V-ELMpiRNAPred: Identification of human piRNAs by the voting-based extreme learning machine (V-ELM) with a new hybrid feature.

PubMed

Pian, Cong; Chen, Yuan-Yuan; Zhang, Jin; Chen, Zhi; Zhang, Guang-Le; Li, Qiang; Yang, Tao; Zhang, Liang-Yun

2017-02-01

Piwi-interacting RNAs (piRNAs) were recently discovered as endogenous small noncoding RNAs. Some recent research suggests that piRNAs may play an important role in cancer. So the precise identification of human piRNAs is a significant work. In this paper, we introduce a series of new features with 80 dimension called short sequence motifs (SSM). A hybrid feature vector with 1444 dimension can be formed by combining 1364 features of [Formula: see text]-mer strings and 80 features of SSM features. We optimize the 1444 dimension features using the feature score criterion (FSC) and list them in descending order according to the scores. The first 462 are selected as the input feature vector in the classifier. Moreover, eight of 80 SSM features appear in the top 20. This indicates that these eight SSM features play an important part in the identification of piRNAs. Since five of the above eight SSM features are associated with nucleotide A and G ('A*G', 'A**G', 'A***G', 'A****G', 'A*****G'). So, we guess there may exist some biological significance. We also use a neural network algorithm called voting-based extreme learning machine (V-ELM) to identify real piRNAs. The Specificity (Sp) and Sensitivity (Sn) of our method are 95.48% and 94.61%, respectively in human species. This result shows that our method is more effective compared with those of the piRPred, piRNApredictor, Asym-Pibomd, Piano and McRUMs. The web service of V-ELMpiRNAPred is available for free at http://mm20132014.wicp.net:38601/velmprepiRNA/Main.jsp .

Resting-state functional connectivity and pitch identification ability in non-musicians

PubMed Central

Hou, Jiancheng; Chen, Chuansheng; Dong, Qi

2015-01-01

Previous studies have used task-related fMRI to investigate the neural basis of pitch identification (PI), but no study has examined the associations between resting-state functional connectivity (RSFC) and PI ability. Using a large sample of Chinese non-musicians (N = 320, with 56 having prior musical training), the current study examined the associations among musical training, PI ability, and RSFC. Results showed that musical training was associated with increased RSFC within the networks for multiple cognitive functions (such as vision, phonology, semantics, auditory encoding, and executive functions). PI ability was associated with RSFC with regions for perceptual and auditory encoding for participants with musical training, and with RSFC with regions for short-term memory, semantics, and phonology for participants without musical training. PMID:25717289

PI3K inhibitors block skeletogenesis but not patterning in sea urchin embryos.

PubMed

Bradham, C A; Miranda, E L; McClay, D R

2004-04-01

Skeletogenesis in the sea urchin embryo is a simple model of biomineralization, pattern formation, and cell-cell communication during embryonic development. The calcium carbonate skeletal spicules are secreted by primary mesenchyme cells (PMCs), but the skeletal pattern is dictated by the embryonic ectoderm. Although the process of skeletogenesis is well characterized, there is little molecular understanding of the basis of patterning within this system. In this study, we examined the contribution of phosphatidylinositide 3-kinase (PI3K)-mediated signaling to the skeletogenic process in sea urchin embryos by using the well-established PI3K inhibitors LY294002 and wortmannin. Our results show that PI3K inhibitors specifically and reversibly block skeletogenesis, and that this blockade occurs within the PMCs rather than in the ectoderm, because the inhibitors block spiculogenesis in cultured micromeres. Our results are consistent with a model in which PI3K signaling is required, not for pattern sensing or interpretation but rather for the biomineralization process itself in the sea urchin embryo. Copyright 2004 Wiley-Liss, Inc.

Development and evaluation of new primers for PCR-based identification of Prevotella intermedia.

PubMed

Zhou, Yanbin; Liu, Dali; Wang, Yiwei; Zhu, Cailian; Liang, Jingping; Shu, Rong

2014-08-01

The aim of this study was to develop new Prevotella intermedia-specific PCR primers based on the 16S rRNA. The new primer set, Pi-192 and Pi-468, increased the accuracy of PCR-based P. intermedia identification and could be useful in the detection of P. intermedia as well as epidemiological studies on periodontal disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Principal component analysis of PiB distribution in Parkinson and Alzheimer diseases

PubMed Central

Markham, Joanne; Flores, Hubert; Hartlein, Johanna M.; Goate, Alison M.; Cairns, Nigel J.; Videen, Tom O.; Perlmutter, Joel S.

2013-01-01

Objective: To use principal component analyses (PCA) of Pittsburgh compound B (PiB) PET imaging to determine whether the pattern of in vivo β-amyloid (Aβ) in Parkinson disease (PD) with cognitive impairment is similar to the pattern found in symptomatic Alzheimer disease (AD). Methods: PiB PET scans were obtained from participants with PD with cognitive impairment (n = 53), participants with symptomatic AD (n = 35), and age-matched controls (n = 67). All were assessed using the Clinical Dementia Rating and APOE genotype was determined in 137 participants. PCA was used to 1) determine the PiB binding pattern in AD, 2) determine a possible unique PD pattern, and 3) directly compare the PiB binding patterns in PD and AD groups. Results: The first 2 principal components (PC1 and PC2) significantly separated the AD and control participants (p < 0.001). Participants with PD with cognitive impairment also were significantly different from participants with symptomatic AD on both components (p < 0.001). However, there was no difference between PD and controls on either component. Even those participants with PD with elevated mean cortical binding potentials were significantly different from participants with AD on both components. Conclusion: Using PCA, we demonstrated that participants with PD with cognitive impairment do not exhibit the same PiB binding pattern as participants with AD. These data suggest that Aβ deposition may play a different pathophysiologic role in the cognitive impairment of PD compared to that in AD. PMID:23825179

The first wave of the 1918 influenza pandemic among soldiers of the Canadian expeditionary force.

PubMed

Rewegan, Alex; Bogaert, Kandace; Yan, Melissa; Gagnon, Alain; Herring, D Ann

2015-01-01

This article evaluates the evidence for the presence of the first, mild wave of the 1918 influenza pandemic among soldiers in the Canadian Expeditionary Force (CEF). Death records for soldiers in the CEF who died in Canada in 1917 and 1918 were extracted from the Commonwealth War Graves Commission and record-linked to the Canada War Graves Registers, Circumstances of Casualty database. Monthly mortality rates from pneumonia and influenza (P&I) were compared with mortality rates from all other causes for 1917 and 1918, and by region for 1918. The herald wave of influenza was present among CEF soldiers in 1918. P&I mortality was significantly higher in March and April 1918 than during the same period in 1917. P&I mortality rates varied across the country and were significantly higher among soldiers who died in the Maritime region of Canada. In March, Maritime P&I mortality was significantly higher than its counterpart in the West; in April it was significantly higher than P&I mortality in both the Central and Western regions. The CEF findings suggest that local, geographic heterogeneity characterized the first wave of the 1918 influenza pandemic in Canada and illustrate the ways in which well-established, historical patterns of cross-border social contact with the United States, coupled with the special conditions created by warfare, disproportionately funnelled influenza into particular regions. Identification of the mild first wave among soldiers in the CEF calls for more research on the civilian experience of both waves of influenza in Canada. © 2015 Wiley Periodicals, Inc.

Detection and identification of alkylating agents by using a bioinspired "chemical nose".

PubMed

Hertzog-Ronen, Carmit; Borzin, Elena; Gerchikov, Yulia; Tessler, Nir; Eichen, Yoav

2009-10-12

Alkylating agents are simple and reactive molecules that are commonly used in many and diverse fields such as organic synthesis, medicine, and agriculture. Some highly reactive alkylating species are also being used as blister chemical-warfare agents. The detection and identification of alkylating agents is not a trivial issue because of their high reactivity and simple structure. Herein, we report on a new multispot luminescence-based approach to the detection and identification of alkylating agents. In order to demonstrate the potential of the approach, seven pi-conjugated oligomers and polymers bearing nucleophilic pyridine groups, 1-7, were adsorbed onto a solid support and exposed to vapors of alkylators 8-15. The alkylation-induced color-shift patterns of the seven-spot array allow clear discrimination of the different alkylators. The spots are sensitive to minute concentrations of alkylators and, because the detection is based on the formation of new covalent bonds, these spots saturate at about 50 ppb.

Intracellular transport and compartmentation of phosphate in plants.

PubMed

Versaw, Wayne K; Garcia, L Rene

2017-10-01

Phosphate (Pi) is an essential macronutrient with structural and metabolic roles within every compartment of the plant cell. Intracellular Pi transporters direct Pi to each organelle and also control its exchange between subcellular compartments thereby providing the means to coordinate compartmented metabolic processes, including glycolysis, photosynthesis, and respiration. In this review we summarize recent advances in the identification and functional analysis of Pi transporters that localize to vacuoles, chloroplasts, non-photosynthetic plastids, mitochondria, and the Golgi apparatus. Electrical potentials across intracellular membranes and the pH of subcellular environments will also be highlighted as key factors influencing the energetics of Pi transport, and therefore pose limits for Pi compartmentation. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Diogene 4 pi detector at Saturne

NASA Technical Reports Server (NTRS)

Alard, J. P.; Arnold, J.; Augerat, J.; Babinet, R.; Bastid, N.; Brochard, F.; Costilhes, J. P.; Crouau, M.; De Marco, N.; Drouet, M.;

Pattern Informatics Approach to Earthquake Forecasting in 3D

NASA Astrophysics Data System (ADS)

Toya, Y.; Tiampo, K. F.; Rundle, J. B.; Chen, C.; Li, H.; Klein, W.

2009-05-01

Natural seismicity is correlated across multiple spatial and temporal scales, but correlations in seismicity prior to a large earthquake are locally subtle (e.g. seismic quiescence) and often prominent in broad scale (e.g., seismic activation), resulting in local and regional seismicity patterns, e.g. a Mogi's donut. Recognizing that patterns in seismicity rate are reflecting the regional dynamics of the directly unobservable crustal stresses, the Pattern Informatics (PI) approach was introduced by Tiampo et al. in 2002 [Europhys. Lett., 60 (3), 481-487,] Rundle et al., 2002 [PNAS 99, suppl. 1, 2514-2521.] In this study, we expand the PI approach to forecasting earthquakes into the third, or vertical dimension, and illustrate its further improvement in the forecasting performance through case studies of both natural and synthetic data. The PI characterizes rapidly evolving spatio-temporal seismicity patterns as angular drifts of a unit state vector in a high dimensional correlation space, and systematically identifies anomalous shifts in seismic activity with respect to the regional background. 3D PI analysis is particularly advantageous over 2D analysis in resolving vertically overlapped seismicity anomalies in a highly complex tectonic environment. Case studies will help to illustrate some important properties of the PI forecasting tool. [Submitted to: Concurrency and Computation: Practice and Experience, Wiley, Special Issue: ACES2008.

Pathway Inspector: a pathway based web application for RNAseq analysis of model and non-model organisms.

PubMed

Bianco, Luca; Riccadonna, Samantha; Lavezzo, Enrico; Falda, Marco; Formentin, Elide; Cavalieri, Duccio; Toppo, Stefano; Fontana, Paolo

2017-02-01

Pathway Inspector is an easy-to-use web application helping researchers to find patterns of expression in complex RNAseq experiments. The tool combines two standard approaches for RNAseq analysis: the identification of differentially expressed genes and a topology-based analysis of enriched pathways. Pathway Inspector is equipped with ad hoc interactive graphical interfaces simplifying the discovery of modulated pathways and the integration of the differentially expressed genes in the corresponding pathway topology. Pathway Inspector is available at the website http://admiral.fmach.it/PI and has been developed in Python, making use of the Django Web Framework. Contact:paolo.fontana@fmach.it

SIZ1 Regulation of Phosphate Starvation-Induced Root Architecture Remodeling Involves the Control of Auxin Accumulation1[C][W][OA

PubMed Central

Miura, Kenji; Lee, Jiyoung; Gong, Qingqiu; Ma, Shisong; Jin, Jing Bo; Yoo, Chan Yul; Miura, Tomoko; Sato, Aiko; Bohnert, Hans J.; Hasegawa, Paul M.

2011-01-01

Phosphate (Pi) limitation causes plants to modulate the architecture of their root systems to facilitate the acquisition of Pi. Previously, we reported that the Arabidopsis (Arabidopsis thaliana) SUMO E3 ligase SIZ1 regulates root architecture remodeling in response to Pi limitation; namely, the siz1 mutations cause the inhibition of primary root (PR) elongation and the promotion of lateral root (LR) formation. Here, we present evidence that SIZ1 is involved in the negative regulation of auxin patterning to modulate root system architecture in response to Pi starvation. The siz1 mutations caused greater PR growth inhibition and LR development of seedlings in response to Pi limitation. Similar root phenotypes occurred if Pi-deficient wild-type seedlings were supplemented with auxin. N-1-Naphthylphthalamic acid, an inhibitor of auxin efflux activity, reduced the Pi starvation-induced LR root formation of siz1 seedlings to a level equivalent to that seen in the wild type. Monitoring of the auxin-responsive reporter DR5::uidA indicated that auxin accumulates in PR tips at early stages of the Pi starvation response. Subsequently, DR5::uidA expression was observed in the LR primordia, which was associated with LR elongation. The time-sequential patterning of DR5::uidA expression occurred earlier in the roots of siz1 as compared with the wild type. In addition, microarray analysis revealed that several other auxin-responsive genes, including genes involved in cell wall loosening and biosynthesis, were up-regulated in siz1 relative to wild-type seedlings in response to Pi starvation. Together, these results suggest that SIZ1 negatively regulates Pi starvation-induced root architecture remodeling through the control of auxin patterning. PMID:21156857

Fire patterns in piñon and juniper land cover types in the Semiarid Western United States from 1984 through 2013

Treesearch

David I. Board; Jeanne C. Chambers; Richard F. Miller; Peter J. Weisberg

2018-01-01

Increases in area burned and fire size have been reported across a wide range of forest and shrubland types in the Western United States in recent decades, but little is known about potential changes in fire regimes of piñon and juniper land cover types. We evaluated spatio-temporal patterns of fire in piñon and juniper land cover types from the National Gap Analysis...

Possibility of large final state interaction phases in light of B --> kpi and pipi data

PubMed

Hou; Yang

2000-05-22

The newly observed &Bmacr;( 0)-->&Kmacr;( 0)pi(0) mode is quite sizable while pi(-)pi(+) is rather small. Data also hint at pi(-)pi(0) greater, similarpi(-)pi(+). Though consistent with zero, central values of CP violating asymmetries in K-pi(+,0) and &Kmacr;( 0)pi(-) show an interesting pattern. Taking cue from these, we suggest that, besides gamma identical witharg(V(*)(ub)) being large, the rescattering phase delta in Kpi and pipi modes may be greater than 90 degrees. If this is true, not only the above trends can be accounted for, but one would also find pi(0)pi(0) approximately pi(-)pi(+,0), and the CP asymmetry in &Bmacr;( 0) vs B0-->pi(-)pi(+) could be as large as -60%. These results can be tested in a couple of years.

DCE-MRI of the prostate using shutter-speed vs. Tofts model for tumor characterization and assessment of aggressiveness.

PubMed

Hectors, Stefanie J; Besa, Cecilia; Wagner, Mathilde; Jajamovich, Guido H; Haines, George K; Lewis, Sara; Tewari, Ashutosh; Rastinehad, Ardeshir; Huang, Wei; Taouli, Bachir

2017-09-01

To quantify Tofts model (TM) and shutter-speed model (SSM) perfusion parameters in prostate cancer (PCa) and noncancerous peripheral zone (PZ) and to compare the diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to Prostate Imaging and Reporting and Data System (PI-RADS) classification for the assessment of PCa aggressiveness. Fifty PCa patients (mean age 60 years old) who underwent MRI at 3.0T followed by prostatectomy were included in this Institutional Review Board-approved retrospective study. DCE-MRI parameters (K trans , v e , k ep [TM&SSM] and intracellular water molecule lifetime τ i [SSM]) were determined in PCa and PZ. Differences in DCE-MRI parameters between PCa and PZ, and between models were assessed using Wilcoxon signed-rank tests. Receiver operating characteristic (ROC) analysis for differentiation between PCa and PZ was performed for individual and combined DCE-MRI parameters. Diagnostic performance of DCE-MRI parameters for identification of aggressive PCa (Gleason ≥8, grade group [GG] ≥3 or pathology stage pT3) was assessed using ROC analysis and compared with PI-RADSv2 scores. DCE-MRI parameters were significantly different between TM and SSM and between PZ and PCa (P < 0.037). Diagnostic performances of TM and SSM for differentiation of PCa from PZ were similar (highest AUC TM: K trans +k ep 0.76, SSM: τ i +k ep 0.80). PI-RADS outperformed TM and SSM DCE-MRI for identification of Gleason ≥8 lesions (AUC PI-RADS: 0.91, highest AUC DCE-MRI: K trans +τ i SSM 0.61, P = 0.002). The diagnostic performance of PI-RADS and DCE-MRI for identification of GG ≥3 and pT3 PCa was not significantly different (P > 0.213). SSM DCE-MRI did not increase the diagnostic performance of DCE-MRI for PCa characterization. PI-RADS outperformed both TM and SSM DCE-MRI for identification of aggressive cancer. 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:837-849. © 2017 International Society for Magnetic Resonance in Medicine.

Structure guided optimization of a fragment hit to imidazopyridine inhibitors of PI3K.

PubMed

Pecchi, Sabina; Ni, Zhi-Jie; Han, Wooseok; Smith, Aaron; Lan, Jiong; Burger, Matthew; Merritt, Hanne; Wiesmann, Marion; Chan, John; Kaufman, Susan; Knapp, Mark S; Janssen, Johanna; Huh, Kay; Voliva, Charles F

2013-08-15

PI3 kinases are a family of lipid kinases mediating numerous cell processes such as proliferation, migration and differentiation. The PI3 Kinase pathway is often de-regulated in cancer through PI3Kα overexpression, gene amplification, mutations and PTEN phosphatase deletion. PI3K inhibitors represent therefore an attractive therapeutic modality for cancer treatment. Herein we describe how the potency of a benzothiazole fragment hit was quickly improved based on structural information and how this early chemotype was further optimized through scaffold hopping. This effort led to the identification of a series of 2-acetamido-5-heteroaryl imidazopyridines showing potent in vitro activity against all class I PI3Ks and attractive pharmacokinetic properties. Copyright © 2013 Elsevier Ltd. All rights reserved.

Identification of a new adapter protein that may link the common beta subunit of the receptor for granulocyte/macrophage colony-stimulating factor, interleukin (IL)-3, and IL-5 to phosphatidylinositol 3-kinase.

PubMed

Jücker, M; Feldman, R A

1995-11-17

Binding of human granulocyte/macrophage colony-stimulating factor (hGM-CSF) to its receptor induces the rapid activation of phosphatidylinositol-3 kinase (PI 3-kinase). As hGM-CSF receptor (hGMR) does not contain a consensus sequence for binding of PI 3-kinase, hGMR must use a distinct mechanism for its association with and activation of PI 3-kinase. Here, we describe the identification of a tyrosine-phosphorylated protein of 76-85 kDa (p80) that associates with the common beta subunit of hGMR and with the SH2 domains of the p85 subunit of PI 3-kinase in hGM-CSF-stimulated cells. Src/Yes and Lyn were tightly associated with the p80.PI 3-kinase complex, suggesting that p80 and other phosphotyrosyl proteins present in the complex were phosphorylated by Src family kinases. Tyrosine phosphorylation of p80 was only detected in hGM-CSF or human interleukin-3-stimulated cells, suggesting that activation of p80 might be specific for signaling via the common beta subunit. We postulate that p80 functions as an adapter protein that may participate in linking the hGM-CSF receptor to the PI 3-kinase signaling pathway.

Consensus model for identification of novel PI3K inhibitors in large chemical library.

PubMed

Liew, Chin Yee; Ma, Xiao Hua; Yap, Chun Wei

2010-02-01

Phosphoinositide 3-kinases (PI3Ks) inhibitors have treatment potential for cancer, diabetes, cardiovascular disease, chronic inflammation and asthma. A consensus model consisting of three base classifiers (AODE, kNN, and SVM) trained with 1,283 positive compounds (PI3K inhibitors), 16 negative compounds (PI3K non-inhibitors) and 64,078 generated putative negatives was developed for predicting compounds with PI3K inhibitory activity of IC(50) < or = 10 microM. The consensus model has an estimated false positive rate of 0.75%. Nine novel potential inhibitors were identified using the consensus model and several of these contain structural features that are consistent with those found to be important for PI3K inhibitory activities. An advantage of the current model is that it does not require knowledge of 3D structural information of the various PI3K isoforms, which is not readily available for all isoforms.

Consensus model for identification of novel PI3K inhibitors in large chemical library

NASA Astrophysics Data System (ADS)

Liew, Chin Yee; Ma, Xiao Hua; Yap, Chun Wei

2010-02-01

Phosphoinositide 3-kinases (PI3Ks) inhibitors have treatment potential for cancer, diabetes, cardiovascular disease, chronic inflammation and asthma. A consensus model consisting of three base classifiers (AODE, kNN, and SVM) trained with 1,283 positive compounds (PI3K inhibitors), 16 negative compounds (PI3K non-inhibitors) and 64,078 generated putative negatives was developed for predicting compounds with PI3K inhibitory activity of IC50 ≤ 10 μM. The consensus model has an estimated false positive rate of 0.75%. Nine novel potential inhibitors were identified using the consensus model and several of these contain structural features that are consistent with those found to be important for PI3K inhibitory activities. An advantage of the current model is that it does not require knowledge of 3D structural information of the various PI3K isoforms, which is not readily available for all isoforms.

Spontaneous switching among multiple spatio-temporal patterns in three-oscillator systems constructed with oscillatory cells of true slime mold

NASA Astrophysics Data System (ADS)

Takamatsu, Atsuko

2006-11-01

Three-oscillator systems with plasmodia of true slime mold, Physarum polycephalum, which is an oscillatory amoeba-like unicellular organism, were experimentally constructed and their spatio-temporal patterns were investigated. Three typical spatio-temporal patterns were found: rotation ( R), partial in-phase ( PI), and partial anti-phase with double frequency ( PA). In pattern R, phase differences between adjacent oscillators were almost 120 ∘. In pattern PI, two oscillators were in-phase and the third oscillator showed anti-phase against the two oscillators. In pattern PA, two oscillators showed anti-phase and the third oscillator showed frequency doubling oscillation with small amplitude. Actually each pattern is not perfectly stable but quasi-stable. Interestingly, the system shows spontaneous switching among the multiple quasi-stable patterns. Statistical analyses revealed a characteristic in the residence time of each pattern: the histograms seem to have Gamma-like distribution form but with a sharp peak and a tail on the side of long period. That suggests the attractor of this system has complex structure composed of at least three types of sub-attractors: a “Gamma attractor”-involved with several Poisson processes, a “deterministic attractor”-the residence time is deterministic, and a “stable attractor”-each pattern is stable. When the coupling strength was small, only the Gamma attractor was observed and switching behavior among patterns R, PI, and PA almost always via an asynchronous pattern named O. A conjecture is as follows: Internal/external noise exposes each pattern of R, PI, and PA coexisting around bifurcation points: That is observed as the Gamma attractor. As coupling strength increases, the deterministic attractor appears then followed by the stable attractor, always accompanied with the Gamma attractor. Switching behavior could be caused by regular existence of the Gamma attractor.

2PI effective action for the SYK model and tensor field theories

NASA Astrophysics Data System (ADS)

Benedetti, Dario; Gurau, Razvan

2018-05-01

We discuss the two-particle irreducible (2PI) effective action for the SYK model and for tensor field theories. For the SYK model the 2PI effective action reproduces the bilocal reformulation of the model without using replicas. In general tensor field theories the 2PI formalism is the only way to obtain a bilocal reformulation of the theory, and as such is a precious instrument for the identification of soft modes and for possible holographic interpretations. We compute the 2PI action for several models, and push it up to fourth order in the 1 /N expansion for the model proposed by Witten in [1], uncovering a one-loop structure in terms of an auxiliary bilocal action.

Characterization of rice blast resistance gene Pi61(t) in rice germplasm

USDA-ARS?s Scientific Manuscript database

Identification of resistance (R) genes to races of Magnaporthe oryzae in rice germplasm is essential for the development of rice cultivars with long lasting blast resistance. In the present study, one major quantitative trait locus, qPi93-3, was fine mapped using a recombinant inbred line (RIL), F8 ...

Identification and molecular mapping of two soybean aphid resistance genes in soybean PI 587732

USDA-ARS?s Scientific Manuscript database

Soybean [Glycine max (L.) Merr.] continues to be plagued by the soybean aphid (Aphis glycines Matsumura: SA) in North America. New soybean resistance sources are needed to combat the four identified SA biotypes. The objectives of this study were to determine the inheritance of SA resistance in PI 58...

Transgenerationally inherited piRNAs trigger piRNA biogenesis by changing the chromatin of piRNA clusters and inducing precursor processing

PubMed Central

Le Thomas, Adrien; Stuwe, Evelyn; Li, Sisi; Marinov, Georgi; Rozhkov, Nikolay; Chen, Yung-Chia Ariel; Luo, Yicheng; Sachidanandam, Ravi; Toth, Katalin Fejes; Patel, Dinshaw; Aravin, Alexei A.

2014-01-01

Small noncoding RNAs that associate with Piwi proteins, called piRNAs, serve as guides for repression of diverse transposable elements in germ cells of metazoa. In Drosophila, the genomic regions that give rise to piRNAs, the so-called piRNA clusters, are transcribed to generate long precursor molecules that are processed into mature piRNAs. How genomic regions that give rise to piRNA precursor transcripts are differentiated from the rest of the genome and how these transcripts are specifically channeled into the piRNA biogenesis pathway are not known. We found that transgenerationally inherited piRNAs provide the critical trigger for piRNA production from homologous genomic regions in the next generation by two different mechanisms. First, inherited piRNAs enhance processing of homologous transcripts into mature piRNAs by initiating the ping-pong cycle in the cytoplasm. Second, inherited piRNAs induce installment of the histone 3 Lys9 trimethylation (H3K9me3) mark on genomic piRNA cluster sequences. The heterochromatin protein 1 (HP1) homolog Rhino binds to the H3K9me3 mark through its chromodomain and is enriched over piRNA clusters. Rhino recruits the piRNA biogenesis factor Cutoff to piRNA clusters and is required for efficient transcription of piRNA precursors. We propose that transgenerationally inherited piRNAs act as an epigenetic memory for identification of substrates for piRNA biogenesis on two levels: by inducing a permissive chromatin environment for piRNA precursor synthesis and by enhancing processing of these precursors. PMID:25085419

Pathway Inspector: a pathway based web application for RNAseq analysis of model and non-model organisms

PubMed Central

Bianco, Luca; Riccadonna, Samantha; Lavezzo, Enrico; Falda, Marco; Formentin, Elide; Cavalieri, Duccio; Toppo, Stefano

2017-01-01

Abstract Summary: Pathway Inspector is an easy-to-use web application helping researchers to find patterns of expression in complex RNAseq experiments. The tool combines two standard approaches for RNAseq analysis: the identification of differentially expressed genes and a topology-based analysis of enriched pathways. Pathway Inspector is equipped with ad hoc interactive graphical interfaces simplifying the discovery of modulated pathways and the integration of the differentially expressed genes in the corresponding pathway topology. Availability and Implementation: Pathway Inspector is available at the website http://admiral.fmach.it/PI and has been developed in Python, making use of the Django Web Framework. Contact: paolo.fontana@fmach.it PMID:28158604

piRNA-directed cleavage of meiotic transcripts regulates spermatogenesis.

PubMed

Goh, Wee Siong Sho; Falciatori, Ilaria; Tam, Oliver H; Burgess, Ralph; Meikar, Oliver; Kotaja, Noora; Hammell, Molly; Hannon, Gregory J

2015-05-15

MIWI catalytic activity is required for spermatogenesis, indicating that piRNA-guided cleavage is critical for germ cell development. To identify meiotic piRNA targets, we augmented the mouse piRNA repertoire by introducing a human meiotic piRNA cluster. This triggered a spermatogenesis defect by inappropriately targeting the piRNA machinery to mouse mRNAs essential for germ cell development. Analysis of such de novo targets revealed a signature for pachytene piRNA target recognition. This enabled identification of both transposable elements and meiotically expressed protein-coding genes as targets of native piRNAs. Cleavage of genic targets began at the pachytene stage and resulted in progressive repression through meiosis, driven at least in part via the ping-pong cycle. Our data support the idea that meiotic piRNA populations must be strongly selected to enable successful spermatogenesis, both driving the response away from essential genes and directing the pathway toward mRNA targets that are regulated by small RNAs in meiotic cells. © 2015 Goh et al.; Published by Cold Spring Harbor Laboratory Press.

Strategies for the enrichment and identification of basic proteins in proteome projects.

PubMed

Bae, Soo-Han; Harris, Andrew G; Hains, Peter G; Chen, Hong; Garfin, David E; Hazell, Stuart L; Paik, Young-Ki; Walsh, Bradley J; Cordwell, Stuart J

2003-05-01

Two-dimensional gel electrophoresis (2-DE) is currently the method of choice for separating complex mixtures of proteins for visual comparison in proteome analysis. This technology, however, is biased against certain classes of proteins including low abundance and hydrophobic proteins. Proteins with extremely alkaline isoelectric points (pI) are often very poorly represented using 2-DE technology, even when complex mixtures are separated using commercially available pH 6-11 or pH 7-10 immobilized pH gradients. The genome of the human gut pathogen, Helicobacter pylori, is dominated by genes encoding basic proteins, and is therefore a useful model for examining methodology suitable for separating such proteins. H. pylori proteins were separated on pH 6-11 and novel pH 9-12 immobilized pH gradients and 65 protein spots were subjected to matrix-assisted laser desorption/ionization-time of flight mass spectrometry, leading to the identification of 49 unique proteins. No proteins were characterized with a theoretical pI of greater than 10.23. A second approach to examine extremely alkaline proteins (pI > 9.0) utilized a prefractionation isoelectric focusing. Proteins were separated into two fractions using Gradiflow technology, and the extremely basic fraction subjected to both sodium dodecyl sulphate-polyacrylamide gel electrophoresis and liquid chromatography (LC) - tandem mass spectrometry post-tryptic digest, allowing the identification of 17 and 13 proteins, respectively. Gradiflow separations were highly specific for proteins with pI > 9.0, however, a single LC separation only allowed the identification of peptides from highly abundant proteins. These methods and those encompassing multiple LC 'dimensions' may be a useful complement to 2-DE for 'near-to-total' proteome coverage in the alkaline pH range.

Isoform-selective induction of human p110δ PI3K expression by TNFα: identification of a new and inducible PIK3CD promoter

PubMed Central

Whitehead, Maria A.; Bombardieri, Michele; Pitzalis, Costantino; Vanhaesebroeck, Bart

2012-01-01

PI3Ks (phosphoinositide 3-kinases) are signalling molecules and drug targets with important biological functions, yet the regulation of PI3K gene expression is poorly understood. Key PI3Ks are the class IA PI3Ks that consist of a catalytic subunit (p110α, p110β and p110δ) in complex with a p85 regulatory subunit. Whereas p110α and p110β are ubiquitously expressed, high levels of p110δ are mainly found in white blood cells, with most non-leucocytes expressing low levels of p110δ. In the present paper we report that TNFα (tumour necrosis factor α) stimulation induces p110δ expression in human ECs (endothelial cells) and synovial fibroblasts, but not in leucocytes, through transcription start sites located in a novel promoter region in the p110δ gene (PIK3CD). This promoter is used in all cell types, including solid tumour cell lines that express p110δ, and is activated by TNFα in ECs and synovial fibroblasts. We further present a detailed biochemical and bioinformatic characterization of p110δ gene regulation, demonstrating that PIK3CD has distinct promoters, some of which can be dynamically activated by pro-inflammatory mediators. This is the first molecular identification of a PI3K promoter under the control of acute extracellular stimulation. PMID:22375552

Live cell imaging of phosphoinositide dynamics during Legionella infection.

PubMed

Weber, Stephen; Hilbi, Hubert

2014-01-01

The "accidental" pathogen Legionella pneumophila replicates intracellularly in a distinct compartment, the Legionella-containing vacuole (LCV). To form this specific pathogen vacuole, the bacteria translocate via the Icm/Dot type IV secretion system approximately 300 different effector proteins into the host cell. Several of these secreted effectors anchor to the cytoplasmic face of the LCV membrane by binding to phosphoinositide (PI) lipids. L. pneumophila thus largely controls the localization of secreted bacterial effectors and the recruitment of host factors to the LCV through the modulation of the vacuole membrane PI pattern. The LCV PI pattern and its dynamics can be studied in real-time using fluorescently labeled protein probes stably produced by the soil amoeba Dictyostelium discoideum. In this chapter, we describe a protocol to (1) construct and handle amoeba model systems as a tool for observing PIs in live cell imaging, (2) capture rapid changes in membrane PI patterning during uptake events, and (3) observe the dynamics of LCV PIs over the course of a Legionella infection.

Identification of Yr59 conferring high-temperature adult-plant resistance to stripe rust in wheat germplasm PI 178759

USDA-ARS?s Scientific Manuscript database

Stripe rust, caused by Puccinia striiformis f. sp. tritici, is one of the most widespread and destructive wheat diseases worldwide. Resistant cultivars are the preferred means of control. The spring wheat germplasm ‘PI 178759’ originating from Iraq showed effective resistance to stripe rust in fie...

Involvement of PI3K/AKT and MAPK Pathways for TNF-α Production in SiHa Cervical Mucosal Epithelial Cells Infected with Trichomonas vaginalis.

PubMed

Yang, Jung-Bo; Quan, Juan-Hua; Kim, Ye-Eun; Rhee, Yun-Ee; Kang, Byung-Hyun; Choi, In-Wook; Cha, Guang-Ho; Yuk, Jae-Min; Lee, Young-Ha

2015-08-01

Trichomonas vaginalis; induces proinflammation in cervicovaginal mucosal epithelium. To investigate the signaling pathways in TNF-α production in cervical mucosal epithelium after T. vaginalis infection, the phosphorylation of PI3K/AKT and MAPK pathways were evaluated in T. vaginalis-infected SiHa cells in the presence and absence of specific inhibitors. T. vaginalis increased TNF-α production in SiHa cells, in a parasite burden-dependent and incubation time-dependent manner. In T. vaginalis-infected SiHa cells, AKT, ERK1/2, p38 MAPK, and JNK were phosphorylated from 1 hr after infection; however, the phosphorylation patterns were different from each other. After pretreatment with inhibitors of the PI3K/AKT and MAPK pathways, TNF-α production was significantly decreased compared to the control; however, TNF-α reduction patterns were different depending on the type of PI3K/MAPK inhibitors. TNF-α production was reduced in a dose-dependent manner by treatment with wortmannin and PD98059, whereas it was increased by SP600125. These data suggested that PI3K/AKT and MAPK signaling pathways are important in regulation of TNF-α production in cervical mucosal epithelial SiHa cells. However, activation patterns of each pathway were different from the types of PI3K/MAPK pathways.

Propidium iodide (PI) stains Nissl bodies and may serve as a quick marker for total neuronal cell count.

PubMed

Niu, Junfei; Li, Chunman; Wu, Haihui; Feng, Xianling; Su, Qingning; Li, Shihe; Zhang, Lihong; Yew, David Tai Wai; Cho, Eric Yu Pang; Sha, Ou

2015-03-01

Propidium iodide (PI) reacts with both DNA and RNA and is a commonly used fluorescent reagent for nucleic acid staining. The aim of the study was to compare the cellular staining patterns of PI with that of Nissl staining in rat nervous tissues and to report a modified staining method that selectively labels Nissl bodies in neurons. Cryosections and paraffin sections of different tissues of normal Sprague-Dawley rats, including trigeminal ganglia, dorsal root ganglia, spinal cord, liver, and small intestine, were stained by either PI or the hematoxylin and eosin method. Some sections were treated with RNase or DNase before the above staining, and some were double stained with PI and a Nissl stain. The sections were observed by light, fluorescence or confocal microscopy. Results showed strong PI signals detected as patterns of granules in the neuronal cytoplasm of all nervous tissues, whereas the staining of neuronal nuclei was weaker. In contrast, nuclei of neuroglial cells were strongly stained by PI, while the cytoplasm was not obviously stained. Pretreatment of the neural tissue with RNase abolished the PI signals. Furthermore, the PI positive granules in neuronal cytoplasm co-localized with Nissl bodies stained by the fluorescent Nissl stain. When the tissue was pretreated with DNase, PI only stained the cytoplasmic granules of neurons, but not that of glial cells. Our results show that PI stains Nissl bodies and may serve as an economical and convenient neuron marker for neuronal cell counting when specific neural markers such as antibodies are not readily available. Copyright © 2015. Published by Elsevier GmbH.

Identification of the Interactome of a Palmitoylated Membrane Protein, Phosphatidylinositol 4-Kinase Type II Alpha.

PubMed

Gokhale, Avanti; Ryder, Pearl V; Zlatic, Stephanie A; Faundez, Victor

2016-01-01

Phosphatidylinositol 4-kinases (PI4K) are enzymes responsible for the production of phosphatidylinositol 4-phosphates, important intermediates in several cell signaling pathways. PI4KIIα is the most abundant membrane-associated kinase in mammalian cells and is involved in a variety of essential cellular functions. However, the precise role(s) of PI4KIIα in the cell is not yet completely deciphered. Here we present an experimental protocol that uses a chemical cross-linker, DSP, combined with immunoprecipitation and immunoaffinity purification to identify novel PI4KIIα interactors. As predicted, PI4KIIα participates in transient, low-affinity interactions that are stabilized by the use of DSP. Using this optimized protocol we have successfully identified actin cytoskeleton regulators-the WASH complex and RhoGEF1, as major novel interactors of PI4KIIα. While this chapter focuses on the PI4KIIα interactome, this protocol can and has been used to generate other membrane interactome networks.

The Story of PI

NASA Technical Reports Server (NTRS)

Apostol, Tom M. (Editor)

1989-01-01

The early history and the uses of the mathematical notation - pi - are presented through both film footage and computer animation in this 'Project Mathematics' series video. Pi comes from the first letter in the Greek word for perimeter. Archimedes, and early Greek mathematician, formulated the equations for the computation of a circle's area using pi and was the first person to seriously approximate pi numerically, although only to a few decimal places. By 1985, pi had been approximated to over one billion decimal places and was found to have no repeating pattern. One use of pi is the application of its approximation calculation as an analytical tool for determining the accuracy of supercomputers and software designs.

Use of molecular markers in identification and characterization of resistance to rice blast in India.

PubMed

Yadav, Manoj Kumar; S, Aravindan; Ngangkham, Umakanta; Shubudhi, H N; Bag, Manas Kumar; Adak, Totan; Munda, Sushmita; Samantaray, Sanghamitra; Jena, Mayabini

2017-01-01

Rice blast disease caused by Magnaporthe oryzae is one of the most destructive disease causing huge losses to rice yield in different parts of the world. Therefore, an attempt has been made to find out the resistance by screening and studying the genetic diversity of eighty released rice varieties by National Rice Research Institute, Cuttack (NRVs) using molecular markers linked to twelve major blast resistance (R) genes viz Pib, Piz, Piz-t, Pik, Pik-p, Pikm Pik-h, Pita/Pita-2, Pi2, Pi9, Pi1 and Pi5. Out of which, nineteen varieties (23.75%) showed resistance, twenty one were moderately resistant (26.25%) while remaining forty varieties (50%) showed susceptible in uniform blast nursery. Rice varieties possessing blast resistance genes varied from four to twelve and the frequencies of the resistance genes ranged from 0 to 100%. The cluster analysis grouped the eighty NRVs into two major clusters at 63% level of genetic similarity coefficient. The PIC value for seventeen markers varied from 0 to 0.37 at an average of 0.20. Out of seventeen markers, only five markers, 195R-1, Pi9-i, Pita3, YL155/YL87 and 40N23r corresponded to three broad spectrum R genes viz. Pi9, Pita/Pita2 and Pi5 were found to be significantly associated with the blast disease with explaining phenotypic variance from 3.5% to 7.7%. The population structure analysis and PCoA divided the entire 80 NRVs into two sub-groups. The outcome of this study would help to formulate strategies for improving rice blast resistance through genetic studies, plant-pathogen interaction, identification of novel R genes, development of new resistant varieties through marker-assisted breeding for improving rice blast resistance in India and worldwide.

Pittsburgh Compound B and AV-1451 positron emission tomography assessment of molecular pathologies of Alzheimer's disease in progressive supranuclear palsy.

PubMed

Whitwell, Jennifer L; Ahlskog, J Eric; Tosakulwong, Nirubol; Senjem, Matthew L; Spychalla, Anthony J; Petersen, Ronald C; Jack, Clifford R; Lowe, Val J; Josephs, Keith A

2018-03-01

Little is known about Alzheimer's disease molecular proteins, beta-amyloid and paired helical filament (PHF) tau, in progressive supranuclear palsy (PSP). Recent techniques have been developed to allow for investigations of these proteins in PSP. We determined the frequency of beta-amyloid deposition in PSP, and whether beta-amyloid deposition in PSP is associated with PHF-tau deposition pattern, or clinical features. Thirty probable PSP participants underwent MRI, [ 18 F]AV-1451 PET and Pittsburgh compound B (PiB) PET. Apolipoprotein (APOE) genotyping was also performed. A global PiB standard-uptake value ratio (SUVR) was calculated. AV-1451 SUVRs were calculated for a set of Alzheimer's disease (AD)-related regions and a set of PSP-related regions. Voxel-level analyses were conducted to assess for differences in AV-1451 uptake patterns and MRI atrophy between PiB(+) and PiB(-) cases compared to 60 normal PiB(-) controls. Statistical testing for correlations and associations between variables of interest were also performed. Twelve subjects (40%) showed beta-amyloid deposition. Higher PiB SUVR correlated with older age but not with AV-1451 SUVR in the AD- or PSP-related regions. Higher AV-1451 SUVR in AD-related regions was associated with higher AV-1451 SUVR in PSP-related regions. We found little evidence for beta-amyloid related differences in clinical metrics, proportion of APOE e4 carriers, pattern of AV-1451 uptake, or pattern of atrophy. Beta-amyloid deposition occurs in a relatively high proportion of PSP subjects. Unlike in Alzheimer's disease, however, there is little evidence that beta-amyloid, and PHF-tau, play a significant role in neurodegeneration in PSP. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification of QTLs for resistance to fire blight (Erwinia amylovora) in Malus sieversii

USDA-ARS?s Scientific Manuscript database

Malus sieversii (Ms) is the progenitor of the domestic apple. Ms PI613981 is elite scion material collected at a xerophytic site in Kazakhstan from a tree free of disease and insect damage. The F1 family GMAL4593 (‘Royal Gala’ X PI631981) is segregating for resistance to both apple scab and fire bl...

Model Predictive Control Based on System Re-Identification (MPC-SRI) to Control Bio-H2 Production from Biomass

NASA Astrophysics Data System (ADS)

Wahid, A.; Taqwallah, H. M. H.

2018-03-01

Compressors and a steam reformer are the important units in biohydrogen from biomass plant. The compressors are useful for achieving high-pressure operating conditions while the steam reformer is the main process to produce H2 gas. To control them, in this research used a model predictive control (MPC) expected to have better controller performance than conventional controllers. Because of the explicit model empowerment in MPC, obtaining a better model is the main objective before employing MPC. The common way to get the empirical model is through the identification system, so that obtained a first-order plus dead-time (FOPDT) model. This study has already improved that way since used the system re-identification (SRI) based on closed loop mode. Based on this method the results of the compressor pressure control and temperature control of steam reformer were that MPC based on system re-identification (MPC-SRI) has better performance than MPC without system re-identification (MPCWSRI) and the proportional-integral (PI) controller, by % improvement of 73% against MPCWSRI and 75% against the PI controller.

Identification of novel alleles of the rice blast resistance gene Pi54

NASA Astrophysics Data System (ADS)

Vasudevan, Kumar; Gruissem, Wilhelm; Bhullar, Navreet K.

2015-10-01

Rice blast is one of the most devastating rice diseases and continuous resistance breeding is required to control the disease. The rice blast resistance gene Pi54 initially identified in an Indian cultivar confers broad-spectrum resistance in India. We explored the allelic diversity of the Pi54 gene among 885 Indian rice genotypes that were found resistant in our screening against field mixture of naturally existing M. oryzae strains as well as against five unique strains. These genotypes are also annotated as rice blast resistant in the International Rice Genebank database. Sequence-based allele mining was used to amplify and clone the Pi54 allelic variants. Nine new alleles of Pi54 were identified based on the nucleotide sequence comparison to the Pi54 reference sequence as well as to already known Pi54 alleles. DNA sequence analysis of the newly identified Pi54 alleles revealed several single polymorphic sites, three double deletions and an eight base pair deletion. A SNP-rich region was found between a tyrosine kinase phosphorylation site and the nucleotide binding site (NBS) domain. Together, the newly identified Pi54 alleles expand the allelic series and are candidates for rice blast resistance breeding programs.

Kidney and Phosphate Metabolism

PubMed Central

2008-01-01

The serum phosphorus level is maintained through a complex interplay between intestinal absorption, exchange intracellular and bone storage pools, and renal tubular reabsorption. The kidney plays a major role in regulation of phosphorus homeostasis by renal tubular reabsorption. Type IIa and type IIc Na+/Pi transporters are important renal Na+-dependent inorganic phosphate (Pi) transporters, which are expressed in the brush border membrane of proximal tubular cells. Both are regulated by dietary Pi intake, vitamin D, fibroblast growth factor 23 (FGF23) and parathyroid hormone. The expression of type IIa Na+/Pi transporter result from hypophosphatemia quickly. However, type IIc appears to act more slowly. Physiological and pathophysiological alteration in renal Pi reabsorption are related to altered brush border membrane expression/content of the type II Na+/Pi cotransporter. Many studies of genetic and acquired renal phosphate wasting disorders have led to the identification of novel genes. Two novel Pi regulating genes, PHEX and FGF23, play a role in the pathophysiology of genetic and acquired renal phosphate wasting disorders and studies are underway to define their mechanism on renal Pi regulation. In recent studies, sodium-hydrogen exchanger regulatory factor 1 (NHERF1) is reported as another new regulator for Pi reabsorption mechanism. PMID:24459526

Phosphate-Dependent Root System Architecture Responses to Salt Stress1[OPEN

PubMed Central

Sommerfeld, Hector Montero; ter Horst, Anneliek; Haring, Michel A.

2016-01-01

Nutrient availability and salinity of the soil affect the growth and development of plant roots. Here, we describe how inorganic phosphate (Pi) availability affects the root system architecture (RSA) of Arabidopsis (Arabidopsis thaliana) and how Pi levels modulate responses of the root to salt stress. Pi starvation reduced main root length and increased the number of lateral roots of Arabidopsis Columbia-0 seedlings. In combination with salt, low Pi dampened the inhibiting effect of mild salt stress (75 mm) on all measured RSA components. At higher salt concentrations, the Pi deprivation response prevailed over the salt stress only for lateral root elongation. The Pi deprivation response of lateral roots appeared to be oppositely affected by abscisic acid signaling compared with the salt stress response. Natural variation in the response to the combination treatment of salt and Pi starvation within 330 Arabidopsis accessions could be grouped into four response patterns. When exposed to double stress, in general, lateral roots prioritized responses to salt, while the effect on main root traits was additive. Interestingly, these patterns were not identical for all accessions studied, and multiple strategies to integrate the signals from Pi deprivation and salinity were identified. By genome-wide association mapping, 12 genomic loci were identified as putative factors integrating responses to salt stress and Pi starvation. From our experiments, we conclude that Pi starvation interferes with salt responses mainly at the level of lateral roots and that large natural variation exists in the available genetic repertoire of accessions to handle the combination of stresses. PMID:27208277

Characteristics of PI-RADS 4 lesions within the prostatic peripheral zone: a retrospective diagnostic accuracy study evaluating 170 lesions.

PubMed

Shankar, Prasad R; Curci, Nicole E; Davenport, Matthew S

2017-12-02

To determine whether peripheral zone PI-RADS 4 observations can be further risk-stratified. This was an IRB-approved HIPAA-compliant retrospective diagnostic accuracy study. Peripheral zone PI-RADS 4 observations prospectively identified at the study institution from 8/1/2015 to 12/31/2016 (n = 170 in 149 mpMRIs) were reviewed independently by two blinded genitourinary radiologists on the basis of (a) PI-RADS v2 shape, (b) pattern of peripheral zone sparing, and (c) rationale for PI-RADS 4 designation. Reference standard was targeted MR-ultrasound fusion biopsy and detection of Gleason 7+ prostate cancer. Positive predictive values (PPVs) were calculated. Predictors were assessed with binary logistic regression. PI-RADS 4 lesions with a DWI score of 4 were more likely to represent Gleason 7+ prostate cancer (p = 0.008-0.01; Reader 1 PPV: 53%; Reader 2 PPV: 48%). Pattern of peripheral zone sparing and most lesion shapes were not predictive (p > 0.05); however, oval lesions were predictive for Reader 1 (PPV = 59%, p = 0.03) and lentiform lesions were predictive for Reader 2 (PPV = 74%, p = 0.01). Lesions scored as "not meeting PI-RADS 4 criteria" had significantly lower PPV (p = 0.016-0.003; Reader 1 PPV: 14%, Reader 2 PPV: 16%). Peripheral zone PI-RADS 4 lesions with a DWI score of 4 are more likely Gleason 7+ cancer than those with a DWI score of 3. Lesions overcalled as PI-RADS 4 have PPV similar to published PI-RADS 3 data. Lesion shape and peripheral zone sparing in general do not predict Gleason 7+ cancer within PI-RADS 4 observations.

The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer .

PubMed

Folkes, Adrian J; Ahmadi, Khatereh; Alderton, Wendy K; Alix, Sonia; Baker, Stewart J; Box, Gary; Chuckowree, Irina S; Clarke, Paul A; Depledge, Paul; Eccles, Suzanne A; Friedman, Lori S; Hayes, Angela; Hancox, Timothy C; Kugendradas, Arumugam; Lensun, Letitia; Moore, Pauline; Olivero, Alan G; Pang, Jodie; Patel, Sonal; Pergl-Wilson, Giles H; Raynaud, Florence I; Robson, Anthony; Saghir, Nahid; Salphati, Laurent; Sohal, Sukhjit; Ultsch, Mark H; Valenti, Melanie; Wallweber, Heidi J A; Wan, Nan Chi; Wiesmann, Christian; Workman, Paul; Zhyvoloup, Alexander; Zvelebil, Marketa J; Shuttleworth, Stephen J

2008-09-25

Phosphatidylinositol-3-kinase (PI3K) is an important target in cancer due to the deregulation of the PI3K/ Akt signaling pathway in a wide variety of tumors. A series of thieno[3,2-d]pyrimidine derivatives were prepared and evaluated as inhibitors of PI3 kinase p110alpha. The synthesis, biological activity, and further profiling of these compounds are described. This work resulted in the discovery of 17, GDC-0941, which is a potent, selective, orally bioavailable inhibitor of PI3K and is currently being evaluated in human clinical trials for the treatment of cancer.

Reversal of hypermethylation and reactivation of glutathione S-transferase pi 1 gene by curcumin in breast cancer cell line.

PubMed

Kumar, Umesh; Sharma, Ujjawal; Rathi, Garima

2017-02-01

One of the mechanisms for epigenetic silencing of tumor suppressor genes is hypermethylation of cytosine residue at CpG islands at their promoter region that contributes to malignant progression of tumor. Therefore, activation of tumor suppressor genes that have been silenced by promoter methylation is considered to be very attractive molecular target for cancer therapy. Epigenetic silencing of glutathione S-transferase pi 1, a tumor suppressor gene, is involved in various types of cancers including breast cancer. Epigenetic silencing of tumor suppressor genes can be reversed by several molecules including natural compounds such as polyphenols that can act as a hypomethylating agent. Curcumin has been found to specifically target various tumor suppressor genes and alter their expression. To check the effect of curcumin on the methylation pattern of glutathione S-transferase pi 1 gene in MCF-7 breast cancer cell line in dose-dependent manner. To check the reversal of methylation pattern of hypermethylated glutathione S-transferase pi 1, MCF-7 breast cancer cell line was treated with different concentrations of curcumin for different time periods. DNA and proteins of treated and untreated cell lines were isolated, and methylation status of the promoter region of glutathione S-transferase pi 1 was analyzed using methylation-specific polymerase chain reaction assay, and expression of this gene was analyzed by immunoblotting using specific antibodies against glutathione S-transferase pi 1. A very low and a nontoxic concentration (10 µM) of curcumin treatment was able to reverse the hypermethylation and led to reactivation of glutathione S-transferase pi 1 protein expression in MCF-7 cells after 72 h of treatment, although the IC 50 value of curcumin was found to be at 20 µM. However, curcumin less than 3 µM of curcumin could not alter the promoter methylation pattern of glutathione S-transferase pi 1. Treatment of breast cancer MCF-7 cells with curcumin causes complete reversal of glutathione S-transferase pi 1 promoter hypermethylation and leads to re-expression of glutathione S-transferase pi 1, suggesting it to be an excellent nontoxic hypomethylating agent.

Pittsburgh compound B (PiB) PET imaging of meningioma and other intracranial tumors.

PubMed

Johnson, Derek R; Hunt, Christopher H; Nathan, Mark A; Parisi, Joseph E; Boeve, Bradley F; Murray, Melissa E; Knopman, David S; Jack, Clifford R; Petersen, Ronald C; Lowe, Val J; Johnson, Geoffrey B

2018-01-01

Meningiomas are the most common intracranial tumors. Diagnosis by MRI is generally straightforward, but lack of imaging specificity can present a diagnostic dilemma, particularly in patients with cancer. We report our experience with meningioma identification on Pittsburgh compound B (PiB) PET/CT. Patients who underwent PiB PET/CT from 2006 to 2015 were reviewed to identify those with intracranial tumors. Tumor types were classified by MR appearance, or by pathology when available. Maximum standardized uptake value (SUVmax) measurements of tumor PiB activity were compared across tumor types. 2472 patients underwent PiB PET/CT in the period of interest; 45 patients (1.8%) had probable or definite intracranial tumor. Tumor types were meningioma (29/45, 64%), vestibular schwannoma (7/45, 16%), pituitary macroadenoma (4/45, 9%), metastatic disease (2/45, 4%), and others (3/45, 7%). In patients with meningioma, the mean lesion SUVmax was 2.05 (SD 1.37), versus 1.00 (SD 0.42) in patients with non-meningioma tumors (p < 0.01). A receiver operating curve was created for lesion:cerebellum SUVmax ratio, with an area under the curve of 0.91 for a value of 1.68. At or above this ratio, specificity for meningioma was 100% (95% CI 79-100%) and sensitivity was 76% (95% CI 57-90%). PiB PET activity within an intracranial tumor is a highly specific and reasonably sensitive marker of meningioma. Further prospective evaluation is warranted to validate this result as well as to assess the performance of commercially available beta-amyloid radiotracers in meningioma identification.

The effect of talker and intonation variability on speech perception in noise in children with dyslexia

PubMed Central

Hazan, Valerie; Messaoud-Galusi, Souhila; Rosen, Stuart

2013-01-01

Purpose To determine whether children with dyslexia (DYS) are more affected than age-matched average readers (AR) by talker and intonation variability when perceiving speech in noise. Method Thirty-four DYS and 25 AR children were tested on their perception of consonants in naturally-produced consonant-vowel (CV) tokens in multi-talker babble. Twelve CVs were presented for identification in four conditions varying in the degree of talker and intonation variability. Consonant place (/bi/-/di/) and voicing (/bi/-/pi/) discrimination was investigated with the same conditions. Results DYS children made slightly more identification errors than AR children but only for conditions with variable intonation. Errors were more frequent for a subset of consonants, generally weakly-encoded for AR children, for tokens with intonation patterns (steady and rise-fall) that occur infrequently in connected discourse. In discrimination tasks, which have a greater memory and cognitive load, DYS children scored lower than AR children across all conditions. Conclusions Unusual intonation patterns had a disproportionate (but small) effect on consonant intelligibility in noise for DYS children but adding talker variability did not. DYS children do not appear to have a general problem in perceiving speech in degraded conditions, which makes it unlikely that they lack robust phonological representations. PMID:22761322

The effect of talker and intonation variability on speech perception in noise in children with dyslexia.

PubMed

Hazan, Valerie; Messaoud-Galusi, Souhila; Rosen, Stuart

2013-02-01

In this study, the authors aimed to determine whether children with dyslexia (hereafter referred to as "DYS children") are more affected than children with average reading ability (hereafter referred to as "AR children") by talker and intonation variability when perceiving speech in noise. Thirty-four DYS and 25 AR children were tested on their perception of consonants in naturally produced CV tokens in multitalker babble. Twelve CVs were presented for identification in four conditions varying in the degree of talker and intonation variability. Consonant place (/bi/-/di/) and voicing (/bi/-/pi/) discrimination were investigated with the same conditions. DYS children made slightly more identification errors than AR children but only for conditions with variable intonation. Errors were more frequent for a subset of consonants, generally weakly encoded for AR children, for tokens with intonation patterns (steady and rise-fall) that occur infrequently in connected discourse. In discrimination tasks, which have a greater memory and cognitive load, DYS children scored lower than AR children across all conditions. Unusual intonation patterns had a disproportionate (but small) effect on consonant intelligibility in noise for DYS children, but adding talker variability did not. DYS children do not appear to have a general problem in perceiving speech in degraded conditions, which makes it unlikely that they lack robust phonological representations.

Detection of piRNAs in whitespotted bamboo shark liver.

PubMed

Yang, Lingrong; Ge, Yinghua; Cheng, Dandan; Nie, Zuoming; Lv, Zhengbing

2016-09-15

Piwi-interacting RNAs (piRNAs) are 26 to 31-nt small non-coding RNAs that have been reported mostly in germ-line cells and cancer cells. However, the presence of piRNAs in the whitespotted bamboo shark liver has not yet been reported. In a previous study of microRNAs in shark liver, some piRNAs were detected from small RNAs sequenced by Solexa technology. A total of 4857 piRNAs were predicted and found in shark liver. We further selected 17 piRNAs with high and significantly differential expression between normal and regenerative liver tissues for subsequent verification by Northern blotting. Ten piRNAs were further identified, and six of these were matched to known piRNAs in piRNABank. The actual expression of six known and four novel piRNAs was validated by qRT-PCR. In addition, a total of 401 target genes of the 10 piRNAs were predicted by miRanda. Through GO and pathway function analyses, only five piRNAs could be annotated with eighteen GO annotations. The results indicated that the identified piRNAs are involved in many important biological responses, including immune inflammation, cell-specific differentiation and development, and angiogenesis. This manuscript provides the first identification of piRNAs in the liver of whitespotted bamboo shark using Solexa technology as well as further elucidation of the regulatory role of piRNAs in whitespotted bamboo shark liver. These findings may provide a useful resource and may facilitate the development of therapeutic strategies against liver damage. Copyright © 2016 Elsevier B.V. All rights reserved.

Integrated β-catenin, BMP, PTEN, and Notch signalling patterns the nephron.

PubMed

Lindström, Nils O; Lawrence, Melanie L; Burn, Sally F; Johansson, Jeanette A; Bakker, Elvira R M; Ridgway, Rachel A; Chang, C-Hong; Karolak, Michele J; Oxburgh, Leif; Headon, Denis J; Sansom, Owen J; Smits, Ron; Davies, Jamie A; Hohenstein, Peter

2015-02-03

The different segments of the nephron and glomerulus in the kidney balance the processes of water homeostasis, solute recovery, blood filtration, and metabolite excretion. When segment function is disrupted, a range of pathological features are presented. Little is known about nephron patterning during embryogenesis. In this study, we demonstrate that the early nephron is patterned by a gradient in β-catenin activity along the axis of the nephron tubule. By modifying β-catenin activity, we force cells within nephrons to differentiate according to the imposed β-catenin activity level, thereby causing spatial shifts in nephron segments. The β-catenin signalling gradient interacts with the BMP pathway which, through PTEN/PI3K/AKT signalling, antagonises β-catenin activity and promotes segment identities associated with low β-catenin activity. β-catenin activity and PI3K signalling also integrate with Notch signalling to control segmentation: modulating β-catenin activity or PI3K rescues segment identities normally lost by inhibition of Notch. Our data therefore identifies a molecular network for nephron patterning.

The Guareschi Pyridine Scaffold as a Valuable Platform for the Identification of Selective PI3K Inhibitors.

PubMed

Galli, Ubaldina; Ciraolo, Elisa; Massarotti, Alberto; Margaria, Jean Piero; Sorba, Giovanni; Hirsch, Emilio; Tron, Gian Cesare

2015-09-18

A novel series of 4-aryl-3-cyano-2-(3-hydroxyphenyl)-6-morpholino-pyridines have been designed as potential phosphatidylinositol-3-kinase (PI3K) inhibitors. The compounds have been synthesized using the Guareschi reaction to prepare the key 4-aryl-3-cyano-2,6-dihydroxypyridine intermediate. A different selectivity according to the nature of the aryl group has been observed. Compound 9b is a selective inhibitor against the PI3Kα isoform, maintaining a good inhibitory activity. Docking studies were also performed in order to rationalize its profile of selectivity.

Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis.

PubMed

Camps, Montserrat; Rückle, Thomas; Ji, Hong; Ardissone, Vittoria; Rintelen, Felix; Shaw, Jeffrey; Ferrandi, Chiara; Chabert, Christian; Gillieron, Corine; Françon, Bernard; Martin, Thierry; Gretener, Denise; Perrin, Dominique; Leroy, Didier; Vitte, Pierre-Alain; Hirsch, Emilio; Wymann, Matthias P; Cirillo, Rocco; Schwarz, Matthias K; Rommel, Christian

2005-09-01

Phosphoinositide 3-kinases (PI3K) have long been considered promising drug targets for the treatment of inflammatory and autoimmune disorders as well as cancer and cardiovascular diseases. But the lack of specificity, isoform selectivity and poor biopharmaceutical profile of PI3K inhibitors have so far hampered rigorous disease-relevant target validation. Here we describe the identification and development of specific, selective and orally active small-molecule inhibitors of PI3Kgamma (encoded by Pik3cg). We show that Pik3cg(-/-) mice are largely protected in mouse models of rheumatoid arthritis; this protection correlates with defective neutrophil migration, further validating PI3Kgamma as a therapeutic target. We also describe that oral treatment with a PI3Kgamma inhibitor suppresses the progression of joint inflammation and damage in two distinct mouse models of rheumatoid arthritis, reproducing the protective effects shown by Pik3cg(-/-) mice. Our results identify selective PI3Kgamma inhibitors as potential therapeutic molecules for the treatment of chronic inflammatory disorders such as rheumatoid arthritis.

Generation of tricyclic imidazo[1,2-a]pyrazines as novel PI3K inhibitors by application of a conformational restriction strategy.

PubMed

Martínez González, Sonia; Rodríguez-Arístegui, Sonsoles; Hernández, Ana Isabel; Varela, Carmen; González Cantalapiedra, Esther; Álvarez, Rosa María; Rodríguez Hergueta, Antonio; Bischoff, James R; Albarrán, María Isabel; Cebriá, Antonio; Cendón, Elena; Cebrián, David; Alfonso, Patricia; Pastor, Joaquín

2017-06-01

The involvement of the phosphoinositide 3-kinases (PI3Ks) in several diseases, especially in the oncology area, has singled it as one of the most explored therapeutic targets in the last two decades. Many different inhibitor classes have been developed by the industry and academia with a diverse selectivity profile within the PI3K family. In the present manuscript we report a further exploration of our lead PI3K inhibitor ETP-46321 (Martínez González et al., 2012) 1 by the application of a conformational restriction strategy. For that purpose we have successfully synthesized novel tricyclic imidazo[1,2-a]pyrazine derivatives as PI3K inhibitors. This new class of compounds had enable the exploration of the solvent-accessible region within PI3K and resulted in the identification of molecule 8q with the best selectivity PI3Kα/δ isoform profile in vitro, and promising in vivo PK data. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer.

PubMed

Burger, Matthew T; Pecchi, Sabina; Wagman, Allan; Ni, Zhi-Jie; Knapp, Mark; Hendrickson, Thomas; Atallah, Gordana; Pfister, Keith; Zhang, Yanchen; Bartulis, Sarah; Frazier, Kelly; Ng, Simon; Smith, Aaron; Verhagen, Joelle; Haznedar, Joshua; Huh, Kay; Iwanowicz, Ed; Xin, Xiaohua; Menezes, Daniel; Merritt, Hanne; Lee, Isabelle; Wiesmann, Marion; Kaufman, Susan; Crawford, Kenneth; Chin, Michael; Bussiere, Dirksen; Shoemaker, Kevin; Zaror, Isabel; Maira, Sauveur-Michel; Voliva, Charles F

2011-10-13

Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the treatment of cancer.

Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer

PubMed Central

2011-01-01

Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the treatment of cancer. PMID:24900266

Decoupling PI Controller Design for a Normal Conducting RF Cavity Using a Recursive LEVENBERG-MARQUARDT Algorithm

NASA Astrophysics Data System (ADS)

Kwon, Sung-il; Lynch, M.; Prokop, M.

2005-02-01

This paper addresses the system identification and the decoupling PI controller design for a normal conducting RF cavity. Based on the open-loop measurement data of an SNS DTL cavity, the open-loop system's bandwidths and loop time delays are estimated by using batched least square. With the identified system, a PI controller is designed in such a way that it suppresses the time varying klystron droop and decouples the In-phase and Quadrature of the cavity field. The Levenberg-Marquardt algorithm is applied for nonlinear least squares to obtain the optimal PI controller parameters. The tuned PI controller gains are downloaded to the low-level RF system by using channel access. The experiment of the closed-loop system is performed and the performance is investigated. The proposed tuning method is running automatically in real time interface between a host computer with controller hardware through ActiveX Channel Access.

Prevalence, mutation patterns, and effects on protease inhibitor susceptibility of the L76V mutation in HIV-1 protease.

PubMed

Young, Thomas P; Parkin, Neil T; Stawiski, Eric; Pilot-Matias, Tami; Trinh, Roger; Kempf, Dale J; Norton, Michael

2010-11-01

Patterns of HIV-1 protease inhibitor (PI) resistance-associated mutations (RAMs) and effects on PI susceptibility associated with the L76V mutation were studied in a large database. Of 20,501 sequences with ≥1 PI RAM, 3.2% contained L76V; L76V was alone in 0.04%. Common partner mutations included M46I, I54V, V82A, I84V, and L90M. L76V was associated with a 2- to 6-fold decrease in susceptibility to lopinavir, darunavir, amprenavir, and indinavir and a 7- to 8-fold increase in susceptibility to atazanavir and saquinavir.

Prevalence, Mutation Patterns, and Effects on Protease Inhibitor Susceptibility of the L76V Mutation in HIV-1 Protease▿ †

PubMed Central

Young, Thomas P.; Parkin, Neil T.; Stawiski, Eric; Pilot-Matias, Tami; Trinh, Roger; Kempf, Dale J.; Norton, Michael

2010-01-01

Patterns of HIV-1 protease inhibitor (PI) resistance-associated mutations (RAMs) and effects on PI susceptibility associated with the L76V mutation were studied in a large database. Of 20,501 sequences with ≥1 PI RAM, 3.2% contained L76V; L76V was alone in 0.04%. Common partner mutations included M46I, I54V, V82A, I84V, and L90M. L76V was associated with a 2- to 6-fold decrease in susceptibility to lopinavir, darunavir, amprenavir, and indinavir and a 7- to 8-fold increase in susceptibility to atazanavir and saquinavir. PMID:20805393

Steroid receptors analysis in human mammary tumors by isoelectric focusing in agarose.

PubMed

Bailleul, S; Gauduchon, P; Malas, J P; Lechevrel, C; Roussel, G; Goussard, J

1988-08-01

A high resolution and quantitative method for isoelectric focusing has been developed to separate the isoforms of estrogen and progesterone receptors in human mammary tumor cytosols stabilized by sodium molybdate. Agarose gels (0.5%) were used. Six samples can be analyzed on one gel in about 2 h, and 35-microliters samples are sufficient to determine the estrogen receptor isoform pattern. The constant yields and the reproducibility of data allow a quantitative analysis of these receptors. Four estrogen receptor isoforms have been observed (pI 4.7, 5.5, 6, and 6.5), isoforms with pI 4.7 and 6.5 being present in all tumors. After incubation at 28 degrees C in high ionic strength, the comparison of isoelectric focusing and high-performance size exclusion chromatography patterns of estrogen receptor confirms the oligomeric structure of the pI 4.7 isoform and suggests a monomeric structure for the pI 6.5 isoform. Under the same conditions of analysis, only one progesterone receptor isoform has been detected with pI 4.7.

Systematic screening identifies dual PI3K and mTOR inhibition as a conserved therapeutic vulnerability in osteosarcoma

PubMed Central

Gupte, Ankita; Baker, Emma K.; Wan, Soo-San; Stewart, Elizabeth; Loh, Amos; Shelat, Anang A.; Gould, Cathryn M.; Chalk, Alistair M.; Taylor, Scott; Lackovic, Kurt; Karlström, Åsa; Mutsaers, Anthony J.; Desai, Jayesh; Madhamshettiwar, Piyush B.; Zannettino, Andrew CW.; Burns, Chris; Huang, David CS.; Dyer, Michael A.; Simpson, Kaylene J.; Walkley, Carl R.

2015-01-01

Purpose Osteosarcoma (OS) is the most common cancer of bone occurring mostly in teenagers. Despite rapid advances in our knowledge of the genetics and cell biology of OS, significant improvements in patient survival have not been observed. The identification of effective therapeutics has been largely empirically based. The identification of new therapies and therapeutic targets are urgently needed to enable improved outcomes for OS patients. Experimental Design We have used genetically engineered murine models of human OS in a systematic, genome wide screen to identify new candidate therapeutic targets. We performed a genome wide siRNA screen, with or without doxorubicin. In parallel a screen of therapeutically relevant small molecules was conducted on primary murine and primary human OS derived cell cultures. All results were validated across independent cell cultures and across human and mouse OS. Results The results from the genetic and chemical screens significantly overlapped, with a profound enrichment of pathways regulated by PI3K and mTOR pathways. Drugs that concurrently target both PI3K and mTOR were effective at inducing apoptosis in primary OS cell cultures in vitro in both human and mouse OS, while specific PI3K or mTOR inhibitors were not effective. The results were confirmed with siRNA and small molecule approaches. Rationale combinations of specific PI3K and mTOR inhibitors could recapitulate the effect on OS cell cultures. Conclusions The approaches described here have identified dual inhibition of the PI3K/mTOR pathway as a sensitive, druggable target in OS and provide rationale for translational studies with these agents. PMID:25862761

External validity of the pediatric cardiac quality of life inventory

PubMed Central

Marino, Bradley S.; Drotar, Dennis; Cassedy, Amy; Davis, Richard; Tomlinson, Ryan S.; Mellion, Katelyn; Mussatto, Kathleen; Mahony, Lynn; Newburger, Jane W.; Tong, Elizabeth; Cohen, Mitchell I.; Helfaer, Mark A.; Kazak, Anne E.; Wray, Jo; Wernovsky, Gil; Shea, Judy A.; Ittenbach, Richard

2012-01-01

Purpose The Pediatric Cardiac Quality of Life Inventory (PCQLI) is a disease-specific, health-related quality of life (HRQOL) measure for pediatric heart disease (HD). The purpose of this study was to demonstrate the external validity of PCQLI scores. Methods The PCQLI development site (Development sample) and six geographically diverse centers in the United States (Composite sample) recruited pediatric patients with acquired or congenital HD. Item response option variability, scores [Total (TS); Disease Impact (DI) and Psychosocial Impact (PI) subscales], patterns of correlation, and internal consistency were compared between samples. Results A total of 3,128 patients and parent participants (1,113 Development; 2,015 Composite) were analyzed. Response option variability patterns of all items in both samples were acceptable. Inter-sample score comparisons revealed no differences. Median item–total (Development, 0.57; Composite, 0.59) and item–subscale (Development, DI 0.58, PI 0.59; Composite, DI 0.58, PI 0.56) correlations were moderate. Subscale–subscale (0.79 for both samples) and subscale–total (Development, DI 0.95, PI 0.95; Composite, DI 0.95, PI 0.94) correlations and internal consistency (Development, TS 0.93, DI 0.90, PI 0.84; Composite, TS 0.93, DI 0.89, PI 0.85) were high in both samples. Conclusion PCQLI scores are externally valid across the US pediatric HD population and may be used for multi-center HRQOL studies. PMID:21188538

Identification of amino acid residues of mammalian mitochondrial phosphate carrier important for its functional expression in yeast cells, as achieved by PCR-mediated random mutation and gap-repair cloning.

