to promote adipocyte differentiation and induce adipocytic insulin resistance, effects likely resulting from activation of glucocorticoid receptor signaling. The present study extends these findings to an in vivo mouse model of dietary TF exposure. After 12 weeks of consumption of a normal chow diet supplemented with 100 parts per million TF, mice exhibited increased body weight gain and an increase in total fat mass, with a specific augmentation in visceral adipose depots. This increased adipose accumulation is proposed to occur through a reduction in lipolytic and fatty acid oxidation gene expression. Dietary TF exposure induced glucose intolerance, insulin resistance, and metabolic inflexibility, while also disrupting diurnal rhythms of energy expenditure and food consumption. Adipose tissue endocrine function was also impaired with a reduction in serum adiponectin levels. Moreover, adipocytes from TF-exposed mice exhibited reduced insulin sensitivity, an effect likely mediated through a specific down-regulation of insulin receptor substrate-1 expression, mirroring effects of ex vivo TF exposure. Finally, gene set enrichment analysis revealed an increase in adipose glucocorticoid receptor signaling with TF treatment. Taken together, these findings identify TF as a novel in vivo endocrine disruptor and obesogen in mice, with dietary exposure leading to alterations in energy homeostasis that recapitulate many features of the metabolic syndrome.

Gastrointestinal tolerance and plasma status of carotenoids, EPA and DHA with a fiber-enriched tube feed in hospitalized patients initiated on tube nutrition: Randomized controlled trial.

PubMed

Jakobsen, L H; Wirth, R; Smoliner, C; Klebach, M; Hofman, Z; Kondrup, J

2017-04-01

During the first days of tube feeding (TF) gastrointestinal (GI) complications are common and administration of sufficient nutrition is a challenge. Not all standard nutritionally complete formulas contain dietary fiber, fish oil or carotenoids, key dietary nutrients for health and wellbeing. The aim of this study was to investigate the effects of a fiber, fish oil and carotenoid enriched TF formula on diarrhea, constipation and nutrient bioavailability. A multi-center randomized, double-blind, controlled, parallel trial compared the effects of a dietary fiber, fish oil and carotenoid-enriched TF formula (test) with an isocaloric non-enriched formula (control) in 51 patients requiring initiation of TF. Incidence of diarrhea and constipation (based on stool frequency and consistency) was recorded daily. Plasma status of EPA, DHA and carotenoids was measured after 7 days. The incidence of diarrhea was lower in patients receiving the test formula compared with the control group (19% vs. 48%, p = 0.034). EPA and DHA status (% of total plasma phospholipids) was higher after 7 days in test compared with control group (EPA: p = 0.002, DHA: p = 0.082). Plasma carotenoid levels were higher after 7 days in the test group compared with control group (lutein: p = 0.024, α-carotene: p = 0.005, lycopene: p = 0.020, β-carotene: p = 0.054). This study suggests that the nutrient-enriched TF formula tested might have a positive effect on GI tolerance with less diarrhea incidence and significantly improved EPA, DHA and carotenoid plasma levels during the initiation of TF in hospitalized patients who are at risk of diarrhea and low nutrient status. This trial was registered at trialregister.nl; registration number 2924. Copyright © 2016. Published by Elsevier Ltd.

Differential co-expression analysis of rheumatoid arthritis with microarray data.

PubMed

Wang, Kunpeng; Zhao, Liqiang; Liu, Xuefeng; Hao, Zhenyong; Zhou, Yong; Yang, Chuandong; Li, Hongqiang

2014-11-01

The aim of the present study was to investigate the underlying molecular mechanisms of rheumatoid arthritis (RA) using microarray expression profiles from osteoarthritis and RA patients, to improve diagnosis and treatment strategies for the condition. The gene expression profile of GSE27390 was downloaded from Gene Expression Omnibus, including 19 samples from patients with RA (n=9) or osteoarthritis (n=10). Firstly, the differentially expressed genes (DEGs) were obtained with the thresholds of |logFC|>1.0 and P<0.05, using the t‑test method in LIMMA package. Then, differentially co-expressed genes (DCGs) and differentially co-expressed links (DCLs) were screened with q<0.25 by the differential coexpression analysis and differential regulation analysis of gene expression microarray data package. Secondly, pathway enrichment analysis for DCGs was performed by the Database for Annotation, Visualization and Integrated Discovery and the DCLs associated with RA were selected by comparing the obtained DCLs with known transcription factor (TF)-targets in the TRANSFAC database. Finally, the obtained TFs were mapped to the known TF-targets to construct the network using cytoscape software. A total of 1755 DEGs, 457 DCGs and 101988 DCLs were achieved and there were 20 TFs in the obtained six TF-target relations (STAT3-TNF, PBX1‑PLAU, SOCS3-STAT3, GATA1-ETS2, ETS1-ICAM4 and CEBPE‑GATA1) and 457 DCGs. A number of TF-target relations in the constructed network were not within DCLs when the TF and target gene were DCGs. The identified TFs may have an important role in the pathogenesis of RA and have the potential to be used as biomarkers for the development of novel diagnostic and therapeutic strategies for RA.

The potential of transferrin-pendant-type polyethyleneglycol liposomes encapsulating decahydrodecaborate-{sup 1}B (GB-10) as {sup 1}B-carriers for boron neutron capture therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Masunaga, Shin-ichiro; Kasaoka, Satoshi; Maruyama, Kazuo

2006-12-01

Purpose: To evaluate GB-10-encapsulating transferrin (TF)-pendant-type polyethyleneglycol (PEG) liposomes as tumor-targeting {sup 1}B-carriers for boron neutron capture therapy. Methods and Materials: A free mercaptoundecahydrododecaborate-{sup 1}B (BSH) or decahydrodecaborate-{sup 1}B (GB-10) solution, bare liposomes, PEG liposomes, or TF-PEG liposomes were injected into SCC VII tumor-bearing mice, and {sup 1}B concentrations in the tumors and normal tissues were measured by {gamma}-ray spectrometry. Meanwhile, tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all intratumor proliferating cells, then injected with these {sup 1}B-carriers containing BSH or GB-10 in the same manner. Right after thermal neutron irradiation, the response of quiescent (Q) cells wasmore » assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The frequency in the total tumor cells was determined from the BrdU nontreated tumors. Results: Transferrin-PEG liposomes showed a prolonged retention in blood circulation, low uptake by reticuloendothelial system, and the most enhanced accumulation of {sup 1}B in solid tumors. In general, the enhancing effects were significantly greater in total cells than Q cells. In both cells, the enhancing effects of GB-10-containing {sup 1}B-carriers were significantly greater than BSH-containing {sup 1}B-carriers, whether loaded in free solution or liposomes. In both cells, whether BSH or GB-10 was employed, the greatest enhancing effect was observed with TF-PEG liposomes followed in decreasing order by PEG liposomes, bare liposomes, and free BSH or GB-10 solution. In Q cells, the decrease was remarkable between PEG and bare liposomes. Conclusions: In terms of biodistribution characteristics and tumor cell-killing effect as a whole, including Q cells, GB-10 TF-PEG liposomes were regarded as promising {sup 1}B-carriers.« less

Adult perceptions of dental fluorosis and select dental conditions-an Asian perspective.

PubMed

Nair, Rahul; Chuang, Janice Cheah Ping; Lee, Pauline Shih Jia; Leo, Song Jie; Yang, Naomi QiYue; Yee, Robert; Tong, Huei Jinn

2016-04-01

To compare lay people's perceptions with regard to various levels of dental fluorosis and select dental defects versus normal dentition. Adults rated digitally created photographs made showing lips (without retraction) and teeth depicting the following conditions: no apparent aesthetic defects (normal, Thylstrup- Fejerskov score 0 - TF0), 6 levels of fluorosis (TF1-6), carious lesions (two cavitated and one noncavitated), malocclusions (Class II, Class III, anterior open bite and greater spacing), extrinsic staining and an incisal chip. The photographs were displayed on colour-calibrated iPads(™) . Participants used a self-administered questionnaire to rate their perceptions on (Item 1) how normal teeth were, (Item 2) how attractive the teeth were, (Item 3) need to seek correction of teeth, (Item 4) how well the person took care of their teeth and (Item 5) whether the person was born like this. Data from Item 5 were excluded due to low reliability. Ratings for Item 1 showed that TF1-4 was similar or significantly better than TF0. For Item 2, TF1 and TF4 were significantly better than TF0, with TF2 and TF3 being similar. For Item 3, there was significantly lower need to seek correction with TF2 and TF4 versus TF0, whereas TF1 and TF3 were similar to TF0. TF5 and TF6 were rated significantly lower than TF0 for Item 1 and Item 2, and significantly higher rating for Item 3 (need to seek correction). Ratings for Item 4 were similar, with TF1, TF2 and TF4 being rated significantly higher than TF0, and TF5 and TF6 being rated lower. Cavitated caries and staining were generally perceived as being significantly less favourable than TF6, with higher need to seek correction as well. Noncavitated carious lesion and incisal chip were rated similar to TF0. Cavitated carious lesions were rated aesthetically similar or significantly worse than TF0 and TF6. Severe fluorosis (TF5 and 6) was perceived to be less aesthetically pleasing and received higher ratings for need to seek correction than normal teeth. Mild-to-moderate fluorosis (TF1-4) showed similar or better aesthetic perceptions and similar or lower need to seek correction, when compared to normal teeth (TF0). Easily visible cavitated dental caries was rated worse than teeth with severe fluorosis (TF6) and normal teeth (TF0). © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Participation in Adult Education for Community Development: A Critical Discourse Analysis of "Training for Transformation"

ERIC Educational Resources Information Center

Krupar, Allyson M.; Prins, Esther

2016-01-01

Participation has become so central to adult education for community development that even the World Bank supports participatory programming. This article analyses how participation is conceptualised in "Training for Transformation" (TfT), a Freirean-inspired curriculum used in international community development settings. TfT seeks to…

A novel transferrin receptor-targeted hybrid peptide disintegrates cancer cell membrane to induce rapid killing of cancer cells

PubMed Central

2011-01-01

Background Transferrin receptor (TfR) is a cell membrane-associated glycoprotein involved in the cellular uptake of iron and the regulation of cell growth. Recent studies have shown the elevated expression levels of TfR on cancer cells compared with normal cells. The elevated expression levels of this receptor in malignancies, which is the accessible extracellular protein, can be a fascinating target for the treatment of cancer. We have recently designed novel type of immunotoxin, termed "hybrid peptide", which is chemically synthesized and is composed of target-binding peptide and lytic peptide containing cationic-rich amino acids components that disintegrates the cell membrane for the cancer cell killing. The lytic peptide is newly designed to induce rapid killing of cancer cells due to conformational change. In this study, we designed TfR binding peptide connected with this novel lytic peptide and assessed the cytotoxic activity in vitro and in vivo. Methods In vitro: We assessed the cytotoxicity of TfR-lytic hybrid peptide for 12 cancer and 2 normal cell lines. The specificity for TfR is demonstrated by competitive assay using TfR antibody and siRNA. In addition, we performed analysis of confocal fluorescence microscopy and apoptosis assay by Annexin-V binding, caspase activity, and JC-1 staining to assess the change in mitochondria membrane potential. In vivo: TfR-lytic was administered intravenously in an athymic mice model with MDA-MB-231 cells. After three weeks tumor sections were histologically analyzed. Results The TfR-lytic hybrid peptide showed cytotoxic activity in 12 cancer cell lines, with IC50 values as low as 4.0-9.3 μM. Normal cells were less sensitive to this molecule, with IC50 values > 50 μM. Competition assay using TfR antibody and knockdown of this receptor by siRNA confirmed the specificity of the TfR-lytic hybrid peptide. In addition, it was revealed that this molecule can disintegrate the cell membrane of T47D cancer cells just in 10 min, to effectively kill these cells and induce approximately 80% apoptotic cell death but not in normal cells. The intravenous administration of TfR-lytic peptide in the athymic mice model significantly inhibited tumor progression. Conclusions TfR-lytic peptide might provide a potent and selective anticancer therapy for patients. PMID:21849092

Reverse Transcription of a Self-Primed Retrotransposon Requires an RNA Structure Similar to the U5-IR Stem-Loop of Retroviruses

PubMed Central

Lin, Jia-Hwei; Levin, Henry L.

1998-01-01

An inverted repeat (IR) within the U5 region of the Rous sarcoma virus (RSV) mRNA forms a structure composed of a 7-bp stem and a 5-nucleotide (nt) loop. This U5-IR structure has been shown to be required for the initiation of reverse transcription. The mRNA of Tf1, long terminal repeat-containing retrotransposon from fission yeast (Schizosaccharomyces pombe) contains nucleotides with the potential to form a U5-IR stem-loop that is strikingly similar to that of RSV. The putative U5-IR stem-loop of Tf1 consists of a 7-bp stem and a 25-nt loop. Results from mutagenesis studies indicate that the U5-IR stem-loop in the mRNA of Tf1 does form and that it is required for Tf1 transposition. Although the loop is required for transposition, we were surprised that the specific sequence of the nucleotides within the loop was unimportant for function. Additional investigation indicates that the loss of transposition activity due to a reduction in the loop size to 6 nt could be rescued by increasing the GC content of the stem. This result indicates that the large loop in the Tf1 mRNA relative to that of the RSV allows the formation of the relatively weak U5-IR stem. The levels of Tf1 proteins expressed and the amounts of Tf1 RNA packaged into the virus-like particles were not affected by mutations in the U5-IR structure. However, all of the mutations in the U5-IR structure that caused defects in transposition produced low amounts of reverse transcripts. A unique feature in the initiation of Tf1 reverse transcription is that, instead of a tRNA, the first 11 nt of the Tf1 mRNA serve as the minus-strand primer. Analysis of the 5′ end of Tf1 mRNA revealed that the mutations in the U5-IR stem-loop that resulted in defects in reverse transcription caused a reduction in the cleavage activity required to generate the Tf1 primer. Our results indicate that the U5-IR stems of Tf1 and RSV are conserved in size, position, and function. PMID:9774699

Divergent Binding and Transactivation by Two Related Steroid Receptors at the Same Response Element*

PubMed Central

Tesikova, Martina; Dezitter, Xavier; Nenseth, Hatice Z.; Klokk, Tove I.; Mueller, Florian; Hager, Gordon L.; Saatcioglu, Fahri

2016-01-01

Transcription factor (TF) recruitment to chromatin is central to activation of transcription. TF-chromatin interactions are highly dynamic, which are evaluated by recovery half time (t1/2) in seconds, determined by fluorescence recovery experiments in living cells, and chromatin immunoprecipitation (ChIP) analysis, measured in minutes. These two states are related: the larger the t1/2, the longer the ChIP occupancy resulting in increased transcription. Here we present data showing that this relationship does not always hold. We found that histone deacetylase inhibitors (HDACis) significantly increased t1/2 of green fluorescent protein (GFP) fused androgen receptor (AR) on a tandem array of positive hormone response elements (HREs) in chromatin. This resulted in increased ChIP signal of GFP-AR. Unexpectedly, however, transcription was inhibited. In contrast, the GFP-fused glucocorticoid receptor (GR), acting through the same HREs, displayed a profile consistent with current models. We provide evidence that these differences are mediated, at least in part, by HDACs. Our results provide insight into TF action in living cells and show that very closely related TFs may trigger significantly divergent outcomes at the same REs. PMID:27056330

A proteome analysis of freezing tolerance in red clover (Trifolium pratense L.).

PubMed

Bertrand, Annick; Bipfubusa, Marie; Castonguay, Yves; Rocher, Solen; Szopinska-Morawska, Aleksandra; Papadopoulos, Yousef; Renaut, Jenny

2016-03-10

Improvement of freezing tolerance of red clover (Trifolium pratense L.) would increase its persistence under cold climate. In this study, we assessed the freezing tolerance and compared the proteome composition of non-acclimated and cold-acclimated plants of two initial cultivars of red clover: Endure (E-TF0) and Christie (C-TF0) and of populations issued from these cultivars after three (TF3) and four (TF4) cycles of phenotypic recurrent selection for superior freezing tolerance. Through this approach, we wanted to identify proteins that are associated with the improvement of freezing tolerance in red clover. Freezing tolerance expressed as the lethal temperature for 50 % of the plants (LT50) increased markedly from approximately -2 to -16 °C following cold acclimation. Recurrent selection allowed a significant 2 to 3 °C increase of the LT50 after four cycles of recurrent selection. Two-dimensional difference gel electrophoresis (2D-DIGE) was used to study variations in protein abundance. Principal component analysis based on 2D-DIGE revealed that the largest variability in the protein data set was attributable to the cold acclimation treatment and that the two genetic backgrounds had differential protein composition in the acclimated state only. Vegetative storage proteins (VSP), which are essential nitrogen reserves for plant regrowth, and dehydrins were among the most striking changes in proteome composition of cold acclimated crowns of red clovers. A subset of proteins varied in abundance in response to selection including a dehydrin that increased in abundance in TF3 and TF4 populations as compared to TF0 in the Endure background. Recurrent selection performed indoor is an effective approach to improve the freezing tolerance of red clover. Significant improvement of freezing tolerance by recurrent selection was associated with differential accumulation of a small number of cold-regulated proteins that may play an important role in the determination of the level of freezing tolerance.

Radical-scavenging abilities and antioxidant properties of theaflavins and their gallate esters in H2O2-mediated oxidative damage system in the HPF-1 cells.

PubMed

Yang, Ziyin; Jie, Guoliang; Dong, Fang; Xu, Yi; Watanabe, Naoharu; Tu, Youying

2008-08-01

The antioxidant properties of theaflavins and their gallate esters, namely theaflavin (TF1), theaflavin-3(3')-gallate (TF2) and theaflavin-3,3'-digallate (TF3) were investigated by comparing with epigallocatechin gallate (EGCG). The order of hydroxyl radicals-scavenging ability was TF3>TF2>TF1>EGCG. The order of 2,2-diphenyl-1-picrylhydrazyl scavenging ability was TF3>TF2>EGCG>TF1. TF1, TF2, and TF3 showed more effective effects than EGCG in protection against H2O2-mediated damage in HPF-1 cells. TF2 was the most potent accelerant of HPF-1 cell proliferation. TF1, TF2 and TF3 suppressed the accumulation of intracellular reactive species in H2O2-mediated damage HPF-1 cells. Pre-treated for 2h and eliminated from the cells, TF1 and TF3 still showed protective effects against H2O2-mediated damage in HPF-1 cells. This suggests that the protective effects of TF1 and TF3 on oxidative damage HPF-1 cells may be responsible for other mechanisms, rather than only scavenging the already formed reactive species. It remains to be determined whether TF1 and TF3 improved the normal HPF-1 cell resistive abilities toward radical-damage in pre-treatment. Further studies of the effects of theaflavins on some enzymes or signal transduction in the normal HPF-1 cells are underway.

CASL VMA FY16 Milestone Report (L3:VMA.VUQ.P13.07) Westinghouse Mixing with COBRA-TF

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gordon, Natalie

2016-09-30

COBRA-TF (CTF) is a low-resolution code currently maintained as CASL's subchannel analysis tool. CTF operates as a two-phase, compressible code over a mesh comprised of subchannels and axial discretized nodes. In part because CTF is a low-resolution code, simulation run time is not computationally expensive, only on the order of minutes. Hi-resolution codes such as STAR-CCM+ can be used to train lower-fidelity codes such as CTF. Unlike STAR-CCM+, CTF has no turbulence model, only a two-phase turbulent mixing coefficient, β. β can be set to a constant value or calculated in terms of Reynolds number using an empirical correlation. Resultsmore » from STAR-CCM+ can be used to inform the appropriate value of β. Once β is calibrated, CTF runs can be an inexpensive alternative to costly STAR-CCM+ runs for scoping analyses. Based on the results of CTF runs, STAR-CCM+ can be run for specific parameters of interest. CASL areas of application are CIPS for single phase analysis and DNB-CTF for two-phase analysis.« less

Analysis of morphological, structural and electrical properties of annealed TiO2 nanowires deposited by GLAD technique

NASA Astrophysics Data System (ADS)

Shougaijam, B.; Swain, R.; Ngangbam, C.; Lenka, T. R.

2017-06-01

The effect of annealing on vertically aligned TiO2 NWs deposited by glancing angle deposition (GLAD) method on Si substrate using pressed and sintered TiO2 pellets as source material is studied. The FE-SEM images reveal the retention of vertically aligned NWs on Si substrate after annealing process. The EDS analysis of TiO2 NWs sample annealed at 600 °C in air for 1 h shows the higher weight percentage ratio of ˜2.6 (i.e., 72.27% oxygen and 27.73% titanium). The XRD pattern reveals that the polycrystalline nature of anatase TiO2 dominates the annealed NWs sample. The electrical characteristics of Al/TiO2-NWs/TiO2-TF/p-Si (NW device) and Al/TiO2-TF/p-Si (TF device) based on annealed samples are compared. It is riveting to observe a lower leakage current of ˜1.32 × 10-7 A/cm2 at +1 V with interface trap density of ˜6.71 × 1011 eV-1 cm-2 in NW device compared to ˜2.23 × 10-7 A/cm2 in TF device. The dominant leakage mechanism is investigated to be generally Schottky emission; however Poole-Frenkel emission also takes place during high reverse bias beyond 4 V for NWs and 3 V for TF device.

Fractional order absolute vibration suppression (AVS) controllers

NASA Astrophysics Data System (ADS)

Halevi, Yoram

2017-04-01

Absolute vibration suppression (AVS) is a control method for flexible structures. The first step is an accurate, infinite dimension, transfer function (TF), from actuation to measurement. This leads to the collocated, rate feedback AVS controller that in some cases completely eliminates the vibration. In case of the 1D wave equation, the TF consists of pure time delays and low order rational terms, and the AVS controller is rational. In all other cases, the TF and consequently the controller are fractional order in both the delays and the "rational parts". The paper considers stability, performance and actual implementation in such cases.

NMR relaxometric probing of ionic liquid dynamics and diffusion under mesoscopic confinement within bacterial cellulose ionogels

NASA Astrophysics Data System (ADS)

Smith, Chip J.; Gehrke, Sascha; Hollóczki, Oldamur; Wagle, Durgesh V.; Heitz, Mark P.; Baker, Gary A.

2018-05-01

Bacterial cellulose ionogels (BCIGs) represent a new class of material comprising a significant content of entrapped ionic liquid (IL) within a porous network formed from crystalline cellulose microfibrils. BCIGs suggest unique opportunities in separations, optically active materials, solid electrolytes, and drug delivery due to the fact that they can contain as much as 99% of an IL phase by weight, coupled with an inherent flexibility, high optical transparency, and the ability to control ionogel cross-sectional shape and size. To allow for the tailoring of BCIGs for a multitude of applications, it is necessary to better understand the underlying principles of the mesoscopic confinement within these ionogels. Toward this, we present a study of the structural, relaxation, and diffusional properties of the ILs, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([emim][Tf2N]) and 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide ([bmpy][Tf2N]), using 1H and 19F NMR T1 relaxation times, rotational correlation times, and diffusion ordered spectroscopy (DOSY) diffusion coefficients, accompanied by molecular dynamics (MD) simulations. We observed that the cation methyl groups in both ILs were primary points of interaction with the cellulose chains and, while the pore size in cellulose is rather large, [emim]+ diffusion was slowed by ˜2-fold, whereas [Tf2N]- diffusion was unencumbered by incorporation in the ionogel. While MD simulations of [bmpy][Tf2N] confinement at the interface showed a diffusion coefficient decrease roughly 3-fold compared to the bulk liquid, DOSY measurements did not reveal any significant changes in diffusion. This suggests that the [bmpy][Tf2N] alkyl chains dominate diffusion through formation of apolar domains. This is in contrast to [emim][Tf2N] where delocalized charge appears to preclude apolar domain formation, allowing interfacial effects to be manifested at a longer range in [emim][Tf2N].

Change in Parental Depressive Symptoms in Trauma-Focused Cognitive-Behavioral Therapy: Results from a Randomized Controlled Trial.

PubMed

Tutus, Dunja; Keller, Ferdinand; Sachser, Cedric; Pfeiffer, Elisa; Goldbeck, Lutz

2017-03-01

Depressive symptoms are frequently described in parents whose children have been exposed to traumatic events. Hence, including nonoffending parents in trauma-focused cognitive-behavioral therapy (TF-CBT) for children and adolescents may help both children and their parents to cope with the trauma. Up to now, three randomized controlled trials have investigated parental depressive symptoms after TF-CBT. Given the ambiguous results, further effectiveness trials are needed to investigate parental benefit from TF-CBT. The aim of this study is to determine whether TF-CBT is superior to waitlist (WL) regarding change in parental depressive symptoms. Parents, N = 84, whose children (age 6-17 years) were randomly assigned to either 12 sessions of TF-CBT (n = 40) or to WL condition (n = 44) completed the Beck Depression Inventory-Second Edition (BDI-II) for pre-post comparison. The group difference was tested through repeated-measures analyses of variance (ANOVA). The change in parental depressive symptoms was additionally categorized using the reliable change index. Repeated-measures ANOVA indicated a significant time effect F(1, 82) = 2.55, p = 0.02, and no significant time-group interaction F(1, 82) = 1.09, p = 0.30, suggesting a similar reduction in parental depressive symptoms in both groups. Across both conditions, most of the parents remained unchanged (n = 62), some of them improved (n = 17), and a few deteriorated (n = 5). There was no significant difference between the conditions (χ 2 (2) = 1.74; p = 0.42). Contrary to findings of several previous studies, our results suggest no superiority of TF-CBT in comparison with WL regarding change in depressive symptoms in parents. This might be due to different types of the child's trauma. Parental benefit from TF-CBT was found in samples of sexually abused, but not in children and adolescents exposed to diverse trauma types.

Kinetics of ATP hydrolysis catalyzed by isolated TF1 and reconstituted TF0F1 ATPase.

PubMed

Rögner, M; Gräber, P

1986-09-01

The rate of ATP hydrolysis catalyzed by isolated TF1 and reconstituted TF0F1 was measured as a function of the ATP concentration in the presence of inhibitors [ADP, Pi and 3'-O-(1-naphthoyl)ATP]. ATP hydrolysis can be described by Michaelis-Menten kinetics with Km(TF1) = 390 microM and Km (TF0F1) = 180 microM. The inhibition constants are for ADP Ki(TF1) = 20 microM and Ki(TF0F1) = 100 microM, for 3'-O-(1-naphthoyl)ATP Ki(TF1) = 150 microM and Ki(TF0F1) = 3 microM, and for Pi Ki(TF1) = 60 mM. From these results it is concluded that upon binding of TF0 to TF1 the mechanism of ATP hydrolysis catalyzed by TF1 is not changed qualitatively; however, the kinetic constants differ quantitatively.

Detection of von Willebrand factor and tissue factor in platelets-fibrin rich coronary thrombi in acute myocardial infarction.

PubMed

Yamashita, Atsushi; Sumi, Takahiro; Goto, Shinya; Hoshiba, Yasunari; Nishihira, Kensaku; Kawamoto, Riichirou; Hatakeyama, Kinta; Date, Haruhiko; Imamura, Takuroh; Ogawa, Hisao; Asada, Yujiro

2006-01-01

The rapid closure of coronary arteries due to occlusive thrombi is the major cause of acute myocardial infarction. However, the mechanisms of coronary thrombus formation have not been elucidated. We immunohistochemically assessed the localizations and their changes over time of glycoprotein IIb/IIIa, fibrin, von Willebrand factor (vWF), and tissue factor (TF), after the onset of chest pain (<4, 4 to 6, or 6 to 12 hours), in fresh coronary thrombi causing acute myocardial infarction. The occlusive thrombi were consistently composed of platelets, fibrin, vWF, and TF from the early phase of onset, and glycoprotein IIb/IIIa and fibrin were closely associated with vWF and TF, respectively. vWF and/or TF may contribute to occlusive thrombus formation and be novel therapeutic candidates for treating patients with coronary thrombosis.

Factors related to fruit, vegetable and traditional food consumption which may affect health among Alaska Native People in Western Alaska

PubMed Central

Johnson, Jennifer S.; Nobmann, Elizabeth D.; Asay, Elvin

2012-01-01

Objectives Determine intake of fruits, vegetables and traditional foods (TF), availability of foods, and attitudes towards increasing their consumption. Study design Establish community baseline through a cross-sectional sample of residents who were weighed, measured and interviewed. Village stores were surveyed for food availability, price and quality. Methods Eighty-eight respondents self-identified as the household member primarily responsible for food shopping and cooking were surveyed in 3 Western Alaska Native villages using a food frequency questionnaire, and village stores were evaluated using food environment surveys. Results Overweight (BMI[kg/m2] >25) was present in 68% of participants. Fruit and vegetable intake (3.3 median servings/day) was low in comparison to recommended intakes of 5–9 servings/d. Seventy-two per cent were eating less than 5 servings/d of fruits and vegetables combined. Thirty-four per cent of respondents were trying to eat more vegetables; 41% were trying to eat more fruits. The median number of servings of TF was 3.2/d (mean 4.3/d). Seventy-seven per cent of respondents reported that they ate enough TF. Conclusion Recommendations to continue use of TF and increase intake of fruits and vegetables are consistent with local attitudes. Our findings indicate that increasing the availability of fruits and vegetables would be well received. Information from this study provides a basis for nutrition education and food supplement programs that is responsive to the needs and perceptions of the residents. Continued TF intake and increased fruit and vegetable intake have the potential to benefit the health of rural residents. PMID:22456043

Patellofemoral joint contact forces during activities with high knee flexion.

PubMed

Trepczynski, Adam; Kutzner, Ines; Kornaropoulos, Evgenios; Taylor, William R; Duda, Georg N; Bergmann, Georg; Heller, Markus O

2012-03-01

The patellofemoral (PF) joint plays an essential role in knee function, but little is known about the in vivo loading conditions at the joint. We hypothesized that the forces at the PF joint exceed the tibiofemoral (TF) forces during activities with high knee flexion. Motion analysis was performed in two patients with telemetric knee implants during walking, stair climbing, sit-to-stand, and squat. TF and PF forces were calculated using a musculoskeletal model, which was validated against the simultaneously measured in vivo TF forces, with mean errors of 10% and 21% for the two subjects. The in vivo peak TF forces of 2.9-3.4 bodyweight (BW) varied little across activities, while the peak PF forces showed significant variability, ranging from less than 1 BW during walking to more than 3 BW during high flexion activities, exceeding the TF forces. Together with previous in vivo measurements at the hip and knee, the PF forces determined here provide evidence that peak forces across these joints reach values of around 3 BW during high flexion activities, also suggesting that the in vivo loading conditions at the knee can only be fully understood if the forces at the TF and the PF joints are considered together. Copyright © 2011 Orthopaedic Research Society.

Clinical features and outcome of typhoid fever and invasive non-typhoidal salmonellosis in a tertiary hospital in Belgium: analysis and review of the literature.