PubMed

Yamagoshi, Ryohei; Yamamoto, Takenori; Hashimoto, Mitsuru; Sugahara, Ryohei; Shiotsuki, Takahiro; Miyoshi, Hideto; Terada, Hiroshi; Shinohara, Yasuo

2017-01-01

The mitochondrial phosphate carrier (PiC) of mammals, but not the yeast one, is synthesized with a presequence. The deletion of this presequence of the mammalian PiC was reported to facilitate the import of the carrier into yeast mitochondria, but the question as to whether or not mammalian PiC could be functionally expressed in yeast mitochondria was not addressed. In the present study, we first examined whether the defective growth on a glycerol plate of yeast cells lacking the yeast PiC gene could be reversed by the introduction of expression vectors of rat PiCs. The introduction of expression vectors encoding full-length rat PiC (rPiC) or rPiC lacking the presequence (ΔNrPiC) was ineffective in restoring growth on the glycerol plates. When we examined the expression levels of individual rPiCs in yeast mitochondria, ΔNrPiC was expressed at a level similar to that of yeast PiC, but that of rPiC was very low. These results indicated that ΔNrPiC expressed in yeast mitochondria is inert. Next, we sought to isolate "revertants" viable on the glycerol plate by expressing randomly mutated ΔNrPiC, and obtained two clones. These clones carried either of two mutations, F267S or F282S; and these mutations restored the transport function of ΔNrPiC in yeast mitochondria. These two Phe residues were conserved in human carrier (hPiC), and the transport function of ΔNhPiC expressed in yeast mitochondria was also markedly improved by their substitutions. Thus, substitution of F267S or F282S was concluded to be important for functional expression of mammalian PiCs in yeast mitochondria. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Lead optimization of N-3-substituted 7-morpholinotriazolopyrimidines as dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors: discovery of PKI-402.

PubMed

Dehnhardt, Christoph M; Venkatesan, Aranapakam M; Delos Santos, Efren; Chen, Zecheng; Santos, Osvaldo; Ayral-Kaloustian, Semiramis; Brooijmans, Natasja; Mallon, Robert; Hollander, Irwin; Feldberg, Larry; Lucas, Judy; Chaudhary, Inder; Yu, Ker; Gibbons, Jay; Abraham, Robert; Mansour, Tarek S

2010-01-28

Herein we describe the identification and lead optimization of triazolopyrimidines as a novel class of potent dual PI3K/mTOR inhibitors, resulting in the discovery of 3 (PKI-402). Compound 3 exhibits good physical properties and PK parameters, low nanomolar potency against PI3Kalpha and mTOR, and excellent inhibition of cell proliferation in several human cancer cell lines. Furthermore, in vitro and in vivo biomarker studies demonstrated the ability of 3 to shut down the PI3K/Akt pathway and induce apoptosis in cancer cells. In addition, 3 showed excellent in vivo efficacy in various human cancer xenografts, validating suppression of PI3K/mTOR signaling as a potential anticancer therapy.

Wheat miRNA TaemiR408 Acts as an Essential Mediator in Plant Tolerance to Pi Deprivation and Salt Stress via Modulating Stress-Associated Physiological Processes.

PubMed

Bai, Qianqian; Wang, Xiaoying; Chen, Xi; Shi, Guiqing; Liu, Zhipeng; Guo, Chengjin; Xiao, Kai

2018-01-01

MicroRNAs (miRNA) families act as critical regulators for plant growth, development, and responses to abiotic stresses. In this study, we characterized TaemiR408, a miRNA family member of wheat ( Triticum aestivum ), for the role in mediating plant responses to Pi starvation and salt stress. TaemiR408 targets six genes that encode proteins involving biochemical metabolism, microtubule organization, and signaling transduction. 5'- and 3'-RACE analyses confirmed the mRNA cleavage of target genes mediated by this wheat miRNA. TaemiR408 showed induced expression patterns upon Pi starvation and salt stress and whose upregulated expression was gradually repressed by the normal recovery treatments. The target genes of TaemiR408 exhibited reverse expression patterns to this miRNA, whose transcripts were downregulated under Pi starvation and salt stress and the reduced expression was recovered by the followed normal condition. These results suggest the regulation of the target genes under TaemiR408 through a cleavage mechanism. Tobacco lines with TaemiR408 overexpression exhibited enhanced stress tolerance, showing improved phenotype, biomass, and photosynthesis behavior compared with wild type under both Pi starvation and salt treatments, which closely associate increased P accumulation upon Pi deprivation and elevated osmolytes under salt stress, respectively. Phosphate transporter (PT) gene NtPT2 displays upregulated transcripts in the Pi-deprived TaemiR408 overexpressors; knockdown of this PT gene reduces Pi acquisition under low-Pi stress, confirming its role in improving plant Pi taken up. Likewise, NtPYL2 and NtSAPK3 , genes encoding abscisic acid (ABA) receptor and SnRK2 protein, respectively, exhibited upregulated transcripts in salt-challenged TaemiR408 overexpressors; knockdown of them caused deteriorated growth and lowered osmolytes amounts of plants upon salt treatment. Thus, TaemiR408 is crucial for plant adaptations to Pi starvation and salt stress through regulating Pi acquisition under low-Pi stress and remodel ABA signaling pathway and osmoprotects biosynthesis under salt stress.

Regulation of DM-20 mRNA expression and intracellular translocation of glutathione-S-transferase pi isoform during oligodendrocyte differentiation in the adult rat spinal cord.

PubMed

Kitada, Masaaki; Takeda, Kazuya; Dezawa, Mari

2016-07-01

We previously demonstrated that NG2-positive oligodendrocyte precursor cells (OPCs) do not express DM-20 mRNA and identified a distinct DM-20 mRNA-positive cell population expressing glutathione-S-transferase pi isoform (GST-pi) in the nucleus (GST-pi(Nuc)) of the adult rat spinal cord. As GST-pi intranuclear localization correlates with progenitor cell properties, we examined the differentiation status of this cell population under the intensive 5-bromo-2'-deoxyuridine (BrdU) administration method, consisting of intraperitoneal BrdU injections every 2 h for 48 h. We observed that a certain population of proliferating/proliferated cells expressed DM-20 mRNA, and sometimes two proliferating/proliferated cells were observed still attached to each other. We performed triple staining for BrdU, DM-20 mRNA, and NG2 and found pairs of neighboring BrdU-positive cells, which were considered to originate from the same progenitor cells and where both cells expressed DM-20 mRNA. Triple staining for BrdU, DM-20 mRNA, and GST-pi detected proliferating/proliferated cells exhibiting the GST-pi(Nuc)/DM-20 mRNA-positive expression pattern. These findings suggested the presence of a GST-pi(Nuc)/DM-20 mRNA-positive oligodendrocyte-lineage progenitor cell population in the adult rat spinal cord. However, we did not find any pair of neighboring BrdU-positive cells with this expression pattern. These observations collectively support the idea that GST-pi(Nuc)/DM-20 mRNA-expressing cells are the progeny of NG2-positive OPCs rather than a novel type of oligodendrocyte-lineage progenitor cells and that DM-20 mRNA expression is dynamically regulated during differentiation of OPCs into oligodendrocytes.

Inhibition profiles of phosphatidylinositol 3-kinase inhibitors against PI3K superfamily and human cancer cell line panel JFCR39.

PubMed

Kong, Dexin; Dan, Shingo; Yamazaki, Kanami; Yamori, Takao

2010-04-01

As accumulating evidences suggest close involvement of phosphatidylinositol 3-kinase (PI3K) in various diseases particularly cancer, considerable competition occurs in development of PI3K inhibitors. Consequently, novel PI3K inhibitors such as ZSTK474, GDC-0941 and NVP-BEZ235 have been developed. Even though all these inhibitors were reported to inhibit class I PI3K but not dozens of protein kinases, whether they have different molecular targets remained unknown. To investigate such molecular target specificity, we have determined the inhibitory effects of these novel inhibitors together with classical PI3K inhibitor LY294002 on PI3K superfamily (including classes I, II, and III PI3Ks, PI4K and PI3K-related kinases) by using several novel non-radioactive biochemical assays. As a result, ZSTK474 and GDC-0941 indicated highly similar inhibition profiles for PI3K superfamily, with class I PI3K specificity much higher than NVP-BEZ235 and LY294002. We further investigated their growth inhibition effects on JFCR39, a human cancer cell line panel which we established for molecular target identification, and analysed their cell growth inhibition profiles (fingerprints) by using COMPARE analysis programme. Interestingly, we found ZSTK474 exhibited a highly similar fingerprint with GDC-0941 (r=0.863), more similar than with that of either NVP-BEZ235 or LY294002, suggesting that ZSTK474 shares more in molecular targets with GDC-0941 than with either of the other two PI3K inhibitors, consistent with the biochemical assay result. The biological implication of the difference in molecular target specificity of these PI3K inhibitors is under investigation. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Autosomal-Recessive Hypophosphatemic Rickets Is Associated with an Inactivation Mutation in the ENPP1 Gene

PubMed Central

Levy-Litan, Varda; Hershkovitz, Eli; Avizov, Luba; Leventhal, Neta; Bercovich, Dani; Chalifa-Caspi, Vered; Manor, Esther; Buriakovsky, Sophia; Hadad, Yair; Goding, James; Parvari, Ruti

2010-01-01

Human disorders of phosphate (Pi) handling and hypophosphatemic rickets have been shown to result from mutations in PHEX, FGF23, and DMP1, presenting as X-linked recessive, autosomal-dominant, and autosomal-recessive patterns, respectively. We present the identification of an inactivating mutation in the ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene causing autosomal-recessive hypophosphatemic rickets (ARHR) with phosphaturia by positional cloning. ENPP1 generates inorganic pyrophosphate (PPi), an essential physiologic inhibitor of calcification, and previously described inactivating mutations in this gene were shown to cause aberrant ectopic calcification disorders, whereas no aberrant calcifications were present in our patients. Our surprising result suggests a different pathway involved in the generation of ARHR and possible additional functions for ENPP1. PMID:20137772

Integrated β-catenin, BMP, PTEN, and Notch signalling patterns the nephron

PubMed Central

Lindström, Nils O; Lawrence, Melanie L; Burn, Sally F; Johansson, Jeanette A; Bakker, Elvira RM; Ridgway, Rachel A; Chang, C-Hong; Karolak, Michele J; Oxburgh, Leif; Headon, Denis J; Sansom, Owen J; Smits, Ron; Davies, Jamie A; Hohenstein, Peter

2015-01-01

The different segments of the nephron and glomerulus in the kidney balance the processes of water homeostasis, solute recovery, blood filtration, and metabolite excretion. When segment function is disrupted, a range of pathological features are presented. Little is known about nephron patterning during embryogenesis. In this study, we demonstrate that the early nephron is patterned by a gradient in β-catenin activity along the axis of the nephron tubule. By modifying β-catenin activity, we force cells within nephrons to differentiate according to the imposed β-catenin activity level, thereby causing spatial shifts in nephron segments. The β-catenin signalling gradient interacts with the BMP pathway which, through PTEN/PI3K/AKT signalling, antagonises β-catenin activity and promotes segment identities associated with low β-catenin activity. β-catenin activity and PI3K signalling also integrate with Notch signalling to control segmentation: modulating β-catenin activity or PI3K rescues segment identities normally lost by inhibition of Notch. Our data therefore identifies a molecular network for nephron patterning. DOI: http://dx.doi.org/10.7554/eLife.04000.001 PMID:25647637

Identification and Characterization of Components of a Putative Petunia S-Locus F-Box–Containing E3 Ligase Complex Involved in S-RNase–Based Self-Incompatibility[W

PubMed Central

Hua, Zhihua; Kao, Teh-hui

2006-01-01

Petunia inflata S-locus F-box (Pi SLF) is thought to function as a typical F-box protein in ubiquitin-mediated protein degradation and, along with Skp1, Cullin-1, and Rbx1, could compose an SCF complex mediating the degradation of nonself S-RNase but not self S-RNase. We isolated three P. inflata Skp1s (Pi SK1, -2, and -3), two Cullin-1s (Pi CUL1-C and -G), and an Rbx1 (Pi RBX1) cDNAs and found that Pi CUL1-G did not interact with Pi RBX1 and that none of the three Pi SKs interacted with Pi SLF2. We also isolated a RING-HC protein, S-RNase Binding Protein1 (Pi SBP1), almost identical to Petunia hybrida SBP1, which interacts with Pi SLFs, S-RNases, Pi CUL1-G, and an E2 ubiquitin-conjugating enzyme, suggesting that Pi CUL1-G, SBP1, and SLF may be components of a novel E3 ligase complex, with Pi SBP1 playing the roles of Skp1 and Rbx1. S-RNases interact more with nonself Pi SLFs than with self Pi SLFs, and Pi SLFs also interact more with nonself S-RNases than with self S-RNases. Bacterially expressed S1-, S2-, and S3-RNases are degraded by the 26S proteasomal pathway in a cell-free system, albeit not in an S-allele–specific manner. Native glycosylated S3-RNase is not degraded to any significant extent; however, deglycosylated S3-RNase is degraded as efficiently as the bacterially expressed S-RNases. Finally, S-RNases are ubiquitinated in pollen tube extracts, but whether this is mediated by the Pi SLF–containing E3 complex is unknown. PMID:17028207

Identification of yrast high-K intrinsic states in {sup 188}Os

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

Modamio, V.; Jungclaus, A.; Instituto de Estructura de la Materia, CSIC, Serrano 113bis, E-28006 Madrid

2009-02-15

The high-spin structure of the Z=76 nucleus {sup 188}Os has been studied using the incomplete fusion reaction {sup 7}Li+{sup 186}W. A K{sup {pi}}=10{sup +} band has been established up to spin (24{sup +}) and its crossing with the ground-state band has been studied. In addition, intrinsic high-K states have been identified and on top of two of them, K{sup {pi}}=7{sup -} and K{sup {pi}}=10{sup -}, regular bands have been observed. The K{sup {pi}}=16{sup +} and K{sup {pi}}=18{sup +} states are yrast whereas the K{sup {pi}}=14{sup +} level lies only 33 keV above the yrast line and decays with a lowmore » reduced hindrance of f{sub {nu}}<1.3 to the ground-state band ({delta}K=14). The results are discussed by means of a systematic comparison with the even-even neighboring nucleus {sup 186}Os. Configuration-constrained multiquasiparticle potential-energy-surface calculations have been performed to identify the configurations of multiquasiparticle states.« less

Personal identification based on blood vessels of retinal fundus images

NASA Astrophysics Data System (ADS)

Fukuta, Keisuke; Nakagawa, Toshiaki; Hayashi, Yoshinori; Hatanaka, Yuji; Hara, Takeshi; Fujita, Hiroshi

2008-03-01

Biometric technique has been implemented instead of conventional identification methods such as password in computer, automatic teller machine (ATM), and entrance and exit management system. We propose a personal identification (PI) system using color retinal fundus images which are unique to each individual. The proposed procedure for identification is based on comparison of an input fundus image with reference fundus images in the database. In the first step, registration between the input image and the reference image is performed. The step includes translational and rotational movement. The PI is based on the measure of similarity between blood vessel images generated from the input and reference images. The similarity measure is defined as the cross-correlation coefficient calculated from the pixel values. When the similarity is greater than a predetermined threshold, the input image is identified. This means both the input and the reference images are associated to the same person. Four hundred sixty-two fundus images including forty-one same-person's image pairs were used for the estimation of the proposed technique. The false rejection rate and the false acceptance rate were 9.9×10 -5% and 4.3×10 -5%, respectively. The results indicate that the proposed method has a higher performance than other biometrics except for DNA. To be used for practical application in the public, the device which can take retinal fundus images easily is needed. The proposed method is applied to not only the PI but also the system which warns about misfiling of fundus images in medical facilities.

Glutathione S-transferase Pi mediates proliferation of androgen-independent prostate cancer cells

PubMed Central

Hokaiwado, Naomi; Takeshita, Fumitaka; Naiki-Ito, Aya; Asamoto, Makoto; Ochiya, Takahiro; Shirai, Tomoyuki

2008-01-01

Prostate cancers generally acquire an androgen-independent growth capacity with progression, resulting in resistance to antiandrogen therapy. Therefore, identification of the genes regulated through this process may be important for understanding the mechanisms of prostate carcinogenesis. We here utilized androgen-dependent/independent transplantable tumors, newly established with the ‘transgenic rat adenocarcinoma in prostate’ (TRAP) model, to analyze their gene expression using microarrays. Among the overexpressed genes in androgen-independent prostate cancers compared with the androgen-dependent tumors, glutathione S-transferase pi (GST-pi) was included. In line with this, human prostate cancer cell lines PC3 and DU145 (androgen independent) had higher expression of GST-pi compared with LNCaP (androgen dependent) as determined by semiquantitative reverse transcription–polymerase chain reaction analysis. To investigate the roles of GST-pi expression in androgen-independent human prostate cancers, GST-pi was knocked down by a small interfering RNA (siRNA), resulting in significant decrease of the proliferation rate in the androgen-independent PC3 cell line. In vivo, administration of GST-pi siRNA–atelocollagen complex decreased GST-pi protein expression, resulting in enhanced numbers of TdT mediated dUTP-biotin nick-end labering (TUNEL)-positive apoptotic cells. These findings suggest that GST-pi might play important roles in proliferation of androgen-independent human prostate cancer cells. PMID:18413363

Evolution of the current system during solar wind pressure pulses based on aurora and magnetometer observations

NASA Astrophysics Data System (ADS)

Nishimura, Yukitoshi; Kikuchi, Takashi; Ebihara, Yusuke; Yoshikawa, Akimasa; Imajo, Shun; Li, Wen; Utada, Hisashi

2016-08-01

We investigated evolution of ionospheric currents during sudden commencements using a ground magnetometer network in conjunction with an all-sky imager, which has the advantage of locating field-aligned currents much more accurately than ground magnetometers. Preliminary (PI) and main (MI) impulse currents showed two-cell patterns propagating antisunward, particularly during a southward interplanetary magnetic field (IMF). Although this overall pattern is consistent with the Araki (solar wind sources of magnetospheric ultra-low-frequency waves. Geophysical monograph series, vol 81. AGU, Washington, DC, pp 183-200, 1994. doi: 10.1029/GM081p0183) model, we found several interesting features. The PI and MI currents in some events were highly asymmetric with respect to the noon-midnight meridian; the post-noon sector did not show any notable PI signal, but only had an MI starting earlier than the pre-noon MI. Not only equivalent currents but also aurora and equatorial magnetometer data supported the much weaker PI response. We suggest that interplanetary shocks impacting away from the subsolar point caused the asymmetric current pattern. Additionally, even when PI currents form in both pre- and post-noon sectors, they can initiate and disappear at different timings. The PI currents did not immediately disappear but coexisted with the MI currents for the first few minutes of the MI. During a southward IMF, the MI currents formed equatorward of a preexisting DP-2, indicating that the MI currents are a separate structure from a preexisting DP-2. In contrast, the MI currents under a northward IMF were essentially an intensification of a preexisting DP-2. The magnetometer and imager combination has been shown to be a powerful means for tracing evolution of ionospheric currents, and we showed various types of ionospheric responses under different upstream conditions.

Growth patterns and cerebro-placental hemodynamics in fetuses with congenital heart disease.

PubMed

Mebius, M J; Clur, S A B; Vink, A S; Pajkrt, E; Kalteren, W S; Kooi, E M W; Bos, A F; du Marchie Sarvaas, G J; Bilardo, C M

2018-05-28

Congenital heart disease (CHD) has been associated with a reduced fetal head circumference (HC). The underlying pathophysiological background remains undetermined. We aimed to define trends in fetal growth and cerebro-placental Doppler flow, and to investigate the association between head growth and cerebro-placental flow in fetuses with CHD. Fetuses with CHD and serial measurements of HC, abdominal circumference (AC), middle cerebral artery pulsatility index (MCA-PI), umbilical artery pulsatility index (UA-PI), and cerebro-placental ratio (CPR) were included. CHD was categorized into 3 groups based on expected cerebral arterial oxygen saturation: normal, mild to moderately reduced, and severely reduced. Trends over time in Z-scores were analyzed using a linear mixed-effects model. 181 fetuses fulfilled the inclusion criteria. Expected cerebral arterial oxygen saturation in CHD was classified as normal in 44, mild to moderately reduced in 84 and severely reduced in 53 cases. HC z-scores showed a tendency to decrease until 23 weeks, then to increase until 33 weeks, followed by a decrease again in the late third trimester. AC increased progressively with advancing gestation. MCA-PI and UA-PI showed significant trends throughout pregnancy, but CPR did not. There were no associations between expected cerebral arterial oxygen saturation and fetal growth. Average trends in MCA-PI were significantly different in the three subgroups (P=0.010), whereas average trends in UA-PI and CPR were similar (P=0.530 and P=0.285). Furthermore, there was no significant association between MCA-PI and HC (P=0.284). Fetal biometry and Doppler flow patterns are within normal ranges in fetuses with CHD, but show trends over time. Fetal head growth is not associated with the cerebral blood flow pattern or placental function and HC is not influenced by the cerebral arterial oxygen saturation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Relationship between Guillain-Barré syndrome, influenza-related hospitalizations, and influenza vaccine coverage.

PubMed

Iqbal, Shahed; Li, Rongxia; Gargiullo, Paul; Vellozzi, Claudia

2015-04-21

Some studies reported an increased risk of Guillain-Barré syndrome (GBS) within six weeks of influenza vaccination. It has also been suggested that this finding could have been confounded by influenza illnesses. We explored the complex relationship between influenza illness, influenza vaccination, and GBS, from an ecologic perspective using nationally representative data. We also studied seasonal patterns for GBS hospitalizations. Monthly hospitalization data (2000-2009) for GBS, and pneumonia and influenza (P&I) in the Nationwide Inpatient Sample were included. Seasonal influenza vaccination coverage for 2004-2005 through the 2008-2009 influenza seasons (August-May) was estimated from the National Health Interview Survey data. GBS seasonality was determined using Poisson regression. GBS and P&I temporal clusters were identified using scan statistics. The association between P&I and GBS hospitalizations in the same month (concurrent) or in the following month (lagged) were determined using negative binomial regression. Vaccine coverage increased over the years (from 19.7% during 2004-2005 to 35.5% during 2008-2009 season) but GBS hospitalization did not follow a similar pattern. Overall, a significant correlation between monthly P&I and GBS hospitalizations was observed (Spearman's correlation coefficient=0.7016, p<0.0001). A significant (p=0.001) cluster of P&I hospitalizations during December 2004-March 2005 overlapped a significant (p=0.001) cluster of GBS hospitalizations during January 2005-February 2005. After accounting for effects of monthly vaccine coverage and age, P&I hospitalization was significantly associated (p<0.0001) with GBS hospitalization in the concurrent month but not with GBS hospitalization in the following month. Monthly vaccine coverage was not associated with GBS hospitalization in adjusted models (both concurrent and lagged). GBS hospitalizations demonstrated a seasonal pattern with winter months having higher rates compared to the month of June. P&I hospitalization rates were significantly correlated with hospitalization rates for GBS. Vaccine coverage did not significantly affect the rates of GBS hospitalization at the population level. Published by Elsevier Ltd.

Comprehensive Genomic Identification and Expression Analysis of the Phosphate Transporter (PHT) Gene Family in Apple

PubMed Central

Sun, Tingting; Li, Mingjun; Shao, Yun; Yu, Lingyan; Ma, Fengwang

2017-01-01

Elemental phosphorus (Pi) is essential to plant growth and development. The family of phosphate transporters (PHTs) mediates the uptake and translocation of Pi inside the plants. Members include five sub-cellular phosphate transporters that play different roles in Pi uptake and transport. We searched the Genome Database for Rosaceae and identified five clusters of phosphate transporters in apple (Malus domestica), including 37 putative genes. The MdPHT1 family contains 14 genes while MdPHT2 has two, MdPHT3 has seven, MdPHT4 has 11, and MdPHT5 has three. Our overview of this gene family focused on structure, chromosomal distribution and localization, phylogenies, and motifs. These genes displayed differential expression patterns in various tissues. For example, expression was high for MdPHT1;12, MdPHT3;6, and MdPHT3;7 in the roots, and was also increased in response to low-phosphorus conditions. In contrast, MdPHT4;1, MdPHT4;4, and MdPHT4;10 were expressed only in the leaves while transcript levels of MdPHT1;4, MdPHT1;12, and MdPHT5;3 were highest in flowers. In general, these 37 genes were regulated significantly in either roots or leaves in response to the imposition of phosphorus and/or drought stress. The results suggest that members of the PHT family function in plant adaptations to adverse growing environments. Our study will lay a foundation for better understanding the PHT family evolution and exploring genes of interest for genetic improvement in apple. PMID:28424713

Specialized piRNA Pathways Act in Germline and Somatic Tissues of the Drosophila Ovary

PubMed Central

Malone, Colin D.; Brennecke, Julius; Dus, Monica; Stark, Alexander; McCombie, W. Richard; Sachidanandam, Ravi; Hannon, Gregory J.

2010-01-01

SUMMARY In Drosophila gonads, Piwi proteins and associated piRNAs collaborate with additional factors to form a small RNA-based immune system that silences mobile elements. Here, we analyzed nine Drosophila piRNA pathway mutants for their impacts on both small RNA populations and the subcellular localization patterns of Piwi proteins. We find that distinct piRNA pathways with differing components function in ovarian germ and somatic cells. In the soma, Piwi acts singularly with the conserved flamenco piRNA cluster to enforce silencing of retroviral elements that may propagate by infecting neighboring germ cells. In the germline, silencing programs encoded within piRNA clusters are optimized via a slicer-dependent amplification loop to suppress a broad spectrum of elements. The classes of transposons targeted by germline and somatic piRNA clusters, though not the precise elements, are conserved among Drosophilids, demonstrating that the architecture of piRNA clusters has coevolved with the transposons that they are tasked to control. PMID:19395010

Observation of CP violation in neutral B meson going to positive kaon-antipion and neutral B meson going to pion-antipion decays with the BABAR detector

NASA Astrophysics Data System (ADS)

Li, Xuanzhong

This dissertation describes the measurement of asymmetries in neutral B meson decays to two-body final states of charged pions and kaons. The results are obtained from a data sample of 383 million Upsilon(4 S) → BB¯ decays collected between 1999 and 2006 with the BABAR detector at the PEP-II asymmetric-energy B factory located at the Stanford Linear Accelerator Center, California. The maximum likelihood fit that incorporates kinematical, event-shape, and particle identification information is used to measure the CP asymmetries in B0 → pi +pi- and K+/- pi∓ decays. The direct CP-violating asymmetry between decays to K-pi + is AKpi = -0.107 +/- 0.018+0.007-0.004 . The time-dependent CP-violating parameters in B0 → pi+pi- decays are Spipi = -0.60 +/- 0.11 +/- 0.03, Cpipi = -0.21 +/- 0.09 +/- 0.02. For all the measurements above, the first error is statistical and the second is systematic.

Cations Form Sequence Selective Motifs within DNA Grooves via a Combination of Cation-Pi and Ion-Dipole/Hydrogen Bond Interactions

PubMed Central

Stewart, Mikaela; Dunlap, Tori; Dourlain, Elizabeth; Grant, Bryce; McFail-Isom, Lori

2013-01-01

The fine conformational subtleties of DNA structure modulate many fundamental cellular processes including gene activation/repression, cellular division, and DNA repair. Most of these cellular processes rely on the conformational heterogeneity of specific DNA sequences. Factors including those structural characteristics inherent in the particular base sequence as well as those induced through interaction with solvent components combine to produce fine DNA structural variation including helical flexibility and conformation. Cation-pi interactions between solvent cations or their first hydration shell waters and the faces of DNA bases form sequence selectively and contribute to DNA structural heterogeneity. In this paper, we detect and characterize the binding patterns found in cation-pi interactions between solvent cations and DNA bases in a set of high resolution x-ray crystal structures. Specifically, we found that monovalent cations (Tl+) and the polarized first hydration shell waters of divalent cations (Mg2+, Ca2+) form cation-pi interactions with DNA bases stabilizing unstacked conformations. When these cation-pi interactions are combined with electrostatic interactions a pattern of specific binding motifs is formed within the grooves. PMID:23940752

Cations form sequence selective motifs within DNA grooves via a combination of cation-pi and ion-dipole/hydrogen bond interactions.

PubMed

Stewart, Mikaela; Dunlap, Tori; Dourlain, Elizabeth; Grant, Bryce; McFail-Isom, Lori

2013-01-01

The fine conformational subtleties of DNA structure modulate many fundamental cellular processes including gene activation/repression, cellular division, and DNA repair. Most of these cellular processes rely on the conformational heterogeneity of specific DNA sequences. Factors including those structural characteristics inherent in the particular base sequence as well as those induced through interaction with solvent components combine to produce fine DNA structural variation including helical flexibility and conformation. Cation-pi interactions between solvent cations or their first hydration shell waters and the faces of DNA bases form sequence selectively and contribute to DNA structural heterogeneity. In this paper, we detect and characterize the binding patterns found in cation-pi interactions between solvent cations and DNA bases in a set of high resolution x-ray crystal structures. Specifically, we found that monovalent cations (Tl⁺) and the polarized first hydration shell waters of divalent cations (Mg²⁺, Ca²⁺) form cation-pi interactions with DNA bases stabilizing unstacked conformations. When these cation-pi interactions are combined with electrostatic interactions a pattern of specific binding motifs is formed within the grooves.

Constructing STR multiplexes for individual identification of Hungarian red deer.

PubMed

Szabolcsi, Zoltan; Egyed, Balazs; Zenke, Petra; Padar, Zsolt; Borsy, Adrienn; Steger, Viktor; Pasztor, Erzsebet; Csanyi, Sandor; Buzas, Zsuzsanna; Orosz, Laszlo

2014-07-01

Red deer is the most valuable game of the fauna in Hungary, and there is a strong need for genetic identification of individuals. For this purpose, 10 tetranucleotide STR markers were developed and amplified in two 5-plex systems. The study presented here includes the flanking region sequence analysis and the allele nomenclature of the 10 loci as well as the PCR optimization of the DeerPlex I and II. LD pairwise tests and cross-species similarity analyses showed the 10 loci to be independently inherited. Considerable levels of genetic differences between two subpopulations were recorded, and F(ST) was 0.034 using AMOVA. The average probability of identity (PI(ave)) was at the value of 2.6736 × 10(-15). This low value for PI(ave) nearly eliminates false identification. An illegal hunting case solved by DeerPlex is described herein. The calculated likelihood ratio (LR) illustrates the potential of the 10 red deer microsatellite markers for forensic investigations. © 2014 American Academy of Forensic Sciences.

Facets of perfectionism in a sample of hypersexual patients.

PubMed

Reid, Rory C; Cooper, Erin B; Prause, Nicole; Li, Desiree S; Fong, Timothy W

2012-11-01

This study investigated the role of perfectionism in a treatment-seeking sample (N = 136) of adult men and women using the Perfectionism Inventory (PI) and the Hypersexual Behavior Inventory (HBI). Several facets of perfectionism were positively correlated with hypersexuality, with the concern over mistakes scale from the PI accounting for most of the predictive variance in patterns of hypersexual behavior measured by the HBI. Items associated with concern over mistakes closely parallel the construct of shame noted in other studies of hypersexual patients. To a lesser degree, the PI scale planfulness also showed a negative relationship with hypersexuality, suggesting tendencies of impulsivity in the current patients. These data reinforce the findings in other studies that patterns of harsh self-criticism and impulsivity seem to strongly influence hypersexual behavior.

Multiparametric MRI of the prostate: diagnostic performance and interreader agreement of two scoring systems.

PubMed

Lin, Wei-Ching; Muglia, Valdair F; Silva, Gyl E B; Chodraui Filho, Salomão; Reis, Rodolfo B; Westphalen, Antonio C

2016-06-01

To compare the diagnostic accuracies and interreader agreements of the Prostate Imaging Reporting and Data System (PI-RADS) v. 2 and University of California San Francisco (UCSF) multiparametric prostate MRI scale for diagnosing clinically significant prostate cancer. This institutional review board-approved retrospective study included 49 males who had 1.5 T endorectal MRI and prostatectomy. Two radiologists scored suspicious lesions on MRI using PI-RADS v. 2 and the UCSF scale. Percent agreement, 2 × 2 tables and the area under the receiver operating characteristic curves (Az) were used to assess and compare the individual and overall scores of these scales. Interreader agreements were estimated with kappa statistics. Reader 1 (R1) detected 78 lesions, and Reader 2 (R2) detected 80 lesions. Both identified 52 of 65 significant cancers. The Az for PI-RADS v. 2 and UCSF scale for R1 were 0.68 and 0.69 [T2 weighted imaging (T2WI)], 0.75 and 0.68 [diffusion-weighted imaging (DWI)] and 0.64 and 0.72 (overall score), respectively, and were 0.72 and 0.75 (T2WI), 0.73 and 0.67 (DWI) and 0.66 and 0.75 (overall score) for R2. The dynamic contrast-enhanced percent agreements between scales were 100% (R1) and 95% (R2). PI-RADS v. 2 DWI of R1 performed better than UCSF DWI (Az = 0.75 vs Az = 0.68; p = 0.05); no other differences were found. The interreader agreements were higher for PI-RADS v. 2 (T2WI: 0.56 vs 0.42; DWI: 0.60 vs 0.46; overall: 0.61 vs 0.42). The UCSF approach to derive the overall PI-RADS v. 2 scores increased the Az for the identification of significant cancer (R1 to 0.76, p < 0.05; R2 to 0.71, p = 0.35). Although PI-RADS v. 2 DWI score may have a higher discriminatory performance than the UCSF scale counterpart to diagnose clinically significant cancer, the utilization of the UCSF scale weighing system for the integration of PI-RADS v. 2 individual parameter scores improved the accuracy its overall score. PI-RADS v. 2 is moderately accurate for the identification of clinically significant prostate cancer, but the utilization of alternative approaches to derive the overall PI-RADS v. 2 score, including the one used by the UCSF system, may improve its diagnostic accuracy.

Distributed Patterns of Brain Activity that Lead to Forgetting

PubMed Central

Öztekin, Ilke; Badre, David

2011-01-01

Proactive interference (PI), in which irrelevant information from prior learning disrupts memory performance, is widely viewed as a major cause of forgetting. However, the hypothesized spontaneous recovery (i.e., automatic retrieval) of interfering information presumed to be at the base of PI remains to be demonstrated directly. Moreover, it remains unclear at what point during learning and/or retrieval interference impacts memory performance. In order to resolve these open questions, we employed a machine-learning algorithm to identify distributed patterns of brain activity associated with retrieval of interfering information that engenders PI and causes forgetting. Participants were scanned using functional magnetic resonance imaging during an item recognition task. We induced PI by constructing sets of three consecutive study lists from the same semantic category. The classifier quantified the magnitude of category-related activity at encoding and retrieval. Category-specific activity during retrieval increased across lists, consistent with the category information becoming increasingly available and producing interference. Critically, this increase was correlated with individual differences in forgetting and the deployment of frontal lobe mechanisms that resolve interference. Collectively, these findings suggest that distributed patterns of brain activity pertaining to the interfering information during retrieval contribute to forgetting. The prefrontal cortex mediates the relationship between the spontaneous recovery of interfering information at retrieval and individual differences in memory performance. PMID:21897814

Identification of a Potent Phosphoinositide 3‐Kinase Pan Inhibitor Displaying a Strategic Carboxylic Acid Group and Development of Its Prodrugs

PubMed Central

Pirali, Tracey; Ciraolo, Elisa; Aprile, Silvio; Massarotti, Alberto; Berndt, Alex; Griglio, Alessia; Serafini, Marta; Mercalli, Valentina; Landoni, Clarissa; Campa, Carlo Cosimo; Margaria, Jean Piero; Silva, Rangel L.; Grosa, Giorgio; Sorba, Giovanni; Williams, Roger

2017-01-01

Abstract Activation of the phosphoinositide 3‐kinase (PI3K) pathway is a key signaling event in cancer, inflammation, and other proliferative diseases. PI3K inhibitors are already approved for some specific clinical indications, but their systemic on‐target toxicity limits their larger use. In particular, whereas toxicity is tolerable in acute treatment of life‐threatening diseases, this is less acceptable in chronic conditions. In the past, the strategy to overcome this drawback was to block selected isoforms mainly expressed in leukocytes, but redundancy within the PI3K family members challenges the effectiveness of this approach. On the other hand, decreasing exposure to selected target cells represents a so‐far unexplored alternative to circumvent systemic toxicity. In this manuscript, we describe the generation of a library of triazolylquinolones and the development of the first prodrug pan‐PI3K inhibitor. PMID:28857471

Pulsatility index variations using two different transit-time flowmeters in coronary artery bypass surgery.

PubMed

Nordgaard, Håvard B; Vitale, Nicola; Astudillo, Rafael; Renzulli, Attilio; Romundstad, Pål; Haaverstad, Rune

2010-05-01

Transit-time flow measurement is widely accepted as an intra-operative assessment in coronary artery bypass grafting (CABG). However, the two most commonly applied flowmeters, manufactured by MediStim ASA and Transonic Inc., have different default filter settings of 20 and 10 Hz, respectively. This may cause different flow measurements, which will influence the reported results. The aim was to compare pulsatility index (PI) values recorded by the MediStim and Transonic flowmeters in two different clinical settings: (1) analysis of the flow patterns recorded simultaneously by both flowmeters in the same CABGs; and (2) evaluation of flow patterns under different levels of filter settings in the same grafts. Graft flow and PI were measured using the two different flowmeters simultaneously in 19 bypass grafts. Finally, eight grafts were assessed under different digital filter settings at 5, 10, 20, 30, 50 and 100 Hz. The Transonic flowmeter provided substantially lower PI as compared with the MediStim flowmeter. By increasing the filter setting in the flowmeter, PI increased considerably. The Transonic flowmeter displayed a lower PI than the MediStim, due to a lower filter setting. In the Transonic,flow signals are filtered at a lower level, rendering a 'smoother' pattern of flow curves. Because different filter settings determine different PIs, caution must be taken when flow values and flowmeters are compared. The type of flowmeter should be indicated whenever graft flow measurements and derived indexes are provided [corrected]. Copyright 2009 European Association for Cardio-Thoracic Surgery. All rights reserved.

Peritumoral stromal remodeling, pattern of invasion and expression of c-met/HGF in advanced squamous cell carcinoma of the cervix uteri, FIGO stages III and IV.

PubMed

Horn, L-C; Hommel, N; Roschlau, U; Bilek, K; Hentschel, B; Einenkel, J

2012-07-01

Different patterns of invasion (PIs) have prognostic impact in several types of cancer and are associated with different grades of peritumoral stromal remodeling, characterized by the desmoplastic stromal response (DSR). One key regulator influencing cellular motility and peritumoral stromal response is c-met/HGF. This study evaluates the association between different PI, peritumoral DSR and its correlation to the expression of c-met/HGF in squamous cell carcinomas of the uterine cervix (CX). 131 advanced stage CX (FIGO III/IV) were re-evaluated histologically regarding PI, using a two-level scoring system. The tumor grows in solid cords/trabeculae in finger-like PI and in very small groups or single cells in spray-like PI. DSR was categorized as none/weak and moderate/strong. The tumors were stained with antibodies against c-met and HGF. The staining of >30% of tumor cells was defined as overexpression. The PI was correlated to the prognostic outcome, different categories of DSR and expression status of c-met and HGF. 66.4% of the tumors showed a finger-like, and 33.6% a spray-like PI. The spray-like PI showed a reduced two-year overall survival when compared to the finger-like PI (14.0% vs. 29.1%, respectively; p=0.012), and was associated with moderate/strong DSR. The majority of the tumors showed overexpression of c-met (85.4%) and HGF (74.8%). There was no correlation between the expression status of c-met/HGF and the FIGO stage, peritumoral DSR or the prognostic outcome. Spray-like PI is of prognostic impact in cervical carcinoma FIGO III/IV and is associated with strong peritumoral stromal remodeling. There is no prognostic impact of the immunohistochemical expression of c-met/HGF in advanced stage cervical carcinomas. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Na+-independent phosphate transport in Caco2BBE cells

PubMed Central

Candeal, Eduardo; Caldas, Yupanqui A.; Guillén, Natalia; Levi, Moshe

2014-01-01

Pi transport in epithelia has both Na+-dependent and Na+-independent components, but so far only Na+-dependent transporters have been characterized in detail and molecularly identified. Consequently, in the present study, we initiated the characterization and analysis of intestinal Na+-independent Pi transport using an in vitro model, Caco2BBE cells. Only Na+-independent Pi uptake was observed in these cells, and Pi uptake was dramatically increased when cells were incubated in high-Pi DMEM (4 mM) from 1 day to several days. No response to low-Pi medium was observed. The increased Pi transport was mainly caused by Vmax changes, and it was prevented by actinomycin D and cycloheximide. Pi transport in cells grown in 1 mM Pi (basal DMEM) decreased at pH > 7.5, and it was inhibited with proton ionophores. Pi transport in cells incubated with 4 mM Pi increased with alkaline pH, suggesting a preference for divalent phosphate. Pi uptake in cells in 1 mM Pi was completely inhibited only by Pi and partially inhibited by phosphonoformate, oxalate, DIDS, SITS, SO42−, HCO3−, and arsenate. This inhibition pattern suggests that more than one Pi transporter is active in cells maintained with 1 mM Pi. Phosphate transport from cells maintained at 4 mM Pi was only partially inhibited by phosphonoformate, oxalate, and arsenate. Attempts to identify the responsible transporters showed that multifunctional anion exchangers of the Slc26 family as well as members of Slc17, Slc20, and Slc37 and the Pi exporter xenotropic and polytropic retrovirus receptor 1 are not involved. PMID:25298422

Flexible and transparent polyimide films containing two-dimensional alumina nanosheets templated by graphene oxide for improved barrier property.

PubMed

Tseng, I-Hsiang; Tsai, Mei-Hui; Chung, Chi-Wei

2014-08-13

Unique two-dimensional alumina nanosheets (Alns) using graphene oxide (GO) as templates are fabricated and successfully incorporated with organo-soluble polyimide (PI) to obtain highly transparent PI nanocomposite films with improved moisture barrier property. The effects of filler types and contents on water vapor transmission rate (WVTR) and transparency of PI are systematically studied. The hydroxyl groups on GO react with aluminum isopropoxide via sol-gel process to obtain alumina coverd-GO (Al-GO), and then thermal decomposition is applied to obtain Alns. Alns are the most efficient fillers among others to restrict the diffusion of water vapor within PI matrix and simultaneously maintain the transparency of PI. XRD pattern, TEM, and AFM images confirm the sheet-like morphology of Alns with ultrahigh aspect ratio. With only 0.01 wt % of Alns, the PI nanocomposite film exhibits the most significant reduction of 95% in WVTR as compared to that of pure PI film. Most importantly, the resultant PI/Alns-0.01 film exhibits excellent optical transparency and high mechanical strength and great thermal stability.

Wavelet-Based Signal and Image Processing for Target Recognition

NASA Astrophysics Data System (ADS)

Sherlock, Barry G.

2002-11-01

The PI visited NSWC Dahlgren, VA, for six weeks in May-June 2002 and collaborated with scientists in the G33 TEAMS facility, and with Marilyn Rudzinsky of T44 Technology and Photonic Systems Branch. During this visit the PI also presented six educational seminars to NSWC scientists on various aspects of signal processing. Several items from the grant proposal were completed, including (1) wavelet-based algorithms for interpolation of 1-d signals and 2-d images; (2) Discrete Wavelet Transform domain based algorithms for filtering of image data; (3) wavelet-based smoothing of image sequence data originally obtained for the CRITTIR (Clutter Rejection Involving Temporal Techniques in the Infra-Red) project. The PI visited the University of Stellenbosch, South Africa to collaborate with colleagues Prof. B.M. Herbst and Prof. J. du Preez on the use of wavelet image processing in conjunction with pattern recognition techniques. The University of Stellenbosch has offered the PI partial funding to support a sabbatical visit in Fall 2003, the primary purpose of which is to enable the PI to develop and enhance his expertise in Pattern Recognition. During the first year, the grant supported publication of 3 referred papers, presentation of 9 seminars and an intensive two-day course on wavelet theory. The grant supported the work of two students who functioned as research assistants.

Spallation of Cu by 500- and 1570-MeV. pi. /sup -/

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

Haustein, P.E.; Ruth, T.J.

1978-11-01

Relative yields of 36 products extending from /sup 7/Be to /sup 65/Zn have been measured for the interaction of 500- and 1570-MeV negative pions with Cu. These results are compared with calculations from the ISOBAR model, with earlier studies of Cu spallation with lower (resonance) energy pions, energetic protons, and heavy ions. Relative yield patterns at both ..pi../sup -/ energies show only slight differences when compared to spallation by protons of comparable energy. Calculations from the ISOBAR model adequately reproduce the shapes of the mass yield and charge yield of the experimental data for 500-MeV ..pi../sup -/. The calculation, however,more » overestimates the yield of neutron-rich isotopes from deep spallation. At the 1570-MeV ..pi../sup -/ energy the yield patterns, charge-dispersion, and mass-yield curves are nearly identical to those for 2-GeV proton spallation. These results suggest that pion-nucleon resonance effects probably decrease at higher energies and that limiting fragmentation and factorization concepts may be applied to understanding high-energy pion spallation.« less

Mapping "old" versus "young" piñon-juniper stands with a predictive topo-climatic model in north-central New Mexico, USA

USGS Publications Warehouse

Jacobs, B. F.; Romme, W.H.; Allen, Craig D.

2008-01-01

Piñon pine and juniper woodlands in the southwestern United States are often represented as an expanding and even invasive vegetation type, a legacy of historic grazing, and culpable in the degradation of western rangelands. A long-standing emphasis on forage production, in combination with recent hazard fuel concerns, has prompted a new era of woodland management with stated restoration objectives. Yet the extent and dynamics of piñon–juniper communities that predate intensive Euro-American settlement activities are poorly known or understood, while the intrinsic ecological, aesthetic, and economic values of old-growth woodlands are often overlooked. Historical changes in piñon–juniper stands include two related, but poorly differentiated processes: recent tree expansion into grass- or shrub-dominated (i.e., non-woodland) vegetation and thickening or infilling of savanna or mosaic woodlands predating settlement. Our work addresses the expansion pattern, modeling the occurrence of “older” savanna and woodland stands extant prior to 1850 in contrast to “younger” piñon–juniper growth of more recent, postsettlement origin. We present criteria in the form of a diagnostic key for distinguishing “older,” pre-Euro-American settlement piñon–juniper from “younger” (post-1850) stands and report results of predictive modeling and mapping efforts within a north-central New Mexico study area. Selected models suggest a primary role for soil moisture in the current distribution of “old” vs. “young” piñon–juniper stands. Presettlement era woodlands are shown to occupy a discrete ecological space, defined by the interaction of effective (seasonal) moisture with landform setting and fine-scale (soil/water) depositional patterns. “Older” stands are generally found at higher elevations or on skeletal soils in upland settings, while “younger” stands (often dominated by one-seed juniper, Juniperus monosperma) are most common at lower elevations or in productive, depositional settings. Modeling at broad regional scales can enhance our general understanding of piñon–juniper ecology, while predictive mapping of local areas has potential to provide products useful for land management. Areas of the southwestern United States with strong monsoonal (summer moisture) patterns appear to have been the most susceptible to historical woodland expansion, but even here the great majority of extant piñon–juniper has presettlement origins (although widely thickened and infilled historically), and old-growth structure is not uncommon in appropriate upland settings.

Serial analysis of gene expression reveals differential expression between endometriosis and normal endometrium. Possible roles for AXL and SHC1 in the pathogenesis of endometriosis

PubMed Central

Honda, Hiroshi; Barrueto, Fermin F; Gogusev, Jean; Im, Dwight D; Morin, Patrice J

2008-01-01

Background Endometriosis is a clinical condition that affects up to 10% of the women of reproductive age. Endometriosis is characterized by the presence of endometrial tissues outside the uterine cavity and can lead to chronic pelvic pain, infertility and, in some cases, to ovarian cancer. Methods In order to better understand the pathogenesis of endometriosis, we have used Serial Analysis of Gene Expression (SAGE) to identify genes differentially in this disease by studying three endometriotic tissues and a normal endometrium sample. Promising candidates (AXL, SHC1, ACTN4, PI3KCA, p-AKT, p-mTOR, and p-ERK) were independently validated by immunohistochemistry in additional normal and endometriotic tissues. Results We identified several genes differentially expressed between endometriosis and normal endometrium. IGF2, ACTN4, AXL, and SHC1 were among the most upregulated genes. Comparison of the endometriosis gene expression profiles with the gene expression patterns observed in normal human tissues allowed the identification of endometriosis-specific genes, which included several members of the MMP family (MMP1,2,3,10,11,14). Immunohistochemical analysis of several candidates confirmed the SAGE findings, and suggested the involvement of the PI3K-Akt and MAPK signaling pathways in endometriosis. Conclusion In human endometriosis, the PI3K-Akt and MAPK signaling pathways may be activated via overexpression of AXL and SHC1, respectively. These genes, as well as others identified as differentially expressed in this study, may be useful for the development of novel strategies for the detection and/or therapy of endometriosis. PMID:19055724

Fabry Disease in Families With Hypertrophic Cardiomyopathy: Clinical Manifestations in the Classic and Later-Onset Phenotypes.

PubMed

Adalsteinsdottir, Berglind; Palsson, Runolfur; Desnick, Robert J; Gardarsdottir, Marianna; Teekakirikul, Polakit; Maron, Martin; Appelbaum, Evan; Neisius, Ulf; Maron, Barry J; Burke, Michael A; Chen, Brenden; Pagant, Silvere; Madsen, Christoffer V; Danielsen, Ragnar; Arngrimsson, Reynir; Feldt-Rasmussen, Ulla; Seidman, Jonathan G; Seidman, Christine E; Gunnarsson, Gunnar Th

2017-08-01

The screening of Icelandic patients clinically diagnosed with hypertrophic cardiomyopathy resulted in identification of 8 individuals from 2 families with X-linked Fabry disease (FD) caused by GLA (α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B). Familial screening of at-risk relatives identified mutations in 16 family A members (8 men and 8 heterozygotes) and 25 family B members (10 men and 15 heterozygotes). Clinical assessments, α-galactosidase A (α-GalA) activities, glycosphingolipid substrate levels, and in vitro mutation expression were used to categorize p.D322E as a classic FD mutation and p.I232T as a later-onset FD mutation. In vitro expression revealed that p.D322E and p.I232T had α-GalA activities of 1.4% and 14.9% of the mean wild-type activity, respectively. Family A men had markedly decreased α-GalA activity and childhood-onset classic manifestations, except for angiokeratoma and cornea verticillata. Family B men had residual α-GalA activity and developed FD manifestations in adulthood. Despite these differences, all family A and family B men >30 years of age had left ventricular hypertrophy, which was mainly asymmetrical, and had similar late gadolinium enhancement patterns. Ischemic stroke and severe white matter lesions were more frequent among family A men, but neither family A nor family B men had overt renal disease. Family A and family B heterozygotes had less severe or no clinical manifestations. Men with classic or later-onset FD caused by GLA missense mutations developed prominent and similar cardiovascular disease at similar ages, despite markedly different α-GalA activities. © 2017 American Heart Association, Inc.

MAEWEST expression in flower development of two petunia species.

PubMed

Segatto, Ana Lúcia A; Turchetto-Zolet, Andreia Carina; Aizza, Lilian Cristina B; Monte-Bello, Carolina C; Dornelas, Marcelo C; Margis, Rogerio; Freitas, Loreta B

2013-07-03

Changes in flower morphology may influence the frequency and specificity of animal visitors. In Petunia (Solanaceae), adaptation to different pollinators is one of the factors leading to species diversification within the genus. This study provides evidence that differential expression patterns of MAWEWEST (MAW) homologs in different Petunia species may be associated with adaptive changes in floral morphology. The Petunia × hybrida MAW gene belongs to the WOX (WUSCHEL-related homeobox) transcription factor family and has been identified as a controller of petal fusion during corolla formation. We analyzed the expression patterns of P. inflata and P. axillaris MAW orthologs (PiMAW and PaMAW, respectively) by reverse transcriptase polymerase chain reaction (RT-PCR), reverse transcription-quantitative PCR (qRT-PCR) and in situ hybridization in different tissues and different developmental stages of flowers in both species. The spatial expression patterns of PiMAW and PaMAW were similar in P. inflata and P. axillaris. Nevertheless, PaMAW expression level in P. axillaris was higher during the late bud development stage as compared to PiMAW in P. inflata. This work represents an expansion of petunia developmental research to wild accessions.

Molecular Evolution of the Rice Blast Resistance Gene Pi-ta in Invasive Weedy Rice in the USA

PubMed Central

Lee, Seonghee; Jia, Yulin; Jia, Melissa; Gealy, David R.; Olsen, Kenneth M.; Caicedo, Ana L.

2011-01-01

The Pi-ta gene in rice has been effectively used to control rice blast disease caused by Magnaporthe oryzae worldwide. Despite a number of studies that reported the Pi-ta gene in domesticated rice and wild species, little is known about how the Pi-ta gene has evolved in US weedy rice, a major weed of rice. To investigate the genome organization of the Pi-ta gene in weedy rice and its relationship to gene flow between cultivated and weedy rice in the US, we analyzed nucleotide sequence variation at the Pi-ta gene and its surrounding 2 Mb region in 156 weedy, domesticated and wild rice relatives. We found that the region at and around the Pi-ta gene shows very low genetic diversity in US weedy rice. The patterns of molecular diversity in weeds are more similar to cultivated rice (indica and aus), which have never been cultivated in the US, rather than the wild rice species, Oryza rufipogon. In addition, the resistant Pi-ta allele (Pi-ta) found in the majority of US weedy rice belongs to the weedy group strawhull awnless (SH), suggesting a single source of origin for Pi-ta. Weeds with Pi-ta were resistant to two M. oryzae races, IC17 and IB49, except for three accessions, suggesting that component(s) required for the Pi-ta mediated resistance may be missing in these accessions. Signatures of flanking sequences of the Pi-ta gene and SSR markers on chromosome 12 suggest that the susceptible pi-ta allele (pi-ta), not Pi-ta, has been introgressed from cultivated to weedy rice by out-crossing. PMID:22043312

Profiling CCK-mediated pancreatic growth: the dynamic genetic program and the role of STATs as potential regulators.

PubMed

Gurda, Grzegorz T; Wang, Jackie Y; Guo, LiLi; Ernst, Stephen A; Williams, John A

2012-01-18

Feeding mice with protease inhibitor (PI) leads to increased endogenous cholecystokinin (CCK) release and results in pancreatic growth. This adaptive response requires calcineurin (CN)-NFAT and AKT-mTOR pathways, but the genes involved, the dynamics of their expression, and other regulatory pathways remain unknown. Here, we examined the early (1-8 h) transcriptional program that underlies pancreatic growth. We found 314 upregulated and 219 downregulated genes with diverse temporal and functional profiles. Several new identifications include the following: stress response genes Gdf15 and Txnip, metabolic mediators Pitpnc1 and Hmges2, as well as components of growth factor response Fgf21, Atf3, and Egr1. The genes fell into seven self-organizing clusters, each with a distinct pattern of expression; a representative gene within each of the upregulated clusters (Egr1, Gadd45b, Rgs2, and Serpinb1a) was validated by qRT-PCR. Genes up at any point throughout the time course and CN-dependent genes were subjected to further bioinformatics-based networking and promoter analysis, yielding STATs as potential transcriptional regulators. As shown by PCR, qPCR, and Western blots, the active phospho-form of STAT3 and the Jak-STAT feedback inhibitor Socs2 were both increased throughout early pancreatic growth. Moreover, immunohistochemistry showed a CCK-dependent and acinar cell-specific increase in nuclear localization of p-STAT3, with >75% nuclear occupancy in PI-fed mice vs. <0.1% in controls. Thus, the study identified novel genes likely to be important for CCK-driven pancreatic growth, characterized and biologically validated the dynamic pattern of their expression and investigated STAT-Socs signaling as a new player in this trophic response.

Physical inactivity as a policy problem: applying a concept from policy analysis to a public health issue.

PubMed

Rütten, Alfred; Abu-Omar, Karim; Gelius, Peter; Schow, Diana

2013-03-07

Despite the recent rapid development of policies to counteract physical inactivity (PI), only a small number of systematic analyses on the evolution of these policies exists. In this article we analyze how PI, as a public health issue, "translates" into a policy-making issue. First, we discuss why PI has become an increasingly important public health issue during the last two decades. We then follow Guy Peters and conceptualize PI as a "policy problem" that has the potential to be linked to policy instruments and policy impact. Analysis indicates that PI is a policy problem that i) is chronic in nature; ii) involves a high degree of political complexity; iii) can be disaggregated into smaller scales; iv) is addressed through interventions that can be difficult to "sell" to the public when their benefits are not highly divisible; v) cannot be solved by government spending alone; vi) must be addressed through a broad scope of activities; and vii) involves interdependencies among both multiple sectors and levels of government.We conclude that the new perspective on PI proposed in this article might be useful and important for i) describing and mapping policies to counteract PI in different contexts; ii) evaluating whether or not existing policy instruments are appropriate to the policy problem of PI, and iii) explaining the factors and processes that underlie policy development and implementation. More research is warranted in all these areas. In particular, we propose to focus on comparative analyses of how the problem of PI is defined and tackled in different contexts, and on the identification of truly effective policy instruments that are designed to "solve" the PI policy problem.

Development of measurement system for gauge block interferometer

NASA Astrophysics Data System (ADS)

Chomkokard, S.; Jinuntuya, N.; Wongkokua, W.

2017-09-01

We developed a measurement system for collecting and analyzing the fringe pattern images from a gauge block interferometer. The system was based on Raspberry Pi which is an open source system with python programming and opencv image manipulation library. The images were recorded by the Raspberry Pi camera with five-megapixel capacity. The noise of images was suppressed for the best result in analyses. The low noise images were processed to find the edge of fringe patterns using the contour technique for the phase shift analyses. We tested our system with the phase shift patterns between a gauge block and a reference plate. The phase shift patterns were measured by a Twyman-Green type of interferometer using the He-Ne laser with the temperature controlled at 20.0 °C. The results of the measurement will be presented and discussed.

Identification and verification of potential piRNAs from domesticated yak testis.

PubMed

Gong, Jishang; Zhang, Quanwei; Wang, Qi; Ma, Youji; Du, Jiaxiang; Zhang, Yong; Zhao, Xingxu

2018-02-01

PIWI-interacting RNAs (piRNA) are small non-coding RNA molecules expressed in animal germ cells that interact with PIWI family proteins to form RNA-protein complexes involved in epigenetic and post-transcriptional gene silencing of retrotransposons and other genetic elements in germ line cells, including reproductive stem cell self-sustainment, differentiation, meiosis and spermatogenesis. In the present study, we performed high-throughput sequencing of piRNAs in testis samples from yaks in different stages of sexual maturity. Deep sequencing of the small RNAs (18-40 nt in length) yielded 4,900,538 unique reads from a total of 53,035,635 reads. We identified yak small RNAs (18-30 nt) and performed functional characterization. Yak small RNAs showed a bimodal length distribution, with two peaks at 22 nt and >28 nt. More than 80% of the 3,106,033 putative piRNAs were mapped to 4637 piRNA-producing genomic clusters using RPKM. 6388 candidate piRNAs were identified from clean reads and the annotations were compared with the yak reference genome repeat region. Integrated network analysis suggested that some differentially expressed genes were involved in spermatogenesis through ECM-receptor interaction and PI3K-Akt signaling pathways. Our data provide novel insights into the molecular expression and regulation similarities and diversities in spermatogenesis and testicular development in yaks at different stages of sexual maturity. © 2018 The authors.

Identification and verification of potential piRNAs from domesticated yak testis

PubMed Central

Gong, Jishang; Zhang, Quanwei; Wang, Qi; Ma, Youji; Du, Jiaxiang; Zhang, Yong

2018-01-01

PIWI-interacting RNAs (piRNA) are small non-coding RNA molecules expressed in animal germ cells that interact with PIWI family proteins to form RNA–protein complexes involved in epigenetic and post-transcriptional gene silencing of retrotransposons and other genetic elements in germ line cells, including reproductive stem cell self-sustainment, differentiation, meiosis and spermatogenesis. In the present study, we performed high-throughput sequencing of piRNAs in testis samples from yaks in different stages of sexual maturity. Deep sequencing of the small RNAs (18–40 nt in length) yielded 4,900,538 unique reads from a total of 53,035,635 reads. We identified yak small RNAs (18–30 nt) and performed functional characterization. Yak small RNAs showed a bimodal length distribution, with two peaks at 22 nt and >28 nt. More than 80% of the 3,106,033 putative piRNAs were mapped to 4637 piRNA-producing genomic clusters using RPKM. 6388 candidate piRNAs were identified from clean reads and the annotations were compared with the yak reference genome repeat region. Integrated network analysis suggested that some differentially expressed genes were involved in spermatogenesis through ECM–receptor interaction and PI3K-Akt signaling pathways. Our data provide novel insights into the molecular expression and regulation similarities and diversities in spermatogenesis and testicular development in yaks at different stages of sexual maturity. PMID:29101267

Structural features of diverse Pin-II proteinase inhibitor genes from Capsicum annuum.

PubMed

Mahajan, Neha S; Dewangan, Veena; Lomate, Purushottam R; Joshi, Rakesh S; Mishra, Manasi; Gupta, Vidya S; Giri, Ashok P

2015-02-01

The proteinase inhibitor (PI) genes from Capsicum annuum were characterized with respect to their UTR, introns and promoter elements. The occurrence of PIs with circularly permuted domain organization was evident. Several potato inhibitor II (Pin-II) type proteinase inhibitor (PI) genes have been analyzed from Capsicum annuum (L.) with respect to their differential expression during plant defense response. However, complete gene characterization of any of these C. annuum PIs (CanPIs) has not been carried out so far. Complete gene architectures of a previously identified CanPI-7 (Beads-on-string, Type A) and a member of newly isolated Bracelet type B, CanPI-69 are reported in this study. The 5' UTR (untranslated region), 3'UTR, and intronic sequences of both the CanPI genes were obtained. The genomic sequence of CanPI-7 exhibited, exon 1 (49 base pair, bp) and exon 2 (740 bp) interrupted by a 294-bp long type I intron. We noted the occurrence of three multi-domain PIs (CanPI-69, 70, 71) with circularly permuted domain organization. CanPI-69 was found to possess exon 1 (49 bp), exon 2 (551 bp) and a 584-bp long type I intron. The upstream sequence analysis of CanPI-7 and CanPI-69 predicted various transcription factor-binding sites including TATA and CAAT boxes, hormone-responsive elements (ABRELATERD1, DOFCOREZM, ERELEE4), and a defense-responsive element (WRKY71OS). Binding of transcription factors such as zinc finger motif MADS-box and MYB to the promoter regions was confirmed using electrophoretic mobility shift assay followed by mass spectrometric identification. The 3' UTR analysis for 25 CanPI genes revealed unique/distinct 3' UTR sequence for each gene. Structures of three domain CanPIs of type A and B were predicted and further analyzed for their attributes. This investigation of CanPI gene architecture will enable the better understanding of the genetic elements present in CanPIs.

Nanoscale chemical imaging by photoinduced force microscopy

PubMed Central

Nowak, Derek; Morrison, William; Wickramasinghe, H. Kumar; Jahng, Junghoon; Potma, Eric; Wan, Lei; Ruiz, Ricardo; Albrecht, Thomas R.; Schmidt, Kristin; Frommer, Jane; Sanders, Daniel P.; Park, Sung

2016-01-01

Correlating spatial chemical information with the morphology of closely packed nanostructures remains a challenge for the scientific community. For example, supramolecular self-assembly, which provides a powerful and low-cost way to create nanoscale patterns and engineered nanostructures, is not easily interrogated in real space via existing nondestructive techniques based on optics or electrons. A novel scanning probe technique called infrared photoinduced force microscopy (IR PiFM) directly measures the photoinduced polarizability of the sample in the near field by detecting the time-integrated force between the tip and the sample. By imaging at multiple IR wavelengths corresponding to absorption peaks of different chemical species, PiFM has demonstrated the ability to spatially map nm-scale patterns of the individual chemical components of two different types of self-assembled block copolymer films. With chemical-specific nanometer-scale imaging, PiFM provides a powerful new analytical method for deepening our understanding of nanomaterials. PMID:27051870

Evaluation of the utility of a glycemic pattern identification system.

PubMed

Otto, Erik A; Tannan, Vinay

2014-07-01

With the increasing prevalence of systems allowing automated, real-time transmission of blood glucose data there is a need for pattern recognition techniques that can inform of deleterious patterns in glycemic control when people test. We evaluated the utility of pattern identification with a novel pattern identification system named Vigilant™ and compared it to standard pattern identification methods in diabetes. To characterize the importance of an identified pattern we evaluated the relative risk of future hypoglycemic and hyperglycemic events in diurnal periods following identification of a pattern in a data set of 536 patients with diabetes. We evaluated events 2 days, 7 days, 30 days, and 61-90 days from pattern identification, across diabetes types and cohorts of glycemic control, and also compared the system to 6 pattern identification methods consisting of deleterious event counts and percentages over 5-, 14-, and 30-day windows. Episodes of hypoglycemia, hyperglycemia, severe hypoglycemia, and severe hyperglycemia were 120%, 46%, 123%, and 76% more likely after pattern identification, respectively, compared to periods when no pattern was identified. The system was also significantly more predictive of deleterious events than other pattern identification methods evaluated, and was persistently predictive up to 3 months after pattern identification. The system identified patterns that are significantly predictive of deleterious glycemic events, and more so relative to many pattern identification methods used in diabetes management today. Further study will inform how improved pattern identification can lead to improved glycemic control. © 2014 Diabetes Technology Society.

Quantitative studies of the distribution pattern for Salmonella Enteritidis in the internal organs of chicken after oral challenge by a real-time PCR.

PubMed

He, G Z; Tian, W Y; Qian, N; Cheng, A C; Deng, S X

2010-12-01

This research was undertaken to identify and understand the regular distribution pattern for Salmonella Enteritidis (S. enteritidis) in the internal organs of chicken after oral challenge over a 3 wk period. We used a real-time, fluorescence-based quantitative polymerase chain reaction (FQ-PCR) to detect genomic DNA of S. enteritidis in the blood and the internal organs, including heart, liver, spleen, kidney, pancreas, and gallbladder, from chicken after oral challenge at different time points. The results showed that the spleen was positive at 12 h post inoculation (PI), and the blood was at 14 h PI. The organism was detected in the liver and heart at 16 h PI, pancrea was positive at 20 h PI, and the final organ to show a positive results were the kidney and gallbladder at 22 h PI. The copy number of S. enteritidis DNA in each tissue reached a peak at 24 h-36 h PI, with the liver and spleen containing high concentrations of S. enteritidis, whereas the blood, heart, kidney, pancreas, and gallbladder had low concentrations. S. enteritidis populations began to decrease and were not detectable at 3 d PI, but were still present up to 12 d PI in the gallbladder, 2 wk for the liver, and 3 wk for the spleen without causing apparent symptoms. The results showed that the liver and spleen may be the primary sites for S. enteritidis setting itself up as a commensa over a long time after oral challenge. Interestingly, it may be the first time reported that the gallbladder is a site of carriage for S. enteritidis over a 12 d period. This study will help to understand the mechanisms of action of S. enteritidis infection in vivo.

Blocked vs. interleaved presentation and proactive interference in episodic memory.

PubMed

Del Missier, Fabio; Sassano, Alessia; Coni, Valentina; Salomonsson, Martina; Mäntylä, Timo

2018-05-01

Although a number of theoretical accounts of proactive interference (PI) in episodic memory have been proposed, existing empirical evidence does not support conclusively a single view yet. In two experiments we tested the predictions of the temporal discrimination theory of PI against alternative accounts by manipulating the presentation schedule of study materials (lists blocked by category vs. interleaved). In line with the temporal discrimination theory, we observed a clear buildup of (and release from) PI in the blocked condition, in which all the lists of the same category were presented sequentially. In the interleaved condition, with alternating lists of different categories, a more gradual and smoother buildup of PI was observed. When participants were left free to choose their presentation schedule, they spontaneously adopted an interleaved schedule, resulting again in more gradual PI. After longer delays, we observed recency effects at the list level in overall recall and, in the blocked condition, PI-related effects. The overall pattern of findings agrees with the predictions of the temporal discrimination theory of PI, complemented with categorical processing of list items, but not with alternative accounts, shedding light on the dynamics and underpinnings of PI under diverse presentation schedules and over different time scales.

Identification and Validation of Established and Novel Biomarkers for Infections in Burns

DTIC Science & Technology

2015-10-01

W81XWH-15-1-0143 (PI: Branski, Ludwik ) 07/01/15-06/30/19 5% Dept of Defense $384,660 " Growth Hormone Therapy for Muscle Regeneration...recombinant human growth hormone (rhGH) supplementation on body composition, such as lean body mass loss and bone mineral content, and to assess if...of 34 ***New award on 7/1/2015.*** W81XWH-15-1-0143 (PI: Branski, Ludwik ) 07/01/15-06/30/19 1% Dept of Defense $384,660 " Growth Hormone

Analysis of Hydra PIWI proteins and piRNAs uncover early evolutionary origins of the piRNA pathway.

PubMed

Lim, Robyn S M; Anand, Amit; Nishimiya-Fujisawa, Chiemi; Kobayashi, Satoru; Kai, Toshie

2014-02-01

To preserve genome integrity, an evolutionarily conserved small RNA-based silencing mechanism involving PIWI proteins and PIWI-interacting RNAs (piRNAs) represses potentially deleterious transposons in animals. Although there has been extensive research into PIWI proteins in bilaterians, these proteins remain to be examined in ancient phyla. Here, we investigated the PIWI proteins Hywi and Hyli in the cnidarian Hydra, and found that both PIWI proteins are enriched in multipotent stem cells, germline stem cells, and in the female germline. Hywi and Hyli localize to the nuage, a perinuclear organelle that has been implicated in piRNA-mediated transposon silencing, together with other conserved nuage and piRNA pathway components. Our findings provide the first report of nuage protein localization patterns in a non-bilaterian. Hydra PIWI proteins possess symmetrical dimethylarginines: modified residues that are known to aid in PIWI protein localization to the nuage and proper piRNA loading. piRNA profiling suggests that transposons are the major targets of the piRNA pathway in Hydra. Our data suggest that piRNA biogenesis through the ping-pong amplification cycle occurs in Hydra and that Hywi and Hyli are likely to preferentially bind primary and secondary piRNAs, respectively. Presumptive piRNA clusters are unidirectionally transcribed and primarily give rise to piRNAs that are antisense to transposons. These results indicate that various conserved features of PIWI proteins, the piRNA pathway, and their associations with the nuage were likely established before the evolution of bilaterians. Copyright © 2013 Elsevier Inc. All rights reserved.

Vesicle Docking Is a Key Target of Local PI(4,5)P2 Metabolism in the Secretory Pathway of INS-1 Cells.

PubMed

Ji, Chen; Fan, Fan; Lou, Xuelin

2017-08-08

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 ) signaling is transient and spatially confined in live cells. How this pattern of signaling regulates transmitter release and hormone secretion has not been addressed. We devised an optogenetic approach to control PI(4,5)P 2 levels in time and space in insulin-secreting cells. Combining this approach with total internal reflection fluorescence microscopy, we examined individual vesicle-trafficking steps. Unlike long-term PI(4,5)P 2 perturbations, rapid and cell-wide PI(4,5)P 2 reduction in the plasma membrane (PM) strongly inhibits secretion and intracellular Ca 2+ concentration ([Ca 2+ ] i ) responses, but not sytaxin1a clustering. Interestingly, local PI(4,5)P 2 reduction selectively at vesicle docking sites causes remarkable vesicle undocking from the PM without affecting [Ca 2+ ] i . These results highlight a key role of local PI(4,5)P 2 in vesicle tethering and docking, coordinated with its role in priming and fusion. Thus, different spatiotemporal PI(4,5)P 2 signaling regulates distinct steps of vesicle trafficking, and vesicle docking may be a key target of local PI(4,5)P 2 signaling in vivo. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

X(3872) as a hadronic molecule and its decays to charmonium states and pions

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

Dong Yubing; Institute of High Energy Physics, Beijing 100049; Theoretical Physics Center for Science Facilities

2009-05-01

The X(3872) with quantum numbers J{sup PC}=1{sup ++} is considered as a composite hadronic state comprised of the dominant molecular D{sup 0}D*{sup 0} component and other hadronic pairs--D{sup {+-}}D*{sup {+-}}, J/{psi}{omega}, and J/{psi}{rho}. Applying the compositeness condition we constrain the couplings of the X(3872) to its constituents. We calculate two- and three-body hadronic decays of the X(3872) to charmonium states {chi}{sub cJ} and pions using a phenomenological Lagrangian approach. Next using the estimated XJ/{psi}{omega} and XJ/{psi}{rho} couplings we calculate the widths of X(3872){yields}J/{psi}+h transitions, where h={pi}{sup +}{pi}{sup -}, {pi}{sup +}{pi}{sup -}{pi}{sup 0}, {pi}{sup 0}{gamma}, and {gamma}. The obtained results formore » the decay pattern of the X(3872) in a molecular interpretation could be useful for running and planned experiments.« less

Identification of a Potent Phosphoinositide 3-Kinase Pan Inhibitor Displaying a Strategic Carboxylic Acid Group and Development of Its Prodrugs.

PubMed

Pirali, Tracey; Ciraolo, Elisa; Aprile, Silvio; Massarotti, Alberto; Berndt, Alex; Griglio, Alessia; Serafini, Marta; Mercalli, Valentina; Landoni, Clarissa; Campa, Carlo Cosimo; Margaria, Jean Piero; Silva, Rangel L; Grosa, Giorgio; Sorba, Giovanni; Williams, Roger; Hirsch, Emilio; Tron, Gian Cesare

2017-09-21

Activation of the phosphoinositide 3-kinase (PI3K) pathway is a key signaling event in cancer, inflammation, and other proliferative diseases. PI3K inhibitors are already approved for some specific clinical indications, but their systemic on-target toxicity limits their larger use. In particular, whereas toxicity is tolerable in acute treatment of life-threatening diseases, this is less acceptable in chronic conditions. In the past, the strategy to overcome this drawback was to block selected isoforms mainly expressed in leukocytes, but redundancy within the PI3K family members challenges the effectiveness of this approach. On the other hand, decreasing exposure to selected target cells represents a so-far unexplored alternative to circumvent systemic toxicity. In this manuscript, we describe the generation of a library of triazolylquinolones and the development of the first prodrug pan-PI3K inhibitor. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene.

PubMed

Levy-Litan, Varda; Hershkovitz, Eli; Avizov, Luba; Leventhal, Neta; Bercovich, Dani; Chalifa-Caspi, Vered; Manor, Esther; Buriakovsky, Sophia; Hadad, Yair; Goding, James; Parvari, Ruti

2010-02-12

Human disorders of phosphate (Pi) handling and hypophosphatemic rickets have been shown to result from mutations in PHEX, FGF23, and DMP1, presenting as X-linked recessive, autosomal-dominant, and autosomal-recessive patterns, respectively. We present the identification of an inactivating mutation in the ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene causing autosomal-recessive hypophosphatemic rickets (ARHR) with phosphaturia by positional cloning. ENPP1 generates inorganic pyrophosphate (PPi), an essential physiologic inhibitor of calcification, and previously described inactivating mutations in this gene were shown to cause aberrant ectopic calcification disorders, whereas no aberrant calcifications were present in our patients. Our surprising result suggests a different pathway involved in the generation of ARHR and possible additional functions for ENPP1. Copyright (c) 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Comparative evaluation of electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) and high-pH reversed phase (Hp-RP) chromatography in profiling of rat kidney proteome.

PubMed

Hao, Piliang; Ren, Yan; Dutta, Bamaprasad; Sze, Siu Kwan

2013-04-26

ERLIC and high-pH RP (Hp-RP) have been reported to be promising alternatives to strong cation exchange (SCX) in proteome fractionation. Here we compared the performance of ERLIC, concatenated ERLIC and concatenated Hp-RP in proteome profiling. The protein identification is comparable in these three strategies, but significantly more unique peptides are identified by the two concatenation methods, resulting in a significant increase of the average protein sequence coverage. The pooling of fractions from spaced intervals results in more uniform distribution of peptides in each fraction compared with the chromatogram-based pooling of adjacent fractions. ERLIC fractionates peptides according to their pI and GRAVY values. These properties remains but becomes less remarkable in concatenated ERLIC. In contrast, the average pI and GRAVY values of the peptides are comparable in each fraction in concatenated Hp-RP. ERLIC performs the best in identifying peptides with pI>9 among the three strategies, while concatenated Hp-RP is good at identifying peptides with pI<4. These advantages are useful when either basic or acidic peptides/proteins are analytical targets. The power of ERLIC in identification of basic peptides seems to be due to their efficient separation from acidic peptides. This study facilitates the choice of proper fractionation strategies based on specific objectives. For in-depth proteomic analysis of a cell, tissue and plasma, multidimensional liquid chromatography (MDLC) is still necessary to reduce sample complexity for improving analytical dynamic range and proteome coverage. This work conducts a direct comparison of three promising first-dimensional proteome fractionation methods. They are comparable in identifying proteins, but concatenated ERLIC and concatenated Hp-RP identify significantly more unique peptides than ERLIC. ERLIC is good at analyzing basic peptides, while concatenated Hp-RP performs the best in analyzing acidic peptides with pI<4. This will facilitate the choice of the proper peptide fractionation strategy based on a specific need. A combination of different fractionation strategies can be used to increase the sequence coverage and number of protein identification due to the complementary effect between different methods. Copyright © 2013 Elsevier B.V. All rights reserved.

Modelling seasonal variations in presentations at a paediatric emergency department.

PubMed

Takase, Miyuki; Carlin, John

2012-09-01

Overcrowding is a phenomenon commonly observed at emergency departments (EDs) in many hospitals, and negatively impacts patients, healthcare professionals and organisations. Health care organisations are expected to act proactively to cope with a high patient volume by understanding and predicting the patterns of ED presentations. The aim of this study was, therefore, to identify the patterns of patient flow at a paediatric ED in order to assist the management of EDs. Data for ED presentations were collected from the Royal Children's Hospital in Melbourne, Australia, with the time-frame of July 2003 to June 2008. A linear regression analysis with trigonometric functions was used to identify the pattern of patient flow at the ED. The results showed that a logarithm of the daily average ED presentations was increasing exponentially (as explained by 0.004t + 0.00005t2 with t representing time, p<0.001). The model also indicated that there was a yearly oscillation in the frequency of ED presentations, in which lower frequencies were observed in summer and higher frequencies during winter (as explained by -0.046 sin(2(pi)t/12)-0.083 cos(2(pi)t/12), p<0.001). In addition, the variation of the oscillations was increasing over time (as explained by -0.002t*sin(2(pi)t/12)-0.001t*cos(2(pi)t/12), p<0.05). The identified regression model explained a total of 96% of the variance in the pattern of ED presentations. This model can be used to understand the trend of the current patient flow as well as to predict the future flow at the ED. Such an understanding will assist health care managers to prepare resources and environment more effectively to cope with overcrowding.

Stress inducible proteinase inhibitor diversity in Capsicum annuum

PubMed Central

2012-01-01

Background Wound-inducible Pin-II Proteinase inhibitors (PIs) are one of the important plant serine PIs which have been studied extensively for their structural and functional diversity and relevance in plant defense against insect pests. To explore the functional specialization of an array of Capsicum annuum (L.) proteinase inhibitor (CanPIs) genes, we studied their expression, processing and tissue-specific distribution under steady-state and induced conditions. Inductions were performed by subjecting C. annuum leaves to various treatments, namely aphid infestation or mechanical wounding followed by treatment with either oral secretion (OS) of Helicoverpa armigera or water. Results The elicitation treatments regulated the accumulation of CanPIs corresponding to 4-, 3-, and 2-inhibitory repeat domains (IRDs). Fourty seven different CanPI genes composed of 28 unique IRDs were identified in total along with those reported earlier. The CanPI gene pool either from uninduced or induced leaves was dominated by 3-IRD PIs and trypsin inhibitory domains. Also a major contribution by 4-IRD CanPI genes possessing trypsin and chymotrypsin inhibitor domains was specifically revealed in wounded leaves treated with OS. Wounding displayed the highest number of unique CanPIs while wounding with OS treatment resulted in the high accumulation of specifically CanPI-4, -7 and −10. Characterization of the PI protein activity through two dimensional gel electrophoresis revealed tissue and induction specific patterns. Consistent with transcript abundance, wound plus OS or water treated C. annuum leaves exhibited significantly higher PI activity and isoform diversity contributed by 3- and 4-IRD CanPIs. CanPI accumulation and activity was weakly elicited by aphid infestation yet resulted in the higher expression of CanPI-26, -41 and −43. Conclusions Plants can differentially perceive various kinds of insect attacks and respond appropriately through activating plant defenses including regulation of PIs at transcriptional and post-translational levels. Based on the differentially elicited CanPI accumulation patterns, it is intriguing to speculate that generating sequence diversity in the form of multi-IRD PIs is a part of elaborative plant defense strategy to obtain a diverse pool of functional units to confine insect attack. PMID:23153298

Release from proactive interference in rat spatial working memory.

PubMed

Roberts, William A; MacDonald, Hayden; Brown, Lyn; Macpherson, Krista

2017-09-01

A three-phase procedure was used to produce proactive interference (PI) in one trial on an eight-arm radial maze. Rats were forced to enter four arms for reward on an initial interference phase, to then enter the four remaining arms on a target phase, and to then choose among all eight arms on a retention test, with only the arms not visited in the target phase containing reward. Control trials involved only the target phase and the retention test. Lower accuracy was found on PI trials than on control trials, but performance on PI trials significantly exceeded chance, showing some retention of target memories. Changes in temporal and reward variables between the interference, target, and retention test phases showed release from PI, but changes in context and pattern of arm entry did not. It is suggested that the release from PI paradigm can be used to understand spatial memory encoding in rats and other species.

MicroRNA-21 accelerates hepatocyte proliferation in vitro via PI3K/Akt signaling by targeting PTEN

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

Yan-nan, Bai; Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Provincial Clinical College of Fujian Medical University, Fuzhou 350001, Fujian Province; Zhao-yan, Yu

2014-01-17

Highlights: •miRNAs-expression patterns of primary hepatocytes under proliferative status. •miR-21 expression level peaked at 12 h after stimulated by EGF. •miR-21 drive rapid S phase entry of primary hepatocytes. •PI3K/Akt signaling was modulated via targeting PTEN by miR-21. -- Abstract: MicroRNAs (miRNAs) are involved in controlling hepatocyte proliferation during liver regeneration. In this study, we established the miRNAs-expression patterns of primary hepatocytes in vitro under stimulation of epidermal growth factor (EGF), and found that microRNA-21 (miR-21) was appreciably up-regulated and peaked at 12 h. In addition, we further presented evidences indicating that miR-21 promotes primary hepatocyte proliferation through in vitromore » transfecting with miR-21 mimics or inhibitor. We further demonstrated that phosphatidylinositol 3′-OH kinase (PI3K)/Akt signaling was altered accordingly, it is, by targeting phosphatase and tensin homologue deleted on chromosome 10, PI3K/Akt signaling is activated by miR-21 to accelerate hepatocyte rapid S-phase entry and proliferation in vitro.« less

A Survey of Aspartate-Phenylalanine and Glutamate-Phenylalanine Interactions in the Protein Data Bank: Searching for Anion-pi Pairs

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

Philip, Vivek M; Harris, Jason B; Adams, Rachel M

Protein structures are stabilized using noncovalent interactions. In addition to the traditional noncovalent interactions, newer types of interactions are thought to be present in proteins. One such interaction, an anion-{pi} pair, in which the positively charged edge of an aromatic ring interacts with an anion, forming a favorable anion-quadrupole interaction, has been previously proposed [Jackson, M. R., et al. (2007) J. Phys. Chem. B111, 8242-8249]. To study the role of anion-{pi} interactions in stabilizing protein structure, we analyzed pairwise interactions between phenylalanine (Phe) and the anionic amino acids, aspartate (Asp) and glutamate (Glu). Particular emphasis was focused on identification ofmore » Phe-Asp or -Glu pairs separated by less than 7 {angstrom} in the high-resolution, nonredundant Protein Data Bank. Simplifying Phe to benzene and Asp or Glu to formate molecules facilitated in silico analysis of the pairs. Kitaura-Morokuma energy calculations were performed on roughly 19000 benzene-formate pairs and the resulting energies analyzed as a function of distance and angle. Edgewise interactions typically produced strongly stabilizing interaction energies (-2 to -7.3 kcal/mol), while interactions involving the ring face resulted in weakly stabilizing to repulsive interaction energies. The strongest, most stabilizing interactions were identified as preferentially occurring in buried residues. Anion-{pi} pairs are found throughout protein structures, in helices as well as {beta} strands. Numerous pairs also had nearby cation-{pi} interactions as well as potential {pi}-{pi} stacking. While more than 1000 structures did not contain an anion-{pi} pair, the 3134 remaining structures contained approximately 2.6 anion-{pi} pairs per protein, suggesting it is a reasonably common motif that could contribute to the overall structural stability of a protein.« less

Comparison of theoretical proteomes: identification of COGs with conserved and variable pI within the multimodal pI distribution.

PubMed

Nandi, Soumyadeep; Mehra, Nipun; Lynn, Andrew M; Bhattacharya, Alok

2005-09-09

Theoretical proteome analysis, generated by plotting theoretical isoelectric points (pI) against molecular masses of all proteins encoded by the genome show a multimodal distribution for pI. This multimodal distribution is an effect of allowed combinations of the charged amino acids, and not due to evolutionary causes. The variation in this distribution can be correlated to the organisms ecological niche. Contributions to this variation maybe mapped to individual proteins by studying the variation in pI of orthologs across microorganism genomes. The distribution of ortholog pI values showed trimodal distributions for all prokaryotic genomes analyzed, similar to whole proteome plots. Pairwise analysis of pI variation show that a few COGs are conserved within, but most vary between, the acidic and basic regions of the distribution, while molecular mass is more highly conserved. At the level of functional grouping of orthologs, five groups vary significantly from the population of orthologs, which is attributed to either conservation at the level of sequences or a bias for either positively or negatively charged residues contributing to the function. Individual COGs conserved in both the acidic and basic regions of the trimodal distribution are identified, and orthologs that best represent the variation in levels of the acidic and basic regions are listed. The analysis of pI distribution by using orthologs provides a basis for resolution of theoretical proteome comparison at the level of individual proteins. Orthologs identified that significantly vary between the major acidic and basic regions maybe used as representative of the variation of the entire proteome.

Cloning and Expression Analysis of a PISTILLATA Homologous Gene from Pineapple (Ananas comosus L. Merr)

PubMed Central

Lv, Ling-Ling; Duan, Jun; Xie, Jiang-Hui; Liu, Yu-Ge; Wei, Chang-Bin; Liu, Sheng-Hui; Zhang, Jian-Xia; Sun, Guang-Ming

2012-01-01

PISTILLATA (PI)-like genes are crucial regulators of flowering in angiosperms. A homologue of PI, designated as AcPI (Genbank accession number HQ717796), was isolated from pineapple cultivar Comte de Paris by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). The cDNA sequence of AcPI is 907 bp in length and contains an open reading frame of 594 bp, which encodes a protein of 197 amino acids. The molecular weight was 2.29 kDa and the isoelectric point was 9.28. The alignment showed that AcPI had a high identity with CsPIC2 (78.6%), AoPI (77.4%), OrcPI (75.7%) and HPI2 (72.4%). Quantitative real-time polymerase chain reaction (qRT-PCR) analyses in different tissues showed that the expression pattern of AcPI was different from the B-class genes in eudicots. AcPI was expressed in all the tissues investigated. The expression level was very low in fruit stems, bracts, leaves and sepals, high in petals and carpels, and moderate in apical meristems, flesh and stamens. The qRT-PCR analyses in different stages indicated that the expression of AcPI reached the highest level at 40 days after flower inducement, when the multiple fruit and floral organs were forming. It proved the important role of AcPI in floral organs and fruit development. The 35S::AcPI transgenic Arabidopsis plants flowered earlier and had more inflorescences or branches than wild type plants. PMID:22312303

Cloning and expression analysis of a PISTILLATA homologous gene from pineapple (Ananas comosus L. Merr).

PubMed

Lv, Ling-Ling; Duan, Jun; Xie, Jiang-Hui; Liu, Yu-Ge; Wei, Chang-Bin; Liu, Sheng-Hui; Zhang, Jian-Xia; Sun, Guang-Ming

2012-01-01

PISTILLATA (PI)-like genes are crucial regulators of flowering in angiosperms. A homologue of PI, designated as AcPI (Genbank accession number HQ717796), was isolated from pineapple cultivar Comte de Paris by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). The cDNA sequence of AcPI is 907 bp in length and contains an open reading frame of 594 bp, which encodes a protein of 197 amino acids. The molecular weight was 2.29 kDa and the isoelectric point was 9.28. The alignment showed that AcPI had a high identity with CsPIC2 (78.6%), AoPI (77.4%), OrcPI (75.7%) and HPI2 (72.4%). Quantitative real-time polymerase chain reaction (qRT-PCR) analyses in different tissues showed that the expression pattern of AcPI was different from the B-class genes in eudicots. AcPI was expressed in all the tissues investigated. The expression level was very low in fruit stems, bracts, leaves and sepals, high in petals and carpels, and moderate in apical meristems, flesh and stamens. The qRT-PCR analyses in different stages indicated that the expression of AcPI reached the highest level at 40 days after flower inducement, when the multiple fruit and floral organs were forming. It proved the important role of AcPI in floral organs and fruit development. The 35S::AcPI transgenic Arabidopsis plants flowered earlier and had more inflorescences or branches than wild type plants.

Predictive biomarkers of sensitivity to the phosphatidylinositol 3' kinase inhibitor GDC-0941 in breast cancer preclinical models.

PubMed

O'Brien, Carol; Wallin, Jeffrey J; Sampath, Deepak; GuhaThakurta, Debraj; Savage, Heidi; Punnoose, Elizabeth A; Guan, Jane; Berry, Leanne; Prior, Wei Wei; Amler, Lukas C; Belvin, Marcia; Friedman, Lori S; Lackner, Mark R

2010-07-15

The class I phosphatidylinositol 3' kinase (PI3K) plays a major role in proliferation and survival in a wide variety of human cancers. A key factor in successful development of drugs targeting this pathway is likely to be the identification of responsive patient populations with predictive diagnostic biomarkers. This study sought to identify candidate biomarkers of response to the selective PI3K inhibitor GDC-0941. We used a large panel of breast cancer cell lines and in vivo xenograft models to identify candidate predictive biomarkers for a selective inhibitor of class I PI3K that is currently in clinical development. The approach involved pharmacogenomic profiling as well as analysis of gene expression data sets from cells profiled at baseline or after GDC-0941 treatment. We found that models harboring mutations in PIK3CA, amplification of human epidermal growth factor receptor 2, or dual alterations in two pathway components were exquisitely sensitive to the antitumor effects of GDC-0941. We found that several models that do not harbor these alterations also showed sensitivity, suggesting a need for additional diagnostic markers. Gene expression studies identified a collection of genes whose expression was associated with in vitro sensitivity to GDC-0941, and expression of a subset of these genes was found to be intimately linked to signaling through the pathway. Pathway focused biomarkers and the gene expression signature described in this study may have utility in the identification of patients likely to benefit from therapy with a selective PI3K inhibitor. Copyright 2010 AACR.

Low cost audiovisual playback and recording triggered by radio frequency identification using Raspberry Pi.

PubMed

Lendvai, Ádám Z; Akçay, Çağlar; Weiss, Talia; Haussmann, Mark F; Moore, Ignacio T; Bonier, Frances

2015-01-01

Playbacks of visual or audio stimuli to wild animals is a widely used experimental tool in behavioral ecology. In many cases, however, playback experiments are constrained by observer limitations such as the time observers can be present, or the accuracy of observation. These problems are particularly apparent when playbacks are triggered by specific events, such as performing a specific behavior, or are targeted to specific individuals. We developed a low-cost automated playback/recording system, using two field-deployable devices: radio-frequency identification (RFID) readers and Raspberry Pi micro-computers. This system detects a specific passive integrated transponder (PIT) tag attached to an individual, and subsequently plays back the stimuli, or records audio or visual information. To demonstrate the utility of this system and to test one of its possible applications, we tagged female and male tree swallows (Tachycineta bicolor) from two box-nesting populations with PIT tags and carried out playbacks of nestling begging calls every time focal females entered the nestbox over a six-hour period. We show that the RFID-Raspberry Pi system presents a versatile, low-cost, field-deployable system that can be adapted for many audio and visual playback purposes. In addition, the set-up does not require programming knowledge, and it easily customized to many other applications, depending on the research questions. Here, we discuss the possible applications and limitations of the system. The low cost and the small learning curve of the RFID-Raspberry Pi system provides a powerful new tool to field biologists.

Characterization and Functional Analysis of Five MADS-Box B Class Genes Related to Floral Organ Identification in Tagetes erecta.

PubMed

Ai, Ye; Zhang, Chunling; Sun, Yalin; Wang, Weining; He, Yanhong; Bao, Manzhu

2017-01-01

According to the floral organ development ABC model, B class genes specify petal and stamen identification. In order to study the function of B class genes in flower development of Tagetes erecta, five MADS-box B class genes were identified and their expression and putative functions were studied. Sequence comparisons and phylogenetic analyses indicated that there were one PI-like gene-TePI, two euAP3-like genes-TeAP3-1 and TeAP3-2, and two TM6-like genes-TeTM6-1 and TeTM6-2 in T. erecta. Strong expression levels of these genes were detected in stamens of the disk florets, but little or no expression was detected in bracts, receptacles or vegetative organs. Yeast hybrid experiments of the B class proteins showed that TePI protein could form a homodimer and heterodimers with all the other four B class proteins TeAP3-1, TeAP3-2, TeTM6-1 and TeTM6-2. No homodimer or interaction was observed between the euAP3 and TM6 clade members. Over-expression of five B class genes of T. erecta in Nicotiana rotundifolia showed that only the transgenic plants of 35S::TePI showed altered floral morphology compared with the non-transgenic line. This study could contribute to the understanding of the function of B class genes in flower development of T. erecta, and provide a theoretical basis for further research to change floral organ structures and create new materials for plant breeding.

Low cost audiovisual playback and recording triggered by radio frequency identification using Raspberry Pi

PubMed Central

Akçay, Çağlar; Weiss, Talia; Haussmann, Mark F.; Moore, Ignacio T.; Bonier, Frances

2015-01-01

Playbacks of visual or audio stimuli to wild animals is a widely used experimental tool in behavioral ecology. In many cases, however, playback experiments are constrained by observer limitations such as the time observers can be present, or the accuracy of observation. These problems are particularly apparent when playbacks are triggered by specific events, such as performing a specific behavior, or are targeted to specific individuals. We developed a low-cost automated playback/recording system, using two field-deployable devices: radio-frequency identification (RFID) readers and Raspberry Pi micro-computers. This system detects a specific passive integrated transponder (PIT) tag attached to an individual, and subsequently plays back the stimuli, or records audio or visual information. To demonstrate the utility of this system and to test one of its possible applications, we tagged female and male tree swallows (Tachycineta bicolor) from two box-nesting populations with PIT tags and carried out playbacks of nestling begging calls every time focal females entered the nestbox over a six-hour period. We show that the RFID-Raspberry Pi system presents a versatile, low-cost, field-deployable system that can be adapted for many audio and visual playback purposes. In addition, the set-up does not require programming knowledge, and it easily customized to many other applications, depending on the research questions. Here, we discuss the possible applications and limitations of the system. The low cost and the small learning curve of the RFID-Raspberry Pi system provides a powerful new tool to field biologists. PMID:25870771

JAK2-V617F-induced MAPK activity is regulated by PI3K and acts synergistically with PI3K on the proliferation of JAK2-V617F-positive cells

PubMed Central

Wolf, Alexandra; Eulenfeld, René; Gäbler, Karoline; Rolvering, Catherine; Haan, Serge; Behrmann, Iris; Denecke, Bernd; Haan, Claude; Schaper, Fred

2013-01-01

The identification of a constitutively active JAK2 mutant, namely JAK2-V617F, was a milestone in the understanding of Philadelphia chromosome-negative myeloproliferative neoplasms. The JAK2-V617F mutation confers cytokine hypersensitivity, constitutive activation of the JAK-STAT pathway, and cytokine-independent growth. In this study we investigated the mechanism of JAK2-V617F-dependent signaling with a special focus on the activation of the MAPK pathway. We observed JAK2-V617F-dependent deregulated activation of the multi-site docking protein Gab1 as indicated by constitutive, PI3K-dependent membrane localization and tyrosine phosphorylation of Gab1. Furthermore, we demonstrate that PI3K signaling regulates MAPK activation in JAK2-V617F-positve cells. This cross-regulation of the MAPK pathway by PI3K affects JAK2-V617F-specific target gene induction, erythroid colony formation, and regulates proliferation of JAK2-V617F-positive patient cells in a synergistically manner. PMID:24069558

Particle Identification in the NIMROD-ISiS Detector Array

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

Wuenschel, S.; Hagel, K.; May, L. W.

Interest in the influence of the neutron-to-proton (N/Z) ratio on multifragmenting nuclei has demanded an improvement in the capabilities of multi-detector arrays as well as the companion analysis methods. The particle identification method used in the NIMROD-ISiS 4{pi} array is described. Performance of the detectors and the analysis method are presented for the reaction of {sup 86}Kr+{sup 64}Ni at 35 MeV/u.

Pressure-sensitive strain sensor based on a single percolated Ag nanowire layer embedded in colorless polyimide

NASA Astrophysics Data System (ADS)

Lee, Chan-Jae; Jun, Sungwoo; Ju, Byeong-Kwon; Kim, Jong-Woong

2017-06-01

This paper presents the fabrication of an elastomer-free, transparent, pressure-sensitive strain sensor consisting of a specially designed silver nanowire (AgNW) pattern and colorless polyimide (cPI). A percolated AgNW network was patterned with a simple tandem compound circuit, which was then embedded in the surface of the cPI via inverted layer processing. The resulting film-type sensor was highly transparent ( 93.5% transmittance at 550 nm) and mechanically stable (capable of resisting 10000 cycles of bending to a 500 μm radius of curvature). We demonstrated that a thin, transparent, and mechanically stable electrode can be produced using a combination of AgNWs and cPI, and used to produce a system sensitive to pressure-induced bending. The capacitance of the AgNW tandem compound electrode pattern grew via fringing, which increased with the pressure-induced bending applied to the surface of the sensor. The sensitivity was four times higher than that of an elastomeric pressure sensor made with the same design. Finally, we demonstrated a skin-like pressure sensor attached to the inside wrist of a human arm.

MAEWEST Expression in Flower Development of Two Petunia Species

PubMed Central

Segatto, Ana Lúcia A.; Turchetto-Zolet, Andreia Carina; Aizza, Lilian Cristina B.; Monte-Bello, Carolina C.; Dornelas, Marcelo C.; Margis, Rogerio; Freitas, Loreta B.

2013-01-01

Changes in flower morphology may influence the frequency and specificity of animal visitors. In Petunia (Solanaceae), adaptation to different pollinators is one of the factors leading to species diversification within the genus. This study provides evidence that differential expression patterns of MAWEWEST (MAW) homologs in different Petunia species may be associated with adaptive changes in floral morphology. The Petunia × hybrida MAW gene belongs to the WOX (WUSCHEL-related homeobox) transcription factor family and has been identified as a controller of petal fusion during corolla formation. We analyzed the expression patterns of P. inflata and P. axillaris MAW orthologs (PiMAW and PaMAW, respectively) by reverse transcriptase polymerase chain reaction (RT-PCR), reverse transcription–quantitative PCR (qRT-PCR) and in situ hybridization in different tissues and different developmental stages of flowers in both species. The spatial expression patterns of PiMAW and PaMAW were similar in P. inflata and P. axillaris. Nevertheless, PaMAW expression level in P. axillaris was higher during the late bud development stage as compared to PiMAW in P. inflata. This work represents an expansion of petunia developmental research to wild accessions. PMID:23823801

Evidence of the immunomodulatory role of dual PI3K/mTOR inhibitors in transplantation: an experimental study in mice.

PubMed

Vilchez, Valery; Turcios, Lilia; Butterfield, David A; Mitov, Mihail I; Coquillard, Cristin L; Brandon, Ja Anthony; Cornea, Virgilius; Gedaly, Roberto; Marti, Francesc

2017-10-01

The PI3K/mTOR signaling cascade is fundamental in T-cell activation and fate decisions. We showed the distinct regulation of PI3K/mTOR in regulatory and effector T-cells and proposed the potential therapeutic benefit of targeting this pathway to control the balance between effector and regulatory T-cell activities. Substantial adverse effects in long-term clinical usage of rapamycin suggest the use of alternative treatments in restraining effector T-cell function in transplant patients. We hypothesize that dual PI3K/mTOR inhibitors may represent an immunosuppressant alternative. Here we show that dual PI3K/mTOR PI-103 and PKI-587 inhibitors interfered IL-2-dependent responses in T-cells. However, in contrast to the inhibitory effects in non-Treg T-cell proliferation and effector functions, dual inhibitors increased the differentiation, preferential expansion, and suppressor activity of iTregs. Rapamycin, PI-103, and PKI-587 targeted different signaling events and induced different metabolic patterns in primary T-cells. Similar to rapamycin, in vivo administration of PI-103 and PKI-587 controlled effectively the immunological response against allogeneic skin graft. These results characterize specific regulatory mechanisms of dual PI3K/mTOR inhibitors in T-cells and support their potential as a novel therapeutic option in transplantation. © 2017 Steunstichting ESOT.

Functional analysis of the Arabidopsis PHT4 family of intracellular phosphate transporters.

PubMed

Guo, B; Jin, Y; Wussler, C; Blancaflor, E B; Motes, C M; Versaw, W K

2008-01-01

The transport of phosphate (Pi) between subcellular compartments is central to metabolic regulation. Although some of the transporters involved in controlling the intracellular distribution of Pi have been identified in plants, others are predicted from genetic, biochemical and bioinformatics studies. Heterologous expression in yeast, and gene expression and localization in plants were used to characterize all six members of an Arabidopsis thaliana membrane transporter family designated here as PHT4. PHT4 proteins share similarity with SLC17/type I Pi transporters, a diverse group of animal proteins involved in the transport of Pi, organic anions and chloride. All of the PHT4 proteins mediate Pi transport in yeast with high specificity. Bioinformatic analysis and localization of PHT4-GFP fusion proteins indicate that five of the proteins are targeted to the plastid envelope, and the sixth resides in the Golgi apparatus. PHT4 genes are expressed in both roots and leaves, although two of the genes are expressed predominantly in leaves and one mostly in roots. These expression patterns, together with Pi transport activities and subcellular locations, suggest roles for PHT4 proteins in the transport of Pi between the cytosol and chloroplasts, heterotrophic plastids and the Golgi apparatus.

The Relationship between the JobMatchTalent Test and the NEO PI-R: Construct Validation of an Instrument Designed for Recruitment of Personnel

PubMed Central

Garcia, Danilo; Nima, Ali Al; Rappe, Catrin; Rapp Ricciardi, Max; Archer, Trevor

2014-01-01

Background Personality measures in recruitment situations need to (1) cover the Big-Five model of personality and (2) focus on interpersonal requirements of jobs. We investigated the relationship between the JobMatchTalent test and the NEO Personality Inventory-Revised (NEO PI-R). The JobMatchTalent consists of three areas (i.e., Stability Patterns, Action Patterns, and Relation Patterns) divided in 10 main scales providing a deeper picture of the employee (e.g., Work Structure, Tolerance). Method The participants (N = 390) were recruited from the professional network LinkedIn and completed online versions of both instruments. We used correlation analysis to investigate the construct validity of the JobMatchTalent test by identifying significant correlation coefficients no lower than ±.30 (i.e., convergent validity) and those with nonsignificant correlations (i.e., discriminant validity). Regression analyses were used to investigate the variance of the NEO PI-R dimensions that was explained by the JobMatchTalent test. Results Four of the NEO PI-R dimensions showed considerable overlap with the following JobMatchTalent main scales: (1) Work structure and Decision Characteristics, which both are measures of thoughtfulness, planning, and order (i.e., Conscientiousness); (2) Inner drive, Activity, Drive, Acting, and Communication, which represent different aspects of being outgoing and extrovert (i.e., Extraversion); (3) Tolerance and Social interest, which measure a person's interest and ability to create social relations (i.e., Agreeableness); and (4) Stress Index, a measure of emotional stability (i.e., the opposite of Neuroticism). All 5 NEO PI-R dimensions overlapped with the JobMatchTalent sub-scales. Conclusions The study suggests that 4 of the NEO PI-R dimensions are logically categorized along the JobMatchTalent main scales: (1) Order and Thoughtfulness, (2) Energy and Extraversion, (3) Social Adaptation and Interest, and (4) Emotion Control. Hence, it suggests substantial overlap between the instruments, but also that the two instruments cannot be considered as equivalent to assess individual differences in recruitment situations. PMID:24594872

First observation of B(s)(0) --> D(s)(+/-)K(-/+) and measurement of the ratio of branching fractions B(B(s)(0) --> D(s)(+/-)K(-/+)/B(B(s)(0) --> D(s)(+)pi(-)).

PubMed

Aaltonen, T; Adelman, J; Akimoto, T; Albrow, M G; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzurri, P; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Bednar, P; Beecher, D; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Beringer, J; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Calancha, C; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Copic, K; Cordelli, M; Cortiana, G; Cox, D J; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lorenzo, G; Dell'Orso, M; Deluca, C; Demortier, L; Deng, J; Deninno, M; Derwent, P F; di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Elagin, A; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Genser, K; Gerberich, H; Gerdes, D; Gessler, A; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Group, R C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Hays, C; Heck, M; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jayatilaka, B; Jeon, E J; Jha, M K; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Knuteson, B; Ko, B R; Koay, S A; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhr, T; Kulkarni, N P; Kurata, M; Kusakabe, Y; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, E; Lee, H S; Lee, S W; Leone, S; Lewis, J D; Lin, C S; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lovas, L; Lu, R-S; Lucchesi, D; Lueck, J; Luci, C; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzione, A; Merkel, P; Mesropian, C; Miao, T; Miladinovic, N; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moggi, N; Moon, C S; Moore, R; Morello, M J; Morlok, J; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Osterberg, K; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Pueschel, E; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, A; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shalhout, S Z; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shiraishi, S; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Tourneur, S; Tu, Y; Turini, N; Ukegawa, F; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner-Kuhr, J; Wagner, W; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Xie, S; Yagil, A; Yamamoto, K; Yamaoka, J; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zheng, Y; Zucchelli, S

2009-11-06

A combined mass and particle identification fit is used to make the first observation of the decay B(s)(0) --> D(s)(+/-)K(-/+) and measure the branching fraction of B(s)(0) --> D(s)(+/-)K(-/+) relative to B(s)(0) --> D(s)(+)pi(-). This analysis uses 1.2 fb(-1) integrated luminosity of pp collisions at square root(s) = 1.96 TeV collected with the CDF II detector at the Fermilab Tevatron collider. We observe a B(s)(0) --> D(s)(+/-)K(-/+) signal with a statistical significance of 8.1 sigma and measure B(B(s)(0) --> D(s)(+/-)K(-/+) /B(B(s)(0) --> D(s)(+)pi(-) 0.097+/-0.018(stat) +/- 0.009(syst).

Phosphatidylinositol-specific phospholipase C activity in Lactobacillus rhamnosus with capacity to translocate.

PubMed

Rodriguez, A V; Baigorí, M D; Alvarez, S; Castro, G R; Oliver, G

2001-10-16

Phosphatidylinositol-specific phospholipase C (PI-PLC) activity was investigated in 25 different lactic acid bacteria (LAB) strains belonging to the genera Lactobacillus, Weisella, and Enterococcus. PI-PLC activity was detected in 44% of the strains studied in culture medium without carbon source. From the PI-PLC positive strains, Lactobacillus rhamnosus ATCC 7469 was selected for translocation studies. Healthy mice were orally administered with a daily dose of 2.0 x 10(9) of viable L. rhamnosus suspension. Viable bacteria were detected in liver and spleen of mice fed with LAB for 7 days. Bacterial colonies isolated from liver were biochemically characterized, and further subjected to randomly amplified polymorphic DNA. Amplification patterns of five strains displayed identical profiles to L. rhamnosus. PI-PLC activity was determined in the strains recovered from liver.

Not all intestinal traumatic injuries are the same: a comparison of surgically treated blunt vs. penetrating injuries.

PubMed

Adam, Nadir; Sorensen, Victor; Skinner, Ruby

2015-01-01

Traumatic intestinal injuries are less common with blunt compared to penetrating mechanisms of trauma and blunt injuries are often associated with diagnostic delays. The purpose of this study is to evaluate differences in the characteristics and outcomes between blunt and penetrating intestinal injuries to facilitate insight into optimal recognition and management. A retrospective analysis of trauma admissions from January 2009 to June 2011 was performed. Patient demographics, ISS, early shock, injury type, timing to OR, blood loss and transfusions, surgical management, infections, EC fistulas, enteric leaks, LOS and mortality were compared. Demographics - There was 3866 blunt admissions and 966 penetrating admissions to our level II trauma centre (Total n=4832) during this interval. The final study group comprised n=131 patients treated for intestinal injuries. Blunt n=54 (BI) vs. penetrating (PI) n=77. Age was similar between the groups: (BI 34 SD 12 vs. PI 30 SD 12). Comorbid conditions were similar as were ED hypotension and blood transfusions. Blunt mechanisms had higher ISS; BI (20 SD 14) vs. PI (16 SD 12), p=0.08 and organ specific injury scales were higher in blunt injuries. Operative Management - Time to operation was higher in BI: (500 SD 676min vs. PI 110 SD 153min, p=0.01). The use of an open abdomen technique was higher for BI: n=19 (35%) vs. PI: n=5 (6%), p=<0.001, as well as delayed intestinal repair in damage control cases. Outcomes - Anastomotic leaks were more prevalent in BI: n=4 (7%) vs. PI: n=2 (3%), p=0.38. Enteric fistulas were: (BI n=8 (15%), vs. PI n=2 (3%), p=0.02). Surgical site infections and other nosocomial infections were: (BI n=11 (20%) vs. PI n=4 (5%), p=0.02), (BI n=11 (20%) vs. PI n=2 (3%), p=0.002), respectively. Hospital and ICU LOS was: (BI=20 SD 14 vs. PI=11 SD 11, p=0.001), (BI=10 SD 10 vs. PI=5 SD 5, p=0.01) respectively. These differences were reflected in higher hospital charges in BI. Blunt and penetrating intestinal injury patterns have high injury severity. Significant operative delays occurred in the blunt injury group as well as, anastomotic failures, enteric fistulas, nosocomial infections, and higher cost. These features underscore the complexity of blunt injury patterns and warrant vigilant injury recognition to improve outcomes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Potato NPH3/RPT2-Like Protein StNRL1, Targeted by a Phytophthora infestans RXLR Effector, Is a Susceptibility Factor.

PubMed

Yang, Lina; McLellan, Hazel; Naqvi, Shaista; He, Qin; Boevink, Petra C; Armstrong, Miles; Giuliani, Licida M; Zhang, Wei; Tian, Zhendong; Zhan, Jiasui; Gilroy, Eleanor M; Birch, Paul R J

2016-05-01

Plant pathogens deliver effectors to manipulate host processes. We know little about how fungal and oomycete effectors target host proteins to promote susceptibility, yet such knowledge is vital to understand crop disease. We show that either transient expression in Nicotiana benthamiana, or stable transgenic expression in potato (Solanum tuberosum), of the Phytophthora infestans RXLR effector Pi02860 enhances leaf colonization by the pathogen. Expression of Pi02860 also attenuates cell death triggered by the P. infestans microbe-associated molecular pattern INF1, indicating that the effector suppresses pattern-triggered immunity. However, the effector does not attenuate cell death triggered by Cf4/Avr4 coexpression, showing that it does not suppress all cell death activated by cell surface receptors. Pi02860 interacts in yeast two-hybrid assays with potato NPH3/RPT2-LIKE1 (NRL1), a predicted CULLIN3-associated ubiquitin E3 ligase. Interaction of Pi02860 in planta was confirmed by coimmunoprecipitation and bimolecular fluorescence complementation assays. Virus-induced gene silencing of NRL1 in N. benthamiana resulted in reduced P. infestans colonization and accelerated INF1-mediated cell death, indicating that this host protein acts as a negative regulator of immunity. Moreover, whereas NRL1 virus-induced gene silencing had no effect on the ability of the P. infestans effector Avr3a to suppress INF1-mediated cell death, such suppression by Pi02860 was significantly attenuated, indicating that this activity of Pi02860 is mediated by NRL1. Transient overexpression of NRL1 resulted in the suppression of INF1-mediated cell death and enhanced P. infestans leaf colonization, demonstrating that NRL1 acts as a susceptibility factor to promote late blight disease. © 2016 American Society of Plant Biologists. All Rights Reserved.

Application of a global magnetospheric-ionospheric current model for dayside and terminator Pi2 pulsations

NASA Astrophysics Data System (ADS)

Imajo, S.; Yoshikawa, A.; Uozumi, T.; Ohtani, S.; Nakamizo, A.; Chi, P. J.

2017-12-01

Pi2 magnetic oscillations on the dayside are considered to be produced by the ionospheric current that is driven by Pi2-associated electric fields from the high-latitude region, but this idea has not been quantitatively tested. The present study numerically tested the magnetospheric-ionospheric current system for Pi2 consisting of field-aligned currents (FACs) localized in the nightside auroral region, the perpendicular magnetospheric current flowing in the azimuthal direction, and horizontal ionospheric currents driven by the FACs. We calculated the spatial distribution of the ground magnetic field produced by these currents using the Biot-Savart law in a stationary state. The calculated magnetic field reproduced the observational features reported by previous studies; (1) the sense of the H component does not change a wide range of local time sectors at low latitudes; (2) the amplitude of the H component on the dayside is enhanced at the equator; (3) The D component reverses its phase near the dawn and dusk terminators; (4) the meridian of the D-component phase reversal near the dusk terminator is shifted more sunward than that near the dawn terminator; (5) the amplitude of the D component in the morning is larger than that in the early evening. We also derived the global distributions of observed equivalent currents for two Pi2 events. The spatial patterns of dayside equivalent currents were similar to the spatial pattern of numerically derived equivalent currents. The results indicate that the oscillation of the magnetospheric-ionospheric current system is a plausible explanation of Pi2s on the dayside and near the terminator. These results are included in an accepted paper by Imajo et al. [2017JGR, DOI: 10.1002/2017JA024246].

Functional analysis of the Arabidopsis PLDZ2 promoter reveals an evolutionarily conserved low-Pi-responsive transcriptional enhancer element

PubMed Central

Oropeza-Aburto, Araceli; Cruz-Ramírez, Alfredo; Acevedo-Hernández, Gustavo J.; Pérez-Torres, Claudia-Anahí; Caballero-Pérez, Juan; Herrera-Estrella, Luis

2012-01-01

Plants have evolved a plethora of responses to cope with phosphate (Pi) deficiency, including the transcriptional activation of a large set of genes. Among Pi-responsive genes, the expression of the Arabidopsis phospholipase DZ2 (PLDZ2) is activated to participate in the degradation of phospholipids in roots in order to release Pi to support other cellular activities. A deletion analysis was performed to identify the regions determining the strength, tissue-specific expression, and Pi responsiveness of this regulatory region. This study also reports the identification and characterization of a transcriptional enhancer element that is present in the PLDZ2 promoter and able to confer Pi responsiveness to a minimal, inactive 35S promoter. This enhancer also shares the cytokinin and sucrose responsive properties observed for the intact PLDZ2 promoter. The EZ2 element contains two P1BS motifs, each of which is the DNA binding site of transcription factor PHR1. Mutation analysis showed that the P1BS motifs present in EZ2 are necessary but not sufficient for the enhancer function, revealing the importance of adjacent sequences. The structural organization of EZ2 is conserved in the orthologous genes of at least eight families of rosids, suggesting that architectural features such as the distance between the two P1BS motifs are also important for the regulatory properties of this enhancer element. PMID:22210906

Identification of a novel aviadenovirus, designated pigeon adenovirus 2 in domestic pigeons (Columba livia).

PubMed

Teske, L; Rubbenstroth, D; Meixner, M; Liere, K; Bartels, H; Rautenschlein, S

2017-01-02

The young pigeon disease syndrome (YPDS) affects mainly young pigeons of less than one year of age and leads to crop stasis, vomitus, diarrhea, anorexia and occasionally death. This disease is internationally a major health problem because of its seasonal appearance during competitions such as homing pigeon races or exhibitions of ornamental birds. While the etiology of YPDS is still unclear, adenoviruses are frequently discussed as potential causative agents. Electron microscopy of feces from a YPDS outbreak revealed massive shedding of adenovirus-like particles. Whole genome sequencing of this sample identified a novel adenovirus tentatively named pigeon adenovirus 2 (PiAdV-2). Phylogenetic and comparative genome analysis suggest PiAdV-2 to belong to a new species within the genus Aviadenovirus, for which we propose the name Pigeon aviadenovirus B. The PiAdV-2 genome shares 54.9% nucleotide sequence identity with pigeon adenovirus 1 (PiAdV-1). In a screening of further YPDS-affected flocks two variants of PiAdV-2 (variant A and B) were detected which shared 97.6% nucleotide identity of partial polymerase sequences, but only 79.7% nucleotide identity of partial hexon sequences. The distribution of both PiAdV-2 variants was further investigated in fecal samples collected between 2008 and 2015 from healthy or YPDS-affected racing pigeons of different lofts. Independent of their health status, approximately 20% of young and 13% of adult pigeon flocks harbored PiAdV-2 variants. Birds were free of PiAdV-1 or other aviadenoviruses as determined by PCRs targeting the aviadenovirus polymerase or the PiAdV-1 fiber gene, respectively. In conclusion, there is no indication of a correlation between YPDS outbreaks and the presence of PiAdV-2 or other aviadenoviruses, arguing against an causative role in this disease complex. Copyright © 2016 Elsevier B.V. All rights reserved.

Mitis group streptococci express variable pilus islet 2 pili.

PubMed

Zähner, Dorothea; Gandhi, Ashish R; Yi, Hong; Stephens, David S

2011-01-01

Streptococcus oralis, Streptococcus mitis, and Streptococcus sanguinis are members of the Mitis group of streptococci and agents of oral biofilm, dental plaque and infective endocarditis, disease processes that involve bacteria-bacteria and bacteria-host interactions. Their close relative, the human pathogen S. pneumoniae uses pilus-islet 2 (PI-2)-encoded pili to facilitate adhesion to eukaryotic cells. PI-2 pilus-encoding genetic islets were identified in S. oralis, S. mitis, and S. sanguinis, but were absent from other isolates of these species. The PI-2 islets resembled the genetic organization of the PI-2 islet of S. pneumoniae, but differed in the genes encoding the structural pilus proteins PitA and PitB. Two and three variants of pitA (a pseudogene in S. pneumoniae) and pitB, respectively, were identified that showed ≈20% difference in nucleotide as well as corresponding protein sequence. Species-independent combinations of pitA and pitB variants indicated prior intra- and interspecies horizontal gene transfer events. Polyclonal antisera developed against PitA and PitB of S. oralis type strain ATCC35037 revealed that PI-2 pili in oral streptococci were composed of PitA and PitB. Electronmicrographs showed pilus structures radiating >700 nm from the bacterial surface in the wild type strain, but not in an isogenic PI-2 deletion mutant. Anti-PitB-antiserum only reacted with pili containing the same PitB variant, whereas anti-PitA antiserum was cross-reactive with the other PitA variant. Electronic multilocus sequence analysis revealed that all PI-2-encoding oral streptococci were closely-related and cluster with non-PI-2-encoding S. oralis strains. This is the first identification of PI-2 pili in Mitis group oral streptococci. The findings provide a striking example of intra- and interspecies horizontal gene transfer. The PI-2 pilus diversity provides a possible key to link strain-specific bacterial interactions and/or tissue tropisms with pathogenic traits in the Mitis group streptococci.

Cloning, identification and functional characterization of a pi-class glutathione-S-transferase from the freshwater mussel Cristaria plicata.

PubMed

Hu, Baoqing; Deng, Lirong; Wen, Chungen; Yang, Xilan; Pei, Pengzu; Xie, Yanhai; Luo, Shaoqing

2012-01-01

Glutathione-S-transferases (GSTs) are multifunctional phase II detoxification enzymes that catalyze the attachment of electrophilic substrates to glutathione and play an important role in protecting organisms against the toxicity of reactive oxygen species (ROS). The piGST cDNA was cloned and sequenced after rapid amplification of cDNA ends (RACE) from the freshwater mussel Cristaria plicata. The comparison of the deduced amino acid sequences with GSTs from other species showed that the enzymes belonged to the pi-class and the amino acids defining the binding sites of glutathione (G-site) and for xenobiotic substrates (H-site) were highly conserved. The Cp-piGST cDNA is 816 nucleotides (nt) in length and contained a 615 nt open reading frame (ORF) encoding 205 amino acid residues, and has 19 nt of 5' untranslated region (UTR) and a 3' UTR of 182 nt including a tailing signal (AATAAA) and a poly (A) tail. The molecular weight of the predicted piGST is 23.4 kDa, with the calculated PI being 5.2. The mRNA transcript of Cp-piGST could be detected in all the examined tissues with highest expression level in hepatopancreas. The expression level of Cp-piGST in hepatopancreas and gill showed similar trend that were significantly increased after bacterial challenge compared to the control group at 12 h. Furthermore, the recombinant Cp-piGST with high enzyme activity was induced to be expressed as a soluble form by IPTG at 20°C for 8 h, and then was purified by using the native Ni(2+) affinity chromatography. The specific activity of the purified soluble Cp-piGST enzyme into pET30 was 2.396 μmol/min/mg, and which into pET32 was 1.706 μmol/min/mg. The recombinant Cp-piGST had a maximum activity at approximately pH 8.0, and its optimum temperature was 37°C. The recombinant Cp-piGST enzyme activity became lower gradually with the denaturant concentration increasing. Copyright © 2011 Elsevier Ltd. All rights reserved.

Searching for non-transposable targets of planarian nuclear PIWI in pluripotent stem cells and differentiated cells.

PubMed

Kashima, Makoto; Agata, Kiyokazu; Shibata, Norito

2018-06-01

Nuclear PIWIs together with their guide RNAs (piRNAs) epigenetically silence various genes including transposons in many organisms. In planarians, the nuclear piwi family gene, DjpiwiB is specifically transcribed in adult pluripotent stem cells (adult PSC, neoblast), but not in differentiated cells. However, the protein accumulates in the nuclei of both neoblasts and their descendant differentiated cells. Interestingly, PIWI(DjPiwiB)-piRNA complexes are indispensable for the repression of transposable genes at the onset of differentiation from neoblasts. Here, we conducted a comparative transcriptome analysis between control and DjpiwiB(RNAi) animals to identify non-transposable target genes of the DjPiwiB-piRNA complexes. Using bioinformatic analyses and RNAi we demonstrate that DjPiwiB-piRNA complexes are required for the proper expression of Djmcm2 and Djhistone h4 in neoblasts and that DjPiwiB-piRNA complexes regulate the transient expression of Djcalu during neoblast differentiation. Thus, DjPiwiB-piRNA complexes regulate the correct expression patterns during neoblast self-renewal and differentiation. © 2018 Japanese Society of Developmental Biologists.

The proinsulin/insulin (PI/I) ratio is reduced by postprandial targeting therapy in type 2 diabetes mellitus: a small-scale clinical study

PubMed Central

2013-01-01

Background An elevated PI/I ratio is attributable to increased secretory demand on β-cells. However, the effect of postprandial targeting therapy on proinsulin level is unknown. We evaluated the metabolic effect of glinide and sulfonylurea (SU) using the meal tolerance test (MTT). Methods MTT was applied to previously untreated Type 2 Diabetes Mellitus (T2DM) subjects. Twenty-two participants were given a test meal (450 kcal). Plasma glucose and insulin were measured at 0 (fasting), 30, 60, 120, and 180 min. Serum proinsulin and C-peptide immunoreactivity (CPR) were measured at 0 and 120 min. Postprandial profile was assessed at baseline and following 3 months treatment with either mitiglinide or glimepiride. Results Plasma glucose level at 30, 60, 120, and 180 min was significantly improved by mitiglinide. Whereas, glimepiride showed a significant improve plasma glucose at 0, 180 min. Peak IRI shifted from 120 to 30 min by mitiglinide treatment. The pattern of insulin secretion was not changed by glimepiride treatment. Whereas mitiglinide did not affect the PI/I ratio, glimepiride tended to increase the PI/I ratio. Moreover, although mitiglinide did not affect PI/I ratio as a whole, marked reduction was noted in some patients treated by mitiglinide. PI/I ratio was reduced significantly in the responder group. The responder subgroup exhibited less insulin resistance and higher insulinogenic index at baseline than non-responders. Moreover, the triglyceride level of responders was significantly lower than that of non-responders. Conclusions Mitiglinide improved postprandial insulin secretion pattern and thereby suppressed postprandial glucose spike. In T2DM patients with low insulin resistance and low triglyceride, mitiglinide recovered impaired β-cell function from the viewpoint of the PI/I ratio. Trial registration UMIN-CTR: UMIN000010467 PMID:24215809

Comparison of theoretical proteomes: Identification of COGs with conserved and variable pI within the multimodal pI distribution

PubMed Central

Nandi, Soumyadeep; Mehra, Nipun; Lynn, Andrew M; Bhattacharya, Alok

2005-01-01

Background Theoretical proteome analysis, generated by plotting theoretical isoelectric points (pI) against molecular masses of all proteins encoded by the genome show a multimodal distribution for pI. This multimodal distribution is an effect of allowed combinations of the charged amino acids, and not due to evolutionary causes. The variation in this distribution can be correlated to the organisms ecological niche. Contributions to this variation maybe mapped to individual proteins by studying the variation in pI of orthologs across microorganism genomes. Results The distribution of ortholog pI values showed trimodal distributions for all prokaryotic genomes analyzed, similar to whole proteome plots. Pairwise analysis of pI variation show that a few COGs are conserved within, but most vary between, the acidic and basic regions of the distribution, while molecular mass is more highly conserved. At the level of functional grouping of orthologs, five groups vary significantly from the population of orthologs, which is attributed to either conservation at the level of sequences or a bias for either positively or negatively charged residues contributing to the function. Individual COGs conserved in both the acidic and basic regions of the trimodal distribution are identified, and orthologs that best represent the variation in levels of the acidic and basic regions are listed. Conclusion The analysis of pI distribution by using orthologs provides a basis for resolution of theoretical proteome comparison at the level of individual proteins. Orthologs identified that significantly vary between the major acidic and basic regions maybe used as representative of the variation of the entire proteome. PMID:16150155

Altered Expression of OsNLA1 Modulates Pi Accumulation in Rice (Oryza sativa L.) Plants

PubMed Central

Zhong, Sihui; Mahmood, Kashif; Bi, Yong-Mei; Rothstein, Steven J.; Ranathunge, Kosala

2017-01-01

Current agricultural practices rely on heavy use of fertilizers for increased crop productivity. However, the problems associated with heavy fertilizer use, such as high cost and environmental pollution, require the development of crop species with increased nutrient use efficiency. In this study, by using transgenic approaches, we have revealed the critical role of OsNLA1 in phosphate (Pi) accumulation of rice plants. When grown under sufficient Pi and nitrate levels, OsNLA1 knockdown (Osnla1-1, Osnla1-2, and Osnla1-3) lines accumulated higher Pi content in their shoot tissues compared to wild-type, whereas, over-expression lines (OsNLA1-OE1, OsNLA1-OE2, and OsNLA1-OE3) accumulated the least levels of Pi. However, under high Pi levels, knockdown lines accumulated much higher Pi content compared to wild-type and exhibited Pi toxicity symptoms in the leaves. In contrast, the over-expression lines had 50–60% of the Pi content of wild-type and did not show such symptoms. When grown under limiting nitrate levels, OsNLA1 transgenic lines also displayed a similar pattern in Pi accumulation and Pi toxicity symptoms compared to wild-type suggesting an existence of cross-talk between nitrogen (N) and phosphorous (P), which is regulated by OsNLA1. The greater Pi accumulation in knockdown lines was a result of enhanced Pi uptake/permeability of roots compared to the wild-type. The cross-talk between N and P was found to be nitrate specific since the knockdown lines failed to over-accumulate Pi under low (sub-optimal) ammonium level. Moreover, OsNLA1 was also found to interact with OsPHO2, a known regulator of Pi homeostasis, in a Yeast Two-Hybrid (Y2H) assay. Taken together, these results show that OsNLA1 is involved in Pi homeostasis regulating Pi uptake and accumulation in rice plants and may provide an opportunity to enhance P use efficiency by manipulating nitrate supply in the soil. PMID:28626465

Decreased expression of GST pi is correlated with a poor prognosis in human esophageal squamous carcinoma

PubMed Central

2010-01-01

Background Glutathione S-transferase pi (GST pi) is a subgroup of GST family, which provides cellular protection against free radical and carcinogenic compounds due to its detoxifying function. Expression patterns of GST pi have been studied in several carcinomas and its down-regulation was implicated to be involved in malignant transformation in patients with Barrett's esophagus. However, neither the exact role of GST pi in the pathogenesis nor its prognostic impact in squamous esophageal carcinoma is fully characterized. Methods Immunohistochemistry was used to investigate GST pi expression on 153 archival squamous esophageal carcinoma specimens with a GST pi monoclonal antibody. Statistic analyses were performed to explore its association with clinicopathological factors and clinical outcome. Results The GST pi expression was greatly reduced in tissues of esophageal carcinomas compared to adjacent normal tissues and residual benign tissues. Absent of GST pi protein expression in cytoplasm, nuclear and cytoplasm/nucleus was found in 51%, 64.7% and 48% of all the carcinoma cases, respectively. GST pi deficiency in cytoplasm, nucleus and cytoplasm/nucleus was significantly correlated to poor differentiation (p < 0.001, p < 0.001 and p < 0.001, respectively). UICC stage and T stage were found significantly correlated to negative expression of GST pi in cytoplasm (p < 0.001 and p = 0.004, respectively) and cytoplasm/nucleus (p = 0.017 and p = 0.031, respectively). In univariate analysis, absent of GST pi protein expression in cytoplasm, nucleus and cytoplasm/nucleus was significantly associated with a shorter overall survival (p < 0.001, p < 0.001 and p < 0.001, respectively), whereas only GST pi cytoplasmic staining retained an independent prognostic significance (p < 0.001) in multivariate analysis. Conclusions Our results show that GST pi expression is down regulated in the squamous esophageal carcinoma, and that the lack of GST pi expression is associated with poor prognosis. Therefore, deficiency of GST pi protein expression may be an important mechanism involved in the carcinogenesis and progression of the squamous esophageal carcinoma, and the underlying mechanisms leading to decreased GST pi expression deserve further investigation. PMID:20602752

The Novaco Anger Scale-Provocation Inventory (1994 version) in Dutch forensic psychiatric patients.

PubMed

Hornsveld, Ruud H J; Muris, Peter; Kraaimaat, Floris W

2011-12-01

We examined the psychometric properties of the Novaco Anger Scale-Provocation Inventory (NAS-PI, 1994 version) in Dutch violent forensic psychiatric patients and secondary vocational students. A confirmatory factor analysis of the subscale structure of the NAS was carried out, reliability was investigated, and relations were calculated between NAS-PI scores and other measures of personality traits and problem behaviors. The 3-subscale structure of the original NAS could not be confirmed. However, the internal consistency of the NAS and the PI was excellent, and the test-retest reliability of the NAS was good. The validity of the NAS and the PI was supported by a meaningful pattern of correlations with alternative measures of anger and personality traits. Forensic psychiatric outpatients displayed higher NAS scores than secondary vocational students, but inpatients scored even lower than this nonclinical control group. Our preliminary conclusion is that the NAS-PI is a valuable instrument for the assessment of anger in Dutch violent forensic psychiatric patients.

Investigations on effect of laser-induced self-assembled patterning on optical properties of flexible polyimide substrates for solar cell applications

NASA Astrophysics Data System (ADS)

Shukla, Ashish K.; Yadav, Vinayak M.; Kumar, Akash; Palani, I. A.; Manivannan, Anbarasu

2018-01-01

Polyimide (PI) offers promising features such as high strength and excellent thermal stability for flexible solar panels. The flexible solar cell demands maximum absorption of solar insolation through stacked layers to enhance its performance. However, the fluorescence emission (FE) in inactive polyimide substrate hinders the absorption of irradiated solar energy. In this research work, an attempt has been made to generate rippled morphology on PI substrate using laser processing that enhances the absorption and moderates the FE. These changes are confirmed by calculating the Urbach energy (Eu) of the rippled structure, which is found to be 2.5 times that of the pristine substrate. Furthermore, to reduce the FE, tungsten (W) was coated on the rippled structure of the laser-processed PI, and a significant reduction of 70% FE is achieved compared to the FE of unprocessed PI. These enhanced characteristics of PI obtained by laser processing will be highly helpful for improving the overall performance of flexible solar cells.

Bayesian evaluation of clinical diagnostic test characteristics of visual observations and remote monitoring to diagnose bovine respiratory disease in beef calves.

PubMed

White, Brad J; Goehl, Dan R; Amrine, David E; Booker, Calvin; Wildman, Brian; Perrett, Tye

2016-04-01

Accurate diagnosis of bovine respiratory disease (BRD) in beef cattle is a critical facet of therapeutic programs through promotion of prompt treatment of diseased calves in concert with judicious use of antimicrobials. Despite the known inaccuracies, visual observation (VO) of clinical signs is the conventional diagnostic modality for BRD diagnosis. Objective methods of remotely monitoring cattle wellness could improve diagnostic accuracy; however, little information exists describing the accuracy of this method compared to traditional techniques. The objective of this research is to employ Bayesian methodology to elicit diagnostic characteristics of conventional VO compared to remote early disease identification (REDI) to diagnose BRD. Data from previous literature on the accuracy of VO were combined with trial data consisting of direct comparison between VO and REDI for BRD in two populations. No true gold standard diagnostic test exists for BRD; therefore, estimates of diagnostic characteristics of each test were generated using Bayesian latent class analysis. Results indicate a 90.0% probability that the sensitivity of REDI (median 81.3%; 95% probability interval [PI]: 55.5, 95.8) was higher than VO sensitivity (64.5%; PI: 57.9, 70.8). The specificity of REDI (median 92.9%; PI: 88.2, 96.9) was also higher compared to VO (median 69.1%; PI: 66.3, 71.8). The differences in sensitivity and specificity resulted in REDI exhibiting higher positive and negative predictive values in both high (41.3%) and low (2.6%) prevalence situations. This research illustrates the potential of remote cattle monitoring to augment conventional methods of BRD diagnosis resulting in more accurate identification of diseased cattle. Copyright © 2016 Elsevier B.V. All rights reserved.

Preference index supported by motivation tests in Nile tilapia

PubMed Central

2017-01-01

The identification of animal preferences is assumed to provide better rearing environments for the animals in question. Preference tests focus on the frequency of approaches or the time an animal spends in proximity to each item of the investigated resource during a multiple-choice trial. Recently, a preference index (PI) was proposed to differentiate animal preferences from momentary responses (Sci Rep, 2016, 6:28328, DOI: 10.1038/srep28328). This index also quantifies the degree of preference for each item. Each choice response is also weighted, with the most recent responses weighted more heavily, but the index includes the entire bank of tests, and thus represents a history-based approach. In this study, we compared this PI to motivation tests, which consider how much effort is expended to access a resource. We performed choice tests over 7 consecutive days for 34 Nile tilapia fish that presented with different colored compartments in each test. We first detected the preferred and non-preferred colors of each fish using the PI and then tested their motivation to reach these compartments. We found that fish preferences varied individually, but the results were consistent with the motivation profiles, as individual fish were more motivated (the number of touches made on transparent, hinged doors that prevented access to the resource) to access their preferred items. On average, most of the 34 fish avoided the color yellow and showed less motivation to reach yellow and red colors. The fish also exhibited greater motivation to access blue and green colors (the most preferred colors). These results corroborate the PI as a reliable tool for the identification of animal preferences. We recommend this index to animal keepers and researchers to identify an animal’s preferred conditions. PMID:28426689

Preference index supported by motivation tests in Nile tilapia.

PubMed

Maia, Caroline Marques; Volpato, Gilson Luiz

2017-01-01

The identification of animal preferences is assumed to provide better rearing environments for the animals in question. Preference tests focus on the frequency of approaches or the time an animal spends in proximity to each item of the investigated resource during a multiple-choice trial. Recently, a preference index (PI) was proposed to differentiate animal preferences from momentary responses (Sci Rep, 2016, 6:28328, DOI: 10.1038/srep28328). This index also quantifies the degree of preference for each item. Each choice response is also weighted, with the most recent responses weighted more heavily, but the index includes the entire bank of tests, and thus represents a history-based approach. In this study, we compared this PI to motivation tests, which consider how much effort is expended to access a resource. We performed choice tests over 7 consecutive days for 34 Nile tilapia fish that presented with different colored compartments in each test. We first detected the preferred and non-preferred colors of each fish using the PI and then tested their motivation to reach these compartments. We found that fish preferences varied individually, but the results were consistent with the motivation profiles, as individual fish were more motivated (the number of touches made on transparent, hinged doors that prevented access to the resource) to access their preferred items. On average, most of the 34 fish avoided the color yellow and showed less motivation to reach yellow and red colors. The fish also exhibited greater motivation to access blue and green colors (the most preferred colors). These results corroborate the PI as a reliable tool for the identification of animal preferences. We recommend this index to animal keepers and researchers to identify an animal's preferred conditions.

EF-2DE Analysis and Protein Identification

USDA-ARS?s Scientific Manuscript database

Isoelectric focusing followed by SDS-PAGE (IEF-2DE) separates proteins in a two-dimensional matrix of protein pI (Protein Isoelectric Point) and molecular weight (MW). The technique is particularly useful to distinguish protein isoforms (Radwan et al., 2012) and proteins that contain post-translatio...

Identification and characterization of the zebrafish glutathione S-transferase Pi-1.

PubMed

Abunnaja, Maryam S; Kurogi, Katsuhisa; Mohammed, Yasir I; Sakakibara, Yoichi; Suiko, Masahito; Hassoun, Ezdihar A; Liu, Ming-Cheh

2017-10-01

Zebrafish has in recent years emerged as a popular vertebrate model for use in pharmacological and toxicological studies. While there have been sporadic studies on the zebrafish glutathione S-transferases (GSTs), the zebrafish GST gene superfamily still awaits to be fully elucidated. We report here the identification of 15 zebrafish cytosolic GST genes in NCBI GenBank database and the expression, purification, and enzymatic characterization of the zebrafish cytosolic GST Pi-1 (GSTP1). The cDNA encoding the zebrafish GSTP1 was cloned from a 3-month-old female zebrafish, expressed in Eschelichia coli host cells, and purified. Purified GSTP1 displayed glutathione-conjugating activity toward 1-chloro-2,4-dinitrobenzene as a representative substrate. The enzymatic characteristics of the zebrafish GSTP1, including pH-dependency, effects of metal cations, and kinetic parameters, were studied. Moreover, the expression of zebrafish GSTP1 at different developmental stages during embryogenesis, throughout larval development, onto maturity was examined. © 2017 Wiley Periodicals, Inc.

"Plasmo2D": an ancillary proteomic tool to aid identification of proteins from Plasmodium falciparum.

PubMed

Khachane, Amit; Kumar, Ranjit; Jain, Sanyam; Jain, Samta; Banumathy, Gowrishankar; Singh, Varsha; Nagpal, Saurabh; Tatu, Utpal

2005-01-01

Bioinformatics tools to aid gene and protein sequence analysis have become an integral part of biology in the post-genomic era. Release of the Plasmodium falciparum genome sequence has allowed biologists to define the gene and the predicted protein content as well as their sequences in the parasite. Using pI and molecular weight as characteristics unique to each protein, we have developed a bioinformatics tool to aid identification of proteins from Plasmodium falciparum. The tool makes use of a Virtual 2-DE generated by plotting all of the proteins from the Plasmodium database on a pI versus molecular weight scale. Proteins are identified by comparing the position of migration of desired protein spots from an experimental 2-DE and that on a virtual 2-DE. The procedure has been automated in the form of user-friendly software called "Plasmo2D". The tool can be downloaded from http://144.16.89.25/Plasmo2D.zip.

Oncogenic NOTCH1 control of MYC and PI3K: challenges and opportunities for anti-NOTCH1 therapy in T-ALL

PubMed Central

Palomero, Teresa; Ferrando, Adolfo

2008-01-01

The identification of activating mutations in NOTCH1 in the majority of T-cell acute lymphoblastic leukemias and lymphomas (T-ALL) has brought much interest in inhibiting NOTCH1 signaling as therapeutic target in this disease. Small molecule inhibitors of the γ-secretase complex, which mediates a critical proteolytic cleavage required for NOTCH1 activation, hold the promise of becoming an effective molecular therapy against relapsed and refractory T-ALL. Recent progress in the elucidation of the transcriptional regulatory networks downstream of oncogenic NOTCH1 has uncovered a central role of NOTCH1 signaling in promoting leukemic cell growth and revealed an intricate circuitry that connects NOTCH1 signaling with MYC and the PI3K-AKT signaling pathway. The identification of the downstream effector pathways controlled by NOTCH1 should pave the way for the rational design of anti-NOTCH1 therapies for the treatment of T-ALL. PMID:18765521

Impacts of strigolactone on shoot branching under phosphate starvation in chrysanthemum (Dendranthema grandiflorum cv. Jinba)

PubMed Central

Xi, Lin; Wen, Chao; Fang, Shuang; Chen, Xiaoli; Nie, Jing; Chu, JinFang; Yuan, Cunquan; Yan, Cunyu; Ma, Nan; Zhao, Liangjun

2015-01-01

Chrysanthemum (Dendranthema grandiflorum cv. Jinba) shoot branching is determined by bud outgrowth during the vegetative growth stage. The degree of axillary bud outgrowth is highly influenced by environmental conditions, such as nutrient availability. Here, we demonstrated that phosphorus (Pi) starvation significantly reduces axillary bud outgrowth in chrysanthemum. A strigolactone (SL) biosynthesis gene, DgCCD7, was isolated and characterized as an ortholog of MAX3/DAD3/RMS5/D17. By using ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS), three putative SLs were identified and levels of all three SLs showed strong increase under Pi starvation conditions. Determinations of the distribution of SLs and regulation of DgCCD7/8 in response to Pi changes in root indicate that SL acts systemically. However, temporal expression patterns of biosynthesis and signaling genes in nodes revealed that Pi starvation causes a local response of SL pathway. Treatment of node segments with or without auxin and Pi revealed that in the absence of exogenous auxin, Pi delayed axillary buds outgrowth and up-regulated local SL pathway genes. These data indicated that an auxin-SL regulatory loop responded to Pi starvation for delaying bud outgrowth locally, root biosynthesized SLs were transported acropetally and functioned in shoot branching inhibition under Pi starvation. We proposed that SLs contributed to chrysanthemum shoot branching control in response to Pi-limiting conditions in a systemic way. PMID:26442011

Age differences in behavioral and neural correlates of proactive interference: Disentangling the role of overall working memory performance.