PubMed

Yombi, J C; Martins, L; Vandercam, B; Rodriguez-Villalobos, H; Robert, A

2015-08-01

Typhoid fever (TF) occurs rarely in industrialized countries because of advances in health care and improvement of drinking water. Conversely, non-typhoid salmonellosis (NTS) remains widespread, because of food contamination or asymptomatic carriage. Non-typhoid salmonellosis can be severe when becoming invasive non-typhoid salmonellosis (iNTS). Although established prognostic indicators of the two pathologies are different, direct comparisons between iNTS and TF in the literature remain scarce. The purpose of this study was to analyse and compare demographic, clinical features and outcome of hospitalized patients with TF and iNTS. Demographic, clinical features and outcome were retrospectively analysed in a series of patients hospitalized between 2007 and 2012. A total of 33 patients were enrolled, including 13 with established TF and 20 with iNTS. No differences between TF and iNTS patients were observed in incidence of fever, abdominal cramps, diarrhoea, headache, nausea and vomiting and duration of antibiotic therapy (≤ 7 days in both groups). Although the clinical outcome of TF patients was identical to that of iNTS patients, including incidence of complications, length of hospitalization and mortality (1/13 (7.7%) vs 2/20 (10%), P = 0.43), comorbidities were less frequent in the TF group than in the iNTS group (2/13 vs 15/20, P = 0.003). The clinical profile and outcome of TF patients are similar to those with iNTS. Although comorbidities are more often associated with iNTS, the results of our study suggest that clinical management of these two diseases should remain similar.

Low-Energy Ultrasound Treatment Improves Regional Tumor Vessel Infarction by Retargeted Tissue Factor.

PubMed

Brand, Caroline; Dencks, Stefanie; Schmitz, Georg; Mühlmeister, Mareike; Stypmann, Jörg; Ross, Rebecca; Hintelmann, Heike; Schliemann, Christoph; Müller-Tidow, Carsten; Mesters, Rolf M; Berdel, Wolfgang E; Schwöppe, Christian

2015-07-01

To enhance the regional antitumor activity of the vascular-targeting agent truncated tissue factor (tTF)-NGR by combining the therapy with low-energy ultrasound (US) treatment. For the in vitro US exposure of human umbilical vein endothelial cells (HUVECs), cells were put in the focus of a US transducer. For analysis of the US-induced phosphatidylserine (PS) surface concentration on HUVECs, flow cytometry was used. To demonstrate the differences in the procoagulatory efficacy of TF-derivative tTF-NGR on binding to HUVECs with a low versus high surface concentration of PS, we performed factor X activation assays. For low-energy US pretreatment, HT1080 fibrosarcoma xenotransplant-bearing nude mice were treated by tumor-regional US-mediated stimulation (ie, destruction) of microbubbles. The therapy cohorts received the tumor vessel-infarcting tTF-NGR protein with or without US pretreatment (5 minutes after US stimulation via intraperitoneal injection on 3 consecutive days). Combination therapy experiments with xenotransplant-bearing nude mice significantly increased the antitumor activity of tTF-NGR by regional low-energy US destruction of vascular microbubbles in tumor vessels shortly before application of tTF-NGR (P < .05). Mechanistic studies proved the upregulation of anionic PS on the outer leaflet of the lipid bilayer of endothelial cell membranes by low-energy US and a consecutive higher potential of these preapoptotic endothelial cells to activate coagulation via tTF-NGR and coagulation factor X as being a basis for this synergistic activity. Combining retargeted tTF to tumor vessels with proapoptotic stimuli for the tumor vascular endothelium increases the antitumor effects of tumor vascular infarction. Ultrasound treatment may thus be useful in this respect for regional tumor therapy. © 2015 by the American Institute of Ultrasound in Medicine.

The Endocrine Disrupting Chemical Tolylfluanid Alters Adipocyte Metabolism via Glucocorticoid Receptor Activation

PubMed Central

Neel, Brian A.; Brady, Matthew J.

2013-01-01

Glucocorticoid signaling plays a critical role in regulating energy metabolism. Emerging data implicate environmental endocrine-disrupting chemicals as contributors to the obesity and diabetes epidemics. Previous studies have shown that the phenylsulfamide fungicide tolylfluanid (TF) augments glucocorticoid receptor (GR)-dependent luciferase expression in 3T3-L1 preadipocytes while modulating insulin action in primary murine and human adipocytes. Studies were performed to interrogate glucocorticoid signaling in primary adipocytes exposed to TF. TF mimicked the gene transcription profile of the murine glucocorticoid corticosterone (Cort). Cellular fractionation assays demonstrated that TF treatment promoted the activating serine phosphorylation of GR, augmenting its cytoplasmic-to-nuclear translocation as well as its enrichment at glucocorticoid response elements on the glucocorticoid-induced leucine zipper gene promoter. After acute treatment, Cort or TF promoted insulin receptor substrate-1 (IRS-1) gene and protein expression. Either treatment also enriched GR binding at an identified glucocorticoid response element in the IRS-1 gene. TF or Cort each increased insulin-stimulated lipogenesis, an effect resulting from increased lipogenic gene expression and enhanced insulin-stimulated dephosphorylation of acetyl-coenzyme A carboxylase. The augmentation of insulin-stimulated lipogenesis was mediated through a specific enhancement of Akt phosphorylation at T308. These findings support modulation of IRS-1 levels as a mechanism for glucocorticoid-mediated changes in insulin action in primary adipocytes. Albeit with less affinity than Cort, in silico analysis suggests that TF can interact with the ligand binding pocket of GR. Collectively, these studies identify TF as a structurally unique environmental glucocorticoid. Glucocorticoid signaling may thus represent a novel pathway by which environmental toxicants promote the development of metabolic diseases. PMID:23340252

Interrelations of secondary structure stability and DNA-binding affinity in the bacteriophage SPO1-encoded type II DNA-binding protein TF1.

PubMed

Andera, L; Spangler, C J; Galeone, A; Mayol, L; Geiduschek, E P

1994-02-11

TF1, a homodimeric DNA-binding and -bending protein with a preference for hydroxymethyluracil-containing DNA is the Bacillus subtilis-encoded homolog of the bacterial HU proteins and of the E. coli integration host factor. A temperature-sensitive mutation at amino acid 25 of TF1 (L25-->A) and two intragenic second site revertants at amino acids 15 (E15-->G) and 32 (L32-->I) were previously identified and their effects on virus development were examined. The DNA-binding properties of these proteins and the thermal stability of their secondary structures have now been analyzed. Amino acids 15 and 32 are far removed from the putative DNA-binding domains of TF1 but changes there exert striking effects on DNA affinity that correlate with effects on structure. The double mutant protein TF1-G15I32 binds to a preferred site in hydroxymethyluracil-containing DNA 40 times more tightly, denatures at higher temperature (delta tm = 21 degrees C), and also exchanges subunits much more slowly than does the wild-type protein. The L25-->A mutation makes TF1 secondary structure and DNA-binding highly salt concentration-dependent. The E15-->G mutation partly suppresses this effect: secondary structure of TF1-A25G15 is restored at 21 degrees C by 1 M NaCl or, at low NaCl concentration, by binding to DNA.

Drivers of U.S. toxicological footprints trajectory 1998-2013

NASA Astrophysics Data System (ADS)

Koh, S. C. L.; Ibn-Mohammed, T.; Acquaye, A.; Feng, K.; Reaney, I. M.; Hubacek, K.; Fujii, H.; Khatab, K.

2016-12-01

By exploiting data from the Toxic Release Inventory of the United States, we have established that the toxicological footprint (TF) increased by 3.3% (88.4 Mt) between 1998 and 1999 and decreased by 39% (1088.5 Mt) between 1999 and 2013. From 1999 to 2006, the decreasing TF was driven by improvements in emissions intensity (i.e. gains in production efficiency) through toxic chemical management options: cleaner production; end of pipe treatment; transfer for further waste management; and production scale. In particular, the mining sector reduced its TF through outsourcing processes. Between 2006 and 2009, decreasing TF was due to decrease in consumption volume triggered by economic recession. Since 2009, the economic recovery increased TF, overwhelming the influence of improved emissions intensity through population growth, consumption and production structures. Accordingly, attaining a less-toxic economy and environment will be influenced by a combination of gains in production efficiency through improvement in emissions mitigation technologies and changes in consumption patterns. Overall, the current analysis highlights the structural dynamics of toxic chemical release and would inform future formulation of effective mitigation standards and management protocols towards the detoxification of the environment.

Changes in salivary periodontal pathogens after orthodontic treatment: An in vivo prospective study.

PubMed

Kim, Kyungsun; Jung, Woo-Sun; Cho, Soha; Ahn, Sug-Joon

2016-11-01

  To analyze the initial changes in salivary levels of periodontal pathogens after orthodontic treatment with fixed appliances.   The subjects consisted of 54 adult patients. The Simplified Oral Hygiene Index, Plaque Index, and Gingival Index were measured as periodontal parameters. Both the plaque and gingival indexes were obtained from the central and lateral incisors and first molars of both arches. Whole saliva and periodontal parameters were obtained at the following four time points: immediately before debonding (T1), 1 week after debonding (T2), 5 weeks after debonding (T3), and 13 weeks after debonding (T4). Repeated measures analysis of variance was used to determine salivary bacterial levels and periodontal parameters among the four time points after quantifying salivary levels of Aggregatibacter actinomycetemcomitans (Aa), Fusobacterium nucleatum (Fn), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Tannerella forsythia (Tf), and total bacteria using the real-time polymerase chain reaction.   All periodontal parameters were significantly decreased immediately after debonding (T2). The salivary levels of total bacteria and Pg were decreased at T3, while Pi and Tf levels were decreased at T4. However, the amount of Aa and Fn remained at similar levels in saliva during the experimental period. Interestingly, Aa and Fn were present in saliva at higher levels than were Pg, Pi, and Tf.   The higher salivary levels of Aa and Fn after debonding suggests that the risk of periodontal problems cannot be completely eliminated by the removal of fixed orthodontic appliances during the initial retention period, despite improved oral hygiene.

Activated factor XI and tissue factor in aortic stenosis: Links with thrombin generation

PubMed Central

Luszczak, Joanna; Undas, Anetta; Gissel, Matthew; Olszowska, Maria; Butenas, Saulius

2011-01-01

Introduction In our previous studies we showed that a significant proportion of patients with various cardiovascular diseases have active tissue factor (TF) and factor (F)XIa in their plasma. Objective To evaluate these two proteins in plasma from patients with aortic stenosis (AS) and established their relationship with the severity of the disease. Methods Fifty-four consecutive patients with AS, including 38 (70.4%) severe AS patients, were studied. Plasma FXIa and TF activity were determined in clotting assays by measuring the response to inhibitory monoclonal antibodies. Results TF activity was detectible in plasma from 14 of 54 patients (25.9%), including 13 of 38 with severe AS (34.2%) and 1 of 16 (6.25%) with moderate AS (p=0.052). FXIa activity was found in 12 (22.2%) patients, mostly in individuals with severe AS (11 of 38, 28.9%, p=0.067). All 12 patients with circulating FXIa had active TF in their plasma as well. Severe AS patients with detectable TF had higher maximal (111±20 vs 97±16 mm Hg, p=0.02) and mean (61±12 vs 53±8 mm Hg, p=0.02) transvalvular gradient, compared with those without such activity in plasma. In severe AS patients with detectable active TF, prothrombin fragment 1.2, a thrombin generation marker, was higher than in patients without TF (375±122 vs. 207±64 pM, p<0.001). Conclusions Detectable FXIa and TF activity was observed for the first time in AS patients, primarily in severe ones. This activity correlates with thrombin generation in those patients. PMID:21519234

Impact of Tissue Factor Localization on Blood Clot Structure and Resistance under Venous Shear.

PubMed

Govindarajan, Vijay; Zhu, Shu; Li, Ruizhi; Lu, Yichen; Diamond, Scott L; Reifman, Jaques; Mitrophanov, Alexander Y

2018-02-27

The structure and growth of a blood clot depend on the localization of tissue factor (TF), which can trigger clotting during the hemostatic process or promote thrombosis when exposed to blood under pathological conditions. We sought to understand how the growth, structure, and mechanical properties of clots under flow are shaped by the simultaneously varying TF surface density and its exposure area. We used an eight-channel microfluidic device equipped with a 20- or 100-μm-long collagen surface patterned with lipidated TF of surface densities ∼0.1 and ∼2 molecules/μm 2 . Human whole blood was perfused at venous shear, and clot growth was continually measured. Using our recently developed computational model of clot formation, we performed simulations to gain insights into the clot's structure and its resistance to blood flow. An increase in TF exposure area resulted not only in accelerated bulk platelet, thrombin, and fibrin accumulation, but also in increased height of the platelet mass and increased clot resistance to flow. Moreover, increasing the TF surface density or exposure area enhanced platelet deposition by approximately twofold, and thrombin and fibrin generation by greater than threefold, thereby increasing both clot size and its viscous resistance. Finally, TF effects on blood flow occlusion were more pronounced for the longer thrombogenic surface than for the shorter one. Our results suggest that TF surface density and its exposure area can independently enhance both the clot's occlusivity and its resistance to blood flow. These findings provide, to our knowledge, new insights into how TF affects thrombus growth in time and space under flow. Copyright © 2018 Biophysical Society. All rights reserved.

Pharmacokinetics and brain uptake of an IgG-TNF decoy receptor fusion protein following intravenous, intraperitoneal, and subcutaneous administration in mice.

PubMed

Sumbria, Rachita K; Zhou, Qing-Hui; Hui, Eric Ka-Wai; Lu, Jeff Zhiqiang; Boado, Ruben J; Pardridge, William M

2013-04-01

Tumor necrosis factor (TNF)-α is a proinflammatory cytokine active in the brain. Etanercept, the TNF decoy receptor (TNFR), does not cross the blood-brain barrier (BBB). The TNFR was re-engineered for BBB penetration as a fusion protein with a chimeric monoclonal antibody (mAb) against the mouse transferrin receptor (TfR), and this fusion protein is designated cTfRMAb-TNFR. The cTfRMAb domain of the fusion protein acts as a molecular Trojan horse and mediates transport via the endogenous BBB TfR. To support future chronic treatment of mouse models of neural disease with daily administration of the cTfRMAb-TNFR fusion protein, a series of pharmacokinetics and brain uptake studies in the mouse was performed. The cTfRMAb-TNFR fusion protein was radiolabeled and injected into mice via the intravenous, intraperitoneal (IP), or subcutaneous (SQ) routes of administration at doses ranging from 0.35 to 10 mg/kg. The distribution of the fusion protein into plasma following the IP or SQ routes was enhanced by increasing the injection dose from 3 to 10 mg/kg. The fusion protein demonstrated long circulation times with high metabolic stability following the IP or SQ routes of injection. The IP or SQ routes produced concentrations of the cTfRMAb-TNFR fusion protein in the brain that exceed by 20- to 50-fold the concentration of TNFα in pathologic conditions of the brain. The SQ injection is the preferred route of administration, as the level of cTfRMAb fusion protein produced in the brain is comparable to that generated with intravenous injection, and at a much lower plasma area under the concentration curve of the fusion protein as compared to IP administration.

Clinical Significance of Tissue Factor and CD13 Double-Positive Microparticles in Sirs Patients with Trauma and Severe Sepsis.

PubMed

Matsumoto, Hisatake; Yamakawa, Kazuma; Ogura, Hiroshi; Koh, Taichin; Matsumoto, Naoya; Shimazu, Takeshi

2017-04-01

Activated immune cells such as monocytes are key factors in systemic inflammatory response syndrome (SIRS) following trauma and sepsis. Activated monocytes induce almost all tissue factor (TF) expression contributing to inflammation and coagulation. TF and CD13 double-positive microparticles (TF/CD13MPs) are predominantly released from these activated monocytes. This study aimed to evaluate TF/CD13MPs and assess their usefulness as a biomarker of pathogenesis in early SIRS following trauma and sepsis. This prospective study comprising 24 trauma patients, 25 severe sepsis patients, and 23 healthy controls was conducted from November 2012 to February 2015. Blood samples were collected from patients within 24 h after injury and diagnosis of severe sepsis and from healthy controls. Numbers of TF/CD13MPs were measured by flow cytometry immediately thereafter. Injury Severity Score (ISS) and Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were calculated at patient enrollment. APACHE II and SOFA scores and International Society of Thrombosis and Haemostasis (ISTH) overt disseminated intravascular coagulation (DIC) diagnostic criteria algorithm were calculated at the time of enrollment of severe sepsis patients. Numbers of TF/CD13MPs were significantly increased in both trauma and severe sepsis patients versus controls and correlated significantly with ISS and APACHE II score in trauma patients and with APACHE II and ISTH DIC scores in severe sepsis patients. Increased numbers of TF/CD13MPs correlated significantly with severities in the acute phase in trauma and severe sepsis patients, suggesting that TF/CD13MPs are important in the pathogenesis of early SIRS following trauma and sepsis.

Simultaneously learning DNA motif along with its position and sequence rank preferences through expectation maximization algorithm.

PubMed

Zhang, ZhiZhuo; Chang, Cheng Wei; Hugo, Willy; Cheung, Edwin; Sung, Wing-Kin

2013-03-01

Although de novo motifs can be discovered through mining over-represented sequence patterns, this approach misses some real motifs and generates many false positives. To improve accuracy, one solution is to consider some additional binding features (i.e., position preference and sequence rank preference). This information is usually required from the user. This article presents a de novo motif discovery algorithm called SEME (sampling with expectation maximization for motif elicitation), which uses pure probabilistic mixture model to model the motif's binding features and uses expectation maximization (EM) algorithms to simultaneously learn the sequence motif, position, and sequence rank preferences without asking for any prior knowledge from the user. SEME is both efficient and accurate thanks to two important techniques: the variable motif length extension and importance sampling. Using 75 large-scale synthetic datasets, 32 metazoan compendium benchmark datasets, and 164 chromatin immunoprecipitation sequencing (ChIP-Seq) libraries, we demonstrated the superior performance of SEME over existing programs in finding transcription factor (TF) binding sites. SEME is further applied to a more difficult problem of finding the co-regulated TF (coTF) motifs in 15 ChIP-Seq libraries. It identified significantly more correct coTF motifs and, at the same time, predicted coTF motifs with better matching to the known motifs. Finally, we show that the learned position and sequence rank preferences of each coTF reveals potential interaction mechanisms between the primary TF and the coTF within these sites. Some of these findings were further validated by the ChIP-Seq experiments of the coTFs. The application is available online.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Huang-Joe; Division of Cardiology, Department of Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 40447, Taiwan; Lo, Wan-Yu

Patients with paclitaxel-eluting stents are concerned with stent thrombosis caused by premature discontinuation of dual antiplatelet therapy or clopidogrel resistance. This study investigates the effect of (-)-epigallocatechin-3-gallate (EGCG) on the expression of thrombin/paclitaxel-induced endothelial tissue factor (TF) expressions in human aortic endothelial cells (HAECs). EGCG was nontoxic to HAECs at 6 h up to a concentration of 25 {mu}mol/L. At a concentration of 25 {mu}mol/L, EGCG pretreatment potently inhibited both thrombin-stimulated and thrombin/paclitaxel-stimulated endothelial TF protein expression. Thrombin and thrombin/paclitaxel-induced 2.6-fold and 2.9-fold increases in TF activity compared with the control. EGCG pretreatment caused a 29% and 38% decrease inmore » TF activity on thrombin and thrombin/paclitaxel treatment, respectively. Real-time polymerase chain reaction (PCR) showed that thrombin and thrombin/paclitaxel-induced 3.0-fold and 4.6-fold TF mRNA expressions compared with the control. EGCG pretreatment caused an 82% and 72% decrease in TF mRNA expression on thrombin and thrombin/paclitaxel treatment, respectively. The c-Jun terminal NH2 kinase (JNK) inhibitor SP600125 reduced thrombin/paclitaxel-induced TF expression. Furthermore, EGCG significantly inhibited the phosphorylation of JNK to 49% of thrombin/paclitaxel-stimulated HAECs at 60 min. Immunofluorescence assay did not show an inhibitory effect of EGCG on P65 NF-{kappa}B nuclear translocation in the thrombin/paclitaxel-stimulated endothelial cells. In conclusion, EGCG can inhibit TF expression in thrombin/paclitaxel-stimulated endothelial cells via the inhibition of JNK phosphorylation. The unique property of EGCG may be used to develop a new drug-eluting stent by co-coating EGCG and paclitaxel.« less

Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer.

PubMed

Kukulj, Suzana; Jaganjac, Morana; Boranic, Milivoj; Krizanac, Simun; Santic, Zarko; Poljak-Blazi, Marija

2010-06-01

The involvement of iron and inflammation parameters on overall survival in non-small-cell lung cancer (NSCLC) patients was studied. Furthermore, transferrin receptors 1 (TfR1) and ferritin expression in tumor tissue, tumor stroma, and normal lung tissue were analyzed. Iron metabolism and inflammation parameters were determined by automated laboratory measurements at the time of diagnosis. TfR1 and ferritin expression were determined by immuno-histochemical methods. About 50% of patients survived 12 months only. At the time of diagnosis more than half of the patients had anemia and significantly elevated serum ferritin. Iron content of serum ferritin (ICF) was below the reference values in 90% of patients. Furthermore, ICF showed positive correlation with iron metabolic parameters and survival but negative correlation with serum ferritin and ESR. The expression of TfR1 and ferritin in tumor cells was observed in 88% or 62% of patients, respectively. Tumor stroma was TfR1 negative and sporadically ferritin positive. Tumor tissue ferritin expression showed negative correlation with serum iron and hematokrit (Ht), and positive correlation with ferritin, erythrocyte sedimentation rate (ESR), alpha-1 globulin, and alpha-2 globulin. Positive correlation was found between TfR1 expression in tumor tissue and alpha-globulin. The correlation between TfR1/ferritin expression in tumor tissue and ICF or survival was not observed. Therefore, we conclude that elevated serum ferritin in sera of NSCLC patients is the result of inflammation and oxidative stress rather than body iron overload. Higher expression of ferritin in tumor tissue may be the consequence of iron deficiency or local toxicity induced by environmental factors.

Fabrication of transferrin functionalized gold nanoclusters/graphene oxide nanocomposite for turn-on near-infrared fluorescent bioimaging of cancer cells and small animals.

PubMed

Wang, Yong; Chen, Jia-Tong; Yan, Xiu-Ping

2013-02-19

Transferrin (Tf)-functionalized gold nanoclusters (Tf-AuNCs)/graphene oxide (GO) nanocomposite (Tf-AuNCs/GO) was fabricated as a turn-on near-infrared (NIR) fluorescent probe for bioimaging cancer cells and small animals. A one-step approach was developed to prepare Tf-AuNCs via a biomineralization process with Tf as the template. Tf acted not only as a stabilizer and a reducer but also as a functional ligand for targeting the transferrin receptor (TfR). The prepared Tf-AuNCs gave intense NIR fluorescence that can avoid interference from biological media such as tissue autofluorescence and scattering light. The assembly of Tf-AuNCs and GO gave the Tf-AuNCs/GO nanocomposite, a turn-on NIR fluorescent probe with negligible background fluorescence due to the super fluorescence quenching property of GO. The NIR fluorescence of the Tf-AuNCs/GO nanocomposite was effectively restored in the presence of TfR, due to the specific interaction between Tf and TfR and the competition of TfR with the GO for the Tf in Tf-AuNCs/GO composite. The developed turn-on NIR fluorescence probe offered excellent water solubility, stability, and biocompatibility, and exhibited high specificity to TfR with negligible cytotoxicity. The probe was successfully applied for turn-on fluorescent bioimaging of cancer cells and small animals.

Overexpression of COUP-TF1 in murine embryonic stem cells reduces retinoic acid-associated growth arrest and increases extraembryonic endoderm gene expression.

PubMed

Zhuang, Yong; Gudas, Lorraine J

2008-09-01

Vitamin A (retinol [Rol]) and its metabolites are essential for embryonic development. The Rol metabolite all-trans retinoic acid (RA) is a biologically active form of Rol. The orphan nuclear receptor chicken ovalbumin upstream promoter-transcription-factors (COUP-TF) proteins have been implicated in the regulation of several important biological processes, such as embryonic development and neuronal cell differentiation. Because there is evidence that COUP-TFs function in the retinoid signaling network during development and differentiation, we generated murine embryonic stem (ES) cell lines which stably and constitutively overexpress COUP-TF1 (NR2F1) and we analyzed RA-induced differentiation. COUP-TF1 overexpression resulted in reduced RA-associated growth arrest. A 2.4+/-0.17-fold higher Nanog mRNA level was seen in COUP-TF1 overexpressing lines, as compared with wild-type (WT) ES cells, after a 72 hr RA treatment. We also showed that COUP-TF1 overexpression enhanced RA-induced extraembryonic endoderm gene expression. Specifically, COUP-TF1 overexpression increased mRNA levels of GATA6 by 3.3+/-0.3-fold, GATA4 by 3.6+/-0.1-fold, laminin B1 (LAMB1) by 3.4+/-0.1-fold, LAMC1 by 3.4+/-0.2-fold, Dab2 by 2.4+0.1-fold, and SOX17 by 2.5-fold at 72 hr after RA treatment plus LIF, as compared with the increases seen in WT ES cells. However, RA-induced neurogenesis was unaffected by COUP-TF1 overexpression, as shown by the equivalent levels of expression of NeuroD1, nestin, GAP43 and other neuronal markers. Our results revealed for the first time that COUP-TF1 is an important signaling molecule during vitamin A (Rol)-mediated very early stage of embryonic development.

Demonstration of thin film pair distribution function analysis (tfPDF) for the study of local structure in amorphous and crystalline thin films

DOE PAGES

Jensen, K. M.Ø.; Blichfeld, A. B.; Bauers, S. R.; ...

2015-07-05

By means of normal incidence, high flux and high energy x-rays, we have obtained total scattering data for Pair Distribution Function (PDF) analysis from thin films (tf), suitable for local structure analysis. By using amorphous substrates as support for the films, the standard Rapid Acquisition PDF setup can be applied and the scattering signal from the film can be isolated from the total scattering data through subtraction of an independently measured background signal. No angular corrections to the data are needed, as would be the case for grazing incidence measurements. We illustrate the ‘tfPDF’ method through studies of as depositedmore » (i.e. amorphous) and crystalline FeSb 3 films, where the local structure analysis gives insight into the stabilization of the metastable skutterudite FeSb 3 phase. The films were prepared by depositing ultra-thin alternating layers of Fe and Sb, which interdiffuse and after annealing crystallize to form the FeSb 3 structure. The tfPDF data show that the amorphous precursor phase consists of corner-sharing FeSb 6 octahedra with motifs highly resembling the local structure in crystalline FeSb 3. Analysis of the amorphous structure allows predicting whether the final crystalline product will form the FeSb 3 phase with or without excess Sb present. The study thus illustrates how analysis of the local structure in amorphous precursor films can help to understand crystallization processes of metastable phases and opens for a range of new local structure studies of thin films.« less

Demonstration of thin film pair distribution function analysis (tfPDF) for the study of local structure in amorphous and crystalline thin films

PubMed Central

Jensen, Kirsten M. Ø.; Blichfeld, Anders B.; Bauers, Sage R.; Wood, Suzannah R.; Dooryhée, Eric; Johnson, David C.; Iversen, Bo B.; Billinge, Simon J. L.

2015-01-01

By means of normal-incidence, high-flux and high-energy X-rays, total scattering data for pair distribution function (PDF) analysis have been obtained from thin films (tf), suitable for local structure analysis. By using amorphous substrates as support for the films, the standard Rapid Acquisition PDF setup can be applied and the scattering signal from the film can be isolated from the total scattering data through subtraction of an independently measured background signal. No angular corrections to the data are needed, as would be the case for grazing incidence measurements. The ‘tfPDF’ method is illustrated through studies of as-deposited (i.e. amorphous) and crystalline FeSb3 films, where the local structure analysis gives insight into the stabilization of the metastable skutterudite FeSb3 phase. The films were prepared by depositing ultra-thin alternating layers of Fe and Sb, which interdiffuse and after annealing crystallize to form the FeSb3 structure. The tfPDF data show that the amorphous precursor phase consists of corner-sharing FeSb6 octahedra with motifs highly resembling the local structure in crystalline FeSb3. Analysis of the amorphous structure allows the prediction of whether the final crystalline product will form the FeSb3 phase with or without excess Sb present. The study thus illustrates how analysis of the local structure in amorphous precursor films can help to understand crystallization processes of metastable phases and opens for a range of new local structure studies of thin films. PMID:26306190

Two-finger (TF) SPUDT cells.

PubMed

Martin, Guenter; Biryukov, Sergey V; Schmidt, Hagen; Steiner, Bernd; Wall, Bert

2011-03-01

SPUDT cells including two fingers are only known thus far for so-called NSPUDT directions. In that case, usual solid-finger cells are used. The purpose of the present paper is to find SPUDT cell types consisting of two fingers only for pure mode directions. Two-finger (TF) cells for pure mode directions on substrates like 128°YX LiNbO(3) and YZ LiNbO(3) were found by means of an optimization procedure. The forward direction of a TF-cell SPUDT on 128°YX LiNbO(3) was determined experimentally. The properties of the new cells are compared with those of conventional SPUDT cells. The reflectivity of TF cells on 128°YX LiNbO(3) turns out to be two to three times larger than that of distributed acoustic reflection transducer (DART) and Hanma-Hunsinger cells at the same metal layer thickness.

DOA-informed source extraction in the presence of competing talkers and background noise

NASA Astrophysics Data System (ADS)

Taseska, Maja; Habets, Emanuël A. P.

2017-12-01

A desired speech signal in hands-free communication systems is often degraded by noise and interfering speech. Even though the number and locations of the interferers are often unknown in practice, it is justified to assume in certain applications that the direction-of-arrival (DOA) of the desired source is approximately known. Using the known DOA, fixed spatial filters such as the delay-and-sum beamformer can be steered to extract the desired source. However, it is well-known that fixed data-independent spatial filters do not provide sufficient reduction of directional interferers. Instead, the DOA information can be used to estimate the statistics of the desired and the undesired signals and to compute optimal data-dependent spatial filters. One way the DOA is exploited for optimal spatial filtering in the literature, is by designing DOA-based narrowband detectors to determine whether a desired or an undesired signal is dominant at each time-frequency (TF) bin. Subsequently, the statistics of the desired and the undesired signals can be estimated during the TF bins where the respective signal is dominant. In a similar manner, a Gaussian signal model-based detector which does not incorporate DOA information has been used in scenarios where the undesired signal consists of stationary background noise. However, when the undesired signal is non-stationary, resulting for example from interfering speakers, such a Gaussian signal model-based detector is unable to robustly distinguish desired from undesired speech. To this end, we propose a DOA model-based detector to determine the dominant source at each TF bin and estimate the desired and undesired signal statistics. We demonstrate that data-dependent spatial filters that use the statistics estimated by the proposed framework achieve very good undesired signal reduction, even when using only three microphones.