PubMed

Loosli, Sandra V; Rahm, Benjamin; Unterrainer, Josef M; Mader, Irina; Weiller, Cornelius; Kaller, Christoph P

2016-02-15

Reliable performance in working memory (WM) critically depends on the ability to resist proactive interference (PI) from previously relevant WM contents. Both WM performance and PI susceptibility are subject to cognitive decline at older adult age. However, the behavioral and neural processes underlying these co-evolving developmental changes and their potential interdependencies are not yet understood. Here, we investigated PI using a recent-probes WM paradigm and functional MRI in a cross-sectional sample of younger (n=18, 10 female, 23.4 ± 2.7 years) and older adults (n=18, 10 female, 70.2 ± 2.7 years). As expected, older adults showed lower WM performance and higher PI susceptibility than younger adults. Resolution of PI activated a mainly bilateral frontal network across all participants. Significant interactions with age indicated reduced neural activation in older adults for PI resolution. A second analysis in a selection of younger and older adults (n=12 each) with matched WM performance also revealed significant differences in PI between both age groups and - on a descriptive level - again a hypo-activation of the older adults' PI network. But the differential effect of age on the neural PI effects did not reach significance in this smaller sample most likely to the reduced statistical power. However, given the highly similar patterns in both the overall and the WM-matched samples, we propose that the hypo-activation of the PI network in the older adults may not be attributable to age-related differences in overall WM performance, hence suggesting that higher PI susceptibility in older adult age does not directly depend on their lower WM performance. Copyright © 2015 Elsevier Inc. All rights reserved.

Selective Loss of Cysteine Residues and Disulphide Bonds in a Potato Proteinase Inhibitor II Family

PubMed Central

Li, Xiu-Qing; Zhang, Tieling; Donnelly, Danielle

2011-01-01

Disulphide bonds between cysteine residues in proteins play a key role in protein folding, stability, and function. Loss of a disulphide bond is often associated with functional differentiation of the protein. The evolution of disulphide bonds is still actively debated; analysis of naturally occurring variants can promote understanding of the protein evolutionary process. One of the disulphide bond-containing protein families is the potato proteinase inhibitor II (PI-II, or Pin2, for short) superfamily, which is found in most solanaceous plants and participates in plant development, stress response, and defence. Each PI-II domain contains eight cysteine residues (8C), and two similar PI-II domains form a functional protein that has eight disulphide bonds and two non-identical reaction centres. It is still unclear which patterns and processes affect cysteine residue loss in PI-II. Through cDNA sequencing and data mining, we found six natural variants missing cysteine residues involved in one or two disulphide bonds at the first reaction centre. We named these variants Pi7C and Pi6C for the proteins missing one or two pairs of cysteine residues, respectively. This PI-II-7C/6C family was found exclusively in potato. The missing cysteine residues were in bonding pairs but distant from one another at the nucleotide/protein sequence level. The non-synonymous/synonymous substitution (Ka/Ks) ratio analysis suggested a positive evolutionary gene selection for Pi6C and various Pi7C. The selective deletion of the first reaction centre cysteine residues that are structure-level-paired but sequence-level-distant in PI-II illustrates the flexibility of PI-II domains and suggests the functionality of their transient gene versions during evolution. PMID:21494600

Production of polyimide ceria nanocomposites by development of molecular hook technology in nano-sonochemistry.

PubMed

Hatami, Mehdi

2018-06-01

Poly(amic acid), the precursor of polyimide (PI), was used for the preparation of PI/CeO 2 nanocomposites (NC)s by ultrasonic assisted technique via insertion of the surface modified CeO 2 nanoparticles (NP)s into PI matrix. In the preparation stages, in the first, the modifications of CeO 2 NPs by using hexadecyltrimethoxysilane (HDTMS) as a binder were targeted using ultrasonic waves. In the second step, newly designed PI structure was formed from the sonochemical imidization process as a molecular hook. In this step two different reactions were occurred. The acetic acid elimination reaction in the main chain of macromolecule, and the acetylation reaction in the side chains of poly(amic acid) were accomplished. By acetylation process the hook structure was created for trapping of the modified nanoparticles. In the final step the preparation of PI NCs were achieved by sonochemical process. The structural and thermal properties of pure PI and PI/CeO 2 NCs were studied by several techniques such as fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray diffraction (XRD), and thermal analyses. FT-IR and 1 H NMR spectra confirmed the success in preparation of PI matrix. The FE-SEM, TEM, and AFM analyses showed the uniform distribution of CeO 2 NPs in PI matrix. The XRD patterns of NCs show the presence of crystalline CeO 2 NPs in amorphous PI matrix. The thermal analysis results reveal that, with increases in the content of CeO 2 NPs in PI matrix, the thermally stability factors of samples were improved. Copyright © 2018 Elsevier B.V. All rights reserved.

Reduced interstitial cells of Cajal and increased intraepithelial lymphocytes are associated with development of small intestinal bacterial overgrowth in post-infectious IBS mouse model.

PubMed

Chen, Binrui; Zhu, Shuwen; Du, Lijun; He, Huiqin; Kim, John J; Dai, Ning

2017-10-01

Intestinal dysmotility and immune activation are likely involved in the pathogenesis of small intestinal bacteria overgrowth (SIBO) in irritable bowel syndrome (IBS). We aimed at investigating the role of interstitial cells of Cajal (ICC) and intestinal inflammation in the development of SIBO using a post-infectious IBS (PI-IBS) mouse model. NIH mice were randomly infected with Trichinella spiralis. Visceral sensitivity and stool pattern were assessed at 8-weeks post-infection (PI). Intestinal bacteria counts from jejunum and ileum were measured by quantitative real-time PCR to evaluate the presence of SIBO. ICC density, intraepithelial lymphocytes (IELs) counts, and intestinal cytokine levels (IL1-β, IL-6, toll-like receptor-4 (TLR-4), IL-10) in the ileum were examined. PI-IBS mice demonstrated increased visceral sensitivity compared with the control group. One-third of the PI-IBS mice developed SIBO (SIBO+/PI-IBS) and was more likely to have abnormal stool form compared with SIBO negative PI-IBS (SIBO-/PI-IBS) mice but without difference in visceral sensitivity. SIBO+/PI-IBS mice had decreased ICC density and increased IELs counts in the ileum compared with SIBO-/PI-IBS mice. No difference in inflammatory cytokine expression levels were detected among the groups except for increased TLR-4 in PI-IBS mice compared with the control group. Development of SIBO in PI-IBS mice was associated with reduced ICC density and increased IELs counts in the ileum. Our findings support the role of intestinal dysmotility and inflammation in the pathogenesis of SIBO in IBS and may provide potential therapeutic targets.

A Conserved Two-Component Signal Transduction System Controls the Response to Phosphate Starvation in Bifidobacterium breve UCC2003

PubMed Central

Alvarez-Martin, Pablo; Fernández, Matilde; O'Connell-Motherway, Mary; O'Connell, Kerry Joan; Sauvageot, Nicolas; Fitzgerald, Gerald F.; MacSharry, John; Zomer, Aldert

2012-01-01

This work reports on the identification and molecular characterization of the two-component regulatory system (2CRS) PhoRP, which controls the response to inorganic phosphate (Pi) starvation in Bifidobacterium breve UCC2003. The response regulator PhoP was shown to bind to the promoter region of pstSCAB, specifying a predicted Pi transporter system, as well as that of phoU, which encodes a putative Pi-responsive regulatory protein. This interaction is assumed to cause transcriptional modulation under conditions of Pi limitation. Our data suggest that the phoRP genes are subject to positive autoregulation and, together with pstSCAB and presumably phoU, represent the complete regulon controlled by the phoRP-encoded 2CRS in B. breve UCC2003. Determination of the minimal PhoP binding region combined with bioinformatic analysis revealed the probable recognition sequence of PhoP, designated here as the PHO box, which together with phoRP is conserved among many high-GC-content Gram-positive bacteria. The importance of the phoRP 2CRS in the response of B. breve to Pi starvation conditions was confirmed by analysis of a B. breve phoP insertion mutant which exhibited decreased growth under phosphate-limiting conditions compared to its parent strain UCC2003. PMID:22635988

The effect of parental involvement laws on teen birth control use.

PubMed

Sabia, Joseph J; Anderson, D Mark

2016-01-01

In Volume 32, Issue 5 of this journal, Colman, Dee, and Joyce (CDJ) used data from the National Youth Risk Behavior Surveys (NYRBS) and found that parental involvement (PI) laws had no effect on the probability that minors abstain from sex or use contraception. We re-examine this question, augmenting the NYRBS with data from the State Youth Risk Behavior Surveys (SYRBS), and use a variety of identification strategies to control for state-level time-varying unmeasured heterogeneity. Consistent with CDJ, we find that PI laws have no effect on minor teen females' abstinence decisions. However, when we exploit additional state policy variation unavailable to CDJ and use non-minor teens as a within-state control group, we find evidence to suggest that PI laws are associated with an increase in the probability that sexually active minor teen females use birth control. Copyright © 2015 Elsevier B.V. All rights reserved.

Distinguishing between demoralization and specific personality traits in clinical assessment with the NEO-PI-R.

PubMed

Noordhof, Arjen; Sellbom, Martin; Eigenhuis, Annemarie; Kamphuis, Jan H

2015-06-01

Demoralization, a nonspecific unpleasant state that is common in clinical practice, has been identified as a potential source of nonspecificity in the assessment of personality and psychopathology. The aim of this research was to distinguish between Demoralization and specific personality traits in a widely used measure of personality: the Neuroticism-Extraversion-Openness Personality Inventory-Revised (NEO-PI-R). NEO-PI-R and Minnesota Multiphasic Personality Inventory-2 questionnaires were completed by 278 patients of a specialized clinic for personality disorders in The Netherlands. Furthermore, a replication sample was used consisting of 405 patients from the same institution who completed NEO-PI-R questionnaires, as well. A measure of Demoralization was derived (NEOdem, a NEO-PI-R-based Demoralization scale) using factor analytic techniques. Results indicated that the Demoralization Scale scores were reliable and showed expected patterns of convergence and divergence with conceptually relevant Minnesota Multiphasic Personality Inventory-2-RF scales. When items contributing to Demoralization-related variance were removed from the NEO-PI-R scales, increased specificity was notable with regard to external correlates. These results provide supportive evidence for the validity and heuristic potential of distinguishing between Demoralization and specific personality traits within the NEO-PI-R. (c) 2015 APA, all rights reserved).

Fabrication of polyimide based microfluidic channels for biosensor devices

NASA Astrophysics Data System (ADS)

Zulfiqar, Azeem; Pfreundt, Andrea; Svendsen, Winnie Edith; Dimaki, Maria

2015-03-01

The ever-increasing complexity of the fabrication process of Point-of-care (POC) devices, due to high demand of functional versatility, compact size and ease-of-use, emphasizes the need of multifunctional materials that can be used to simplify this process. Polymers, currently in use for the fabrication of the often needed microfluidic channels, have limitations in terms of their physicochemical properties. Therefore, the use of a multipurpose biocompatible material with better resistance to the chemical, thermal and electrical environment, along with capability of forming closed channel microfluidics is inevitable. This paper demonstrates a novel technique of fabricating microfluidic devices using polyimide (PI) which fulfills the aforementioned properties criteria. A fabrication process to pattern microfluidic channels, using partially cured PI, has been developed by using a dry etching method. The etching parameters are optimized and compared to those used for fully cured PI. Moreover, the formation of closed microfluidic channel on wafer level by bonding two partially cured PI layers or a partially cured PI to glass with high bond strength has been demonstrated. The reproducibility in uniformity of PI is also compared to the most commonly used SU8 polymer, which is a near UV sensitive epoxy resin. The potential applications of PI processing are POC and biosensor devices integrated with microelectronics.

Global expression pattern comparison between low phosphorus insensitive 4 and WT Arabidopsis reveals an important role of reactive oxygen species and jasmonic acid in the root tip response to phosphate starvation

PubMed Central

Chacón-López, Alejandra; Ibarra-Laclette, Enrique; Sánchez-Calderón, Lenin; Gutiérrez-Alanís, Dolores

2011-01-01

Plants are exposed to several biotic and abiotic stresses. A common environmental stress that plants have to face both in natural and agricultural ecosystems that impacts both its growth and development is low phosphate (Pi) availability. There has been an important progress in the knowledge of the molecular mechanisms by which plants cope with Pi deficiency. However, the mechanisms that mediate alterations in the architecture of the Arabidopsis root system responses to Pi starvation are still largely unknown. One of the most conspicuous developmental effects of low Pi on the Arabidopsis root system is the inhibition of primary root growth that is accompanied by loss of root meristematic activity. To identify signalling pathways potentially involved in the Arabidpsis root meristem response to Pi-deprivation, here we report the global gene expression analysis of the root tip of wild type and low phosphorus insensitive4 (lpi4) mutant grown under Pi limiting conditions. Differential gene expression analysis and physiological experiments show that changes in the redox status, probably mediated by jasmonic acid and ethylene, play an important role in the primary root meristem exhaustion process triggered by Pi-starvation. PMID:21368582

Construction of an 800-kb contig in the near-centromeric region of the rice blast resistance gene Pi-ta2 using a highly representative rice BAC library.

PubMed

Nakamura, S; Asakawa, S; Ohmido, N; Fukui, K; Shimizu, N; Kawasaki, S

1997-05-01

We constructed a rice Bacterial Artificial Chromosome (BAC) library from green leaf protoplasts of the cultivar Shimokita harboring the rice blast resistance gene Pi-ta. The average insert size of 155 kb and the library size of seven genome equivalents make it one of the most comprehensive BAC libraries available, and larger than many plant YAC libraries. The library clones were plated on seven high density membranes of microplate size, enabling efficient colony identification in colony hybridization experiments. Seven percent of clones carried chloroplast DNA. By probing with markers close to the blast resistance genes Pi-ta2(closely linked to Pi-ta) and Pi-b, respectively located in the centromeric region of chromosome 12 and near the telomeric end of chromosome 2, on average 2.2 +/- 1.3 and 8.0 +/- 2.6 BAC clones/marker were isolated. Differences in chromosomal structures may contribute to this wide variation in yield. A contig of about 800 kb, consisting of 19 clones, was constructed in the Pi-ta2 region. This region had a high frequency of repetitive sequences. To circumvent this difficulty, we devised a "two-step walking" method. The contig spanned a 300 kb region between markers located at 0 cM and 0.3 cM from Pi-ta. The ratio of physical to genetic distances (> 1,000 kb/cM) was more than three times larger than the average of rice (300 kb/cM). The low recombination rate and high frequency of repetitive sequences may also be related to the near centromeric character of this region. Fluorescent in situ hybridization (FISH) with a BAC clone from the Pi-b region yielded very clear signals on the long arm of chromosome 2, while a clone from the Pi-ta2 region showed various cross-hybridizing signals near the centromeric regions of all chromosomes.

Physiological control of a rotary blood pump with selectable therapeutic options: control of pulsatility gradient.

PubMed

Arndt, Andreas; Nüsser, Peter; Graichen, Kurt; Müller, Johannes; Lampe, Bernhard

2008-10-01

A control strategy for rotary blood pumps meeting different user-selectable control objectives is proposed: maximum support with the highest feasible flow rate versus medium support with maximum ventricular washout and controlled opening of the aortic valve (AoV). A pulsatility index (PI) is calculated from the pressure difference, which is deduced from the axial thrust measured by the magnetic bearing of the pump. The gradient of PI with respect to pump speed (GPI) is estimated via online system identification. The outer loop of a cascaded controller regulates GPI to a reference value satisfying the selected control objective. The inner loop controls the PI to a reference value set by the outer loop. Adverse pumping states such as suction and regurgitation can be detected on the basis of the GPI estimates and corrected by the controller. A lumped-parameter computer model of the assisted circulation was used to simulate variations of ventricular contractility, pulmonary venous pressure, and aortic pressure. The performance of the outer control loop was demonstrated by transitions between the two control modes. Fast reaction of the inner loop was tested by stepwise reduction of venous return. For maximum support, a low PI was maintained without inducing ventricular collapse. For maximum washout, the pump worked at a high PI in the transition region between the opening and the permanently closed AoV. The cascaded control of GPI and PI is able to meet different control objectives and is worth testing in vitro and in vivo.

Characterization of Novel PI3Kδ Inhibitors as Potential Therapeutics for SLE and Lupus Nephritis in Pre-Clinical Studies

PubMed Central

Haselmayer, Philipp; Camps, Montserrat; Muzerelle, Mathilde; El Bawab, Samer; Waltzinger, Caroline; Bruns, Lisa; Abla, Nada; Polokoff, Mark A.; Jond-Necand, Carole; Gaudet, Marilène; Benoit, Audrey; Bertschy Meier, Dominique; Martin, Catherine; Gretener, Denise; Lombardi, Maria Stella; Grenningloh, Roland; Ladel, Christoph; Petersen, Jørgen Søberg; Gaillard, Pascale; Ji, Hong

2014-01-01

SLE is a complex autoimmune inflammatory disease characterized by pathogenic autoantibody production as a consequence of uncontrolled T–B cell activity and immune-complex deposition in various organs, including kidney, leading to tissue damage and function loss. There is a high unmet need for better treatment options other than corticosteroids and immunosuppressants. Phosphoinositol-3 kinase δ (PI3Kδ) is a promising target in this respect as it is essential in mediating B- and T-cell function in mouse and human. We report the identification of selective PI3Kδ inhibitors that blocked B-, T-, and plasmacytoid dendritic cell activities in human peripheral blood and in primary cell co-cultures (BioMAP®) without detecting signs of undesired toxicity. In an IFNα-accelerated mouse SLE model, our PI3Kδ inhibitors blocked nephritis development, whether administered at the onset of autoantibody appearance or the onset of proteinuria. Disease amelioration correlated with normalized immune cell numbers in the spleen, reduced immune-complex deposition as well as reduced inflammation, fibrosis, and tissue damage in the kidney. Improvements were similar to those achieved with a frequently prescribed drug for lupus nephritis, the potent immunosuppressant mycophenolate mofetil. Finally, we established a pharmacodynamics/pharmacokinetic/efficacy model that revealed that a sustained PI3Kδ inhibition of 50% is sufficient to achieve full efficacy in our disease model. These data demonstrate the therapeutic potential of PI3Kδ inhibitors in SLE and lupus nephritis. PMID:24904582

Characterization of Novel PI3Kδ Inhibitors as Potential Therapeutics for SLE and Lupus Nephritis in Pre-Clinical Studies.

PubMed

Haselmayer, Philipp; Camps, Montserrat; Muzerelle, Mathilde; El Bawab, Samer; Waltzinger, Caroline; Bruns, Lisa; Abla, Nada; Polokoff, Mark A; Jond-Necand, Carole; Gaudet, Marilène; Benoit, Audrey; Bertschy Meier, Dominique; Martin, Catherine; Gretener, Denise; Lombardi, Maria Stella; Grenningloh, Roland; Ladel, Christoph; Petersen, Jørgen Søberg; Gaillard, Pascale; Ji, Hong

2014-01-01

SLE is a complex autoimmune inflammatory disease characterized by pathogenic autoantibody production as a consequence of uncontrolled T-B cell activity and immune-complex deposition in various organs, including kidney, leading to tissue damage and function loss. There is a high unmet need for better treatment options other than corticosteroids and immunosuppressants. Phosphoinositol-3 kinase δ (PI3Kδ) is a promising target in this respect as it is essential in mediating B- and T-cell function in mouse and human. We report the identification of selective PI3Kδ inhibitors that blocked B-, T-, and plasmacytoid dendritic cell activities in human peripheral blood and in primary cell co-cultures (BioMAP(®)) without detecting signs of undesired toxicity. In an IFNα-accelerated mouse SLE model, our PI3Kδ inhibitors blocked nephritis development, whether administered at the onset of autoantibody appearance or the onset of proteinuria. Disease amelioration correlated with normalized immune cell numbers in the spleen, reduced immune-complex deposition as well as reduced inflammation, fibrosis, and tissue damage in the kidney. Improvements were similar to those achieved with a frequently prescribed drug for lupus nephritis, the potent immunosuppressant mycophenolate mofetil. Finally, we established a pharmacodynamics/pharmacokinetic/efficacy model that revealed that a sustained PI3Kδ inhibition of 50% is sufficient to achieve full efficacy in our disease model. These data demonstrate the therapeutic potential of PI3Kδ inhibitors in SLE and lupus nephritis.

Quantifying the impacts of piñon mortality on ecosystem-scale carbon and water cycling: a twinned flux tower approach

NASA Astrophysics Data System (ADS)

Fox, A. M.; Litvak, M. E.; McDowell, N.; Rahn, T.; Ryan, M. G.

2010-12-01

Piñon-juniper (PJ) woodlands, which occupy 24 million ha throughout the Southwest, proved to be extremely vulnerable to an extended drought that began in 1999, leading to an abrupt die-off of 40 to 95% of piñon pine (Pinus edulis) and 2-25% of juniper (Juniperus monosperma) in less than 3 years. Climate predictions for the region suggest such droughts are likely to become more frequent and widespread in the future, extending northwards. Such large-scale change in vegetation has the potential to trigger rapid changes in ecosystem carbon dynamics and the local and regional hydrologic cycle. We are using a twinned ecosystem-scale manipulation study to quantify the transient dynamics of carbon and water flux responses to piñon mortality. A combination of eddy covariance, soil respiration and moisture, sap flow and biomass carbon pool measurements are being made at an undisturbed PJ woodland (control) site and at a manipulation site within 2 miles of the control where all piñon trees greater than 7 cm diameter at breast height within the 4 ha flux footprint were killed in September 2009 using girdling and herbicide injection following 6 months of background measurements. We hypothesis that piñon mortality alters the local scale carbon cycle by shifting a large stock of carbon from productive biomass to detritus, leading to an initial decrease in net primary production and an increase in ecosystem respiration and net carbon flux to the atmosphere. However, reduced competition for water in these water-limited ecosystems and increased light availability may lead to compensatory growth in surviving small piñon, juniper and understory vegetation, offsetting or exceeding the expected reduction in NPP from piñon mortality. Because litter and coarse woody debris are slow to decompose in semiarid environments we hypothesize that the manipulation site will continue to be net carbon sources even after NPP recovers. Our general hypothesis for the local scale water cycle is that piñon mortality will alter the vertical and horizontal pattern of infiltration of precipitation and the sources and patterns of water use by remaining small piñon, juniper, understory vegetation and surface evaporation. Pinon mortality may not significantly alter cumulative ecosystem evaportranspiration, but associated changes in litter, bare soil fraction and replacement vegetation will likely alter seasonal variation in evaporation, transpiration and water-use efficiency. Here we present an initial analysis contrasting ecosystem response to environmental drivers pre- and post-manipulation and between manipulation and control sites, identifying and quantifying the impacts of piñon mortality over naturally occurring inter-annual and inter-site variability.

Specific gene expression signatures induced by the multiple oncogenic alterations that occur within the PTEN/PI3K/AKT pathway in lung cancer.

PubMed

De Marco, Carmela; Laudanna, Carmelo; Rinaldo, Nicola; Oliveira, Duarte Mendes; Ravo, Maria; Weisz, Alessandro; Ceccarelli, Michele; Caira, Elvira; Rizzuto, Antonia; Zoppoli, Pietro; Malanga, Donatella; Viglietto, Giuseppe

2017-01-01

Hyperactivation of the phosphatydil-inositol-3' phosphate kinase (PI3K)/AKT pathway is observed in most NSCLCs, promoting proliferation, migration, invasion and resistance to therapy. AKT can be activated through several mechanisms that include loss of the negative regulator PTEN, activating mutations of the catalytic subunit of PI3K (PIK3CA) and/or mutations of AKT1 itself. However, number and identity of downstream targets of activated PI3K/AKT pathway are poorly defined. To identify the genes that are targets of constitutive PI3K/AKT signalling in lung cancer cells, we performed a comparative transcriptomic analysis of human lung epithelial cells (BEAS-2B) expressing active mutant AKT1 (AKT1-E17K), active mutant PIK3CA (PIK3CA-E545K) or that are silenced for PTEN. We found that, altogether, aberrant PI3K/AKT signalling in lung epithelial cells regulated the expression of 1,960/20,436 genes (9%), though only 30 differentially expressed genes (DEGs) (15 up-regulated, 12 down-regulated and 3 discordant) out of 20,436 that were common among BEAS-AKT1-E17K, BEAS-PIK3CA-E545K and BEAS-shPTEN cells (0.1%). Conversely, DEGs specific for mutant AKT1 were 133 (85 up-regulated; 48 down-regulated), DEGs specific for mutant PIK3CA were 502 (280 up-regulated; 222 down-regulated) and DEGs specific for PTEN loss were 1549 (799 up-regulated, 750 down-regulated). The results obtained from array analysis were confirmed by quantitative RT-PCR on selected up- and down-regulated genes (n = 10). Treatment of BEAS-C cells and the corresponding derivatives with pharmacological inhibitors of AKT (MK2206) or PI3K (LY294002) further validated the significance of our findings. Moreover, mRNA expression of selected DEGs (SGK1, IGFBP3, PEG10, GDF15, PTGES, S100P, respectively) correlated with the activation status of the PI3K/AKT pathway assessed by S473 phosphorylation in NSCLC cell lines (n = 6). Finally, we made use of Ingenuity Pathway Analysis (IPA) to investigate the relevant BioFunctions enriched by the costitutive activation of AKT1-, PI3K- or PTEN-dependent signalling in lung epithelial cells. Expectedly, the analysis of the DEGs common to all three alterations highlighted a group of BioFunctions that included Cell Proliferation of tumor cell lines (14 DEGs), Invasion of cells (10 DEGs) and Migration of tumour cell lines (10 DEGs), with a common core of 5 genes (ATF3, CDKN1A, GDF15, HBEGF and LCN2) that likely represent downstream effectors of the pro-oncogenic activities of PI3K/AKT signalling. Conversely, IPA analysis of exclusive DEGs led to the identification of different downstream effectors that are modulated by mutant AKT1 (TGFBR2, CTSZ, EMP1), mutant PIK3CA (CCND2, CDK2, IGFBP2, TRIB1) and PTEN loss (ASNS, FHL2). These findings not only shed light on the molecular mechanisms that are activated by aberrant signalling through the PI3K/AKT pathway in lung epithelial cells, but also contribute to the identification of previously unrecognised molecules whose regulation takes part in the development of lung cancer.

Physical interventions to manage patients with brain injury: an audit on its use and staff and patient injuries from the techniques.

PubMed

Stubbs, Brendon; Alderman, Nick

2008-08-01

To report the use of physical interventions (PI) used to manage aggressive behaviour in a neurobehavioural unit and any injuries that were sustained to patients and staff during its implementation. A retrospective audit was adopted utilizing a standard accident and incident recording database. Records of PI utilized to manage the aggressive behaviour of 75 adults with acquired brain injury were analysed over the course of one calendar year. In addition duration PI, frequency of use and injuries sustained to staff and patients from its application were investigated. During the 12 month period records were audited, PI was used on 1427 occasions. The majority (90.1%) lasted less than 10 minutes. Injury rates to patients (0.98%) and staff (6.5%) were both considerably lower than those rates reported for other clinical populations. Use of PI with people who have an acquired brain injury is particularly challenging due to complex patterns of physical impairment that can be an outcome of this condition. This study describes how a multidisciplinary approach to the application of PI and the contribution of the physiotherapist in particular can result in comparatively low injury rates.

Functionalization of biomineral reinforcement in crustacean cuticle: Calcite orientation in the partes incisivae of the mandibles of Porcellio scaber and the supralittoral species Tylos europaeus (Oniscidea, Isopoda).

PubMed

Huber, Julia; Griesshaber, Erika; Nindiyasari, Fitriana; Schmahl, Wolfgang W; Ziegler, Andreas

2015-05-01

In arthropods the cuticle forms an exoskeleton with its physical and chemical properties adapted to functions of distinct skeletal elements. The cuticle of the partes incisivae (PI) in mandibles of terrestrial isopods is a composite of chitin-protein fibrils/fibres and minerals. It consists of an unmineralized tip, a middle region with organic fibrils reinforced mainly with amorphous calcium phosphate and a base region mineralized with amorphous calcium carbonate and calcite. In this study we extend our work on the structure and material properties of the incisive cuticle employing electron backscatter diffraction (EBSD), and investigate calcite orientation patterns in the PI of two terrestrial isopod species from different habitats. We trace small-scale differences in texture sharpness and calcite microstructure, and compare calcite organization and orientation patterns in the PI with those in the tergites of the same isopod species. We observe that in the PI calcite orientation, the degree of crystal alignment, and mode of crystalline domain assemblage is highly varied within short length scales. This contrasts to calcite organization in the tergite cuticle, where calcite has only one specific texture pattern. Such a large range in the variation of calcite organization has not been observed in other carbonate biological hard tissues, such as shells and teeth, where one specific texture and microstructure prevails. Thus, the investigated isopod species are able to control crystallization of the amorphous carbonate precursor in a differential way, most probably related to the function of the individual skeletal element and the animals' behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Seasonal variation in the acute effect of particulate air pollution on mortality in the China Air Pollution and Health Effects Study (CAPES)

PubMed Central

Chen, Renjie; Peng, Roger D.; Meng, Xia; Zhou, Zhijun; Chen, Bingheng; Kan, Haidong

2013-01-01

Epidemiological findings concerning the seasonal variation in the acute effect of particulate matter (PM) are inconsistent. We investigated the seasonality in the association between PM with an aerodynamic diameter of less than 10 μm (PM10) and daily mortality in 17 Chinese cities. We fitted the “main” time-series model after adjustment for time-varying confounders using smooth functions with natural splines. We established a “seasonal” model to obtain the season-specific effect estimates of PM10, and a “harmonic” model to show the seasonal pattern that allows PM10 effects to vary smoothly with the day in a year. At the national level, a 10 μg/m3 increase in the two-day moving average concentrations (lag 01) of PM10 was associated with 0.45% [95% posterior interval (PI), 0.15% to 0.76%], 0.17% (95% PI, −0.09% to 0.43%), 0.55% (95% PI, 0.15% to 0.96%) and 0.25% (95%PI, −0.05% to 0.56%) increases in total mortality for winter, spring, summer and fall, respectively. For the smoothly-varying plots of seasonality, we identified a two-peak pattern in winter and summer. The observed seasonal pattern was generally insensitive to model specifications. Our analyses suggest that the acute effect of particulate air pollution could vary by seasons with the largest effect in winter and summer in China. To our knowledge, this is the first multicity study in developing countries to analyze the seasonal variations of PM-related health effects. PMID:23500824

Temporal pattern changes in duodenal protein tyrosine nitration events in response to Eimeria acervulina infection in chickens.

PubMed

Elsasser, Ted H; Miska, Kate; Kahl, Stanislaw; Fetterer, Raymond H; Martínez Ramirez, Alfredo

2018-06-04

Intracellular generation of nitric oxide (NO) and superoxide anion (SOA) can result in the formation of 3'-nitrotyrosine proteins (NTp). Nitrated proteins usually are associated with significant perturbation in protein function, apoptosis, autophagy, and cell death. We undertook the present study to establish the temporal dynamics of NTp generation in cytokeratin-18-positive epithelial cells (ETCs) of broiler chickens in response to infection with Eimeria acervulina. Duodenal tissue was harvested from noninfected (NOI) and infected (INF) broilers on days (d) 1, 3, 6, 7, and 10 postinfection (PI) and fixed, embedded, and sectioned for quantitative image analysis, immunohistochemistry with antibodies specific to NTp and the SOA-generating enzyme xanthine oxidase (XO). The pixel density characteristics for NTp and XO representative of ETCs demonstrated that NTp and XO increased in intestinal villi as early as d1 PI (P < 0.05 vs. NOI). Progressive increases in NTp were evident in ETCs through d6 PI. For XO, increases in cell content increased only through d3. On d6 and d7 PI, high levels of NTp were present in immune infiltrating cells (IIC) where no XO was detected. The increases in ETC NTp occurred in a defined pattern, significant by villus-to-crypt location for day of infection, initiating in the distal villus and progressing down into the crypts. Two NTp patterns were observed for ETCs: a high level associated with ETCs harboring parasites and a low-level increase in ETCs not containing Eimeria but in proximity to such. The data suggest that NTp and XO responses may mediate some of the processes through which ETCs respond to Eimeria to limit the extent of infection by this pathogen.

Identification of a soybean rust resistance gene in PI 567104B

USDA-ARS?s Scientific Manuscript database

Asian soybean rust (SBR), caused by the fungus Phakopsora pachyrhizi Syd. & P. Syd., is one of the most economically important diseases that affect soybean production worldwide. A long-term strategy for minimizing the effects of SBR is the development of genetically resistant cultivars integrated wi...

Identification of a single gene for seed coat impermeability in soybean PI 594619

USDA-ARS?s Scientific Manuscript database

High temperatures during seed fill increase the occurrence of soybeans with impermeable seed coat, which is associated with non-uniform and delayed germination and emergence. This has become an issue in soybean production areas with excessively high-temperature environments. The objectives of the pr...

Root traits of a soybean (Glycinemax) recombinant inbred population segregating for flooding tolerance.

USDA-ARS?s Scientific Manuscript database

Soybeans (Glycine max) are known to be sensitive to flooding stress. Flooding at the reproductive stage can reduce soybean yield by 50%. However, recent screening efforts have resulted in the identification of genotypes differing in susceptibility to flooding. The flooding tolerant genotype PI 40810...

Arabidopsis Type II Phosphatidylinositol 4-Kinase PI4Kγ5 Regulates Auxin Biosynthesis and Leaf Margin Development through Interacting with Membrane-Bound Transcription Factor ANAC078

PubMed Central

Tan, Shu-Tang; Xue, Hong-Wei

2016-01-01

Normal leaf margin development is important for leaf morphogenesis and contributes to diverse leaf shapes in higher plants. We here show the crucial roles of an atypical type II phosphatidylinositol 4-kinase, PI4Kγ5, in Arabidopsis leaf margin development. PI4Kγ5 presents a dynamics expression pattern along with leaf development and a T-DNA mutant lacking PI4Kγ5, pi4kγ5–1, presents serrated leaves, which is resulted from the accelerated cell division and increased auxin concentration at serration tips. Studies revealed that PI4Kγ5 interacts with and phosphorylates a membrane-bound NAC transcription factor, ANAC078. Previous studies demonstrated that membrane-bound transcription factors regulate gene transcription by undergoing proteolytic process to translocate into nucleus, and ANAC078 undergoes proteolysis by cleaving off the transmembrane region and carboxyl terminal. Western blot analysis indeed showed that ANAC078 deleting of carboxyl terminal is significantly reduced in pi4kγ5–1, indicating that PI4Kγ5 is important for the cleavage of ANAC078. This is consistent with the subcellular localization observation showing that fluorescence by GFP-ANAC078 is detected at plasma membrane but not nucleus in pi4kγ5–1 mutant and that expression of ANAC078 deleting of carboxyl terminal, driven by PI4Kγ5 promoter, could rescue the leaf serration defects of pi4kγ5–1. Further analysis showed that ANAC078 suppresses the auxin synthesis by directly binding and regulating the expression of auxin synthesis-related genes. These results indicate that PI4Kγ5 interacts with ANAC078 to negatively regulate auxin synthesis and hence influences cell proliferation and leaf development, providing informative clues for the regulation of in situ auxin synthesis and cell division, as well as the cleavage and functional mechanism of membrane-bound transcription factors. PMID:27529511

Source identification of PM2.5 at a port and an adjacent urban site in a coastal city of China: Impact of ship emissions and port activities.

PubMed

Xu, Lingling; Jiao, Ling; Hong, Zhenyu; Zhang, Yanru; Du, Wenjiao; Wu, Xin; Chen, Yanting; Deng, Junjun; Hong, Youwei; Chen, Jinsheng

2018-09-01

Daily PM 2.5 samples were collected simultaneously at an urban site (UB) and a nearby port-industrial site (PI) on the coast of southeastern China from April 2015 to January 2016. The PM 2.5 mass concentration at the PI (51.9μgm -3 ) was significantly higher than that at the UB. The V concentration at the PI was also significantly higher and well-correlated to the urban value, which suggests that shipping emissions had a significant impact on the PI and, to a lesser extent, on the urban area. A positive matrix factorization (PMF) analysis showed that secondary aerosols were the dominant contribution of PM 2.5 at both sites (36.4% at the PI and 27.2% at the UB), while the contribution of industry and ship emissions identified by V, Mn, and Ba at the PI (26.1%) were double those at the UB. The difference in each source contribution among the trajectory clusters that included significant differences and insignificant differences from the UB to the PI provided insight into the role of local impacts. With regards to the UB, local potential sources play important roles in industry and ship emissions, traffic emissions, fugitive dust, and in their contributions to secondary aerosols. A conditional probability function further revealed that the ship emissions and port activities distributed in the NE, E, and SSE wind sectors were responsible for the source contributions of industry and ship emissions and secondary aerosols at the UB. This study provides an example of investigating the impact of ship emissions and port activities on the surrounding air environment using land-based measurements. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparison between target magnetic resonance imaging (MRI) in-gantry and cognitively directed transperineal or transrectal-guided prostate biopsies for Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 MRI lesions.

PubMed

Yaxley, Anna J; Yaxley, John W; Thangasamy, Isaac A; Ballard, Emma; Pokorny, Morgan R

2017-11-01

To compare the detection rates of prostate cancer (PCa) in men with Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 abnormalities on 3-Tesla multiparametric (mp) magnetic resonance imaging (MRI) using in-bore MRI-guided biopsy compared with cognitively directed transperineal (cTP) biopsy and transrectal ultrasonography (cTRUS) biopsy. This was a retrospective single-centre study of consecutive men attending the private practice clinic of an experienced urologist performing MRI-guided biopsy and an experienced urologist performing cTP and cTRUS biopsy techniques for PI-RADS 3-5 lesions identified on 3-Tesla mpMRI. There were 595 target mpMRI lesions from 482 men with PI-RADS 3-5 regions of interest during 483 episodes of biopsy. The abnormal mpMRI target lesion was biopsied using the MRI-guided method for 298 biopsies, the cTP method for 248 biopsies and the cTRUS method for 49 biopsies. There were no significant differences in PCa detection among the three biopsy methods in PI-RADS 3 (48.9%, 40.0% and 44.4%, respectively), PI-RADS 4 (73.2%, 81.0% and 85.0%, respectively) or PI-RADS 5 (95.2, 92.0% and 95.0%, respectively) lesions, and there was no significant difference in detection of significant PCa among the biopsy methods in PI-RADS 3 (42.2%, 30.0% and 33.3%, respectively), PI-RADS 4 (66.8%, 66.0% and 80.0%, respectively) or PI-RADS 5 (90.5%, 89.8% and 90.0%, respectively) lesions. There were also no differences in PCa or significant PCa detection based on lesion location or size among the methods. We found no significant difference in the ability to detect PCa or significant PCa using targeted MRI-guided, cTP or cTRUS biopsy methods. Identification of an abnormal area on mpMRI appears to be more important in increasing the detection of PCa than the technique used to biopsy an MRI abnormality. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Molecular cloning, characterization, and functional analysis of pigeon (Columba livia) Toll-like receptor 5.

PubMed

Xiong, Dan; Song, Li; Pan, Zhiming; Jiao, Xinan

2018-06-26

Toll-like receptors (TLRs) are pattern recognition receptors that are vital for the recognition of pathogen-associated molecular patterns. TLR5 is responsible for the recognition of bacterial flagellin to induce the NF-κB activation and innate immune responses. In this study, we cloned and identified the TLR5 gene from the King pigeon (Columba livia) designated as PiTLR5. Full-length PiTLR5 cDNA (2583 bp) encoded an 860-amino acid protein containing a signal peptide sequence, 10 leucine-rich repeat domains, a leucine-rich repeat C-terminal domain, a transmembrane domain, and an intracellular Toll-interleukin-1 receptor domain. Pigeon TLR5 mRNA expression was quantified by performing quantitative real-time PCR (qRT-PCR), which showed that PiTLR5 was broadly expressed in all examined tissues, with the highest expression in the liver, peripheral blood mononuclear cells, and spleen. PiTLR5-mediated innate immune responses were measured by determining its effects on NF-κB activation and cytokine expression. The results showed that HEK293T cells transfected with PiTLR5 robustly activated the NF-κB response to flagellin, but not other TLR stimuli, and induced significant upregulation of IL-1β, IL-8, TNF-α, and IFN-γ, indicating that PiTLR5 is a functional TLR5 homolog. Additionally, following flagellin stimulation of pigeon splenic lymphocytes, the levels of TLR5, NF-κB, IL-6, IL-8, CCL5, and IFN-γ mRNA, assessed using qRT-PCR, were significantly upregulated. Besides, TLR5 knockdown resulted in the significantly downregulated expression of NF-κB and related cytokines/chemokines. Triggering pigeon TLR5 contributes to significant upregulation of inflammatory cytokines and chemokines, suggesting that pigeon TLR5 plays an important role in the innate immune responses.

High-performance polyimide nanocomposites with core-shell AgNWs@BN for electronic packagings

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

Zhou, Yongcun; Liu, Feng, E-mail: liufeng@nwpu.edu.cn

2016-08-22

The increasing density of electronic devices underscores the need for efficient thermal management. Silver nanowires (AgNWs), as one-dimensional nanostructures, possess a high aspect ratio and intrinsic thermal conductivity. However, high electrical conductivity of AgNWs limits their application for electronic packaging. We synthesized boron nitride-coated silver nanowires (AgNWs@BN) using a flexible and fast method followed by incorporation into synthetic polyimide (PI) for enhanced thermal conductivity and dielectric properties of nanocomposites. The thinner boron nitride intermediate nanolayer on AgNWs not only alleviated the mismatch between AgNWs and PI but also enhanced their interfacial interaction. Hence, the maximum thermal conductivity of an AgNWs@BN/PImore » composite with a filler loading up to 20% volume was increased to 4.33 W/m K, which is an enhancement by nearly 23.3 times compared with that of the PI matrix. The relative permittivity and dielectric loss were about 9.89 and 0.015 at 1 MHz, respectively. Compared with AgNWs@SiO{sub 2}/PI and Ag@BN/PI composites, boron nitride-coated core-shell structures effectively increased the thermal conductivity and reduced the permittivity of nanocomposites. The relative mechanism was studied and discussed. This study enables the identification of appropriate modifier fillers for polymer matrix nanocomposites.« less

Identification of the Phosphorylated Residues in TveIF5A by Mass Spectrometry

PubMed Central

Quintas-Granados, Laura Itzel; López-Camarillo, César; Armas, Jesús Fandiño; Mendoza Hernandez, Guillermo; Alvarez-Sánchez, María Elizbeth

2013-01-01

The initiation factor eIF5A in Trichomonas vaginalis (TveIF5A) is previously shown to undergo hypusination, phosphorylation and glycosylation. Three different pI isoforms of TveIF5A have been reported. The most acidic isoform (pI 5.2) corresponds to the precursor TveIF5A, whereas the mature TveIF5A appears to be the most basic isoform (pI 5.5). In addition, the intermediary isoform (pI 5.3) is found only under polyamine-depleted conditions and restored with exogenous putrescine. We propose that differences in PI are due to phosphorylation of the TveIF5A isoforms. Here, we have identified phosphorylation sites using mass spectrometry. The mature TveIF5A contains four phosphorylated residues (S3, T55, T78 and T82). Phosphorylation at S3 and T82 is also identified in the intermediary TveIF5A, while no phosphorylated residues are found in the precursor TveIF5A. It has been demonstrated that eIF5A proteins from plants and yeast are phosphorylated by a casein kinase 2 (CK2). Interestingly, a gene encoding a protein highly similar to CK2 (TvCK2) is found in T. vaginalis, which might be involved in the phosphorylation of TveIF5A in T. vaginalis. PMID:24308916

Development of phosphocellulose paper-based screening of inhibitors of lipid kinases: case study with PI3Kβ.

PubMed

Yanamandra, Mahesh; Kole, Labanyamoy; Giri, Archana; Mitra, Sayan

2014-03-15

The phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that regulate the cellular signal transduction pathways involved in cell growth, proliferation, survival, apoptosis, and adhesion. Deregulation of these pathways are common in oncogenesis, and they are known to be altered in other metabolic disorders as well. Despite its huge potential as an attractive target in these diseases, there is an unmet need for the development of a successful inhibitor. Unlike protein kinase inhibitors, screening for lipid kinase inhibitors has been challenging. Here we report, for the first time, the development of a radioactive lipid kinase screening platform using a phosphocellulose plate that involves transfer of radiolabeled [γ-(32)P]ATP to phosphatidylinositol 4,5-phosphate forming phosphatidylinositol 3,4,5-phosphate, captured on the phosphocellulose plate. Enzyme kinetics and inhibitory properties were established in the plate format using standard inhibitors, such as LY294002, TGX-221, and wortmannin, having different potencies toward PI3K isoforms. ATP and lipid apparent Km for both were determined and IC50 values generated that matched the historical data. Here we report the use of a phosphocellulose plate for a lipid kinase assay (PI3Kβ as the target) as an excellent platform for the identification of novel chemical entities in PI3K drug discovery. Copyright © 2013 Elsevier Inc. All rights reserved.

A novel gene, Pi40(t), linked to the DNA markers derived from NBS-LRR motifs confers broad spectrum of blast resistance in rice.

PubMed

Jeung, J U; Kim, B R; Cho, Y C; Han, S S; Moon, H P; Lee, Y T; Jena, K K

2007-11-01

Rice blast disease caused by Magnaporthe grisea is a continuous threat to stable rice production worldwide. In a modernized agricultural system, the development of varieties with broad-spectrum and durable resistance to blast disease is essential for increased rice production and sustainability. In this study, a new gene is identified in the introgression line IR65482-4-136-2-2 that has inherited the resistance gene from an EE genome wild Oryza species, O. australiensis (Acc. 100882). Genetic and molecular analysis localized a major resistance gene, Pi40(t), on the short arm of chromosome 6, where four blast resistance genes (Piz, Piz-5, Piz-t, and Pi9) were also identified, flanked by the markers S2539 and RM3330. Through e-Landing, 14 BAC/PAC clones within the 1.81-Mb equivalent virtual contig were identified on Rice Pseudomolecule3. Highly stringent primer sets designed for 6 NBS-LRR motifs located within PAC clone P0649C11 facilitated high-resolution mapping of the new resistance gene, Pi40(t). Following association analysis and detailed haplotyping approaches, a DNA marker, 9871.T7E2b, was identified to be linked to the Pi40(t) gene at the 70 Kb chromosomal region, and differentiated the Pi40(t) gene from the LTH monogenic differential lines possessing genes Piz, Piz-5, Piz-t, and Pi-9. Pi40(t) was validated using the most virulent isolates of Korea as well as the Philippines, suggesting a broad spectrum for the resistance gene. Marker-assisted selection (MAS) and pathotyping of BC progenies having two japonica cultivar genetic backgrounds further supported the potential of the resistance gene in rice breeding. Our study based on new gene identification strategies provides insight into novel genetic resources for blast resistance as well as future studies on cloning and functional analysis of a blast resistance gene useful for rice improvement.

Identification and Targeting of Upstream Tyrosine Kinases Mediating PI3 Kinase Activation in PTEN Deficient Prostate Cancer

DTIC Science & Technology

2010-06-01

tyrosine phosphorylated proteins, but they were not recognized by an anti-pYxxM motif antibody and were not found in PTEN deficient PC3 PCa cells. LC/MS...p85 binding motif antibody (pYxxM). failed to detect Therefore, we next focused on identification of p85 associated proteins using liquid...LC/MS/MS analysis of the p85 immunoprecipitates using a more sensitive Orbitrap XL mass spectrometer, we also detected GAB1 (Table 1). However, we

Hepatitis C Virus Genotype 1 to 6 Protease Inhibitor Escape Variants: In Vitro Selection, Fitness, and Resistance Patterns in the Context of the Infectious Viral Life Cycle

PubMed Central

Serre, Stéphanie B. N.; Jensen, Sanne B.; Ghanem, Lubna; Humes, Daryl G.; Ramirez, Santseharay; Li, Yi-Ping; Krarup, Henrik; Bukh, Jens

2016-01-01

Hepatitis C virus (HCV) NS3 protease inhibitors (PIs) are important components of novel HCV therapy regimens. Studies of PI resistance initially focused on genotype 1. Therefore, knowledge about the determinants of PI resistance for the highly prevalent genotypes 2 to 6 remains limited. Using Huh7.5 cell culture-infectious HCV recombinants with genotype 1 to 6 NS3 protease, we identified protease positions 54, 155, and 156 as hot spots for the selection of resistance substitutions under treatment with the first licensed PIs, telaprevir and boceprevir. Treatment of a genotype 2 isolate with the newer PIs vaniprevir, faldaprevir, simeprevir, grazoprevir, paritaprevir, and deldeprevir identified positions 156 and 168 as hot spots for resistance; the Y56H substitution emerged for three newer PIs. Substitution selection also depended on the specific recombinant. The substitutions identified conferred cross-resistance to several PIs; however, most substitutions selected under telaprevir or boceprevir treatment conferred less resistance to certain newer PIs. In a single-cycle production assay, across genotypes, PI treatment primarily decreased viral replication, which was rescued by PI resistance substitutions. The substitutions identified resulted in differential effects on viral fitness, depending on the original recombinant and the substitution. Across genotypes, fitness impairment induced by resistance substitutions was due primarily to decreased replication. Most combinations of substitutions that were identified increased resistance or fitness. Combinations of resistance substitutions with fitness-compensating substitutions either rescued replication or compensated for decreased replication by increasing assembly. This comprehensive study provides insight into the selection patterns and effects of PI resistance substitutions for HCV genotypes 1 to 6 in the context of the infectious viral life cycle, which is of interest for clinical and virological HCV research. PMID:27021330

4Pi-SHG imaging of mammalian myofibrillar structures

NASA Astrophysics Data System (ADS)

Vogel, Martin; Hahn, Dorothea; Schürmann, Sebastian; Lang, Marion; Wegner, Frederic v.; Friedrich, Oliver; Engelhardt, Johann; Hell, Stefan W.; Fink, Rainer H.

2006-02-01

Intrinsic Second Harmonic Generation (SHG) signals obtained from the motor protein myosin are of particular interest for 3D-imaging of living muscle cells. In addition, the new and powerful tool of 4Pi microscopy allows to markedly enhance the optical resolution of microscopy as well as the sensitivity for small objects because of the high peak intensities due to the interference pattern created in the focus. In the present study, we report, to our knowledge for the first time, measurements of intrinsic SHG signals under 4Pi conditions of type A. These measurements on mammalian myofibrilar structures are combined with very high resolution 4Pi fluorescence data obtained from the same preparations. We have chosen myofibrillar preparations of isolated mammalian muscle fibers as they (i) possess a regular repetitive pattern of actin and myosin filaments within sarcomers 2 to 3 μm in length, (ii) consist of single myofibrils of small total diameter of approximately 1 μm and (iii) are ideally suited to study the biomedically important process of force generation via calcium regulated motor protein interactions. Myofibrillar preparations were obtained from murine skeletal and heart muscle by using a combined chemical and mechanical fractionation1 (Both et al. 2004, JBO 9(5):882-892). BODIPY FL phallacidin has been used to fluorescently label the actin filaments. The experiments were carried out with a Leica SP2 multi photon microscope modified for 4Pi measurements using a Ti:Sa laser tuned to 850-900 nm. SHG as well as fluorescence photons were detected confocally by a counting APD detector. The approach taken our study provides new 3D-data for the analysis and simulation of the important process of excitation-contraction coupling under normal physiological as well as under pathophysiological conditions.

Live-cell imaging of phosphoinositide dynamics and membrane architecture during Legionella infection.

PubMed

Weber, Stephen; Wagner, Maria; Hilbi, Hubert

2014-01-28

The causative agent of Legionnaires' disease, Legionella pneumophila, replicates in amoebae and macrophages in a distinct membrane-bound compartment, the Legionella-containing vacuole (LCV). LCV formation is governed by the bacterial Icm/Dot type IV secretion system that translocates ~300 different "effector" proteins into host cells. Some of the translocated effectors anchor to the LCV membrane via phosphoinositide (PI) lipids. Here, we use the soil amoeba Dictyostelium discoideum, producing fluorescent PI probes, to analyze the LCV PI dynamics by live-cell imaging. Upon uptake of wild-type or Icm/Dot-deficient L. pneumophila, PtdIns(3,4,5)P3 transiently accumulated for an average of 40 s on early phagosomes, which acquired PtdIns(3)P within 1 min after uptake. Whereas phagosomes containing ΔicmT mutant bacteria remained decorated with PtdIns(3)P, more than 80% of wild-type LCVs gradually lost this PI within 2 h. The process was accompanied by a major rearrangement of PtdIns(3)P-positive membranes condensing to the cell center. PtdIns(4)P transiently localized to early phagosomes harboring wild-type or ΔicmT L. pneumophila and was cleared within minutes after uptake. During the following 2 h, PtdIns(4)P steadily accumulated only on wild-type LCVs, which maintained a discrete PtdIns(4)P identity spatially separated from calnexin-positive endoplasmic reticulum (ER) for at least 8 h. The separation of PtdIns(4)P-positive and ER membranes was even more pronounced for LCVs harboring ΔsidC-sdcA mutant bacteria defective for ER recruitment, without affecting initial bacterial replication in the pathogen vacuole. These findings elucidate the temporal and spatial dynamics of PI lipids implicated in LCV formation and provide insight into host cell membrane and effector protein interactions. The environmental bacterium Legionella pneumophila is the causative agent of Legionnaires' pneumonia. The bacteria form in free-living amoebae and mammalian immune cells a replication-permissive compartment, the Legionella-containing vacuole (LCV). To subvert host cell processes, the bacteria secrete the amazing number of ~300 different proteins into host cells. Some of these proteins bind phosphoinositide (PI) lipids to decorate the LCV. PI lipids are crucial factors involved in host cell membrane dynamics and LCV formation. Using Dictyostelium amoebae producing one or two distinct fluorescent probes, we elucidated the dynamic LCV PI pattern in high temporal and spatial resolution. Notably, the endocytic PI lipid PtdIns(3)P was slowly cleared from LCVs, thus incapacitating the host cell's digestive machinery, while PtdIns(4)P gradually accumulated on the LCV, enabling critical interactions with host organelles. The LCV PI pattern underlies the spatiotemporal configuration of bacterial effector proteins and therefore represents a crucial aspect of LCV formation.

Frequency of Rare Alpha-1 Antitrypsin Variants in Polish Patients with Chronic Respiratory Disorders.

PubMed

Duk, K; Zdral, A; Szumna, B; Roży, A; Chorostowska-Wynimko, J

2016-01-01

The SERPINA1 gene encoding the alpha-1 antitrypsin (A1AT) protein is highly polymorphic. It is known that, apart from the most prevalent PI*S and PI*Z A1AT deficiency variants, other so-called rare variants also predispose individuals to severe chronic respiratory disorders such as emphysema and chronic obstructive pulmonary disease. Our aim was to assess the frequencies of common and rare SERPINA1 mutations in a group of 1033 Polish patients referred for A1AT deficiency diagnostics due to chronic respiratory disorders in the period of January 2014-September 2015. All blood samples were analyzed according to the routine diagnostic protocol, including A1AT serum concentration assessment by nephelometry and immune isoelectric focusing, followed by PCR genotyping and direct sequencing when necessary. A total of 890 out of the 1033 samples (86 %) carried the normal PI*MM genotype, whereas, in 143 samples (14 %), at least one A1AT deficiency variant was detected. In 132 subjects, PI*S (2.1 %) and PI*Z (10.8 %) common deficiency alleles were identified, yielding frequencies of 0.011 and 0.062, respectively. Rare SERPINA1 variants were detected in nine patients: PI*F (c.739C>T) (n = 5) and PI*I (c.187C>T) (n = 4). Samples from the patients with an A1AT serum concentration below 120 mg/dl and presenting a PI*MM-like phenotypic pattern were retrospectively analyzed by direct sequencing for rare SERPINA1 mutations, revealing a PI*M2Obernburg (c.514G>T) mutation in one patient and a non-pathogenic mutation (c.922G>T) in another. We conclude that the deficiency PI*Z A1AT allele is considerably more common in patients with chronic respiratory disorders than in the general Polish population. The prevalence of the PI*F allele seems higher than in other European studies.

X-ray microanalysis of rotavirus-infected mouse intestine: A new concept of diarrhoeal secretion

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

Spencer, A.J.; Osborne, M.P.; Haddon, S.J.

1990-05-01

Neonatal mice were infected at 7 days of age with rotavirus (epizootic diarrhea of infant mice (EDIM) virus) and killed at 24-h intervals postinfection (PI). Cytoplasmic concentrations of Na, Mg, P, S, Cl, K, and Ca intestinal epithelial cells from infected and age-matched control animals were measured by x-ray microanalysis. In villus tip cells, Ca concentration increased at 24-96 h PI; Na concentration increased at 24-72 h PI; Ca and Na concentrations were near normal by 168 h PI. K concentration decreased 24-72 h PI, and Cl concentration decreased 48-96 h PI. In crypt cells, changes were observed without amore » discernible pattern: at 96 h PI, Na, Mg, S, and Cl concentrations increased and K concentration decreased; at 120 h PI, the concentrations of all elements except Na and Ca increased. In villus base cells, the mean concentrations of all elements except Ca peaked at 48-72 h PI and at 120 h PI. Na and Cl concentrations increased dramatically in some cells from 48 h PI onward. All the above concentration values were obtained from freeze-dried specimens and expressed in millimoles per kilogram of dry weight. Conversion of a limited number of data, pertaining to villus base cells, from dry weight to wet weight was possible. This conversion revealed that villus base cells in infected animals were more hydrated than corresponding cells from control animals. Also, the Na and Cl concentrations in mmol/kg H2O were significantly higher in villus base cells from infected animals than in those from corresponding controls: 137 +/- 7 versus 38 +/- 4 (Na) and 121 +/- 5 versus 89 +/- 6 (Cl). Wet weight concentrations of other elements were either the same (Mg) or lower (P, S, and K) after infection with virus.« less

Identification of the self-incompatibility locus F-box protein-containing complex in Petunia inflata.

PubMed

Li, Shu; Sun, Penglin; Williams, Justin Stephen; Kao, Teh-hui

2014-03-01

The polymorphic S-locus regulating self-incompatibility (SI) in Petunia contains the S-RNase gene and a number of S-locus F-box (SLF) genes. While penetrating the style through the stigma, a pollen tube takes up all S-RNases, but only self S-RNase inhibits pollen tube growth. Recent evidence suggests that SLFs produced by pollen collectively interact with and detoxify non-self S-RNases, but none can interact with self S-RNase. An SLF may be the F-box protein component of an SCF complex (containing Cullin1, Skp1 and Rbx1), which mediates ubiquitination of protein substrates for degradation by the 26S proteasome. However, the precise nature of the complex is unknown. We used pollen extracts of a transgenic plant over-expressing GFP-fused S2-SLF1 (SLF1 of S 2-haplotype) for co-immunoprecipitation (Co-IP) followed by mass spectrometry (MS). We identified PiCUL1-P (a pollen-specific Cullin1), PiSSK1 (a pollen-specific Skp1-like protein) and PiRBX1 (an Rbx1). To validate the results, we raised transgenic plants over-expressing PiSSK1:FLAG:GFP and used pollen extracts for Co-IP-MS. The results confirmed the presence of PiCUL1-P and PiRBX1 in the complex and identified two different SLFs as the F-box protein component. Thus, all but Rbx1 of the complex may have evolved in SI, and all SLFs may be the F-box component of similar complexes.

Association of serum inorganic phosphate with sex steroid hormones and vitamin D in a nationally representative sample of men.

PubMed

Wulaningsih, W; Van Hemelrijck, M; Michaelsson, K; Kanarek, N; Nelson, W G; Ix, J H; Platz, E A; Rohrmann, S

2014-11-01

Defects in bone regulatory pathways have been linked to chronic diseases including cardiovascular disease and cancer. In men, a link between bone metabolism and gonadal hormones has been suggested. However, to date, there is lack of evidence on the association between serum inorganic phosphate (Pi) and sex steroid hormones. The objective of this study was to investigate the association between Pi, sex steroid hormones and a known Pi metabolic regulator, vitamin D, in men in the National Health and Nutrition Examination Survey III (NHANES III). From NHANES III, we selected 1412 men aged 20+ who participated in the morning session of Phase I (1988-1991) with serum measurements of Pi, sex hormones, and vitamin D. Multivariable linear regression was used to calculate crude and geometric mean Pi by total and estimated free testosterone and estradiol, sex hormone-binding globulin, androstanediol glucuronide (AAG), and vitamin D. Similar analyses were performed while stratifying by race/ethnicity and vitamin D levels. We found a lack of statistically significant difference in geometric means of Pi across quintiles of concentrations of sex hormones, indicating a tight regulation of Pi. However, Pi levels were inversely associated with calculated free testosterone in non-Hispanic black men, with geometric mean levels of Pi of 1.16 and 1.02 ng/mL for those in the lowest and highest quintiles of free testosterone, respectively (p-trend < 0.05). A similar but weaker pattern was seen between total testosterone and Pi. An inverse association was also seen between AAG and Pi in men with vitamin D concentration below the median (<24.2 ng/mL). No associations were observed among men with vitamin D levels at or above the median. Our findings suggest a weak link among sex hormones, vitamin D, and Pi in men. The observed effects of race/ethnicity and vitamin D indicate a complex association involving various regulators of Pi homeostasis. © 2014 American Society of Andrology and European Academy of Andrology.

Simultaneously measuring multiple protein interactions and their correlations in a cell by Protein-interactome Footprinting

PubMed Central

Luo, Si-Wei; Liang, Zhi; Wu, Jia-Rui

2017-01-01

Quantitatively detecting correlations of multiple protein-protein interactions (PPIs) in vivo is a big challenge. Here we introduce a novel method, termed Protein-interactome Footprinting (PiF), to simultaneously measure multiple PPIs in one cell. The principle of PiF is that each target physical PPI in the interactome is simultaneously transcoded into a specific DNA sequence based on dimerization of the target proteins fused with DNA-binding domains. The interaction intensity of each target protein is quantified as the copy number of the specific DNA sequences bound by each fusion protein dimers. Using PiF, we quantitatively reveal dynamic patterns of PPIs and their correlation network in E. coli two-component systems. PMID:28338015

Impact of the integration of proton magnetic resonance imaging spectroscopy to PI-RADS 2 for prediction of high grade and high stage prostate cancer.

PubMed

Leapman, Michael S; Wang, Zhen J; Behr, Spencer C; Kurhanewicz, John; Zagoria, Ronald J; Carroll, Peter R; Westphalen, Antonio C

2017-01-01

To compare the predictions of dominant Gleason pattern ≥ 4 or non-organ confined disease with Prostate Imaging Reporting and Data System (PI-RADS v2) with or without proton magnetic resonance spectroscopic imaging ( 1 H-MRSI). Thirty-nine men underwent 3-tesla endorectal multiparametric MRI including 1 H-MRSI and prostatectomy. Two radiologists assigned PI-RADS v2 and 1 H-MRSI scores to index lesions. Statistical analyses used logistic regressions, receiver operating characteristic (ROC) curves, and 2x2 tables for diagnostic accuracies. The sensitivity and specificity of 1 H-MRSI and PI-RADS v2 for high-grade prostate cancer (PCa) were 85.7% (57.1%) and 92.9% (100%), and 56% (68.0%) and 24.0% (24.0%). The sensitivity and specificity of 1 H-MRSI and PI-RADS v2 for extra-prostatic extension (EPE) were 64.0% (40%) and 20.0% (48%), and 50.0% (57.1%) and 71.4% (64.3%). The area under the ROC curves (AUC) for prediction of high-grade prostate cancer were 0.65 and 0.61 for PI-RADS v2 and 0.72 and 0.70 when combined with 1 H-MRSI (readers 1 and 2, p = 0.04 and 0.21). For prediction of EPE the AUC were 0.54 and 0.60 for PI-RADS v2 and 0.55 and 0.61 when combined with 1 H-MRSI ( p > 0.05). 1 H-MRSI might improve the discrimination of high-grade prostate cancer when combined to PI-RADS v2, particularly for PI-RADS v2 score 4 lesions, but it does not affect the prediction of EPE.

Marker development for rice blast resistance gene Pi66(t) and application in USDA rice mini-core collection

USDA-ARS?s Scientific Manuscript database

Molecular markers are useful for the identification of critical genes controlling agricultural traits of interest in crop germplasm and for the utilization of these genes in crop improvement using marker assisted selection (MAS). The improvement of blast disease resistance of rice varieties is one o...

Convergence of Personality and Interests: Meta-Analysis of the Multidimensional Personality Questionnaire and the Strong Interest Inventory

ERIC Educational Resources Information Center

Staggs, Gena D.; Larson, Lisa M.; Borgen, Fred H.

2007-01-01

Using meta-analysis, we revised Ackerman and Heggestad's (1997) identification of four trait complexes that propose personality and interest (P-I) linkages. Studies that had reported correlations between general and specific measures of vocational interests (Strong Interest Inventory [Strong; Hansen & Campbell, 1985; Harmon, Hansen, Borgen,…

Mortality in Subalpine Forests of the Sierra Nevada, California, USA: Differential Response of Pines (Pinus albicaulis and P. flexilis) to Climate Variability

NASA Astrophysics Data System (ADS)

Millar, C. I.; Westfall, R. D.; Delany, D. L.

2010-12-01

Widespread forest mortality in high-elevation forests has been increasing across western North American mountains in recent years, with climate, insects, and disease the primary causes. Subalpine forests in the eastern Sierra Nevada, by contrast, have experienced far less mortality than other ranges, and mortality events have been patchy and episodic. This situation, and lack of significant effect of non-native white-pine blister rust, enable investigation of fine-scale response of two subalpine Sierran species, whitebark pine (Pinus albicaulis, PiAl) and limber pine (P. flexilis, PiFl), to climate variability. We report similarities and differences between the two major mortality events in these pines in the last 150 years: 1988-1992 for PiFl and 2006-ongoing for PiAl. In both species, the events occurred within monotypic, closed-canopy, relatively young stands (< 200 yrs PiAl, < 300 yrs in PiFl); were localized to central-eastern Sierra Nevada; and occurred at 2740-2840 m along the eastern edge of the escarpment on north/northeast aspects with slopes > 40%. Mortality patches averaged 40-80 ha in both species, with mean stand mortality of trees > 10 cm diameter 91% in PiAl and 60% in PiFl. The ultimate cause of tree death was mountain pine beetle (Dendroctonus ponderosae) in both species, with increasing 20th/21st C minimum temperatures combined with drought the pre-conditioning factors. Overall growth in the past 150 years suggests that PiFl is more drought hardy than PiAl but responds sensitively to the combined effects of drought and increasing warmth. After the 1988-1992 drought, surviving PiFl recovered growth. PiAl trees grew very poorly during that drought, and continued poor growth in the years until 2006 when the mortality event occurred in PiAl. A significant species effect is the apparent difference in levels of within-stand genetic diversity for climate factors. Differential growth between 19th C (cool, wet) and 20th/21st C (warming, drying) of PiFl trees that died versus survivors indicates that considerable within-stand genetic diversity for climate existed in PiFl. For PiFl, the late 20th C mortality event acted as strong natural selection to improve within-stand fitness for warmer and drier conditions. PiFl trees that survived the 1988-1992 drought remained healthy through subsequent droughts, including the drought that is currently causing PiAl mortality. By contrast, the PiAl stands do not appear to have contained adaptive genetic diversity for drought and warmth, and PiAl trees growth behavior over the past 150 years was similar in pattern to the PiFl trees that died. As a result, the mortality event in PiAl is creating forest openings, with unknown future stand conditions, rather than rapid within-species adaptation that occurred in PiFl.

Patterns and causes of observed piñon pine mortality in the southwestern United States

USGS Publications Warehouse

Meddens, Arjan J.H.; Hicke, Jeff H.; Macalady, Alison K.; Buotte, P.C.; Cowles, T.R.; Allen, Craig D.

2015-01-01

Recently, widespread piñon pine die-off occurred in the southwestern United States. Here we synthesize observational studies of this event and compare findings to expected relationships with biotic and abiotic factors. Agreement exists on the occurrence of drought, presence of bark beetles and increased mortality of larger trees. However, studies disagree about the influences of stem density, elevation and other factors, perhaps related to study design, location and impact of extreme drought. Detailed information about bark beetles is seldom reported and their role is poorly understood. Our analysis reveals substantial limits to our knowledge regarding the processes that produce mortality patterns across space and time, indicating a poor ability to forecast mortality in response to expected increases in future droughts.

Identification of Glutathione S-Transferase Pi as a Protein Involved in Parkinson Disease Progression

PubMed Central

Shi, Min; Bradner, Joshua; Bammler, Theo K.; Eaton, David L.; Zhang, JianPeng; Ye, ZuCheng; Wilson, Angela M.; Montine, Thomas J.; Pan, Catherine; Zhang, Jing

2009-01-01

Parkinson disease (PD) typically affects the cortical regions during the later stages of disease, with neuronal loss, gliosis, and formation of diffuse cortical Lewy bodies in a significant portion of patients with dementia. To identify novel proteins involved in PD progression, we prepared synaptosomal fractions from the frontal cortices of pathologically verified PD patients at different stages along with age-matched controls. Protein expression profiles were compared using a robust quantitative proteomic technique. Approximately 100 proteins displayed significant differences in their relative abundances between PD patients at various stages and controls; three of these proteins were validated using independent techniques. One of the confirmed proteins, glutathione S-transferase Pi, was further investigated in cellular models of PD, demonstrating that its level was intimately associated with several critical cellular processes that are directly related to neurodegeneration in PD. These results have, for the first time, suggested that the levels of glutathione S-transferase Pi may play an important role in modulating the progression of PD. PMID:19498008

Hereditary hypophosphatemic rickets with hypercalciuria and nephrolithiasis-identification of a novel SLC34A3/NaPi-IIc mutation.

PubMed

Phulwani, Priya; Bergwitz, Clemens; Jaureguiberry, Graciana; Rasoulpour, Majjid; Estrada, Elizabeth

2011-03-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is characterized by rickets, hyperphosphaturia, hypophosphatemia, elevated 1,25-dihydroxyvitamin-D, increased gastrointestinal calcium absorption and hypercalciuria. Serum calcium, 25-hydroxyvitamin-D and PTH levels are normal. Here we describe a boy with HHRH, nephrolithiasis, and compound heterozygosity for one previously described mutation (g.4225_50del) and a novel splice mutation (g.1226G>A) in SLC34A3, the gene encoding the renal sodium-phosphate co-transporter NaPi-IIc. The patient's mother and grandmother are carriers of g.4225_50del, and both have a history of nephrolithiasis associated with hypercalciuria and elevated 1,25-dihydroxyvitamin-D. His three siblings (2-6 years old), who are also carriers of g.4225_50del, have hypercalciuria but so far their renal ultrasounds are normal. Thus, SLC34A3/NaPi-IIc mutations appear to be associated with variable phenotypic changes at presentation, which can include recurrent nephrolithiasis. Copyright © 2011 Wiley-Liss, Inc.

Hereditary Hypophosphatemic Rickets With Hypercalciuria and Nephrolithiasis—Identification of a Novel SLC34A3/NaPi-IIc Mutation

PubMed Central

Phulwani, Priya; Bergwitz, Clemens; Jaureguiberry, Graciana; Rasoulpour, Majjid; Estrada, Elizabeth

2015-01-01

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is characterized by rickets, hyperphosphaturia, hypophosphatemia, elevated 1,25-dihydroxyvitamin-D, increased gastrointestinal calcium absorption and hypercalciuria. Serum calcium, 25-hydroxyvitamin-D and PTH levels are normal. Here we describe a boy with HHRH, nephrolithiasis, and compound heterozygosity for one previously described mutation (g.4225_50del) and a novel splice mutation (g.1226G>A) in SLC34A3, the gene encoding the renal sodium-phosphate co-transporter NaPi-IIc. The patient’s mother and grandmother are carriers of g.4225_50del, and both have a history of nephrolithiasis associated with hypercalciuria and elevated 1,25-dihydroxyvitamin-D. His three siblings (2–6 years old), who are also carriers of g.4225_50del, have hypercalciuria but so far their renal ultrasounds are normal. Thus, SLC34A3/NaPi-IIc mutations appear to be associated with variable phenotypic changes at presentation, which can include recurrent nephrolithiasis. PMID:21344632

Source and path identification of metals pollution in a mining area by PMF and rare earth element patterns in road dust.