Functional role of pyruvate kinase from Lactobacillus bulgaricus in acid tolerance and identification of its transcription factor by bacterial one-hybrid

PubMed Central

Zhai, Zhengyuan; An, Haoran; Wang, Guohong; Luo, Yunbo; Hao, Yanling

2015-01-01

Lactobacillus delbrueckii subsp. bulgaricus develops acid tolerance response when subjected to acid stress conditions, such as the induction of enzymes associated with carbohydrate metabolism. In this study, pyk gene encoding pyruvate kinase was over-expressed in heterologous host Lactococcus lactis NZ9000, and SDS-PAGE analysis revealed the successful expression of this gene in NZ9000. The survival rate of Pyk-overproducing strain was 45-fold higher than the control under acid stress condition (pH 4.0). In order to determine the transcription factor (TF) which regulates the expression of pyk by bacterial one-hybrid, we constructed a TF library including 65 TFs of L. bulgaricus. Western blotting indicated that TFs in this library could be successfully expressed in host strains. Subsequently, the promoter of pfk-pyk operon in L. bulgaricus was identified by 5′-RACE PCR. The bait plasmid pH3U3-p01 carrying the deletion fragment of pfk-pyk promoter captured catabolite control protein A (CcpA) which could regulate the expression of pyk by binding to a putative catabolite-responsive element (5′-TGTAAGCCCTAACA-3′) upstream the -35 region. Real-time qPCR analysis revealed the transcription of pyk was positively regulated by CcpA. This is the first report about identifying the TF of pyk in L. bulgaricus, which will provide new insight into the regulatory network. PMID:26581248

Preliminary LOCA analysis of the westinghouse small modular reactor using the WCOBRA/TRAC-TF2 thermal-hydraulics code

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, J.; Kucukboyaci, V. N.; Nguyen, L.

2012-07-01

The Westinghouse Small Modular Reactor (SMR) is an 800 MWt (> 225 MWe) integral pressurized water reactor (iPWR) with all primary components, including the steam generator and the pressurizer located inside the reactor vessel. The reactor core is based on a partial-height 17x17 fuel assembly design used in the AP1000{sup R} reactor core. The Westinghouse SMR utilizes passive safety systems and proven components from the AP1000 plant design with a compact containment that houses the integral reactor vessel and the passive safety systems. A preliminary loss of coolant accident (LOCA) analysis of the Westinghouse SMR has been performed using themore » WCOBRA/TRAC-TF2 code, simulating a transient caused by a double ended guillotine (DEG) break in the direct vessel injection (DVI) line. WCOBRA/TRAC-TF2 is a new generation Westinghouse LOCA thermal-hydraulics code evolving from the US NRC licensed WCOBRA/TRAC code. It is designed to simulate PWR LOCA events from the smallest break size to the largest break size (DEG cold leg). A significant number of fluid dynamics models and heat transfer models were developed or improved in WCOBRA/TRAC-TF2. A large number of separate effects and integral effects tests were performed for a rigorous code assessment and validation. WCOBRA/TRAC-TF2 was introduced into the Westinghouse SMR design phase to assist a quick and robust passive cooling system design and to identify thermal-hydraulic phenomena for the development of the SMR Phenomena Identification Ranking Table (PIRT). The LOCA analysis of the Westinghouse SMR demonstrates that the DEG DVI break LOCA is mitigated by the injection and venting from the Westinghouse SMR passive safety systems without core heat up, achieving long term core cooling. (authors)« less

A Sensitivity Analysis of an Inverted Pendulum Balance Control Model.

PubMed

Pasma, Jantsje H; Boonstra, Tjitske A; van Kordelaar, Joost; Spyropoulou, Vasiliki V; Schouten, Alfred C

2017-01-01

Balance control models are used to describe balance behavior in health and disease. We identified the unique contribution and relative importance of each parameter of a commonly used balance control model, the Independent Channel (IC) model, to identify which parameters are crucial to describe balance behavior. The balance behavior was expressed by transfer functions (TFs), representing the relationship between sensory perturbations and body sway as a function of frequency, in terms of amplitude (i.e., magnitude) and timing (i.e., phase). The model included an inverted pendulum controlled by a neuromuscular system, described by several parameters. Local sensitivity of each parameter was determined for both the magnitude and phase using partial derivatives. Both the intrinsic stiffness and proportional gain shape the magnitude at low frequencies (0.1-1 Hz). The derivative gain shapes the peak and slope of the magnitude between 0.5 and 0.9 Hz. The sensory weight influences the overall magnitude, and does not have any effect on the phase. The effect of the time delay becomes apparent in the phase above 0.6 Hz. The force feedback parameters and intrinsic stiffness have a small effect compared with the other parameters. All parameters shape the TF magnitude and phase and therefore play a role in the balance behavior. The sensory weight, time delay, derivative gain, and the proportional gain have a unique effect on the TFs, while the force feedback parameters and intrinsic stiffness contribute less. More insight in the unique contribution and relative importance of all parameters shows which parameters are crucial and critical to identify underlying differences in balance behavior between different patient groups.

Derivation and Characterization of Pathogenic Transmitted/Founder Molecular Clones from Simian Immunodeficiency Virus SIVsmE660 and SIVmac251 following Mucosal Infection

PubMed Central

Lopker, Michael J.; Del Prete, Gregory Q.; Estes, Jacob D.; Li, Hui; Reid, Carolyn; Newman, Laura; Lipkey, Leslie; Camus, Celine; Easlick, Juliet L.; Wang, Shuyi; Decker, Julie M.; Bar, Katharine J.; Learn, Gerald; Pal, Ranajit; Weiss, Deborah E.; Hahn, Beatrice H.; Lifson, Jeffrey D.; Shaw, George M.

2016-01-01

ABSTRACT Currently available simian immunodeficiency virus (SIV) infectious molecular clones (IMCs) and isolates used in nonhuman primate (NHP) models of AIDS were originally derived from infected macaques during chronic infection or end stage disease and may not authentically recapitulate features of transmitted/founder (T/F) genomes that are of particular interest in transmission, pathogenesis, prevention, and treatment studies. We therefore generated and characterized T/F IMCs from genetically and biologically heterogeneous challenge stocks of SIVmac251 and SIVsmE660. Single-genome amplification (SGA) was used to identify full-length T/F genomes present in plasma during acute infection resulting from atraumatic rectal inoculation of Indian rhesus macaques with low doses of SIVmac251 or SIVsmE660. All 8 T/F clones yielded viruses that were infectious and replication competent in vitro, with replication kinetics similar to those of the widely used chronic-infection-derived IMCs SIVmac239 and SIVsmE543. Phenotypically, the new T/F virus strains exhibited a range of neutralization sensitivity profiles. Four T/F virus strains were inoculated into rhesus macaques, and each exhibited typical SIV replication kinetics. The SIVsm T/F viruses were sensitive to TRIM5α restriction. All T/F viruses were pathogenic in rhesus macaques, resulting in progressive CD4+ T cell loss in gastrointestinal tissues, peripheral blood, and lymphatic tissues. The animals developed pathological immune activation; lymphoid tissue damage, including fibrosis; and clinically significant immunodeficiency leading to AIDS-defining clinical endpoints. These T/F clones represent a new molecular platform for the analysis of virus transmission and immunopathogenesis and for the generation of novel “bar-coded” challenge viruses and next-generation simian-human immunodeficiency viruses that may advance the HIV/AIDS vaccine agenda. IMPORTANCE Nonhuman primate research has relied on only a few infectious molecular clones for a myriad of diverse research projects, including pathogenesis, preclinical vaccine evaluations, transmission, and host-versus-pathogen interactions. With new data suggesting a selected phenotype of the virus that causes infection (i.e., the transmitted/founder virus), we sought to generate and characterize infectious molecular clones from two widely used simian immunodeficiency virus lineages (SIVmac251 and SIVsmE660). Although the exact requirements necessary to be a T/F virus are not yet fully understood, we generated cloned viruses with all the necessary characteristic of a successful T/F virus. The cloned viruses revealed typical acute and set point viral-load dynamics with pathological immune activation, lymphoid tissue damage progressing to significant immunodeficiency, and AIDS-defining clinical endpoints in some animals. These T/F clones represent a new molecular platform for studies requiring authentic T/F viruses. PMID:27412591

Evaluation of PET texture features with heterogeneous phantoms: complementarity and effect of motion and segmentation method

NASA Astrophysics Data System (ADS)

Carles, M.; Torres-Espallardo, I.; Alberich-Bayarri, A.; Olivas, C.; Bello, P.; Nestle, U.; Martí-Bonmatí, L.

2017-01-01

A major source of error in quantitative PET/CT scans of lung cancer tumors is respiratory motion. Regarding the variability of PET texture features (TF), the impact of respiratory motion has not been properly studied with experimental phantoms. The primary aim of this work was to evaluate the current use of PET texture analysis for heterogeneity characterization in lesions affected by respiratory motion. Twenty-eight heterogeneous lesions were simulated by a mixture of alginate and 18 F-fluoro-2-deoxy-D-glucose (FDG). Sixteen respiratory patterns were applied. Firstly, the TF response for different heterogeneous phantoms and its robustness with respect to the segmentation method were calculated. Secondly, the variability for TF derived from PET image with (gated, G-) and without (ungated, U-) motion compensation was analyzed. Finally, TF complementarity was assessed. In the comparison of TF derived from the ideal contour with respect to TF derived from 40%-threshold and adaptive-threshold PET contours, 7/8 TF showed strong linear correlation (LC) (p  <  0.001, r  >  0.75), despite a significant volume underestimation. Independence of lesion movement (LC in 100% of the combined pairs of movements, p  <  0.05) was obtained for 1/8 TF with U-image (width of the volume-activity histogram, WH) and 4/8 TF with G-image (WH and energy (ENG), local-homogeneity (LH) and entropy (ENT), derived from the co-ocurrence matrix). Their variability in terms of the coefficient of variance ({{C}\\text{V}} ) resulted in {{C}\\text{V}} (WH)  =  0.18 on the U-image and {{C}\\text{V}} (WH)  =  0.24, {{C}\\text{V}} (ENG)  =  0.15, {{C}\\text{V}} (LH)  =  0.07 and {{C}\\text{V}} (ENT)  =  0.06 on the G-image. Apart from WH (r  >  0.9, p  <  0.001), not one of these TF has shown LC with C max. Complementarity was observed for the TF pairs: ENG-LH, CONT (contrast)-ENT and LH-ENT. In conclusion, the effect of respiratory motion should be taken into account when the heterogeneity of lung cancer is quantified on PET/CT images. Despite inaccurate volume delineation, TF derived from 40% and COA contours could be reliable for their prognostic use. The TF that exhibited simultaneous added value and independence of lesion movement were ENG and ENT computed from the G-image. Their use is therefore recommended for heterogeneity quantification of lesions affected by respiratory motion.

III-Vs at Scale: A PV Manufacturing Cost Analysis of the Thin Film Vapor-Liquid-Solid Growth Mode

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Maxwell; Horowitz, Kelsey; Woodhouse, Michael

The authors present a manufacturing cost analysis for producing thin-film indium phosphide modules by combining a novel thin-film vapor-liquid-solid (TF-VLS) growth process with a standard monolithic module platform. The example cell structure is ITO/n-TiO2/p-InP/Mo. For a benchmark scenario of 12% efficient modules, the module cost is estimated to be $0.66/W(DC) and the module cost is calculated to be around $0.36/W(DC) at a long-term potential efficiency of 24%. The manufacturing cost for the TF-VLS growth portion is estimated to be ~$23/m2, a significant reduction compared with traditional metalorganic chemical vapor deposition. The analysis here suggests the TF-VLS growth mode could enablemore » lower-cost, high-efficiency III-V photovoltaics compared with manufacturing methods used today and open up possibilities for other optoelectronic applications as well.« less

Vascular infarction by subcutaneous application of tissue factor targeted to tumor vessels with NGR-peptides: activity and toxicity profile.

PubMed

Dreischalück, Johannes; Schwöppe, Christian; Spieker, Tilmann; Kessler, Torsten; Tiemann, Klaus; Liersch, Ruediger; Schliemann, Christoph; Kreuter, Michael; Kolkmeyer, Astrid; Hintelmann, Heike; Mesters, Rolf M; Berdel, Wolfgang E

2010-12-01

tTF-NGR consists of the extracellular domain of the (truncated) tissue factor (tTF), a central molecule for coagulation in vivo, and the peptide GNGRAHA (NGR), a ligand of the surface protein aminopeptidase N (CD13). After deamidation of the NGR-peptide moiety, the fusion protein is also a ligand for integrin αvβ3 (CD51/CD61). Both surface proteins are upregulated on endothelial cells of tumor vessels. tTF-NGR showed binding to specific binding sites on endothelial cells in vitro as shown by flow cytometry. Subcutaneous injection of tTF-NGR into athymic mice bearing human HT1080 fibrosarcoma tumors induced tumor growth retardation and delay. Contrast enhanced ultrasound detected a decrease in tumor blood flow in vivo after application of tTF-NGR. Histological analysis of the tumors revealed vascular disruption due to blood pooling and thrombotic occlusion of tumor vessels. Furthermore, a lack of resistance was shown by re-exposure of tumor-bearing mice to tTF-NGR after regrowth following a first cycle of treatment. However, after subcutaneous (s.c.) push injection with therapeutic doses (1-5 mg/kg bw) side effects have been observed, such as skin bleeding and reduced performance. Since lethality started within the therapeutic dose range (LD10 approximately 2 mg/kg bw) no safe therapeutic window could be found. Limiting toxicity was represented by thrombo-embolic events in major organ systems as demonstrated by histology. Thus, subcutaneous injection of tTF-NGR represents an active, but toxic application procedure and compares unfavourably to intravenous infusion.

Curated collection of yeast transcription factor DNA binding specificity data reveals novel structural and gene regulatory insights

PubMed Central

2011-01-01

Background Transcription factors (TFs) play a central role in regulating gene expression by interacting with cis-regulatory DNA elements associated with their target genes. Recent surveys have examined the DNA binding specificities of most Saccharomyces cerevisiae TFs, but a comprehensive evaluation of their data has been lacking. Results We analyzed in vitro and in vivo TF-DNA binding data reported in previous large-scale studies to generate a comprehensive, curated resource of DNA binding specificity data for all characterized S. cerevisiae TFs. Our collection comprises DNA binding site motifs and comprehensive in vitro DNA binding specificity data for all possible 8-bp sequences. Investigation of the DNA binding specificities within the basic leucine zipper (bZIP) and VHT1 regulator (VHR) TF families revealed unexpected plasticity in TF-DNA recognition: intriguingly, the VHR TFs, newly characterized by protein binding microarrays in this study, recognize bZIP-like DNA motifs, while the bZIP TF Hac1 recognizes a motif highly similar to the canonical E-box motif of basic helix-loop-helix (bHLH) TFs. We identified several TFs with distinct primary and secondary motifs, which might be associated with different regulatory functions. Finally, integrated analysis of in vivo TF binding data with protein binding microarray data lends further support for indirect DNA binding in vivo by sequence-specific TFs. Conclusions The comprehensive data in this curated collection allow for more accurate analyses of regulatory TF-DNA interactions, in-depth structural studies of TF-DNA specificity determinants, and future experimental investigations of the TFs' predicted target genes and regulatory roles. PMID:22189060

Tissue Factor promotes breast cancer stem cell activity in vitro.

PubMed

Shaker, Hudhaifah; Harrison, Hannah; Clarke, Robert; Landberg, Goran; Bundred, Nigel J; Versteeg, Henri H; Kirwan, Cliona C

2017-04-18

Cancer stem cells (CSCs) are a subpopulation of cells that can self-renew and initiate tumours. The clotting-initiating protein Tissue Factor (TF) promotes metastasis and may be overexpressed in cancer cells with increased CSC activity. We sought to determine whether TF promotes breast CSC activity in vitro using human breast cancer cell lines. TF expression was compared in anoikis-resistant (CSC-enriched) and unselected cells. In cells sorted into of TF-expressing and TF-negative (FACS), and in cells transfected to knockdown TF (siRNA) and overexpress TF (cDNA), CSC activity was compared by (i) mammosphere forming efficiency (MFE) (ii) holoclone colony formation (Hc) and (iii) ALDH1 activity. TF expression was increased in anoikis-resistant and high ALDH1-activity T47D cells compared to unselected cells. FACS sorted TF-expressing T47Ds and TF-overexpressing MCF7s had increased CSC activity compared to TF-low cells. TF siRNA cells (MDAMB231,T47D) had reduced CSC activity compared to control cells. FVIIa increased MFE and ALDH1 in a dose-dependent manner (MDAMB231, T47D). The effects of FVIIa on MFE were abrogated by TF siRNA (T47D). Breast CSCs (in vitro) demonstrate increased activity when selected for high TF expression, when induced to overexpress TF, and when stimulated (with FVIIa). Targeting the TF pathway in vivo may abrogate CSC activity.

Performance evaluation of the Ingenuity TF PET/CT scanner with a focus on high count-rate conditions

NASA Astrophysics Data System (ADS)

Kolthammer, Jeffrey A.; Su, Kuan-Hao; Grover, Anu; Narayanan, Manoj; Jordan, David W.; Muzic, Raymond F.

2014-07-01

This study evaluated the positron emission tomography (PET) imaging performance of the Ingenuity TF 128 PET/computed tomography (CT) scanner which has a PET component that was designed to support a wider radioactivity range than is possible with those of Gemini TF PET/CT and Ingenuity TF PET/MR. Spatial resolution, sensitivity, count rate characteristics and image quality were evaluated according to the NEMA NU 2-2007 standard and ACR phantom accreditation procedures; these were supplemented by additional measurements intended to characterize the system under conditions that would be encountered during quantitative cardiac imaging with 82Rb. Image quality was evaluated using a hot spheres phantom, and various contrast recovery and noise measurements were made from replicated images. Timing and energy resolution, dead time, and the linearity of the image activity concentration, were all measured over a wide range of count rates. Spatial resolution (4.8-5.1 mm FWHM), sensitivity (7.3 cps kBq-1), peak noise-equivalent count rate (124 kcps), and peak trues rate (365 kcps) were similar to those of the Gemini TF PET/CT. Contrast recovery was higher with a 2 mm, body-detail reconstruction than with a 4 mm, body reconstruction, although the precision was reduced. The noise equivalent count rate peak was broad (within 10% of peak from 241-609 MBq). The activity measured in phantom images was within 10% of the true activity for count rates up to those observed in 82Rb cardiac PET studies.

Effects of hyaluronic acid on bleeding following third molar extraction.

PubMed

Gocmen, Gokhan; Aktop, Sertac; Tüzüner, Burcin; Goker, Bahar; Yarat, Aysen

2017-01-01

To explore the effects of hyaluronic acid (HA) on bleeding and associated outcomes after third molar extraction. Forty patients who had undergone molar extraction were randomly divided into two groups; 0.8% (w/v) HA was applied to the HA group (n=20) whereas a control group (n=20) was not treated. Salivary and gingival tissue factor (TF) levels, bleeding time, maximum interincisal opening (MIO), pain scored on a visual analog scale (VAS), and the swelling extent were compared between the two groups. HA did not significantly affect gingival TF levels. Salivary TF levels increased significantly 1 week after HA application but not in the control group. Neither the VAS pain level nor MIO differed significantly between the two groups. The swelling extent on day 3 and the bleeding time were greater in the HA group than in the control group. Local injection of HA at 0.8% prolonged the bleeding time, and increased hemorrhage and swelling in the early postoperative period after third molar extractions.

The significance of measuring monocyte tissue factor activity in patients with breast and colorectal cancer

PubMed Central

Lwaleed, B A; Chisholm, M; Francis, J L

1999-01-01

Monocytes express tissue factor (mTF) in several conditions including cancer where levels may be valuable in assessing tumour presence and progression. Using a two-stage kinetic chromogenic assay (KCA), mTF levels were measured in controls [normal subjects (n = 60) and patients undergoing hernia repair or cholecystectomy (n = 60)], in patients with benign and malignant disease of the breast (n = 83) and of the large bowel (n = 62). This was performed under fresh (resting) conditions and after incubation for 6 h without (unstimulated) and with (stimulated) Escherichia coli endotoxin. The malignant groups showed higher mTF levels than each of the three controls for resting (P < 0.05 breast, P < 0.05 colorectal) unstimulated (P < 0.05 breast, P < 0.05 colorectal) and stimulated cells (P < 0.001 breast, P < 0.01 colorectal). Similarly, the benign inflammatory groups had higher mTF levels than controls for resting (P < 0.05 colorectal), unstimulated (P < 0.05 colorectal) and stimulated cells (P < 0.01 breast, P < 0.01 colorectal). There was no significant difference between malignant and benign inflammatory groups in each organ. mTF levels showed an increase corresponding to that of histological tumour progression and were higher in non-surviving patients. In conclusion, mTF levels are raised in malignant and inflammatory disease compared to controls and patients with non-inflammatory conditions. Stimulated cells give better discrimination between the groups and may be of value in identifying high risk individuals. mTF levels showed an association with tumour grade or stage and the patients' survival time. © 1999 Cancer Research Campaign PMID:10390009

Establishment of the Inducible Tet-On System for the Activation of the Silent Trichosetin Gene Cluster in Fusarium fujikuroi

PubMed Central

Janevska, Slavica; Arndt, Birgit; Baumann, Leonie; Apken, Lisa Helene; Mauriz Marques, Lucas Maciel; Humpf, Hans-Ulrich; Tudzynski, Bettina

2017-01-01

The PKS-NRPS-derived tetramic acid equisetin and its N-desmethyl derivative trichosetin exhibit remarkable biological activities against a variety of organisms, including plants and bacteria, e.g., Staphylococcus aureus. The equisetin biosynthetic gene cluster was first described in Fusarium heterosporum, a species distantly related to the notorious rice pathogen Fusarium fujikuroi. Here we present the activation and characterization of a homologous, but silent, gene cluster in F. fujikuroi. Bioinformatic analysis revealed that this cluster does not contain the equisetin N-methyltransferase gene eqxD and consequently, trichosetin was isolated as final product. The adaption of the inducible, tetracycline-dependent Tet-on promoter system from Aspergillus niger achieved a controlled overproduction of this toxic metabolite and a functional characterization of each cluster gene in F. fujikuroi. Overexpression of one of the two cluster-specific transcription factor (TF) genes, TF22, led to an activation of the three biosynthetic cluster genes, including the PKS-NRPS key gene. In contrast, overexpression of TF23, encoding a second Zn(II)2Cys6 TF, did not activate adjacent cluster genes. Instead, TF23 was induced by the final product trichosetin and was required for expression of the transporter-encoding gene MFS-T. TF23 and MFS-T likely act in consort and contribute to detoxification of trichosetin and therefore, self-protection of the producing fungus. PMID:28379186

Establishment of the Inducible Tet-On System for the Activation of the Silent Trichosetin Gene Cluster in Fusarium fujikuroi.

PubMed

Janevska, Slavica; Arndt, Birgit; Baumann, Leonie; Apken, Lisa Helene; Mauriz Marques, Lucas Maciel; Humpf, Hans-Ulrich; Tudzynski, Bettina

2017-04-05

The PKS-NRPS-derived tetramic acid equisetin and its N -desmethyl derivative trichosetin exhibit remarkable biological activities against a variety of organisms, including plants and bacteria, e.g., Staphylococcus aureus . The equisetin biosynthetic gene cluster was first described in Fusarium heterosporum , a species distantly related to the notorious rice pathogen Fusarium fujikuroi . Here we present the activation and characterization of a homologous, but silent, gene cluster in F. fujikuroi . Bioinformatic analysis revealed that this cluster does not contain the equisetin N -methyltransferase gene eqxD and consequently, trichosetin was isolated as final product. The adaption of the inducible, tetracycline-dependent Tet-on promoter system from Aspergillus niger achieved a controlled overproduction of this toxic metabolite and a functional characterization of each cluster gene in F. fujikuroi . Overexpression of one of the two cluster-specific transcription factor (TF) genes, TF22 , led to an activation of the three biosynthetic cluster genes, including the PKS-NRPS key gene. In contrast, overexpression of TF23 , encoding a second Zn(II)₂Cys₆ TF, did not activate adjacent cluster genes. Instead, TF23 was induced by the final product trichosetin and was required for expression of the transporter-encoding gene MFS-T . TF23 and MFS-T likely act in consort and contribute to detoxification of trichosetin and therefore, self-protection of the producing fungus.

Stimulus dependent neural oscillatory patterns show reliable statistical identification of autism spectrum disorder in a face perceptual decision task.

PubMed

Castelhano, João; Tavares, Paula; Mouga, Susana; Oliveira, Guiomar; Castelo-Branco, Miguel

2018-05-01

Electroencephalographic biomarkers have been widely investigated in autism, in the search for diagnostic, prognostic and therapeutic outcome measures. Here we took advantage of the information available in temporal oscillatory patterns evoked by simple perceptual decisions to investigate whether stimulus dependent oscillatory signatures can be used as potential biomarkers in autism spectrum disorder (ASD). We studied an extensive set of stimuli (9 categories of faces) and performed data driven classification (Support vector machine, SVM) of ASD vs. Controls with features based on the EEG power responses. We carried out an extensive time-frequency and synchrony analysis of distinct face categories requiring different processing mechanisms in terms of non-holistic vs. holistic processing. We found that the neuronal oscillatory responses of low gamma frequency band, locked to photographic and abstract two-tone (Mooney) face stimulus presentation are decreased in ASD vs. the control group. We also found decreased time-frequency (TF) responses in the beta band in ASD after 350 ms, possibly related to motor preparation. On the other hand, synchrony in the 30-45 Hz band showed a distinct spatial pattern in ASD. These power changes enabled accurate classification of ASD with an SVM approach. SVM accuracy was approximately 85%. ROC curves showed about 94% AUC (area under the curve). Combination of Mooney and Photographic face stimuli evoked features enabled a better separation between groups, reaching an AUC of 98.6%. We identified a relative decrease in EEG responses to face stimuli in ASD in the beta (15-30 Hz; >350 ms) and gamma (30-45 Hz; 55-80 Hz; 50-350 ms) frequency ranges. These can be used as input of a machine learning approach to separate between groups with high accuracy. Future studies can use EEG time-frequency patterns evoked by particular types of faces as a diagnostic biomarker and potentially as outcome measures in therapeutic trials. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Effects of tissue factor, PAR-2 and MMP-9 expression on human breast cancer cell line MCF-7 invasion.

PubMed

Lin, Zeng-Mao; Zhao, Jian-Xin; Duan, Xue-Ning; Zhang, Lan-Bo; Ye, Jing-Ming; Xu, Ling; Liu, Yin-Hua

2014-01-01

This study aimed to explore the expression of tissue factor (TF), protease activated receptor-2 (PAR-2), and matrix metalloproteinase-9 (MMP-9) in the MCF-7 breast cancer cell line and influence on invasiveness. Stable MCF-7 cells transfected with TF cDNA and with TF ShRNA were established. TF, PAR-2, and MMP-9 protein expression was analyzed using indirect immunofluorescence and invasiveness was evaluated using a cell invasion test. Effects of an exogenous PAR-2 agonist were also examined. TF protein expression significantly differed between the TF cDNA and TF ShRNA groups. MMP-9 protein expression was significantly correlated with TF protein expression, but PAR-2 protein expression was unaffected. The PAR- 2 agonist significantly enhanced MMP-9 expression and slightly increased TF and PAR-2 expression in the TF ShRNA group, but did not significantly affect protein expression in MCF-7 cells transfected with TF cDNA. TF and MMP-9 expression was positively correlated with the invasiveness of tumor cells. TF, PAR-2, and MMP-9 affect invasiveness of MCF-7 cells. TF may increase MMP-9 expression by activating PAR-2.

Evolutionary reconstructions of the transferrin receptor of Caniforms supports canine parvovirus being a re-emerged and not a novel pathogen in dogs.

PubMed

Kaelber, Jason T; Demogines, Ann; Harbison, Carole E; Allison, Andrew B; Goodman, Laura B; Ortega, Alicia N; Sawyer, Sara L; Parrish, Colin R

2012-01-01

Parvoviruses exploit transferrin receptor type-1 (TfR) for cellular entry in carnivores, and specific interactions are key to control of host range. We show that several key mutations acquired by TfR during the evolution of Caniforms (dogs and related species) modified the interactions with parvovirus capsids by reducing the level of binding. These data, along with signatures of positive selection in the TFRC gene, are consistent with an evolutionary arms race between the TfR of the Caniform clade and parvoviruses. As well as the modifications of amino acid sequence which modify binding, we found that a glycosylation site mutation in the TfR of dogs which provided resistance to the carnivore parvoviruses which were in circulation prior to about 1975 predates the speciation of coyotes and dogs. Because the closely-related black-backed jackal has a TfR similar to their common ancestor and lacks the glycosylation site, reconstructing this mutation into the jackal TfR shows the potency of that site in blocking binding and infection and explains the resistance of dogs until recent times. This alters our understanding of this well-known example of viral emergence by indicating that canine parvovirus emergence likely resulted from the re-adaptation of a parvovirus to the resistant receptor of a former host.

Evolutionary Reconstructions of the Transferrin Receptor of Caniforms Supports Canine Parvovirus Being a Re-emerged and Not a Novel Pathogen in Dogs

PubMed Central

Kaelber, Jason T.; Demogines, Ann; Harbison, Carole E.; Allison, Andrew B.; Goodman, Laura B.; Ortega, Alicia N.; Sawyer, Sara L.; Parrish, Colin R.

2012-01-01

Parvoviruses exploit transferrin receptor type-1 (TfR) for cellular entry in carnivores, and specific interactions are key to control of host range. We show that several key mutations acquired by TfR during the evolution of Caniforms (dogs and related species) modified the interactions with parvovirus capsids by reducing the level of binding. These data, along with signatures of positive selection in the TFRC gene, are consistent with an evolutionary arms race between the TfR of the Caniform clade and parvoviruses. As well as the modifications of amino acid sequence which modify binding, we found that a glycosylation site mutation in the TfR of dogs which provided resistance to the carnivore parvoviruses which were in circulation prior to about 1975 predates the speciation of coyotes and dogs. Because the closely-related black-backed jackal has a TfR similar to their common ancestor and lacks the glycosylation site, reconstructing this mutation into the jackal TfR shows the potency of that site in blocking binding and infection and explains the resistance of dogs until recent times. This alters our understanding of this well-known example of viral emergence by indicating that canine parvovirus emergence likely resulted from the re-adaptation of a parvovirus to the resistant receptor of a former host. PMID:22570610

Isomeric organic semiconductors containing fused-thiophene cores: molecular packing and charge transport.

PubMed

Dang, Dongfeng; Zhou, Pei; Wu, Yong; Xu, Yanzi; Zhi, Ying; Zhu, Weiguo

2018-05-16

Isomeric TF1 and TF2 with highly fused thiophene cores were designed and synthesized here, in which a highly planar molecular structure was obtained for TF1 with the face-to-face sulfur atoms in the lateral region and a twisted molecular backbone was observed for TF2 with the back-to-back sulfur atoms. It is worth noting that different intermolecular interactions dominated in TF1 and TF2 caused by their isomeric thiophene cores, in which strong π-π stacking was achieved for TF1, whereas sulphur-involved nonbonding intermolecular interactions dominated in TF2, leading to the different fluorescence behaviors and also the altered liquid crystalline phases. Finally, typical P-type charge transport behaviors were achieved in both TF1- and TF2-based solution-processed OFETs. Also owing to the much ordered molecular packing in TF1, a higher charge carrier mobility of 3.7 × 10-3 cm2 V-1 s-1 was achieved for TF1-based OFETs compared to TF2-based OFETs.

Spectroscopic studies of the interaction mechanisms between mono-caffeoylquinic acids and transferrin

NASA Astrophysics Data System (ADS)

Guan, Yanqing; Dong, Jing; Chen, Shizhong; Liu, Meixian; Wang, Daidong; Zhang, Xiaotian; Wang, Hong; Lin, Zongtao

2017-06-01

Transferrin (Tf) is an important protein responsible for circulating and transporting iron into cytoplasm. Tf can be taken into cells through endocytosis mediated by Tf receptor, which usually overexpresses in cancer cells. The Tf-Tf receptor pathway opens a possible avenue for novel targeted cancer therapy by utilizing Tf-binding active compounds. Among which, anti-cancer active caffeoylquinic acids (CQAs) were recently found to be promising Tf-binders by our group. For better understanding the anti-cancer activities of CQAs, it is important to unveil the binding mechanisms between CQAs and Tf. In this study, the fluorescence quenching, surface plasmon resonance (SPR), circular dichroism (CD) and molecular docking were used to investigate the interactions between CQA and Tf. The results showed that the calculated apparent association constants of interactions between 1-, 3-, 4- and 5-CQA and Tf at 298 K were 7.97 × 105 M- 1, 4.36 × 107 M- 1, 6.58 × 105 M- 1 and 4.42 × 106 M- 1, respectively. The thermodynamic parameters indicated that the interaction between 1-, 3-, 5-CQA and Tf is due to H-bonding, and electrostatic interactions were likely involved in the binding of 4-CQA and Tf. The CD results indicated that bindings of 1-CQA, 4-CQA and 5-CQA with Tf resulted in more stretched β-turn and random coil translated from β-sheet. In contrast, 3-CQA led to more stable a-helix conformation. Molecular docking studies of CQAs with Tf further displayed that CQAs were able to interact with residues near Fe3 + binding site. The spectroscopic studies revealed the action mechanisms, thermodynamics and interacting forces between CQAs and Tf, and thus are helpful for future design and discovery of Tf-binders for targeted cancer therapy applying Tf-Tf receptor pathway.

Fluorescent adduct formation with terbium: a novel strategy for transferrin glycoform identification in human body fluids and carbohydrate-deficient transferrin HPLC method validation.

PubMed

Sorio, Daniela; De Palo, Elio Franco; Bertaso, Anna; Bortolotti, Federica; Tagliaro, Franco

2017-02-01

This paper puts forward a new method for the transferrin (Tf) glycoform analysis in body fluids that involves the formation of a transferrin-terbium fluorescent adduct (TfFluo). The key idea is to validate the analytical procedure for carbohydrate-deficient transferrin (CDT), a traditional biochemical serum marker to identify chronic alcohol abuse. Terbium added to a human body-fluid sample produced TfFluo. Anion exchange HPLC technique, with fluorescence detection (λ exc 298 nm and λ em 550 nm), permitted clear separation and identification of Tf glycoform peaks without any interfering signals, allowing selective Tf sialoforms analysis in human serum and body fluids (cadaveric blood, cerebrospinal fluid, and dried blood spots) hampered for routine test. Serum samples (n = 78) were analyzed by both traditional absorbance (Abs) and fluorescence (Fl) HPLC methods and CDT% levels demonstrated a significant correlation (p < 0.001 Pearson). Intra- and inter-runs CV% was 3.1 and 4.6%, respectively. The cut-off of 1.9 CDT%, related to the HPLC Abs proposed as the reference method, by interpolation in the correlation curve with the present method demonstrated a 1.3 CDT% cut-off. Method comparison by Passing-Bablok and Bland-Altman tests demonstrated Fl versus Abs agreement. In conclusion, the novel method is a reliable test for CDT% analysis and provides a substantial analytical improvement offering important advantages in terms of types of body fluid analysis. Its sensitivity and absence of interferences extend clinical applications being reliable for CDT assay on body fluids usually not suitable for routine test. Graphical Abstract The formation of a transferrin-terbium fluorescent adduct can be used to analyze the transferrin glycoforms. The HPLC method for carbohydrate-deficient transferrin (CDT%) measurement was validated and employed to determine the levels in different body fluids.

Soluble tissue factor has unique angiogenic activities that selectively promote migration and differentiation but not proliferation of endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

He Yingbo; Chang Guodong; Zhan Shunli

2008-06-06

The level of circulating tissue factor (TF) is up-regulated in human angiogenesis-related malignancies. However, whether circulating TF has angiogenic activities has not been determined. Soluble TF (sTF) is the main domain of circulating TF. Here, using cell migration, wound healing, and tubule formation assays, human recombinant sTF was found to significantly promote the migration and differentiation of endothelial cells. The stress fiber formation and rearrangement induced by sTF observed through immunofluorescence microscope may be responsible for the stimulatory migration effect of sTF. Nevertheless, sTF had no effects on endothelial cell proliferation. Interestingly, sTF can be internalized by endothelial cells, whichmore » implies a novel mechanism for sTF in angiogenesis. These results suggest that sTF has unique angiogenic activities and may serve as a potential therapeutic target to treat diseases associated with angiogenesis such as cancer and rheumatoid arthritis.« less

Transapical aortic valve replacement is a safe option in patients with poor left ventricular ejection fraction: results from the Italian Transcatheter Balloon-Expandable Registry (ITER).

PubMed

D'Onofrio, Augusto; Salizzoni, Stefano; Filippini, Claudia; Agrifoglio, Marco; Alfieri, Ottavio; Chieffo, Alaide; Tarantini, Giuseppe; Gabbieri, Davide; Savini, Carlo; Immè, Sebastiano; Ribichini, Flavio; Cugola, Diego; Raviola, Eliana; Loi, Bruno; Pompei, Esmeralda; Cappai, Antioco; Cassese, Mauro; Luzi, Giampaolo; Aiello, Marco; Santini, Francesco; Rinaldi, Mauro; Gerosa, Gino

2017-11-01

The most commonly used accesses for transcatheter aortic valve implantation (TAVI) are the transfemoral (TF-TAVI) and the transapical (TA-TAVI) ones. There are concerns about TA-TAVI use in patients with reduced left ventricular ejection fraction (LVEF). The aim of this retrospective multicentre study was to compare the outcomes of TA-TAVI and TF-TAVI in patients with poor LVEF. Patients with LVEF ≤35% were included in the analysis. Data were obtained from the Italian Transcatheter Balloon-Expandable Registry (ITER), which enrolled patients undergoing TAVI with the Sapien bioprosthesis in 33 national centres. Patients were divided into 2 groups according to the access: TA or TF. A multivariable logistic regression analysis was performed in order to evaluate whether the type of approach (TA and TF) has an impact on outcomes. Between 2007 and 2012, 1882 patients were enrolled in the Registry. LVEF ≤35% was found in 208 (11.1%) patients. TA-TAVI and TF-TAVI were performed in 69 (33.2%) and 139 (66.8%) patients, respectively. Overall 30-day mortality was 11.6% and 7.9% in TA and TF patients, respectively (P = 0.45). Overall Kaplan-Meier survival was significantly higher in the TF-TAVI group (log rank: P = 0.003). Age [odds ratio (OR) 1.066, P = 0.016], creatinine (OR: 2.301, P < 0.001), preoperative permanent pacemaker (OR: 4.662, P = 0.035) and TA approach (OR: 2.577, P = 0.006) were identified as independent predictors of overall mortality at follow-up. However, the TA approach resulted an independent variable of mortality only 3 years after TAVI. TAVI yields good results in patients with depressed LVEF. Age, preoperative creatinine and preoperative pacemaker are independently associated with mortality. The TA access is associated with mortality only after 3 years of follow-up, thus probably reflecting a worse general clinical status of these patients. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

PlantTFDB 4.0: toward a central hub for transcription factors and regulatory interactions in plants.

PubMed

Jin, Jinpu; Tian, Feng; Yang, De-Chang; Meng, Yu-Qi; Kong, Lei; Luo, Jingchu; Gao, Ge

2017-01-04

With the goal of providing a comprehensive, high-quality resource for both plant transcription factors (TFs) and their regulatory interactions with target genes, we upgraded plant TF database PlantTFDB to version 4.0 (http://planttfdb.cbi.pku.edu.cn/). In the new version, we identified 320 370 TFs from 165 species, presenting a more comprehensive genomic TF repertoires of green plants. Besides updating the pre-existing abundant functional and evolutionary annotation for identified TFs, we generated three new types of annotation which provide more directly clues to investigate functional mechanisms underlying: (i) a set of high-quality, non-redundant TF binding motifs derived from experiments; (ii) multiple types of regulatory elements identified from high-throughput sequencing data; (iii) regulatory interactions curated from literature and inferred by combining TF binding motifs and regulatory elements. In addition, we upgraded previous TF prediction server, and set up four novel tools for regulation prediction and functional enrichment analyses. Finally, we set up a novel companion portal PlantRegMap (http://plantregmap.cbi.pku.edu.cn) for users to access the regulation resource and analysis tools conveniently. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Comparison of canal transportation and centering ability of twisted files, Pathfile-ProTaper system, and stainless steel hand K-files by using computed tomography.

PubMed

Gergi, Richard; Rjeily, Joe Abou; Sader, Joseph; Naaman, Alfred

2010-05-01

The purpose of this study was to compare canal transportation and centering ability of 2 rotary nickel-titanium (NiTi) systems (Twisted Files [TF] and Pathfile-ProTaper [PP]) with conventional stainless steel K-files. Ninety root canals with severe curvature and short radius were selected. Canals were divided randomly into 3 groups of 30 each. After preparation with TF, PP, and stainless steel files, the amount of transportation that occurred was assessed by using computed tomography. Three sections from apical, mid-root, and coronal levels of the canal were recorded. Amount of transportation and centering ability were assessed. The 3 groups were statistically compared with analysis of variance and Tukey honestly significant difference test. Less transportation and better centering ability occurred with TF rotary instruments (P < .0001). K-files showed the highest transportation followed by PP system. PP system showed significant transportation when compared with TF (P < .0001). The TF system was found to be the best for all variables measured in this study. Copyright (c) 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Drivers of U.S. toxicological footprints trajectory 1998–2013

PubMed Central

Koh, S. C. L.; Ibn-Mohammed, T.; Acquaye, A.; Feng, K.; Reaney, I. M.; Hubacek, K.; Fujii, H.; Khatab, K.

2016-01-01

By exploiting data from the Toxic Release Inventory of the United States, we have established that the toxicological footprint (TF) increased by 3.3% (88.4 Mt) between 1998 and 1999 and decreased by 39% (1088.5 Mt) between 1999 and 2013. From 1999 to 2006, the decreasing TF was driven by improvements in emissions intensity (i.e. gains in production efficiency) through toxic chemical management options: cleaner production; end of pipe treatment; transfer for further waste management; and production scale. In particular, the mining sector reduced its TF through outsourcing processes. Between 2006 and 2009, decreasing TF was due to decrease in consumption volume triggered by economic recession. Since 2009, the economic recovery increased TF, overwhelming the influence of improved emissions intensity through population growth, consumption and production structures. Accordingly, attaining a less-toxic economy and environment will be influenced by a combination of gains in production efficiency through improvement in emissions mitigation technologies and changes in consumption patterns. Overall, the current analysis highlights the structural dynamics of toxic chemical release and would inform future formulation of effective mitigation standards and management protocols towards the detoxification of the environment. PMID:28000739

Analysis of semiclassical approximations in the framework of quantumhadrodynamics

NASA Astrophysics Data System (ADS)

Speicher, C.; Engel, E.; Dreizler, R. M.

1993-10-01

We examine the importance of gradient corrections to the Thomas-Fermi (TF) approximation for the description of semi-infinite nuclear matter and nuclei within the framework of quantumhadrodynamics. The discussion of semi-infinite nuclear matter exhibits most clearly how surface properties depend on the parametrisation of the effective interaction. In agreement with earlier studies it is found that for parametrisations with low effective mass the original extended TF (ETF) equations cannot be solved. We present a scheme to overcome this problem which is very much in the spirit of the semiclassical approach and allows for a solution in any situation. For the case of nuclei the results of the TF and ETF approximations are compared to those of Hartree calculations which serve as a standard in this context. In accordance with the sensitivity of semi-infinite nuclear matter results to the specific parametrisation, ETF does not yield a consistent improvement over TF for all parametrisations. However, by examining a larger number of parametrisations it is shown that those cases where TF results are closer to Hartree data have to be regarded as fortuitous and that on average the agreement between ETF and Hartree results is clearly better.

The effect of corn trypsin inhibitor and inhibiting antibodies for FXIa and FXIIa on coagulation of plasma and whole blood.

PubMed

Hansson, K M; Nielsen, S; Elg, M; Deinum, J

2014-10-01

Corn trypsin inhibitor (CTI), an inhibitor of FXIIa, is used to prevent plasma coagulation by contact activation, to specifically investigate tissue factor (TF)-initiated coagulation. In the present work the specificity of CTI for factor (F) XIIa is questioned. In the commercial available plasma coagulation assays CTI was found to double activated partial thromboplastin time (APTT) at a plasma concentration of 7.3 ± 1.5 μm CTI (assay concentration 2.4 μm). No effect was found on the prothrombin time (PT) when high TF concentrations were used. Also, with specific antibodies for FXIIa and for FXIa only APTT was found to be extended but not PT. With specific enzyme assays using chromogenic substrates CTI was shown to be a strong inhibitor of FXIIa and a competitive inhibitor of FXIa with Ki  = 8.1 ± 0.3 μm, without effect on the coagulation factors FVIIa, FIXa, FXa and thrombin. In thrombin generation and coagulation (free oscillation rheometry, FOR) assays, initiated with low TF concentrations, no effect of CTI (plasma concentrations of 4.4 and 13.6 μm CTI, 25 resp. 100 mg L(-1) in blood) was found with ≥ 1 pm TF. At ≤ 0.1 pm TF in the FOR whole blood assay the coagulation time (CT) concentration dependently increased while the plasma CT became longer than the observation time. To avoid inhibition of FXIa and the thrombin feedback loop we recommend that for coagulation assays the concentration of CTI in blood should be below 20 mg L(-1) (1.6 μm) and in plasma below 3 μm. © 2014 International Society on Thrombosis and Haemostasis.

Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index.

PubMed

Skikne, Barry S; Punnonen, Kari; Caldron, Paul H; Bennett, Michael T; Rehu, Mari; Gasior, Gail H; Chamberlin, Janna S; Sullivan, Linda A; Bray, Kurtis R; Southwick, Paula C

2011-11-01

Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access(®) sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD. Copyright © 2011 Wiley-Liss, Inc.

Effects of an acidic environment on coagulation dynamics.

PubMed

Gissel, M; Brummel-Ziedins, K E; Butenas, S; Pusateri, A E; Mann, K G; Orfeo, T

2016-10-01

Essentials Acidosis, an outcome of traumatic injury, has been linked to impaired procoagulant efficiency. In vitro model systems were used to assess coagulation dynamics at pH 7.4 and 7.0. Clot formation dynamics are slightly enhanced at pH 7.0 in blood ex vivo. Acidosis induced decreases in antithrombin efficacy offset impairments in procoagulant activity. Background Disruption of hydrogen ion homeostasis is a consequence of traumatic injury often associated with clinical coagulopathy. Mechanisms by which acidification of the blood leads to aberrant coagulation require further elucidation. Objective To examine the effects of acidified conditions on coagulation dynamics using in vitro models of increasing complexity. Methods Coagulation dynamics were assessed at pH 7.4 and 7.0 as follows: (i) tissue factor (TF)-initiated coagulation proteome mixtures (±factor [F]XI, ±fibrinogen/FXIII), with reaction progress monitored as thrombin generation or fibrin formation; (ii) enzyme/inhibitor reactions; and (iii) TF-dependent or independent clot dynamics in contact pathway-inhibited blood via viscoelastometry. Results Rate constants for antithrombin inhibition of FXa and thrombin were reduced by ~ 25-30% at pH 7.0. At pH 7.0 (+FXI), TF-initiated thrombin generation showed a 20% increase in maximum thrombin levels and diminished thrombin clearance rates. Viscoelastic analyses showed a 25% increase in clot time and a 25% reduction in maximum clot firmness (MCF). A similar MCF reduction was observed at pH 7.0 when fibrinogen/FXIII were reacted with thrombin. In contrast, in contact pathway-inhibited blood (n = 6) at pH 7.0, MCF values were elevated 6% (95% confidence interval [CI]: 1%-11%) in TF-initiated blood and 15% (95% CI: 1%- 29%) in the absence of TF. Clot times at pH 7.0 decreased 32% (95% CI: 15%-49%) in TF-initiated blood and 51% (95% CI: 35%-68%) in the absence of TF. Conclusions Despite reported decreased procoagulant catalysis at pH 7.0, clot formation dynamics are slightly enhanced in blood ex vivo and suppression of thrombin generation is not observed. A decrease in antithrombin reactivity is one potential mechanism contributing to these outcomes. © 2016 International Society on Thrombosis and Haemostasis.

Analysis of distortion data from TF30-P-3 mixed compression inlet test

NASA Technical Reports Server (NTRS)

King, R. W.; Schuerman, J. A.; Muller, R. G.

1976-01-01

A program was conducted to reduce and analyze inlet and engine data obtained during testing of a TF30-P-3 engine operating behind a mixed compression inlet. Previously developed distortion analysis techniques were applied to the data to assist in the development of a new distortion methodology. Instantaneous distortion techniques were refined as part of the distortion methodology development. A technique for estimating maximum levels of instantaneous distortion from steady state and average turbulence data was also developed as part of the program.

Combinatorial Regulation of Stilbene Synthase Genes by WRKY and MYB Transcription Factors in Grapevine (Vitis vinifera L.).

PubMed

Vannozzi, Alessandro; Wong, Darren Chern Jan; Höll, Janine; Hmmam, Ibrahim; Matus, José Tomás; Bogs, Jochen; Ziegler, Tobias; Dry, Ian; Barcaccia, Gianni; Lucchin, Margherita

2018-05-01

Stilbene synthase (STS) is the key enzyme leading to the biosynthesis of resveratrol. Recently we reported two R2R3-MYB transcription factor (TF) genes that regulate the stilbene biosynthetic pathway in grapevine: VviMYB14 and VviMYB15. These genes are strongly co-expressed with STS genes under a range of stress and developmental conditions, in agreement with the specific activation of STS promoters by these TFs. Genome-wide gene co-expression analysis using two separate transcriptome compendia based on microarray and RNA sequencing data revealed that WRKY TFs were the top TF family correlated with STS genes. On the basis of correlation frequency, four WRKY genes, namely VviWRKY03, VviWRKY24, VviWRKY43 and VviWRKY53, were further shortlisted and functionally validated. Expression analyses under both unstressed and stressed conditions, together with promoter-luciferase reporter assays, suggested different hierarchies for these TFs in the regulation of the stilbene biosynthetic pathway. In particular, VviWRKY24 seems to act as a singular effector in the activation of the VviSTS29 promoter, while VviWRKY03 acts through a combinatorial effect with VviMYB14, suggesting that these two regulators may interact at the protein level as previously reported in other species.

Structural modulation of factor VIIa by full-length tissue factor (TF1-263): implication of novel interactions between EGF2 domain and TF.

PubMed

Prasad, Ramesh; Sen, Prosenjit

2018-02-01

Tissue factor (TF)-mediated factor VII (FVII) activation and a subsequent proteolytic TF-FVIIa binary complex formation is the key step initiating the coagulation cascade, with implications in various homeostatic and pathologic scenarios. TF binding allosterically modifies zymogen-like free FVIIa to its highly catalytically active form. As a result of unresolved crystal structure of the full-length TF 1-263 -FVIIa binary complex and free FVIIa, allosteric alterations in FVIIa following its binding to full-length TF and the consequences of these on function are not entirely clear. The present study aims to map and identify structural alterations in FVIIa and TF resulting from full-length TF binding to FVIIa and the key events responsible for enhanced FVIIa activity in coagulation. We constructed the full-length TF 1-263 -FVIIa membrane bound complex using computational modeling and subjected it to molecular dynamics (MD) simulations. MD simulations showed that TF alters the structure of each domain of FVIIa and these combined alterations contribute to enhanced TF-FVIIa activity. Detailed, domain-wise investigation revealed several new non-covalent interactions between TF and FVIIa that were not found in the truncated soluble TF-FVIIa crystal structure. The structural modulation of each FVIIa domain imparted by TF indicated that both inter and intra-domain communication is crucial for allosteric modulation of FVIIa. Our results suggest that these newly formed interactions can provide additional stability to the protease domain and regulate its activity profile by governing catalytic triad (CT) orientation and localization. The unexplored newly formed interactions between EGF2 and TF provides a possible explanation for TF-induced allosteric activation of FVIIa.

Detection of cerebrospinal fluid leakage by specific measurement of transferrin glycoforms.

PubMed

Kwon, Seok-Joon; Zhang, Fuming; Dordick, Jonathan S; Sonstein, William J; Linhardt, Robert J

2015-10-01

A simple and rapid detection of cerebrospinal fluid (CSF) leakage would benefit spine surgeons making critical postoperative decisions on patient care. We have assessed novel approaches to selectively determine CSF β2-transferrin (β2TF), an asialo-transferrin (aTF) biomarker, without interference from serum sialo-transferrin (sTF) in test samples. First, we performed mild periodate oxidation to selectively generate aldehyde groups in sTF for capture with magnetic hydrazide microparticles, and selective removal with a magnetic separator. Using this protocol sTF was selectively removed from mixtures of CSF and serum containing CSF aTF (β2TF) and serum sTF, respectively. Second, a two-step enzymatic method was developed with neuraminidase and galactose oxidase for generating aldehyde groups in sTF present in CSF and serum mixtures for magnetic hydrazide microparticle capture. After selectively removing sTF from mixtures of CSF and serum, ELISA could detect significant TF signal only in CSF, while the TF signal in serum was negligible. The new approach for selective removal of only sTF in test samples will be promising for the required intervention by a spine surgeon. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mathematical modeling of mutant transferrin-CRM107 molecular conjugates for cancer therapy.

PubMed

Yoon, Dennis J; Chen, Kevin Y; Lopes, André M; Pan, April A; Shiloach, Joseph; Mason, Anne B; Kamei, Daniel T

2017-03-07

The transferrin (Tf) trafficking pathway is a promising mechanism for use in targeted cancer therapy due to the overexpression of transferrin receptors (TfRs) on cancerous cells. We have previously developed a mathematical model of the Tf/TfR trafficking pathway to improve the efficiency of Tf as a drug carrier. By using diphtheria toxin (DT) as a model toxin, we found that mutating the Tf protein to change its iron release rate improves cellular association and efficacy of the drug. Though this is an improvement upon using wild-type Tf as the targeting ligand, conjugated toxins like DT are unfortunately still highly cytotoxic at off-target sites. In this work, we address this hurdle in cancer research by developing a mathematical model to predict the efficacy and selectivity of Tf conjugates that use an alternative toxin. For this purpose, we have chosen to study a mutant of DT, cross-reacting material 107 (CRM107). First, we developed a mathematical model of the Tf-DT trafficking pathway by extending our Tf/TfR model to include intracellular trafficking via DT and DT receptors. Using this mathematical model, we subsequently investigated the efficacy of several conjugates in cancer cells: DT and CRM107 conjugated to wild-type Tf, as well as to our engineered mutant Tf proteins (K206E/R632A Tf and K206E/R534A Tf). We also investigated the selectivity of mutant Tf-CRM107 against non-neoplastic cells. Through the use of our mathematical model, we predicted that (i) mutant Tf-CRM107 exhibits a greater cytotoxicity than wild-type Tf-CRM107 against cancerous cells, (ii) this improvement was more drastic with CRM107 conjugates than with DT conjugates, and (iii) mutant Tf-CRM107 conjugates were selective against non-neoplastic cells. These predictions were validated with in vitro cytotoxicity experiments, demonstrating that mutant Tf-CRM107 conjugates is indeed a more suitable therapeutic agent. Validation from in vitro experiments also confirmed that such whole-cell kinetic models can be useful in cancer therapeutic design. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sundanese ancient manuscripts search engine using probability approach

NASA Astrophysics Data System (ADS)

Suryani, Mira; Hadi, Setiawan; Paulus, Erick; Nurma Yulita, Intan; Supriatna, Asep K.

2017-10-01

Today, Information and Communication Technology (ICT) has become a regular thing for every aspect of live include cultural and heritage aspect. Sundanese ancient manuscripts as Sundanese heritage are in damage condition and also the information that containing on it. So in order to preserve the information in Sundanese ancient manuscripts and make them easier to search, a search engine has been developed. The search engine must has good computing ability. In order to get the best computation in developed search engine, three types of probabilistic approaches: Bayesian Networks Model, Divergence from Randomness with PL2 distribution, and DFR-PL2F as derivative form DFR-PL2 have been compared in this study. The three probabilistic approaches supported by index of documents and three different weighting methods: term occurrence, term frequency, and TF-IDF. The experiment involved 12 Sundanese ancient manuscripts. From 12 manuscripts there are 474 distinct terms. The developed search engine tested by 50 random queries for three types of query. The experiment results showed that for the single query and multiple query, the best searching performance given by the combination of PL2F approach and TF-IDF weighting method. The performance has been evaluated using average time responds with value about 0.08 second and Mean Average Precision (MAP) about 0.33.

Distinct Modes of Regulation of Transcription of Hepatitis B Virus by the Nuclear Receptors HNF4α and COUP-TF1

PubMed Central

Yu, Xianming; Mertz, Janet E.

2003-01-01

To study the effects of the nuclear receptors (NRs) HNF4α and COUP-TF1 on the life cycle of hepatitis B virus (HBV), the human hepatoma cell line Huh7 was transiently cotransfected with plasmids containing the HBV genome and encoding these two NRs. Overexpression of HNF4α and COUP-TF1 led to a 9-fold increase and a 7- to 10-fold decrease, respectively, in viral DNA synthesis. These two NRs also exhibited distinct modes of regulation of viral transcription. Overexpression of HNF4α led to a more-than-10-fold increase in synthesis of the pregenomic RNA but to only a 2- to 3-fold increase in synthesis of the pre-C and S RNAs. Moreover, the NR response element within the pre-C promoter, NRREpreC, played the major role in activation of pregenomic RNA synthesis by HNF4α. On the other hand, overexpression of COUP-TF1 led to an over-10-fold repression of synthesis of both pre-C and pregenomic RNAs mediated through either NRREpreC or NRREenhI. HNF4α and COUP-TF1 antagonized each other's effects on synthesis of pregenomic RNA and viral DNA when they were co-overexpressed. A naturally occurring HBV variant which allows for binding by HNF4α but not COUP-TF1 in its NRREpreC exhibited significantly higher levels of synthesis of pregenomic RNA and viral DNA than wild-type HBV in coexpression experiments. Last, deletion analysis revealed that non-NRRE sequences located within both the C and pre-S1 regions are also essential for maximum activation of the pregenomic promoter by HNF4α but not for repression by COUP-TF1. Thus, HNF4α and COUP-TF1 function through different mechanisms to regulate expression of the HBV genes. PMID:12551987

Distinct modes of regulation of transcription of hepatitis B virus by the nuclear receptors HNF4alpha and COUP-TF1.

PubMed

Yu, Xianming; Mertz, Janet E

2003-02-01

To study the effects of the nuclear receptors (NRs) HNF4alpha and COUP-TF1 on the life cycle of hepatitis B virus (HBV), the human hepatoma cell line Huh7 was transiently cotransfected with plasmids containing the HBV genome and encoding these two NRs. Overexpression of HNF4alpha and COUP-TF1 led to a 9-fold increase and a 7- to 10-fold decrease, respectively, in viral DNA synthesis. These two NRs also exhibited distinct modes of regulation of viral transcription. Overexpression of HNF4alpha led to a more-than-10-fold increase in synthesis of the pregenomic RNA but to only a 2- to 3-fold increase in synthesis of the pre-C and S RNAs. Moreover, the NR response element within the pre-C promoter, NRRE(preC,) played the major role in activation of pregenomic RNA synthesis by HNF4alpha. On the other hand, overexpression of COUP-TF1 led to an over-10-fold repression of synthesis of both pre-C and pregenomic RNAs mediated through either NRRE(preC) or NRRE(enhI). HNF4alpha and COUP-TF1 antagonized each other's effects on synthesis of pregenomic RNA and viral DNA when they were co-overexpressed. A naturally occurring HBV variant which allows for binding by HNF4alpha but not COUP-TF1 in its NRRE(preC) exhibited significantly higher levels of synthesis of pregenomic RNA and viral DNA than wild-type HBV in coexpression experiments. Last, deletion analysis revealed that non-NRRE sequences located within both the C and pre-S1 regions are also essential for maximum activation of the pregenomic promoter by HNF4alpha but not for repression by COUP-TF1. Thus, HNF4alpha and COUP-TF1 function through different mechanisms to regulate expression of the HBV genes.

Parameterization of Photon Tunneling with Application to Ice Cloud Optical Properties at Terrestrial Wavelengths

NASA Astrophysics Data System (ADS)

Mitchell, D. L.

2006-12-01

Sometimes deep physical insights can be gained through the comparison of two theories of light scattering. Comparing van de Hulst's anomalous diffraction approximation (ADA) with Mie theory yielded insights on the behavior of the photon tunneling process that resulted in the modified anomalous diffraction approximation (MADA). (Tunneling is the process by which radiation just beyond a particle's physical cross-section may undergo large angle diffraction or absorption, contributing up to 40% of the absorption when wavelength and particle size are comparable.) Although this provided a means of parameterizing the tunneling process in terms of the real index of refraction and size parameter, it did not predict the efficiency of the tunneling process, where an efficiency of 100% is predicted for spheres by Mie theory. This tunneling efficiency, Tf, depends on particle shape and ranges from 0 to 1.0, with 1.0 corresponding to spheres. Similarly, by comparing absorption efficiencies predicted by the Finite Difference Time Domain Method (FDTD) with efficiencies predicted by MADA, Tf was determined for nine different ice particle shapes, including aggregates. This comparison confirmed that Tf is a strong function of ice crystal shape, including the aspect ratio when applicable. Tf was lowest (< 0.36) for aggregates and plates, and largest (> 0.9) for quasi- spherical shapes. A parameterization of Tf was developed in terms of (1) ice particle shape and (2) mean particle size regarding the large mode (D > 70 mm) of the ice particle size distribution. For the small mode, Tf is only a function of ice particle shape. When this Tf parameterization is used in MADA, absorption and extinction efficiency differences between MADA and FDTD are within 14% over the terrestrial wavelength range 3-100 mm for all size distributions and most crystal shapes likely to be found in cirrus clouds. Using hyperspectral radiances, it is demonstrated that Tf can be retrieved from ice clouds. Since Tf is a function of ice particle shape, this may provide a means of retrieving qualitative information on ice particle shape.