PubMed

Tian, Shuhan; Liang, Tao; Li, Kexin; Wang, Lingqing

2018-08-15

To better assess pollution and offer efficient protection for local residents, it is necessary to both conduct an exhaustive investigation into pollution levels and quantify its contributing sources and paths. As it is the biggest light rare earth element (REE) reserve in the world, Bayan Obo deposit releases large amounts of heavy metals into the surrounding environment. In this study, road dust from zones located at different distances to the mining area was collected and sieved using seven sizes. This allowed for subsequent analysis of size-dependent influences of mining activities. A receptor model was used to quantitatively assess mine contributions. REE distribution patterns and other REE parameters were compared with those in airborne particulates and the surrounding soil to analyze pollution paths. Results showed that 27 metals were rated as moderately to extremely polluted (2

{pi}-{pi} Interactions and magnetic properties in a series of hybrid inorganic-organic crystals

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

Gonzalez, M.; Lemus-Santana, A.A.; Rodriguez-Hernandez, J.

The series of hybrid inorganic-organic solids T(Im){sub 2}[Ni(CN){sub 4}] with T=Fe, Co, Ni and Im=imidazole were prepared by soft chemical routes from aqueous solutions of the involved building units: imidazole, T{sup 2+} metal and the [Ni(CN){sub 4}]{sup 2-} anionic block. The obtained samples were characterized from infrared and UV-vis spectroscopies, and thermogravimetric, X-ray diffraction and magnetic measurements. Anhydrous solids which crystallize with a monoclinic unit cell, in the I2/a space group with four formula units per cell (Z=4) were obtained. Their crystal structure was solved ab initio from the recorded X-ray powder patterns and then refined by the Rietveld method.more » The metal T is found with octahedral coordination to four N ends of CN groups and two imidazole molecules while the inner Ni atom preserves its planar coordination. The system of layers remains stacked in an ordered 3D structure through dipole-dipole and {pi}-{pi} interactions between imidazole rings from neighboring layers. In this way, a pillared structure is achieved without requiring the coordination of both nitrogen atoms from imidazole ring. The recorded magnetic data indicate the occurrence of a predominant ferromagnetic interaction at low temperature for Co and Ni but not for Fe. Such magnetic ordering is more favorable for Ni with transition temperature of 14.67 K, which was ascribed to the relatively high polarizing power for this metal. Within the considered T metals, to nickel the highest electron-withdrawing ability corresponds and this leads to an increase for the metal-ligand electron clouds overlapping and to a stronger {pi}-{pi} attractive interaction, two factors that result into a higher magnetic ordering temperature. - Graphical Abstract: Magnetic ordering through the {pi}-{pi} interaction between the imidazole rings. Highlights: Black-Right-Pointing-Pointer Hybrid inorganic-organic solids. Black-Right-Pointing-Pointer Hybrid inorganic-organic molecular based magnets. Black-Right-Pointing-Pointer Ferromagnetic interaction through {pi}-{pi} stacking of imidazole rings. Black-Right-Pointing-Pointer Organic pillars formed through {pi}-{pi} stacking.« less

Classification of Regional Radiographic Emphysematous Patterns Using Low-Attenuation Gap Length Matrix

NASA Astrophysics Data System (ADS)

Tan, Kok Liang; Tanaka, Toshiyuki; Nakamura, Hidetoshi; Shirahata, Toru; Sugiura, Hiroaki

The standard computer-tomography-based method for measuring emphysema uses percentage of area of low attenuation which is called the pixel index (PI). However, the PI method is susceptible to the problem of averaging effect and this causes the discrepancy between what the PI method describes and what radiologists observe. Knowing that visual recognition of the different types of regional radiographic emphysematous tissues in a CT image can be fuzzy, this paper proposes a low-attenuation gap length matrix (LAGLM) based algorithm for classifying the regional radiographic lung tissues into four emphysema types distinguishing, in particular, radiographic patterns that imply obvious or subtle bullous emphysema from those that imply diffuse emphysema or minor destruction of airway walls. Neural network is used for discrimination. The proposed LAGLM method is inspired by, but different from, former texture-based methods like gray level run length matrix (GLRLM) and gray level gap length matrix (GLGLM). The proposed algorithm is successfully validated by classifying 105 lung regions that are randomly selected from 270 images. The lung regions are hand-annotated by radiologists beforehand. The average four-class classification accuracies in the form of the proposed algorithm/PI/GLRLM/GLGLM methods are: 89.00%/82.97%/52.90%/51.36%, respectively. The p-values from the correlation analyses between the classification results of 270 images and pulmonary function test results are generally less than 0.01. The classification results are useful for a followup study especially for monitoring morphological changes with progression of pulmonary disease.

Slow wave sleep in the chronically fatigued: Power spectra distribution patterns in chronic fatigue syndrome and primary insomnia.

PubMed

Neu, Daniel; Mairesse, Olivier; Verbanck, Paul; Le Bon, Olivier

2015-10-01

To investigate slow wave sleep (SWS) spectral power proportions in distinct clinical conditions sharing non-restorative sleep and fatigue complaints without excessive daytime sleepiness (EDS), namely the chronic fatigue syndrome (CFS) and primary insomnia (PI). Impaired sleep homeostasis has been suspected in both CFS and PI. We compared perceived sleep quality, fatigue and sleepiness symptom-intensities, polysomnography (PSG) and SWS spectral power distributions of drug-free CFS and PI patients without comorbid sleep or mental disorders, with a good sleeper control group. Higher fatigue without EDS and impaired perceived sleep quality were confirmed in both patient groups. PSG mainly differed in sleep fragmentation and SWS durations. Spectral analysis revealed a similar decrease in central ultra slow power (0.3-0.79Hz) proportion during SWS for both CFS and PI and an increase in frontal power proportions of faster frequencies during SWS in PI only. The latter was correlated to affective symptoms whereas lower central ultra slow power proportions were related to fatigue severity and sleep quality impairment. In combination with normal (PI) or even increased SWS durations (CFS), we found consistent evidence for lower proportions of slow oscillations during SWS in PI and CFS. Observing normal or increased SWS durations but lower proportions of ultra slow power, our findings suggest a possible quantitative compensation of altered homeostatic regulation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Wearable polyimide-PDMS electrodes for intrabody communication

NASA Astrophysics Data System (ADS)

Moon, Jin-Hee; Baek, Dong Hyun; Choi, Yoon Young; Lee, Kwang Ho; Kim, Hee Chan; Lee, Sang-Hoon

2010-02-01

In this paper, we introduce a novel wearable electrode for an intra-body area network (I-BAN) by employing the advantages of polyimide (PI) which is a well-known substrate material for flexible electrodes and polydimethylsiloxane (PDMS) which is a biocompatible and representative soft-lithography adaptable material. Electrodes were patterned onto thin and flexible PI substrates and encapsulated in PDMS to enhance skin compatibility. For this purpose, we developed an electrode fabrication process on thin PI substrates and a PDMS encapsulation technique by bonding two PDMS layers on the front and back surfaces of the PI electrode. The mechanical property and communication performance of electrodes were characterized through spectrum analysis to optimize the role as an I-BAN electrode. Skin-compatibility and cyto-toxicity tests using human mesenchymal stem cells (hMSCs) were carried out to demonstrate the non-toxicity of the electrode after continuous wearing. Sinusoidal signals of 45 MHz were successfully transmitted with high fidelity between electrodes separated by 30 cm.

Analysis of physiological and miRNA responses to Pi deficiency in alfalfa (Medicago sativa L.).

PubMed

Li, Zhenyi; Xu, Hongyu; Li, Yue; Wan, Xiufu; Ma, Zhao; Cao, Jing; Li, Zhensong; He, Feng; Wang, Yufei; Wan, Liqiang; Tong, Zongyong; Li, Xianglin

2018-03-01

The induction of miR399 and miR398 and the inhibition of miR156, miR159, miR160, miR171, miR2111, and miR2643 were observed under Pi deficiency in alfalfa. The miRNA-mediated genes involved in basic metabolic process, root and shoot development, stress response and Pi uptake. Inorganic phosphate (Pi) deficiency is known to be a limiting factor in plant development and growth. However, the underlying miRNAs associated with the Pi deficiency-responsive mechanism in alfalfa are unclear. To elucidate the molecular mechanism at the miRNA level, we constructed four small RNA (sRNA) libraries from the roots and shoots of alfalfa grown under normal or Pi-deficient conditions. In the present study, alfalfa plants showed reductions in biomass, photosynthesis, and Pi content and increases in their root-to-shoot ratio and citric, malic, and succinic acid contents under Pi limitation. Sequencing results identified 47 and 44 differentially expressed miRNAs in the roots and shoots, respectively. Furthermore, 909 potential target genes were predicted, and some targets were validated by RLM-RACE assays. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed prominent enrichment in signal transducer activity, binding and basic metabolic pathways for carbohydrates, fatty acids and amino acids; cellular response to hormone stimulus and response to auxin pathways were also enriched. qPCR results verified that the differentially expressed miRNA profile was consistent with sequencing results, and putative target genes exhibited opposite expression patterns. In this study, the miRNAs associated with the response to Pi limitation in alfalfa were identified. In addition, there was an enrichment of miRNA-targeted genes involved in biological regulatory processes such as basic metabolic pathways, root and shoot development, stress response, Pi transportation and citric acid secretion.

A Sorghum bicolor expression atlas reveals dynamic genotype-specific expression profiles for vegetative tissues of grain, sweet and bioenergy sorghums.

PubMed

Shakoor, Nadia; Nair, Ramesh; Crasta, Oswald; Morris, Geoffrey; Feltus, Alex; Kresovich, Stephen

2014-01-23

Effective improvement in sorghum crop development necessitates a genomics-based approach to identify functional genes and QTLs. Sequenced in 2009, a comprehensive annotation of the sorghum genome and the development of functional genomics resources is key to enable the discovery and deployment of regulatory and metabolic genes and gene networks for crop improvement. This study utilizes the first commercially available whole-transcriptome sorghum microarray (Sorgh-WTa520972F) to identify tissue and genotype-specific expression patterns for all identified Sorghum bicolor exons and UTRs. The genechip contains 1,026,373 probes covering 149,182 exons (27,577 genes) across the Sorghum bicolor nuclear, chloroplast, and mitochondrial genomes. Specific probesets were also included for putative non-coding RNAs that may play a role in gene regulation (e.g., microRNAs), and confirmed functional small RNAs in related species (maize and sugarcane) were also included in our array design. We generated expression data for 78 samples with a combination of four different tissue types (shoot, root, leaf and stem), two dissected stem tissues (pith and rind) and six diverse genotypes, which included 6 public sorghum lines (R159, Atlas, Fremont, PI152611, AR2400 and PI455230) representing grain, sweet, forage, and high biomass ideotypes. Here we present a summary of the microarray dataset, including analysis of tissue-specific gene expression profiles and associated expression profiles of relevant metabolic pathways. With an aim to enable identification and functional characterization of genes in sorghum, this expression atlas presents a new and valuable resource to the research community.

A Sorghum bicolor expression atlas reveals dynamic genotype-specific expression profiles for vegetative tissues of grain, sweet and bioenergy sorghums

PubMed Central

2014-01-01

Background Effective improvement in sorghum crop development necessitates a genomics-based approach to identify functional genes and QTLs. Sequenced in 2009, a comprehensive annotation of the sorghum genome and the development of functional genomics resources is key to enable the discovery and deployment of regulatory and metabolic genes and gene networks for crop improvement. Results This study utilizes the first commercially available whole-transcriptome sorghum microarray (Sorgh-WTa520972F) to identify tissue and genotype-specific expression patterns for all identified Sorghum bicolor exons and UTRs. The genechip contains 1,026,373 probes covering 149,182 exons (27,577 genes) across the Sorghum bicolor nuclear, chloroplast, and mitochondrial genomes. Specific probesets were also included for putative non-coding RNAs that may play a role in gene regulation (e.g., microRNAs), and confirmed functional small RNAs in related species (maize and sugarcane) were also included in our array design. We generated expression data for 78 samples with a combination of four different tissue types (shoot, root, leaf and stem), two dissected stem tissues (pith and rind) and six diverse genotypes, which included 6 public sorghum lines (R159, Atlas, Fremont, PI152611, AR2400 and PI455230) representing grain, sweet, forage, and high biomass ideotypes. Conclusions Here we present a summary of the microarray dataset, including analysis of tissue-specific gene expression profiles and associated expression profiles of relevant metabolic pathways. With an aim to enable identification and functional characterization of genes in sorghum, this expression atlas presents a new and valuable resource to the research community. PMID:24456189

Attendance fingerprint identification system using arduino and single board computer

NASA Astrophysics Data System (ADS)

Muchtar, M. A.; Seniman; Arisandi, D.; Hasanah, S.

2018-03-01

Fingerprint is one of the most unique parts of the human body that distinguishes one person from others and is easily accessed. This uniqueness is supported by technology that can automatically identify or recognize a person called fingerprint sensor. Yet, the existing Fingerprint Sensor can only do fingerprint identification on one machine. For the mentioned reason, we need a method to be able to recognize each user in a different fingerprint sensor. The purpose of this research is to build fingerprint sensor system for fingerprint data management to be centralized so identification can be done in each Fingerprint Sensor. The result of this research shows that by using Arduino and Raspberry Pi, data processing can be centralized so that fingerprint identification can be done in each fingerprint sensor with 98.5 % success rate of centralized server recording.

The Two-Component System PhoPR of Clostridium acetobutylicum Is Involved in Phosphate-Dependent Gene Regulation ▿

PubMed Central

Fiedler, Tomas; Mix, Maren; Meyer, Uta; Mikkat, Stefan; Glocker, Michael O.; Bahl, Hubert; Fischer, Ralf-Jörg

2008-01-01

The phoPR gene locus of Clostridium acetobutylicum ATCC 824 comprises two genes, phoP and phoR. Deduced proteins are predicted to represent a response regulator and sensor kinase of a phosphate-dependent two-component regulatory system. We analyzed the expression patterns of phoPR in Pi-limited chemostat cultures and in response to Pi pulses. A basic transcription level under high-phosphate conditions was shown, and a significant increase in mRNA transcript levels was found when external Pi concentrations dropped below 0.3 mM. In two-dimensional gel electrophoresis experiments, a 2.5-fold increase in PhoP was observed under Pi-limiting growth conditions compared to growth with an excess of Pi. At least three different transcription start points for phoP were determined by primer extension analyses. Proteins PhoP and an N-terminally truncated *PhoR were individually expressed heterologously in Escherichia coli and purified. Autophosphorylation of *PhoR and phosphorylation of PhoP were shown in vitro. Electromobility shift assays proved that there was a specific binding of PhoP to the promoter region of the phosphate-regulated pst operon of C. acetobutylicum. PMID:18689481

4Pi microscopy of the nuclear pore complex.

PubMed

Kahms, Martin; Hüve, Jana; Peters, Reiner

2015-01-01

4Pi microscopy is a far-field fluorescence microscopy technique, in which the wave fronts of two opposing illuminating beams are adjusted to constructively interfere in a common focus. This yields a diffraction pattern in the direction of the optical axis, which essentially consists of a main focal spot accompanied by two smaller side lobes. At optimal conditions, the main peak of this so-called point spread function has a full width at half maximum: fixed phrase of 100 nm in the direction of the optical axis, and thus is 6-7-fold smaller than that of a confocal microscope. In this chapter, we describe the basic features of 4Pi microscopy and its application to cell biology using the example of the nuclear pore complex, a large protein assembly spanning the nuclear envelope.

BayesPI-BAR: a new biophysical model for characterization of regulatory sequence variations

PubMed Central

Wang, Junbai; Batmanov, Kirill

2015-01-01

Sequence variations in regulatory DNA regions are known to cause functionally important consequences for gene expression. DNA sequence variations may have an essential role in determining phenotypes and may be linked to disease; however, their identification through analysis of massive genome-wide sequencing data is a great challenge. In this work, a new computational pipeline, a Bayesian method for protein–DNA interaction with binding affinity ranking (BayesPI-BAR), is proposed for quantifying the effect of sequence variations on protein binding. BayesPI-BAR uses biophysical modeling of protein–DNA interactions to predict single nucleotide polymorphisms (SNPs) that cause significant changes in the binding affinity of a regulatory region for transcription factors (TFs). The method includes two new parameters (TF chemical potentials or protein concentrations and direct TF binding targets) that are neglected by previous methods. The new method is verified on 67 known human regulatory SNPs, of which 47 (70%) have predicted true TFs ranked in the top 10. Importantly, the performance of BayesPI-BAR, which uses principal component analysis to integrate multiple predictions from various TF chemical potentials, is found to be better than that of existing programs, such as sTRAP and is-rSNP, when evaluated on the same SNPs. BayesPI-BAR is a publicly available tool and is able to carry out parallelized computation, which helps to investigate a large number of TFs or SNPs and to detect disease-associated regulatory sequence variations in the sea of genome-wide noncoding regions. PMID:26202972

Preliminary identification of QTLs controlling water use efficiency in 'Gala' apple (Malus x domestica)

USDA-ARS?s Scientific Manuscript database

Water use efficiency (WUE) in plants is measured by the ratio of dry matter accumulation per unit of transpiration. The goal of this study was to determine if genomic regions positively affecting WUE could be identified in a ‘Royal Gala’ apple X Malus sieversii PI613981 mapping population (GMAL4593...

Survey of rice blast race identity for blast resistance gene identification in the USA and Puerto Rico

USDA-ARS?s Scientific Manuscript database

Rice blast disease is a significant threat to stable rice production in the USA and worldwide. The major resistance gene (Pi-ta) located within a cluster of resistance genes on rice chromosome 12 has been demonstrated to confer resistance to the rice blast disease. Katy, a rice cultivar released in ...

Understanding protein-nanoparticle interaction: a new gateway to disease therapeutics.

PubMed

Giri, Karuna; Shameer, Khader; Zimmermann, Michael T; Saha, Sounik; Chakraborty, Prabir K; Sharma, Anirudh; Arvizo, Rochelle R; Madden, Benjamin J; Mccormick, Daniel J; Kocher, Jean-Pierre A; Bhattacharya, Resham; Mukherjee, Priyabrata

2014-06-18

Molecular identification of protein molecules surrounding nanoparticles (NPs) may provide useful information that influences NP clearance, biodistribution, and toxicity. Hence, nanoproteomics provides specific information about the environment that NPs interact with and can therefore report on the changes in protein distribution that occurs during tumorigenesis. Therefore, we hypothesized that characterization and identification of protein molecules that interact with 20 nm AuNPs from cancer and noncancer cells may provide mechanistic insights into the biology of tumor growth and metastasis and identify new therapeutic targets in ovarian cancer. Hence, in the present study, we systematically examined the interaction of the protein molecules with 20 nm AuNPs from cancer and noncancerous cell lysates. Time-resolved proteomic profiles of NP-protein complexes demonstrated electrostatic interaction to be the governing factor in the initial time-points which are dominated by further stabilization interaction at longer time-points as determined by ultraviolet-visible spectroscopy (UV-vis), dynamic light scattering (DLS), ζ-potential measurements, transmission electron microscopy (TEM), and tandem mass spectrometry (MS/MS). Reduction in size, charge, and number of bound proteins were observed as the protein-NP complex stabilized over time. Interestingly, proteins related to mRNA processing were overwhelmingly represented on the NP-protein complex at all times. More importantly, comparative proteomic analyses revealed enrichment of a number of cancer-specific proteins on the AuNP surface. Network analyses of these proteins highlighted important hub nodes that could potentially be targeted for maximal therapeutic advantage in the treatment of ovarian cancer. The importance of this methodology and the biological significance of the network proteins were validated by a functional study of three hubs that exhibited variable connectivity, namely, PPA1, SMNDC1, and PI15. Western blot analysis revealed overexpression of these proteins in ovarian cancer cells when compared to normal cells. Silencing of PPA1, SMNDC1, and PI15 by the siRNA approach significantly inhibited proliferation of ovarian cancer cells and the effect correlated with the connectivity pattern obtained from our network analyses.

Identification of Insulin Receptor Substrate 1 (IRS-1) and IRS-2 as Signaling Intermediates in the α6β4 Integrin-Dependent Activation of Phosphoinositide 3-OH Kinase and Promotion of Invasion

PubMed Central

Shaw, Leslie M.

2001-01-01

Expression of the α6β4 integrin increases the invasive potential of carcinoma cells by a mechanism that involves activation of phosphoinositide 3-OH kinase (PI3K). In the present study, we investigated the signaling pathway by which the α6β4 integrin activates PI3K. Neither the α6 nor the β4 cytoplasmic domain contains the consensus binding motif for PI3K, pYMXM, indicating that additional proteins are likely to be involved in the activation of this lipid kinase by the α6β4 integrin. We identified insulin receptor substrate 1 (IRS-1) and IRS-2 as signaling intermediates in the activation of PI3K by the α6β4 integrin. IRS-1 and IRS-2 are cytoplasmic adapter proteins that do not contain intrinsic kinase activity but rather function by recruiting proteins to surface receptors, where they organize signaling complexes. Ligation of the α6β4 receptor promotes tyrosine phosphorylation of IRS-1 and IRS-2 and increases their association with PI3K, as determined by coimmunoprecipitation. Moreover, we identified a tyrosine residue in the cytoplasmic domain of the β4 subunit, Y1494, that is required for α6β4-dependent phosphorylation of IRS-2 and activation of PI3K in response to receptor ligation. Most importantly, Y1494 is essential for the ability of the α6β4 integrin to promote carcinoma invasion. Taken together, these results imply a key role for the IRS proteins in the α6β4-dependent promotion of carcinoma invasion. PMID:11438664

Use of molecular and milk production information for the cost-effective diagnosis of bovine viral diarrhoea infection in New Zealand dairy cattle.

PubMed

Hill, F I; Reichel, M P; Tisdall, D J

2010-04-21

An increase in veterinary and farmer interest in bovine viral diarrhoea (BVD) in New Zealand over recent years led to requests for cost-effective identification of BVD virus (BVDV) infected herds and individuals. This study was undertaken to determine if the use of real-time reverse transcriptase polymerase chain reaction (RT-PCR) technology and dairy cow production data could identify persistently infected (PI) animals in milking herds. Milk samples were collected from the vats of dairy herds and tested for the presence of BVDV by RT-PCR till four herds were found containing PI animals. Individual serum samples were then collected from every cow in the herd and tested by both RT-PCR and antigen capture enzyme-linked immunosorbent assays (ACE) to identify the PI animals. Individual animal testing found 1/223, 1/130, 2/800 and 1/275 PI's respectively in the four herds. Based on these results a maximum pool size of 400 cows contributing to the bulk tank milk was selected. After removal of the PI from the herds, further bulk milk samples were shown to be BVDV negative by RT-PCR. All the PI animals identified by this method were found in the lowest producing 10-20% of herd. This approach of targeted testing of dairy herds using PCR technology, in conjunction with animal production information, markedly reduced the cost of diagnostic testing for BVDV in dairy herds in New Zealand. Questionnaire follow-up on 81 BVDV-positive herds (15% of those tested) indicated the stratification approach identified milking PIs successfully over 90% of the time and reduced the number of individual tests to 12% of the milking herd. Copyright 2009 Elsevier B.V. All rights reserved.

Six Years (2011–2016) of Mandatory Nationwide Bovine Viral Diarrhea Control in Germany—A Success Story

PubMed Central

Gethmann, Jörn; Schirrmeier, Horst; Schröder, Ronald; Conraths, Franz J.; Beer, Martin

2017-01-01

Bovine viral diarrhea (BVD) is one of the most important infectious diseases in cattle, causing major economic losses worldwide. Therefore, control programs have been implemented in several countries. In Germany, an obligatory nationwide eradication program has been in force since 2011. Its centerpiece is the detection of animals persistently infected (PI) with BVD virus, primarily based on the testing of ear tissue samples of all newborn calves for viral genome or antigen, and their removal from the cattle population. More than 48,000 PI animals have so far been detected and removed. Between the onset of the program and the end of 2016, the prevalence of these animals among all newborn calves decreased considerably, from 0.5% to less than 0.03%. The number of cattle holdings with PI animals likewise decreased from 3.44% in 2011 to only 0.16% in 2016. Since a large number of naïve, fully susceptible animals are now confronted with BVD virus, which is still present in the German cattle population, the challenge of the coming years will be the identification of remaining PI animals as quickly and efficiently as possible, and the efficient protection of BVD-free farms from reinfection. PMID:29057796

Double phosphorylation of the myosin regulatory light chain during rigor mortis of bovine Longissimus muscle.

PubMed

Muroya, Susumu; Ohnishi-Kameyama, Mayumi; Oe, Mika; Nakajima, Ikuyo; Shibata, Masahiro; Chikuni, Koichi

2007-05-16

To investigate changes in myosin light chains (MyLCs) during postmortem aging of the bovine longissimus muscle, we performed two-dimensional gel electrophoresis followed by identification with matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The results of fluorescent differential gel electrophoresis showed that two spots of the myosin regulatory light chain (MyLC2) at pI values of 4.6 and 4.7 shifted toward those at pI values of 4.5 and 4.6, respectively, by 24 h postmortem when rigor mortis was completed. Meanwhile, the MyLC1 and MyLC3 spots did not change during the 14 days postmortem. Phosphoprotein-specific staining of the gels demonstrated that the MyLC2 proteins at pI values of 4.5 and 4.6 were phosphorylated. Furthermore, possible N-terminal region peptides containing one and two phosphoserine residues were detected in each mass spectrum of the MyLC2 spots at pI values of 4.5 and 4.6, respectively. These results demonstrated that MyLC2 became doubly phosphorylated during rigor formation of the bovine longissimus, suggesting involvement of the MyLC2 phosphorylation in the progress of beef rigor mortis. Bovine; myosin regulatory light chain (RLC, MyLC2); phosphorylation; rigor mortis; skeletal muscle.

A conserved two-component signal transduction system controls the response to phosphate starvation in Bifidobacterium breve UCC2003.

PubMed

Alvarez-Martin, Pablo; Fernández, Matilde; O'Connell-Motherway, Mary; O'Connell, Kerry Joan; Sauvageot, Nicolas; Fitzgerald, Gerald F; MacSharry, John; Zomer, Aldert; van Sinderen, Douwe

2012-08-01

This work reports on the identification and molecular characterization of the two-component regulatory system (2CRS) PhoRP, which controls the response to inorganic phosphate (P(i)) starvation in Bifidobacterium breve UCC2003. The response regulator PhoP was shown to bind to the promoter region of pstSCAB, specifying a predicted P(i) transporter system, as well as that of phoU, which encodes a putative P(i)-responsive regulatory protein. This interaction is assumed to cause transcriptional modulation under conditions of P(i) limitation. Our data suggest that the phoRP genes are subject to positive autoregulation and, together with pstSCAB and presumably phoU, represent the complete regulon controlled by the phoRP-encoded 2CRS in B. breve UCC2003. Determination of the minimal PhoP binding region combined with bioinformatic analysis revealed the probable recognition sequence of PhoP, designated here as the PHO box, which together with phoRP is conserved among many high-GC-content Gram-positive bacteria. The importance of the phoRP 2CRS in the response of B. breve to P(i) starvation conditions was confirmed by analysis of a B. breve phoP insertion mutant which exhibited decreased growth under phosphate-limiting conditions compared to its parent strain UCC2003.

A survey on hysteresis modeling, identification and control

NASA Astrophysics Data System (ADS)

Hassani, Vahid; Tjahjowidodo, Tegoeh; Do, Thanh Nho

2014-12-01

The various mathematical models for hysteresis such as Preisach, Krasnosel'skii-Pokrovskii (KP), Prandtl-Ishlinskii (PI), Maxwell-Slip, Bouc-Wen and Duhem are surveyed in terms of their applications in modeling, control and identification of dynamical systems. In the first step, the classical formalisms of the models are presented to the reader, and more broadly, the utilization of the classical models is considered for development of more comprehensive models and appropriate controllers for corresponding systems. In addition, the authors attempt to encourage the reader to follow the existing mathematical models of hysteresis to resolve the open problems.

Arbuscular mycorrhizal fungi differ in their ability to regulate the expression of phosphate transporters in maize (Zea mays L.).

PubMed

Tian, Hui; Drijber, Rhae A; Li, Xiaolin; Miller, Daniel N; Wienhold, Brian J

2013-08-01

Previous studies have found that some phosphate (Pi) starvation inducible transporter genes are downregulated and arbuscular mycorrhizal (AM) inducible Pi transporter genes are upregulated in maize roots associated with the fungus Glomus intraradices. However, little is known about the functional diversity of different AM fungal species in influencing the expression of Pi transporters in maize roots. Here, we studied the expression of two Pi transporter genes ZEAma:Pht1;3 (Pi starvation inducible) and ZEAma:Pht1;6 (AM inducible) in maize root colonized by different AM fungal inoculants. Non-mycorrhizal maize, maize colonized by Glomus deserticola (CA113), Glomus intraradices (IA506), Glomus mosseae (CA201), Gigaspora gigantea (MN922A) and the co-inoculation of all four species were established. The expression patterns of the two genes were quantified using real-time, reverse transcription polymerase chain reaction. The expression level of ZEAma:Pht1;6 was 26-135 times higher in AM plants than in non-mycorrhizal maize roots, whereas the expression level of ZEAma:Pht1;3 was five to 44 times lower in AM plants than in non-mycorrhizal plants. Expression of the two genes differed with inoculation treatment, and increasing the diversity of AM fungi in maize roots led to greater expression of ZEAma:Pht1;6 as well as Pi uptake in shoots. The expression of ZEAma:Pht1;6 was significantly positively correlated with AM colonization rate, concentration of AM biomarkers in maize roots, Pi uptake and dry weight of shoot, but negatively correlated with the expression of ZEAma:Pht1;3. Addition of Pi fertilizer at a low concentration significantly increased the expression of ZEAma:Pht1;6 but had no effect on the expression of ZEAma:Pht1;3.

Sleep-related memory consolidation in primary insomnia.

PubMed

Nissen, Christoph; Kloepfer, Corinna; Feige, Bernd; Piosczyk, Hannah; Spiegelhalder, Kai; Voderholzer, Ulrich; Riemann, Dieter

2011-03-01

It has been suggested that healthy sleep facilitates the consolidation of newly acquired memories and underlying brain plasticity. The authors tested the hypothesis that patients with primary insomnia (PI) would show deficits in sleep-related memory consolidation compared to good sleeper controls (GSC). The study used a four-group parallel design (n=86) to investigate the effects of 12 h of night-time, including polysomnographically monitored sleep ('sleep condition' in PI and GSC), versus 12 h of daytime wakefulness ('wake condition' in PI and GSC) on procedural (mirror tracing task) and declarative memory consolidation (visual and verbal learning task). Demographic characteristics and memory encoding did not differ between the groups at baseline. Polysomnography revealed a significantly disturbed sleep profile in PI compared to GSC in the sleep condition. Night-time periods including sleep in GSC were associated with (i) a significantly enhanced procedural and declarative verbal memory consolidation compared to equal periods of daytime wakefulness in GSC and (ii) a significantly enhanced procedural memory consolidation compared to equal periods of daytime wakefulness and night-time sleep in PI. Across retention intervals of daytime wakefulness, no differences between the experimental groups were observed. This pattern of results suggests that healthy sleep fosters the consolidation of new memories, and that this process is impaired for procedural memories in patients with PI. Future work is needed to investigate the impact of treatment on improving sleep and memory. © 2010 European Sleep Research Society.

Spallation of Cu by. pi. /sup -/ across the T = 1/2 resonances and at high energy

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

Haustein, P.E.

1979-09-01

Relative yields of 11 selected products (/sup 24/Na, /sup 43,44,46,47,48/Sc, /sup 55,56,57,58,60/Co) have been measured for the interaction of 0.6- and 0.9-GeV negative pions with Cu. In addition, the yields of /sup 24/Na and /sup 58/Co from Cu have been measured for 12-GeV ..pi../sup -/. Results at the two lower energies which correspond to the first two isospin T = 1/2 pion-nucleon resonances are compared with earlier studies of Cu spallation by ..pi../sup -/ at energies across the first T = 3/2 resonance, i.e., 50 to 350 MeV. The 12-GeV ..pi../sup -/ results are compared with similar investigations in whichmore » both energetic protons and heavy ions were used. For E/sub ..pi../ > or = 0.5 GeV no evidence of strong resonance effects can be found in the pattern of the spallation yields. As the pion energy is raised a smooth trend of enhanced yields of deep spallation products to near-target yields closely parallels the same trend observed for both high-energy proton and heavy-ion spallation of Cu. These results indicate that at high energy, pi-mesic spallation exhibits the same features of limiting fragmentation and factorization of the isotopic yields that have been observed previously in hadron induced spallation.« less

Characteristics of sarcoidosis in Maori and Pacific Islanders.

PubMed

Wilsher, Margaret L; Young, Lisa M; Hopkins, Raewyn; Cornere, Megan

2017-02-01

Ethnicity is strongly associated with variable clinical presentation in sarcoidosis but the association between ethnicity and clinical characteristics has not previously been described in patients of Polynesian ancestry, Maori and Pacific Islander (PI). The objective of this study was to describe the clinical characteristics of sarcoidosis in Maori and PI patients and determine if those were different to European patients. A retrospective review of the medical records of 406 patients (69 Maori/PI) attending a specialist interstitial lung disease (ILD) clinic. The population (207 females, mean age at presentation: 36) reflected the current New Zealand census data (2013) with only people of Indian ethnicity over-represented. Parenchymal lung involvement was uncommon in Maori and PI patients (21% Scadding stage 2, 2% stage 3), and no patient had extensive pulmonary fibrosis (stage 4). Computed tomography (CT) patterns of sarcoid parenchymal lung involvement were less commonly reported for Maori/PI. There were no differences in respect of baseline lung function or requirement for treatment. Ocular and skin involvement occurred more frequently in Maori and PI (P = 0.0045, P = 0.03), and erythema nodosum was more common in Caucasians (P = 0.0008). People of Polynesian ancestry appear to have less pulmonary and more extra-pulmonary manifestations of sarcoidosis. This adds to our knowledge that sarcoidosis heterogeneity is influenced by ethnicity. © 2016 Asian Pacific Society of Respirology.

Comparison of Electroacupuncture and Morphine-Mediated Analgesic Patterns in a Plantar Incision-Induced Pain Model

PubMed Central

Tsai, Shih-Ying; Chen, Kuen-Bao; Hsu, Sheng-Feng; Chen, Julia Yi-Ru

2014-01-01

Electroacupuncture (EA) is a complementary therapy to improve morphine analgesia for postoperative pain, but underlying mechanism is not well-known. Herein, we investigated EA-induced analgesic effect in a plantar incision (PI) model in male Sprague-Dawley rats. PI was performed at the left hind paw. EA of 4 Hz and high intensity or sham needling was conducted at right ST36 prior to PI and repeated for another 2 days. Behavioral responses to mechanical and thermal stimuli, spinal phospho-ERK, and Fos expression were all analyzed. In additional groups, naloxone and morphine were administered to elucidate involvement of opioid receptors and for comparison with EA. EA pretreatment significantly reduced post-PI tactile allodynia for over 1 day; repeated treatments maintained analgesic effect. Intraperitoneal naloxone could reverse EA analgesia. Low-dose subcutaneous morphine (1 mg/kg) had stronger inhibitory effect on PI-induced allodynia than EA for 1 h. However, analgesic tolerance appeared after repeated morphine injections. Both EA and morphine could equally inhibit PI-induced p-ERK and Fos inductions. We conclude that though EA and morphine attenuate postincision pain through opioid receptor activations, daily EA treatments result in analgesic accumulation whereas daily morphine injections develop analgesic tolerance. Discrepant pathways and mechanisms underlying two analgesic means may account for the results. PMID:25530786

Face recognition system and method using face pattern words and face pattern bytes

DOEpatents

Zheng, Yufeng

2014-12-23

The present invention provides a novel system and method for identifying individuals and for face recognition utilizing facial features for face identification. The system and method of the invention comprise creating facial features or face patterns called face pattern words and face pattern bytes for face identification. The invention also provides for pattern recognitions for identification other than face recognition. The invention further provides a means for identifying individuals based on visible and/or thermal images of those individuals by utilizing computer software implemented by instructions on a computer or computer system and a computer readable medium containing instructions on a computer system for face recognition and identification.

Talking to Strangers--A Sociolinguistic Experiment: Variation in Initial Dyadic Interactions between Spanish-Speakers in Early 21st Century Buenos Aires, Argentina

ERIC Educational Resources Information Center

Dziugis, Mary Ann

2010-01-01

What are the chances of a dyad of Spanish-speaking strangers using informal address in casual, initial interactions in Buenos Aires, Argentina, today? To discover the pattern(s) of contemporary address, the Principal Investigator (PI) conducted a sociolinguistic experiment focusing on strangers' initial interactions to minimize the influence of…

Magnetic Excitations of Stripes

NASA Astrophysics Data System (ADS)

Yao, Daoxin; Carlson, Erica; Campbell, David

2005-03-01

Competing tendencies in electronic systems with strong correlations can lead to spontaneous nanoscale structure, pattern formation, and even long-range spatial order. There has been continued interest in various ``stripe'' phases of electrons, as well as more recent interest in possible ``checkerboard'' patterns. New experimental techniques allow for the extraction of detailed and reproducible neutron scattering spectra in copper oxide superconductors and related nickelate compounds. We discuss the magnetic excitations of well-ordered stripe phases, including the high energy magnetic excitations of recent interest and possible connections to the ``resonance peak'' in cuprate superconductors. Using a suitably parametrized Heisenberg model and spin wave theory, we study a variety of possible stripe configurations, including vertical, diagonal, staircase, and zigzag stripes. We calculate the expected neutron scattering intensities as a function of energy and momentum. Constant energy cuts at high energy often reveal a square-like scattering pattern, and occasionally a circular pattern. Bond-centered stripes have weight gathered near (pi,pi) at low energy, indicating that only part of the spin wave cone is expected to be resolvable experimentally. In addition, we present a litmus test for experimentally distinguishing bond-centered stripes from site-centered stripes using low energy data.

Identification of single nucleotide polymorphisms of the PI3K-AKT-mTOR pathway as a risk factor of central nervous system metastasis in metastatic breast cancer.

PubMed

Le Rhun, Emilie; Bertrand, Nicolas; Dumont, Aurélie; Tresch, Emmanuelle; Le Deley, Marie-Cécile; Mailliez, Audrey; Preusser, Matthias; Weller, Michael; Revillion, Françoise; Bonneterre, Jacques

2017-12-01

The PI3K-AKT-mTOR pathway may be involved in the development of central nervous system (CNS) metastasis from breast cancer. Accordingly, herein we explored whether single nucleotide polymorphisms (SNPs) of this pathway are associated with altered risk of CNS metastasis formation in metastatic breast cancer patients. The GENEOM study (NCT00959556) included blood sample collection from breast cancer patients treated in the neoadjuvant, adjuvant or metastatic setting. We identified patients with CNS metastases for comparison with patients without CNS metastasis, defined as either absence of neurological symptoms or normal brain magnetic resonance imaging (MRI) before death or during 5-year follow-up. Eighty-eight SNPs of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian (or mechanistic) target of rapamycin (mTOR) pathway genes were selected for analysis: AKT1 (17 SNPs), AKT2 (4), FGFR1 (2), mTOR (7), PDK1 (4), PI3KR1 (11), PI3KCA (20), PTEN (17), RPS6KB1 (6). Of 342 patients with metastases, 207 fulfilled the inclusion criteria: One-hundred-and-seven patients remained free of CNS metastases at last follow-up or date of death whereas 100 patients developed CNS metastases. Among clinical parameters, hormonal and human epidermal growth factor receptor-2 (HER2) status as well as vascular tumour emboli was associated with risk of CNS metastasis. Only PI3KR1-rs706716 was associated with CNS metastasis in univariate analysis after Bonferroni correction (p < 0.00085). Multivariate analysis showed associations between AKT1-rs3803304, AKT2-rs3730050, PDK1-rs11686903 and PI3KR1-rs706716 and CNS metastasis . PI3KR1-rs706716 may be associated with CNS metastasis in metastatic breast cancer patients and could be included in a predictive composite score to detect early CNS metastasis irrespective of breast cancer subtype. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhibition of phosphatidylinositol 3,5-bisphosphate production has pleiotropic effects on various membrane trafficking routes in Arabidopsis.

PubMed

Hirano, Tomoko; Munnik, Teun; Sato, Masa H

2017-01-01

Phosphoinositides play an important role in various membrane trafficking events in eukaryotes. One of them, however, phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], has not been studied widely in plants. Using a combination of fluorescent reporter proteins and the PI(3,5)P2-specific inhibitor YM202636, here we demonstrated that in Arabidopsis thaliana, PI(3,5)P2 affects various membrane trafficking events, mostly in the post-Golgi routes. We found that YM201636 treatment effectively reduced PI(3,5)P2 concentration not only in the wild type but also in FAB1A-overexpressing Arabidopsis plants. In particular, reduced PI(3,5)P2 levels caused abnormal membrane dynamics of plasma membrane proteins, AUX1 and BOR1, with different trafficking patterns. Secretion and morphological characteristics of late endosomes and vacuoles were also affected by the decreased PI(3,5)P2 production. These pleiotropic defects in the post-Golgi trafficking events were caused by the inhibition of PI(3,5)P2 production. This effect is probably mediated by the inhibition of maturation of FAB1-positive late endosomes, thereby impairing late endosome function. In conclusion, our results imply that in Arabidopsis, late endosomes are involved in multiple post-Golgi membrane trafficking routes including not only vacuolar trafficking and endocytosis but also secretion. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Phonologic errors as a clinical marker of the logopenic variant of PPA.

PubMed

Leyton, Cristian E; Ballard, Kirrie J; Piguet, Olivier; Hodges, John R

2014-05-06

To disentangle the clinical heterogeneity of nonsemantic variants of primary progressive aphasia (PPA) and to identify a coherent linguistic-anatomical marker for the logopenic variant of PPA (lv-PPA). Key speech and language features of 14 cases of lv-PPA and 18 cases of nonfluent/agrammatic variant of PPA were systematically evaluated and scored by an independent rater blinded to diagnosis. Every case underwent a structural MRI and a Pittsburgh compound B (PiB)-PET scan, a putative biomarker of Alzheimer disease. Key speech and language features that showed association with the PiB-PET status were entered into a hierarchical cluster analysis. The linguistic features and patterns of cortical thinning in each resultant cluster were analyzed. The cluster analysis revealed 3 coherent clinical groups, each of which was linked to a specific PiB-PET status. The first cluster was linked to high PiB retention and characterized by phonologic errors and cortical thinning focused on the left superior temporal gyrus. The second and third clusters were characterized by grammatical production errors and motor speech disorders, respectively, and were associated with low PiB brain retention. A fourth cluster, however, demonstrated nonspecific language deficits and unpredictable PiB-PET status. These findings suggest that despite the clinical and pathologic heterogeneity of nonsemantic variants, discrete clinical syndromes can be distinguished and linked to specific likelihood of PiB-PET status. Phonologic errors seem to be highly predictive of high amyloid burden in PPA and can provide a specific clinical marker for lv-PPA.

Quantifying the risk of spread of bovine viral diarrhoea virus (BVDV) between contiguous herds in Ireland.

PubMed

Graham, D A; Clegg, T A; Thulke, H-H; O'Sullivan, P; McGrath, G; More, S J

2016-04-01

The control of bovine viral diarrhoea virus (BVDV) mainly focuses on the identification and restriction of persistently infected (PI) animals. However, other transmission pathways can also result in new breakdowns, including the movement of animals pregnant with PI calves (Trojan animals) and the spread of infection between contiguous farms. Contiguous spread is likely an important problem in the BVD eradication programme in Ireland, given the spatial distribution of residual infection, and the highly fragmented nature of land holdings on many Irish farms. In this study, we seek to quantify the risk of BVD spread between contiguous herds in Ireland. Multivariable logistic models were used to estimate the risk of a herd having BVD positive calves in January to June 2014 (the study period) when contiguous to a herd that had at least one BVD positive calf born in 2013. The models included risk factors relating to the study herd and to neighbouring herds. Separate multivariable models were built for each of four "PI-neighbour" factors relating to the presence of BVD+ animals and/or the presence of offspring of PI breeding animals. In total, 58,483 study herds were enrolled. The final model contained the province, the log of the number of calf births born during the study period, the number of cattle purchased between January 2013 and January 2014, and with a two-way interaction between the number of animals of unknown BVD status in the study herd and the PI-neighbour risk factor. When the number of PI-neighbour herds was used as the PI-neighbour risk factor, the odds ratio (OR) associated with the number of PI-neighbour herds ranged from 1.07 to 3.02, depending on the number of unknown animals present. To further explore the risk associated with PI-neighbour factors, the models were repeated using a subset of the study herds (n=7440) that contained no animals of unknown status. The best fitting model including "any PI-neighbour" as the PI-neighbour factor and also contained the log of the number of calf births born during the study period and the number of cattle purchased. The OR associated with "any PI-neighbour" was 1.92 (95% C.I. 1.37-2.70). This study provides the first quantitative information on the risks posed by the presence of BVD+ animals in neighbouring herds and also highlights the importance of clarifying the BVD status of animals that have not yet been tested in the context of the Irish eradication programme. Copyright © 2016 Elsevier B.V. All rights reserved.

The effects of exposure of susceptible alpacas to alpacas persistently infected with bovine viral diarrhea virus

PubMed Central

Byers, Stacey R.; Evermann, James F.; Bradway, Daniel S.; Grimm, Amanda L.; Ridpath, Julia F.; Parish, Steven M.; Tibary, Ahmed; Barrington, George M.

2011-01-01

Reports of bovine viral diarrhea virus (BVDV) infections in alpacas have been increasing in recent years but much is still unknown about the mechanisms of disease in this species. This report characterizes the transmission of BVDV from persistently infected (PI) alpacas to BVDV naïve alpacas, documents shedding patterns, and characterizes the disease effects in both PI and transiently infected alpacas. Two PI alpacas shed BVDV Type 1b virus in most body fluids, and commonly available diagnostic tests verified their status. Bovine viral diarrhea virus Type 1b transient infections produced only mild signs of disease in BVDV naïve alpacas. Viremia was detected in whole blood, but viral shedding during the acute phase was not detected and antibody appeared to be protective upon re-exposure to the virus. PMID:21629418

The Role of Shape in Semantic Memory Organization of Objects: An Experimental Study Using PI-Release.

PubMed

van Weelden, Lisanne; Schilperoord, Joost; Swerts, Marc; Pecher, Diane

2015-01-01

Visual information contributes fundamentally to the process of object categorization. The present study investigated whether the degree of activation of visual information in this process is dependent on the contextual relevance of this information. We used the Proactive Interference (PI-release) paradigm. In four experiments, we manipulated the information by which objects could be categorized and subsequently be retrieved from memory. The pattern of PI-release showed that if objects could be stored and retrieved both by (non-perceptual) semantic and (perceptual) shape information, then shape information was overruled by semantic information. If, however, semantic information could not be (satisfactorily) used to store and retrieve objects, then objects were stored in memory in terms of their shape. The latter effect was found to be strongest for objects from identical semantic categories.

Identification, introgression, and molecular marker genetic analysis and selection of a highly effective novel oat crown rust resistance from diploid oat, Avena strigosa

USDA-ARS?s Scientific Manuscript database

A new highly effective resistance to oat crown rust (Puccinia coronata f. sp. avenae) was identified in the diploid oat Avena strigosa PI 258731 and introgressed into hexaploid cultivated oat. Young plants with this resistance show moderate susceptibility, whereas older plant tissues and adult plant...

Identification of amino acid changes in the envelope glycoproteins of bovine viral diarrhea viruses isolated from alpaca that may be involved in host adaptation

USDA-ARS?s Scientific Manuscript database

Bovine viral diarrhea viruses (BVDV) are most commonly associated with infections of cattle. However, BVDV is often isolated from closely related ruminants with a number of BVDV-1b viruses being isolated from alpacas that were both acutely and persistently infected (PI). The complete nucleotide se...

Phosphatidylinositol 3-kinase coordinately activates the MEK/ERK and AKT/NFkappaB pathways to maintain osteoclast survival.

PubMed

Gingery, Anne; Bradley, Elizabeth; Shaw, Aubie; Oursler, Merry Jo

2003-05-01

We have examined highly purified osteoclasts that were generated in vitro from murine co-culture of marrow precursors with stromal support cells and have found evidence of activation of the MEK/ERK and AKT/NFkappaB survival pathways. Many mature marrow-derived osteoclasts survived for at least 48 h in culture whether or not they are maintained with stromal cells. Moreover, supplementing purified osteoclasts with RANKL and/or M-CSF had no impact on their survival pattern. In addition, spleen-derived osteoclasts generated with RANKL and M-CSF treatment exhibited a similar survival pattern. Blocking MEK, AKT, or NFkappaB activity resulted in apoptosis of many, but not all, of the osteoclasts in purified marrow-derived osteoclasts, marrow-derived osteoclasts co-cultured with stromal cells, and spleen-derived osteoclasts maintained with RANKL and M-CSF. These data support that both the MEK/ERK and AKT/NFkappaB pathways contribute to osteoclast survival. Since PI3K has been shown to activate either of these pathways, we have examined its role in osteoclast survival. PI3K inhibition caused apoptosis of nearly all osteoclasts in purified and co-cultured marrow-derived osteoclasts and spleen-derived osteoclasts maintained with RANKL and M-CSF. Interestingly, in marrow-derived co-cultures, the apoptotic response was restricted to osteoclasts as there was no evidence of stromal support cell apoptosis. PI3K inhibition also blocked MEK1/2, ERK1/2, and AKT phosphorylation and NFkappaB activation in purified osteoclasts. Simultaneous blockage of both AKT and MEK1/2 caused rapid apoptosis of nearly all osteoclasts, mimicking the response to PI3K inhibition. These data reveal that PI3K coordinately activates two distinct survival pathways that are both important in osteoclast survival. Copyright 2003 Wiley-Liss, Inc.

Hepatitis C Virus Genotype 1 to 6 Protease Inhibitor Escape Variants: In Vitro Selection, Fitness, and Resistance Patterns in the Context of the Infectious Viral Life Cycle.

PubMed

Serre, Stéphanie B N; Jensen, Sanne B; Ghanem, Lubna; Humes, Daryl G; Ramirez, Santseharay; Li, Yi-Ping; Krarup, Henrik; Bukh, Jens; Gottwein, Judith M

2016-06-01

Hepatitis C virus (HCV) NS3 protease inhibitors (PIs) are important components of novel HCV therapy regimens. Studies of PI resistance initially focused on genotype 1. Therefore, knowledge about the determinants of PI resistance for the highly prevalent genotypes 2 to 6 remains limited. Using Huh7.5 cell culture-infectious HCV recombinants with genotype 1 to 6 NS3 protease, we identified protease positions 54, 155, and 156 as hot spots for the selection of resistance substitutions under treatment with the first licensed PIs, telaprevir and boceprevir. Treatment of a genotype 2 isolate with the newer PIs vaniprevir, faldaprevir, simeprevir, grazoprevir, paritaprevir, and deldeprevir identified positions 156 and 168 as hot spots for resistance; the Y56H substitution emerged for three newer PIs. Substitution selection also depended on the specific recombinant. The substitutions identified conferred cross-resistance to several PIs; however, most substitutions selected under telaprevir or boceprevir treatment conferred less resistance to certain newer PIs. In a single-cycle production assay, across genotypes, PI treatment primarily decreased viral replication, which was rescued by PI resistance substitutions. The substitutions identified resulted in differential effects on viral fitness, depending on the original recombinant and the substitution. Across genotypes, fitness impairment induced by resistance substitutions was due primarily to decreased replication. Most combinations of substitutions that were identified increased resistance or fitness. Combinations of resistance substitutions with fitness-compensating substitutions either rescued replication or compensated for decreased replication by increasing assembly. This comprehensive study provides insight into the selection patterns and effects of PI resistance substitutions for HCV genotypes 1 to 6 in the context of the infectious viral life cycle, which is of interest for clinical and virological HCV research. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The Akt signaling pathway

PubMed Central

Madhunapantula, SubbaRao V; Mosca, Paul J

2011-01-01

Studies using cultured melanoma cells and patient tumor biopsies have demonstrated deregulated PI3 kinase-Akt3 pathway activity in ∼70% of melanomas. Furthermore, targeting Akt3 and downstream PRAS40 has been shown to inhibit melanoma tumor development in mice. Although these preclinical studies and several other reports using small interfering RNAs and pharmacological agents targeting key members of this pathway have been shown to retard melanoma development, analysis of early Phase I and Phase II clinical trials using pharmacological agents to target this pathway demonstrate the need for (1) selection of patients whose tumors have PI3 kinase-Akt pathway deregulation, (2) further optimization of therapeutic agents for increased potency and reduced toxicity, (3) the identification of additional targets in the same pathway or in other signaling cascades that synergistically inhibit the growth and progression of melanoma, and (4) better methods for targeted delivery of pharmaceutical agents inhibiting this pathway. In this review we discuss key potential targets in PI3K-Akt3 signaling, the status of pharmacological agents targeting these proteins, drugs under clinical development, and strategies to improve the efficacy of therapeutic agents targeting this pathway. PMID:22157148

Spacelab simulation using a Lear Jet aircraft: Mission no. 4 (ASSESS program)

NASA Technical Reports Server (NTRS)

Reller, J. O., Jr.; Neel, C. B.; Mason, R. H.

1975-01-01

The fourth ASSESS Spacelab simulation mission utilizing a Lear Jet aircraft featured trained experiment operators (EOs) in place of the participating scientists, to simulate the role and functions of payload specialists in Spacelab who may conduct experiments developed by other scientists. The experiment was a broadband infrared photometer coupled to a 30-cm, open port, IR telescope. No compromises in equipment design or target selection were made to simplify operator tasks; the science goals of the mission were selected to advance the mainline research program of the principle investigator (PI). Training of the EOs was the responsibility of the PI team and consisted of laboratory sessions, on-site training during experiment integration, and integrated mission training using the aircraft as a high-fidelity simulator. The EO permission experience in these several disciplines proved adequate for normal experiment operations, but marginal for the identification and remedy of equipment malfunctions. During the mission, the PI utilized a TV communication system to assist the EOs to overcome equipment difficulties; both science and operations were successfully implemented.

Identification of Psilocybe cubensis spore allergens by immunoprinting.

PubMed

Helbling, A; Horner, W E; Lehrer, S B

1993-01-01

Previous studies established that Psilocybe cubensis contains potent allergens, and that a significant percentage of atopic subjects were sensitized to P. cubensis spores. The objective of this study was to identify P. cubensis spore allergens using isoelectric focusing (IEF) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) immunoprinting. Coomassie blue staining of IEF gels detected approximately 20 bands between pI 3.6 and 9.3. Immunoprints obtained with 15 P. cubensis skin test- and RAST-positive sera revealed 13 IgE-binding bands; the most reactive were at pI 5.0 (80%), 5.6 (87%), 8.7 (80%) and 9.3 (100%). SDS-PAGE resolved 27 proteins ranging from about 13 to 112 kD. SDS-PAGE immunoprints conducted with 11 skin test- and RAST-positive sera demonstrated 18 IgE-binding bands; most sera reacted to 16 (82%), 35 (100%) and 76 kD (91%) allergens. Both electrophoretic procedures demonstrated a single allergen (at pI 9.3 and 35 kD) that reacted with all sera tested. This study corroborates the allergenic significance of P. cubensis spores and identifies the allergens of greatest importance.

Cost effective raspberry pi-based radio frequency identification tagging of mice suitable for automated in vivo imaging.

PubMed

Bolaños, Federico; LeDue, Jeff M; Murphy, Timothy H

2017-01-30

Automation of animal experimentation improves consistency, reduces potential for error while decreasing animal stress and increasing well-being. Radio frequency identification (RFID) tagging can identify individual mice in group housing environments enabling animal-specific tracking of physiological parameters. We describe a simple protocol to radio frequency identification (RFID) tag and detect mice. RFID tags were injected sub-cutaneously after brief isoflurane anesthesia and do not require surgical steps such as suturing or incisions. We employ glass-encapsulated 125kHz tags that can be read within 30.2±2.4mm of the antenna. A raspberry pi single board computer and tag reader enable automated logging and cross platform support is possible through Python. We provide sample software written in Python to provide a flexible and cost effective system for logging the weights of multiple mice in relation to pre-defined targets. The sample software can serve as the basis of any behavioral or physiological task where users will need to identify and track specific animals. Recently, we have applied this system of tagging to automated mouse brain imaging within home-cages. We provide a cost effective solution employing open source software to facilitate adoption in applications such as automated imaging or tracking individual animal weights during tasks where food or water restriction is employed as motivation for a specific behavior. Copyright © 2016 Elsevier B.V. All rights reserved.

Computer-Aided Discovery Tools for Volcano Deformation Studies with InSAR and GPS

NASA Astrophysics Data System (ADS)

Pankratius, V.; Pilewskie, J.; Rude, C. M.; Li, J. D.; Gowanlock, M.; Bechor, N.; Herring, T.; Wauthier, C.

2016-12-01

We present a Computer-Aided Discovery approach that facilitates the cloud-scalable fusion of different data sources, such as GPS time series and Interferometric Synthetic Aperture Radar (InSAR), for the purpose of identifying the expansion centers and deformation styles of volcanoes. The tools currently developed at MIT allow the definition of alternatives for data processing pipelines that use various analysis algorithms. The Computer-Aided Discovery system automatically generates algorithmic and parameter variants to help researchers explore multidimensional data processing search spaces efficiently. We present first application examples of this technique using GPS data on volcanoes on the Aleutian Islands and work in progress on combined GPS and InSAR data in Hawaii. In the model search context, we also illustrate work in progress combining time series Principal Component Analysis with InSAR augmentation to constrain the space of possible model explanations on current empirical data sets and achieve a better identification of deformation patterns. This work is supported by NASA AIST-NNX15AG84G and NSF ACI-1442997 (PI: V. Pankratius).

Artificial Immune System for Flight Envelope Estimation and Protection

DTIC Science & Technology

2014-12-31

Throttle Failure 103 5.3. Estimation Algorithms for Sensor AC 108 5.3.1. Roll Rate Sensor Bias 108...4.13. Reference Features-Pattern for a Roll Rate Sensor Under Low Severity Failure 93 Figure 4.14. Reference Features-Pattern for a Roll Rate...Average PI for Different ACs 134 Figure 6.9. Roll Response Under High Magnitude Stabilator Failure 135 Figure 6.10. Pitch

A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity.

PubMed

Rajasethupathy, Priyamvada; Antonov, Igor; Sheridan, Robert; Frey, Sebastian; Sander, Chris; Tuschl, Thomas; Kandel, Eric R

2012-04-27

Small RNA-mediated gene regulation during development causes long-lasting changes in cellular phenotypes. To determine whether small RNAs of the adult brain can regulate memory storage, a process that requires stable and long-lasting changes in the functional state of neurons, we generated small RNA libraries from the Aplysia CNS. In these libraries, we discovered an unexpectedly abundant expression of a 28 nucleotide sized class of piRNAs in brain, which had been thought to be germline specific. These piRNAs have unique biogenesis patterns, predominant nuclear localization, and robust sensitivity to serotonin, a modulatory transmitter that is important for memory. We find that the Piwi/piRNA complex facilitates serotonin-dependent methylation of a conserved CpG island in the promoter of CREB2, the major inhibitory constraint of memory in Aplysia, leading to enhanced long-term synaptic facilitation. These findings provide a small RNA-mediated gene regulatory mechanism for establishing stable long-term changes in neurons for the persistence of memory. Copyright © 2012 Elsevier Inc. All rights reserved.

Elucidating the Small Regulatory RNA Repertoire of the Sea Anemone Anemonia viridis Based on Whole Genome and Small RNA Sequencing

PubMed Central

Patel, Hardip; Forêt, Sylvain; Karlsen, Bård Ove; Jørgensen, Tor Erik; Hall-Spencer, Jason M

2018-01-01

Abstract Cnidarians harbor a variety of small regulatory RNAs that include microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs), but detailed information is limited. Here, we report the identification and expression of novel miRNAs and putative piRNAs, as well as their genomic loci, in the symbiotic sea anemone Anemonia viridis. We generated a draft assembly of the A. viridis genome with putative size of 313 Mb that appeared to be composed of about 36% repeats, including known transposable elements. We detected approximately equal fractions of DNA transposons and retrotransposons. Deep sequencing of small RNA libraries constructed from A. viridis adults sampled at a natural CO2 gradient off Vulcano Island, Italy, identified 70 distinct miRNAs. Eight were homologous to previously reported miRNAs in cnidarians, whereas 62 appeared novel. Nine miRNAs were recognized as differentially expressed along the natural seawater pH gradient. We found a highly abundant and diverse population of piRNAs, with a substantial fraction showing ping–pong signatures. We identified nearly 22% putative piRNAs potentially targeting transposable elements within the A. viridis genome. The A. viridis genome appeared similar in size to that of other hexacorals with a very high divergence of transposable elements resembling that of the sea anemone genus Exaiptasia. The genome encodes and expresses a high number of small regulatory RNAs, which include novel miRNAs and piRNAs. Differentially expressed small RNAs along the seawater pH gradient indicated regulatory gene responses to environmental stressors. PMID:29385567

Bovine Viral Diarrhea Virus in Zoos: A Perspective from the Veterinary Team

PubMed Central

Kottwitz, Jack J.; Ortiz, Melissa

2016-01-01

The many different species in close proximity make zoological collections a unique environment for disease transmission. Bovine Viral Diarrhea Virus (BVDV) is of special concern with zoos due to the numerous exotic ruminant species that this virus can infect. BVDV occurs as both a non-cytopathic and a cytopathic strain both of which are capable of infecting exotic ruminants. The cytopathic strain causes mucosal disease (MD) and death. Infection with the non-cytopathic strain may produce persistently infected (PI) animals. PI individuals may show vague clinical signs, including abortion. Management of BVDV in zoos should focus on identification of PI individuals and prevention of infection of other animals of the collection. Variability makes serological testing as the sole method of screening for BVDV infection undesirable in exotic ruminants. Combination testing provides a definitive answer, especially in sensitive wildlife. Use of a combination of antigen-capture ELISA (ACE) with haired skin, Real Time-PCR (RT-PCR) on whole blood, and antibody detection via serum neutralization has the greatest potential to identify PI animals. An animal that is positive on both ACE and RT-PCR, but is negative on serology should be considered highly suspicious of being a PI, and should be isolated and undergo repeat testing 4–6 weeks later to confirm positive status. This testing methodology also allows screening of pregnant and newborn animals. Isolation or culling may need to be considered in animals determined to be positive via combination testing. These decisions should only be made after careful consideration and evaluation, especially with endangered species. PMID:26779151

Bovine Viral Diarrhea Virus in Zoos: A Perspective from the Veterinary Team.

PubMed

Kottwitz, Jack J; Ortiz, Melissa

2015-01-01

The many different species in close proximity make zoological collections a unique environment for disease transmission. Bovine Viral Diarrhea Virus (BVDV) is of special concern with zoos due to the numerous exotic ruminant species that this virus can infect. BVDV occurs as both a non-cytopathic and a cytopathic strain both of which are capable of infecting exotic ruminants. The cytopathic strain causes mucosal disease (MD) and death. Infection with the non-cytopathic strain may produce persistently infected (PI) animals. PI individuals may show vague clinical signs, including abortion. Management of BVDV in zoos should focus on identification of PI individuals and prevention of infection of other animals of the collection. Variability makes serological testing as the sole method of screening for BVDV infection undesirable in exotic ruminants. Combination testing provides a definitive answer, especially in sensitive wildlife. Use of a combination of antigen-capture ELISA (ACE) with haired skin, Real Time-PCR (RT-PCR) on whole blood, and antibody detection via serum neutralization has the greatest potential to identify PI animals. An animal that is positive on both ACE and RT-PCR, but is negative on serology should be considered highly suspicious of being a PI, and should be isolated and undergo repeat testing 4-6 weeks later to confirm positive status. This testing methodology also allows screening of pregnant and newborn animals. Isolation or culling may need to be considered in animals determined to be positive via combination testing. These decisions should only be made after careful consideration and evaluation, especially with endangered species.

Modeling spatial variation in avian survival and residency probabilities

USGS Publications Warehouse

Saracco, James F.; Royle, J. Andrew; DeSante, David F.; Gardner, Beth

2010-01-01

The importance of understanding spatial variation in processes driving animal population dynamics is widely recognized. Yet little attention has been paid to spatial modeling of vital rates. Here we describe a hierarchical spatial autoregressive model to provide spatially explicit year-specific estimates of apparent survival (phi) and residency (pi) probabilities from capture-recapture data. We apply the model to data collected on a declining bird species, Wood Thrush (Hylocichla mustelina), as part of a broad-scale bird-banding network, the Monitoring Avian Productivity and Survivorship (MAPS) program. The Wood Thrush analysis showed variability in both phi and pi among years and across space. Spatial heterogeneity in residency probability was particularly striking, suggesting the importance of understanding the role of transients in local populations. We found broad-scale spatial patterning in Wood Thrush phi and pi that lend insight into population trends and can direct conservation and research. The spatial model developed here represents a significant advance over approaches to investigating spatial pattern in vital rates that aggregate data at coarse spatial scales and do not explicitly incorporate spatial information in the model. Further development and application of hierarchical capture-recapture models offers the opportunity to more fully investigate spatiotemporal variation in the processes that drive population changes.

Propidium iodide staining: a new application in fluorescence microscopy for analysis of cytoarchitecture in adult and developing rodent brain.

PubMed

Hezel, Marcus; Ebrahimi, Fahim; Koch, Marco; Dehghani, Faramarz

2012-10-01

Immunohistochemical visualization of antigens in specimen has evolved to an indispensable technique in biomedical research for investigations of cell morphology and pathology both in bright field and fluorescence microscopy. While there are couple of staining methods that reveal entire cytoarchitecture in bright field microscopy such as Nissl or hemalaun-eosin, there are still limitations in visualizations of cytoarchitecture in fluorescence microscopy. The present study reports a simple staining method that provides the required illustration of cell allocations and cellular composition in fluorescence microscopy in adult and in developing rodent central nervous system using the fluorophore propidium iodide (PI, 5μg/mL). PI is a well-accepted marker for degenerating cells when applied prior to fixation (pre-fixation PI staining). Here, PI was added to the sections after the fixation (post-fixation PI staining). This revised labeling procedure led to similar cytoarchitectural staining patterns in fluorescence microscopy as observed with hemalaun in bright field microscopy. This finding was proven in organotypic hippocampal slice cultures (OHSC) and brain sections obtained from different postnatal developmental stages. Excitotoxically lesioned OHSC subjected to pre-fixation PI staining merely showed brightly labeled condensed nuclei of degenerating neurons. In contrast, post-fixation PI staining additionally revealed extensive labeling of neuronal cell bodies and glial cells within the OHSC, thus allowing visualization of stratification of neuronal layers and cell morphology. Furthermore, post-fixation PI staining was combined with NeuN, calbindin, calretinin, glial fibrillary acidic protein or Griffonia simplicifolia isolectin B4 (IB(4)) in post natal (p1 and p9) and adult rats. In early post-natal brain sections almost all mentioned cellular markers led to an incomplete staining of the native cell organization and resulted in an inaccurate estimation of cell morphology when compared to adult brains. In contrast, post-fixation PI staining allowed investigation of the whole cytoarchitecture independent of the developmental stage. Taken together, post-fixation PI staining provides a detailed insight in the morphology of both developing and adult brain tissues in fluorescence microscopy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Discovery of phosphoinositide 3-kinases (PI3K) p110β isoform inhibitor 4-[2-hydroxyethyl(1-naphthylmethyl)amino]-6-[(2S)-2-methylmorpholin-4-yl]-1H-pyrimidin-2-one, an effective antithrombotic agent without associated bleeding and insulin resistance.

PubMed

Giordanetto, Fabrizio; Wållberg, Andreas; Ghosal, Saswati; Iliefski, Tommy; Cassel, Johan; Yuan, Zhong-Qing; von Wachenfeldt, Henrik; Andersen, Søren M; Inghardt, Tord; Tunek, Anders; Nylander, Sven

2012-11-01

Structure-based evolution of the original fragment leads resulted in the identification of 4-[2-hydroxyethyl(1-naphthylmethyl)amino]-6-[(2S)-2-methylmorpholin-4-yl]-1H-pyrimidin-2-one, (S)-21, a potent, selective phosphoinositide 3-kinases (PI3K) p110β isoform inhibitor with favourable in vivo antiplatelet effect. Despite its antiplatelet action, (S)-21 did not significantly increase bleeding time in dogs. Additionally, due to its enhanced selectivity over p110α, (S)-21 did not induce any insulin resistance in rats. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Sexual violence against children in a family environment attended by SAMVVIS, Teresina, PI].

PubMed

Monteiro, Claudete Ferreira de Souza; Teles, Delma Castelo Branco Soares; Castro, Karoline Lopes; Vasconcelos, Nayane Sieglyne Veras de; Magalhães, Rosilane de Lima Brito; de Deus, Maria Castelo Branco Rocha

2008-01-01

This study deals with the characterization of sexual violence in children seen at the Services for the Assistance of Women Victims of Sexual Violence (SAMVVIS) from 2004 to 2007 in Teresina, PI. Data collected from 229 charts indicate that the age of the children varies from less than one year up to 12 years of age. The identification of the aggressor was the neighbor (29.7%), stepfather (11.4%), father (9.4%) and uncle with 8.4%. In regards to the occupation of the aggressor, 20.35% are students, unemployed (26.85%) and retired (3.89%). It follows that there is the need for more efficiency in the policy of child protection and a need for campaigns to alert the mothers when choosing the caretakers of their daughters.

Polymorphism of alpha 1 antitrypsin in North American species of Canis

USGS Publications Warehouse

Federoff, N.E.; Kueppers, F.

2000-01-01

a1-Antitrypsin (A1AT) is a major protease inhibitor present in all mammalian sera that have thus far been investigated. A1AT is also highly polymorphic and is therefore a useful genetic marker. Previously reported A1AT polymorphism in domestic dogs consisted of two alleles designated as PiM and PiS which exhibited frequencies of 0.72 and 0.28, respectively, in a group of randomly collected mongrel dogs. North American species of Canis, which included gray wolves (n=29), Mexican wolves (n=20), coyotes (n=24), wolfdog crosses (n=9), and red wolves (n=27) were tested for A1AT polymorphism. A1AT phenotypes were determined by isoelectric focusing, followed by direct immunoblotting using a specific antiserum. A1AT concentrations were determined by radial immunodiffusion. Concentrations of A1AT were similar to those found in domestic dogs (2.26 + 0.3 mg/ml SD) and tended to be higher in females than in males, possibly indicating that A1AT may be hormonally influenced in females. Three phenotypic band patterns were observed (M, MS, S). The allele frequencies for domestic dogs and gray wolves were very similar, 0.72 and 0.69 for PiM and 0.28 and 0.31 for PiS, respectively. The Mexican wolves had a significantly lower frequency of PiS= 0.10. Coyotes and red wolves were all found to be monomorphic for the PiS allele and were indistinguishable from each other in that respect.

Positional signaling and expression of ENHANCER OF TRY AND CPC1 are tuned to increase root hair density in response to phosphate deficiency in Arabidopsis thaliana.

PubMed

Savage, Natasha; Yang, Thomas J W; Chen, Chung Ying; Lin, Kai-Lan; Monk, Nicholas A M; Schmidt, Wolfgang

2013-01-01

Phosphate (Pi) deficiency induces a multitude of responses aimed at improving the acquisition of Pi, including an increased density of root hairs. To understand the mechanisms involved in Pi deficiency-induced alterations of the root hair phenotype in Arabidopsis (Arabidopsis thaliana), we analyzed the patterning and length of root epidermal cells under control and Pi-deficient conditions in wild-type plants and in four mutants defective in the expression of master regulators of cell fate, CAPRICE (CPC), ENHANCER OF TRY AND CPC 1 (ETC1), WEREWOLF (WER) and SCRAMBLED (SCM). From this analysis we deduced that the longitudinal cell length of root epidermal cells is dependent on the correct perception of a positional signal ('cortical bias') in both control and Pi-deficient plants; mutants defective in the receptor of the signal, SCM, produced short cells characteristic of root hair-forming cells (trichoblasts). Simulating the effect of cortical bias on the time-evolving probability of cell fate supports a scenario in which a compromised positional signal delays the time point at which non-hair cells opt out the default trichoblast pathway, resulting in short, trichoblast-like non-hair cells. Collectively, our data show that Pi-deficient plants increase root hair density by the formation of shorter cells, resulting in a higher frequency of hairs per unit root length, and additional trichoblast cell fate assignment via increased expression of ETC1.