Structural modelling and molecular dynamics of a multi-stress responsive WRKY TF-DNA complex towards elucidating its role in stress signalling mechanisms in chickpea.

PubMed

Konda, Aravind Kumar; Farmer, Rohit; Soren, Khela Ram; P S, Shanmugavadivel; Setti, Aravind

2017-07-28

Chickpea is a premier food legume crop with high nutritional quality and attains prime importance in the current era of 795 million people being undernourished worldwide. Chickpea production encounters setbacks due to various stresses and understanding the role of key transcription factors (TFs) involved in multiple stresses becomes inevitable. We have recently identified a multi-stress responsive WRKY TF in chickpea. The present study was conducted to predict the structure of WRKY TF to identify the DNA-interacting residues and decipher DNA-protein interactions. Comparative modelling approach produced 3D model of the WRKY TF with good stereochemistry, local/global quality and further revealed W19, R20, K21, and Y22 motifs within a vicinity of 5 Å to the DNA amongst R18, G23, Q24, K25, Y36, Y37, R38 and K47 and these positions were equivalent to the 2LEX WRKY domain of Arabidopsis. Molecular simulations analysis of reference protein -PDB ID 2LEX, along with Car-WRKY TF modelled structure with the DNA coordinates derived from PDB ID 2LEX and docked using HADDOCK were executed. Root Mean Square (RMS) Deviation and RMS Fluctuation values yielded consistently stable trajectories over 50 ns simulation. Strengthening the obtained results, neither radius of gyration, distance and total energy showed any signs of DNA-WRKY complex falling apart nor any significant dissociation event over 50 ns run. Therefore, the study provides first insights into the structural properties of multi-stress responsive WRKY TF-DNA complex in chickpea, enabling genome wide identification of TF binding sites and thereby deciphers their gene regulatory networks.

Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction

PubMed Central

Parashurama, Natesh; Ahn, Byeong-Cheol; Ziv, Keren; Ito, Ken; Paulmurugan, Ramasamy; Willmann, Jürgen K.; Chung, Jaehoon; Ikeno, Fumiaki; Swanson, Julia C.; Merk, Denis R.; Lyons, Jennifer K.; Yerushalmi, David; Teramoto, Tomohiko; Kosuge, Hisanori; Dao, Catherine N.; Ray, Pritha; Patel, Manishkumar; Chang, Ya-fang; Mahmoudi, Morteza; Cohen, Jeff Eric; Goldstone, Andrew Brooks; Habte, Frezghi; Bhaumik, Srabani; Yaghoubi, Shahriar; Robbins, Robert C.; Dash, Rajesh; Yang, Phillip C.; Brinton, Todd J.; Yock, Paul G.; McConnell, Michael V.

2016-01-01

Purpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow–derived MSC that expressed a multimodality triple fusion (TF) reporter gene. The TF reporter gene (fluc2-egfp-sr39ttk) consisted of a human promoter, ubiquitin, driving firefly luciferase 2 (fluc2), enhanced green fluorescent protein (egfp), and the sr39tk positron emission tomography reporter gene. Serial bioluminescence imaging of MSC-TF and ex vivo luciferase assays were performed. Correlations were analyzed with the Pearson product-moment correlation, and serial imaging results were analyzed with a mixed-effects regression model. Results Analysis of the MSC-TF after cardiac cell therapy showed significantly lower signal on days 8 and 14 than on day 2 (P = .011 and P = .001, respectively). MSC-TF with MI demonstrated significantly higher signal than MSC-TF without MI at days 4, 8, and 14 (P = .016). Ex vivo luciferase activity assay confirmed the presence of MSC-TF on days 8 and 14 after MI. Conclusion Multimodality reporter-gene imaging was successfully used to assess serial MSC survival after therapy for MI, and it was determined that the requisite preclinical imaging end point, 14 days of MSC survival, was met prior to a follow-up large-animal MSC study. © RSNA, 2016 Online supplemental material is available for this article. PMID:27308957

Single-Nucleotide-Specific Targeting of the Tf1 Retrotransposon Promoted by the DNA-Binding Protein Sap1 of Schizosaccharomyces pombe.

PubMed

Hickey, Anthony; Esnault, Caroline; Majumdar, Anasuya; Chatterjee, Atreyi Ghatak; Iben, James R; McQueen, Philip G; Yang, Andrew X; Mizuguchi, Takeshi; Grewal, Shiv I S; Levin, Henry L

2015-11-01

Transposable elements (TEs) constitute a substantial fraction of the eukaryotic genome and, as a result, have a complex relationship with their host that is both adversarial and dependent. To minimize damage to cellular genes, TEs possess mechanisms that target integration to sequences of low importance. However, the retrotransposon Tf1 of Schizosaccharomyces pombe integrates with a surprising bias for promoter sequences of stress-response genes. The clustering of integration in specific promoters suggests that Tf1 possesses a targeting mechanism that is important for evolutionary adaptation to changes in environment. We report here that Sap1, an essential DNA-binding protein, plays an important role in Tf1 integration. A mutation in Sap1 resulted in a 10-fold drop in Tf1 transposition, and measures of transposon intermediates support the argument that the defect occurred in the process of integration. Published ChIP-Seq data on Sap1 binding combined with high-density maps of Tf1 integration that measure independent insertions at single-nucleotide positions show that 73.4% of all integration occurs at genomic sequences bound by Sap1. This represents high selectivity because Sap1 binds just 6.8% of the genome. A genome-wide analysis of promoter sequences revealed that Sap1 binding and amounts of integration correlate strongly. More important, an alignment of the DNA-binding motif of Sap1 revealed integration clustered on both sides of the motif and showed high levels specifically at positions +19 and -9. These data indicate that Sap1 contributes to the efficiency and position of Tf1 integration. Copyright © 2015 by the Genetics Society of America.

Single-Nucleotide-Specific Targeting of the Tf1 Retrotransposon Promoted by the DNA-Binding Protein Sap1 of Schizosaccharomyces pombe

PubMed Central

Hickey, Anthony; Esnault, Caroline; Majumdar, Anasuya; Chatterjee, Atreyi Ghatak; Iben, James R.; McQueen, Philip G.; Yang, Andrew X.; Mizuguchi, Takeshi; Grewal, Shiv I. S.; Levin, Henry L.

2015-01-01

Transposable elements (TEs) constitute a substantial fraction of the eukaryotic genome and, as a result, have a complex relationship with their host that is both adversarial and dependent. To minimize damage to cellular genes, TEs possess mechanisms that target integration to sequences of low importance. However, the retrotransposon Tf1 of Schizosaccharomyces pombe integrates with a surprising bias for promoter sequences of stress-response genes. The clustering of integration in specific promoters suggests that Tf1 possesses a targeting mechanism that is important for evolutionary adaptation to changes in environment. We report here that Sap1, an essential DNA-binding protein, plays an important role in Tf1 integration. A mutation in Sap1 resulted in a 10-fold drop in Tf1 transposition, and measures of transposon intermediates support the argument that the defect occurred in the process of integration. Published ChIP-Seq data on Sap1 binding combined with high-density maps of Tf1 integration that measure independent insertions at single-nucleotide positions show that 73.4% of all integration occurs at genomic sequences bound by Sap1. This represents high selectivity because Sap1 binds just 6.8% of the genome. A genome-wide analysis of promoter sequences revealed that Sap1 binding and amounts of integration correlate strongly. More important, an alignment of the DNA-binding motif of Sap1 revealed integration clustered on both sides of the motif and showed high levels specifically at positions +19 and −9. These data indicate that Sap1 contributes to the efficiency and position of Tf1 integration. PMID:26358720

Evaluation of a dense seismic array for acquisition of high quality data in the ACROSS observation

NASA Astrophysics Data System (ADS)

Tsuruga, K.; Kunitomo, T.; Hasada, Y.; Kumazawa, M.; Shigeta, N.; Kasahara, J.

2004-12-01

ACROSS is an active monitoring methodology to detect any subtle temporal change of physical properties in the Earth's interior. We demonstrate the potentiality of the ACROSS observation with a dense sensor array. We have conducted a dense seismic array observation at the distance of 1 km from the ACROSS source since 2003. The array is composed of 36 three-component velocity seismometers buried at 1.8 m deep in an area 25 m square. All the data are recorded accurately referring to a GPS clock. We derived and analyzed a transfer function (TF) from the source to a receiver by the following steps: (1) evaluating a force vector as source characteristics, (2) converting the observed data to the displacement vectors by incorporating all the corrections of the instruments, (3) stacking the observed data for an enough time to suppress the temporal noise, (4) extracting ACROSS signal and evaluating noise level, (5) representing TF in a tensor form with the estimated errors, (6) slant-stacking with variable ray parameters, (7) estimating the travel times and amplitudes of the wave arrivals by Sompi Event Analysis (Hasada et al., 2001) and representing the result by a pulse sequence, and (8) deriving the polarization vector for each arrival to identify all the wave modes. We analyzed TF of SH-wave component from 16 to 20 Hz as an example. We obtained good quality TF with S/N ratio up to 104 by stacking for 12 days at the step (3). The spatial noise originated from the local heterogeneity around the array was eliminated by the step (6). Several arrivals were recognized within the time windows from 0.6 to 1.8 s. The maximum amplitude of event traces was detected at the travel time of 1.064 s with a ray parameter of 7.9x10-4 s/m. We also found the scattered waves probably generated by the heterogeneities around the array. The ACROSS dense array observation would provide a lot of information on the underground heterogeneities. Consequently, we have the important and challenging subjects: (1) optimum designing of ACROSS array to acquire the better data and (2) development of new theoretical method to deal with the variable types of the wave.

Electromagnetic Launching for Affordable Agile Access to Space

DTIC Science & Technology

2006-04-15

requirements are advantageous compared to other EM launch technologies. 14 I Pp TRI TF1 (P) TR2 TF2 (P) ... TRM TFM (P) TF1 TRI(n) TF2 TH .)񔰣 -n F- on 71...some integer M. The distance between the rear coil TRI and the corresponding front coil TF1 is MxPT. PP: distance between coils in the projectile, PT...TRI with TFI/p), TR2 with TF2(P) ..., and also TR/("),with TF1 , TR2(n)with TF2, etc. ). * For a slender projectile (i.e. length >> diameter), it is

Transmitted/Founder Viruses Rapidly Escape from CD8+ T Cell Responses in Acute Hepatitis C Virus Infection.

PubMed

Bull, Rowena A; Leung, Preston; Gaudieri, Silvana; Deshpande, Pooja; Cameron, Barbara; Walker, Melanie; Chopra, Abha; Lloyd, Andrew R; Luciani, Fabio

2015-05-01

The interaction between hepatitis C virus (HCV) and cellular immune responses during very early infection is critical for disease outcome. To date, the impact of antigen-specific cellular immune responses on the evolution of the viral population establishing infection and on potential escape has not been studied. Understanding these early host-virus dynamics is important for the development of a preventative vaccine. Three subjects who were followed longitudinally from the detection of viremia preseroconversion until disease outcome were analyzed. The evolution of transmitted/founder (T/F) viruses was undertaken using deep sequencing. CD8(+) T cell responses were measured via enzyme-linked immunosorbent spot (ELISpot) assay using HLA class I-restricted T/F epitopes. T/F viruses were rapidly extinguished in all subjects associated with either viral clearance (n = 1) or replacement with viral variants leading to establishment of chronic infection (n = 2). CD8(+) T cell responses against 11 T/F epitopes were detectable by 33 to 44 days postinfection, and 5 of these epitopes had not previously been reported. These responses declined rapidly in those who became chronically infected and were maintained in the subject who cleared infection. Higher-magnitude CD8(+) T cell responses were associated with rapid development of immune escape variants at a rate of up to 0.1 per day. Rapid escape from CD8(+) T cell responses has been quantified for the first time in the early phase of primary HCV infection. These rapid escape dynamics were associated with higher-magnitude CD8(+) T cell responses. These findings raise questions regarding optimal selection of immunogens for HCV vaccine development and suggest that detailed analysis of individual epitopes may be required. A major limitation in our detailed understanding of the role of immune response in HCV clearance has been the lack of data on very early primary infection when the transmitted viral variants successfully establish the acute infection. This study was made possible through the availability of specimens from a unique cohort of asymptomatic primary infection cases in whom the first available viremic samples were collected approximately 3 weeks postinfection and at regular intervals thereafter. The study included detailed examination of both the evolution of the viral population and the host cellular immune responses against the T/F viruses. The findings here provide the first evidence of host cellular responses targeting T/F variants and imposing a strong selective force toward viral escape. The results of this study provide useful insight on how virus escapes the host response and consequently on future analysis of vaccine-induced immunity. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Long-term efficacy and safety of rilpivirine plus abacavir and lamivudine in HIV-1 infected patients with undetectable viral load.

PubMed

Galizzi, Nadia; Galli, Laura; Poli, Andrea; Gianotti, Nicola; Carini, Elisabetta; Bigoloni, Alba; Tambussi, Giuseppe; Nozza, Silvia; Lazzarin, Adriano; Castagna, Antonella; Mancusi, Daniela; Termini, Roberta

2018-01-01

A regimen with rilpivirine (RPV), abacavir (ABC) and lamivudine (3TC) is simple and may allow the sparing of tenofovir and protease inhibitors. However, data on use of this combination as a strategy of switch are limited. Aims of the study were to assess the long-term efficacy and safety of this regimen. Retrospective study on HIV-1 infected patients followed at the Infectious Disease Department of the San Raffaele Scientific Institute, HBsAg-negative, HLA B5701-negative, with no documented resistance to RPV, ABC and 3TC, with HIV-RNA<50 copies/mL who started RPV plus ABC/3TC from March 2013 to September 2015. The primary outcome was durability [no treatment failure (TF)]. Secondary objectives were to evaluate changes in immunological, metabolic and other safety parameters. TF was defined as the occurrence of virological failure (VF, 2 consecutive values >50 copies/mL) or discontinuation of any drug in the regimen for any reason. Patients' follow-up accrued from the date of RPV plus ABC/3TC initiation to the date of TF (VF or discontinuation of any drug in the regimen) or to the date of last available visit. Time to TF was evaluated by use of the Kaplan-Meier curves. Mixed linear models were applied to evaluate changes in immunological, metabolic and other safety parameters. In this analysis, 100 patients starting RPV plus ABC/3TC were included. By 12, 24 and 36 months after switching to RPV plus ABC/3TC, the proportions of individuals without TF were 88% [95% confidence interval (CI): 79%-93%], 82% (95% CI:73%-89%) and 78% (95% CI:68%-86%), respectively. Time to TF was not significantly influenced by CD4+ nadir (≤200 vs >200 cells/μl; log-rank test: p = 0.311) or pre-ART viral load (<100000 vs ≥100000 copies/mL; log-rank test: p = 0.574) or the type of previous antiretroviral regimen (PI+2NRTIs vs NNRTI+2NRTIs vs Other; log-rank test: p = 0.942). Over a median follow-up of 2.9 years (IQR: 1.9-3.5), 26 subjects discontinued the treatment [10 due to toxicity, 7 for interactions with other drugs, 3 due to cardiovascular risk concern, 2 due to single viral blip, 1 due to VF, 1 for asthma, 1 patient's decision, 1 due to enrolment in a study protocol]. In this retrospective study, long-term use of RPV plus ABC/3TC regimen is effective and safe. Efficacy of this regimen was not found to be affected by low CD4+ nadir or high pre-ART viral load.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robison, W L; Hamilton, T F; Bogen, K

Inter-plant concentration ratios (IPCR), [Bq g{sup -1} {sup 137}Cs in coral atoll tree food-crops/Bq g{sup -1} {sup 137}Cs in leaves of native plant species whose roots share a common soil volume], can replace transfer factors (TF) to predict {sup 137}Cs concentration in tree food-crops in a contaminated area with an aged source term. The IPCR strategy has significant benefits relative to TF strategy for such purposes in the atoll ecosystem. IPCR strategy applied to specific assessments takes advantage of the fact tree roots naturally integrate 137Cs over large volumes of soil. Root absorption of {sup 137}Cs replaces large-scale, expensive soilmore » sampling schemes to reduce variability in {sup 137}Cs concentration due to inhomogeneous radionuclide distribution. IPCR [drinking-coconut meat (DCM)/Scaevola (SCA) and Tournefortia (TOU) leaves (native trees growing on all atoll islands)] are log normally distributed (LND) with geometric standard deviation (GSD) = 1.85. TF for DCM from Enewetak, Eneu, Rongelap and Bikini Atolls are LND with GSD's of 3.5, 3.0, 2.7, and 2.1, respectively. TF GSD for Rongelap copra coconut meat is 2.5. IPCR of Pandanus fruit to SCA and TOU leaves are LND with GSD = 1.7 while TF GSD is 2.1. Because IPCR variability is much lower than TF variability, relative sampling error of an IPCR field sample mean is up 6- to 10-fold lower than that of a TF sample mean if sample sizes are small (10 to 20). Other IPCR advantages are that plant leaf samples are collected and processed in far less time with much less effort and cost than soil samples.« less

Evaluation of procoagulant tissue factor expression in canine hemangiosarcoma cell lines.

PubMed

Witter, Lauren E; Gruber, Erika J; Lean, Fabian Z X; Stokol, Tracy

2017-01-01

OBJECTIVE To evaluate expression of procoagulant tissue factor (TF) by canine hemangiosarcoma cells in vitro. SAMPLES 4 canine hemangiosarcoma cell lines (SB-HSA [mouse-passaged cutaneous tumor], Emma [primary metastatic brain tumor], and Frog and Dal-1 [primary splenic tumors]) and 1 nonneoplastic canine endothelial cell line (CnAoEC). PROCEDURES TF mRNA and TF antigen expression were evaluated by quantitative real-time PCR assay and flow cytometry, respectively. Thrombin generation was measured in canine plasma and in coagulation factor-replete or specific coagulation factor-deficient human plasma by calibrated automated thrombography. Corn trypsin inhibitor and annexin V were used to examine contributions of contact activation and membrane-bound phosphatidylserine, respectively, to thrombin generation. RESULTS All cell lines expressed TF mRNA and antigen, with significantly greater expression of both products in SB-HSA and Emma cells than in CnAoEC. A greater percentage of SB-HSA cells expressed TF antigen, compared with other hemangiosarcoma cell lines. All hemangiosarcoma cell lines generated significantly more thrombin than did CnAoEC in canine or factor-replete human plasma. Thrombin generation induced by SB-HSA cells was significantly lower in factor VII-deficient plasma than in factor-replete plasma and was abolished in factor X-deficient plasma; residual thrombin generation in factor VII-deficient plasma was abolished by incubation of cells with annexin V. Thrombin generation by SB-HSA cells was unaffected by the addition of corn trypsin inhibitor. CONCLUSIONS AND CLINICAL RELEVANCE Hemangiosarcoma cell lines expressed procoagulant TF in vitro. Further research is needed to determine whether TF can be used as a biomarker for hemostatic dysfunction in dogs with hemangiosarcoma.

Evaluation of procoagulant tissue factor expression in canine hemangiosarcoma cell lines

PubMed Central

Witter, Lauren E.; Gruber, Erika J.; Lean, Fabian Z. X.; Stokol, Tracy

2017-01-01

OBJECTIVE To evaluate expression of procoagulant tissue factor (TF) by canine hemangiosarcoma cells in vitro. SAMPLES 4 canine hemangiosarcoma cell lines (SB-HSA [mouse-passaged cutaneous tumor], Emma [primary metastatic brain tumor], and Frog and Dal-1 [primary splenic tumors]) and 1 nonneoplastic canine endothelial cell line (CnAoEC). PROCEDURES TF mRNA and TF antigen expression were evaluated by quantitative real-time PCR assay and flow cytometry, respectively. Thrombin generation was measured in canine plasma and in coagulation factor–replete or specific coagulation factor–deficient human plasma by calibrated automated thrombography. Corn trypsin inhibitor and annexin V were used to examine contributions of contact activation and membrane-bound phosphatidylserine, respectively, to thrombin generation. RESULTS All cell lines expressed TF mRNA and antigen, with significantly greater expression of both products in SB-HSA and Emma cells than in CnAoEC. A greater percentage of SB-HSA cells expressed TF antigen, compared with other hemangiosarcoma cell lines. All hemangiosarcoma cell lines generated significantly more thrombin than did CnAoEC in canine or factor-replete human plasma. Thrombin generation induced by SB-HSA cells was significantly lower in factor VII-deficient plasma than in factor-replete plasma and was abolished in factor X–deficient plasma; residual thrombin generation in FVII-deficient plasma was abolished by incubation of cells with annexin V. Thrombin generation by SB-HSA cells was unaffected by the addition of corn trypsin inhibitor. CONCLUSIONS AND CLINICAL RELEVANCE Hemangiosarcoma cell lines expressed procoagulant TF in vitro. Further research is needed to determine whether TF can be used as a biomarker for hemostatic dysfunction in dogs with hemangiosarcoma. PMID:28029283

Microparticle-associated tissue factor activity correlates with plasma levels of bacterial lipopolysaccharides in meningococcal septic shock.

PubMed

Hellum, Marit; Øvstebø, Reidun; Brusletto, Berit S; Berg, Jens P; Brandtzaeg, Petter; Henriksson, Carola E

2014-03-01

The plasma level of bacterial lipopolysaccharides (LPS) is associated with activation of the coagulation system, inhibition of fibrinolysis and the nature of the clinical presentation and outcome in patients with meningococcal disease. Tissue factor (TF)-bearing microparticles (MPs) appear to contribute to the pathogenesis of disseminated intravascular coagulation (DIC). The aim of this study was to investigate the relationship between MP-associated TF activity and the level of bacterial LPS in plasma from patients with meningococcal septic shock and meningitis. MPs isolated from citrated plasmas were assessed for TF-dependent activity with both a plasma-based thrombin generation assay (CAT) and whole blood-based thromboelastometry (ROTEM). The LPS level was measured using a chromogenic Limulus amebocyte lysate assay. MPs obtained from patients with meningococcal septic shock initiated significantly more efficient and TF-dependent thrombin generation in the CAT assay compared to MPs from patients with meningococcal meningitis. Differences in MP-associated TF activity between the septic shock patients and the meningitis patients were also evident when MPs were added to whole blood using ROTEM. The level of plasma LPS in patients with septic shock (range 2-2,100 EU/mL) was correlated with thrombogram parameters in the CAT assay; lagtime (r(s)=-0.84), time to peak (rs=-0.83), peak (r(s)=0.85) and ETP (r(s)=0.83). MPs obtained from patients with meningococcal septic shock displayed more efficient TF-dependent thrombin generation and clot formation compared to MPs from meningitis patients. MP-associated TF activity was closely associated with plasma LPS levels in the septic shock group. Copyright © 2013 Elsevier Ltd. All rights reserved.

IgG sera levels against a subset of periodontopathogens and severity of disease in aggressive periodontitis patients: a cross-sectional study of selected pocket sites.

PubMed

Saraiva, Luciana; Rebeis, Estela S; Martins, Eder de S; Sekiguchi, Ricardo T; Ando-Suguimoto, Ellen S; Mafra, Carlos Eduardo S; Holzhausen, Marinella; Romito, Giuseppe A; Mayer, Marcia P A

2014-10-01

To evaluate the association among serum immunoglobulin G (IgG) responses to Aggregatibacter actinomycetemcomitans (Aa) serotypes a, b and c, Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf) and clinical parameters in Aggressive Periodontitis (AP) subjects. Associations between periodontal pathogens and clinical and immunological parameters were also evaluated. Thirty-eight subjects diagnosed with generalized AP (GAP) and localized AP (LAP) were included. Ten healthy controls were also evaluated. Clinical parameters were assessed and percentages of subgingival levels of Aa, Pg and Tf (beyond bacterial load), were determined by quantitative real-time polymerase chain reaction. Serum IgG antibody levels against Aa, Pg and Tf were evaluated by enzyme-linked immunosorbent assay. Percentages of Aa, Pg and Tf were significantly higher in AP than in controls. The response to Aa serotype c was higher in LAP subjects than in controls. There were no differences in microbial composition or antibodies responses between GAP and LAP, except for IgG response to Tf. Pg levels were correlated with probing depth (PD), BoP and CAL in GAP but not in LAP subjects. Tf levels correlated with PD and CAL in GAP subjects. In GAP, the infection levels of Aa and Pg correlated with the corresponding IgG levels to Aa serotype c and Pg. Given the evidences that IgG response in AP patients correlated with bacterial infection level in GAP, but not in LAP, and that LAP patients lack a response to Tf, despite harbouring this species, our data suggest a difference in host immune defence between these two forms of aggressive periodontitis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identification of Transcription Factor Genes and Their Correlation with the High Diversity of Stramenopiles

PubMed Central

Buitrago-Flórez, Francisco Javier; Restrepo, Silvia; Riaño-Pachón, Diego Mauricio

2014-01-01

The biological diversity among Stramenopiles is striking; they range from large multicellular seaweeds to tiny unicellular species, they embrace many ecologically important autothrophic (e.g., diatoms, brown algae), and heterotrophic (e.g., oomycetes) groups. Transcription factors (TFs) and other transcription regulators (TRs) regulate spatial and temporal gene expression. A plethora of transcriptional regulatory proteins have been identified and classified into families on the basis of sequence similarity. The purpose of this work is to identify the TF and TR complement in diverse species belonging to Stramenopiles in order to understand how these regulators may contribute to their observed diversity. We identified and classified 63 TF and TR families in 11 species of Stramenopiles. In some species we found gene families with high relative importance. Taking into account the 63 TF and TR families identified, 28 TF and TR families were established to be positively correlated with specific traits like number of predicted proteins, number of flagella and number of cell types during the life cycle. Additionally, we found gains and losses in TF and TR families specific to some species and clades, as well as, two families with high abundance specific to the autotrophic species and three families with high abundance specific to the heterotropic species. For the first time, there is a systematic search of TF and TR families in Stramenopiles. The attempts to uncover relationships between these families and the complexity of this group may be of great impact, considering that there are several important pathogens of plants and animals, as well as, important species involved in carbon cycling. Specific TF and TR families identified in this work appear to be correlated with particular traits in the Stramenopiles group and may be correlated with the high complexity and diversity in Stramenopiles. PMID:25375671

Identification of transcription factor genes and their correlation with the high diversity of stramenopiles.

PubMed

Buitrago-Flórez, Francisco Javier; Restrepo, Silvia; Riaño-Pachón, Diego Mauricio

2014-01-01

The biological diversity among Stramenopiles is striking; they range from large multicellular seaweeds to tiny unicellular species, they embrace many ecologically important autothrophic (e.g., diatoms, brown algae), and heterotrophic (e.g., oomycetes) groups. Transcription factors (TFs) and other transcription regulators (TRs) regulate spatial and temporal gene expression. A plethora of transcriptional regulatory proteins have been identified and classified into families on the basis of sequence similarity. The purpose of this work is to identify the TF and TR complement in diverse species belonging to Stramenopiles in order to understand how these regulators may contribute to their observed diversity. We identified and classified 63 TF and TR families in 11 species of Stramenopiles. In some species we found gene families with high relative importance. Taking into account the 63 TF and TR families identified, 28 TF and TR families were established to be positively correlated with specific traits like number of predicted proteins, number of flagella and number of cell types during the life cycle. Additionally, we found gains and losses in TF and TR families specific to some species and clades, as well as, two families with high abundance specific to the autotrophic species and three families with high abundance specific to the heterotropic species. For the first time, there is a systematic search of TF and TR families in Stramenopiles. The attempts to uncover relationships between these families and the complexity of this group may be of great impact, considering that there are several important pathogens of plants and animals, as well as, important species involved in carbon cycling. Specific TF and TR families identified in this work appear to be correlated with particular traits in the Stramenopiles group and may be correlated with the high complexity and diversity in Stramenopiles.

Uremic Solute-Aryl Hydrocarbon Receptor-Tissue Factor Axis Associates with Thrombosis after Vascular Injury in Humans.

PubMed

Kolachalama, Vijaya B; Shashar, Moshe; Alousi, Faisal; Shivanna, Sowmya; Rijal, Keshab; Belghasem, Mostafa E; Walker, Joshua; Matsuura, Shinobu; Chang, Gary H; Gibson, C Michael; Dember, Laura M; Francis, Jean M; Ravid, Katya; Chitalia, Vipul C

2018-03-01

Individuals with CKD are particularly predisposed to thrombosis after vascular injury. Using mouse models, we recently described indoxyl sulfate, a tryptophan metabolite retained in CKD and an activator of tissue factor (TF) through aryl hydrocarbon receptor (AHR) signaling, as an inducer of thrombosis across the CKD spectrum. However, the translation of findings from animal models to humans is often challenging. Here, we investigated the uremic solute-AHR-TF thrombosis axis in two human cohorts, using a targeted metabolomics approach to probe a set of tryptophan products and high-throughput assays to measure AHR and TF activity. Analysis of baseline serum samples was performed from 473 participants with advanced CKD from the Dialysis Access Consortium Clopidogrel Prevention of Early AV Fistula Thrombosis trial. Participants with subsequent arteriovenous thrombosis had significantly higher levels of indoxyl sulfate and kynurenine, another uremic solute, and greater activity of AHR and TF, than those without thrombosis. Pattern recognition analysis using the components of the thrombosis axis facilitated clustering of the thrombotic and nonthrombotic groups. We further validated these findings using 377 baseline samples from participants in the Thrombolysis in Myocardial Infarction II trial, many of whom had CKD stage 2-3. Mechanistic probing revealed that kynurenine enhances thrombosis after vascular injury in an animal model and regulates thrombosis in an AHR-dependent manner. This human validation of the solute-AHR-TF axis supports further studies probing its utility in risk stratification of patients with CKD and exploring its role in other diseases with heightened risk of thrombosis. Copyright © 2018 by the American Society of Nephrology.

Optimum Design Methods for Structural Sandwich Panels

DTIC Science & Technology

1989-02-01

B)*ROS TF1 -STRE?4*SS**2/(Cl(CONFI)*AFA*(ROCl/ROS)**(2*A/3. )*TCI) Wlm(2* TF1 *WS*SS*ROF+TCi*WS*SS*ROCI)/1728000. IF (W1.LT.WEIGHT) THEN TF- TF1 TC-TC1...B)*ROS W1-(2* TF1 *WS*SS*ROF+TC1*WS*SS*RoC1)/172800O. IF (WI.LT.WEIGHT) THEN TF- TF1 TC-TC1 ROC-ROC1 WEIGHT-Wi FAIL-3 END IF END IF WRITE(*, 260)TC,TF...8217THE PROGRAM IS RUNNING. PL.EASE WAIT!’ DO 273 1-1,999 * TCl-P*SS/(C1 lrONFI)*YF*WS*TFI) COEFF-C5 (CONFI )*EF*P*SS* TF1 *TC1/ (CG*C6 (CONFI ) *E) COEFF

Quantitative Analysis of Major Phytochemicals in Orthodox tea (Camellia sinensis), Oxidized under Compressed Air Environment.