Amplification of Chromosome 1q Genes Encoding the Phosphoinositide Signalling Enzymes PI4KB, AKT3, PIP5K1A and PI3KC2B in Breast Cancer

PubMed Central

Waugh, Mark G.

2014-01-01

Little is known about the possible oncogenic roles of genes encoding for the phosphatidylinositol 4-kinases, a family of enzymes that regulate an early step in phosphoinositide signalling. To address this issue, the mutational status of all four human phosphatidylinositol 4-kinases genes was analyzed across 852 breast cancer samples using the COSMIC data resource. Point mutations in the phosphatidylinositol 4-kinase genes were uncommon and appeared in less than 1% of the patient samples however, 62% of the tumours had increases in gene copy number for PI4KB which encodes the phosphatidylinositol 4-kinase IIIbeta isozyme. Extending this analysis to subsequent enzymes in the phosphoinositide signalling cascades revealed that the only PIP5K1A, PI3KC2B and AKT3 genes exhibited similar patterns of gene copy number variation. By comparison, gene copy number increases for established oncogenes such as EGFR and HER2/Neu were only evident in 20% of the samples. The PI4KB, PIP5K1A, PI3KC2B and AKT3 genes are related in that they all localize to chromosome 1q which is often structurally and numerically abnormal in breast cancer. These results demonstrate that a gene quartet encoding a potential phosphoinositide signalling pathway is amplified in a subset of breast cancers. PMID:25368680

Recessive Loci Pps-1 and OM Differentially Regulate PISTILLATA-1 and APETALA3-1 Expression for Sepal and Petal Development in Papaver somniferum

PubMed Central

Singh, Sharad K.; Shukla, Ashutosh K.; Dhawan, Om P.; Shasany, Ajit K.

2014-01-01

The involvement of PISTILLATA (PI) and APETALA (AP) transcription factors in the development of floral organs has previously been elucidated but little is known about their upstream regulation. In this investigation, two novel mutants generated in Papaver somniferum were analyzed - one with partially petaloid sepals and another having sepaloid petals. Progeny from reciprocal crosses of respective mutant parent genotypes showed a good fit to the monogenic Mendelian inheritance model, indicating that the mutant traits are likely controlled by the single, recessive nuclear genes named “Pps-1” and “OM” in the partially petaloid sepal and sepaloid petal phenotypes, respectively. Both paralogs of PISTILLATA (PapsPI-1 and PapsPI-3) were obtained from the sepals and petals of P. somniferum. Ectopic expression of PapsPI-1 in tobacco resulted in a partially petaloid sepal phenotype at a low frequency. Upregulation of PapsPI-1 and PapsAP3-1 in the petal and the petal part of partially petaloid sepal mutant and down-regulation of the same in sepaloid petal mutant indicates a differential pattern of regulation for flowering-related genes in various whorls. Similarly, it was found that the recessive mutation OM in sepaloid petal mutant downregulates PapsPI-1 and PapsAP3-1 transcripts. The recessive nature of the mutations was confirmed by the segregation ratios obtained in this analysis. PMID:24979593

Proton magnetic resonance spectroscopy predicts proliferative activity in diffuse low-grade gliomas.

PubMed

Guillevin, Remy; Menuel, Carole; Duffau, Hugues; Kujas, Michel; Capelle, Laurent; Aubert, Agnès; Taillibert, Sophie; Idbaih, Ahmed; Pallud, Joan; Demarco, Giovanni; Costalat, Robert; Hoang-Xuan, Khê; Chiras, Jacques; Vallée, Jean-Noel

2008-04-01

The aim of the study was to investigate the ability of (1)HMRS to reflect proliferative activity of diffuse low-grade gliomas (WHO grade II). Between November 2002 and March 2007, a prospective study was performed on consecutive patients with suspected supratentorial hemispheric diffuse low-grade tumors. All the patients underwent MR examination using uniform procedures, and then surgical resection or biopsy within 2 weeks of the MR examination. Proliferative activity of the tumors was assessed by Ki-67 immunochemistry (Mb-1) on paraffin embedded tumor sections. Spectroscopic data was compared with Ki-67 labeling index and other histologic data such as histological subtype, cellular atypia, cellular density using univariate and multivariate analysis. 82 of 97 consecutive patients had histologically confirmed WHO grade 2 gliomas. Ki-67 proliferation index (PI) was correlated with specific spectral patterns: (1) low PI (<4%) was associated with increased Cho/Cr and absence of both free lipids or lactates; (2) intermediate PI (4-8%) was associated with resonance of lactates; and (3) high PI (>8%) was characterized by a resonance of free lipids. On multivariate analysis, resonance of lactates and resonance of free lipids appeared as independent predictors of intermediate PI (P < 0.001) and high PI (P < 0.001), respectively; moreover, free lipids resonance was correlated with cellular atypia (P < 0.05). This study suggests that (1)HMRS is a reliable tool to evaluate the proliferation activity of WHO grade 2 glioma and to identify potentially more aggressive clinical behavior.

Positional Signaling and Expression of ENHANCER OF TRY AND CPC1 Are Tuned to Increase Root Hair Density in Response to Phosphate Deficiency in Arabidopsis thaliana

PubMed Central

Savage, Natasha; Yang, Thomas J. W.; Chen, Chung Ying; Lin, Kai-Lan; Monk, Nicholas A. M.; Schmidt, Wolfgang

2013-01-01

Phosphate (Pi) deficiency induces a multitude of responses aimed at improving the acquisition of Pi, including an increased density of root hairs. To understand the mechanisms involved in Pi deficiency-induced alterations of the root hair phenotype in Arabidopsis (Arabidopsis thaliana), we analyzed the patterning and length of root epidermal cells under control and Pi-deficient conditions in wild-type plants and in four mutants defective in the expression of master regulators of cell fate, CAPRICE (CPC), ENHANCER OF TRY AND CPC 1 (ETC1), WEREWOLF (WER) and SCRAMBLED (SCM). From this analysis we deduced that the longitudinal cell length of root epidermal cells is dependent on the correct perception of a positional signal (‘cortical bias’) in both control and Pi-deficient plants; mutants defective in the receptor of the signal, SCM, produced short cells characteristic of root hair-forming cells (trichoblasts). Simulating the effect of cortical bias on the time-evolving probability of cell fate supports a scenario in which a compromised positional signal delays the time point at which non-hair cells opt out the default trichoblast pathway, resulting in short, trichoblast-like non-hair cells. Collectively, our data show that Pi-deficient plants increase root hair density by the formation of shorter cells, resulting in a higher frequency of hairs per unit root length, and additional trichoblast cell fate assignment via increased expression of ETC1. PMID:24130712

Flow Pattern Identification of Horizontal Two-Phase Refrigerant Flow Using Neural Networks

DTIC Science & Technology

2015-12-31

AFRL-RQ-WP-TP-2016-0079 FLOW PATTERN IDENTIFICATION OF HORIZONTAL TWO-PHASE REFRIGERANT FLOW USING NEURAL NETWORKS (POSTPRINT) Abdeel J...Journal Article Postprint 01 October 2013 – 22 June 2015 4. TITLE AND SUBTITLE FLOW PATTERN IDENTIFICATION OF HORIZONTAL TWO-PHASE REFRIGERANT FLOW USING...networks were used to automatically identify two-phase flow patterns for refrigerant R-134a flowing in a horizontal tube. In laboratory experiments

48-hours administration of fenoterol in spontaneous preterm labor - Doppler blood flow assessment of placental and fetal circulation.

PubMed

Grzesiak, Mariusz; Hincz, Piotr; Forys, Sebastian; Ahmed, Rehana B; Wilczynski, Jan

2013-01-01

The aims were to investigate whether any changes in placental and fetal circulation were observed during fenoterol tocolysis within the first 48 hours of therapy. Doppler evaluation of placental and fetal circulation was performed prior to fenoterol administration and then after 24 and 48 hours. Maternal heart rate and pulsatility index (PI) in uterine arteries were assessed. FHR, RI and PI of umbilical artery and middle cerebral artery were measured. E/A ratio for A-V valves, the myocardial performance index (MPI) and shortening fraction (SF) were calculated for both ventricles independently. The blood flow pattern in DV was assessed using PI, S/a ratio and peak velocity index for the vein. To determine changes over time in all study variable analysis of variance (ANOVA) for repeated measurements followed by Tukey-Kramer's multiple comparison test was used. The effects of additional clinical covariates were checked. Uterine and fetal arterial blood flow patterns were not altered significantly during 48 hours of tocolysis. No significant changes were observed in fetal cardiac function parameters as well. The evaluation of Doppler parameters in the DV revealed a significant increase in PVIV after 48 hours. Additionally after 48 hours of successful tocolysis S/a ratio values were significantly lower. Short term intravenous administration of fenoterol seems not to alter uterine and fetal arterial blood flow pattern. Direct fetal cardiac function remained unaffected. However significant changes of selected Doppler parameters in DV may suggest further studies should be performed to assess more precisely fetal venous blood flow.

Single Charged Particle Identification in Nuclear Emulsion Using Multiple Coulomb Scattering Method

NASA Astrophysics Data System (ADS)

Tint, Khin T.; Endo, Yoko; Hoshino, Kaoru; Ito, Hiroki; Itonaga, Kazunori; Kinbara, Shinji; Kobayashi, Hidetaka; Mishina, Akihiro; Soe, Myint K.; Yoshida, Junya; Nakazawa, Kazuma

Development of particle identification technique for single charged particles such as Ξ- hyperon, proton, K- and π- mesons is on-going by measuring multiple Coulomb scattering in nuclear emulsion. We generated several thousands of tracks of the single charged particles in nuclear emulsion stacks with GEANT 4 simulation and obtained second difference in constant Sagitta Method. We found that recognition of Ξ- hyperon from π- mesons is well satisfied, although that from K- and proton are a little difficult. On the other hand, the consistency of second difference of real Ξ- hyperon and pi meson tracks and simulation results were also confirmed.

Palatal rugae pattern: An aid for sex identification

PubMed Central

Gadicherla, Prahlad; Saini, Divya; Bhaskar, Milana

2017-01-01

Background: Palatal rugoscopy, or palatoscopy, is the process by which human identification can be obtained by inspecting the transverse palatal rugae inside the mouth. Aim: The aim of the study is to investigate the potential of using palatal rugae as an aid for sex identification in Bengaluru population. Materials and Methods: One hundred plaster casts equally distributed between males and females belonging to age range of 4–16 years were examined for different rugae patterns. Thomas and Kotze classification was adopted for identification of these rugae patterns. Statistical Analysis: The data obtained were subjected to discriminant function analysis to determine the applicability of palatal rugae pattern as an aid for sex identification. Results: Difference in unification patterns among males and females was found to be statistically significant. No significant difference was found between males and females in terms of number of rugae. Overall, wavy and curvy were the most predominant type of rugae seen. Discriminant function analysis enabled sex identification with an accuracy of 80%. Conclusion: This preliminary study undertaken showed the existence of a distinct pattern of distribution of palatal rugae between males and females of Bengaluru population. This study opens scope for further research with a larger sample size to establish palatal rugae as a valuable tool for sex identification for forensic purposes. PMID:28584485

mTOR inhibition elicits a dramatic response in PI3K-dependent colon cancers.

PubMed

Deming, Dustin A; Leystra, Alyssa A; Farhoud, Mohammed; Nettekoven, Laura; Clipson, Linda; Albrecht, Dawn; Washington, Mary Kay; Sullivan, Ruth; Weichert, Jamey P; Halberg, Richard B

2013-01-01

The phosphatidylinositide-3-kinase (PI3K) signaling pathway is critical for multiple cellular functions including metabolism, proliferation, angiogenesis, and apoptosis, and is the most commonly altered pathway in human cancers. Recently, we developed a novel mouse model of colon cancer in which tumors are initiated by a dominant active PI3K (FC PIK3ca). The cancers in these mice are moderately differentiated invasive mucinous adenocarcinomas of the proximal colon that develop by 50 days of age. Interestingly, these cancers form without a benign intermediary or aberrant WNT signaling, indicating a non-canonical mechanism of tumorigenesis. Since these tumors are dependent upon the PI3K pathway, we investigated the potential for tumor response by the targeting of this pathway with rapamycin, an mTOR inhibitor. A cohort of FC PIK3ca mice were treated with rapamycin at a dose of 6 mg/kg/day or placebo for 14 days. FDG dual hybrid PET/CT imaging demonstrated a dramatic tumor response in the rapamycin arm and this was confirmed on necropsy. The tumor tissue remaining after treatment with rapamycin demonstrated increased pERK1/2 or persistent phosphorylated ribosomal protein S6 (pS6), indicating potential resistance mechanisms. This unique model will further our understanding of human disease and facilitate the development of therapeutics through pharmacologic screening and biomarker identification.

Contrast-enhanced transrectal ultrasound for prediction of prostate cancer aggressiveness: The role of normal peripheral zone time-intensity curves.

PubMed

Huang, Hui; Zhu, Zheng-Qiu; Zhou, Zheng-Guo; Chen, Ling-Shan; Zhao, Ming; Zhang, Yang; Li, Hong-Bo; Yin, Li-Ping

2016-12-08

To assess the role of time-intensity curves (TICs) of the normal peripheral zone (PZ) in the identification of biopsy-proven prostate nodules using contrast-enhanced transrectal ultrasound (CETRUS). This study included 132 patients with 134 prostate PZ nodules. Arrival time (AT), peak intensity (PI), mean transit time (MTT), area under the curve (AUC), time from peak to one half (TPH), wash in slope (WIS) and time to peak (TTP) were analyzed using multivariate linear logistic regression and receiver operating characteristic (ROC) curves to assess whether combining nodule TICs with normal PZ TICs improved the prediction of prostate cancer (PCa) aggressiveness. The PI, AUC (p < 0.001 for both), MTT and TPH (p = 0.011 and 0.040 respectively) values of the malignant nodules were significantly higher than those of the benign nodules. Incorporating the PI and AUC values (both, p < 0.001) of the normal PZ TIC, but not the MTT and TPH values (p = 0.076 and 0.159 respectively), significantly improved the AUC for prediction of malignancy (PI: 0.784-0.923; AUC: 0.758-0.891) and assessment of cancer aggressiveness (p < 0.001). Thus, all these findings indicate that incorporating normal PZ TICs with nodule TICs in CETRUS readings can improve the diagnostic accuracy for PCa and cancer aggressiveness assessment.

Exploiting PI3K/mTOR signaling to accelerate epithelial wound healing.

PubMed

Castilho, R M; Squarize, C H; Gutkind, J S

2013-09-01

The molecular circuitries controlling the process of skin wound healing have gained new significant insights in recent years. This knowledge is built on landmark studies on skin embryogenesis, maturation, and differentiation. Furthermore, the identification, characterization, and elucidation of the biological roles of adult skin epithelial stem cells and their influence in tissue homeostasis have provided the foundation for the overall understanding of the process of skin wound healing and tissue repair. Among numerous signaling pathways associated with epithelial functions, the PI3K/Akt/mTOR signaling route has gained substantial attention with the generation of animal models capable of dissecting individual components of the pathway, thereby providing a novel insight into the molecular framework underlying skin homeostasis and tissue regeneration. In this review, we focus on recent findings regarding the mechanisms involved in wound healing associated with the upregulation of the activity of the PI3K/Akt/mTOR circuitry. This review highlights critical findings on the molecular mechanisms controlling the activation of mTOR, a downstream component of the PI3K-PTEN pathway, which is directly involved in epithelial migration and proliferation. We discuss how this emerging information can be exploited for the development of novel pharmacological intervention strategies to accelerate the healing of critical size wounds. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The role of phosphoinositide 3-kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractions

PubMed Central

O’Neil, T K; Duffy, L R; Frey, J W; Hornberger, T A

2009-01-01

Resistance exercise induces a hypertrophic response in skeletal muscle and recent studies have begun to shed light on the molecular mechanisms involved in this process. For example, several studies indicate that signalling by the mammalian target of rapamycin (mTOR) is necessary for a hypertrophic response. Furthermore, resistance exercise has been proposed to activate mTOR signalling through an upstream pathway involving the phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB); however, this hypothesis has not been thoroughly tested. To test this hypothesis, we first evaluated the temporal pattern of signalling through PI3K–PKB and mTOR following a bout of resistance exercise with eccentric contractions (EC). Our results indicated that the activation of signalling through PI3K–PKB is a transient event (<15 min), while the activation of mTOR is sustained for a long duration (>12 h). Furthermore, inhibition of PI3K–PKB activity did not prevent the activation of mTOR signalling by ECs, indicating that PI3K–PKB is not part of the upstream regulatory pathway. These observations led us to investigate an alternative pathway for the activation of mTOR signalling involving the synthesis of phosphatidic acid (PA) by phospholipase D (PLD). Our results demonstrate that ECs induce a sustained elevation in [PA] and inhibiting the synthesis of PA by PLD prevented the activation of mTOR. Furthermore, we determined that similar to ECs, PA activates mTOR signalling through a PI3K–PKB-independent mechanism. Combined, the results of this study indicate that the activation of mTOR following eccentric contractions occurs through a PI3K–PKB-independent mechanism that requires PLD and PA. PMID:19470781

Iron-induced oxidative injury differentially regulates PI3K/Akt/GSK3beta pathway in synaptic endings from adult and aged rats.

PubMed

Uranga, Romina María; Giusto, Norma María; Salvador, Gabriela Alejandra

2009-10-01

In this work we study the state of phosphoinositide-3-kinase/Akt/glycogen synthase kinase 3 beta (PI3K/Akt/GSK3beta) signaling during oxidative injury triggered by free iron using cerebral cortex synaptic endings isolated from adult (4-month-old) and aged (28-month-old) rats. Synaptosomes were exposed to FeSO4 (50 microM) for different periods of time and synaptosomal viability and the state of the PI3K/Akt/GSK3beta pathway were evaluated in adult and aged animals. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction and lactate dehydrogenase leakage were significantly affected in both age groups. However, aged animals showed a greater susceptibility to oxidative stress. In adults, Akt was activated after a brief exposure time (5 min), whereas in aged animals activation occurred after 5 and 30 min of incubation with the metal ion. GSK3beta phosphorylation showed the same activation pattern as that observed for Akt. Both Akt and GSK3beta phosphorylation were dependent on PI3K activation. Extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation was temporally coincident with Akt activation and was PI3K dependent in adults, whereas ERK1/2 activation in aged rats was higher than that observed in adults and showed no dependence on PI3K activity. We demonstrate here that synaptic endings from adult and aged animals subjected to iron-induced neurotoxicity show a differential profile in the activation of PI3K/Akt/GSK3beta. Our results strongly suggest that the increased susceptibility of aged animals to oxidative injury provokes a differential modulation of key signaling pathways involved in synaptic plasticity and neuronal survival.

Glutathione S-transferases in neonatal liver disease.

PubMed Central

Mathew, J.; Cattan, A. R.; Hall, A. G.; Hines, J. E.; Nelson, R.; Eastham, E.; Burt, A. D.

1992-01-01

AIMS: To investigate the distribution of alpha and pi class glutathione S-transferases (GST) in normal fetal, neonatal, and adult liver; and to examine changes in GST expression in neonatal liver disease. METHODS: alpha and pi class GST were immunolocalised in sections of formalin fixed liver tissue obtained from human fetuses (n = 21), neonates (n = 8), young children (n = 9) and adults (n = 10), and from neonates with extrahepatic biliary atresia (n = 15) and neonatal hepatitis (n = 12). Monospecific rabbit polyclonal antibodies were used with a peroxidase-antiperoxidase method. RESULTS: Expression of pi GST was localised predominantly within biliary epithelial cells of developing and mature bile ducts of all sizes from 16 weeks' gestation until term and in neonatal and adult liver. Coexpression of pi and alpha GST was seen in hepatocytes of developing fetal liver between 16 and 34 weeks' gestation. Although pi GST was seen in occasional hepatocytes up to six months of life, this isoenzyme was not expressed by hepatocytes in adult liver. By contrast, alpha GST continued to be expressed by hepatocytes in adult liver; this isoenzyme was also seen in some epithelial cells of large bile ducts in adult liver. No change was observed in the distribution of alpha GST in either neonatal hepatitis or extrahepatic biliary atresia. However, aberrant expression of pi GST was identified in hepatocytes of all but one case of extrahepatic biliary atresia but in only two cases of neonatal hepatitis. CONCLUSIONS: The phenotypic alterations noted in extrahepatic biliary atresia may result from the effect of cholate stasis. Evaluation of the pattern of pi and alpha GST distribution by immunohistochemical staining may provide valuable information in distinguishing between these two forms of neonatal liver disease. Images PMID:1401176

A Sorghum bicolor expression atlas reveals dynamic genotype-specific expression profiles for vegetative tissues of grain, sweet and bioenergy sorghums

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

Shakoor, N; Nair, R; Crasta, O

2014-01-23

Background: Effective improvement in sorghum crop development necessitates a genomics-based approach to identify functional genes and QTLs. Sequenced in 2009, a comprehensive annotation of the sorghum genome and the development of functional genomics resources is key to enable the discovery and deployment of regulatory and metabolic genes and gene networks for crop improvement. Results: This study utilizes the first commercially available whole-transcriptome sorghum microarray (Sorgh-WTa520972F) to identify tissue and genotype-specific expression patterns for all identified Sorghum bicolor exons and UTRs. The genechip contains 1,026,373 probes covering 149,182 exons (27,577 genes) across the Sorghum bicolor nuclear, chloroplast, and mitochondrial genomes. Specificmore » probesets were also included for putative non-coding RNAs that may play a role in gene regulation (e. g., microRNAs), and confirmed functional small RNAs in related species (maize and sugarcane) were also included in our array design. We generated expression data for 78 samples with a combination of four different tissue types (shoot, root, leaf and stem), two dissected stem tissues (pith and rind) and six diverse genotypes, which included 6 public sorghum lines (R159, Atlas, Fremont, PI152611, AR2400 and PI455230) representing grain, sweet, forage, and high biomass ideotypes. Conclusions: Here we present a summary of the microarray dataset, including analysis of tissue-specific gene expression profiles and associated expression profiles of relevant metabolic pathways. With an aim to enable identification and functional characterization of genes in sorghum, this expression atlas presents a new and valuable resource to the research community.« less

Paternity tests in Mexico: Results obtained in 3005 cases.

PubMed

García-Aceves, M E; Romero Rentería, O; Díaz-Navarro, X X; Rangel-Villalobos, H

2018-04-01

National and international reports regarding the paternity testing activity scarcely include information from Mexico and other Latin American countries. Therefore, we report different results from the analysis of 3005 paternity cases analyzed during a period of five years in a Mexican paternity testing laboratory. Motherless tests were the most frequent (77.27%), followed by trio cases (20.70%); the remaining 2.04% included different cases of kinship reconstruction. The paternity exclusion rate was 29.58%, higher but into the range reported by the American Association of Blood Banks (average 24.12%). We detected 65 mutations, most of them involving one-step (93.8% and the remaining were two-step mutations (6.2%) thus, we were able to estimate the paternal mutation rate for 17 different STR loci: 0.0018 (95% CI 0.0005-0.0047). Five triallelic patterns and 12 suspected null alleles were detected during this period; however, re-amplification of these samples with a different Human Identification (HID) kit confirmed the homozygous genotypes, which suggests that most of these exclusions actually are one-step mutations. HID kits with ≥20 STRs detected more exclusions, diminishing the rate of inconclusive results with isolated exclusions (<3 loci), and leading to higher paternity indexes (PI). However, the Powerplex 21 kit (20 STRs) and Powerplex Fusion kit (22 STRs) offered similar PI (p = 0.379) and average number of exclusions (PE) (p = 0.339) when a daughter was involved in motherless tests. In brief, besides to report forensic parameters from paternity tests in Mexico, results describe improvements to solve motherless paternity tests using HID kits with ≥20 STRs instead of one including 15 STRs. Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

[Study on the relation between Pi-deficiency pattern and metabolic syndrome in patients with polycystic ovarian syndrome].

PubMed

Wang, Xing-Juan; Jin, Hua-Liang; Liu, Ying

2010-11-01

To evaluate the relation between Pi-deficiency syndrome (PDS) pattern and metabolic syndrome (MS) in patients with polycystic ovarian syndrome (PCOS), for exploring their internal pathologic mechanism. Among the 102 PCOS patients, 22 complicated with MS (PCOS-MS) and 80 not complicated with MS (PCOS-NMS), the Chinese medicine syndrome pattern was differentiated as PDS in 50 patients and non-PDS in 52. The clinical data, in terms of fasting blood glucose (FBG), fasting insulin (FINS), waistline, body weight (BW), stature, blood pressure (BP), etc. was collected and compared and the relation between data was analyzed. Levels of FINS and homeostasis model of assessment for insulin resistence index (HOMA-IR), in PCOS-MS patients were significantly higher than those in PCOS-NMS patients, also higher in patients of PDS pattern than those of non-PDS pattern (P < 0.01); the occurrences of MS and PDS were highly positively correlated with levels of FINS and HOMA-IR (P < 0.01); incidence of MS in patients of PDS pattern was significantly higher than those in patients of non-PDS pattern (P < 0.05); presenting of PDS was positively related with the existence of MS (P < 0.05), but in case of the FINS or HOMA-IR factor being controlled, statistical meaning of the relativity between them turned to insignificant (P > 0.05). PCOS patients of PDS pattern are the high-risk population of MS, which might be related with the insulin resistance. So, early treatment of PCOS, especially on patients of PDS pattern, is of important significance for preventing the complication, as MS, of the disease.

Improving credibility and transparency of conservation impact evaluations through the partial identification approach.

PubMed

McConnachie, Matthew M; Romero, Claudia; Ferraro, Paul J; van Wilgen, Brian W

2016-04-01

The fundamental challenge of evaluating the impact of conservation interventions is that researchers must estimate the difference between the outcome after an intervention occurred and what the outcome would have been without it (counterfactual). Because the counterfactual is unobservable, researchers must make an untestable assumption that some units (e.g., organisms or sites) that were not exposed to the intervention can be used as a surrogate for the counterfactual (control). The conventional approach is to make a point estimate (i.e., single number along with a confidence interval) of impact, using, for example, regression. Point estimates provide powerful conclusions, but in nonexperimental contexts they depend on strong assumptions about the counterfactual that often lack transparency and credibility. An alternative approach, called partial identification (PI), is to first estimate what the counterfactual bounds would be if the weakest possible assumptions were made. Then, one narrows the bounds by using stronger but credible assumptions based on an understanding of why units were selected for the intervention and how they might respond to it. We applied this approach and compared it with conventional approaches by estimating the impact of a conservation program that removed invasive trees in part of the Cape Floristic Region. Even when we used our largest PI impact estimate, the program's control costs were 1.4 times higher than previously estimated. PI holds promise for applications in conservation science because it encourages researchers to better understand and account for treatment selection biases; can offer insights into the plausibility of conventional point-estimate approaches; could reduce the problem of advocacy in science; might be easier for stakeholders to agree on a bounded estimate than a point estimate where impacts are contentious; and requires only basic arithmetic skills. © 2015 Society for Conservation Biology.

Can a barcode scanner for blood collection improve patient identification integrity in the emergency department? A prospective before-and-after study.

PubMed

Spain, David; Crilly, Julia; Pierce, John; Steele, Michael; Scuffham, Paul; Keijzers, Gerben

2015-02-01

To describe the effect of interventions designed to improve patient identification (PI) during pathology collection in the ED. A prospective before-and-after intervention study was conducted between June 2009 and June 2010 in a regional ED in Queensland, Australia. Interventions aimed to improve PI and specimen labelling, and consisted of: (i) education alone; and (ii) education plus an armband scanner that voice-prompted collector behaviour. Main outcomes measured included: frequency of correct key behaviours (KBs) during specimen collection, pathology integrity errors and cost of interventions. Data from 282 ED pathology collections were analysed (before: n = 115, after with education: n = 95, after with education plus armband scanner: n = 72). KBs for PI and labelling improved significantly following education plus armband scanner use. Application of armbands before sample collection increased (36% vs 90%, P < 0.001), as did asking the patient to state their name (25% vs 93%, P < 0.001) and date of birth (22% vs 93%, P < 0.001). These results were similar, albeit less pronounced, when the effect of education only was assessed. No primary patient misidentification was detected in this small study. The annual costs for a hospital to adopt the education programme with and without the armband scanner were $104,045 and $5330 respectively. ED staff had poor behaviours for identifying patients and labelling pathology specimens before intervention. These safety behaviours were considered an assumed skill. Education alone improved critical KBs markedly that was further augmented by the armband scanner. The cost to adopt education alone is relatively low compared to the addition of armband scanner technology. © 2015 The Authors. Emergency Medicine Australasia published by Wiley Publishing Asia Pty Ltd on behalf of Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

An Autonomous Star Identification Algorithm Based on One-Dimensional Vector Pattern for Star Sensors

PubMed Central

Luo, Liyan; Xu, Luping; Zhang, Hua

2015-01-01

In order to enhance the robustness and accelerate the recognition speed of star identification, an autonomous star identification algorithm for star sensors is proposed based on the one-dimensional vector pattern (one_DVP). In the proposed algorithm, the space geometry information of the observed stars is used to form the one-dimensional vector pattern of the observed star. The one-dimensional vector pattern of the same observed star remains unchanged when the stellar image rotates, so the problem of star identification is simplified as the comparison of the two feature vectors. The one-dimensional vector pattern is adopted to build the feature vector of the star pattern, which makes it possible to identify the observed stars robustly. The characteristics of the feature vector and the proposed search strategy for the matching pattern make it possible to achieve the recognition result as quickly as possible. The simulation results demonstrate that the proposed algorithm can effectively accelerate the star identification. Moreover, the recognition accuracy and robustness by the proposed algorithm are better than those by the pyramid algorithm, the modified grid algorithm, and the LPT algorithm. The theoretical analysis and experimental results show that the proposed algorithm outperforms the other three star identification algorithms. PMID:26198233

An Autonomous Star Identification Algorithm Based on One-Dimensional Vector Pattern for Star Sensors.

PubMed

Luo, Liyan; Xu, Luping; Zhang, Hua

2015-07-07

In order to enhance the robustness and accelerate the recognition speed of star identification, an autonomous star identification algorithm for star sensors is proposed based on the one-dimensional vector pattern (one_DVP). In the proposed algorithm, the space geometry information of the observed stars is used to form the one-dimensional vector pattern of the observed star. The one-dimensional vector pattern of the same observed star remains unchanged when the stellar image rotates, so the problem of star identification is simplified as the comparison of the two feature vectors. The one-dimensional vector pattern is adopted to build the feature vector of the star pattern, which makes it possible to identify the observed stars robustly. The characteristics of the feature vector and the proposed search strategy for the matching pattern make it possible to achieve the recognition result as quickly as possible. The simulation results demonstrate that the proposed algorithm can effectively accelerate the star identification. Moreover, the recognition accuracy and robustness by the proposed algorithm are better than those by the pyramid algorithm, the modified grid algorithm, and the LPT algorithm. The theoretical analysis and experimental results show that the proposed algorithm outperforms the other three star identification algorithms.

The influence of semantic and morphological complexity of verbs on sentence recall: Implications for the nature of conceptual representation and category-specific deficits.

PubMed

Mobayyen, Forouzan; de Almeida, Roberto G

2005-03-01

One hundred and forty normal undergraduate students participated in a Proactive Interference (PI) experiment with sentences containing verbs from four different semantic and morphological classes (lexical causatives, morphological causatives, and morphologically complex and simplex perception verbs). Past research has shown significant PI build-up effects for semantically and morphologically complex verbs in isolation (de Almeida & Mobayyen, 2004). The results of the present study show that, when embedded into sentence contexts, semantically and morphologically complex verbs do not produce significant PI build-up effects. Different verb classes, however, yield different recall patterns: sentences with semantically complex verbs (e.g., causatives) were recalled significantly better than sentences with semantically simplex verbs (e.g., perception verbs). The implications for the nature of both verb-conceptual representations and category-specific semantic deficits are discussed.

Pro-inflammatory Cytokine Expression of Spleen Dendritic Cells in Mouse Toxoplasmosis

PubMed Central

Nam, Ho-Woo; Ahn, Hye-Jin

2011-01-01

Dendritic cells have been known as a member of strong innate immune cells against infectious organelles. In this study, we evaluated the cytokine expression of splenic dendritic cells in chronic mouse toxoplasmosis by tissue cyst-forming Me49 strain and demonstrated the distribution of lymphoid dendritic cells by fluorescence-activated cell sorter (FACS). Pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-6, and IL-10 increased rapidly at week 1 post-infection (PI) and peaked at week 3 PI. Serum IL-10 level followed the similar patterns. FACS analysis showed that the number of CD8α+/CD11c+ splenic dendritic cells increased at week 1 and peaked at week 3 PI. In conclusion, mouse splenic dendritic cells showed early and rapid cytokine changes and may have important protective roles in early phases of murine toxoplasmosis. PMID:21738265

The plastid ribosomal proteins. Identification of all the proteins in the 30 S subunit of an organelle ribosome (chloroplast).

PubMed

Yamaguchi, K; von Knoblauch, K; Subramanian, A R

2000-09-15

Identification of all the protein components of a plastid (chloroplast) ribosomal 30 S subunit has been achieved, using two-dimensional gel electropholesis, high performance liquid chromatography purification, N-terminal sequencing, polymerase chain reaction-based screening of cDNA library, nucleotide sequencing, and mass spectrometry (electrospray ionization, matrix-assisted laser desorption/ionization time-of-flight, and reversed-phase HPLC coupled with electrospray ionization mass spectrometry). 25 proteins were identified, of which 21 are orthologues of all Escherichia coli 30 S ribosomal proteins (S1-S21), and 4 are plastid-specific ribosomal proteins (PSRPs) that have no homologues in the mitochondrial, archaebacterial, or cytosolic ribosomal protein sequences in data bases. 12 of the 25 plastid 30 S ribosomal proteins (PRPs) are encoded in the plastid genome, whereas the remaining 13 are encoded by the nuclear genome. Post-translational transit peptide cleavage sites for the maturation of the 13 cytosolically synthesized PRPs, and post-translational N-terminal processing in the maturation of the 12 plastid synthesized PRPs are described. Post-translational modifications in several PRPs were observed: alpha-N-acetylation of S9, N-terminal processings leading to five mature forms of S6 and two mature forms of S10, C-terminal and/or internal modifications in S1, S14, S18, and S19, leading to two distinct forms differing in mass and/or charge (the corresponding modifications are not observed in E. coli). The four PSRPs in spinach plastid 30 S ribosomal subunit (PSRP-1, 26.8 kDa, pI 6.2; PSRP-2, 21.7 kDa, pI 5.0; PSRP-3, 13.8 kDa, pI 4.9; PSRP-4, 5.2 kDa, pI 11.8) comprise 16% (67.6 kDa) of the total protein mass of the 30 S subunit (429.3 kDa). PSRP-1 and PSRP-3 show sequence similarities with hypothetical photosynthetic bacterial proteins, indicating their possible origins in photosynthetic bacteria. We propose the hypothesis that PSRPs form a "plastid translational regulatory module" on the 30 S ribosomal subunit structure for the possible mediation of nuclear factors on plastid translation.

OsWRKY74, a WRKY transcription factor, modulates tolerance to phosphate starvation in rice.

PubMed

Dai, Xiaoyan; Wang, Yuanyuan; Zhang, Wen-Hao

2016-02-01

The WRKY transcription factor family has 109 members in the rice genome, and has been reported to be involved in the regulation of biotic and abiotic stress in plants. Here, we demonstrated that a rice OsWRKY74 belonging to group III of the WRKY transcription factor family was involved in tolerance to phosphate (Pi) starvation. OsWRKY74 was localized in the nucleus and mainly expressed in roots and leaves. Overexpression of OsWRKY74 significantly enhanced tolerance to Pi starvation, whereas transgenic lines with down-regulation of OsWRKY74 were sensitive to Pi starvation. Root and shoot biomass, and phosphorus (P) concentration in rice OsWRKY74-overexpressing plants were ~16% higher than those of wild-type (WT) plants in Pi-deficient hydroponic solution. In soil pot experiments, >24% increases in tiller number, grain weight and P concentration were observed in rice OsWRKY74-overexpressing plants compared to WT plants when grown in P-deficient medium. Furthermore, Pi starvation-induced changes in root system architecture were more profound in OsWRKY74-overexpressing plants than in WT plants. Expression patterns of a number of Pi-responsive genes were altered in the OsWRKY74-overexpressing and RNA interference lines. In addition, OsWRKY74 may also be involved in the response to deficiencies in iron (Fe) and nitrogen (N) as well as cold stress in rice. In Pi-deficient conditions, OsWRKY74-overexpressing plants exhibited greater accumulation of Fe and up-regulation of the cold-responsive genes than WT plants. These findings highlight the role of OsWRKY74 in modulation of Pi homeostasis and potential crosstalk between P starvation and Fe starvation, and cold stress in rice. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Biochemical and Genetic Evidence for the Presence of Multiple Phosphatidylinositol- and Phosphatidylinositol 4,5-Bisphosphate-Specific Phospholipases C in Tetrahymena▿‡

PubMed Central

Leondaritis, George; Sarri, Theoni; Dafnis, Ioannis; Efstathiou, Antonia; Galanopoulou, Dia

2011-01-01

Eukaryotic phosphoinositide-specific phospholipases C (PI-PLC) specifically hydrolyze phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], produce the Ca2+-mobilizing agent inositol 1,4,5-trisphosphate, and regulate signaling in multicellular organisms. Bacterial PtdIns-specific PLCs, also present in trypanosomes, hydrolyze PtdIns and glycosyl-PtdIns, and they are considered important virulence factors. All unicellular eukaryotes studied so far contain a single PI-PLC-like gene. In this report, we show that ciliates are an exception, since we provide evidence that Tetrahymena species contain two sets of functional genes coding for both bacterial and eukaryotic PLCs. Biochemical characterization revealed two PLC activities that differ in their phosphoinositide substrate utilization, subcellular localization, secretion to extracellular space, and sensitivity to Ca2+. One of these activities was identified as a typical membrane-associated PI-PLC activated by low-micromolar Ca2+, modestly activated by GTPγS in vitro, and inhibited by the compound U73122 [1-(6-{[17β-3-methoxyestra-1,3,5(10)-trien-17-yl]amino}hexyl)-1H-pyrrole-2,5-dione]. Importantly, inhibition of PI-PLC in vivo resulted in rapid upregulation of PtdIns(4,5)P2 levels, suggesting its functional importance in regulating phosphoinositide turnover in Tetrahymena. By in silico and molecular analysis, we identified two PLC genes that exhibit significant similarity to bacterial but not trypanosomal PLC genes and three eukaryotic PI-PLC genes, one of which is a novel inactive PLC similar to proteins identified only in metazoa. Comparative studies of expression patterns and PI-PLC activities in three T. thermophila strains showed a correlation between expression levels and activity, suggesting that the three eukaryotic PI-PLC genes are functionally nonredundant. Our findings imply the presence of a conserved and elaborate PI-PLC-Ins(1,4,5)P3-Ca2+ regulatory axis in ciliates. PMID:21169416

Antibody response to Ehrlichia risticii and antibody reactivity to the component antigens in horses with induced Potomac horse fever.

PubMed

Dutta, S K; Mattingly, B L; Shankarappa, B

1989-10-01

The antibody response and the antibody reactivity to component antigens of Ehrlichia risticii were studied in horses with induced Potomac horse fever. These horses had no detectable antibodies to E. risticii in their preinoculation (PrI) sera by indirect fluorescent-antibody assay and enzyme-linked immunosorbent assay (ELISA). All the horses exhibited typical disease features following experimental infection and responded with specific antibodies, as measured by ELISA and indirect fluorescent-antibody assay. A primary antibody response was detected in 70% of the horses, while a secondary-type antibody response was detected in 30% of the horses by ELISA. In the primary antibody response, a distinct titer was observed at 2 weeks postinoculation (PI), when the immunoglobulin M (IgM)/IgG ratio was 2 to 5, and the overall antibody titer peaked at 6 to 8 weeks PI. The secondary-type antibody response exhibited a characteristic titer at 1 week PI, the IgM and IgG titers were about equal at 2 weeks PI, and the overall antibody titer peaked at 6 weeks PI. A transient depression in the IgG response at 4 weeks PI was observed in both response types. The antibody was maintained at a high titer for over a year in all horses. Western immunoblot reactivity showed that the antisera collected from these infected horses at 4 to 5 weeks PI recognized some or all of the six major E. risticii component antigens (70, 55, 51, 44, 33, and 28 kilodaltons), all of which were apparent surface components. The 6- to 8-week PI antisera recognized up to 16 component antigens, including 9 major antigens (110, 86, 70, 55, 51, 49, 44, 33, and 28 kilodaltons). However, the PrI sera of these horses showed reactivity at various intensities with one to seven of the component antigens. There was no apparent correlation between this reactivity pattern and the subsequent antibody response types.

Cell wall-bound cationic and anionic class III isoperoxidases of pea root: biochemical characterization and function in root growth.

PubMed

Kukavica, Biljana M; Veljovicc-Jovanovicc, Sonja D; Menckhoff, Ljiljana; Lüthje, Sabine

2012-07-01

Cell wall isolated from pea roots was used to separate and characterize two fractions possessing class III peroxidase activity: (i) ionically bound proteins and (ii) covalently bound proteins. Modified SDS-PAGE separated peroxidase isoforms by their apparent molecular weights: four bands of 56, 46, 44, and 41kDa were found in the ionically bound fraction (iPOD) and one band (70kDa) was resolved after treatment of the cell wall with cellulase and pectinase (cPOD). Isoelectric focusing (IEF) patterns for iPODs and cPODs were significantly different: five iPODs with highly cationic pI (9.5-9.2) were detected, whereas the nine cPODs were anionic with pI values between pH 3.7 and 5. iPODs and cPODs showed rather specific substrate affinity and different sensitivity to inhibitors, heat, and deglycosylation treatments. Peroxidase and oxidase activities and their IEF patterns for both fractions were determined in different zones along the root and in roots of different ages. New iPODs with pI 9.34 and 9.5 were induced with root growth, while the activity of cPODs was more related to the formation of the cell wall in non-elongating tissue. Treatment with auxin that inhibits root growth led to suppression of iPOD and induction of cPOD. A similar effect was obtained with the widely used elicitor, chitosan, which also induced cPODs with pI 5.3 and 5.7, which may be specifically related to pathogen defence. The differences reported here between biochemical properties of cPOD and iPOD and their differential induction during development and under specific treatments implicate that they are involved in specific and different physiological processes.

Evaluation of the acrosomal status in Lama glama sperm incubated with acrosome reaction inducers.

PubMed

Carretero, M I; Fumuso, F G; Neild, D M; Giuliano, S M; Cetica, P; Miragaya, M H

2015-09-01

The objectives of this study were to evaluate the effect of different acrosome reaction (AR) inducers on viability and acrosomal status in llama spermatozoa, by using the FITC-PNA/PI technique and evaluate if there is a positive correlation between the FITC-PNA/PI and the Coomassie blue (CB) staining techniques. After incubating twenty ejaculates in 0.1% collagenase the centrifuged pellets were resuspended in TALP-BSA medium. An aliquot was sonicated to remove the acrosomal content (positive control). The rest of the sample was incubated for 3h at 38 °C with 5% CO2 and 100% humidity. Three aliquots were further incubated 1h with one of the following AR inducers: calcium ionophore, ionomycin or progesterone. One without inducers and the other, incubated with dimethyl sulfoxide (vehicle of the inducing agents). Acrosomes were evaluated at time 0 and after 4h incubation. Calcium ionophore was the most potent agent for inducing the AR (67.2 ± 14.4% live+dead AR sperm) (P < 0.05). These samples showed no motility and viability was very low (0-30%). Both ionomycin and progesterone presented significantly higher (P < 0.05) percentages of total AR sperm than the controls, but had similar percentages of dead reacted sperm to the controls. A positive correlation was observed between the intact acrosome FITC-PNA/PI pattern (live+dead sperm) and the acrosome-present CB pattern (r = 0.64; P = 0.000) in all the evaluated samples. the FITC-PNA/PI technique simultaneously evaluates viability and acrosomal status in llama spermatozoa and calcium ionophore could be used as a control of AR. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification and classification of genes regulated by phosphatidylinositol 3-kinase- and TRKB-mediated signalling pathways during neuronal differentiation in two subtypes of the human neuroblastoma cell line SH-SY5Y.

PubMed

Nishida, Yuichiro; Adati, Naoki; Ozawa, Ritsuko; Maeda, Aasami; Sakaki, Yoshiyuki; Takeda, Tadayuki

2008-10-28

SH-SY5Y cells exhibit a neuronal phenotype when treated with all-trans retinoic acid (RA), but the molecular mechanism of activation in the signalling pathway mediated by phosphatidylinositol 3-kinase (PI3K) is unclear. To investigate this mechanism, we compared the gene expression profiles in SK-N-SH cells and two subtypes of SH-SY5Y cells (SH-SY5Y-A and SH-SY5Y-E), each of which show a different phenotype during RA-mediated differentiation. SH-SY5Y-A cells differentiated in the presence of RA, whereas RA-treated SH-SY5Y-E cells required additional treatment with brain-derived neurotrophic factor (BDNF) for full differentiation. After exposing cells to a PI3K inhibitor, LY294002, we identified 386 genes and categorised these genes into two clusters dependent on the PI3K signalling pathway during RA-mediated differentiation in SH-SY5Y-A cells. Transcriptional regulation of the gene cluster, including 158 neural genes, was greatly reduced in SK-N-SH cells and partially impaired in SH-SY5Y-E cells, which is consistent with a defect in the neuronal phenotype of these cells. Additional stimulation with BDNF induced a set of neural genes that were down-regulated in RA-treated SH-SY5Y-E cells but were abundant in differentiated SH-SY5Y-A cells. We identified gene clusters controlled by PI3K- and TRKB-mediated signalling pathways during the differentiation of two subtypes of SH-SY5Y cells. The TRKB-mediated bypass pathway compensates for impaired neural function generated by defects in several signalling pathways, including PI3K in SH-SY5Y-E cells. Our expression profiling data will be useful for further elucidation of the signal transduction-transcriptional network involving PI3K or TRKB.

Hard quark-quark scattering with exclusive reactions

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

Barton, D.S.; Bunce, G.M.; Carroll, A.S.

1984-07-19

We have begun a program designed to study hard quark-quark scattering with exclusive reactions, focusing on quasi-elastic two-body reactions with all possible quark flavor exchanges. Examples are ..pi../sup -/p ..-->.. ..pi../sup -/p, rho/sup -/p, ..pi../sup +/..delta../sup -/, K/sup +/..sigma../sup -/, or K..lambda... Of the two-body exclusives, only elastic scattering had been measured at such large t previous to our experiment. By comparing the relative importance of different final states, the energy dependence of the production ratios of these states, the prominence of resonances such as rho/sup -/ over background in this region, and measuring polarizations where accessible, we have collectedmore » a large body of data on hard scattering in a completely new domain. Previously, essential all short distance QCD tests have been for inclusive processes. We have taken data with both negative and positive incident beam at 10 GeV/c on a hydrogen target and will present the first results, for ..pi../sup -/p ..-->.. ..pi../sup -/p and rho/sup -/p at THETA/sub cm/ = 90/sup 0/, -t = 9 GeV/sup 2//c/sup 2/. The apparatus consists of a magnetic spectrometer, with Cerenkov particle identification, which selects stable charged particles (protons in this case) at high momentum near 90/sup 0/ in the center-of-mass. A large aperture array of PWCs observes the recoil particle or charged decay products. Cross sections are extremely low, approximately a 1 nb/(GeV/c)/sup 2/ for elastic scattering. We will report on a sample of more than 1000 ..pi../sup -/p elastic events, and on rho/sup -/p, where the rho/sup -/ decay distribution was observed. We find a surprisingly large rho/sup -/p cross section in this large momentum transfer region, with rho/sup -/p about half the elastic cross section, and a striking spin alignment of the rho/sup -/.« less

Epidermal growth factor-induced phosphatidylinositol 3-kinase activation and DNA synthesis. Identification of Grb2-associated binder 2 as the major mediator in rat hepatocytes.

PubMed

Kong, M; Mounier, C; Wu, J; Posner, B I

2000-11-17

In previous work we showed that the phosphatidylinositol 3-kinase (PI3-kinase), not the mitogen-activated protein kinase, pathway is necessary and sufficient to account for insulin- and epidermal growth factor (EGF)-induced DNA synthesis in rat hepatocytes. Here, using a dominant-negative p85, we confirmed the key role of EGF-induced PI3-kinase activation and sought to identify the mechanism by which this is effected. Our results show that EGF activates PI3-kinase with a time course similar to that of the association of p85 with three principal phosphotyrosine proteins (i. e. PY180, PY105, and PY52). We demonstrated that each formed a distinct p85-associated complex. PY180 and PY52 each constituted about 10% of EGF-activated PI3-kinase, whereas PY105 was responsible for 80%. PY105 associated with Grb2 and SHP-2, and although it behaved like Gab1, none of the latter was detected in rat liver. We therefore cloned a cDNA from rat liver, which was found to be 95% homologous to the mouse Grb2-associated binder 2 (Gab2) cDNA sequence. Using a specific Gab2 antibody, we demonstrated its expression in and association with p85, SHP-2, and Grb2 upon EGF treatment of rat hepatocytes. Gab2 accounted for most if not all of the PY105 species, since immunoprecipitation of Gab2 with specific antibodies demonstrated parallel immunodepletion of Gab2 and PY105 from the residual supernatants. We also found that the PI3-kinase activity associated with Gab2 was totally abolished by dominant negative p85. Thus, Gab2 appears to be the principal EGF-induced PY protein recruiting and activating PI3-kinase and mitogenesis.

Pathway-based identification of biomarkers for targeted therapeutics: personalized oncology with PI3K pathway inhibitors.

PubMed

Andersen, Jannik N; Sathyanarayanan, Sriram; Di Bacco, Alessandra; Chi, An; Zhang, Theresa; Chen, Albert H; Dolinski, Brian; Kraus, Manfred; Roberts, Brian; Arthur, William; Klinghoffer, Rich A; Gargano, Diana; Li, Lixia; Feldman, Igor; Lynch, Bethany; Rush, John; Hendrickson, Ronald C; Blume-Jensen, Peter; Paweletz, Cloud P

2010-08-04

Although we have made great progress in understanding the complex genetic alterations that underlie human cancer, it has proven difficult to identify which molecularly targeted therapeutics will benefit which patients. Drug-specific modulation of oncogenic signaling pathways in specific patient subpopulations can predict responsiveness to targeted therapy. Here, we report a pathway-based phosphoprofiling approach to identify and quantify clinically relevant, drug-specific biomarkers for phosphatidylinositol 3-kinase (PI3K) pathway inhibitors that target AKT, phosphoinositide-dependent kinase 1 (PDK1), and PI3K-mammalian target of rapamycin (mTOR). We quantified 375 nonredundant PI3K pathway-relevant phosphopeptides, all containing AKT, PDK1, or mitogen-activated protein kinase substrate recognition motifs. Of these phosphopeptides, 71 were drug-regulated, 11 of them by all three inhibitors. Drug-modulated phosphoproteins were enriched for involvement in cytoskeletal reorganization (filamin, stathmin, dynamin, PAK4, and PTPN14), vesicle transport (LARP1, VPS13D, and SLC20A1), and protein translation (S6RP and PRAS40). We then generated phosphospecific antibodies against selected, drug-regulated phosphorylation sites that would be suitable as biomarker tools for PI3K pathway inhibitors. As proof of concept, we show clinical translation feasibility for an antibody against phospho-PRAS40(Thr246). Evaluation of binding of this antibody in human cancer cell lines, a PTEN (phosphatase and tensin homolog deleted from chromosome 10)-deficient mouse prostate tumor model, and triple-negative breast tumor tissues showed that phospho-PRAS40(Thr246) positively correlates with PI3K pathway activation and predicts AKT inhibitor sensitivity. In contrast to phosphorylation of AKT(Thr308), the phospho-PRAS40(Thr246) epitope is highly stable in tissue samples and thus is ideal for immunohistochemistry. In summary, our study illustrates a rational approach for discovery of drug-specific biomarkers toward development of patient-tailored treatments.

Photodissociation of PbI2 in the ultraviolet: analysis of the A rightarrow X band of PbI

NASA Astrophysics Data System (ADS)

Rodriguez, G.; Herring, C. M.; Fraser, R. D.; Eden, J. G.

1996-07-01

Emission and absorption studies of lead moniodide (PbI) have been carried out by photodissociation of PbI2 vapor at one of several wavelengths (193, 248, 266, 308, and 351 nm) in the ultraviolet. Strong emission on the A \\rightarrow X2 Pi 1/2 band (14400-22800 cm -1 ; 440 \\similar-or-less lambda \\similar-or-less 695 nm) occurs when PbI2 is photodissociated at 248 or 266 nm. Also, absorption bands attributed to the B \\leftarrow X2 Pi 1/2,3/2 , D \\leftarrow X2 Pi 1/2,3/2 , and E \\leftarrow X2 Pi 1/2,3/2 transitions of the diatomic molecule have been observed at 290 and 380, 225 and 265, and 203 and 240 nm, respectively, as have emission bands peaking at 397.6, 531.6, 582.0, 595.1, 639.7, 685.9, and 707.9 nm that appear to arise from PbI2 itself. Analysis and computer simulations of the A \\rightarrow X2 Pi 1/2 emission spectra have resulted in identifications for virtually all (>120) of the observed vibrational bandheads. Several spectroscopic constants for the A and the X2 Pi 1/2 states of PbI have been determined to be Te(A)=20659+/-130 cm-1 , omega e\\prime =132.2+/-1.0cm -1 , omega e\\prime xe\\prime =1.91+/-0.06cm -1 , omega e\\prime \\prime=160.3+/-0.6cm-1 , and omega e\\prime \\primexe \\prime\\prime=0.24+/-0.03cm -1 . Also, the difference between the equilibrium internuclear separations for the X2 Pi 1/2 and the A states has been determined to be Delta Re=0.45+/-0.05 . The spontaneous-emission lifetime for the PbI(A) state and the rate constant for quenching of this state by PbI2 (in two-body collisions) have been measured to be (94.3+/-8.8) ns and (4.3+/-0.4) \\times 10-10 cm3s -1 , respectively.

Genome‑wide identification of long noncoding RNAs in CCl4‑induced liver fibrosis via RNA sequencing.

PubMed

Gong, Zhenghua; Tang, Jialin; Xiang, Tianxin; Lin, Jiayu; Deng, Chaowen; Peng, Yanzhong; Zheng, Jie; Hu, Guoxin

2018-05-07

Liver fibrosis occurs as a result of chronic liver lesions, which may subsequently develop into liver cirrhosis and hepatocellular carcinoma. The involvement of long noncoding RNAs (lncRNAs) in liver fibrosis is being increasingly recognized. However, the exact mechanisms and functions of the majority of lncRNAs are poorly characterized. In the present study, the hepatotoxic substance carbon tetrachloride (CCl4) was employed to induce liver fibrosis in an animal model and agenome‑wide identification of lncRNAs in fibrotic liver tissues compared with CCl4 untreated liver tissues was performed using RNA sequencing. Sprague‑Dawley rats were treated with CCl4 for 8 weeks. Histopathogical alterations were observed in liver tissues, and serum levels of alanine aminotransferase, aspartate aminotransferase, transforming growth factor‑β1 and tumor necrosis factor‑α were significantly higher, in the CCl4‑treated group compared with the CCl4 untreated group. RNA sequencing of liver tissues demonstrated that 231 lncRNAs and 1,036 mRNAs were differentially expressed between the two groups. Furthermore, bioinformatics analysis demonstrated that the differentially expressed mRNAs were predominantly enriched in 'ECM‑receptor interaction', 'PI3K‑Akt signaling pathway' and 'focal adhesion' pathways, all of which are essential for liver fibrosis development. Validation of 12 significantly aberrant lncRNAs by reverse transcription‑quantitative polymerase chain reaction indicated that the expression patterns of 11 lncRNAs were consistent with the sequencing data. Furthermore, overexpression of lncRNA NR_002155.1, which was markedly downregulated in CCl4‑treated liver tissues, was demonstrated to inhibit HSC‑T6 cell proliferation in vitro. In conclusion, the present study determined the expression patterns of mRNAs and lncRNAs in fibrotic liver tissue induced by CCl4. The identified differentially expressed lncRNAs may serve as novel diagnostic biomarkers and therapeutic targets for liver fibrosis.

Frequency and pattern of Chinese herbal medicine prescriptions for urticaria in Taiwan during 2009: analysis of the national health insurance database

PubMed Central

2013-01-01

Background Large-scale pharmaco-epidemiological studies of Chinese herbal medicine (CHM) for treatment of urticaria are few, even though clinical trials showed some CHM are effective. The purpose of this study was to explore the frequencies and patterns of CHM prescriptions for urticaria by analysing the population-based CHM database in Taiwan. Methods This study was linked to and processed through the complete traditional CHM database of the National Health Insurance Research Database in Taiwan during 2009. We calculated the frequencies and patterns of CHM prescriptions used for treatment of urticaria, of which the diagnosis was defined as the single ICD-9 Code of 708. Frequent itemset mining, as applied to data mining, was used to analyse co-prescription of CHM for patients with urticaria. Results There were 37,386 subjects who visited traditional Chinese Medicine clinics for urticaria in Taiwan during 2009 and received a total of 95,765 CHM prescriptions. Subjects between 18 and 35 years of age comprised the largest number of those treated (32.76%). In addition, women used CHM for urticaria more frequently than men (female:male = 1.94:1). There was an average of 5.54 items prescribed in the form of either individual Chinese herbs or a formula in a single CHM prescription for urticaria. Bai-Xian-Pi (Dictamnus dasycarpus Turcz) was the most commonly prescribed single Chinese herb while Xiao-Feng San was the most commonly prescribed Chinese herbal formula. The most commonly prescribed CHM drug combination was Xiao-Feng San plus Bai-Xian-Pi while the most commonly prescribed triple drug combination was Xiao-Feng San, Bai-Xian-Pi, and Di-Fu Zi (Kochia scoparia). Conclusions In view of the popularity of CHM such as Xiao-Feng San prescribed for the wind-heat pattern of urticaria in this study, a large-scale, randomized clinical trial is warranted to research their efficacy and safety. PMID:23947955

Frequency and pattern of Chinese herbal medicine prescriptions for urticaria in Taiwan during 2009: analysis of the national health insurance database.

PubMed

Chien, Pei-Shan; Tseng, Yu-Fang; Hsu, Yao-Chin; Lai, Yu-Kai; Weng, Shih-Feng

2013-08-15

Large-scale pharmaco-epidemiological studies of Chinese herbal medicine (CHM) for treatment of urticaria are few, even though clinical trials showed some CHM are effective. The purpose of this study was to explore the frequencies and patterns of CHM prescriptions for urticaria by analysing the population-based CHM database in Taiwan. This study was linked to and processed through the complete traditional CHM database of the National Health Insurance Research Database in Taiwan during 2009. We calculated the frequencies and patterns of CHM prescriptions used for treatment of urticaria, of which the diagnosis was defined as the single ICD-9 Code of 708. Frequent itemset mining, as applied to data mining, was used to analyse co-prescription of CHM for patients with urticaria. There were 37,386 subjects who visited traditional Chinese Medicine clinics for urticaria in Taiwan during 2009 and received a total of 95,765 CHM prescriptions. Subjects between 18 and 35 years of age comprised the largest number of those treated (32.76%). In addition, women used CHM for urticaria more frequently than men (female:male = 1.94:1). There was an average of 5.54 items prescribed in the form of either individual Chinese herbs or a formula in a single CHM prescription for urticaria. Bai-Xian-Pi (Dictamnus dasycarpus Turcz) was the most commonly prescribed single Chinese herb while Xiao-Feng San was the most commonly prescribed Chinese herbal formula. The most commonly prescribed CHM drug combination was Xiao-Feng San plus Bai-Xian-Pi while the most commonly prescribed triple drug combination was Xiao-Feng San, Bai-Xian-Pi, and Di-Fu Zi (Kochia scoparia). In view of the popularity of CHM such as Xiao-Feng San prescribed for the wind-heat pattern of urticaria in this study, a large-scale, randomized clinical trial is warranted to research their efficacy and safety.

The Effect of Blood Alcohol Level and Pre-Injury Chronic Alcohol Use on Outcome from Severe Traumatic Brain Injury in Hispanics, Anglo-Caucasians, and African Americans

PubMed Central

O’Dell, Keira M.; Hannay, H. Julia; Biney, Fedora O.; Robertson, Claudia S.; Tian, T. Siva

2012-01-01

Objective To examine a) ethnic differences in blood alcohol level (BAL) and pre-injury chronic alcohol use (PI-ETOH) within a severe closed head injury (CHI) sample, and b) the main and interaction effects of BAL, PI-ETOH, and ethnicity on functional outcome following severe CHI. Participants 434 Hispanic, Anglo-Caucasian, and African American individuals with severe CHI. Design Retrospective cohort study. Setting Consecutive admissions to a level one trauma center. Main measures BAL upon admission to the trauma center was collected for each patient. Additional information regarding PI-ETOH was collected in a subset of patients (N=116). Functional outcome was measured using the Disability Rating Scale (DRS) at 6 months post-injury. Results A one-way ANOVA revealed ethnic differences in mean BAL. Hierarchical multiple regression indicated that BAL did not predict DRS outcomes after controlling for pertinent covariates. An interaction effect between PI-ETOH and ethnicity was observed, such that presence of chronic alcohol use predicted worse functional outcome for Anglo-Caucasians and African Americans, but more favorable outcome for Hispanics. Conclusions Ethnic differences in BALs within our severe TBI sample mirrored ethnic drinking patterns observed in the general population, with Hispanics having the highest BALs. A paradoxical relationship between PI-ETOH and functional outcome was observed for Hispanics. PMID:22955101

miR-21 is associated with fibrosis and right ventricular failure

PubMed Central

Hu, Dong-Qing; Zhao, Mingming; Blay, Eddie; Sandeep, Nefthi; Ong, Sang-Ging; Jung, Gwanghyun; Kooiker, Kristina B.; Coronado, Michael; Fajardo, Giovanni; Bernstein, Daniel

2017-01-01

Combined pulmonary insufficiency (PI) and stenosis (PS) is a common long-term sequela after repair of many forms of congenital heart disease, causing progressive right ventricular (RV) dilation and failure. Little is known of the mechanisms underlying this combination of preload and afterload stressors. We developed a murine model of PI and PS (PI+PS) to identify clinically relevant pathways and biomarkers of disease progression. Diastolic dysfunction was induced (restrictive RV filling, elevated RV end-diastolic pressures) at 1 month after generation of PI+PS and progressed to systolic dysfunction (decreased RV shortening) by 3 months. RV fibrosis progressed from 1 month (4.4% ± 0.4%) to 3 months (9.2% ± 1%), along with TGF-β signaling and tissue expression of profibrotic miR-21. Although plasma miR-21 was upregulated with diastolic dysfunction, it was downregulated with the onset of systolic dysfunction), correlating with RV fibrosis. Plasma miR-21 in children with PI+PS followed a similar pattern. A model of combined RV volume and pressure overload recapitulates the evolution of RV failure unique to patients with prior RV outflow tract surgery. This progression was characterized by enhanced TGF-β and miR-21 signaling. miR-21 may serve as a plasma biomarker of RV failure, with decreased expression heralding the need for valve replacement. PMID:28469078

Expansion of Genes Encoding piRNA-Associated Argonaute Proteins in the Pea Aphid: Diversification of Expression Profiles in Different Plastic Morphs

PubMed Central

Lu, Hsiao-ling; Tanguy, Sylvie; Rispe, Claude; Gauthier, Jean-Pierre; Walsh, Tom; Gordon, Karl; Edwards, Owain; Tagu, Denis; Chang, Chun-che; Jaubert-Possamai, Stéphanie

2011-01-01

Piwi-interacting RNAs (piRNAs) are known to regulate transposon activity in germ cells of several animal models that propagate sexually. However, the role of piRNAs during asexual reproduction remains almost unknown. Aphids that can alternate sexual and asexual reproduction cycles in response to seasonal changes of photoperiod provide a unique opportunity to study piRNAs and the piRNA pathway in both reproductive modes. Taking advantage of the recently sequenced genome of the pea aphid Acyrthosiphon pisum, we found an unusually large lineage-specific expansion of genes encoding the Piwi sub-clade of Argonaute proteins. In situ hybridisation showed differential expressions between the duplicated piwi copies: while Api-piwi2 and Api-piwi6 are “specialised” in germ cells their most closely related copy, respectively Api-piwi5 and Api-piwi3, are expressed in the somatic cells. The differential expression was also identified in duplicated ago3: Api-ago3a in germ cells and Api-ago3b in somatic cells. Moreover, analyses of expression profiles of the expanded piwi and ago3 genes by semi-quantitative RT-PCR showed that expressions varied according to the reproductive types. These specific expression patterns suggest that expanded aphid piwi and ago3 genes have distinct roles in asexual and sexual reproduction. PMID:22162754

Regulation of CDP-diacylglycerol synthesis and utilization by inositol and choline in Schizosaccharomyces pombe.

PubMed Central

Gaynor, P M; Greenberg, M L

1992-01-01

CDP-diacylglycerol (CDP-DG) is an important branchpoint intermediate in eucaryotic phospholipid biosynthesis and could be a key regulatory site in phospholipid metabolism. Therefore, we examined the effects of growth phase, phospholipid precursors, and the disruption of phosphatidylcholine (PC) synthesis on the membrane-associated phospholipid biosynthetic enzymes CDP-DG synthase, phosphatidylglycerolphosphate (PGP) synthase, phosphatidylinositol (PI) synthase, and phosphatidylserine (PS) synthase in cell extracts of the fission yeast Schizosaccharomyces pombe. In complete synthetic medium containing inositol, maximal expression of CDP-DG synthase, PGP synthase, PI synthase, and PS synthase in wild-type cells occurred in the exponential phase of growth and decreased two- to fourfold in the stationary phase of growth. In cells starved for inositol, this decrease in PGP synthase, PI synthase, and PS synthase expression was not observed. Starvation for inositol resulted in a twofold derepression of PGP synthase and PS synthase expression, while PI synthase expression decreased initially and then remained constant. Upon the addition of inositol to inositol-starved cells, there was a rapid and continued increase in PI synthase expression. We examined expression of these enzymes in cho2 and cho1 mutants, which are blocked in the methylation pathway for synthesis of PC. Choline starvation resulted in a decrease in PS synthase and CDP-DG synthase expression in cho1 but not cho2 cells. Expression of PGP synthase and PI synthase was not affected by choline starvation. Inositol starvation resulted in a 1.7-fold derepression of PGP synthase expression in cho2 but not cho1 cells when PC was synthesized. PS synthase expression was not depressed, while CDP-DG synthase and PI synthase expression decreased in cho2 and cho1 cells in the absence of inositol. These results demonstrate that (i) CDP-DG synthase, PGP synthase, PI synthase, and PS synthase are similarly regulated by growth phase; (ii) inositol affects the expression of PGP synthase, PI synthase, and PS synthase; (iii) disruption of the methylation pathway results in aberrant patterns of regulation of growth phase and phospholipid precursors. Important differences between S. pombe and Saccharomyces cerevisiae with regard to regulation of these enzymes are discussed. PMID:1324908

Basics of identification measurement technology

NASA Astrophysics Data System (ADS)

Klikushin, Yu N.; Kobenko, V. Yu; Stepanov, P. P.

2018-01-01

All available algorithms and suitable for pattern recognition do not give 100% guarantee, therefore there is a field of scientific night activity in this direction, studies are relevant. It is proposed to develop existing technologies for pattern recognition in the form of application of identification measurements. The purpose of the study is to identify the possibility of recognizing images using identification measurement technologies. In solving problems of pattern recognition, neural networks and hidden Markov models are mainly used. A fundamentally new approach to the solution of problems of pattern recognition based on the technology of identification signal measurements (IIS) is proposed. The essence of IIS technology is the quantitative evaluation of the shape of images using special tools and algorithms.

Daytime Symptoms in Primary Insomnia: A Prospective Analysis Using Ecological Momentary Assessment

PubMed Central

Buysse, Daniel J.; Thompson, Wesley; Scott, John; Franzen, Peter L.; Germain, Anne; Hall, Martica L.; Moul, Douglas E.; Nofzinger, Eric A.; Kupfer, David J.

2007-01-01

Objectives To prospectively characterize and compare daytime symptoms in primary insomnia (PI) and good sleeper control (GSC) subjects using ecological momentary assessment; to examine relationships between daytime symptom factors, retrospective psychological and sleep reports, and concurrent sleep diary reports. Methods Subjects included 47 PI and 18 GSC. Retrospective self-reports of daytime and sleep symptoms were collected. Daytime symptoms and sleep diary information were then collected for one week on hand-held computers. The Daytime Insomnia Symptom Scale (DISS) consisted of 19 visual analog scales completed four times per day. Factors for the DISS were derived using functional principal components analysis. Nonparametric tests were used to contrast DISS, retrospective symptom ratings, and sleep diary results in PI and GSC subjects, and to examine relationships among them. Results Four principal components were identified for the DISS: Alert Cognition, Negative Mood, Positive Mood, and Sleepiness/Fatigue. PI scored significantly worse than GSC on all four factors (p < .0003 for each). Among PI subjects DISS scales and retrospective psychological symptoms were related to each other in plausible ways. DISS factors were also related to self-report measures of sleep, whereas retrospective psychological symptom measures were not. Conclusions Daytime symptom factors of alertness, positive and negative mood, and sleepiness/fatigue, collected with ecological momentary assessment, showed impairment in PI versus GSC. DISS factors showed stronger relationships to retrospective sleep symptoms and concurrent sleep diary reports than retrospective psychological symptoms. The diurnal pattern of symptoms may inform studies of the pathophysiology and treatment outcome of insomnia. PMID:17368098

A Picrinine N-Methyltransferase Belongs to a New Family of γ-Tocopherol-Like Methyltransferases Found in Medicinal Plants That Make Biologically Active Monoterpenoid Indole Alkaloids1[OPEN

PubMed Central

Levac, Dylan; Cázares, Paulo; Yu, Fang

2016-01-01

Members of the Apocynaceae plant family produce a large number of monoterpenoid indole alkaloids (MIAs) with different substitution patterns that are responsible for their various biological activities. A novel N-methyltransferase involved in the vindoline pathway in Catharanthus roseus showing distinct similarity to γ-tocopherol C-methyltransferases was used in a bioinformatic screen of transcriptomes from Vinca minor, Rauvolfia serpentina, and C. roseus to identify 10 γ-tocopherol-like N-methyltransferases from a large annotated transcriptome database of different MIA-producing plant species (www.phytometasyn.ca). The biochemical function of two members of this group cloned from V. minor (VmPiNMT) and R. serpentina (RsPiNMT) have been characterized by screening their biochemical activities against potential MIA substrates harvested from the leaf surfaces of MIA-accumulating plants. The approach was validated by identifying the MIA picrinine from leaf surfaces of Amsonia hubrichtii as a substrate of VmPiNMT and RsPiNMT. Recombinant proteins were shown to have high substrate specificity and affinity for picrinine, converting it to N-methylpicrinine (ervincine). Developmental studies with V. minor and R. serpentina showed that RsPiNMT and VmPiNMT gene expression and biochemical activities were highest in younger leaf tissues. The assembly of at least 150 known N-methylated MIAs within members of the Apocynaceae family may have occurred as a result of the evolution of the γ-tocopherol-like N-methyltransferase family from γ-tocopherol methyltransferases. PMID:26848097

Development and evaluation of a de-identification procedure for a case register sourced from mental health electronic records.

PubMed

Fernandes, Andrea C; Cloete, Danielle; Broadbent, Matthew T M; Hayes, Richard D; Chang, Chin-Kuo; Jackson, Richard G; Roberts, Angus; Tsang, Jason; Soncul, Murat; Liebscher, Jennifer; Stewart, Robert; Callard, Felicity

2013-07-11

Electronic health records (EHRs) provide enormous potential for health research but also present data governance challenges. Ensuring de-identification is a pre-requisite for use of EHR data without prior consent. The South London and Maudsley NHS Trust (SLaM), one of the largest secondary mental healthcare providers in Europe, has developed, from its EHRs, a de-identified psychiatric case register, the Clinical Record Interactive Search (CRIS), for secondary research. We describe development, implementation and evaluation of a bespoke de-identification algorithm used to create the register. It is designed to create dictionaries using patient identifiers (PIs) entered into dedicated source fields and then identify, match and mask them (with ZZZZZ) when they appear in medical texts. We deemed this approach would be effective, given high coverage of PI in the dedicated fields and the effectiveness of the masking combined with elements of a security model. We conducted two separate performance tests i) to test performance of the algorithm in masking individual true PIs entered in dedicated fields and then found in text (using 500 patient notes) and ii) to compare the performance of the CRIS pattern matching algorithm with a machine learning algorithm, called the MITRE Identification Scrubber Toolkit - MIST (using 70 patient notes - 50 notes to train, 20 notes to test on). We also report any incidences of potential breaches, defined by occurrences of 3 or more true or apparent PIs in the same patient's notes (and in an additional set of longitudinal notes for 50 patients); and we consider the possibility of inferring information despite de-identification. True PIs were masked with 98.8% precision and 97.6% recall. As anticipated, potential PIs did appear, owing to misspellings entered within the EHRs. We found one potential breach. In a separate performance test, with a different set of notes, CRIS yielded 100% precision and 88.5% recall, while MIST yielded a 95.1% and 78.1%, respectively. We discuss how we overcome the realistic possibility - albeit of low probability - of potential breaches through implementation of the security model. CRIS is a de-identified psychiatric database sourced from EHRs, which protects patient anonymity and maximises data available for research. CRIS demonstrates the advantage of combining an effective de-identification algorithm with a carefully designed security model. The paper advances much needed discussion of EHR de-identification - particularly in relation to criteria to assess de-identification, and considering the contexts of de-identified research databases when assessing the risk of breaches of confidential patient information.

Active Authentication Linguistic Modalities

DTIC Science & Technology

2013-12-01

Rosenberg Self - Esteem Scale, the Myers-Briggs Personality Inventory (MBTI), the NEO PI-R, the Multiple Intelligences Developmental Assessment Scales (MIDAS...two categories, male and female, as reported by self -identification. • Self - Esteem : The Rosenberg Self - Esteem Scale provides a numerical measure...MBTI - T/F 59.15% 79.62% MBTI - J/P 50.70% 83.57% Rosenberg Self - Esteem 57.50% 80.47% MIDAS - Primary Catagories 22.10% 70.74% MIDAS

US Army Medical Department Journal, April - June 2007

DTIC Science & Technology

2007-06-01

through early identification and occupational hazards , and food and water reduced stigma. vulnerabilities. All have various causes and effects, and all... meat barely palatable, but it was all to be had amid that remaining ones was given to food and ammunition. desolate country of want.3(pi49) The men...held in Oklahoma during the summer decades. In addition, many military missions support of 2005. uniquely hazardous industrial operations, including

Identification of Borrelia protein candidates in mouse skin for potential diagnosis of disseminated Lyme borreliosis.

PubMed

Grillon, Antoine; Westermann, Benoît; Cantero, Paola; Jaulhac, Benoît; Voordouw, Maarten J; Kapps, Delphine; Collin, Elody; Barthel, Cathy; Ehret-Sabatier, Laurence; Boulanger, Nathalie

2017-12-01

In vector-borne diseases, the skin plays an essential role in the transmission of vector-borne pathogens between the vertebrate host and blood-feeding arthropods and in pathogen persistence. Borrelia burgdorferi sensu lato is a tick-borne bacterium that causes Lyme borreliosis (LB) in humans. This pathogen may establish a long-lasting infection in its natural vertebrate host where it can persist in the skin and some other organs. Using a mouse model, we demonstrate that Borrelia targets the skin regardless of the route of inoculation, and can persist there at low densities that are difficult to detect via qPCR, but that were infective for blood-feeding ticks. Application of immunosuppressive dermocorticoids at 40 days post-infection (PI) significantly enhanced the Borrelia population size in the mouse skin. We used non-targeted (Ge-LC-MS/MS) and targeted (SRM-MS) proteomics to detect several Borrelia-specific proteins in the mouse skin at 40 days PI. Detected Borrelia proteins included flagellin, VlsE and GAPDH. An important problem in LB is the lack of diagnosis methods capable of detecting active infection in humans suffering from disseminated LB. The identification of Borrelia proteins in skin biopsies may provide new approaches for assessing active infection in disseminated manifestations.

Reinforced carbon nanotubes as electrically conducting and flexible films for space applications.

PubMed

Atar, Nurit; Grossman, Eitan; Gouzman, Irina; Bolker, Asaf; Hanein, Yael

2014-11-26

Chemical vapor deposition (CVD)-grown entangled carbon nanotube (CNT) sheets are characterized by high electrical conductivity and durability to bending and folding. However, since freestanding CNT sheets are mechanically weak, they cannot be used as stand-alone flexible films. In this work, polyimide (PI) infiltration into entangled cup-stacked CNT (CSCNT) sheets was studied to form electrically conducting, robust, and flexible films for space applications. The infiltration process preserved CNTs' advantageous properties (i.e., conductivity and flexibility), prevented CNT agglomeration, and enabled CNT patterning. In particular, the CNT-PI films exhibited ohmic electrical conductance in both the lateral and vertical directions, with a sheet resistivity as low as 122 Ω/□, similar to that of as-grown CNT sheets, with minimal effect of the insulating matrix. Moreover, this high conductivity was preserved under mechanical and thermal manipulations. These properties make the reported CNT-PI films excellent candidates for applications where flexibility, thermal stability, and electrical conductivity are required. Particularly, the developed CNT-PI films were found to be durable in space environment hazards such as high vacuum, thermal cycling, and ionizing radiation, and hence they are suggested as an alternative for the electrostatic discharge (ESD) protection layer in spacecraft thermal blankets.

Expression of the Retrotransposon Helena Reveals a Complex Pattern of TE Deregulation in Drosophila Hybrids

PubMed Central

Romero-Soriano, Valèria; Garcia Guerreiro, Maria Pilar

2016-01-01

Transposable elements (TEs), repeated mobile sequences, are ubiquitous in the eukaryotic kingdom. Their mobilizing capacity confers on them a high mutagenic potential, which must be strongly regulated to guarantee genome stability. In the Drosophila germline, a small RNA-mediated silencing system, the piRNA (Piwi-interacting RNA) pathway, is the main responsible TE regulating mechanism, but some stressful conditions can destabilize it. For instance, during interspecific hybridization, genomic stress caused by the shock of two different genomes can lead, in both animals and plants, to higher transposition rates. A recent study in D. buzatii—D. koepferae hybrids detected mobilization of 28 TEs, yet little is known about the molecular mechanisms explaining this transposition release. We have characterized one of the mobilized TEs, the retrotransposon Helena, and used quantitative expression to assess whether its high transposition rates in hybrids are preceded by increased expression. We have also localized Helena expression in the gonads to see if cellular expression patterns have changed in the hybrids. To give more insight into changes in TE regulation in hybrids, we analysed Helena-specific piRNA populations of hybrids and parental species. Helena expression is not globally altered in somatic tissues, but male and female gonads have different patterns of deregulation. In testes, Helena is repressed in F1, increasing then its expression up to parental values. This is linked with a mislocation of Helena transcripts along with an increase of their specific piRNA levels. Ovaries have additive levels of Helena expression, but the ping-pong cycle efficiency seems to be reduced in F1 hybrids. This could be at the origin of new Helena insertions in hybrids, which would be transmitted to F1 hybrid female progeny. PMID:26812285

Body composition at birth and its relationship with neonatal anthropometric ratios: the newborn body composition study of the INTERGROWTH-21st project

PubMed Central

Villar, José; Puglia, Fabien A; Fenton, Tanis R; Cheikh Ismail, Leila; Staines-Urias, Eleonora; Giuliani, Francesca; Ohuma, Eric O; Victora, Cesar G; Sullivan, Peter; Barros, Fernando C; Lambert, Ann; Papageorghiou, Aris T; Ochieng, Roseline; Jaffer, Yasmin A; Altman, Douglas G; Noble, Alison J; Gravett, Michael G; Purwar, Manorama; Pang, Ruyan; Uauy, Ricardo; Kennedy, Stephen H; Bhutta, Zulfiqar A

2017-01-01

Background We aimed to describe newborn body composition and identify which anthropometric ratio (weight/length; BMI; or ponderal index, PI) best predicts fat mass (FM) and fat-free mass (FFM). Methods Air-displacement plethysmography (PEA POD) was used to estimate FM, FFM, and body fat percentage (BF%). Associations between FFM, FM, and BF% and weight/length, BMI, and PI were evaluated in 1,019 newborns using multivariate regression analysis. Charts for FM, FFM, and BF% were generated using a prescriptive subsample (n=247). Standards for the best-predicting anthropometric ratio were calculated utilizing the same population used for the INTERGROWTH-21st Newborn Size Standards (n=20,479). Results FFM and FM increased consistently during late pregnancy. Differential FM, BF%, and FFM patterns were observed for those born preterm (34+0−36+6 weeks’ gestation) and with impaired intrauterine growth. Weight/length by gestational age (GA) was a better predictor of FFM and FM (adjusted R2=0.92 and 0.71, respectively) than BMI or PI, independent of sex, GA, and timing of measurement. Results were almost identical when only preterm newborns were studied. We present sex-specific centiles for weight/length ratio for GA. Conclusions Weight/length best predicts newborn FFM and FM. There are differential FM, FFM, and BF% patterns by sex, GA, and size at birth. PMID:28445454

Body composition at birth and its relationship with neonatal anthropometric ratios: the newborn body composition study of the INTERGROWTH-21st project.

PubMed

Villar, José; Puglia, Fabien A; Fenton, Tanis R; Cheikh Ismail, Leila; Staines-Urias, Eleonora; Giuliani, Francesca; Ohuma, Eric O; Victora, Cesar G; Sullivan, Peter; Barros, Fernando C; Lambert, Ann; Papageorghiou, Aris T; Ochieng, Roseline; Jaffer, Yasmin A; Altman, Douglas G; Noble, Alison J; Gravett, Michael G; Purwar, Manorama; Pang, Ruyan; Uauy, Ricardo; Kennedy, Stephen H; Bhutta, Zulfiqar A

2017-08-01

BackgroundWe aimed to describe newborn body composition and identify which anthropometric ratio (weight/length; BMI; or ponderal index, PI) best predicts fat mass (FM) and fat-free mass (FFM).MethodsAir-displacement plethysmography (PEA POD) was used to estimate FM, FFM, and body fat percentage (BF%). Associations between FFM, FM, and BF% and weight/length, BMI, and PI were evaluated in 1,019 newborns using multivariate regression analysis. Charts for FM, FFM, and BF% were generated using a prescriptive subsample (n=247). Standards for the best-predicting anthropometric ratio were calculated utilizing the same population used for the INTERGROWTH-21 st Newborn Size Standards (n=20,479).ResultsFFM and FM increased consistently during late pregnancy. Differential FM, BF%, and FFM patterns were observed for those born preterm (34 +0 -36 +6 weeks' gestation) and with impaired intrauterine growth. Weight/length by gestational age (GA) was a better predictor of FFM and FM (adjusted R 2 =0.92 and 0.71, respectively) than BMI or PI, independent of sex, GA, and timing of measurement. Results were almost identical when only preterm newborns were studied. We present sex-specific centiles for weight/length ratio for GA.ConclusionsWeight/length best predicts newborn FFM and FM. There are differential FM, FFM, and BF% patterns by sex, GA, and size at birth.

AGARD Flight Test Techniques Series. Volume 3. Identification of Dynamic Systems-Applications to Aircraft. Part 2. Nonlinear Analysis and Manoeuvre Design. (L’Identification des Systemes Dynamiques-Applications aux Aeronefs Titre 2; L’analyse non-lineaire et la Conception de la Manoeuvre)

DTIC Science & Technology

1994-05-01

matrix K(i+1) is calculated from the vector can be reconstructed by simple integration. covariance matrix P(i+1 Ii) by: In reality not all components...is preferable to use a symbolic algebra favorable wheather conditions, for flight tests with package such as Maple or Mathematica, which will large...proved to be virtually A A identical. IZX(r, + (Pro + kp)(q%, + kq)) The actual application of the extended Kalman M AxrPq filter and smoother to

Eliminating the zero spectrum in Fourier transform profilometry using empirical mode decomposition.

PubMed

Li, Sikun; Su, Xianyu; Chen, Wenjing; Xiang, Liqun

2009-05-01

Empirical mode decomposition is introduced into Fourier transform profilometry to extract the zero spectrum included in the deformed fringe pattern without the need for capturing two fringe patterns with pi phase difference. The fringe pattern is subsequently demodulated using a standard Fourier transform profilometry algorithm. With this method, the deformed fringe pattern is adaptively decomposed into a finite number of intrinsic mode functions that vary from high frequency to low frequency by means of an algorithm referred to as a sifting process. Then the zero spectrum is separated from the high-frequency components effectively. Experiments validate the feasibility of this method.

Rate heterogeneity in six protein-coding genes from the holoparasite Balanophora (Balanophoraceae) and other taxa of Santalales

PubMed Central

Su, Huei-Jiun; Hu, Jer-Ming

2012-01-01

Background and Aims The holoparasitic flowering plant Balanophora displays extreme floral reduction and was previously found to have enormous rate acceleration in the nuclear 18S rDNA region. So far, it remains unclear whether non-ribosomal, protein-coding genes of Balanophora also evolve in an accelerated fashion and whether the genes with high substitution rates retain their functionality. To tackle these issues, six different genes were sequenced from two Balanophora species and their rate variation and expression patterns were examined. Methods Sequences including nuclear PI, euAP3, TM6, LFY and RPB2 and mitochondrial matR were determined from two Balanophora spp. and compared with selected hemiparasitic species of Santalales and autotrophic core eudicots. Gene expression was detected for the six protein-coding genes and the expression patterns of the three B-class genes (PI, AP3 and TM6) were further examined across different organs of B. laxiflora using RT-PCR. Key Results Balanophora mitochondrial matR is highly accelerated in both nonsynonymous (dN) and synonymous (dS) substitution rates, whereas the rate variation of nuclear genes LFY, PI, euAP3, TM6 and RPB2 are less dramatic. Significant dS increases were detected in Balanophora PI, TM6, RPB2 and dN accelerations in euAP3. All of the protein-coding genes are expressed in inflorescences, indicative of their functionality. PI is restrictively expressed in tepals, synandria and floral bracts, whereas AP3 and TM6 are widely expressed in both male and female inflorescences. Conclusions Despite the observation that rates of sequence evolution are generally higher in Balanophora than in hemiparasitic species of Santalales and autotrophic core eudicots, the five nuclear protein-coding genes are functional and are evolving at a much slower rate than 18S rDNA. The mechanism or mechanisms responsible for rapid sequence evolution and concomitant rate acceleration for 18S rDNA and matR are currently not well understood and require further study in Balanophora and other holoparasites. PMID:23041381

Systems analysis of apoptotic priming in ovarian cancer identifies vulnerabilities and predictors of drug response.

PubMed

Zervantonakis, Ioannis K; Iavarone, Claudia; Chen, Hsing-Yu; Selfors, Laura M; Palakurthi, Sangeetha; Liu, Joyce F; Drapkin, Ronny; Matulonis, Ursula; Leverson, Joel D; Sampath, Deepak; Mills, Gordon B; Brugge, Joan S

2017-08-28

The lack of effective chemotherapies for high-grade serous ovarian cancers (HGS-OvCa) has motivated a search for alternative treatment strategies. Here, we present an unbiased systems-approach to interrogate a panel of 14 well-annotated HGS-OvCa patient-derived xenografts for sensitivity to PI3K and PI3K/mTOR inhibitors and uncover cell death vulnerabilities. Proteomic analysis reveals that PI3K/mTOR inhibition in HGS-OvCa patient-derived xenografts induces both pro-apoptotic and anti-apoptotic signaling responses that limit cell killing, but also primes cells for inhibitors of anti-apoptotic proteins. In-depth quantitative analysis of BCL-2 family proteins and other apoptotic regulators, together with computational modeling and selective anti-apoptotic protein inhibitors, uncovers new mechanistic details about apoptotic regulators that are predictive of drug sensitivity (BIM, caspase-3, BCL-X L ) and resistance (MCL-1, XIAP). Our systems-approach presents a strategy for systematic analysis of the mechanisms that limit effective tumor cell killing and the identification of apoptotic vulnerabilities to overcome drug resistance in ovarian and other cancers.High-grade serous ovarian cancers (HGS-OvCa) frequently develop chemotherapy resistance. Here, the authors through a systematic analysis of proteomic and drug response data of 14 HGS-OvCa PDXs demonstrate that targeting apoptosis regulators can improve response of these tumors to inhibitors of the PI3K/mTOR pathway.

Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes.

PubMed

Yang, Ying; Zhou, Tai-Cheng; Liu, Yong-Ying; Li, Xiao; Wang, Wen-Xue; Irwin, David M; Zhang, Ya-Ping

2016-01-01

Maturity-onset diabetes of the young (MODY) is characterized by the onset of diabetes before the age of 25 years, positive family history, high genetic predisposition, monogenic mutations, and an autosomal dominant mode of inheritance. Here, we aimed to investigate the mutations and to characterize the phenotypes of a Han Chinese family with early-onset maternally inherited type 2 diabetes. Detailed clinical assessments and genetic screening for mutations in the HNF4α, GCK, HNF-1α, IPF-1, HNF1β, and NEUROD1 genes were carried out in this family. One HNF4A mutation (p.T130I) and two HNF1A polymorphisms (p.I27L and p.S487N) were identified. Mutation p.T130I was associated with both early-onset and late-onset diabetes and caused downregulated HNF4A expression, whereas HNF1A polymorphisms p.I27L and p.S487N were associated with the age of diagnosis of diabetes. We demonstrated that mutation p.T130I in HNF4A was pathogenic as were the predicted polymorphisms p.I27L and p.S487N in HNF1A by genetic and functional analysis. Our results show that mutations in HNF4A and HNF1A genes might account for this early-onset inherited type 2 diabetes.

Identification of medically relevant Nocardia species with an abbreviated battery of tests.

PubMed

Kiska, Deanna L; Hicks, Karen; Pettit, David J

2002-04-01

Identification of Nocardia to the species level is useful for predicting antimicrobial susceptibility patterns and defining the pathogenicity and geographic distribution of these organisms. We sought to develop an identification method which was accurate, timely, and employed tests which would be readily available in most clinical laboratories. We evaluated the API 20C AUX yeast identification system as well as several biochemical tests and Kirby-Bauer susceptibility patterns for the identification of 75 isolates encompassing the 8 medically relevant Nocardia species. There were few biochemical reactions that were sufficiently unique for species identification; of note, N. nova were positive for arylsulfatase, N. farcinica were positive for opacification of Middlebrook 7H11 agar, and N. brasiliensis and N. pseudobrasiliensis were the only species capable of liquefying gelatin. API 20C sugar assimilation patterns were unique for N. transvalensis, N. asteroides IV, and N. brevicatena. There was overlap among the assimilation patterns for the other species. Species-specific patterns of susceptibility to gentamicin, tobramycin, amikacin, and erythromycin were obtained for N. nova, N. farcinica, and N. brevicatena, while there was overlap among the susceptibility patterns for the other isolates. No single method could identify all Nocardia isolates to the species level; therefore, a combination of methods was necessary. An algorithm utilizing antibiotic susceptibility patterns, citrate utilization, acetamide utilization, and assimilation of inositol and adonitol accurately identified all isolates. The algorithm was expanded to include infrequent drug susceptibility patterns which have been reported in the literature but which were not seen in this study.

Cerebral Hemodynamics Patterns by Transcranial Doppler in Patients With Acute Liver Failure.

PubMed

Abdo, A; Pérez-Bernal, J; Hinojosa, R; Porras, F; Castellanos, R; Gómez, F; Gutiérrez, J; Castellanos, A; Leal, G; Espinosa, N; Gómez-Bravo, M

2015-11-01

About half of patients with acute liver failure (ALF) show clinical signs of cerebral edema and intracranial hypertension. Neuroimaging diagnostics and electroencephalography have poor correlation with intracranial pressure measurement. The objective of this study was to characterize the cerebral hemodynamics patterns with transcranial Doppler (TCD) sonography in patients with ALF. We studied 21 patients diagnosed with ALF, admitted to the intensive care unit (ICU) at the Centro de Investigaciones Médico Quirúrgicas of Cuba. All of these patients had a TCD performed on arrival at ICU, evaluating the following: systolic (SV), diastolic (DV), and medium (MV) flows velocities and pulsatility index (PI) in right middle cerebral artery (RMCA) via temporal windows. The sonographic patterns of cerebral hemodynamics were as follows: low-flow, 12 patients (57.1%); high resistance, 5 patients (23.8%); and hyperemic, 4 patients (19%). Patients who died while waiting had lower MV RMCA (56.1 vs 58.1 cm/s) and higher PI (1.71 vs 1.41) than patients who could undergo transplantation (P = .800 and P = .787, respectively). In patients diagnosed with ALF admitted to the ICU the predominating cerebral hemodynamic pattern was low-flow with resistance increase. The TCD was shown to be a useful tool in the initial evaluation for prognosis and treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Met Nuclear Localization and Signaling in Breast Cancer

DTIC Science & Technology

2006-05-01

and in germinal regions of many tissues using 4 unique antibodies . Cell fractionation reveals a 60kDa band recognized by C-terminal Met antibodies ...cascades such as Gab1 , Grb2 and PI3K, leading to proliferation, scattering, increased motility, invasion and branching morphogenesis (reviewed in (2...Identification of Met antibodies for use on tissue microarray of normal and cancerous cells, Months 12-24 Task 2. Definition of the domain

A Search for the Decay B+ --> K+ nu nubar

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

Aubert, B

In this work the authors report the results of a search for the exclusive decay mode B{sup +} --> K{sup +}{nu}{bar {nu}}. By modifying the particle identification (PID) criteria used in the search, they additionally obtain a limit on the related decay B{sup +} --> {pi}{sup +}{nu}{bar {nu}}. The data used in this analysis were collected with the BABAR detector at the PEP-II asymmetric-energy e{sup +}e{sup -} storage ring.

Unique identification code for medical fundus images using blood vessel pattern for tele-ophthalmology applications.

PubMed

Singh, Anushikha; Dutta, Malay Kishore; Sharma, Dilip Kumar

2016-10-01

Identification of fundus images during transmission and storage in database for tele-ophthalmology applications is an important issue in modern era. The proposed work presents a novel accurate method for generation of unique identification code for identification of fundus images for tele-ophthalmology applications and storage in databases. Unlike existing methods of steganography and watermarking, this method does not tamper the medical image as nothing is embedded in this approach and there is no loss of medical information. Strategic combination of unique blood vessel pattern and patient ID is considered for generation of unique identification code for the digital fundus images. Segmented blood vessel pattern near the optic disc is strategically combined with patient ID for generation of a unique identification code for the image. The proposed method of medical image identification is tested on the publically available DRIVE and MESSIDOR database of fundus image and results are encouraging. Experimental results indicate the uniqueness of identification code and lossless recovery of patient identity from unique identification code for integrity verification of fundus images. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Unique white matter microstructural patterns in ADHD presentations-a diffusion tensor imaging study.

PubMed

Svatkova, Alena; Nestrasil, Igor; Rudser, Kyle; Goldenring Fine, Jodene; Bledsoe, Jesse; Semrud-Clikeman, Margaret

2016-09-01

Attention-deficit/hyperactivity disorder predominantly inattentive (ADHD-PI) and combined (ADHD-C) presentations are likely distinct disorders that differ neuroanatomically, neurochemically, and neuropsychologically. However, to date, little is known about specific white matter (WM) regions differentiating ADHD presentations. This study examined differences in WM microstructure using diffusion tensor imaging (DTI) data from 20 ADHD-PI, 18 ADHD-C, and 27 typically developed children. Voxel-wise analysis of DTI measurements in major fiber bundles was carried out using tract-based spatial statistics (TBSS). Clusters showing diffusivity abnormalities were used as regions of interest for regression analysis between fractional anisotropy (FA) and neuropsychological outcomes. Compared to neurotypicals, ADHD-PI children showed higher FA in the anterior thalamic radiations (ATR), bilateral inferior longitudinal fasciculus (ILF), and in the left corticospinal tract (CST). In contrast, the ADHD-C group exhibited higher FA in the bilateral cingulum bundle (CB). In the ADHD-PI group, differences in FA in the left ILF and ATR were accompanied by axial diffusivity (AD) abnormalities. In addition, the ADHD-PI group exhibited atypical mean diffusivity in the forceps minor (FMi) and left ATR and AD differences in right CB compared to healthy subjects. Direct comparison between ADHD presentations demonstrated radial diffusivity differences in FMi. WM clusters with FA irregularities in ADHD were associated with neurobehavioral performance across groups. In conclusion, differences in WM microstructure in ADHD presentations strengthen the theory that ADHD-PI and ADHD-C are two distinct disorders. Regions with WM irregularity seen in both ADHD presentations might serve as predictors of executive and behavioral functioning across groups. Hum Brain Mapp 37:3323-3336, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Detection of BVDV persistently infected animals in Belgium: evaluation of the strategy implemented.

PubMed

Letellier, C; De Meulemeester, L; Lomba, M; Mijten, E; Kerkhofs, P

2005-11-15

Until now, no official bovine virus diarrhea virus (BVDV) control program has been implemented in Belgium. The only legislation dealing with the detection of BVDV-infected animals concerns the purchase of animals. A strategy of control, based on the identification and elimination of persistently infected (PI) animals and the vaccination of cows before insemination has been designed in both the Northern and the Southern part of the country. The strategy of detection of PI animals relies on PCR testing of pools of blood. Individual blood samples corresponding to the positive pools are then tested by BVDV-antigen ELISA. A first evaluation of the measures already applied in Belgium is presented. Data obtained in 2003 are presented and discussed regarding the validation of the laboratory strategy, the prevalence of positive herds, the genotype of circulating viruses, the outcome of antigen positive animals and the need for improvement of the current legislation.

Phytochemical Evaluation of Moth Bean (Vigna aconitifolia L.) Seeds and Their Divergence

PubMed Central

Gupta, Neha; Shrivastava, Nidhi; Singh, Pramod Kumar; Bhagyawant, Sameer S.

2016-01-01

In the present study, phytochemical contents of 25 moth bean (Vigna aconitifolia) seed accessions were evaluated. This includes protease inhibitors, phytic acid, radical scavenging activity, and tannins. The studies revealed significant variation in the contents of theses phytochemicals. Presence of photochemical composition was correlated with seed storage proteins like albumin and globulin. Qualitative identification of total seed storage protein abundance across two related moth bean accessions using two-dimensional gel electrophoresis (2D-GE) was performed. Over 20 individual protein fractions were distributed over the gel as a series of spots in two moth bean accessions. Seed proteome accumulated spots of high intensity over a broad range of pI values of 3–10 in a molecular weight range of 11–170 kDa. In both seed accessions maximum protein spots are seen in the pI range of 6–8. PMID:27239343

Phytochemical Evaluation of Moth Bean (Vigna aconitifolia L.) Seeds and Their Divergence.

PubMed

Gupta, Neha; Shrivastava, Nidhi; Singh, Pramod Kumar; Bhagyawant, Sameer S

2016-01-01

In the present study, phytochemical contents of 25 moth bean (Vigna aconitifolia) seed accessions were evaluated. This includes protease inhibitors, phytic acid, radical scavenging activity, and tannins. The studies revealed significant variation in the contents of theses phytochemicals. Presence of photochemical composition was correlated with seed storage proteins like albumin and globulin. Qualitative identification of total seed storage protein abundance across two related moth bean accessions using two-dimensional gel electrophoresis (2D-GE) was performed. Over 20 individual protein fractions were distributed over the gel as a series of spots in two moth bean accessions. Seed proteome accumulated spots of high intensity over a broad range of pI values of 3-10 in a molecular weight range of 11-170 kDa. In both seed accessions maximum protein spots are seen in the pI range of 6-8.

Study of the dc and 100kHz glow discharges in acetylene-nitrogen mixture by means of optical emission spectroscopy

NASA Astrophysics Data System (ADS)

Jamroz, P.; Zyrnicki, W.

2002-09-01

The dc and 100 kHz low pressure discharges in acetylene-nitrogen mixture have been studied here. Optical emission spectroscopy was used for identification of active plasma components and to determine plasma temperature. Relative concentrations of H, CH and CN were investigated versus experimental conditions by optical actinometry techniques. Emission intensities of N2 and N2^+ normalized to intensity of argon line were also monitored as a function of experimental parameters. The rotational temperatures from the N2^+ B^2Σ_u^+-X^2Σ_g^+ (0-0) and CN B^2Σ^+-X^2Σ^+ (0-0) bands and vibrational temperatures from the CN (B^2Σ^+-X^2Σ^+) and N2 (C^3Pi_u-B^3Pi_g) spectra were determined. Plasma processes and plasma equilibrium state were discussed.

Laterality and Plantar Pressure Distribution During Gait in Healthy Children: Comment on Mayolas Pi, Arrese, Aparicio, and Masià (2015).

PubMed

Zverev, Yury

2016-08-01

In a recent paper, Mayolas Pi, Arrese, Aparicio, and Masià reported the absence of significant bilateral differences between legs in the average plantar pressure during walking in six- to seven-year-old children. However, the authors demonstrated bilateral differences in the distribution of plantar pressure during walking independent of foot preference in three tests: kicking a ball with precision, balancing on one foot, and jumping on one foot. From the results, Mayolas Pi et al. proposed that this asymmetric pattern of plantar pressure distribution is not caused by laterality. This paper suggests that the selected age range of participants and methods of diagnosing of laterality and data analysis could have significant effects on the results. Indeed, according to the literature, laterality in humans is a multidimensional trait with poor stabilization and conformity between different dimensions in preschool and younger school children. © The Author(s) 2016.

Retrospective analyses of the bottleneck in purification of eukaryotic proteins from Escherichia coli as affected by molecular weight, cysteine content and isoelectric point

PubMed Central

Jeon, Won Bae

2015-01-01

Experimental bioinformatics data obtained from an E. coli cell-based eukaryotic protein purification experiment were analyzed in order to identify any bottleneck as well as the factors affecting the target purification. All targets were expressed as His-tagged maltose-binding protein (MBP) fusion constructs and were initially purified by immobilized metal affinity chromatography (IMAC). The targets were subsequently separated from the His-tagged MBP through TEV protease cleavage followed by a second IMAC isolation. Of the 743 total purification trials, 342 yielded more than 3 mg of target proteins for structural studies. The major reason for failure of target purification was poor TEV proteolysis. The overall success rate for target purification decreased linearly as cysteine content or isoelectric point (pI) of the target increased. This pattern of pI versus overall success rate strongly suggests that pI should be incorporated into target scoring criteria with a threshold value. PMID:20510014

Simulation of the westward traveling surge and Pi 2 pulsations during substorms

NASA Technical Reports Server (NTRS)

Kan, J. R.; Sun, W.

1985-01-01

The westward traveling surge and the Pi2 pulsations are simulated as a consequence of an enhanced magnetospheric convection in a model of magnetosphere coupling. The coupling is characterized by the bouncing of Alfven waves launched by the enhanced convection. The reflection of Alfven waves from the ionosphere is treated in which the height-integrated conductivity is allowed to be highly nonuniform and fully anisotropic. The reflection of Alfven waves from the magnetosphere is characterized by the coefficient Rm, depending on whether the field lines are open or closed. The conductivity in the model is self-consistently enhanced with increasing upward field-aligned current density. The results of the simulation, including the convection pattern, the electrojets, the field-aligned current, the conductivity enhancement, the oscillation of the westward electrojet, and the average speed of the westward surge are in reasonable agreement with the features of the westward traveling surge and the Pi 2 pulsations observed during substorms.

Fosamprenavir calcium plus ritonavir for HIV infection.

PubMed

Torres, Harrys A; Arduino, Roberto C

2007-06-01

Fosamprenavir is a protease inhibitor (PI) approved for the treatment of HIV-1 infection. Fosamprenavir is a prodrug of amprenavir developed to reduce the pill burden yet maintain the unique resistance pattern and efficacy associated with amprenavir. In a head-to-head, noninferiority trial in antiretroviral treatment-naive HIV-infected patients, the antiviral efficacy and tolerability of ritonavir-boosted fosamprenavir was not inferior to ritonavir-boosted lopinavir, when the PIs were combined with two other nucleoside reverse transcriptase inhibitors. There are fewer studies published about fosamprenavir use in antiretroviral treatment-experienced HIV-infected patients. The high genetic barrier to the development of resistance to fosamprenavir and the low level of cross-resistance between ritonavir-boosted fosamprenavir and other PI regimens are notable. As with amprenavir, gastrointestinal disturbance and rash are the most frequent short-term treatment-limiting events with fosamprenavir. Treatment with ritonavir-boosted fosamprenavir can produce a durable response. To date, fosamprenavir is one of the recommended preferred PI components for the treatment of antiretroviral-naive HIV-infected patients.

Parallel ICA of FDG-PET and PiB-PET in three conditions with underlying Alzheimer's pathology

PubMed Central

Laforce, Robert; Tosun, Duygu; Ghosh, Pia; Lehmann, Manja; Madison, Cindee M.; Weiner, Michael W.; Miller, Bruce L.; Jagust, William J.; Rabinovici, Gil D.

2014-01-01

The relationships between clinical phenotype, β-amyloid (Aβ) deposition and neurodegeneration in Alzheimer's disease (AD) are incompletely understood yet have important ramifications for future therapy. The goal of this study was to utilize multimodality positron emission tomography (PET) data from a clinically heterogeneous population of patients with probable AD in order to: (1) identify spatial patterns of Aβ deposition measured by (11C)-labeled Pittsburgh Compound B (PiB-PET) and glucose metabolism measured by FDG-PET that correlate with specific clinical presentation and (2) explore associations between spatial patterns of Aβ deposition and glucose metabolism across the AD population. We included all patients meeting the criteria for probable AD (NIA–AA) who had undergone MRI, PiB and FDG-PET at our center (N = 46, mean age 63.0 ± 7.7, Mini-Mental State Examination 22.0 ± 4.8). Patients were subclassified based on their cognitive profiles into an amnestic/dysexecutive group (AD-memory; n = 27), a language-predominant group (AD-language; n = 10) and a visuospatial-predominant group (AD-visuospatial; n = 9). All patients were required to have evidence of amyloid deposition on PiB-PET. To capture the spatial distribution of Aβ deposition and glucose metabolism, we employed parallel independent component analysis (pICA), a method that enables joint analyses of multimodal imaging data. The relationships between PET components and clinical group were examined using a Receiver Operator Characteristic approach, including age, gender, education and apolipoprotein E ε4 allele carrier status as covariates. Results of the first set of analyses independently examining the relationship between components from each modality and clinical group showed three significant components for FDG: a left inferior frontal and temporoparietal component associated with AD-language (area under the curve [AUC] 0.82, p = 0.011), and two components associated with AD-visuospatial (bilateral occipito-parieto-temporal [AUC 0.85, p = 0.009] and right posterior cingulate cortex [PCC]/precuneus and right lateral parietal [AUC 0.69, p = 0.045]). The AD-memory associated component included predominantly bilateral inferior frontal, cuneus and inferior temporal, and right inferior parietal hypometabolism but did not reach significance (AUC 0.65, p = 0.062). None of the PiB components correlated with clinical group. Joint analysis of PiB and FDG with pICA revealed a correlated component pair, in which increased frontal and decreased PCC/precuneus PiB correlated with decreased FDG in the frontal, occipital and temporal regions (partial r = 0.75, p < 0.0001). Using multivariate data analysis, this study reinforced the notion that clinical phenotype in AD is tightly linked to patterns of glucose hypometabolism but not amyloid deposition. These findings are strikingly similar to those of univariate paradigms and provide additional support in favor of specific involvement of the language network, higher-order visual network, and default mode network in clinical variants of AD. The inverse relationship between Aβ deposition and glucose metabolism in partially overlapping brain regions suggests that Aβ may exert both local and remote effects on brain metabolism. Applying multivariate approaches such as pICA to multimodal imaging data is a promising approach for unraveling the complex relationships between different elements of AD pathophysiology. PMID:24818077

From grid cells and visual place cells to multimodal place cell: a new robotic architecture

PubMed Central

Jauffret, Adrien; Cuperlier, Nicolas; Gaussier, Philippe

2015-01-01

In the present study, a new architecture for the generation of grid cells (GC) was implemented on a real robot. In order to test this model a simple place cell (PC) model merging visual PC activity and GC was developed. GC were first built from a simple “several to one” projection (similar to a modulo operation) performed on a neural field coding for path integration (PI). Robotics experiments raised several practical and theoretical issues. To limit the important angular drift of PI, head direction information was introduced in addition to the robot proprioceptive signal coming from the wheel rotation. Next, a simple associative learning between visual place cells and the neural field coding for the PI has been used to recalibrate the PI and to limit its drift. Finally, the parameters controlling the shape of the PC built from the GC have been studied. Increasing the number of GC obviously improves the shape of the resulting place field. Yet, other parameters such as the discretization factor of PI or the lateral interactions between GC can have an important impact on the place field quality and avoid the need of a very large number of GC. In conclusion, our results show our GC model based on the compression of PI is congruent with neurobiological studies made on rodent. GC firing patterns can be the result of a modulo transformation of PI information. We argue that such a transformation may be a general property of the connectivity from the cortex to the entorhinal cortex. Our model predicts that the effect of similar transformations on other kinds of sensory information (visual, tactile, auditory, etc…) in the entorhinal cortex should be observed. Consequently, a given EC cell should react to non-contiguous input configurations in non-spatial conditions according to the projection from its different inputs. PMID:25904862

Transit Time Flowmetry in Coronary Artery Bypass Grafting-experience at Queen Alia Heart Institute, Jordan

PubMed Central

Harahsheh, Basel

2012-01-01

Objectives To assess the results of transit time flowmetry (TTF) on a consecutive group of coronary artery bypass grafting (CABG) patients at Queen Alia Heart Institute. Methods Intraoperative flow measurements of a consecutive group of 436 CABG patients. The flow pattern for each coronary artery system was assessed including mean flows, pulsatility index (PI) and the need for revision. Results A total of 1394 grafts in 436 patients were assessed (3.2 grafts per patient), wherein 100 grafts showed inadequate flowmetry results (7.2%); most of which were in the circumflex and right coronary artery systems with a percentage of 9.4% and the least in the LAD system with a percentage of 4.4%. The mean flow of grafts to the LAD system was 33.4±5.3 mL/min with a PI of 2.4±0.4; while the mean for grafts to the circumflex artery system was 35.1±7.2 mL/min with a PI of 3.5±0.7. The mean for the right coronary artery was 38.4±5.9 mL/min with a PI of 2.6±0.6. Revisions occurred in five patients (1.1%). Suboptimal grafts to the LAD system exhibited a flow of 14.1±7.4 mL/min with a PI of 6.9±1.7. While for the circumflex system a flow of 5.5±3.6 mL/min was reported with a PI of 10.4±7.8; and for the right coronary system a flow of 7.2±5.3 mL/min with a PI of 9.1±5.7 was reported. Conclusion Grafts to the LAD system showed the best flowmetry results compared to grafts to the circumflex and right coronary systems. A proportion of poor grafts were revised. PMID:23226818

In situ measurements of angular-dependent light scattering by aerosols over the contiguous United States

NASA Astrophysics Data System (ADS)

Reed Espinosa, W.; Vanderlei Martins, J.; Remer, Lorraine A.; Puthukkudy, Anin; Orozco, Daniel; Dolgos, Gergely

2018-03-01

This work provides a synopsis of aerosol phase function (F11) and polarized phase function (F12) measurements made by the Polarized Imaging Nephelometer (PI-Neph) during the Studies of Emissions, Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) and the Deep Convection Clouds and Chemistry (DC3) field campaigns. In order to more easily explore this extensive dataset, an aerosol classification scheme is developed that identifies the different aerosol types measured during the deployments. This scheme makes use of ancillary data that include trace gases, chemical composition, aerodynamic particle size and geographic location, all independent of PI-Neph measurements. The PI-Neph measurements are then grouped according to their ancillary data classifications and the resulting scattering patterns are examined in detail. These results represent the first published airborne measurements of F11 and -F12/F11 for many common aerosol types. We then explore whether PI-Neph light-scattering measurements alone are sufficient to reconstruct the results of this ancillary data classification algorithm. Principal component analysis (PCA) is used to reduce the dimensionality of the multi-angle PI-Neph scattering data and the individual measurements are examined as a function of ancillary data classification. Clear clustering is observed in the PCA score space, corresponding to the ancillary classification results, suggesting that, indeed, a strong link exists between the angular-scattering measurements and the aerosol type or composition. Two techniques are used to quantify the degree of clustering and it is found that in most cases the results of the ancillary data classification can be predicted from PI-Neph measurements alone with better than 85 % recall. This result both emphasizes the validity of the ancillary data classification as well as the PI-Neph's ability to distinguish common aerosol types without additional information.

Impaired insulin signaling pathway in ovarian follicles of cows with cystic ovarian disease.

PubMed

Hein, G J; Panzani, C G; Rodríguez, F M; Salvetti, N R; Díaz, P U; Gareis, N C; Benítez, G A; Ortega, H H; Rey, F

2015-05-01

Cystic ovarian disease (COD) is an important cause of infertility in dairy cattle. Follicular cell steroidogenesis and proliferation in ovulatory follicles is stimulated by hormones such as insulin and its necessary post-receptor response. The aim of this study was to determine the expression of insulin receptor (IR), IR substrate-1 (IRS1) and phosphatidylinositol 3-kinase (PI3K), key intermediates in the insulin pathway, in control cows and cows with spontaneous COD and ACTH-induced COD. IR and IRS1 mRNA levels were greater in granulosa cells and lower in follicular cysts than in control tertiary follicles. PI3K mRNA levels were similar in all follicles evaluated, whereas the expression of IR, IRS1 and PI3K was similar in theca cells. Protein expression of IR was higher in control tertiary follicles than in the same structures in animals with COD and with cysts. IRS1 and PI3K protein expression showed the same pattern in tertiary and cystic follicles. However, the protein expression of subunit alpha p85 of PI3K was greater in theca cells from tertiary follicles than in cystic follicles. These results provide new insights into the insulin response in cows with COD. The lower gene and protein expressions of some insulin downstream effectors at an early stage of the signaling pathway could negatively influence the functionality of ovaries and contribute to follicle persistence. Copyright © 2015 Elsevier B.V. All rights reserved.

Two differentially regulated phosphate transporters from the symbiotic fungus Hebeloma cylindrosporum and phosphorus acquisition by ectomycorrhizal Pinus pinaster.

PubMed

Tatry, Marie-Violaine; El Kassis, Elie; Lambilliotte, Raphaël; Corratgé, Claire; van Aarle, Ingrid; Amenc, Laurie K; Alary, Rémi; Zimmermann, Sabine; Sentenac, Hervé; Plassard, Claude

2009-03-01

Ectomycorrhizal symbiosis markedly improves plant phosphate uptake, but the molecular mechanisms underlying this benefit are still poorly understood. We identified two ESTs in a cDNA library prepared from the ectomycorrhizal basidiomycete Hebeloma cylindrosporum with significant similarities to phosphate transporters from the endomycorrhizal fungus Glomus versiforme and from non-mycorrhizal fungi. The full-length cDNAs corresponding to these two ESTs complemented a yeast phosphate transport mutant (Deltapho84). Measurements of (33)P-phosphate influx into yeast expressing either cDNA demonstrated that the encoded proteins, named HcPT1 and HcPT2, were able to mediate Pi:H(+) symport with different affinities for Pi (K(m) values of 55 and 4 mum, respectively). Real-time RT-PCR showed that Pi starvation increased the levels of HcPT1 transcripts in H. cylindrosporum hyphae grown in pure culture. Transcript levels of HcPT2 were less dependent on Pi availability. The two transporters were expressed in H. cylindrosporum associated with its natural host plant, Pinus pinaster, grown under low or high P conditions. The presence of ectomycorrhizae increased net Pi uptake rates into intact Pinus pinaster roots at low or high soil P levels. The expression patterns of HcPT1 and HcPT2 indicate that the two fungal phosphate transporters may be involved in uptake of phosphate from the soil solution under the two soil P availability conditions used.

Photosynthetic characteristics and estimated growth rates indicate grazing is the proximate control of primary production in the equatorial Pacific

NASA Technical Reports Server (NTRS)

Cullen, John J.; Lewis, Marlon R.; Davis, Curtiss O.; Barber, Richard T.

1992-01-01

Macronutrients persist in the surface layer of the equatorial Pacific because the production of phytoplankton is limited; the nature of this limitation has yet to be resolved. Measurements of photosynthesis as a function of irradiance (P-I) provide information on the control of primary productivity, a question of great biogeochemical importance. Accordingly, P-I was measured in the equatorial Pacific along 150 deg W, during February-March 1988. Diel variability of P-I showed a pattern consistent with nocturnal vertical mixing in the upper 20 m followed by diurnal stratification, causing photoinhibition near the surface at midday. Otherwise, the distribution of photosynthetic parameters with depth and the stability of P-I during simulated in situ incubations over 2 days demonstrated that photoadaptation was nearly complete at the time of sampling: photoadaptation had not been effectively countered by upwelling or vertical mixing. Measurements of P-I and chlorophyll during manipulations of trace elements showed that simple precautions to minimize contamination were sufficient to obtain valid rate measurements and that the specific growth rates of phytoplankton were fairly high in situ, a minimum of 0.6/d. Diel variability of beam attenuation also indicated high specific growth rates of phytoplankton and a strong coupling of production with grazing. It appears that grazing is the proximate control on the standing crop of phytoplankton. Nonetheless, the supply of a trace nutrient such as iron might ultimately regulate productivity by influencing species composition and food-web structure.

Patterns of Cognitive Strengths and Weaknesses: Identification Rates, Agreement, and Validity for Learning Disabilities Identification

ERIC Educational Resources Information Center

Miciak, Jeremy; Fletcher, Jack M.; Stuebing, Karla K.; Vaughn, Sharon; Tolar, Tammy D.

2014-01-01

Few empirical investigations have evaluated learning disabilities (LD) identification methods based on a pattern of cognitive strengths and weaknesses (PSW). This study investigated the reliability and validity of two proposed PSW methods: the concordance/discordance method (C/DM) and cross battery assessment (XBA) method. Cognitive assessment…

Identification of differentially expressed lncRNAs involved in transient regeneration of the neonatal C57BL/6J mouse heart by next-generation high-throughput RNA sequencing.

PubMed

Chen, Yu-Mei; Li, Hua; Fan, Yi; Zhang, Qi-Jun; Li, Xing; Wu, Li-Jie; Chen, Zi-Jie; Zhu, Chun; Qian, Ling-Mei

2017-04-25

Previous studies have shown that mammalian cardiac tissue has a regenerative capacity. Remarkably, neonatal mice can regenerate their cardiac tissue for up to 6 days after birth, but this capacity is lost by day 7. In this study, we aimed to explore the expression pattern of long noncoding RNA (lncRNA) during this period and examine the mechanisms underlying this process. We found that 685 lncRNAs and 1833 mRNAs were differentially expressed at P1 and P7 by the next-generation high-throughput RNA sequencing. The coding genes associated with differentially expressed lncRNAs were mainly involved in metabolic processes and cell proliferation, and also were potentially associated with several key regeneration signalling pathways, including PI3K-Akt, MAPK, Hippo and Wnt. In addition, we identified some correlated targets of highly-dysregulated lncRNAs such as Igfbp3, Trnp1, Itgb6, and Pim3 by the coding-noncoding gene co-expression network. These data may offer a reference resource for further investigation about the mechanisms by which lncRNAs regulate cardiac regeneration.

Characterization of Anthocyanins in Perilla frutescens var. acuta Extract by Advanced UPLC-ESI-IT-TOF-MSn Method and Their Anticancer Bioactivity.

PubMed

He, Yan-Kang; Yao, You-Yuan; Chang, Ya-Ning

2015-05-19

The anthocyanin extract from a domestic Perilla cultivar (Perilla frutescens var. acuta) were isolated and characterized with high mass accuracy and multi-dimensional fragmentation by means of ultra-performance liquid chromatography (UPLC) and electrospray ionization-ion trap-time of flight mass spectrometry analysis (ESI-IT-TOF-MSn). The new developed and applied LC-MS method focused on in-depth screening of anthocyanin compounds with similar structures which also provided a new approach of anthocyanin characterization without the use of external standards. Selective detection of interested anthocyanins was achieved utilizing extracted ion chromatogram (EIC) analysis, while MSn spectra were recorded to allow identification of the anthocyanin based on characteristic fragmentation patterns. Seven anthocyanins including one feruloyl (Cyanidin 3-O-feruloylglucoside-5-O-glucoside), two caffeoyl (Cyanidin 3-O-caffeoylglucoside-5-O-glucoside, Cyanidin 3-O-caffeoylglucoside-5-O-malonylglucoside) and four coumaroyl substituted anthocyanins (Cis-shisonin, Malonyl-cis-shisonin, Shisonin, and Malonyl-shisonin) were identified. Annexin-V FITC/PI flow cytometric assay was performed to analyze the influence of anthocyanin extract of P. frutescens var. acuta on cell apoptosis. The results suggested that Perilla anthocyanins can induce Hela cell apoptosis by a dose dependent manner.

TabHLH1, a bHLH-type transcription factor gene in wheat, improves plant tolerance to Pi and N deprivation via regulation of nutrient transporter gene transcription and ROS homeostasis.

PubMed

Yang, Tongren; Hao, Lin; Yao, Sufei; Zhao, Yuanyuan; Lu, Wenjing; Xiao, Kai

2016-07-01

Basic helix-loop-helix (bHLH) transcription factors (TFs) comprise a large TF family and act as crucial regulators in various biological processes in plants. Here, we report the functional characterization of TabHLH1, a bHLH TF member in wheat (Triticum aestivum). TabHLH1 shares conserved bHLH domain and targets to nucleus with transactivation activity. Upon Pi and N deprivation, the expression of TabHLH1 was up-regulated in roots and leaves, showing a pattern to be gradually increased within 23-h treatment regimes. The lines with overexpression of TabHLH1 exhibited drastically improved tolerance to Pi and N deprivation, showing larger plant phenotype, more biomass, higher concentration and more accumulation of P and N than wild type (WT) upon the Pi- and N-starvation stresses. NtPT1 and NtNRT2.2, the genes encoding phosphate transporter (PT) and nitrate transporter (NRT) in tobacco, respectively, showed up-regulated expression in TabHLH1-overexpressing plants; knockdown expression of them led to deteriorated growth feature, lowered biomass, and decreased nutrient accumulation of plants under Pi- and N-deficient conditions. Compared with WT, the TabHLH1-overexpressing plants also showed lowered reactive oxygen species (ROS) accumulation and improved antioxidant enzyme (AE) activities, such as those of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD). NtSOD1, NtCAT1, and NtPOD1;6 that encode SOD, CAT, and POD, respectively, were up-regulated in TabHLH1-overexpressing plants. Further knockdown of these AE gene expression caused reduced antioxidant enzymatic activities, indicative of their crucial roles in mediating cellular ROS homeostasis in Pi- and N-starvation conditions. Together, TabHLH1 plays an important role in mediating adaptation to the Pi- and N-starvation stresses through transcriptional regulation of a set of genes encoding PT, NRT and AEs that mediate the taken up of Pi and N and the cellular homeostasis of ROS initiated by the nutrient stresses. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Diagnostic performance and reproducibility of T2w based and diffusion weighted imaging (DWI) based PI-RADSv2 lexicon descriptors for prostate MRI.

PubMed

Benndorf, Matthias; Hahn, Felix; Krönig, Malte; Jilg, Cordula Annette; Krauss, Tobias; Langer, Mathias; Dovi-Akué, Philippe

2017-08-01

To examine the diagnostic performance of PI-RADSv2 T2w and diffusion weighted imaging (DWI) based lexicon descriptors, inter-observer agreement for descriptor assignment and diagnostic accuracy of the PI-RADSv2 assessment categories for multiparametric prostate MRI. 176 lesions in 79 consecutive patients are analyzed, lesions are histopathologically verified by MRI-ultrasound fusion biopsy. All lesions are rated according to the PI-RADSv2 lexicon, descriptors for T2w and DWI sequences and resulting assessment categories are assigned by two independent blinded radiologists. We perform receiver-operating-characteristic analysis using the assessment categories. To analyze inter-observer agreement, we calculate weighted kappa values for assessment category assignment and unweighted kappa values for descriptor assignment. PI-RADSv2 assessment categories yield an area under the curve of 0.76/0.74 (radiologist 1/radiologist 2), P >0.05. Weighted kappa for agreement is 0.601 in the peripheral zone and 0.580 in the transition zone. We detect a difference in the cancer rate for PI-RADSv2 category 3 between peripheral zone (32%) and transition zone (12%), P <0.05. We obtain moderate agreement at most for descriptor assignment with kappa values ranging from 0.082 (T2w shape in the transition zone) to 0.407 (T2w signal intensity in the peripheral zone) and 0.493 (ADC pattern in the peripheral zone). Our analysis corroborates typical descriptors for benign/malignant lesions, but also reveals insights into potential pitfalls - T2w wedge shaped lesions in the peripheral zone have a considerable cancer rate, despite being labelled category 2 in the lexicon. Agreement for descriptor assignment in the PI-RADSv2 lexicon is at most moderate in our study. Typical descriptors for benign and malignant lesions are validated, whereas the discriminatory power of some descriptors is challenged. The difference in the cancer rate for PI-RADSv2 category 3 between peripheral zone and transition zone should be considered when management recommendations are linked to assessment categories in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional pools of oxidative and glycolytic fibers in human muscle observed by 31P magnetic resonance spectroscopy during exercise.

PubMed Central

Park, J H; Brown, R L; Park, C R; McCully, K; Cohn, M; Haselgrove, J; Chance, B

1987-01-01

Quantitative probing of heterogeneous regions in muscle is feasible with phosphorus-31 magnetic resonance spectroscopy because of the differentiation of metabolic patterns of glycolytic and oxidative fibers. A differential recruitment of oxidative and glycolytic fibers during exercise was demonstrated in 4 of 10 untrained young men by following changes in phosphate metabolites. Concentrations of inorganic phosphate (Pi), phosphocreatine, and ATP were estimated in the wrist flexor muscles of the forearm at rest, during two cycles of three grades of exercise, and in recovery. At high work levels (40% of maximum strength), two distinct Pi peaks were observed and identified with Pi pools at pH 6.9 and pH 5.9-6.4, respectively. These could be accounted for as follows. At the lowest level of work (using 20% of maximum strength), early recruitment primarily of oxidative (type I) and possibly some intermediate (type IIA) muscle fibers occurs with relatively little net lactate production and consequently little decrease in pH. At higher work loads, however, primarily glycolytic (type IIB) muscle fibers are recruited, which have relatively high net lactate production and therefore generate a second pool of Pi at low pH. ATP depletion (35-54%) and Pi losses accompanied the reduction in ability to perform during the first exercise cycle. When the cycle of graded exercise was repeated immediately, the total Pi remained high but gave rise to only one peak at pH 6.8-7.0. These observations indicated exhaustion of glycolytic type IIB fibers, removal of lactate by high local blood flow, and sustained contractions largely by oxidative type I and IIA fibers. A functional differentiation of fiber types could also be demonstrated during recovery if exercise was stopped while two pools of Pi were still apparent. In the first 3 min of recovery, the Pi peak at pH 6.8-6.9 disappeared almost entirely, whereas the Pi peak at pH 6.0 remained unaltered, reflecting the faster recovery of oxidative type I fibers. The potential of magnetic resonance spectroscopy to characterize oxidative and glycolytic fibers, predict capacity for aerobic performance, and signal the presence of muscle pathology is discussed. PMID:3480522

Characterization of the soybean GmALMT family genes and the function of GmALMT5 in response to phosphate starvation.

PubMed

Peng, Wenting; Wu, Weiwei; Peng, Junchu; Li, Jiaojiao; Lin, Yan; Wang, Yanan; Tian, Jiang; Sun, Lili; Liang, Cuiyue; Liao, Hong

2018-03-01

A potential mechanism to enhance utilization of sparingly soluble forms of phosphorus (P) is the root secretion of malate, which is mainly mediated by the ALMT gene family in plants. In this study, a total of 34 GmALMT genes were identified in the soybean genome. Expression patterns diverged considerably among GmALMTs in response to phosphate (Pi) starvation in leaves, roots and flowers, with expression altered by P availability in 26 of the 34 GmALMTs. One root-specific GmALMT whose expression was significantly enhanced by Pi-starvation, GmALMT5, was studied in more detail to determine its possible role in soybean P nutrition. Analysis of GmALMT5 tissue expression patterns, subcellular localization, and malate exudation from transgenic soybean hairy roots overexpressing GmALMT5, demonstrated that GmALMT5 is a plasma membrane protein that mediates malate efflux from roots. Furthermore, both growth and P content of transgenic Arabidopsis overexpressing GmALMT5 were significantly increased when sparingly soluble Ca-P was used as the external P source. Taken together, these results indicate that members of the soybean GmALMT gene family exhibit diverse responses to Pi starvation. One member of this family, GmALMT5, might contribute to soybean P efficiency by enhancing utilization of sparingly soluble P sources under P limited conditions. © 2017 Institute of Botany, Chinese Academy of Sciences.

A critical source area phosphorus index with topographic transport factors using high resolution LiDAR digital elevation models

NASA Astrophysics Data System (ADS)

Thomas, Ian; Murphy, Paul; Fenton, Owen; Shine, Oliver; Mellander, Per-Erik; Dunlop, Paul; Jordan, Phil

2015-04-01

A new phosphorus index (PI) tool is presented which aims to improve the identification of critical source areas (CSAs) of phosphorus (P) losses from agricultural land to surface waters. In a novel approach, the PI incorporates topographic indices rather than watercourse proximity as proxies for runoff risk, to account for the dominant control of topography on runoff-generating areas and P transport pathways. Runoff propensity and hydrological connectivity are modelled using the Topographic Wetness Index (TWI) and Network Index (NI) respectively, utilising high resolution digital elevation models (DEMs) derived from Light Detection and Ranging (LiDAR) to capture the influence of micro-topographic features on runoff pathways. Additionally, the PI attempts to improve risk estimates of particulate P losses by incorporating an erosion factor that accounts for fine-scale topographic variability within fields. Erosion risk is modelled using the Unit Stream Power Erosion Deposition (USPED) model, which integrates DEM-derived upslope contributing area and Universal Soil Loss Equation (USLE) factors. The PI was developed using field, sub-field and sub-catchment scale datasets of P source, mobilisation and transport factors, for four intensive agricultural catchments in Ireland representing different agri-environmental conditions. Datasets included soil test P concentrations, degree of P saturation, soil attributes, land use, artificial subsurface drainage locations, and 2 m resolution LiDAR DEMs resampled from 0.25 m resolution data. All factor datasets were integrated within a Geographical Information System (GIS) and rasterised to 2 m resolution. For each factor, values were categorised and assigned relative risk scores which ranked P loss potential. Total risk scores were calculated for each grid cell using a component formulation, which summed the products of weighted factor risk scores for runoff and erosion pathways. Results showed that the new PI was able to predict in-field risk variability and hence was able to identify CSAs at the sub-field scale. PI risk estimates and component scores were analysed at catchment and subcatchment scales, and validated using measured dissolved, particulate and total P losses at subcatchment snapshot sites and gauging stations at catchment outlets. The new PI provides CSA delineations at higher precision compared to conventional PIs, and more robust P transport risk estimates. The tool can be used to target cost-effective mitigation measures for P management within single farm units and wider catchments.

Comparing visual and objective skin assessment with pressure injury risk.

PubMed

Borzdynski, Caroline J; McGuiness, William; Miller, Charne

2016-08-01

Contemporary approaches to pressure injury (PI) risk identification rely on the use of risk assessment tools and visual skin assessment. Objective biophysical measures that assess skin hydration, melanin, erythema and lipids have not been traditionally used in PI risk; however, these may prove useful as a risk assessment tool. The relationship between subjective visual assessments of skin condition, biophysical measures and PI risk warrants investigation. This study used a descriptive correlational design to examine the relationship between measures of skin hydration, colour (melanin and erythema) and lipids at PI-prone areas amongst geriatric persons (n = 38), obtained using biophysical skin measures and visual skin assessment. Twice daily measures of epidermal hydration, colour and lipids were assessed using the SD202 Skin Diagnostic (Courage + Khazaka GmBH, Cologne, Germany) over pressure-prone areas of the body of study participants over seven consecutive days. Concurrent visual assessment of skin hydration and colour was performed. Results obtained using the SD202 Skin Diagnostic were compared with results gathered from visual assessment and examined for their association with participants' PI risk based on scores of the Norton Risk Assessment Scale. While epidermal hydration and skin colour reading scores did not vary significantly over the data collection period, lipid readings could not be registered on any occasion. With the exception of skin dryness, skin parameters via both objective and subjective means had significant, positive correlations. Statistically significant correlations emerged between visual assessment of skin wetness at the sacrum (r = -0·441, P < 0·01) and ischia (r = -0·468, P < 0·01) and Norton Risk Assessment Scale scores. It was found that the objective assessment of epidermal hydration (skin wetness) was also significantly associated with PI risk at the sacrum (r = -0·528, P < 0·01), as well as the right ischia (r = -0·410, P < 0·05) and left ischia (r = -0·407, P < 0·05). Erythema, when assessed objectively, was significantly correlated with PI risk at the sacrum (r = -0·322, P < 0·05). Such findings indicating that the finer measures afforded by the SD202 Skin Diagnostic in the assessment of the subtle red hues displayed in erythematous skin may provide an additional advantage over traditional, clinician assessment. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Histopathology of experimental scuticociliatosis in turbot Scophthalmus maximus.

PubMed

Puig, L; Traveset, R; Palenzuela, O; Padrós, F

2007-06-29

A scuticociliate strain (B-2), originally isolated from an outbreak in a turbot Scophthalmus maximus (= Psetta maxima) farm in Galicia (northwestern Spain) and maintained in axenic culture, was injected intracoelomically (lethal dose 80 equivalent, LD80) in healthy turbot (50 g). Ciliate-injected fish were kept under controlled conditions in a recirculating seawater system and sampled on Days 1 through 8, 10, 12 and 14 postinfection (PI). Necropsies were conducted and included blood collection from the caudal vein and samples of liver, spleen, heart, digestive tract, kidney, gills, abdominal wall and neurocranium taken for routine histology. Mortality occurred from Day 6 until Day 12 PI and reached 66.7% by the end of the experiment. Presence of ciliates in the coelomic fluid was scarce until Day 4 PI. Parasitaemia was only observed from Day 5 until Day 10 PI and its incidence was always low. Presence of scuticociliates in tissue sections followed a progressive pattern of diffusion, with ciliates showing preference for loose connective tissue and also a clear haematophagous activity. The most severely affected organs were the pancreas and digestive tract. No special tropism for nervous tissues was observed in this study. The inflammatory reaction was variable depending on the tissue. After 3 wk, survivors had apparently managed to extinguish the infection.

Alzheimer risk genes modulate the relationship between plasma apoE and cortical PiB binding

DOE PAGES

Lazaris, Andreas; Hwang, Kristy S.; Goukasian, Naira; ...

2015-10-15

Objective: We investigated the association between apoE protein plasma levels and brain amyloidosis and the effect of the top 10 Alzheimer disease (AD) risk genes on this association. Methods: Our dataset consisted of 18 AD, 52 mild cognitive impairment, and 3 cognitively normal Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) participants with available [ 11C]-Pittsburgh compound B (PiB) and peripheral blood protein data. We used cortical pattern matching to study associations between plasma apoE and cortical PiB binding and the effect of carrier status for the top 10 AD risk genes. Results: Low plasma apoE was significantly associated with high PiBmore » SUVR, except in the sensorimotor and entorhinal cortex. For BIN1 rs744373, the association was observed only in minor allele carriers. For CD2AP rs9349407 and CR1 rs3818361, the association was preserved only in minor allele noncarriers. We did not find evidence for modulation by CLU, PICALM, ABCA7, BIN1, and MS4A6A. Conclusions: Our data show that BIN1 rs744373, CD2AP rs9349407, and CR1 rs3818361 genotypes modulate the association between apoE protein plasma levels and brain amyloidosis, implying a potential epigenetic/downstream interaction.« less

Neotectonic and Geomorphological Characteristics of the Ma Pi Leng Area (Ha Giang Province, North Vietnam): Implications for Improving the Worth of Vietnamese Geological Heritage

NASA Astrophysics Data System (ADS)

Van Bui, Thom; Huy Nguyen, Thinh; Duc Nguyen, Tung

2018-03-01

Ma Pi Leng area is the core part of Dong Van karst plateau geopark, and is a region of high diversity of geology and tectonics in Vietnam. This region has experienced strong uplift motions that have created three grades of regional relief: 1400-1600 m; 1100-1200 m and 500-600 m. This geomorphology is in turn strongly eroded by the stream systems and divided into different structural blocks controlled by the faults. During the neotectonic stage, several modes of faulting have occurred in Ma Pi Leng such as strikeslip, normal, extension, riverse faults. The NW-SE fault system had a decisive role in determining the structural pattern of the region. The tectonic fractures, at the largest scale, are hundreds of meters high and up to a kilometer long. Tectonic activities, together with exogenic processes, have made regional relief strongly diverse with strips of horsts and grabens as well as laddersteps-shaped escarpments, inverse topography, high cliffs and deep canyons. Besides that there are also the caves at varying levels of height, chains of sinkholes, and pyramidal mountainous peaks. Ma Pi Leng area is truly majestic and worthy of tourist attractions both in terms of scientific value and natural landscape.

EEG power during waking and NREM sleep in primary insomnia.

PubMed

Wu, You Meme; Pietrone, Regina; Cashmere, J David; Begley, Amy; Miewald, Jean M; Germain, Anne; Buysse, Daniel J

2013-10-15

Pathophysiological models of insomnia invoke the concept of 24-hour hyperarousal, which could lead to symptoms and physiological findings during waking and sleep. We hypothesized that this arousal could be seen in the waking electroencephalogram (EEG) of individuals with primary insomnia (PI), and that waking EEG power would correlate with non-REM (NREM) EEG. Subjects included 50 PI and 32 good sleeper controls (GSC). Five minutes of eyes closed waking EEG were collected at subjects' usual bedtimes, followed by polysomnography (PSG) at habitual sleep times. An automated algorithm and visual editing were used to remove artifacts from waking and sleep EEGs, followed by power spectral analysis to estimate power from 0.5-32 Hz. We did not find significant differences in waking or NREM EEG spectral power of PI and GSC. Significant correlations between waking and NREM sleep power were observed across all frequency bands in the PI group and in most frequency bands in the GSC group. The absence of significant differences between groups in waking or NREM EEG power suggests that our sample was not characterized by a high degree of cortical arousal. The consistent correlations between waking and NREM EEG power suggest that, in samples with elevated NREM EEG beta activity, waking EEG power may show a similar pattern.

Intraplacental villous artery resistance indices and identification of placenta-mediated diseases.

PubMed

Babic, I; Ferraro, Z M; Garbedian, K; Oulette, A; Ball, C G; Moretti, F; Gruslin, A

2015-10-01

Placenta-mediated diseases (PMDs) including preeclampsia and fetal growth restriction are often characterized by shallow trophoblast invasion and incomplete spiral artery remodeling leading to impaired placental perfusion. In this context, umbilical artery (UA) Doppler can be used to detect high resistance to flow characteristic of very late-stage placental disease. We propose that evaluation of intraplacental villous artery (IPVA) resistance can provide earlier detection of increased resistance in placental flow. Seventy-five patients were recruited from the Ottawa Hospital. All had scans at 18 to 20, 28 and 34 weeks of gestation. IPVAs arising perpendicular to the chorionic plate in three regions (placental tips 4 cm away from cord insertion and within 1 cm from cord insertion) were sampled at each gestational age for resistance index (RI) and pulsatility index (PI). UA Doppler was also obtained from a free loop of cord. Pregnancy outcomes were collected from a chart review. Data were analyzed using SAS version 9.4 and standard statistic tests (mean±s.d., Student's t-test, mixed-effects modeling). A total of 53 patients completed the study. Of these, 38 had normal pregnancy outcomes (controls) and 15 (cases) developed PMD (preeclampsia, n=8 and low birth weight/intrauterine growth restriction, n=7). Mean birth weight in the study group was 2482.1±518.85 g. At 18 to 20, 28 and 34 weeks gestation, the mean IPVA resistance indices in the control group were 0.86±0.16, 0.81±0.12 and 0.71±0.12 for PI and 0.57±0.07, 0.55±0.06 and 0.49±0.06 for RI, respectively. However, in the cases developing PMDs, the PIs were 1.09±0.17, 0.95±0.21 and 0.78±0.07 and RIs 0.66±0.07, 0.60±0.07 and 0.54±0.04, respectively (P<0.05). UA PI and RI Doppler did not differ between the groups as early as 18 to 20 weeks gestation. Doppler measures of IPVA appear superior to UA in detecting early changes related to PMD. IPVA PI and RI Doppler may be useful in the early identification of patients at risk of PMD.

Simulation of LD Identification Accuracy Using a Pattern of Processing Strengths and Weaknesses Method with Multiple Measures

ERIC Educational Resources Information Center

Miciak, Jeremy; Taylor, W. Pat; Stuebing, Karla K.; Fletcher, Jack M.

2018-01-01

We investigated the classification accuracy of learning disability (LD) identification methods premised on the identification of an intraindividual pattern of processing strengths and weaknesses (PSW) method using multiple indicators for all latent constructs. Known LD status was derived from latent scores; values at the observed level identified…

Connecting Self-Esteem and Achievement: Diversity in Academic Identification and Dis-Identification Patterns among Black College Students

ERIC Educational Resources Information Center

Hope, Elan C.; Chavous, Tabbye M.; Jagers, Robert J.; Sellers, Robert M.

2013-01-01

Using a person-oriented approach, we explored patterns of self-esteem and achievement among 324 Black college students across the freshman college year and identified four academic identification profiles. Multivariate analyses revealed profile differences in academic and psychological outcomes at beginning and end of freshman year (academic…

Comparative analysis of lip with thumbprints: An identification tool in personal authentication.

PubMed

Naik, Rashmi; Ahmed Mujib, B R; Telagi, Neethu; Hallur, Jaydeva

2017-01-01

Identification of person living or dead using diverse characteristics is the basis in forensic science. The uniqueness of lip and fingerprints and further, association between them can be useful in establishing facts in legal issues. The present study was carried out to determine the distribution of different lip print patterns among subjects having different thumbprint patterns and to determine the correlation between lip print patterns and thumbprint patterns. The study sample comprised 100 students randomly selected from Bapuji Dental College Hospital, Davangere, Karnataka, 50 males and 50 females aged between 18 and 20 years. Red colored lipstick was applied on the lips by a lipstick applicator brush. Lip and thumb impressions were made on No. 1 Whatman filter paper and visualized using magnifying lens. Three main types of fingerprints (loop, whorl and arch) were identified; Tsuchihashi Y classification of lip print patterns was followed in the study. Chi-square test was used to see the association between lip and thumbprints. The correlation between lip and left thumb print patterns for gender identification was statistically significant. In both males and females, Type II lip pattern associated with loop finger pattern were most significant and in males, Type III lip pattern with whorl type of finger pattern showed statistical significance. We conclude that the correlation found between lip print and thumbprint can be utilized in the field of forensic science for gender identification.

Rapid condition assessment of structural condition after a blast using state-space identification

NASA Astrophysics Data System (ADS)

Eskew, Edward; Jang, Shinae

2015-04-01

After a blast event, it is important to quickly quantify the structural damage for emergency operations. In order improve the speed, accuracy, and efficiency of condition assessments after a blast, the authors have previously performed work to develop a methodology for rapid assessment of the structural condition of a building after a blast. The method involved determining a post-event equivalent stiffness matrix using vibration measurements and a finite element (FE) model. A structural model was built for the damaged structure based on the equivalent stiffness, and inter-story drifts from the blast are determined using numerical simulations, with forces determined from the blast parameters. The inter-story drifts are then compared to blast design conditions to assess the structures damage. This method still involved engineering judgment in terms of determining significant frequencies, which can lead to error, especially with noisy measurements. In an effort to improve accuracy and automate the process, this paper will look into a similar method of rapid condition assessment using subspace state-space identification. The accuracy of the method will be tested using a benchmark structural model, as well as experimental testing. The blast damage assessments will be validated using pressure-impulse (P-I) diagrams, which present the condition limits across blast parameters. Comparisons between P-I diagrams generated using the true system parameters and equivalent parameters will show the accuracy of the rapid condition based blast assessments.