PubMed

Panda, Brajesh Kumar; Datta, Ashis Kumar

2016-04-01

This study describes major changes in phytochemical composition of orthodox tea (Camellia sinensis var. Assamica) oxidized under compressed air (CA). The experiments for oxidation were conducted under air pressure (101, 202, and 303 kPa) for 150 min. Relative change in the concentrations of caffeine, catechins, theaflavins (TF), and thearubigins (TR) were analyzed. Effect of CA pressure was found to be nonsignificant in regulating caffeine concentration during oxidation. But degradation in different catechins as well as formation of different TF was significantly affected by CA pressure. At high CA pressure, TF showed highest peak value. TR was found to have slower rate of formation during initial phase of oxidation than TF. Even though the rate of TR formation was significantly influenced by CA, a portion of catechins remained unoxidized at end of oxidation. Except caffeine, the percent change in rate of formation or degradation were more prominent at 202 kPa. © 2016 Institute of Food Technologists®

Thermal sensation and comfort during exposure to local airflow to face or legs.

PubMed

Yamashita, Kazuaki; Matsuo, Juntaro; Tochihara, Yutaka; Kondo, Youichiro; Takayama, Shizuka; Nagayama, Hiroki

2005-01-01

The present study examined the contribution of local airflow temperature to thermal sensation and comfort in humans. Eight healthy male students were exposed to local airflow to their faces (summer condition) or legs (winter condition) for 30 minutes. Local airflow temperature (Tf) was maintained at 18 degrees C to 36 degrees C, and ambient temperature (Ta) was maintained at 17.4 degrees C to 31.4 degrees C. Each subject was exposed to 16 conditions chosen from the combination of Tf and Ta. Based on the results of multiple regression analysis, the standardized partial regression coefficient of Tf and Ta were determined to be 0.93 and 0.13 in the summer condition, and 0.71 and 0.36 in the winter condition at the end of the exposure. Also, thermal comfort was observed to depend closely on the interrelation between Tf and Ta. The present data suggested that local airflow temperature is an important thermal factor regarding thermal sensation and comfort.

Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.

PubMed

Bradley, Todd; Fera, Daniela; Bhiman, Jinal; Eslamizar, Leila; Lu, Xiaozhi; Anasti, Kara; Zhang, Ruijung; Sutherland, Laura L; Scearce, Richard M; Bowman, Cindy M; Stolarchuk, Christina; Lloyd, Krissey E; Parks, Robert; Eaton, Amanda; Foulger, Andrew; Nie, Xiaoyan; Karim, Salim S Abdool; Barnett, Susan; Kelsoe, Garnett; Kepler, Thomas B; Alam, S Munir; Montefiori, David C; Moody, M Anthony; Liao, Hua-Xin; Morris, Lynn; Santra, Sampa; Harrison, Stephen C; Haynes, Barton F

2016-01-05

Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The Long Terminal Repeat Retrotransposons Tf1 and Tf2 of Schizosaccharomyces pombe.

PubMed

Esnault, Caroline; Levin, Henry L

2015-08-01

The long terminal repeat (LTR) retrotransposons Tf1 and Tf2 of Schizosaccharomyces pombe are active mobile elements of the Ty3/gypsy family. The mobilization of these retrotransposons depends on particle formation, reverse transcription and integration, processes typical of other LTR retrotransposons. However, Tf1 and Tf2 are distinct from other LTR elements in that they assemble virus-like particles from a single primary translation product, initiate reverse transcription with an unusual self-priming mechanism, and, in the case of Tf1, integrate with a pattern that favors specific promoters of RNA pol II-transcribed genes. To avoid the chromosome instability and genome damage that results from increased copy number, S. pombe applies a variety of defense mechanisms that restrict Tf1 and Tf2 activity. The mRNA of the Tf elements is eliminated by an exosome-based pathway when cells are in favorable conditions whereas nutrient deprivation triggers an RNA interference-dependent pathway that results in the heterochromatization of the elements. Interestingly, Tf1 integrates into the promoters of stress-induced genes and these insertions are capable of increasing the expression of adjacent genes. These properties of Tf1 transposition raise the possibility that Tf1 benefits cells with specific insertions by providing resistance to environmental stress.

Learning Curves Among All Patients Undergoing Transcatheter Aortic Valve Implantation in Germany: A Retrospective Observational Study.

PubMed

Kaier, Klaus; Reinecke, Holger; Schmoor, Claudia; Frankenstein, Lutz; Vach, Werner; Hehn, Philip; Zirlik, Andreas; Bode, Christoph; Zehender, Manfred; Reinöhl, Jochen

2017-05-15

Transcatheter aortic valve implantation (TAVI) is a rapidly evolving technique for therapy of aortic stenosis. Previous studies report learning curves with respect to in-hospital mortality and clinical complications. We aim to determine whether observed improvements of in-hospital outcomes after TAVI are the result of improvements in procedures or due to a change in the patient population, and whether improvements differ between the transfemoral (TF) and the transapical (TA) approach. Data was analyzed using risk-adjusted regression analyses in order to track the development of clinical outcomes of all isolated TAVI procedures performed in Germany from 2008 to 2013 (N=32.436) in all German hospitals performing TAVI. Measurements include in-hospital mortality, stroke, bleeding, and mechanical ventilation. Unadjusted mortality rates decrease over time for both TA-TAVI and TF-TAVI. Reductions in mortality were smaller for TA-TAVI than for TF-TAVI. These trends could also be observed for risk-adjusted (standardized) mortality rates, indicating that time trends and differences between TA-TAVI (around 7% in 2013) and TF-TAVI (around 4% in 2013) cannot be explained by changes in the risk factor composition of the patient populations. Bleeding complications decreased for both access routes. Both unadjusted and standardized bleeding rates were substantially higher for TA-TAVI. In addition, TA-TAVI procedures were associated with an increased likelihood of requiring >48h of mechanical ventilation. Observed improvements in TAVI-related in-hospital mortality are not due to a change in patient population. The results indicate the superiority of a TF-first approach. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Reassessment of the role of enteral tube feedings for patients with esophageal cancer.

PubMed

Starr, Brett; Davis, Stephanie; Ayala-Peacock, Diandra; Blackstock, William A; Levine, Edward A

2014-08-01

Nutrition is important for patients with esophageal cancer because dysphagia can be exacerbated by chemoradiotherapy. Some centers suggest routine enteral tube placement (TF) to facilitate nutrition. This investigation was to evaluate the use of TF access for patients undergoing multimodality therapy for esophageal carcinoma. This retrospective study analyzed 113 patients who underwent esophagectomy and 97 patients who underwent definition chemoradiotherapy for esophageal cancer between 2001 and 2013. Throughout this time period, a strategy for selective tube placement was used. Nutrition was assessed through absolute lymphocyte counts, protein, and albumin levels. A total of 28 (30%) patients during preoperative chemoradiotherapy and 31 (32%) of those undergoing definitive chemoradiation received TFs. There were 16 Dobhoff tubes, 28 gastrostomy tubes, and 15 jejunostomies. Tubes were maintained an average of 3.9 months with 20 (34%) of these patients reporting tube-related complications. At the time of surgery, there was no statistical difference in any of the nutritional assessments between those patients who received TF and those who did not. Both groups experienced similar total postoperative complication rates (64% vs 65%) and similar median length of hospital stay (12 to 13 days). Chemoradiotherapy resulted in decreased nutritional parameters; however, there was no difference in the degree of reduction between those who underwent TF and those who did not. The data show that routine placement of enteral access is not necessary for esophageal carcinoma. In fact, the risks of placing enteral access may outweigh the benefits. Administration of TF should be restricted to select patients during chemoradiotherapy or before esophagectomy.

Costs to Community Mental Health Agencies to Sustain an Evidence-Based Practice.

PubMed

Roundfield, Katrina D; Lang, Jason M

2017-09-01

Dissemination of evidence-based practices (EBPs) has become a priority in children's mental health services. Although implementation approaches and initiatives are proliferating, little is known about sustainment of EBPs, but evidence suggests that most EBPs are not sustained for more than a few years. Cost is the most frequently cited barrier to sustainment, yet very little is known about these costs. This study provides a method for quantifying incremental costs of an EBP compared with usual care and preliminary data on the costs in staff time, lost revenue, and other expenses of sustaining an EBP (trauma-focused cognitive-behavioral therapy [TF-CBT]) in community mental health settings. Fourteen community mental health agencies (CMHAs) completed a measure developed for this study to collect administrative data on implementation costs to sustain TF-CBT. Survey items captured activities that were related specifically to TF-CBT and that would not otherwise be conducted for usual care, such as TF-CBT training. Staff time in hours was converted to monetary estimates. Costs varied widely across agencies. Preliminary results indicated that agencies spent on average $65,192 per year (2014 U.S.$) on incremental costs for TF-CBT sustainment (excluding costs of external trainers and other support); the average incremental cost per client was $1,896. The costs to sustain the EBP suggest that maintaining an EBP is a financial burden for CMHAs and that these costs can be a potential barrier to broader EBP uptake. Implications for public policy include providing reimbursement rates and financial incentives to offset potential implementation costs and promote sustainment of EBPs.

Iron, transferrin and myelinogenesis

NASA Astrophysics Data System (ADS)

Sergeant, C.; Vesvres, M. H.; Devès, G.; Baron, B.; Guillou, F.

2003-09-01

Transferrin (Tf), the iron binding protein of vertebrates serum, is known to be synthesized by oligodendrocytes (Ols) in the central nervous system. It has been postulated that Tf is involved in Ols maturation and myelinogenesis. This link is particularly important in the understanding of a severe human pathology: the multiple sclerosis, which remains without efficient treatment. We generated transgenic mice containing the complete human Tf gene and extensive regulatory sequences from the 5 ' and 3 ' untranslated regions that specifically overexpress Tf in Ols. Brain cytoarchitecture of the transgenic mice appears to be normal in all brain regions examined, total myelin content is increased by 30% and motor coordination is significantly improved when compared with non-transgenic littermates. Tf role in the central nervous system may be related to its affinity for metallic cations. Normal and transgenic mice were used for determination of trace metals (iron, copper and zinc) and minerals (potassium and calcium) concentration in cerebellum and corpus callosum. The freeze-dried samples were prepared to allow proton-induced X-ray emission and Rutherford backscattering spectrometry analyses with the nuclear microprobe in Bordeaux. Preliminary results were obtained and carbon distribution was revealed as a very good analysis to distinguish precisely the white matter region. A comparison of metallic and mineral elements contents in brain between normal and transgenic mice shows that iron, copper and zinc levels remained constant. This result provides evidence that effects of Tf overexpression in the brain do not solely relate to iron transport.

Lutibacter litoralis gen. nov., sp. nov., a marine bacterium of the family Flavobacteriaceae isolated from tidal flat sediment.

PubMed

Choi, Dong H; Cho, Byung C

2006-04-01

A rod-shaped marine bacterium, designated strain CL-TF09T, isolated from a tidal flat in Ganghwa, Korea, was characterized based on its physiological and biochemical features, fatty acid profile and phylogenetic position. 16S rRNA gene sequence analysis revealed a clear affiliation with the family Flavobacteriaceae. Strain CL-TF09T showed the closest phylogenetic relationship with the genera Tenacibaculum and Polaribacter; sequence similarities between CL-TF09T and the type strains of Tenacibaculum and Polaribacter species ranged from 90.7 to 91.8 %. Cells of strain CL-TF09T were non-motile and grew on solid media as yellow colonies. The strain grew in the presence of 1-5 % sea salts, within a temperature range of 5-30 degrees C and at pH 7-8. The strain had iso-C(15 : 0) 3-OH (17.4 %), iso-C(15 : 0) (16.7 %), anteiso-C(15 : 0) (15.1 %) and iso-C(16 : 0) 3-OH (13.4 %) as predominant fatty acids. The DNA G+C content was 33.9 mol%. Based on the physiological, fatty acid composition and phylogenetic data presented, strain CL-TF09T is considered to represent a novel genus and species of the family Flavobacteriaceae, for which the name Lutibacter litoralis gen. nov., sp. nov. is proposed. The type strain is CL-TF09T (=KCCM 42118T = JCM 13034T).

The relationship between phenolics and flavonoids production with total non structural carbohydrate and photosynthetic rate in Labisia pumila Benth. under high CO2 and nitrogen fertilization.

PubMed

Ibrahim, Mohd Hafiz; Jaafar, Hawa Z E; Rahmat, Asmah; Rahman, Zaharah Abdul

2010-12-29

A factorial split plot 4 × 3 experiment was designed to examine and characterize the relationship among production of secondary metabolites (total phenolics, TP; total flavonoids, TF), carbohydrate content and photosynthesis of three varieties of the Malaysian medicinal herb Labisia pumila Benth. namely the varieties alata, pumila and lanceolata under CO(2) enrichment (1,200 µmol mol(-1)) combined with four levels of nitrogen fertilization (0, 90, 180 and 270 kg N ha(-1)). No varietal differences were observed, however, as the levels of nitrogen increased from 0 to 270 kg N ha(-1), the production of TP and TF decreased in the order leaves>roots>stems. The production of TP and TF was related to increased total non structural carbohydrate (TNC), where the increase in starch content was larger than that in sugar concentration. Nevertheless, the regression analysis exhibited a higher influence of soluble sugar concentration (r(2) = 0.88) than starch on TP and TF biosynthesis. Photosynthesis, on the other hand, displayed a significant negative relationship with TP and TF production (r(2) = -0.87). A decrease in photosynthetic rate with increasing secondary metabolites might be due to an increase in the shikimic acid pathway that results in enhanced production of TP and TF. Chlorophyll content exhibited very significant negative relationships with total soluble sugar, starch and total non structural carbohydrate.

Effects of Nitrogen Fertilization and Thinning Treatments on Subsurface Soil Carbon and Nitrogen

NASA Astrophysics Data System (ADS)

Gross, C. D.; James, J. N.; Harrison, R. B.

2016-12-01

Increases in intensively managed forest plantations have caused concern for the long-term productivity and sustainability of these stands, as decreased organic matter retention and shorter rotations can substantially impact soil nutrition both in the short- and long-term. This study aims to provide data for regional responses of soil carbon (C) and nitrogen (N) by depth to fertilization and thinning treatments. Soil was sampled at an intensively managed Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) plantation in northwestern Oregon, USA. Nine 0.2-ha plots were sampled with at least three pits per plot. Management regimes included no treatment (control), fertilization (F+), minimal thinning (mT), repeated thinning (rT), and combination treatments (mTF+ and rTF+). Fertilized plots received a total of 1120 kg N ha-1 as urea over 16 years. Bulk density and chemical analysis samples were taken in the middle of succeeding soil layers at depths of 0.1, 0.2, 0.5, 1.0, and 1.5 m. Forest floor samples were collected from a randomly placed quadrat. Preliminary results show an increase in total soil C and N of 113 and 106%, respectively, on the mTF+ plot compared to a control plot. The subsoil, defined here as below 0.2 m, contained over 50% of both soil C and N on the mTF+ plot and experienced greater C and N increases than the surface soil following treatment. This study demonstrates that forest management practices over a relatively short time span (<30 years) can significantly alter subsoil, which comprises a substantial portion of biologically available C and N in terrestrial ecosystems. Subsoil processes are critical to our understanding of changes in soil quality and our ability to accurately assess changes in soil C and N reservoirs.

A dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-β1-42-injected mice.

PubMed

Jia, Tingting; Sun, Zhiguo; Lu, Ying; Gao, Jie; Zou, Hao; Xie, Fangyuan; Zhang, Guoqing; Xu, Hao; Sun, Duxin; Yu, Yuan; Zhong, Yanqiang

2016-01-01

Due to the impermeability of the blood-brain barrier and the nonselective distribution of drugs in the brain, the therapeutic access to intractable neurological disorders is challenging. In this study, dual brain-targeting polymersomes (POs) functionalized by transferrin and Tet-1 peptide (Tf/Tet-1-POs) promoted the transportation of curcumin into the brain and provided neuroprotection. The modification of the ligands that bind to the surface of POs was revealed by X-ray photoelectron spectroscopy analysis. The cell uptake of a coculture model of mouse brain capillary endothelial cells with neurons showed that the Tf/Tet-1-POs had significant transportation properties and possessed affinity for neurons. The pharmacokinetic analysis showed that the blood-brain barrier permeability-surface efficiency of the Tf/Tet-1-POs was 0.28 mL/h/g and that the brain tissue uptake rate (% ID/g) was 0.08, which were significant compared with the controls (P<0.05). The curcumin-encapsulated Tf/Tet-1-POs provided neuroprotection and ameliorated cognitive dysfunction in intrahippocampal amyloid-β1-42-injected mice. These results suggest that the dual brain-targeting POs are more capable of drug delivery to the brain that can be exploited as a multiple noninvasive vehicle for targeting therapeutics.

Associations of TF Gene Polymorphisms with the Risk of Ischemic Stroke.

PubMed

Cai, Yi; Wu, Shaofang; Zeng, Chaosheng; Su, Qingjie; Zhou, Jingxia; Li, Pengxiang; Dai, Mingming; Wang, Desheng; Long, Faqing

2018-06-23

Ischemic stroke (IS) is the main cause of mortality and disability in China; thus, this study aimed to examine the association between six variants and their haplotypes within the transferrin (TF) gene and the risk of IS in the Southern Chinese Han population. Genotyping was performed using the Sequenom MassARRAY platform for 249 IS patients and 249 age- and sex-matched controls. The association between polymorphisms and IS risk was tested by Chi squared test and haplotype and stratification analysis. Odds ratios (ORs) and confidence intervals (CIs) were estimated by unconditional logistic regression analysis. The results of genetic model analyses indicated that the two SNPs (rs1880669 and rs2692695) were associated with decreased IS risk under the co-dominant, dominant, and additive models. Additionally, rs4525863 was also associated with decreased IS risk both under the dominant and additive models in males. Moreover, the CG haplotype of TF (rs1880669 and rs2692695) was significantly associated with a decreased risk of IS in the total population and males. Our findings suggested that polymorphisms (rs4525863, rs1880669, and rs2692695) of the TF gene might be a protective factor for IS in Southern Chinese Han population. Further large prospective studies are required to confirm these findings.

The aesthetic impact of enamel fluorosis on Irish adolescents.

PubMed

Browne, Deirdre; Whelton, Helen; O'Mullane, Denis; Tavener, Jacqueline; Flannery, Edel

2011-04-01

To assess the impact of differing degrees of enamel fluorosis on dental aesthetics according to Irish adolescents. The same participants also aesthetically rated other variations in dental appearances including a carious lesion, bleached teeth and a demarcated opacity. One hundred and fifty adolescents examined seven identical template photographs of an attractive dental smile displaying varying levels of enamel fluorosis (TF1, TF2, TF3), a demarcated opacity, no fluorosis (TF0), anterior caries and very white or bleached teeth. By indicating their level of agreement or disagreement with five statements on a five-point Likert scale, the participants rated the aesthetic acceptability of each of the photographs. Using paired t-tests with the Bonferroni correction, it was found that the photographs depicting the very white teeth and anterior caries were rated as the most and least aesthetically pleasing images, respectively. There was no significant difference in the ratings of the photographs displaying TF0, TF1 and TF2 levels of fluorosis indicating that these photographs were viewed similarly (P>0.002). The remaining two photographs (TF3 and the demarcated opacity) were rated similarly and significantly worse (P<0.002) than the photographs showing no or low grades of fluorosis (TF0, TF1 and TF2). TF3 level of fluorosis represented the break point at which enamel fluorosis became aesthetically objectionable to these participants. Low grades of fluorosis (TF1 and TF2) were rated similarly to the photograph depicting no fluorosis (TF0). © 2011 John Wiley & Sons A/S.

AC loss, interstrand resistance and mechanical properties of prototype EU DEMO TF conductors up to 30 000 load cycles

NASA Astrophysics Data System (ADS)

Yagotintsev, K.; Nijhuis, A.

2018-07-01

Two prototype Nb3Sn cable-in-conduit conductors conductors were designed and manufactured for the toroidal field (TF) magnet system of the envisaged European DEMO fusion reactor. The AC loss, contact resistance and mechanical properties of two sample conductors were tested in the Twente Cryogenic Cable Press under cyclic load up to 30 000 cycles. Though both conductors were designed to operate at 82 kA in a background magnetic field of 13.6 T, they reflect different approaches with respect to the magnet winding pack assembly. The first approach is based on react and wind technology while the second is the more common wind and react technology. Each conductor was tested first for AC loss in virgin condition without handling. The impact of Lorentz load during magnet operation was simulated using the cable press. In the press each conductor specimen was subjected to transverse cyclic load up to 30 000 cycles in liquid helium bath at 4.2 K. Here a summary of results for AC loss, contact resistance, conductor deformation, mechanical heat production and conductor stiffness evolution during cycling of the load is presented. Both conductors showed similar mechanical behaviour but quite different AC loss. In comparison with previously tested ITER TF conductors, both DEMO TF conductors possess very low contact resistance resulting in high coupling loss. At the same time, load cycling has limited impact on properties of DEMO TF conductors in comparison with ITER TF conductors.

Thermal fatigue and thermal shock in bedrock: An attempt to unravel the geomorphic processes and products

NASA Astrophysics Data System (ADS)

Hall, Kevin; Thorn, Colin E.

2014-02-01

Widespread acceptance in science at-large notwithstanding, the ability of thermal stresses to produce thermal fatigue (TF) and/or thermal shock (TS) in bedrock and coarse debris in the field is often doubted. Commonly called insolation weathering in geomorphology, the results of questionable laboratory experiments have led many geomorphologists to consider terrestrial temperatures to be inadequate to generate thermally induced stresses leading to rock failure; the exceptions are the action of fire or lightning. We comprehensively survey the general scientific literature on TF and TS while rigorously scrutinizing that relating to geomorphology. Findings indicate theoretical and experimental information is adequate to establish the feasibility of TF and TS in rock stemming from rock temperatures monitored in the field. While TS may exhibit fracture patterns that are uniquely diagnostic, those of TF lack any such attributes. It would appear unlikely that TF can prepare or weaken rock to increase the likelihood of TS. The question of whether widespread polygonal versus rectilinear cracking is diagnostic of TS is presently an open one as possible explanations invoke process(es) and/or host material(s) and, consequently, to assign palaeoenvironmental significance to such fracture patterns is premature at this time. Further geomorphological laboratory research into TF and TS is merited as sufficient theoretical underpinning already exists. However, laboratory experimentation needs to be much more rigorously defined and executed and is faced with significant hurdles if it is to be effectively linked to field observations.

TUW at the First Total Recall Track

DTIC Science & Technology

2015-11-20

Appen- dix A were ignored. 2.1. Term weighting. The bmi used the basic tf.idf weighting scheme, as given by: (1) weightT (t, d) = (1 + log( tft ,d)) ⇤ log(N...dft); where t is a term, d a document, tft ,d the term frequency, dft the document frequency, and N is the number of documents in the collection. For...save us some training e↵ort. The used weight, marked by “B” in the run names, is given by: (2) weightB(t, d) = tft ,d⇣ 1 mavgtf avgtfd mavgtf + (1 1

Phosphatidylserine index as a marker of the procoagulant phenotype of acute myelogenous leukemia cells

NASA Astrophysics Data System (ADS)

Tormoen, Garth W.; Recht, Olivia; Gruber, András; Levine, Ross L.; McCarty, Owen J. T.

2013-10-01

Patients with acute myelogenous leukemia (AML) are at risk for thrombotic complications. Risk to develop thrombosis is closely tied to leukemia subtype, and studies have shown an association between leukocytosis and thrombosis in AML M3. We evaluated the relative roles of cell count and the surface expression of tissue factor (TF) and phosphatidylserine (PS) in the procoagulant phenotype of AML cell lines. The TF-positive AML M3 cell lines, NB4 and HL60, and AML M2 cell line, AML14, exhibited both extrinsic tenase and prothrombinase activity in a purified system and promoted experimental thrombus formation. In contrast, the TF-negative AML cell line, HEL, exhibited only prothrombinase activity and did not affect the rate of occlusive thrombus formation. In plasma, NB4, HL60 and AML14 shortened clotting times in a cell-count, PS- and TF-dependent manner. Exposure of cultured NB4, HL60, and AML14 cells to the chemotherapeutic agent daunorubicin increased their extrinsic tenase activity and PS expression. Clot initiation time inversely correlated with logarithm of PS index, defined as the product of multiplying leukocyte count with cell surface PS exposure. We propose that leukemia cell PS index may serve as a biomarker for procoagulant activity.

Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo

PubMed Central

Thomas, Grace M.; Panicot-Dubois, Laurence; Lacroix, Romaric; Dignat-George, Françoise; Lombardo, Dominique

2009-01-01

Recent publications have demonstrated the presence of tissue factor (TF)–bearing microparticles (MPs) in the blood of patients suffering from cancer. However, whether these MPs are involved in thrombosis remains unknown. We show that pancreatic and lung cancer cells produce MPs that express active TF and P-selectin glycoprotein ligand 1 (PSGL-1). Cancer cell–derived MPs aggregate platelets via a TF-dependent pathway. In vivo, cancer cell–derived MPs, but not their parent cells, infused into a living mouse accumulate at the site of injury and reduce tail bleeding time and the time to occlusion of venules and arterioles. This thrombotic state is also observed in mice developing tumors. In such mice, the amount of circulating platelet-, endothelial cell–, and cancer cell–derived MPs is increased. Endogenous cancer cell–derived MPs shed from the growing tumor are able to accumulate at the site of injury. Infusion of a blocking P-selectin antibody abolishes the thrombotic state observed after injection of MPs or in mice developing a tumor. Collectively, our results indicate that cancer cell–derived MPs bearing PSGL-1 and TF play a key role in thrombus formation in vivo. Targeting these MPs could be of clinical interest in the prevention of thrombosis and to limit formation of metastasis in cancer patients. PMID:19667060

Modeling and optimization of ultrasound-assisted extraction of polyphenolic compounds from Aronia melanocarpa by-products from filter-tea factory.

PubMed

Ramić, Milica; Vidović, Senka; Zeković, Zoran; Vladić, Jelena; Cvejin, Aleksandra; Pavlić, Branimir

2015-03-01

Aronia melanocarpa by-product from filter-tea factory was used for the preparation of extracts with high content of bioactive compounds. Extraction process was accelerated using sonication. Three level, three variable face-centered cubic experimental design (FCD) with response surface methodology (RSM) was used for optimization of extraction in terms of maximized yields for total phenolics (TP), flavonoids (TF), anthocyanins (MA) and proanthocyanidins (TPA) contents. Ultrasonic power (X₁: 72-216 W), temperature (X₂: 30-70 °C) and extraction time (X₃: 30-90 min) were investigated as independent variables. Experimental results were fitted to a second-order polynomial model where multiple regression analysis and analysis of variance were used to determine fitness of the model and optimal conditions for investigated responses. Three-dimensional surface plots were generated from the mathematical models. The optimal conditions for ultrasound-assisted extraction of TP, TF, MA and TPA were: X₁=206.64 W, X₂=70 °C, X₃=80.1 min; X₁=210.24 W, X₂=70 °C, X₃=75 min; X₁=216 W, X₂=70 °C, X₃=45.6 min and X₁=199.44 W, X₂=70 °C, X₃=89.7 min, respectively. Generated model predicted values of the TP, TF, MA and TPA to be 15.41 mg GAE/ml, 9.86 mg CE/ml, 2.26 mg C3G/ml and 20.67 mg CE/ml, respectively. Experimental validation was performed and close agreement between experimental and predicted values was found (within 95% confidence interval). Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of sol aging on resistive switching behaviors of HfOx resistive memories

NASA Astrophysics Data System (ADS)

Hsu, Chih-Chieh; Sun, Jhen-Kai; Tsao, Che-Chang; Chen, Yu-Ting

2017-03-01

This work investigates effects of long-term sol-aging time on sol-gel HfOx resistive random access memories (RRAMs). A nontoxic solvent of ethanol is used to replace toxic 2-methoxyethanol, which is usually used in sol-gel processes. The top electrodes are fabricated by pressing indium balls onto the HfOx surface rather than by using conventional sputtering or evaporation processes. The maximum process temperature is limited to be 100 ℃. Therefore, influences of plasma and high temperature on HfOx film can be avoided. Under this circumstance, effects of sol aging time on the HfOx films can be more clearly studied. The current conduction mechanisms in low and high electric regions of the HfOx RRAM are found to be dominated by Ohmic conduction and trap-filled space charge limited conduction (TF-SCLC), respectively. When the sol aging time increases, the resistive switching characteristic of the HfOx layer becomes unstable and the transition voltage from Ohmic conduction to TF-SCLC is also increased. This suggests that an exceedingly long aging time will give a HfOx film with more defect states. The XPS results are consistent with FTIR analysis and they can further explain the unstable HfOx resistive switching characteristic induced by sol aging.

The tactile speed aftereffect depends on the speed of adapting motion across the skin rather than other spatiotemporal features

PubMed Central

Seizova-Cajic, Tatjana; Holcombe, Alex O.

2015-01-01

After prolonged exposure to a surface moving across the skin, this felt movement appears slower, a phenomenon known as the tactile speed aftereffect (tSAE). We asked which feature of the adapting motion drives the tSAE: speed, the spacing between texture elements, or the frequency with which they cross the skin. After adapting to a ridged moving surface with one hand, participants compared the speed of test stimuli on adapted and unadapted hands. We used surfaces with different spatial periods (SPs; 3, 6, 12 mm) that produced adapting motion with different combinations of adapting speed (20, 40, 80 mm/s) and temporal frequency (TF; 3.4, 6.7, 13.4 ridges/s). The primary determinant of tSAE magnitude was speed of the adapting motion, not SP or TF. This suggests that adaptation occurs centrally, after speed has been computed from SP and TF, and/or that it reflects a speed cue independent of those features in the first place (e.g., indentation force). In a second experiment, we investigated the properties of the neural code for speed. Speed tuning predicts that adaptation should be greatest for speeds at or near the adapting speed. However, the tSAE was always stronger when the adapting stimulus was faster (242 mm/s) than the test (30–143 mm/s) compared with when the adapting and test speeds were matched. These results give no indication of speed tuning and instead suggest that adaptation occurs at a level where an intensive code dominates. In an intensive code, the faster the stimulus, the more the neurons fire. PMID:26631149

PlantPAN 2.0: an update of plant promoter analysis navigator for reconstructing transcriptional regulatory networks in plants.

PubMed

Chow, Chi-Nga; Zheng, Han-Qin; Wu, Nai-Yun; Chien, Chia-Hung; Huang, Hsien-Da; Lee, Tzong-Yi; Chiang-Hsieh, Yi-Fan; Hou, Ping-Fu; Yang, Tien-Yi; Chang, Wen-Chi

2016-01-04

Transcription factors (TFs) are sequence-specific DNA-binding proteins acting as critical regulators of gene expression. The Plant Promoter Analysis Navigator (PlantPAN; http://PlantPAN2.itps.ncku.edu.tw) provides an informative resource for detecting transcription factor binding sites (TFBSs), corresponding TFs, and other important regulatory elements (CpG islands and tandem repeats) in a promoter or a set of plant promoters. Additionally, TFBSs, CpG islands, and tandem repeats in the conserve regions between similar gene promoters are also identified. The current PlantPAN release (version 2.0) contains 16 960 TFs and 1143 TF binding site matrices among 76 plant species. In addition to updating of the annotation information, adding experimentally verified TF matrices, and making improvements in the visualization of transcriptional regulatory networks, several new features and functions are incorporated. These features include: (i) comprehensive curation of TF information (response conditions, target genes, and sequence logos of binding motifs, etc.), (ii) co-expression profiles of TFs and their target genes under various conditions, (iii) protein-protein interactions among TFs and their co-factors, (iv) TF-target networks, and (v) downstream promoter elements. Furthermore, a dynamic transcriptional regulatory network under various conditions is provided in PlantPAN 2.0. The PlantPAN 2.0 is a systematic platform for plant promoter analysis and reconstructing transcriptional regulatory networks. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Relationship between rabbit transferrin electrophoretic patterns and plasma iron concentrations.

PubMed

Zaragoza, P; Arana, A; Amorena, B

1987-01-01

Rabbit transferrin (Tf) was studied electrophoretically using 1141 blood samples from individuals belonging to seven populations (Spanish Common, Spanish Giant, Butterfly, Lyoné de Bourgogne, New Zealand White, Californian and New Zealand White X Californian hybrids). No Tf polymorphism was found by starch gel electrophoresis, but six patterns, differing in the presence and/or intensity of three bands ('a', anodic; 'b', intermediate; and 'c', cathodic) were observed by polyacrylamide gel electrophoresis. No genetic model could explain these patterns, since they reflect differences in plasma Tf iron content. The electrophoretic test allowed a direct observation of the relative in vivo levels of the different Tf molecular species; saturated (band 'a', Fe2Tf); semi-saturated (band 'b', Fe1Tf); and without iron (band 'c' Fe0Tf, apotransferrin). The degree of iron saturation of Tf varied among individuals and throughout the individual's life. Specifically, in pregnant females, Fe2Tf and Fe1Tf are generally observed, except in late pregnancy (from day 25 to parturition), when mainly apotransferrin is observed. Significantly, within 24 h post-partum, high levels of Fe2Tf are reached in the female's serum.

USF-related transcription factor, HIV-TF1, stimulates transcription of human immunodeficiency virus-1.

PubMed

Maekawa, T; Sudo, T; Kurimoto, M; Ishii, S

1991-09-11

The transcription factor HIV-TF1, which binds to a region about 60 bp upstream from the enhancer of the human immunodeficiency virus-1 (HIV-1), was purified from human B cells. HIV-TF1 had a molecular weight of 39,000. Binding of HIV-TF1 to the HIV long terminal repeat (LTR) activated transcription from the HIV promoter in vitro. The HIV-TF1-binding site in HIV LTR was similar to the site recognized by upstream stimulatory factor (USF) in the adenovirus major late promoter. DNA-binding properties of HIV-TF1 suggested that HIV-TF1 might be identical or related to USF. Interestingly, treatment of purified HIV-TF1 by phosphatase greatly reduced its DNA-binding activity, suggesting that phosphorylation of HIV-TF1 was essential for DNA binding. The disruption of HIV-TF1-binding site induced a 60% decrease in the level of transcription from the HIV promoter in vivo. These results suggest that HIV-TF1 is involved in transcriptional regulation of HIV-1.

Ionic residues of human serum transferrin affect binding to the transferrin receptor and iron release.

PubMed

Steere, Ashley N; Miller, Brendan F; Roberts, Samantha E; Byrne, Shaina L; Chasteen, N Dennis; Smith, Valerie C; MacGillivray, Ross T A; Mason, Anne B

2012-01-17

Efficient delivery of iron is critically dependent on the binding of diferric human serum transferrin (hTF) to its specific receptor (TFR) on the surface of actively dividing cells. Internalization of the complex into an endosome precedes iron removal. The return of hTF to the blood to continue the iron delivery cycle relies on the maintenance of the interaction between apohTF and the TFR after exposure to endosomal pH (≤6.0). Identification of the specific residues accounting for the pH-sensitive nanomolar affinity with which hTF binds to TFR throughout the cycle is important to fully understand the iron delivery process. Alanine substitution of 11 charged hTF residues identified by available structures and modeling studies allowed evaluation of the role of each in (1) binding of hTF to the TFR and (2) TFR-mediated iron release. Six hTF mutants (R50A, R352A, D356A, E357A, E367A, and K511A) competed poorly with biotinylated diferric hTF for binding to TFR. In particular, we show that Asp356 in the C-lobe of hTF is essential to the formation of a stable hTF-TFR complex: mutation of Asp356 in the monoferric C-lobe hTF background prevented the formation of the stoichiometric 2:2 (hTF:TFR monomer) complex. Moreover, mutation of three residues (Asp356, Glu367, and Lys511), whether in the diferric or monoferric C-lobe hTF, significantly affected iron release when in complex with the TFR. Thus, mutagenesis of charged hTF residues has allowed identification of a number of residues that are critical to formation of and release of iron from the hTF-TFR complex.

Stoichiometry of DNA binding by the bacteriophage SP01-encoded type II DNA-binding protein TF1.

PubMed

Schneider, G J; Geiduschek, E P

1990-06-25

The stoichiometry of DNA binding by the bacteriophage SP01-encoded type II DNA-binding protein TF1 has been determined. 3H-Labeled TF1 was allowed to bind to a 32P-labeled DNA fragment containing a TF1 binding site. Multiple TF1-DNA complexes were resolved from each other and from unbound DNA by native gel electrophoresis. DNA-protein complexes were cut from polyacrylamide gels, and the amounts of 3H and 32P contained in each slice were measured. A ratio of 1.12 +/- 0.06 TF1 dimer/DNA molecule was calculated for the fastest-migrating TF1-DNA complex. We conclude that TF1 has a DNA-binding unit of one dimer. More slowly migrating complexes are apparently formed by serial addition of single TF1 dimers.

Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy.

PubMed

Hu, Zhiwei; Cheng, Jijun; Xu, Jie; Ruf, Wolfram; Lockwood, Charles J

2017-02-01

Identification of target molecules specific for angiogenic vascular endothelial cells (VEC), the inner layer of pathological neovasculature, is critical for discovery and development of neovascular-targeting therapy for angiogenesis-dependent human diseases, notably cancer, macular degeneration and endometriosis, in which vascular endothelial growth factor (VEGF) plays a central pathophysiological role. Using VEGF-stimulated vascular endothelial cells (VECs) isolated from microvessels, venous and arterial blood vessels as in vitro angiogenic models and unstimulated VECs as a quiescent VEC model, we examined the expression of tissue factor (TF), a membrane-bound receptor on the angiogenic VEC models compared with quiescent VEC controls. We found that TF is specifically expressed on angiogenic VECs in a time-dependent manner in microvessels, venous and arterial vessels. TF-targeted therapeutic agents, including factor VII (fVII)-IgG1 Fc and fVII-conjugated photosensitizer, can selectively bind angiogenic VECs, but not the quiescent VECs. Moreover, fVII-targeted photodynamic therapy can selectively and completely eradicate angiogenic VECs. We conclude that TF is an angiogenic-specific receptor and the target molecule for fVII-targeted therapeutics. This study supports clinical trials of TF-targeted therapeutics for the treatment of angiogenesis-dependent diseases such as cancer, macular degeneration and endometriosis.

Matrix effects on secondary ion emission from a room-temperature ionic liquid, 1-ethyl-3-methylimidazolium bis[trifluoromethanesulfonyl]imide

NASA Astrophysics Data System (ADS)

Souda, Ryutaro

2009-06-01

The ionization mechanism of room-temperature ionic liquids has been investigated using time-of-flight secondary ion mass spectrometry in the temperature range of 15-300 K. Analyses of 1-ethyl-3-methylimidazolium bis[trifluoromethanesulfonyl]imide ([emim][Tf2N]) deposited on a Ni(111) substrate revealed that the [emim]+ and [Tf2N]- yields increase together with the Ni+ yield at monolayer coverage; no such increase was observed for the films deposited on a D2O spacer layer. Results indicated that the [emim][Tf2N] molecule is not perfectly ionized; the Ni(111) surface accepts (for [emim]+) or donates (for [Tf2N]-) an electron with higher efficiency than the counterion because of the metal band effect. This phenomenon might be induced by electrostatic interactions between the separated cation and anion during sputtering. It is also suggested that the sputtered Ni atom can be ionized nonadiabatically by the formation of a quasimolecule with adspecies. The multilayer of [emim][Tf2N] deposited at 15 K has a porous structure, resembling that of polar molecules, because of nonionic intermolecular interactions. The phase transition is identifiable, together with the morphological change in the crystalline film, from temperature evolutions of the secondary ion yields.

Analysis of Simulation Tools for the Study of Advanced Marine Power Systems.

DTIC Science & Technology

1992-09-01

model of a steam turbine prime mover which accounts for both plant and servo/steam valve time constants is given in Fig. 14. 41 + Figure 14 Second order...given in Fig. 12 of Chapter VI. The parameters for this device as given by Mayer are [14]: "* KE=l "* KA= 2 0 0 "* KF=0.3 "* TA=0.0 2 seconds 92 " TF1

Regression Analysis of Combined Gene Expression Regulation in Acute Myeloid Leukemia

PubMed Central

Li, Yue; Liang, Minggao; Zhang, Zhaolei

2014-01-01

Gene expression is a combinatorial function of genetic/epigenetic factors such as copy number variation (CNV), DNA methylation (DM), transcription factors (TF) occupancy, and microRNA (miRNA) post-transcriptional regulation. At the maturity of microarray/sequencing technologies, large amounts of data measuring the genome-wide signals of those factors became available from Encyclopedia of DNA Elements (ENCODE) and The Cancer Genome Atlas (TCGA). However, there is a lack of an integrative model to take full advantage of these rich yet heterogeneous data. To this end, we developed RACER (Regression Analysis of Combined Expression Regulation), which fits the mRNA expression as response using as explanatory variables, the TF data from ENCODE, and CNV, DM, miRNA expression signals from TCGA. Briefly, RACER first infers the sample-specific regulatory activities by TFs and miRNAs, which are then used as inputs to infer specific TF/miRNA-gene interactions. Such a two-stage regression framework circumvents a common difficulty in integrating ENCODE data measured in generic cell-line with the sample-specific TCGA measurements. As a case study, we integrated Acute Myeloid Leukemia (AML) data from TCGA and the related TF binding data measured in K562 from ENCODE. As a proof-of-concept, we first verified our model formalism by 10-fold cross-validation on predicting gene expression. We next evaluated RACER on recovering known regulatory interactions, and demonstrated its superior statistical power over existing methods in detecting known miRNA/TF targets. Additionally, we developed a feature selection procedure, which identified 18 regulators, whose activities clustered consistently with cytogenetic risk groups. One of the selected regulators is miR-548p, whose inferred targets were significantly enriched for leukemia-related pathway, implicating its novel role in AML pathogenesis. Moreover, survival analysis using the inferred activities identified C-Fos as a potential AML prognostic marker. Together, we provided a novel framework that successfully integrated the TCGA and ENCODE data in revealing AML-specific regulatory program at global level. PMID:25340776

Palmitoylation of Sindbis Virus TF Protein Regulates Its Plasma Membrane Localization and Subsequent Incorporation into Virions.

PubMed

Ramsey, Jolene; Renzi, Emily C; Arnold, Randy J; Trinidad, Jonathan C; Mukhopadhyay, Suchetana

2017-02-01

Palmitoylation is a reversible, posttranslational modification that helps target proteins to cellular membranes. The alphavirus small membrane proteins 6K and TF have been reported to be palmitoylated and to positively regulate budding. 6K and TF are isoforms that are identical in their N termini but unique in their C termini due to a -1 ribosomal frameshift during translation. In this study, we used cysteine (Cys) mutants to test differential palmitoylation of the Sindbis virus 6K and TF proteins. We modularly mutated the five Cys residues in the identical N termini of 6K and TF, the four additional Cys residues in TF's unique C terminus, or all nine Cys residues in TF. Using these mutants, we determined that TF palmitoylation occurs primarily in the N terminus. In contrast, 6K is not palmitoylated, even on these shared residues. In the C-terminal Cys mutant, TF protein levels increase both in the cell and in the released virion compared to the wild type. In viruses with the N-terminal Cys residues mutated, TF is much less efficiently localized to the plasma membrane, and it is not incorporated into the virion. The three Cys mutants have minor defects in cell culture growth but a high incidence of abnormal particle morphologies compared to the wild-type virus as determined by transmission electron microscopy. We propose a model where the C terminus of TF modulates the palmitoylation of TF at the N terminus, and palmitoylated TF is preferentially trafficked to the plasma membrane for virus budding. Alphaviruses are a reemerging viral cause of arthritogenic disease. Recently, the small 6K and TF proteins of alphaviruses were shown to contribute to virulence in vivo Nevertheless, a clear understanding of the molecular mechanisms by which either protein acts to promote virus infection is missing. The TF protein is a component of budded virions, and optimal levels of TF correlate positively with wild-type-like particle morphology. In this study, we show that the palmitoylation of TF regulates its localization to the plasma membrane, which is the site of alphavirus budding. Mutants in which TF is not palmitoylated display drastically reduced plasma membrane localization, which effectively prevents TF from participating in budding or being incorporated into virus particles. Investigation of the regulation of TF will aid current efforts in the alphavirus field searching for approaches to mitigate alphaviral disease in humans. Copyright © 2017 American Society for Microbiology.

Genetic variability in the Guahibo population from Venezuela.

PubMed

Moral, Pedro; Marini, Elisabetta; Esteban, Esther; Mameli, Giuseppa Elisa; Succa, Valeria; Vona, Giuseppe

2002-01-01

Four communities from Guahibo of Venezuela were analyzed for the genetic variants of nine erythrocyte enzymes and five serum proteins. Of the 14 loci determined, four were monomorphic. Significant frequency differentiation among communities, was present for ESD and TF markers. In general, Guahibo allele frequencies are in the variation ranges described for South American groups. The analysis indicates a relatively higher affinity of Guahibos with other Venezuelan groups within an irregular pattern of genetic distances that are likely related to the complex demographic history of the South American groups. Genetic diversity estimates reveal a moderate degree of genetic structure between the four Guahibo communities. This intra-tribal variability in Guahibo appears to be lower than in Venezuelan Piaroa but higher than in other Amerindians and could be attributed to a combined effect of low population size and relative isolation of communities. At a continental level, the distribution of genetic diversity is consistent with preferential population movements along the eastern and western coastal areas.

Identification of Genetic on Blood Serum Protein of Prolific Ewes

NASA Astrophysics Data System (ADS)

Sutiyono; Ondho, Y. S.; Setiatin, E. T.; Sutopo; Laily, A. N.; Prasetyowati, D. E.; Noviani, F.

2018-02-01

The aim of the research was to identify the genetic specification of blood plasma protein in ewes that are prolific. The material of study of local sheep in Bawen and Jambu Sub-district of Semarang Regency is 132 which is determined by purposive sampling that have been give lambing three times. Ewes were divided into three groups that always has a single child (L1), ever had twins (L2) and twins more than two (LM2). Blood sampling was performed using dispossible syringe in jugular vein as much as 5 ml per ewe. Blood plasma was analyzed by Polyacrylamide Gel Electrophoresis-Thin Layer (PAGETLE) method in Biochemistry Laboratory of Veterinary Faculty of Gadjah Mada University. Data analysis is using descriptive statistics and the laws of equilibrium Hardy-Weberg. The research parameters were comparison type of ewes and frequency genetic of protein of blood serum. The results showed that the parent comparisons of L1, L2 and LM2 were 66 (50.00%), 49 (37.12%) and 17 (12.88%), respectively. The frequency genes haven a high propensity to relationship of prolificacy nature parent are Pal2, AlbB, CPF, TFB, PTFS and AmlB on pointes, 67.65, 55.88, 91.17, 70.59, 79.41 and 91.18%. Conclusion the mostly LM2 ewes have genotypes Pal1Pal2, AlbBAlbC, CpFCpF, TfATfB, PtfSPtfS and AmlBAmlB whit frequency are 52.94%, 52.94%, 88.24, 47.06, 64.71 and 88.24% respectively.

Application of the weighted total field-scattering field technique to 3D-PSTD light scattering model

NASA Astrophysics Data System (ADS)

Hu, Shuai; Gao, Taichang; Liu, Lei; Li, Hao; Chen, Ming; Yang, Bo

2018-04-01

PSTD (Pseudo Spectral Time Domain) is an excellent model for the light scattering simulation of nonspherical aerosol particles. However, due to the particularity of its discretization form of the Maxwell's equations, the traditional Total Field/Scattering Field (TF/SF) technique for FDTD (Finite Differential Time Domain) is not applicable to PSTD, and the time-consuming pure scattering field technique is mainly applied to introduce the incident wave. To this end, the weighted TF/SF technique proposed by X. Gao is generalized and applied to the 3D-PSTD scattering model. Using this technique, the incident light can be effectively introduced by modifying the electromagnetic components in an inserted connecting region between the total field and the scattering field region with incident terms, where the incident terms are obtained by weighting the incident field by a window function. To optimally determine the thickness of connection region and the window function type for PSTD calculations, their influence on the modeling accuracy is firstly analyzed. To further verify the effectiveness and advantages of the weighted TF/SF technique, the improved PSTD model is validated against the PSTD model equipped with pure scattering field technique in both calculation accuracy and efficiency. The results show that, the performance of PSTD seems to be not sensitive to variation of window functions. The number of the connection layer required decreases with the increasing of spatial resolution, where for spatial resolution of 24 grids per wavelength, a 6-layer region is thick enough. The scattering phase matrices and integral scattering parameters obtained by the improved PSTD show an excellent consistency with those well-tested models for spherical and nonspherical particles, illustrating that the weighted TF/SF technique can introduce the incident precisely. The weighted TF/SF technique shows higher computational efficiency than pure scattering technique.

Binding affinity of aluminium to human serum transferrin and effects of carbohydrate chain modification as studied by HPLC/high-resolution ICP-MS--speciation of aluminium in human serum.

PubMed

Nagaoka, Megumi Hamano; Maitani, Tamio

2005-09-01

Aluminium (Al) in the blood is bound to transferrin (Tf), a glycoprotein of about 80kDa that is characterized by its need for a synergistic anion. In this focused review, the binding affinity of Al to Tf is surveyed in the context of our recent studies using on-line high-performance liquid chromatography/high-resolution inductively coupled plasma mass spectrometry (HPLC/HR-ICP-MS). Al in human serum without any in vitro Al-spikes was present in a form bound to the N-lobe site of Tf. The influences of sialic acid in the carbohydrate chain of human serum Tf (hTf) were studied using asialo-hTf, obtained by treatment with sialidase. The binding affinity of Fe was similar between asialo-hTf and native-hTf, while that of Al for asialo-hTf was larger than that for native-hTf, especially in the presence of oxalate, a synergistic anion. The above findings are discussed in relation to diseases in which the serum concentrations of carbohydrate-deficient Tf and oxalate are augmented.

Evaluation of surface antigen TF1.17 in feline Tritrichomonas foetus isolates.

PubMed

Gould, E N; Corbeil, L B; Kania, S A; Tolbert, M K

2017-09-15

Tritrichomonas foetus (T. foetus) is a flagellated protozoa that infects the distal ileum and proximal colon of domestic cats, as well as the urogenital tract of cattle. Feline trichomonosis is recognized as a prevalent cause of chronic diarrhea in cats worldwide. The suspected route of transmission is fecal-oral, with cats in densely crowded environments at highest risk for infection. Thus, the recommended strategy for minimizing spread of infection is to identify and isolate T. foetus-positive cats from the general population. Rapid identification of infected cats can be challenging due to the inability to accurately and quickly detect the organism in samples at point of care facilities. Thus, identification of targets for use in development of a novel diagnostic test, as well as a vaccine or therapy for T. foetus infection is a significant area of research. Despite a difference in organ tropism between T. foetus genotypes, evidence exists for conserved virulence factors between feline and bovine T. foetus. The bovine T. foetus surface antigen, TF1.17, is an adhesin that is conserved across isolates. Vaccination with the purified antigen results in amelioration of cytopathogenicity and more rapid clearance of infection in cattle. We previously showed that three feline isolates of T. foetus were positive for TF1.17 antigen so we further hypothesized that TF1.17 is conserved across feline T. foetus isolates and that this antigen would represent an attractive target for development of a novel diagnostic test or therapy for feline trichomonosis. In these studies, we used monoclonal antibodies previously generated against 1.15 and 1.17 epitopes of the bovine T. foetus TF1.17 antigen, to evaluate for the presence and role of TF1.17 in the cytopathogenicity of feline T. foetus. A previously validated in vitro co-culture approach was used to model feline T. foetus infection. Immunoblotting, immunofluorescence assays, and flow cytometric analysis confirmed the presence and surface localization of antigen TF1.17 across all feline T. foetus isolates tested. Antigen TF1.17 was notably absent in the presumably nonpathogenic intestinal trichomonad, Pentatrichomonas hominis, a parasite that can be confused microscopically with T. foetus. Similar to bovine trichomoniasis, TF1.17 was found to promote T. foetus adhesion to the intestinal epithelium. These results support further characterization and development of the TF1.17 antigen as a possible target for the diagnosis and prevention of feline T. foetus infection. Copyright © 2017 Elsevier B.V. All rights reserved.

The Dependence of Solar Flare Limb Darkening on Emission Peak Formation Temperature

NASA Astrophysics Data System (ADS)

Thiemann, Edward; Epp, Luke; Eparvier, Francis; Chamberlin, Phillip C.

2017-08-01

Solar limb effects are local brightening or darkening of an emission that depend on where in the Sun's atmosphere it forms. Near the solar limb, optically thick (thin) emissions will darken (brighten) as the column of absorbers (emitters) along the line-of-sight increases. Note that in limb brightening, emission sources are re-arranged whereas in limb darkening they are obscured. Thus, only limb darkening is expected to occur in disk integrated observations. Limb darkening also results in center-to-limb variations of disk-integrated solar flare spectra, with important consequences for how planetary atmospheres are affected by flares. Flares are typically characterized by their flux in the optically thin 0.1-0.8 nm band measured by the X-ray Sensor (XRS) on board the Geostationary Operational Environmental Satellite (GOES). On the other hand, Extreme Ultraviolet (EUV) line emissions can limb darken because they are sensitive to resonant scattering, resulting in a flare's location on the solar disk controlling the amount of ionizing radiation that reaches a planet. For example, an X-class flare originating from disk center may significantly heat a planet's thermosphere, whereas the same flare originating near the limb may have no effect because much of the effective emissions are scattered in the solar corona.To advance the relatively poor understanding of flare limb darkening, we use over 300 M-class or larger flares observed by the EUV Variability Experiment (EVE) onboard the Solar Dynamics Observatory (SDO) to characterize limb darkening as a function of emission peak formation temperature, Tf. For hot coronal emissions (Tf>2 MK), these results show a linear relationship between the degree of limb darkening and Tf where lines with Tf=2 MK darken approximately 7 times more than lines with Tf=16 MK. Because the extent of limb darkening is dependent on the height of the source plasma, we use simple Beer-Lambert radiative transfer analysis to interpret these results and characterize the average thermal structure of the flares considered. As such, these results can be used to constrain both empirical flare irradiance models and more sophisticated flare loop hydrodynamic models.

Ultras-stable Physical Vapor Deposited Amorphous Teflon Films with Extreme Fictive Temperature Reduction

NASA Astrophysics Data System (ADS)

McKenna, Gregory; Yoon, Heedong; Koh, Yung; Simon, Sindee

In the present work, we have produced highly stable amorphous fluoropolymer (Teflon AF® 1600) films to study the calorimetric and relaxation behavior in the deep in the glassy regime. Physical vapor deposition (PVD) was used to produce 110 to 700 nm PVD films with substrate temperature ranging from 0.70 Tg to 0.90 Tg. Fictive temperature (Tf) was measured using Flash DSC with 600 K/s heating and cooling rates. Consistent with prior observations for small molecular weight glasses, large enthalpy overshoots were observed in the stable amorphous Teflon films. The Tf reduction for the stable Teflon films deposited in the vicinity of 0.85 Tg was approximately 70 K compared to the Tgof the rejuvenated system. The relaxation behavior of stable Teflon films was measured using the TTU bubble inflation technique and following Struik's protocol in the temperature range from Tf to Tg. The results show that the relaxation time decreases with increasing aging time implying that devitrification is occurring in this regime.

Root uptake of 137Cs by natural and semi-natural grasses as a function of texture and moisture of soils.

PubMed

Grytsyuk, N; Arapis, G; Davydchuk, V

2006-01-01

This work studies the dependence of 137Cs root uptake on the structure of landscape, especially on texture and moisture of soils, under natural conditions, on abandoned radiopolluted lands in Northern Ukraine. Researches were carried out on a wide range of landscape conditions, at various levels of 137Cs contamination (from 20 up to 5000 kBqm(-2)), with different types of soils (approx. 20 soil varieties), which differ in texture, granulometric composition, degrees of gleyization and water regime, and anthropogenic transformation. The results showed that transfer factor (TF) values of 137Cs differ 50 times for the natural grassy coenoses and 8 times for the semi-natural ones. The lowest 137Cs TF values were measured in the herbages of dry meadows at automorphous loamy soils, while the highest were observed in wetland meadows at organic soils. Finally, the correlation between 137Cs TF values and granulometric composition of soil was determined for both automorphic and hydromorphic mineral soils.

Mechanisms of anomalous compressibility of vitreous silica

NASA Astrophysics Data System (ADS)

Clark, Alisha N.; Lesher, Charles E.; Jacobsen, Steven D.; Sen, Sabyasachi

2014-11-01

The anomalous compressibility of vitreous silica has been known for nearly a century, but the mechanisms responsible for it remain poorly understood. Using GHz-ultrasonic interferometry, we measured longitudinal and transverse acoustic wave travel times at pressures up to 5 GPa in vitreous silica with fictive temperatures (Tf) ranging between 985 °C and 1500 °C. The maximum in ultrasonic wave travel times-corresponding to a minimum in acoustic velocities-shifts to higher pressure with increasing Tf for both acoustic waves, with complete reversibility below 5 GPa. These relationships reflect polyamorphism in the supercooled liquid, which results in a glassy state possessing different proportions of domains of high- and low-density amorphous phases (HDA and LDA, respectively). The relative proportion of HDA and LDA is set at Tf and remains fixed on compression below the permanent densification pressure. The bulk material exhibits compression behavior systematically dependent on synthesis conditions that arise from the presence of floppy modes in a mixture of HDA and LDA domains.

Comparison of risk of acute kidney injury after primary percutaneous coronary interventions with the transradial approach versus the transfemoral approach (from the PRIPITENA urban registry).

PubMed

Cortese, Bernardo; Sciahbasi, Alessandro; Sebik, Rodrigo; Rigattieri, Stefano; Alonzo, Alessandro; Silva-Orrego, Pedro; Belloni, Flavia; Seregni, Romano G; Giovannelli, Francesca; Tespili, Maurizio; Ricci, Roberto; Berni, Andrea

2014-09-15

The risk of acute kidney injury (AKI) is a major issue after percutaneous coronary interventions (PCIs), especially in the setting of ST-elevation myocardial infarction. Preliminary data from large retrospective registries seem to show a reduction of AKI when a transradial (TR) approach for PCI is adopted. Little is known about the relation between vascular access and AKI after emergent PCI. We here report the results of the Primary PCI from Tevere to Navigli (PRIPITENA), a retrospective database of primary PCI performed at high-volume centers in the urban areas of Rome and Milan. Primary end point of this study was the occurrence of AKI in the TR and transfemoral (TF) access site groups. Secondary end points were major adverse cardiovascular events, stent thrombosis, and Thrombolysis in Myocardial Infarction major and minor bleedings. The database included 1,330 patients, 836 treated with a TR and 494 with a TF approach. After a propensity-matched analysis performed to exclude possible confounders, we identified 450 matched patients (225 TR and 225 TF). The incidence of AKI in the 2 matched groups was lower in patients treated with TR primary PCI (8.4% vs 16.9%, p = 0.007). Major adverse cardiovascular events and stent thrombosis were not different among study groups, whereas major bleedings were more often seen in the TF group. At multivariate analysis, femoral access was an independent predictor of AKI (odds ratio 1.654, 95% confidence interval 1.084 to 2.524, p = 0.042). In conclusion, in this database of primary PCI, the risk of AKI was lower with a TR approach, and the TF approach was an independent predictor for the occurrence of this complication. Copyright © 2014 Elsevier Inc. All rights reserved.

Elucidation of hepatitis C virus transmission and early diversification by single genome sequencing.

PubMed

Li, Hui; Stoddard, Mark B; Wang, Shuyi; Blair, Lily M; Giorgi, Elena E; Parrish, Erica H; Learn, Gerald H; Hraber, Peter; Goepfert, Paul A; Saag, Michael S; Denny, Thomas N; Haynes, Barton F; Hahn, Beatrice H; Ribeiro, Ruy M; Perelson, Alan S; Korber, Bette T; Bhattacharya, Tanmoy; Shaw, George M

2012-01-01

A precise molecular identification of transmitted hepatitis C virus (HCV) genomes could illuminate key aspects of transmission biology, immunopathogenesis and natural history. We used single genome sequencing of 2,922 half or quarter genomes from plasma viral RNA to identify transmitted/founder (T/F) viruses in 17 subjects with acute community-acquired HCV infection. Sequences from 13 of 17 acute subjects, but none of 14 chronic controls, exhibited one or more discrete low diversity viral lineages. Sequences within each lineage generally revealed a star-like phylogeny of mutations that coalesced to unambiguous T/F viral genomes. Numbers of transmitted viruses leading to productive clinical infection were estimated to range from 1 to 37 or more (median = 4). Four acutely infected subjects showed a distinctly different pattern of virus diversity that deviated from a star-like phylogeny. In these cases, empirical analysis and mathematical modeling suggested high multiplicity virus transmission from individuals who themselves were acutely infected or had experienced a virus population bottleneck due to antiviral drug therapy. These results provide new quantitative and qualitative insights into HCV transmission, revealing for the first time virus-host interactions that successful vaccines or treatment interventions will need to overcome. Our findings further suggest a novel experimental strategy for identifying full-length T/F genomes for proteome-wide analyses of HCV biology and adaptation to antiviral drug or immune pressures.

Characterizing regulatory and functional differentiation between maize mesophyll and bundle sheath cells by transcriptomic analysis.

PubMed

Chang, Yao-Ming; Liu, Wen-Yu; Shih, Arthur Chun-Chieh; Shen, Meng-Ni; Lu, Chen-Hua; Lu, Mei-Yeh Jade; Yang, Hui-Wen; Wang, Tzi-Yuan; Chen, Sean C-C; Chen, Stella Maris; Li, Wen-Hsiung; Ku, Maurice S B

2012-09-01

To study the regulatory and functional differentiation between the mesophyll (M) and bundle sheath (BS) cells of maize (Zea mays), we isolated large quantities of highly homogeneous M and BS cells from newly matured second leaves for transcriptome profiling by RNA sequencing. A total of 52,421 annotated genes with at least one read were found in the two transcriptomes. Defining a gene with more than one read per kilobase per million mapped reads as expressed, we identified 18,482 expressed genes; 14,972 were expressed in M cells, including 53 M-enriched transcription factor (TF) genes, whereas 17,269 were expressed in BS cells, including 214 BS-enriched TF genes. Interestingly, many TF gene families show a conspicuous BS preference in expression. Pathway analyses reveal differentiation between the two cell types in various functional categories, with the M cells playing more important roles in light reaction, protein synthesis and folding, tetrapyrrole synthesis, and RNA binding, while the BS cells specialize in transport, signaling, protein degradation and posttranslational modification, major carbon, hydrogen, and oxygen metabolism, cell division and organization, and development. Genes coding for several transporters involved in the shuttle of C(4) metabolites and BS cell wall development have been identified, to our knowledge, for the first time. This comprehensive data set will be useful for studying M/BS differentiation in regulation and function.

Elucidation of Hepatitis C Virus Transmission and Early Diversification by Single Genome Sequencing

PubMed Central

Li, Hui; Stoddard, Mark B.; Wang, Shuyi; Blair, Lily M.; Giorgi, Elena E.; Parrish, Erica H.; Learn, Gerald H.; Hraber, Peter; Goepfert, Paul A.; Saag, Michael S.; Denny, Thomas N.; Haynes, Barton F.; Hahn, Beatrice H.; Ribeiro, Ruy M.; Perelson, Alan S.; Korber, Bette T.; Bhattacharya, Tanmoy; Shaw, George M.

2012-01-01

A precise molecular identification of transmitted hepatitis C virus (HCV) genomes could illuminate key aspects of transmission biology, immunopathogenesis and natural history. We used single genome sequencing of 2,922 half or quarter genomes from plasma viral RNA to identify transmitted/founder (T/F) viruses in 17 subjects with acute community-acquired HCV infection. Sequences from 13 of 17 acute subjects, but none of 14 chronic controls, exhibited one or more discrete low diversity viral lineages. Sequences within each lineage generally revealed a star-like phylogeny of mutations that coalesced to unambiguous T/F viral genomes. Numbers of transmitted viruses leading to productive clinical infection were estimated to range from 1 to 37 or more (median = 4). Four acutely infected subjects showed a distinctly different pattern of virus diversity that deviated from a star-like phylogeny. In these cases, empirical analysis and mathematical modeling suggested high multiplicity virus transmission from individuals who themselves were acutely infected or had experienced a virus population bottleneck due to antiviral drug therapy. These results provide new quantitative and qualitative insights into HCV transmission, revealing for the first time virus-host interactions that successful vaccines or treatment interventions will need to overcome. Our findings further suggest a novel experimental strategy for identifying full-length T/F genomes for proteome-wide analyses of HCV biology and adaptation to antiviral drug or immune pressures. PMID:22927816

Light output improvement of GaN-based light-emitting diodes grown on Si (111) by a via-thin-film structure

NASA Astrophysics Data System (ADS)

Li, Zengcheng; Feng, Bo; Deng, Biao; Liu, Legong; Huang, Yingnan; Feng, Meixin; Zhou, Yu; Zhao, Hanmin; Sun, Qian; Wang, Huaibing; Yang, Xiaoli; Yang, Hui

2018-04-01

This work reports the fabrication of via-thin-film light-emitting diode (via-TF-LED) to improve the light output power (LOP) of blue/white GaN-based LEDs grown on Si (111) substrates. The as-fabricated via-TF-LEDs were featured with a roughened n-GaN surface and the p-GaN surface bonded to a wafer carrier with a silver-based reflective electrode, together with an array of embedded n-type via pillar metal contact from the p-GaN surface etched through the multiple-quantum-wells (MQWs) into the n-GaN layer. When operated at 350 mA, the via-TF-LED gave an enhanced blue LOP by 7.8% and over 3.5 times as compared to the vertical thin-film LED (TF-LED) and the conventional lateral structure LED (LS-LED). After covering with yellow phosphor that converts some blue photons into yellow light, the via-TF-LED emitted an enhanced white luminous flux by 13.5% and over 5 times, as compared with the white TF-LED and the white LS-LED, respectively. The significant LOP improvement of the via-TF-LED was attributed to the elimination of light absorption by the Si (111) epitaxial substrate and the finger-like n-electrodes on the roughened emitting surface. Project supported by the National Key R&D Program (Nos. 2016YFB0400100, 2016YFB0400104), the National Natural Science Foundation of China (Nos. 61534007, 61404156, 61522407, 61604168, 61775230), the Key Frontier Scientific Research Program of the Chinese Academy of Sciences (No. QYZDB-SSW-JSC014), the Science and Technology Service Network Initiative of the Chinese Academy of Sciences, the Key R&D Program of Jiangsu Province (No. BE2017079), the Natural Science Foundation of Jiangsu Province (No. BK20160401), and the China Postdoctoral Science Foundation (No. 2016M591944). This work was also supported by the Open Fund of the State Key Laboratory of Luminescence and Applications (No. SKLA-2016-01), the Open Fund of the State Key Laboratory on Integrated Optoelectronics (Nos. IOSKL2016KF04, IOSKL2016KF07), and the Seed Fund from SINANO, CAS (No. Y5AAQ51001).

Counselor and Participant Perspectives of Trauma-Focused Cognitive Behavioral Therapy for Children in Zambia: A Qualitative Study

PubMed Central

Murray, Laura K.; Skavenski, Stephanie; Michalopoulos, Lynn M.; Bolton, Paul A.; Bass, Judith K.; Familiar, Itziar; Imasiku, Mwiya; Cohen, Judy

2014-01-01

Objective This study examined Zambian counselors, children, and caregivers' perceptions of an evidence-based treatment (EBT) for trauma (Trauma-Focused Cognitive Behavioral Therapy, TF-CBT) utilized in Zambia to address mental health problems in children. Method Semi-structured interviews were conducted with local counselors trained in TF-CBT (N=19; 90% of those trained; 12 Female) and children/caregivers who had received TF-CBT in a small feasibility study (N=18; 86% of the children and N=16; 76% of the caregivers) who completed TF-CBT (Total completed; N=21). Each client was asked six open-ended questions, and domain analysis was used to explore the data. Results Counselors were positive about the program, liked the structure and flexibility, reported positive changes in their clients, and discussed the cultural adaptation around activities and language. Counselors stated the training was too short, and the supervision was necessary. Challenges included client engagement and attendance, availability of location, funding, and a lack of community understanding of “therapy.” Children and caregivers stated multiple positive changes they attributed to TF-CBT, such as better family communication, reduction of problem behaviors, and ability to speak about the trauma. They recommended continuing the program. Conclusion This study brings a critical examination of providers' and clients' perspectives of the implementation of an EBT for children in a low-resource setting. Clinical implications include changing implementation methods based on responses. Research implications include future study directions such as an effectiveness trial of TF-CBT and an examination of implementation factors. PMID:24400677

Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma

PubMed Central

Kumar, Amit; Smith, Claire E. P.; Giorgi, Elena E.; Martinez, David R.; Yusim, Karina; Stamper, Lisa; McGuire, Erin; Montefiori, David C.

2018-01-01

Despite extensive genetic diversity of HIV-1 in chronic infection, a single or few maternal virus variants become the founders of an infant’s infection. These transmitted/founder (T/F) variants are of particular interest, as a maternal or infant HIV vaccine should raise envelope (Env) specific IgG responses capable of blocking this group of viruses. However, the maternal or infant factors that contribute to selection of infant T/F viruses are not well understood. In this study, we amplified HIV-1 env genes by single genome amplification from 16 mother-infant transmitting pairs from the U.S. pre-antiretroviral era Women Infant Transmission Study (WITS). Infant T/F and representative maternal non-transmitted Env variants from plasma were identified and used to generate pseudoviruses for paired maternal plasma neutralization sensitivity analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma. Yet, all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies and variably sensitive to heterologous plasma neutralizing antibodies. Also, these infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants (p = 0.012). Altogether, our findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could further reduce infant HIV-1 infection risk. PMID:29672607

Tenacibaculum litoreum sp. nov., isolated from tidal flat sediment.

PubMed

Choi, Dong Han; Kim, Yoon-Gon; Hwang, Chung Yeon; Yi, Hana; Chun, Jongsik; Cho, Byung Cheol

2006-03-01

A rod-shaped bacterium, designated CL-TF13T, was isolated from a tidal flat in Ganghwa, Korea. Analysis of the 16S rRNA gene sequence revealed an affiliation with the genus Tenacibaculum. The sequence similarities between CL-TF13T and type strains of members of the genus Tenacibaculum were from 94.2 to 97.4%. Cells were motile by means of gliding. Strain CL-TF13T grew on solid medium as pale-yellow colonies with an irregular spreading edge. The strain was able to grow in NaCl at a range of 3-5%. They grew within a temperature range of 5-40 degrees C and at pH range of 6-10. The major fatty acids were summed feature 3 (C(16:1)omega7c and/or iso-C(15:0) 2-OH, 19.6%), iso-C(15:0) (18.8%) and iso-C(17:0) 3-OH (13.6%). Fatty acids such as C(18:3)omega6c (6,9,12) (1.5%) and summed feature 4 (iso I- and/or anteiso B-C(17:1), 1.3%) were uniquely found in minor quantities in CL-TF13T among Tenacibaculum species. The DNA G + C content was 30 mol%. According to physiological data, fatty-acid composition and 16S rRNA gene sequence, CL-TF13T could be assigned to the genus Tenacibaculum but distinguished from the recognized species of the genus. Therefore, strain CL-TF13T (= KCCM 42115T = JCM 13039T) represents a novel species, for which the name Tenacibaculum litoreum sp. nov. is proposed.

A transcriptional dynamic network during Arabidopsis thaliana pollen development.

PubMed

Wang, Jigang; Qiu, Xiaojie; Li, Yuhua; Deng, Youping; Shi, Tieliu

2011-01-01

To understand transcriptional regulatory networks (TRNs), especially the coordinated dynamic regulation between transcription factors (TFs) and their corresponding target genes during development, computational approaches would represent significant advances in the genome-wide expression analysis. The major challenges for the experiments include monitoring the time-specific TFs' activities and identifying the dynamic regulatory relationships between TFs and their target genes, both of which are currently not yet available at the large scale. However, various methods have been proposed to computationally estimate those activities and regulations. During the past decade, significant progresses have been made towards understanding pollen development at each development stage under the molecular level, yet the regulatory mechanisms that control the dynamic pollen development processes remain largely unknown. Here, we adopt Networks Component Analysis (NCA) to identify TF activities over time course, and infer their regulatory relationships based on the coexpression of TFs and their target genes during pollen development. We carried out meta-analysis by integrating several sets of gene expression data related to Arabidopsis thaliana pollen development (stages range from UNM, BCP, TCP, HP to 0.5 hr pollen tube and 4 hr pollen tube). We constructed a regulatory network, including 19 TFs, 101 target genes and 319 regulatory interactions. The computationally estimated TF activities were well correlated to their coordinated genes' expressions during the development process. We clustered the expression of their target genes in the context of regulatory influences, and inferred new regulatory relationships between those TFs and their target genes, such as transcription factor WRKY34, which was identified that specifically expressed in pollen, and regulated several new target genes. Our finding facilitates the interpretation of the expression patterns with more biological relevancy, since the clusters corresponding to the activity of specific TF or the combination of TFs suggest the coordinated regulation of TFs to their target genes. Through integrating different resources, we constructed a dynamic regulatory network of Arabidopsis thaliana during pollen development with gene coexpression and NCA. The network illustrated the relationships between the TFs' activities and their target genes' expression, as well as the interactions between TFs, which provide new insight into the molecular mechanisms that control the pollen development.

Tissue factor deficiency increases alveolar hemorrhage and death in influenza A virus-infected mice.

PubMed

Antoniak, S; Tatsumi, K; Hisada, Y; Milner, J J; Neidich, S D; Shaver, C M; Pawlinski, R; Beck, M A; Bastarache, J A; Mackman, N

2016-06-01

Essentials H1N1 Influenza A virus (IAV) infection is a hemostatic challenge for the lung. Tissue factor (TF) on lung epithelial cells maintains lung hemostasis after IAV infection. Reduced TF-dependent activation of coagulation leads to alveolar hemorrhage. Anticoagulation might increase the risk for hemorrhages into the lung during severe IAV infection. Background Influenza A virus (IAV) infection is a common respiratory tract infection that causes considerable morbidity and mortality worldwide. Objective To investigate the effect of genetic deficiency of tissue factor (TF) in a mouse model of IAV infection. Methods Wild-type mice, low-TF (LTF) mice and mice with the TF gene deleted in different cell types were infected with a mouse-adapted A/Puerto Rico/8/34 H1N1 strain of IAV. TF expression was measured in the lungs, and bronchoalveolar lavage fluid (BALF) was collected to measure extracellular vesicle TF, activation of coagulation, alveolar hemorrhage, and inflammation. Results IAV infection of wild-type mice increased lung TF expression, activation of coagulation and inflammation in BALF, but also led to alveolar hemorrhage. LTF mice and mice with selective deficiency of TF in lung epithelial cells had low basal levels of TF and failed to increase TF expression after infection; these two strains of mice had more alveolar hemorrhage and death than controls. In contrast, deletion of TF in either myeloid cells or endothelial cells and hematopoietic cells did not increase alveolar hemorrhage or death after IAV infection. These results indicate that TF expression in the lung, particularly in epithelial cells, is required to maintain alveolar hemostasis after IAV infection. Conclusion Our study indicates that TF-dependent activation of coagulation is required to limit alveolar hemorrhage and death after IAV infection. © 2016 International Society on Thrombosis and Haemostasis.

The removal of RNA primers from DNA synthesized by the reverse transcriptase of the retrotransposon Tf1 is stimulated by Tf1 integrase.

PubMed

Herzig, Eytan; Voronin, Nickolay; Hizi, Amnon

2012-06-01

The Tf1 retrotransposon represents a group of long terminal repeat retroelements that use an RNA self-primer for initiating reverse transcription while synthesizing the minus-sense DNA strand. Tf1 reverse transcriptase (RT) was found earlier to generate the self-primer in vitro. Here, we show that this RT can remove from the synthesized cDNA the entire self-primer as well as the complete polypurine tract (PPT) sequence (serving as a second primer for cDNA synthesis). However, these primer removals, mediated by the RNase H activity of Tf1 RT, are quite inefficient. Interestingly, the integrase of Tf1 stimulated the specific Tf1 RT-directed cleavage of both the self-primer and PPT, although there was no general enhancement of the RT's RNase H activity (and the integrase by itself is devoid of any primer cleavage). The RTs of two prototype retroviruses, murine leukemia virus and human immunodeficiency virus, showed only a partial and nonspecific cleavage of both Tf1-associated primers with no stimulation by Tf1 integrase. Mutagenesis of Tf1 integrase revealed that the complete Tf1 integrase protein (excluding its chromodomain) is required for stimulating the Tf1 RT primer removal activity. Nonetheless, a double mutant integrase that has lost its integration functions can still stimulate the RT's activity, though heat-inactivated integrase cannot enhance primer removals. These findings suggest that the enzymatic activity of Tf1 integrase is not essential for stimulating the RT-mediated primer removal, while the proper folding of this protein is obligatory for this function. These results highlight possible new functions of Tf1 integrase in the retrotransposon's reverse transcription process.

The Removal of RNA Primers from DNA Synthesized by the Reverse Transcriptase of the Retrotransposon Tf1 Is Stimulated by Tf1 Integrase

PubMed Central

Herzig, Eytan; Voronin, Nickolay

2012-01-01

The Tf1 retrotransposon represents a group of long terminal repeat retroelements that use an RNA self-primer for initiating reverse transcription while synthesizing the minus-sense DNA strand. Tf1 reverse transcriptase (RT) was found earlier to generate the self-primer in vitro. Here, we show that this RT can remove from the synthesized cDNA the entire self-primer as well as the complete polypurine tract (PPT) sequence (serving as a second primer for cDNA synthesis). However, these primer removals, mediated by the RNase H activity of Tf1 RT, are quite inefficient. Interestingly, the integrase of Tf1 stimulated the specific Tf1 RT-directed cleavage of both the self-primer and PPT, although there was no general enhancement of the RT's RNase H activity (and the integrase by itself is devoid of any primer cleavage). The RTs of two prototype retroviruses, murine leukemia virus and human immunodeficiency virus, showed only a partial and nonspecific cleavage of both Tf1-associated primers with no stimulation by Tf1 integrase. Mutagenesis of Tf1 integrase revealed that the complete Tf1 integrase protein (excluding its chromodomain) is required for stimulating the Tf1 RT primer removal activity. Nonetheless, a double mutant integrase that has lost its integration functions can still stimulate the RT's activity, though heat-inactivated integrase cannot enhance primer removals. These findings suggest that the enzymatic activity of Tf1 integrase is not essential for stimulating the RT-mediated primer removal, while the proper folding of this protein is obligatory for this function. These results highlight possible new functions of Tf1 integrase in the retrotransposon's reverse transcription process. PMID:22491446

The Microbiota Is Essential for the Generation of Black Tea Theaflavins-Derived Metabolites

PubMed Central

Chen, Huadong; Hayek, Saeed; Rivera Guzman, Javier; Gillitt, Nicholas D.; Ibrahim, Salam A.; Jobin, Christian; Sang, Shengmin

2012-01-01

Background Theaflavins including theaflavin (TF), theaflavin-3-gallate (TF3G), theaflavin-3′-gallate (TF3′G), and theaflavin-3,3′-digallate (TFDG), are the most important bioactive polyphenols in black tea. Because of their poor systemic bioavailability, it is still unclear how these compounds can exert their biological functions. The objective of this study is to identify the microbial metabolites of theaflavins in mice and in humans. Methods and Findings In the present study, we gavaged specific pathogen free (SPF) mice and germ free (GF) mice with 200 mg/kg TFDG and identified TF, TF3G, TF3′G, and gallic acid as the major fecal metabolites of TFDG in SPF mice. These metabolites were absent in TFDG- gavaged GF mice. The microbial bioconversion of TFDG, TF3G, and TF3′G was also investigated in vitro using fecal slurries collected from three healthy human subjects. Our results indicate that TFDG is metabolized to TF, TF3G, TF3′G, gallic acid, and pyrogallol by human microbiota. Moreover, both TF3G and TF3′G are metabolized to TF, gallic acid, and pyrogallol by human microbiota. Importantly, we observed interindividual differences on the metabolism rate of gallic acid to pyrogallol among the three human subjects. In addition, we demonstrated that Lactobacillus plantarum 299v and Bacillus subtilis have the capacity to metabolize TFDG. Conclusions The microbiota is important for the metabolism of theaflavins in both mice and humans. The in vivo functional impact of microbiota-generated theaflavins-derived metabolites is worthwhile of further study. PMID:23227227

Differential effects of somatostatin on circulating tissue factor procoagulant activity and protein.

PubMed

Boden, Guenther; Vaidyula, Vijender; Homko, Carol; Mozzoli, Maria; Rao, A Koneti

2007-05-01

The tissue factor (TF) pathway is the primary mechanism for initiation of blood coagulation. Circulating blood contains TF, which originates mainly from monocytes and is thrombogenic. The presence of somatostatin (SMS) receptors on monocytes suggests the possibility that SMS may regulate TF synthesis and/or release. Circulating TF procoagulant activity (TF-PCA), factor VIIa activity (FVIIa; clotting assays), TF antigen (TF-Ag; ELISA), prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complexes (ELISAs), CD40 ligand expression on platelets, and monocyte-platelet aggregates (flow cytometry) were determined in blood from normal volunteers undergoing 24 h of basal glucose/basal insulin (BG/BI) clamps and high-glucose/high-insulin (HG/HI) clamps with and without SMS. Infusions of SMS under basal conditions (BG/BI) raised TF-PCA 1.8-fold (P < 0.03), TF-Ag 2.3-fold (P < 0.001), and TF expression on monocytes by 36% (P < 0.001) and decreased plasma levels of FVIIa by 30% (P < 0.001). Infusion of SMS reduced the 8.6-fold HG/HI-induced increase in TF-Ag by 26% and the 8.6-fold increase in TF-PCA by 100%. SMS also prevented the 60% increase in TF expression on monocytes, the 2.2-fold increase in F1.2, the 40% increase in CD40L expression on platelets, and the 17% increase in monocyte-platelet aggregates seen during HG/HI. We conclude that SMS completely prevented HG/HI-induced TF activation in normal volunteers and may be of use to reduce the procoagulant state and acute vascular events in hyperinsulinemic insulin-resistant patients with type 2 diabetes.

A Pilot Study of Tissue Factor-Tissue Factor Pathway Inhibitor Axis and Other Selected Coagulation Parameters in Broiler Chickens Administered in Ovo with Selected Prebiotics*.

PubMed

Buzala, Mateusz; Ponczek, Michal Blazej; Slomka, Artur; Roslewska, Aleksandra; Janicki, Bogdan; Zekanowska, Ewa; Bednarczyk, Marek

The tissue factor (TF) - tissue factor pathway inhibitor (TFPI) axis plays a major role in hemostasis. Disorders of the coagulation system are commonly diagnosed with the help of screening tests such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and plasma fibrinogen concentration (PFC). However, the effect of prebiotics on the hemostasis system has not been characterized in poultry yet. This study was designed to determine the effect of in ovo administration ofprebiotics on blood coagulation parameters of broiler chickens depending on their age. The study was conducted with 180 broiler chick embryos, the air cells of which were injected on day 12 of incubation with prebiotics (experimental groups: Bi2tos, DiNovoo and RFO) or physiological saline solution (control group). At 1, 21 and 42 days of rearing, blood was sampled from 15 broiler chickens from each group. An enzyme immunoassay was performed to determine plasma TF and TFPI levels, and PT, aPTT and PFC were determined in the chicken blood. We demonstrated that: 1) total TF levels increased with age in the experimental groups, 2) prebiotics had no significant effect on TF levels between the groups at a particular age, 3) total TFPI levels differed between both the type of in ovo injected substance and the broiler chicken age, 4) in the control group, PT and aPTT were found to increase with age whilst fibrinogen concentration decreased. The main conclusion from this pilot study is that total TF and TFPI levels change with age, however no clear patterns regarding TFPI were detected yet. The levels of PT, aPTT and PFC varied with the prebiotics administered in ovo as well as with the age of broiler chickens.

Initial HIV-1 Antigen-Specific CD8+ T Cells in Acute HIV-1 Infection Inhibit Transmitted/Founder Virus Replication

PubMed Central

Freel, Stephanie A.; Picking, Ralph A.; Ferrari, Guido; Ding, Haitao; Ochsenbauer, Christina; Kappes, John C.; Kirchherr, Jennifer L.; Soderberg, Kelly A.; Weinhold, Kent J.; Cunningham, Coleen K.; Denny, Thomas N.; Crump, John A.; Cohen, Myron S.; McMichael, Andrew J.; Haynes, Barton F.

2012-01-01

CD8-mediated virus inhibition can be detected in HIV-1-positive subjects who naturally control virus replication. Characterizing the inhibitory function of CD8+ T cells during acute HIV-1 infection (AHI) can elucidate the nature of the CD8+ responses that can be rapidly elicited and that contribute to virus control. We examined the timing and HIV-1 antigen specificity of antiviral CD8+ T cells during AHI. Autologous and heterologous CD8+ T cell antiviral functions were assessed longitudinally during AHI in five donors from the CHAVI 001 cohort using a CD8+ T cell-mediated virus inhibition assay (CD8 VIA) and transmitted/founder (T/F) viruses. Potent CD8+ antiviral responses against heterologous T/F viruses appeared during AHI at the first time point sampled in each of the 5 donors (Fiebig stages 1/2 to 5). Inhibition of an autologous T/F virus was durable to 48 weeks; however, inhibition of heterologous responses declined concurrent with the resolution of viremia. HIV-1 viruses from 6 months postinfection were more resistant to CD8+-mediated virus inhibition than cognate T/F viruses, demonstrating that the virus escapes early from CD8+ T cell-mediated inhibition of virus replication. CD8+ T cell antigen-specific subsets mediated inhibition of T/F virus replication via soluble components, and these soluble responses were stimulated by peptide pools that include epitopes that were shown to drive HIV-1 escape during AHI. These data provide insights into the mechanisms of CD8-mediated virus inhibition and suggest that functional analyses will be important for determining whether similar antigen-specific virus inhibition can be induced by T cell-directed vaccine strategies. PMID:22514337

The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?

PubMed Central

2010-01-01

Background High concentrations of recombinant activated factor VII (rFVIIa) can stop bleeding in hemophilic patients. However the rFVIIa dose needed for stopping haemhorrage in off-label indications is unknown. Since thrombin is the main hemostatic agent, this study investigated the effect of rFVIIa and tissue factor (TF) on thrombin generation (TG) in vitro. Methods Lag time (LT), time to peak (TTP), peak TG (PTG), and area under the curve after 35 min (AUCo-35 min) with the calibrated automated thrombography was used to evaluate TG. TG was assayed in platelet-rich plasma (PRP) samples from 29 healthy volunteers under basal conditions and after platelet stimulation with 5.0 μg/ml, 2.6 μg/ml, 0.5 μg/ml, 0.25 μg/ml, and 0.125 μg/ml rFVIIa alone and in normal platelet-poor plasma (PPP) samples from 22 healthy volunteers, rFVIIa in combination with various concentrations of TF (5.0, 2.5, 1.25 and 0.5 pM). Results In PRP activated by rFVIIa, there was a statistically significant increase in TG compared to basal values. A significant TF dose-dependent shortening of LT and increased PTG and AUCo→35 min were obtained in PPP. The addition of rFVIIa increased the effect of TF in shorting the LT and increasing the AUCo→35 min with no effect on PTG but were independent of rFVIIa concentration. Conclusion Low concentrations of rFVIIa were sufficient to form enough thrombin in normal PRP or in PPP when combined with TF, and suggest low concentrations for normalizing hemostasis in off-label indications. PMID:20444280

The Intracellular Trafficking Pathway of Transferrin

PubMed Central

Mayle, Kristine M.; Le, Alexander M.; Kamei, Daniel T.

2011-01-01

Background Transferrin (Tf) is an iron-binding protein that facilitates iron-uptake in cells. Iron-loaded Tf first binds to the Tf receptor (TfR) and enters the cell through clathrin-mediated endocytosis. Inside the cell, Tf is trafficked to early endosomes, delivers iron, and then is subsequently directed to recycling endosomes to be taken back to the cell surface. Scope of Review We aim to review the various methods and techniques that researchers have employed for elucidating the Tf trafficking pathway and the cell-machinery components involved. These experimental methods can be categorized as microscopy, radioactivity, and surface plasmon resonance (SPR). Major Conclusions Qualitative experiments, such as total internal reflectance fluorescence (TIRF), electron, laser-scanning confocal, and spinning-disk confocal microscopy, have been utilized to determine the roles of key components in the Tf trafficking pathway. These techniques allow temporal resolution and are useful for imaging Tf endocytosis and recycling, which occur on the order of seconds to minutes. Additionally, radiolabeling and SPR methods, when combined with mathematical modeling, have enabled researchers to estimate quantitative kinetic parameters and equilibrium constants associated with Tf binding and trafficking. General Significance Both qualitative and quantitative data can be used to analyze the Tf trafficking pathway. The valuable information that is obtained about the Tf trafficking pathway can then be combined with mathematical models to identify design criteria to improve the ability of Tf to deliver anticancer drugs. PMID:21968002

Protein functionalized tramadol-loaded PLGA nanoparticles: preparation, optimization, stability and pharmacodynamic studies.

PubMed

Lalani, Jigar; Rathi, Mohan; Lalan, Manisha; Misra, Ambikanandan

2013-06-01

Poly (d,l-lactide-co-glycolide acid) (PLGA) Nanoparticles (NPs) with sustained drug release and enhanced circulation time presents widely explored non-invasive approach for drug delivery to brain. However, blood-brain barrier (BBB) limits the drug delivery to brain. This can be overcome by anchoring endogenous ligand like Transferrin (Tf) and Lactoferrin (Lf) on the surface of NPs, allowing efficient brain delivery via receptor-mediated endocytosis. The aim of the present investigation was preparation, optimization, characterization and comparative evaluation of targeting efficiency of Tf- vs. Lf-conjugated NPs. Tramadol-loaded PLGA NPs were prepared by nanoprecipitation techniques and optimized using 3(3) factorial design. The effect of polymer concentration, stabilizer concentration and organic:aqueous phase ratio were evaluated on particle size (PS) and entrapment efficiency (EE). The formulation was optimized based on desirability for lower PS (<150 nm) and higher EE (>70%). Optimized PLGA NPs were conjugated with Tf and Lf, characterized and evaluated for stability study. Pharmacodynamic study was performed in rat after intravenous administration. The optimized formulation had 100 mg of PLGA, 1% polyvinyl alcohol (PVA) and 1:2 acetone:water ratio. The Lf and Tf conjugation to PLGA NPs was estimated to 186 Tf and 185 Lf molecules per NPs. Lyophilization was optimized at 1:2 ratio of NPs:trehalose. The NPs were found stable for 6 months at refrigerated condition. Pharmacodynamic study demonstrated enhanced efficacy of ligand-conjugated NPs against unconjugated NPs. Conjugated NPs demonstrated significantly higher pharmacological effect over a period of 24 h. Furthermore Lf functionalized NPs exhibited better antinociceptive effect as compared to Tf functionalized NPs.

μSR Study of Organic Superconductor λ-(BETS)2GaCl4

NASA Astrophysics Data System (ADS)

Sari, D. P.; Asih, R.; Mohm-Tajudin, S. S.; Adam, N.; Hiraki, K.; Ishii, Y.; Takahashi, T.; Nakano, T.; Nozue, Y.; Sulaiman, S.; Mohamed-Ibrahim, M. I.; Watanabe, I.

2017-05-01

Muon-spin-relaxation (μSR) measurements in the transverse-field (TF) of 30 G were carried out from 7 K down to 1.8 K on the non-magnetic anion-based organic superconductor λ-(BETS)2GaCl4. The TF-μSR time spectrum showed a significant increase with the Gaussian-type damping behavior below the superconducting transition temperature TC = 5 K confirming the bulk SC state with the full volume fraction. The zero-field (ZF) μSR time spectrum did not show any change against the temperature down to 1.7 K, suggesting that the time reversal symmetry of the Cooper pair might not be broken.