Can Polyphosphate Biochemistry Affect Biological Apatite Saturation?

NASA Astrophysics Data System (ADS)

Omelon, S. J.; Matsuura, N.; Gorelikov, I.; Wynnyckyj, C.; Grynpas, M. D.

2010-12-01

Phosphorus (P) is an important and limiting element for life. One strategy for storing ortho phosphates (Pi) is polymerization. Polymerized Pi's (polyphosphates: (PO3-)n: polyPs) serve as a Pi bank, as well as a catiion chelator, energy source, & regulator of responses to stresses in the stationary phase of culture growth and development1. PolyP biochemistry has been investigated in yeasts, bacteria & plants2. Bigeochemical cycling of P includes the condensation of Pi into pyro (P2O7-4), & polyPs, & the release of Pi from these compounds by the hydrolytic degradation of Pi from phosphomonoester bonds. Alkaline phosphatase (ALP) is one of the predominate enzymes for regenerating Pi in aquatic systems3, & it cleaves Pi from polyPs. ALP is also the enzyme associated with apatite biomineralization in vertebrates4. PolyP was proposed to be the ALP substrate in bone mineralization5. Where calcium ions are plentiful in many aquatic environments, there is no requirement for aquatic life to generate Ca-stores. However, terrestrial vertebrates benefit from a bioavailable Ca-store such as apatite. The Pi storage strategy of polymerizing PO4-3 into polyPs dovetails well with Ca-banking, as polyPs sequester Ca, forming a neutral calcium polyphosphate (Ca-polyP: (Ca(PO3)2)n) complex. This neutral complex represents a high total [Ca+2] & [PO4-3], without the threat of inadvertent apatite precipitation, as the free [Ca+2] & [PO4-3], and therefore apatite saturation, are zero. Recent identification of polyP in regions of bone resorption & calcifying cartilage5 suggests that vertebrates may use polyP chemistry to bank Ca+2 and PO4-3. In vitro experiments with nanoparticulate Ca-polyP & ALP were undertaken to determine if carbonated apatite could precipitate from 1M Ca-polyP in Pi-free “physiological fluid” (0.1 M NaCl, 2 mM Ca+2, 0.8 mM Mg+2, pH ~8.0 ±0.5, 37 °C), as this is estimated to generate the [Ca+2] & [PO4-3] required to form the apatite content of bone tissue (estimated to be 1 g apatite/mL). Carbonates (as NaHCO3 or CaCO3) were used to buffer the protons produced upon polyP hydrolytic degradation to Pi, releasing Ca+2, increasing apatite saturation for precipitation. Initial Ca:P ratios (by EDS) was <1, indicative of Ca-polyP. After incubation, Ca:P ratios were >1, suggesting the formation of Ca-PO4 minerals. XRD results identified Na-Ca- carbonate phases, & hydroxyapatite & carbonated apatite, & residual carbonate reagent. Further optimization of this biological apatite precipitation system will be presented. 1 Kornberg, A., Ann Rev Biochem 1999 (68) 89 2 Kulaev IS, Vagabov VM, Kulakovskaya TV (2004) The Biochemistry of Inorganic Polyphosphates. Chichester, England, John Wiley & Sons, Ltd. 3 Blake, R. E., O’Neil, J.R., and Surov, A. Am J Sci 2005 (305) 596 4 Heersche, J. N. M. et al. (1990) Bone Regulatory Factors; Plenum Press: New York 5 Omelon et al., PLoS ONE 2009 4(5), e5634

qPMS9: An Efficient Algorithm for Quorum Planted Motif Search

NASA Astrophysics Data System (ADS)

Nicolae, Marius; Rajasekaran, Sanguthevar

2015-01-01

Discovering patterns in biological sequences is a crucial problem. For example, the identification of patterns in DNA sequences has resulted in the determination of open reading frames, identification of gene promoter elements, intron/exon splicing sites, and SH RNAs, location of RNA degradation signals, identification of alternative splicing sites, etc. In protein sequences, patterns have led to domain identification, location of protease cleavage sites, identification of signal peptides, protein interactions, determination of protein degradation elements, identification of protein trafficking elements, discovery of short functional motifs, etc. In this paper we focus on the identification of an important class of patterns, namely, motifs. We study the (l, d) motif search problem or Planted Motif Search (PMS). PMS receives as input n strings and two integers l and d. It returns all sequences M of length l that occur in each input string, where each occurrence differs from M in at most d positions. Another formulation is quorum PMS (qPMS), where the motif appears in at least q% of the strings. We introduce qPMS9, a parallel exact qPMS algorithm that offers significant runtime improvements on DNA and protein datasets. qPMS9 solves the challenging DNA (l, d)-instances (28, 12) and (30, 13). The source code is available at https://code.google.com/p/qpms9/.

Dietary flavonoid fisetin: A novel dual inhibitor of PI3K/Akt and mTOR for prostate cancer management

PubMed Central

Adhami, Vaqar Mustafa; Syed, Deeba; Khan, Naghma; Mukhtar, Hasan

2013-01-01

Epidemiologic and case control population based studies over the past few decades have identified diet as an important determinant of cancer risk. This evidence has kindled an interest into research on bioactive food components and has till date resulted in the identification of many compounds with cancer preventive and therapeutic potential. Among such compounds has been fisetin (3,7,3’,4’-tetrahydroxyflavone), a flavonol and a member of the flavonoid polyphenols that also include quercetin, myricetin and kaempferol. Fisetin is commonly found in many fruits and vegetables such as apples, persimmons, grapes, kiwis, strawberries, onions and cucumbers. We evaluated the effects of fisetin against melanoma and cancers of the prostate, pancreas and the lungs. Using prostate and lung adenocarcinoma cells, we observed that fisetin acts as a dual inhibitor of the PI3K/Akt and the mTOR pathways. This is a significant finding considering the fact that mTOR is phosphorylated and its activation is more frequent in tumors with overexpression of PI3K/Akt. Dual inhibitors of PI3K/Akt and mTOR signaling have been suggested as valuable agents for treating such cancers. Here, we summarize our findings on the dietary flavonoid fisetin and its effects on cancer with particular focus on prostate cancer. Our observations and findings from other laboratories suggest that fisetin could be a useful chemotherapeutic agent that could be used either alone or as an adjuvant with conventional chemotherapeutic drugs for the management of prostate and other cancers. PMID:22842629

Identification of abnormal accident patterns at intersections

DOT National Transportation Integrated Search

1999-08-01

This report presents the findings and recommendations based on the Identification of Abnormal Accident Patterns at Intersections. This project used a statistically valid sampling method to determine whether a specific intersection has an abnormally h...

Phosphate assimilation in Rhizobium (Sinorhizobium) meliloti: identification of a pit-like gene.

PubMed

Bardin, S D; Voegele, R T; Finan, T M

1998-08-01

Rhizobium meliloti mutants defective in the phoCDET-encoded phosphate transport system form root nodules on alfalfa plants that fail to fix nitrogen (Fix-). We have previously reported that two classes of second-site mutations can suppress the Fix- phenotype of phoCDET mutants to Fix+. Here we show that one of these suppressor loci (sfx1) contains two genes, orfA and pit, which appear to form an operon transcribed in the order orfA-pit. The Pit protein is homologous to various phosphate transporters, and we present evidence that three suppressor mutations arose from a single thymidine deletion in a hepta-thymidine sequence centered 54 nucleotides upstream of the orfA transcription start site. This mutation increased the level of orfA-pit transcription. These data, together with previous biochemical evidence, show that the orfA-pit genes encode a Pi transport system that is expressed in wild-type cells grown with excess Pi but repressed in cells under conditions of Pi limitation. In phoCDET mutant cells, orfA-pit expression is repressed, but this repression is alleviated by the second-site suppressor mutations. Suppression increases orfA-pit expression compensating for the deficiencies in phosphate assimilation and symbiosis of the phoCDET mutants.

Development of neural network techniques for finger-vein pattern classification

NASA Astrophysics Data System (ADS)

Wu, Jian-Da; Liu, Chiung-Tsiung; Tsai, Yi-Jang; Liu, Jun-Ching; Chang, Ya-Wen

2010-02-01

A personal identification system using finger-vein patterns and neural network techniques is proposed in the present study. In the proposed system, the finger-vein patterns are captured by a device that can transmit near infrared through the finger and record the patterns for signal analysis and classification. The biometric system for verification consists of a combination of feature extraction using principal component analysis and pattern classification using both back-propagation network and adaptive neuro-fuzzy inference systems. Finger-vein features are first extracted by principal component analysis method to reduce the computational burden and removes noise residing in the discarded dimensions. The features are then used in pattern classification and identification. To verify the effect of the proposed adaptive neuro-fuzzy inference system in the pattern classification, the back-propagation network is compared with the proposed system. The experimental results indicated the proposed system using adaptive neuro-fuzzy inference system demonstrated a better performance than the back-propagation network for personal identification using the finger-vein patterns.

Phosphatidylinositol 3,4,5-trisphosphate activity probes for the labeling and proteomic characterization of protein binding partners.

PubMed

Rowland, Meng M; Bostic, Heidi E; Gong, Denghuang; Speers, Anna E; Lucas, Nathan; Cho, Wonhwa; Cravatt, Benjamin F; Best, Michael D

2011-12-27

Phosphatidylinositol polyphosphate lipids, such as phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P₃], regulate critical biological processes, many of which are aberrant in disease. These lipids often act as site-specific ligands in interactions that enforce membrane association of protein binding partners. Herein, we describe the development of bifunctional activity probes corresponding to the headgroup of PI(3,4,5)P₃ that are effective for identifying and characterizing protein binding partners from complex samples, namely cancer cell extracts. These probes contain both a photoaffinity tag for covalent labeling of target proteins and a secondary handle for subsequent detection or manipulation of labeled proteins. Probes bearing different secondary tags were exploited, either by direct attachment of a fluorescent dye for optical detection or by using an alkyne that can be derivatized after protein labeling via click chemistry. First, we describe the design and modular synthetic strategy used to generate multiple probes with different reporter tags of use for characterizing probe-labeled proteins. Next, we report initial labeling studies using purified protein, the PH domain of Akt, in which probes were found to label this target, as judged by in-gel detection. Furthermore, protein labeling was abrogated by controls including competition with an unlabeled PI(3,4,5)P₃ headgroup analogue as well as through protein denaturation, indicating specific labeling. In addition, probes featuring linkers of different lengths between the PI(3,4,5)P₃ headgroup and photoaffinity tag led to variations in protein labeling, indicating that a shorter linker was more effective in this case. Finally, proteomic labeling studies were performed using cell extracts; labeled proteins were observed by in-gel detection and characterized using postlabeling with biotin, affinity chromatography, and identification via tandem mass spectrometry. These studies yielded a total of 265 proteins, including both known and novel candidate PI(3,4,5)P₃-binding proteins.

Phosphatidylinositol (3,4,5)-Trisphosphate Activity Probes for the Labeling and Proteomic Characterization of Protein Binding Partners

PubMed Central

Rowland, Meng M.; Bostic, Heidi E.; Gong, Denghuang; Speers, Anna E.; Lucas, Nathan; Cho, Wonhwa; Cravatt, Benjamin F.; Best, Michael D.

2013-01-01

Phosphatidylinositol polyphosphate lipids, such as phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3), regulate critical biological processes, many of which are aberrant in disease. These lipids often act as site-specific ligands in interactions that enforce membrane-association of protein binding partners. Herein, we describe the development of bifunctional activity probes corresponding to the headgroup of PI(3,4,5)P3 that are effective for identifying and characterizing protein binding partners from complex samples, namely cancer cell extracts. These probes contain both a photoaffinity tag for covalent labeling of target proteins as well as a secondary handle for subsequent detection or manipulation of labeled proteins. Probes bearing different secondary tags were exploited, either by direct attachment of a fluorescent dye for optical detection or by using an alkyne that can be derivatized after protein labeling via click chemistry. First, we describe the design and modular synthetic strategy used to generate multiple probes with different reporter tags of use for characterizing probe-labeled proteins. Next, we report initial labeling studies using purified protein, the PH domain of Akt, in which probes were found to label this target, as judged by on-gel detection. Furthermore, protein labeling was abrogated by controls including competition with an unlabeled PI(3,4,5)P3 headgroup analog as well as through protein denaturation, indicating specific labeling. In addition, probes featuring different linker lengths between the PI(3,4,5)P3 headgroup and photoaffinity tag led to variations in protein labeling, indicating that a shorter linker was more effective in this case. Finally, proteomic labeling studies were performed using cell extracts, labeled proteins were observed by in-gel detection and characterized using post-labeling with biotin, affinity chromatography and identification via tandem mass spectrometry. These studies yielded a total of 265 proteins, including both known and novel candidate PI(3,4,5)P3-binding proteins. PMID:22074223

Defining Genomic Changes in Triple Negative Breast Cancer in Women of African Descent

DTIC Science & Technology

2013-07-01

Triple negative breast cancer , Ethnic disparities, Breast cancer amongst African - Americans and Africans , Gene expression... Americans . Adjacent Normal AA Native African TN BC Tissue Figure 1. Gene Expression Pattern of Native African Triple Negative Breast Cancer ...and African - American Adjacent Normal Breast Tissue Genes PI: Pegram & Baumbach

Regiochemistry of Poly(3-Hexylthiophene): Synthesis and Investigation of a Conducting Polymer

ERIC Educational Resources Information Center

Pappenfus, Ted M.; Hermanson, David L.; Kohl, Stuart G.; Melby, Jacob H.; Thoma, Laura M.; Carpenter, Nancy E.; Filho, Demetrio A. da Silva; Bredas, Jean-Luc

2010-01-01

A series of experiments for undergraduate laboratory courses (e.g., organic, polymer, inorganic) have been developed. These experiments focus on understanding the regiochemistry of the conducting polymer poly(3-hexylthiophene) (P3HT). The substitution patterns in P3HTs control their conformational features, which, in turn, dictates the [pi]…

Distribution, evolution, and diversity of retrotransposons at the flamenco locus reflect the regulatory properties of piRNA clusters

PubMed Central

Zanni, Vanessa; Eymery, Angéline; Coiffet, Michael; Zytnicki, Matthias; Luyten, Isabelle; Quesneville, Hadi; Vaury, Chantal; Jensen, Silke

2013-01-01

Most of our understanding of Drosophila heterochromatin structure and evolution has come from the annotation of heterochromatin from the isogenic y; cn bw sp strain. However, almost nothing is known about the heterochromatin’s structural dynamics and evolution. Here, we focus on a 180-kb heterochromatic locus producing Piwi-interacting RNAs (piRNA cluster), the flamenco (flam) locus, known to be responsible for the control of at least three transposable elements (TEs). We report its detailed structure in three different Drosophila lines chosen according to their capacity to repress or not to repress the expression of two retrotransposons named ZAM and Idefix, and we show that they display high structural diversity. Numerous rearrangements due to homologous and nonhomologous recombination, deletions and segmental duplications, and loss and gain of TEs are diverse sources of active genomic variation at this locus. Notably, we evidence a correlation between the presence of ZAM and Idefix in this piRNA cluster and their silencing. They are absent from flam in the strain where they are derepressed. We show that, unexpectedly, more than half of the flam locus results from recent TE insertions and that most of the elements concerned are prone to horizontal transfer between species of the melanogaster subgroup. We build a model showing how such high and constant dynamics of a piRNA master locus open the way to continual emergence of new patterns of piRNA biogenesis leading to changes in the level of transposition control. PMID:24248389

Organic/Inorganic Nano-hybrids with High Dielectric Constant for Organic Thin Film Transistor Applications

NASA Astrophysics Data System (ADS)

Yu, Yang-Yen; Jiang, Ai-Hua; Lee, Wen-Ya

2016-11-01

The organic material soluble polyimide (PI) and organic-inorganic hybrid PI-barium titanate (BaTiO3) nanoparticle dielectric materials (IBX, where X is the concentration of BaTiO3 nanoparticles in a PI matrix) were successfully synthesized through a sol-gel process. The effects of various BaTiO3 contents on the hybrid film performance and performance optimization were investigated. Furthermore, pentacene-based organic thin film transistors (OTFTs) with PI-BaTiO3/polymethylmethacrylate or cyclic olefin copolymer (COC)-modified gate dielectrics were fabricated and examined. The hybrid materials showed effective dispersion of BaTiO3 nanoparticles in the PI matrix and favorable thermal properties. X-ray diffraction patterns revealed that the BaTiO3 nanoparticles had a perovskite structure. The hybrid films exhibited high formability and planarity. The IBX hybrid dielectric films exhibited tunable insulating properties such as the dielectric constant value and capacitance in ranges of 4.0-8.6 and 9.2-17.5 nF cm-2, respectively. Adding the modified layer caused the decrease of dielectric constant values and capacitances. The modified dielectric layer without cross-linking displayed a hydrophobic surface. The electrical characteristics of the pentacene-based OTFTs were enhanced after the surface modification. The optimal condition for the dielectric layer was 10 wt% hybrid film with the COC-modified layer; moreover, the device exhibited a threshold voltage of 0.12 V, field-effect mobility of 4.32 × 10-1 cm2 V-1 s-1, and on/off current of 8.4 × 107.

In vivo effect of single oral dose of artemether against early juvenile stages of Schistosoma mansoni Egyptian strain.

PubMed

El-Beshbishi, Samar N; Taman, Amira; El-Malky, Mohamed; Azab, Manar S; El-Hawary, Amira K; El-Tantawy, Dina A

2013-10-01

The current treatment and control of schistosomiasis, rely on a single drug, praziquantel, although, it has minor activity against juvenile stages of the parasite. Studies have shown that artemether (ART) exhibits effects against juveniles of Schistosoma mansoni Liberian and Puerto Rican strains, Schistosoma japonicum and Schistosoma haematobium. Aiming to assess the in vivo activity of single oral dose of ART against early juvenile stages of S. mansoni Egyptian strain, this study was established. Mice were treated with ART (400 mg/kg) at two time points evenly spaced over the period of larval development (7 and 21 days post-infection; pi), and a third treatment point (day 49 pi) was included to elucidate when susceptibility decreases. Administration of ART on day 7 pi reduced the total worm burden by 85.94%. The greatest reductions were seen when treatment was given on day 21 pi, with total and female worm burden reductions of 91.52% and 90.57%, respectively, and cessation of oviposition. Similar dose given on day 49 pi reduced total worm burden by 55.17% and female worm burden by 66.51%. Moreover, it induced significant reduction in the tissue egg load and significant alterations in the oogram pattern with decreased immature eggs and increased dead eggs. Antipathological activities were evident in significant reductions in granulomata count and diameter. In conclusion, ART exhibits major in vivo schistosomicidal effects against the early larval migratory stages of S. mansoni Egyptian strain, mainly the 21-day old schistosomula, hence preventing disease progression and morbidity. Copyright © 2013 Elsevier Inc. All rights reserved.

Field theory of pattern identification

NASA Astrophysics Data System (ADS)

Agu, Masahiro

1988-06-01

Based on the psychological experimental fact that images in mental space are transformed into other images for pattern identification, a field theory of pattern identification of geometrical patterns is developed with the use of gauge field theory in Euclidean space. Here, the ``image'' or state function ψ[χ] of the brain reacting to a geometrical pattern χ is made to correspond to the electron's wave function in Minkowski space. The pattern identification of the pattern χ with the modified pattern χ+Δχ is assumed to be such that their images ψ[χ] and ψ[χ+Δχ] in the brain are transformable with each other through suitable transformation groups such as parallel transformation, dilatation, or rotation. The transformation group is called the ``image potential'' which corresponds to the vector potential of the gauge field. An ``image field'' derived from the image potential is found to be induced in the brain when the two images ψ[χ] and ψ[χ+Δχ] are not transformable through suitable transformation groups or gauge transformations. It is also shown that, when the image field exists, the final state of the image ψ[χ] is expected to be different, depending on the paths of modifications of the pattern χ leading to a final pattern. The above fact is interpreted as a version of the Aharonov and Bohm effect of the electron's wave function [A. Aharonov and D. Bohm, Phys. Rev. 115, 485 (1959)]. An excitation equation of the image field is also derived by postulating that patterns are identified maximally for the purpose of minimizing the number of memorized standard patterns.

Time series analysis of the transcriptional responses of Biomphalaria glabrata throughout the course of intramolluscan development of Schistosoma mansoni and Echinostoma paraensei

PubMed Central

Hanington, Patrick C.; Lun, Cheng-Man; Adema, Coen M; Loker, Eric S

2010-01-01

Successful colonization of a compatible snail host by a digenetic trematode miracidium initiates a complex, proliferative development program requiring weeks to reach culmination in the form of production of cercariae which, once started, may persist for the remainder of the life span of the infected snail. How are such proliferative and invasive parasites able to circumvent host defenses and establish chronic infections? Using a microarray designed to monitor the internal defense and stress-related responses of the freshwater snail Biomphalaria glabrata, we have undertaken a time course study to monitor snail responses following exposure to two different trematode species to which the snail is susceptible: the medically important Schistosoma mansoni, exemplifying sporocyst production in its larval development, or Echinostoma paraensei, representing an emphasis on rediae production in its larval development. We sampled eight time points (0.5, 1, 2, 4, 8, 16 and 32 days p.i.) that cover the period required for cercariae to be produced. Following exposure to S. mansoni, there was a preponderance of up-regulated over down-regulated array features through 2 days p.i. but by 4 days p.i. and thereafter, this pattern was strongly reversed. For E. paraensei, there was a preponderance of down-regulated array features over up-regulated features at even 0.5 days p.i., a pattern that persists throughout the course of infection except for 1 day p.i., when up-regulated array features slightly outnumbered down-regulated features. Examination of particular array features revealed several that were up-regulated by both parasites early in the course of infection and one, fibrinogen related protein 4 (FREP 4), that remained significantly elevated throughout the course of infection with either parasite, effectively serving as a marker of infection. Many defense-related transcripts were persistently down-regulated, including several fibrinogen-containing lectins and homologs of molecules best known from vertebrate phagocytic cells. Our results are consistent with earlier studies suggesting that both parasites are able to interfere with host defense responses, including a tendency for E. paraensei to do so more rapidly and strongly than S. mansoni They further suggest mechanisms for how trematodes are able to establish the chronic infections necessary for their continued success. PMID:20083115

Can the Fear Recognition Deficits Associated with Callous-Unemotional Traits be Identified in Early Childhood?

PubMed Central

Briggs-Gowan, Margaret J.; Voss, Joel L.; Petitclerc, Amelie; McCarthy, Kimberly; Blair, R. James R.; Wakschlag, Lauren S.

2016-01-01

Introduction Callous-unemotional (CU) traits in the presence of conduct problems are associated with increased risk of severe antisocial behavior. Developmentally sensitive methods of assessing CU traits have recently been generated, but their construct validity in relation to neurocognitive underpinnings of CU has not been demonstrated. The current study sought to investigate whether the fear-specific emotion recognition deficits associated with CU traits in older individuals are developmentally expressed in young children as low concern for others and punishment insensitivity. Methods A sub-sample of 337 preschoolers (mean age 4.8 years [SD=.8]) who completed neurocognitive tasks was taken from a larger project of preschool psychopathology. Children completed an emotional recognition task in which they were asked to identify the emotional face from the neutral faces in an array. CU traits were assessed using the Low Concern (LC) and Punishment Insensitivity (PI) subscales of the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB), which were specifically designed to differentiate the normative misbehavior of early childhood from atypical patterns. Results High LC, but not PI, scores were associated with a fear-specific deficit in emotion recognition. Girls were more accurate than boys in identifying emotional expressions but no significant interaction between LC or PI and sex was observed. Conclusions Fear recognition deficits associated with CU traits in older individuals were observed in preschoolers with developmentally-defined patterns of low concern for others. Confirming that the link between CU-related impairments in empathy and distinct neurocognitive deficits is present in very young children suggests that developmentally-specified measurement can detect the substrates of these severe behavioral patterns beginning much earlier than prior work. Exploring the development of CU traits and disruptive behavior disorders at very early ages may provide insights critical to early intervention and prevention of severe antisocial behavior. PMID:27167866

Identification of Cytoplasmic Proteins Interacting with the Mammary Cell Transforming Domain of Ese-1

DTIC Science & Technology

2009-04-01

selected for the prestigious 2008 AACR-Minorities in Cancer Research - Jane Cooke Wright Lectureship Award. 2. Arthur Gutierrez-Hartmann, PI, was...member is encoded by the v-ets oncogene in the E26 retrovirus, which causes hematopoietic malignancies in chickens [1–3]. In humans, ETS factors are also...signaling cascade, with MAPK directly phosphorylating chicken ETS1 [3]. Site-specific mutation of the ETS1 Thr82 MAPK phos- phorylation site to Ala results

Identification of G-Protein-Coupled Receptors (GPCRs) in Pulmonary Artery Smooth Muscle Cells as Novel Therapeutic Targets

DTIC Science & Technology

2017-10-01

available pharmacological agents (in particular, for which FDA-approved drugs exist) and that we predict have a pathophysiological impact. The Sub-tasks...on the responses to a known receptor agonist. To be completed by 8/2018.   3e. Pending results of studies in Sub-tasks 2-4, test ability of drugs ...cardiac and lung fibroblasts as possible drug targets for tissue fibrosis. R21AG053568 (PI: P. Insel) 9/30/2016-4/30/2018

A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition

PubMed Central

Shi, Hubing; Hong, Aayoung; Kong, Xiangju; Koya, Richard C.; Song, Chunying; Moriceau, Gatien; Hugo, Willy; Yu, Clarissa C.; Ng, Charles; Chodon, Thinle; Scolyer, Richard A.; Kefford, Richard F.; Ribas, Antoni; Long, Georgina V.; Lo, Roger S.

2013-01-01

BRAF inhibitor (BRAFi) therapy leads to remarkable anti-melanoma responses, but the initial tumor shrinkage is commonly incomplete, providing a nidus for subsequent disease progression. Adaptive signaling may underlie early BRAFi resistance and influence the selection pattern for genetic variants causing late, acquired resistance. We show here that BRAFi (or BRAFi+MEKi) therapy in patients frequently led to rebound p-AKT levels in their melanomas early on treatment. In cell lines, BRAFi treatment led to rebound levels of RTKs (including PDGFRβ), PIP3, pleckstrin homology domain (PHD) recruitment, and p-AKT. PTEN expression limited this BRAFi-elicited PI3K-AKT signaling, which could be rescued by introduction of a mutant AKT1 (Q79K) kown to confer acquired BRAFi resistance. Functionally, AKT1 Q79K conferred BRAFi resistance via amplifying BRAFi-elicited PI3K-AKT signaling. Additionally, MAPK pathway inhibition enhanced clonogenic growth dependency on PI3K or AKT. Thus, adaptive or genetic upregulation of AKT critically participates in melanoma survival during BRAFi therapy. PMID:24265152

Retrospective seasonal prediction of summer monsoon rainfall over West Central and Peninsular India in the past 142 years

NASA Astrophysics Data System (ADS)

Li, Juan; Wang, Bin; Yang, Young-Min

2017-04-01

Prediction of Indian summer (June-September) rainfall on regional scales remains an open issue. The operational predictions of West Central Indian summer rainfall (WCI-R) and Peninsular Indian summer rainfall (PI-R) made by the Indian Meteorological Department (IMD) had no skills during 2004-2012. This motivates the present study aiming at better understanding the predictability sources and physical processes governing summer rainfall variability over these two regions. Analysis of 133 year data reveal that although the lower boundary forcing that associated with enhanced WCI-R and PI-R featured a similar developing La-Nina and "east high west low" sea-level pressure (SLP) dipole pattern across the Indo-Pacific, the anomalous high sea surface temperature (SST) over the northern Indian Ocean and weak low pressure over northern Asia tended to enhance PI-R but reduce WCI-R. Based on our understanding of physical linkages with the predictands, we selected four and two causative predictors for predictions of the WCI-R and PI-R, respectively. The intensified summer WCI-R is preceded by (a) Indian Ocean zonal dipole-like SST tendency (west-warming and east-cooling), (b) tropical Pacific zonal dipole SST tendency (west-warming and east-cooling), (c) central Pacific meridional dipole SST tendency (north-cooling and south-warming), and (d) decreasing SLP tendency over northern Asia in the previous season. The enhanced PI-R was lead by the central-eastern Pacific cooling and 2-m temperature cooling tendency east of Lake Balkhash in the previous seasons. These causative processes linking the predictors and WCI-R and PI-R are supported by ensemble numerical experiments using a coupled climate model. For the period of 1871-2012, the physics-based empirical (P-E) prediction models built on these predictors result in cross-validated forecast temporal correlation coefficient skills of 0.55 and 0.47 for WCI-R and PI-R, respectively. The independent forecast skill is significantly higher than the skill of operational seasonal forecast made by the IMD for the period of 2004-2012. These prediction models offer a tool for seasonal prediction and their retrospective forecast skills provide an estimation of the lower bound of the predictability for WCI-R and PI-R.

A concentration-dependent multi-term linear free energy relationship for sorption of organic compounds to soils based on the hexadecane dilute-solution reference state.

PubMed

Zhu, Dongqiang; Pignatello, Joseph J

2005-11-15

A LFER of the type in the title is applied to sorption of numerous compounds to polyethylene and three soils for which sorption to natural organic matter (NOM) is presumed dominant. It provides fractional contributions to the Gibbs free energy of sorption corresponding to hydrophobic effects, dipolar/polarizability (D/P) effects in excess of the reference state, and the sum of possible specific forces such as H-bonding and pi-pi electron donor-acceptor (pi-pi EDA) interactions in excess of the reference state. Minimal inputs are the isotherm, the n-hexadecane-water partition coefficient and the Abraham pi parameter representing D/P effects. Sorption of all compounds to polyethylene can be described by considering only hydrophobic effects. Sorption of a calibration set of apolar compounds (aromatic and aliphatic hydrocarbons and chlorinated hydrocarbons) to the natural sorbents is well-described by a combination of hydrophobic and D/P effects. For the apolar set, D/P contributes approximately 15-40% (2-8% for cyclohexane) of sorption free energy. D/P effects increase with the degree of chlorination for aliphatic compounds. For aromatic compounds D/P effects increase with fused ring size but do not vary with degree of chlorination and chlorine substitution pattern. H-bonding contributes substantially to sorption of alcohols, and similarly for 2-nonanol and 2,4-dichlorophenol (33-44%). pi-pi EDA forces contribute to phenanthrene sorption in one case. The effects of concentration, sorbent aromaticity (literature NMR), and sorbent polarity [(O + N)/C] on hydrophobic and D/P contributions for all compounds indicate that (a) molecules fill sites of progressively greater hydrophilic character; (b) the energy penalty for cavity formation in the solid decreases with concentration due to plasticization and greater intermolecular contact; (c) sorbent aromatic content more than sorbent polarity controls D/P interactions. Basing free energy on an inert electrostatic chemical environment afforded by n-hexadecane permits evaluation of direct electrostatic forces in NOM that contribute to sorption.

Viral kinetics are associated with changes in cytokines and chemokines in serum and target organs of SSM-CVB3-infected macaques.

PubMed

Han, Tiesuo; Zhao, Kui; Wu, Chenchen; Lu, Huijun; Song, Deguang; He, Wenqi; Gao, Feng

2013-02-01

To determine the relationship between viral kinetics and the expression patterns for different cytokines and chemokines in the serum and organs of coxsackievirus B3 (SSM-CVB3)-infected macaques over the course of infection. SSM-CVB3 levels in serum and organs were measured using the Spearman-Karber 50% tissue culture infectious dose (TCID(50)) method. Cytokine and chemokine levels in the serum and organs were measured by indirect-ELISA. Low viral titers were detected in the serum samples on the first day post-inoculation (p.i.) and peaked at 6 to 10 days p.i. in the serum samples from five macaques. Serum levels of IL-1β, IL-2, IL-6, IL-12p40, IL-17α, IFN-γ, TNF-α, MCP-1 and MIP-1β were detected each day and, similar to the viral titers, peaked at 6 to 10 days. IL-10 was only detected on days 10 to 14 p.i. Additionally, higher viral titers and relative viral mRNA levels were associated with higher cytokine and chemokine levels in selected tissues from infected macaques including heart, liver, spleen, lung, kidney and brain. The results indicate that patterns of cytokine and chemokine response are associated with viral kinetics in the serum and target organs of SSM-CVB3-infected macaques, suggesting that the changes in cytokines and chemokines could help further our understanding of the progress of CVB3 infections in clinical settings. Copyright © 2012 Elsevier Inc. All rights reserved.

A unique cell-surface protein phenotype distinguishes human small-cell from non-small-cell lung cancer

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

Baylin, S.B.; Gazdar, A.F.; Minna, J.D.

1982-08-01

Radioiodination (/sup 125/I) and two-dimensional polyacrylamide gel electrophoresis was used to determine that small-(oat) cell lung carcinoma (SCC)-a tumor with neuroedocrine features-possesses a surface protein pattern distinct from the other types of lung cancer cells (squamous, adeno-, and large-cell undifferentiated carcinoma). Twelve distinguishing proteins, 40 to 70 kilodaltons (kDal), characterized four separate lines of SCC; three of these, designated E (60 kDal; pI = 7.3), S (30 kDal; pI = 6.0), and U 57 kDal; pI = 5.6), may be unique SCC gene products and were identified only in (/sup 35/S)methionine labeling of SCC and not in non-SCC or humanmore » fibroblasts. Two lines of adeno-, one of squamous, and one of undifferentiated large-cell lung carcinoma exhibited similar surface protein patterns to one another. Nine distinguishing proteins (40 to 100 kDal) and at least five large proteins (>100 kDal) were unique to these lines. The surface protein phenotypes for SCC and non-SCC were distinct from those for human lymphoblastoid cells and fibroblasts. However, the neuroendocrine features of SCC were further substantiated because 6 of the 12 distinguishing SCC surface proteins, including E and U, were identified on human neuroblastoma cells. The proteins identified should (i) help define differentiation steps for normal and neoplastic bronchial epithelial cells, (ii) prove useful in better classifying lung cancers, and (iii) be instrumental in tracing formation of neuroendocrine cells.« less

Reconstruction of an SSR-based Magnaporthe oryzae physical map to locate avirulence gene AvrPi12.

PubMed

Li, Tonghui; Wen, Jianqiang; Zhang, Yaling; Correll, James; Wang, Ling; Pan, Qinghua

2018-05-31

Pathogen avirulence (Avr) genes can evolve rapidly when challenged by the widespread deployment of host genes for resistance. They can be effectively isolated by positional cloning provided a robust and well-populated genetic map is available. An updated, SSR-based physical map of the rice blast pathogen Magnaporthe oryzae (Mo) has been constructed based on 116 of the 120 SSRs used to assemble the last map, along with 18 newly developed ones. A comparison between the two versions of the map has revealed an altered marker content and order within most of the Mo chromosomes. The avirulence gene AvrPi12 was mapped in a population of 219 progeny derived from a cross between the two Mo isolates CHL42 and CHL357. A bulked segregant analysis indicated that the gene was located on chromosome 6, a conclusion borne out by an analysis of the pattern of segregation shown by individual isolates. Six additional PCR-based markers were developed to improve the map resolution in the key region. AvrPi12 was finally located within the sub-telomeric region of chromosome 6, distal to the SSR locus LSM6-5. The improved SSR-based linkage map should be useful as a platform for gene mapping and isolation in Mo. It was used to establish the location of AvrPi12, thereby providing a starting point for its positional cloning.

Deep sequencing reveals unique small RNA repertoire that is regulated during head regeneration in Hydra magnipapillata.

PubMed

Krishna, Srikar; Nair, Aparna; Cheedipudi, Sirisha; Poduval, Deepak; Dhawan, Jyotsna; Palakodeti, Dasaradhi; Ghanekar, Yashoda

2013-01-07

Small non-coding RNAs such as miRNAs, piRNAs and endo-siRNAs fine-tune gene expression through post-transcriptional regulation, modulating important processes in development, differentiation, homeostasis and regeneration. Using deep sequencing, we have profiled small non-coding RNAs in Hydra magnipapillata and investigated changes in small RNA expression pattern during head regeneration. Our results reveal a unique repertoire of small RNAs in hydra. We have identified 126 miRNA loci; 123 of these miRNAs are unique to hydra. Less than 50% are conserved across two different strains of Hydra vulgaris tested in this study, indicating a highly diverse nature of hydra miRNAs in contrast to bilaterian miRNAs. We also identified siRNAs derived from precursors with perfect stem-loop structure and that arise from inverted repeats. piRNAs were the most abundant small RNAs in hydra, mapping to transposable elements, the annotated transcriptome and unique non-coding regions on the genome. piRNAs that map to transposable elements and the annotated transcriptome display a ping-pong signature. Further, we have identified several miRNAs and piRNAs whose expression is regulated during hydra head regeneration. Our study defines different classes of small RNAs in this cnidarian model system, which may play a role in orchestrating gene expression essential for hydra regeneration.

Deep sequencing reveals unique small RNA repertoire that is regulated during head regeneration in Hydra magnipapillata

PubMed Central

Krishna, Srikar; Nair, Aparna; Cheedipudi, Sirisha; Poduval, Deepak; Dhawan, Jyotsna; Palakodeti, Dasaradhi; Ghanekar, Yashoda

2013-01-01

Small non-coding RNAs such as miRNAs, piRNAs and endo-siRNAs fine-tune gene expression through post-transcriptional regulation, modulating important processes in development, differentiation, homeostasis and regeneration. Using deep sequencing, we have profiled small non-coding RNAs in Hydra magnipapillata and investigated changes in small RNA expression pattern during head regeneration. Our results reveal a unique repertoire of small RNAs in hydra. We have identified 126 miRNA loci; 123 of these miRNAs are unique to hydra. Less than 50% are conserved across two different strains of Hydra vulgaris tested in this study, indicating a highly diverse nature of hydra miRNAs in contrast to bilaterian miRNAs. We also identified siRNAs derived from precursors with perfect stem–loop structure and that arise from inverted repeats. piRNAs were the most abundant small RNAs in hydra, mapping to transposable elements, the annotated transcriptome and unique non-coding regions on the genome. piRNAs that map to transposable elements and the annotated transcriptome display a ping–pong signature. Further, we have identified several miRNAs and piRNAs whose expression is regulated during hydra head regeneration. Our study defines different classes of small RNAs in this cnidarian model system, which may play a role in orchestrating gene expression essential for hydra regeneration. PMID:23166307

Involvement of protein kinase B and mitogen-activated protein kinases in experimental normothermic liver ischaemia-reperfusion injury.

PubMed

Cursio, R; Filippa, N; Miele, C; Van Obberghen, E; Gugenheim, J

2006-06-01

This study evaluated the role of protein kinase B (PKB), phosphatidylinositol 3-kinase (PI3-K), Bcl-2-associated death protein (BAD) and mitogen-activated protein kinases (MAPKs) in normothermic ischaemia-reperfusion (IR)-induced apoptosis in rat liver. Rats were divided into two groups that received either phosphate-buffered saline (control) or the caspase inhibitor Z-Asp-2,6-dichorobenzoyloxymethylketone (Z-Asp-cmk), injected intravenously 2 min before the induction of 120 min of normothermic liver ischaemia. Liver apoptosis was assessed by the terminal deoxyribonucleotidyltransferase-mediated dUTP nick end labelling (TUNEL) method. PI3-K, PKB, BAD and MAPK activities were measured in ischaemic and non-ischaemic lobes at various times after reperfusion. The number of TUNEL-positive cells was significantly decreased after pretreatment with Z-Asp-cmk. In controls, PI3-K and PKB activities and BAD phosphorylation were inhibited in ischaemic liver lobes. The MAPKs (extracellular signal-regulated kinases, c-Jun N-terminal kinase and p38) showed different patterns of activation during IR. PKB activity was not modified by pretreatment with Z-Asp-cmk. Induction of apoptosis during IR liver injury might be triggered by inactivation of the antiapoptotic PI3-K-PKB pathway and activation of the proapoptotic MAPKs. Copyright (c) 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Structure-Based Design: Synthesis, X-ray Crystallography, and Biological Evaluation of N-Substituted-4-Hydroxy-2-Quinolone-3-Carboxamides as Potential Cytotoxic Agents.

PubMed

Sabbah, Dima A; Hishmah, Bayan; Sweidan, Kamal; Bardaweel, Sanaa; AlDamen, Murad; Zhong, Haizhen A; Abu Khalaf, Reema; Hasan Ibrahim, Ameerah; Al-Qirim, Tariq; Abu Sheikha, Ghassan; Mubarak, Mohammad S

2018-01-01

Oncogenic potential of phosphatidylinositol 3-kinase (PI3Kα) has been highlighted as a therapeutic target for anticancer drug design. Target compounds were designed to address the effect of different substitution patterns at the N atom of the carboxamide moiety on the bioactivity of this series. Synthesis of the targeted compounds, crystallography, biological evaluation tests against human colon carcinoma (HCT-116), and Glide docking studies. A new series of N-substituted- 4-hydroxy-2-quinolone-3-carboxamides was prepared and characterized by means of FT-IR, 1H and 13C NMR, and elemental analysis. In addition, the identity of the core nucleus 5 was successfully characterized with the aid of X-ray crystallography. Biological activity of prepared compounds was investigated in vitro against human colon carcinoma (HCT-116) cell line. Results revealed that these compounds inhibit cell proliferation and induce apoptosis through an increase in caspase-3 activity and a decrease in DNA cellular content. Compounds 7, 14, and 17 which have H-bond acceptor moiety on p-position displayed promising PI3Kα inhibitory activity. On the other hand, derivatives tailored with bulky and hydrophobic motifs (16 and 18) on o- and m-positions exhibited moderate activity. Molecular docking studies against PI3Kα and caspase-3 showed an agreement between the predicted binding affinity (ΔGobsd) and IC50 values of the derivatives for the caspase-3 model. Furthermore, Glide docking studies against PI3Kα demonstrated that the newly synthesized compounds accommodate PI3Kα kinase catalytic domain and form H-bonding with key binding residues. The series exhibited a potential PI3Kα inhibitory activity in HCT-116 cell line. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Information-driven self-organization: the dynamical system approach to autonomous robot behavior.

PubMed

Ay, Nihat; Bernigau, Holger; Der, Ralf; Prokopenko, Mikhail

2012-09-01

In recent years, information theory has come into the focus of researchers interested in the sensorimotor dynamics of both robots and living beings. One root for these approaches is the idea that living beings are information processing systems and that the optimization of these processes should be an evolutionary advantage. Apart from these more fundamental questions, there is much interest recently in the question how a robot can be equipped with an internal drive for innovation or curiosity that may serve as a drive for an open-ended, self-determined development of the robot. The success of these approaches depends essentially on the choice of a convenient measure for the information. This article studies in some detail the use of the predictive information (PI), also called excess entropy or effective measure complexity, of the sensorimotor process. The PI of a process quantifies the total information of past experience that can be used for predicting future events. However, the application of information theoretic measures in robotics mostly is restricted to the case of a finite, discrete state-action space. This article aims at applying the PI in the dynamical systems approach to robot control. We study linear systems as a first step and derive exact results for the PI together with explicit learning rules for the parameters of the controller. Interestingly, these learning rules are of Hebbian nature and local in the sense that the synaptic update is given by the product of activities available directly at the pertinent synaptic ports. The general findings are exemplified by a number of case studies. In particular, in a two-dimensional system, designed at mimicking embodied systems with latent oscillatory locomotion patterns, it is shown that maximizing the PI means to recognize and amplify the latent modes of the robotic system. This and many other examples show that the learning rules derived from the maximum PI principle are a versatile tool for the self-organization of behavior in complex robotic systems.

Synaptic potentials in respiratory neurones during evoked phase switching after NMDA receptor blockade in the cat

PubMed Central

Pierrefiche, O; Haji, A; Foutz, A S; Takeda, R; Champagnat, J; Denavit-Saubié, M

1998-01-01

Blockade of NMDA receptors by dizocilpine impairs the inspiratory off-switch (IOS) of central origin but not the IOS evoked by stimulation of sensory afferents. To investigate whether this difference was due to the effects of different patterns of synaptic interactions on respiratory neurones, we stimulated electrically the superior laryngeal nerve (SLN) or vagus nerve in decerebrate cats before and after i.v. administration of dizocilpine, whilst recording intracellularly. Phrenic nerve responses to ipsilateral SLN or vagal stimulation were: at mid-inspiration, a transient inhibition often followed by a brief burst of activity; at late inspiration, an IOS; and at mid-expiration, a late burst of activity. In all neurones (n = 16), SLN stimulation at mid-inspiration evoked an early EPSP during phase 1 (latency to the arrest of phrenic nerve activity), followed by an IPSP in inspiratory (I) neurones (n = 8) and by a wave of EPSPs in post-inspiratory (PI) neurones (n = 8) during phase 2 (inhibition of phrenic activity). An EPSP in I neurones and an IPSP in PI neurones occurred during phase 3 (brief phrenic burst) following phase 2. Evoked IOS was associated with a fast (phase 1) activation of PI neurones, whereas during spontaneous IOS, a progressive (30-50 ms) depolarization of PI neurones preceded the arrest of phrenic activity. Phase 3 PSPs were similar to those occurring during the burst of activity seen at the start of spontaneous inspiration. Dizocilpine did not suppress the evoked phrenic inhibition and the late burst of activity. The shapes and timing of the evoked PSPs and the changes in membrane potential in I and PI neurones during the phase transition were not altered. We hypothesize that afferent sensory pathways not requiring NMDA receptors (1) terminate inspiration through a premature activation of PI neurones, and (2) evoke a late burst of phrenic activity which might be the first stage of the inspiratory on-switch. PMID:9508816

Gα12 facilitates shortening in human airway smooth muscle by modulating phosphoinositide 3-kinase-mediated activation in a RhoA-dependent manner.

PubMed

Yoo, Edwin J; Cao, Gaoyuan; Koziol-White, Cynthia J; Ojiaku, Christie A; Sunder, Krishna; Jude, Joseph A; Michael, James V; Lam, Hong; Pushkarsky, Ivan; Damoiseaux, Robert; Di Carlo, Dino; Ahn, Kwangmi; An, Steven S; Penn, Raymond B; Panettieri, Reynold A

2017-12-01

PI3K-dependent activation of Rho kinase (ROCK) is necessary for agonist-induced human airway smooth muscle cell (HASMC) contraction, and inhibition of PI3K promotes bronchodilation of human small airways. The mechanisms driving agonist-mediated PI3K/ROCK axis activation, however, remain unclear. Given that G 12 family proteins activate ROCK pathways in other cell types, their role in M 3 muscarinic acetylcholine receptor-stimulated PI3K/ROCK activation and contraction was examined. Gα 12 coupling was evaluated using co-immunoprecipitation and serum response element (SRE)-luciferase reporter assays. siRNA and pharmacological approaches, as well as overexpression of a regulator of G-protein signaling (RGS) proteins were applied in HASMCs. Phosphorylation levels of Akt, myosin phosphatase targeting subunit-1 (MYPT1), and myosin light chain-20 (MLC) were measured. Contraction and shortening were evaluated using magnetic twisting cytometry (MTC) and micro-pattern deformation, respectively. Human precision-cut lung slices (hPCLS) were utilized to evaluate bronchoconstriction. Knockdown of M 3 receptors or Gα 12 attenuated activation of Akt, MYPT1, and MLC phosphorylation. Gα 12 coimmunoprecipitated with M 3 receptors, and p115RhoGEF-RGS overexpression inhibited carbachol-mediated induction of SRE-luciferase reporter. p115RhoGEF-RGS overexpression inhibited carbachol-induced activation of Akt, HASMC contraction, and shortening. Moreover, inhibition of RhoA blunted activation of PI3K. Lastly, RhoA inhibitors induced dilation of hPCLS. Gα 12 plays a crucial role in HASMC contraction via RhoA-dependent activation of the PI3K/ROCK axis. Inhibition of RhoA activation induces bronchodilation in hPCLS, and targeting Gα 12 signaling may elucidate novel therapeutic targets in asthma. These findings provide alternative approaches to the clinical management of airway obstruction in asthma. © 2017 The British Pharmacological Society.

Electronic structure and reactivity of three-coordinate iron complexes.

PubMed

Holland, Patrick L

2008-08-01

[Reaction: see text]. The identity and oxidation state of the metal in a coordination compound are typically thought to be the most important determinants of its reactivity. However, the coordination number (the number of bonds to the metal) can be equally influential. This Account describes iron complexes with a coordination number of only three, which differ greatly from iron complexes with octahedral (six-coordinate) geometries with respect to their magnetism, electronic structure, preference for ligands, and reactivity. Three-coordinate complexes with a trigonal-planar geometry are accessible using bulky, anionic, bidentate ligands (beta-diketiminates) that steer a monodentate ligand into the plane of their two nitrogen donors. This strategy has led to a variety of three-coordinate iron complexes in which iron is in the +1, +2, and +3 oxidation states. Systematic studies on the electronic structures of these complexes have been useful in interpreting their properties. The iron ions are generally high spin, with singly occupied orbitals available for pi interactions with ligands. Trends in sigma-bonding show that iron(II) complexes favor electronegative ligands (O, N donors) over electropositive ligands (hydride). The combination of electrostatic sigma-bonding and the availability of pi-interactions stabilizes iron(II) fluoride and oxo complexes. The same factors destabilize iron(II) hydride complexes, which are reactive enough to add the hydrogen atom to unsaturated organic molecules and to take part in radical reactions. Iron(I) complexes use strong pi-backbonding to transfer charge from iron into coordinated alkynes and N 2, whereas iron(III) accepts charge from a pi-donating imido ligand. Though the imidoiron(III) complex is stabilized by pi-bonding in the trigonal-planar geometry, addition of pyridine as a fourth donor weakens the pi-bonding, which enables abstraction of H atoms from hydrocarbons. The unusual bonding and reactivity patterns of three-coordinate iron compounds may lead to new catalysts for oxidation and reduction reactions and may be used by nature in transient intermediates of nitrogenase enzymes.

Analysis of the APETALA3- and PISTILLATA-like genes in Hedyosmum orientale (Chloranthaceae) provides insight into the evolution of the floral homeotic B-function in angiosperms

PubMed Central

Liu, Shujun; Sun, Yonghua; Du, Xiaoqiu; Xu, Qijiang; Wu, Feng; Meng, Zheng

2013-01-01

Background and Aims According to the floral ABC model, B-function genes appear to play a key role in the origin and diversification of the perianth during the evolution of angiosperms. The basal angiosperm Hedyosmum orientale (Chloranthaceae) has unisexual inflorescences associated with a seemingly primitive reproductive morphology and a reduced perianth structure in female flowers. The aim of this study was to investigate the nature of the perianth and the evolutionary state of the B-function programme in this species. Methods A series of experiments were conducted to characterize B-gene homologues isolated from H. orientale, including scanning electron microscopy to observe the development of floral organs, phylogenetic analysis to reconstruct gene evolutionary history, reverse transcription–PCR, quantitative real-time PCR and in situ hybridization to identify gene expression patterns, the yeast two-hybrid assay to explore protein dimerization affinities, and transgenic analyses in Arabidopsis thaliana to determine activities of the encoded proteins. Key Results The expression of HoAP3 genes was restricted to stamens, whereas HoPI genes were broadly expressed in all floral organs. HoAP3 was able to partially restore the stamen but not petal identity in Arabidopsis ap3-3 mutants. In contrast, HoPI could rescue aspects of both stamen and petal development in Arabidopsis pi-1 mutants. When the complete C-terminal sequence of HoPI was deleted, however, no or weak transgenic phenotypes were observed and homodimerization capability was completely abolished. Conclusions The results suggest that Hedyosmum AP3-like genes have an ancestral function in specifying male reproductive organs, and that the activity of the encoded PI-like proteins is highly conserved between Hedyosmum and Arabidopsis. Moreover, there is evidence that the C-terminal region is important for the function of HoPI. Our findings indicate that the development of the proposed perianth in Hedyosmum does not rely on the B homeotic function. PMID:23956161

Multi-Target/Multi-Sensor Tracking using Only Range and Doppler Measurements

DTIC Science & Technology

2009-04-01

I+1) k ) represents a global maximum, given the Gaussian components used in our model, and given that P(I) has been fixed using parameter values...on Pattern Analysis and Machine Intelligence, 24 (2002), 381—396. [37] Perlovsky, L. I., Plum, C. P., Franchi , P. R., Tichovolsky, E. J., Choi, D. S

Identification of an enhancer element of class Pi glutathione S-transferase gene required for expression by a co-planar polychlorinated biphenyl.

PubMed Central

Matsumoto, M; Imagawa, M; Aoki, Y

1999-01-01

3,3',4,4',5-Pentachlorobiphenyl (PenCB), one of the most toxic co-planar polychlorinated biphenyl congeners, specifically induces class Pi glutathione S-transferase (GSTP1) as well as cytochrome P-450 1A1 in primary cultured rat liver parenchymal cells [Aoki, Matsumoto and Suzuki (1993) FEBS Lett. 333, 114-118]. However, the 5'-flanking sequence of the GSTP1 gene does not contain a xenobiotic responsive element, to which arylhydrocarbon receptor binds. Using a chloramphenicol acetyltransferase assay we demonstrate here that the enhancer termed GSTP1 enhancer I (GPEI) is necessary for the stimulation by PenCB of GSTP1 gene expression in primary cultured rat liver parenchymal cells. GPEI is already known to contain a dyad of PMA responsive element-like elements oriented palindromically. It is suggested that a novel signal transduction pathway activated by PenCB contributes to the stimulation of GSTP1 expression. PMID:10051428

Alterations in Glutathione S-transferase pi expression following exposure to MPP+-induced oxidative stress in blood of Parkinson’s disease patients

PubMed Central

Korff, Ane; Pfeiffer, Brenda; Smeyne, Michelle; Kocak, Mehmet; Pfeiffer, Ronald F.

2012-01-01

The major motor symptoms of Parkinson’s disease do not occur until a majority of the dopaminergic neurons in the midbrain SNpc have already died. For this reason, it is critical to identify biomarkers that will allow for the identification of presymptomatic individuals. In this study, we examine the baseline expression of the antioxidant protein Glutathione S-transferase pi (GSTpi) in blood of PD and environmental and age-matched controls and compare it to GSTpi levels following exposure to 1-methyl-4-phenylpyridinium (MPP+), an agent that has been shown to induce oxidative stress. We find that 4 hours of exposure to MPP+, significant increases in GSTpi levels can be observed in the leukocytes of PD patients. No changes were seen in other blood components. This suggests that GSTpi and potentially other members of this and other anti-oxidant families may be viable biomarkers for PD. PMID:21840241

Alterations in glutathione S-transferase pi expression following exposure to MPP+ -induced oxidative stress in the blood of Parkinson's disease patients.

PubMed

Korff, Ane; Pfeiffer, Brenda; Smeyne, Michelle; Kocak, Mehmet; Pfeiffer, Ronald F; Smeyne, Richard Jay

2011-12-01

The major motor symptoms of Parkinson's disease do not occur until a majority of the dopaminergic neurons in the midbrain SNpc have already died. For this reason, it is critical to identify biomarkers that will allow for the identification of presymptomatic individuals. In this study, we examine the baseline expression of the anti-oxidant protein glutathione S-transferase pi (GSTpi) in the blood of PD patients and environmentally- and age-matched controls and compare it to GSTpi levels following exposure to 1-methyl-4-phenylpyridinium (MPP(+)), an agent that has been shown to induce oxidative stress. We find that after 4 h of exposure to MPP(+), significant increases in GSTpi levels can be observed in the leukocytes of PD patients. No changes were seen in other blood components. This suggests that GSTpi and potentially other members of this and other anti-oxidant families may be viable biomarkers for PD. Copyright © 2011 Elsevier Ltd. All rights reserved.

Identification of a major yolk protein as an allergen in sea urchin roe.

PubMed

Yamasaki, Ayako; Higaki, Hiromi; Nakashima, Keiko; Yamamoto, Osamu; Hein, Kyaw Zaw; Takahashi, Hitoshi; Chinuki, Yuko; Morita, Eishin

2010-05-01

Anaphylaxis after eating sea urchin roe has been reported. However, its major allergens have not yet been identified. The aim of this study was to identify the major allergens of sea urchin roe. Proteins of sea urchin roe were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and two-dimensional electrophoresis (2-DE). An immunoglobulin (Ig)E-binding protein was detected by immunoblotting using the patient's serum. An allergen isolated from 2DE-gel was identified by peptide mass fingerprinting using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry. Immunoblot analysis of sea urchin extracts showed that a 160-kDa protein at pI 6-7 was recognized by the patient's IgE. Peptide mass fingerprint analysis revealed that the protein was the major yolk protein (152 kDa, pI 6.9) of sea urchins. The results show that a major allergen of sea urchin roe is the major yolk protein.

Therapeutic monoclonal antibodies and the need for targeted pharmacovigilance in India

PubMed Central

Kalaivani, M; Singh, Abhishank; Kalaiselvan, V

2015-01-01

A growing number of innovative mAb therapeutics are on the global market, and biosimilar versions have now also been approved, including in India. Although efficacy and safety is demonstrated prior to approval, targeted pharmacovigilance is essential for the identification and assessment of risk for any mAb products. We analyzed the ADR data related to mAbs reported to the NCC-PvPI through the spontaneous reporting system Vigiflow during April 2011 to February 2014 to identify mAbs with the highest number of ADR including fatal/serious ADR. Only 0.72% reports were related to mAbs. Although 15 mAbs are approved in the country, only 6 mAbs were reported through Vigiflow. Rituximab was highly reported, and no fatal/serious ADR related to any mAbs were reported during the study period. Our study shows that PvPI is effective and robust system in the detection and assessment of risks associated with the use of mAbs. PMID:25523367

Activation of the PI3K/AKT pathway induces urothelial carcinoma of the renal pelvis: identification in human tumors and confirmation in animal models.

PubMed

Qian, Chao-Nan; Furge, Kyle A; Knol, Jared; Huang, Dan; Chen, Jindong; Dykema, Karl J; Kort, Eric J; Massie, Aaron; Khoo, Sok Kean; Vanden Beldt, Kristin; Resau, James H; Anema, John; Kahnoski, Richard J; Morreau, Hans; Camparo, Philippe; Comperat, Eva; Sibony, Mathilde; Denoux, Yves; Molinie, Vincent; Vieillefond, Annick; Eng, Charis; Williams, Bart O; Teh, Bin Tean

2009-11-01

Urothelial carcinoma of the renal pelvis is a deadly disease with an unclear tumorigenic mechanism. We conducted gene expression profiling on a set of human tumors of this type and identified a phosphatidylinositol 3-kinase (PI3K)/AKT activation expression signature in 76.9% (n = 13) of our samples. Sequence analysis found both activating mutations of PIK3CA (13.6%, n = 22) and loss of heterozygosity at the PTEN locus (25%, n = 8). In contrast, none of the other subtypes of kidney neoplasms (e.g., clear-cell renal cell carcinoma) harbored PIK3CA mutations (n = 87; P < 0.001). Immunohistochemical analysis of urothelial carcinoma samples found loss of PTEN protein expression (36.4%, n = 11) and elevation of phosphorylated mammalian target of rapamycin (mTOR; 63.6%, n = 11). To confirm the role of the PI3K/AKT pathway in urothelial carcinoma, we generated mice containing biallelic inactivation of Pten in the urogenital epithelia. These mice developed typical renal pelvic urothelial carcinomas, with an incidence of 57.1% in mice older than 1 year. Laser capture microdissection followed by PCR confirmed the deletion of Pten exons 4 and 5 in the animal tumor cells. Immunohistochemical analyses showed increased phospho-mTOR and phospho-S6K levels in the animal tumors. Renal lymph node metastases were found in 15.8% of the animals with urothelial carcinoma. In conclusion, we identified and confirmed an important role for the PI3K/AKT pathway in the development of urothelial carcinoma and suggested that inhibitors of this pathway (e.g., mTOR inhibitor) may serve as effective therapeutic agents.

Activation of the PI3K/AKT pathway induces urothelial carcinoma of the renal pelvis: Identification in human tumors and confirmation in animal models

PubMed Central

Qian, Chao-Nan; Furge, Kyle A.; Knol, Jared; Huang, Dan; Chen, Jindong; Dykema, Karl J.; Kort, Eric J.; Massie, Aaron; Khoo, Sok Kean; VandenBeldt, Kristin; Resau, James H.; Anema, John; Kahnoski, Richard J.; Morreau, Hans; Camparo, Philippe; Comperat, Eva; Sibony, Mathilde; Denoux, Yves; Molinie, Vincent; Vieillefond, Annick; Eng, Charis; Williams, Bart O.; Teh, Bin Tean

2009-01-01

Urothelial carcinoma of the renal pelvis is a deadly disease with an unclear tumorigenic mechanism. We conducted gene expression profiling on a set of human tumors of this type, and identified a PI3K/AKT activation expression signature in 76.9% (n=13) of our samples. Sequence analysis found both activating mutations of PIK3CA (13.6%, n = 22) and loss of heterozygosity at the PTEN locus (25%, n = 8). In contrast, none of the other subtypes of kidney neoplasms (e.g., clear cell renal cell carcinoma) harbored PIK3CA mutations (n = 87; P < 0.001). Immunohistochemical analysis of urothelial carcinoma samples found loss of PTEN protein expression (36.4%, n = 11) and elevation of phospho-mTOR (63.6%, n = 11). To confirm the role of the PI3K/AKT pathway in urothelial carcinoma, we generated mice containing biallelic inactivation of Pten in the urogenital epithelia. These mice developed typical renal pelvic urothelial carcinomas, with an incidence of 57.1% in mice older than one year. Laser capture microdissection followed by PCR confirmed the deletion of Pten exons 4 and 5 in the animal tumor cells. Immunohistochemical analyses demonstrated increased phospho-mTOR and phospho-S6K levels in the animal tumors. Renal lymph node metastases were found in 15.8% of the animals with urothelial carcinoma. In conclusion, we identified and confirmed an important role for the PI3K/AKT pathway in the development of urothelial carcinoma and suggested that inhibitors of this pathway (e.g. mTOR inhibitor) may serve as effective therapeutic agents. PMID:19843858

Tangeretin alters neuronal apoptosis and ameliorates the severity of seizures in experimental epilepsy-induced rats by modulating apoptotic protein expressions, regulating matrix metalloproteinases, and activating the PI3K/Akt cell survival pathway.

PubMed

Guo, Xiao-Qian; Cao, Yu-Ling; Hao, Fang; Yan, Zhong-Rui; Wang, Mei-Ling; Liu, Xue-Wu

2017-09-01

Epilepsy is complex neural disarray categorized by recurring seizures. Despite recent advances in pharmacotherapies for epilepsy, its treatment remains a challenge due to the contrary effects of the drugs. As a result, the identification of novel anti-epileptic drugs (AEDs) with neuroprotective properties and few side effects is of great value. Thus, the present study assessed the treatment effects of tangeretin using a rat model of pilocarpine-induced epilepsy. Separate groups of male Wistar rats received oral administrations of tangeretin at 50, 100, or 200mg/kg for 10 days and then, on the 10th day, they received an intraperitoneal injection of pilocarpine (30mg/kg). Subsequently, neuronal degeneration and apoptosis were assessed using Nissl staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay procedures. Additionally, the expressions of phosphatidylinositol-3-kinase (PI3K/Akt) pathway proteins, cleaved caspase-3, Bad, Bcl-2, Bcl-xL, and Bax were determined using Western blot analyses. Tangeretin reduced the seizure scores and latency to first seizure of the rats and effectively activated the pilocarpine-induced suppression of PI3K/Akt signaling. Additionally, tangeretin effectively regulated the levels of apoptosis-inducing factor (AIF) in mitochondria as well as the expressions of apoptotic pathway proteins. Seizure-induced elevations in the activities and expressions of matrix metalloproteinases (MMPs)-2 and -9 were also modulated. The present results indicate that tangeretin exerted potent neuroprotective effects against pilocarpine-induced seizures via the activation of PI3K/Akt signaling and the regulation of MMPs. Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

Monitoring the response of patients with cutaneous leishmaniasis to treatment with pentamidine isethionate by quantitative real-time PCR, and identification of Leishmania parasites not responding to therapy.

PubMed

Mans, D R A; Kent, A D; Hu, R V; Lai A Fat, E J; Schoone, G J; Adams, E R; Rood, E J; Alba, S; Sabajo, L O A; Lai A Fat, R F; de Vries, H J C; Schallig, H D F H

2016-08-01

Leishmania (Viannia) guyanensis is believed to be the principal cause of cutaneous leishmaniasis (CL) in Suriname. This disease is treated with pentamidine isethionate (PI), but treatment failure has increasingly been reported. To evaluate PI for its clinical efficacy, to compare parasite load, and to assess the possibility of treatment failure due to other infecting Leishmania species. Parasite load of patients with CL was determined in skin biopsies using real-time quantitative PCR before treatment and 6 and 12 weeks after treatment. Clinical responses were evaluated at week 12 and compared with parasite load. In parallel, molecular species differentiation was performed. L. (V.) guyanensis was the main infecting species in 129 of 143 patients (about 90%). PI treatment led to a significant decrease (P < 0.001) in parasite counts, and cured about 75% of these patients. Treatment failure was attributable to infections with Leishmania (Viannia) braziliensis, Leishmania (Leishmania) amazonensis and L. (V.) guyanensis (1/92, 1/92 and 22/92 evaluable cases, respectively). There was substantial agreement beyond chance between the parasite load at week 6 and the clinical outcome at week 12, as indicated by the κ value of 0.61. L. (V.) guyanensis is the main infecting species of CL in Suriname, followed by L. (V.) braziliensis and L. (L.) amazonensis. Furthermore, patient response to PI can be better anticipated based on the parasite load 6 weeks after the treatment rather than on parasite load before treatment. © 2015 The Authors Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists, North American Clinical Dermatologic Society and St Johns Dermatological Society.

Determination of parts per trillion levels of organophosphorus pesticides in groundwater by automated on-line liquid-solid extraction followed by liquid chromatography/atmospheric pressure chemical ionization mass spectrometry using positive and negative ion modes of operation.

PubMed

Lacorte, S; Barceló, D

1996-08-01

Liquid chromatography/atmospheric pressure chemical ionization mass spectrometry with positive and negative ion modes of operations was used for the trace determination of several organophosphorus pesticides, (E)- and (Z)-mevinphos, dichlorvos, azinphos-methyl, azinphosethyl, parathion-methyl, parathion-ethyl, malathion, fenitrothion, fenthion, chlorfenvinphos, and diazinon, in groundwater. This method required only 100 mL of water, and it was combined with a prior automated online liquid-solid extraction step using an OSP-2 autosampler containing C18 cartridges. The limit of quantitation (LOQ) varied between 5 and 37 ng/L in positive ion (PI) mode. Under negative ion (NI) mode of operation, only the parathion group (both parathions and fenitrothion) had a better sensitivity as compared to that in PI mode, with a LOQ of 5-15 ng/L, whereas the rest of pesticides had 2-4 times higher LOQs as compared to those in PI mode. Selected ion monitoring of the group-specific fragment of the organophosphorus pesticides, e.g., [(CH3O)2PO2]- or the [M + H]+ ions, under NI or PI mode, respectively, was used. Sample cone voltage varied from 10 to 130 V. This parameter influenced the transmission and fragmentation of quasi-molecular ions, and it was optimized to achieve identification capabilities with the highest sensitivity. At 20 V, good fragmentation was obtained for most of the studied analytes. The system was used for the certification of a groundwater sample spiked at the nanograms per liter level with organophosphorus pesticides provided by Aquachek.

The dual PI3K/mTOR inhibitor NVP-BEZ235 and chloroquine synergize to trigger apoptosis via mitochondrial-lysosomal cross-talk.

PubMed

Seitz, Christian; Hugle, Manuela; Cristofanon, Silvia; Tchoghandjian, Aurélie; Fulda, Simone

2013-06-01

On the basis of our previous identification of aberrant phosphatidylinositol-3-kinase (PI3K)/Akt signaling as a novel poor prognostic factor in neuroblastoma, we evaluated the dual PI3K/mTOR inhibitor BEZ235 in the present study. Here, BEZ235 acts in concert with the lysosomotropic agent chloroquine (CQ) to trigger apoptosis in neuroblastoma cells in a synergistic manner, as calculated by combination index (CI < 0.5). Surprisingly, inhibition of BEZ235-induced autophagy is unlikely the primary mechanism of this synergism as reported in other cancers, since neither inhibition of autophagosome formation by knockdown of Atg7 or Atg5 nor disruption of the autophagic flux by Bafilomycin A1 (BafA1) enhance BEZ235-induced apoptosis. BEZ235 stimulates enlargement of the lysosomal compartment and generation of reactive oxygen species (ROS), while CQ promotes lysosomal membrane permeabilization (LMP). In combination, BEZ235 and CQ cooperate to trigger LMP, Bax activation, loss of mitochondrial membrane potential (MMP) and caspase-dependent apoptosis. Lysosome-mediated apoptosis occurs in a ROS-dependent manner, as ROS scavengers significantly reduce BEZ235/CQ-induced loss of MMP, LMP and apoptosis. There is a mitochondrial-lysosomal cross-talk, since lysosomal enzyme inhibitors significantly decrease BEZ235- and CQ-induced drop of MMP and apoptosis. In conclusion, BEZ235 and CQ act in concert to trigger LMP and lysosome-mediated apoptosis via a mitochondrial-lysosomal cross-talk. These findings have important implications for the rational development of PI3K/mTOR inhibitor-based combination therapies. Copyright © 2012 UICC.

Development of propidium iodide as a fluorescence probe for the on-line screening of non-specific DNA-intercalators in Fufang Banbianlian Injection.

PubMed

Niu, Yanyan; Li, Sensen; Lin, Zongtao; Liu, Meixian; Wang, Daidong; Wang, Hong; Chen, Shizhong

2016-09-09

Fufang Banbianlian Injection (FBI) has been widely used as an anti-inflammatory and anti-tumor prescription. To understand the relationships between its bioactive ingredients and pharmacological efficacies, our previous study has been successfully identified some DNA-binding compounds in FBI using an established on-line screening system, in which 4',6-diamidino-2-phenylindole (DAPI) was developed as a probe. However, DAPI can be only used to screen ATT-specific DNA minor groove binders, leaving the potential active intercalators unknown in FBI. As a continuation of our studies on FBI, here we present a sensitive analytical method for rapid identification and evaluation of DNA-intercalators using propidium iodide (PI) as a fluorescent probe. We have firstly established the technique of high-performance liquid chromatography-diode-array detector-multistage mass spectrometry-deoxyribonucleic acid-propidium iodide-fluorescence detector (HPLC-DAD-MS(n)-DNA-PI-FLD) system. As a result, 38 of 58 previously identified compounds in FBI were DNA-intercalation active. Interestingly, all previously reported DNA-binders also showed intercalative activities, suggesting they are dual-mode DNA-binders. Quantitative study showed that flavonoid glycosides and chlorogenic acids were the main active compounds in FBI, and displayed similar DNA-binding ability using either DAPI or PI. In addition, 13 active compounds were used to establish the structure-activity relationships. In this study, PI was developed into an on-line method for identifying DNA-intercalators for the first time, and thus it will be a useful high-throughput screening technique for other related samples. Copyright © 2016 Elsevier B.V. All rights reserved.

PiHi Observations at the ATA, Conventional and Unconventional SETI

NASA Astrophysics Data System (ADS)

Harp, Gerald; Wilcox, B.; Arbunich, J.; Blair, S.; Backus, P. R.; Tarter, J. C.; Shostak, S.; Jordan, J.; Kilsdonk, T.; Ackermann, R. F.; Ross, J.; ATA Team

2010-01-01

Many radio SETI searches focus on the frequency range where the HI (1.42 GHz) and OH lines (1.6-1.7 GHz) lines are landmarks delineating the water hole This is only a small fraction of the terrestrial microwave window (TMW) from 1-10 GHz. This survey occurs near the center of the TMW at 4.462336275 GHz or π times the HI frequency. We call this the PiHI ("pie high") survey. The inspiration for PiHI observations comes from Carl Sagan in his book, Contact. This survey builds upon and extends a previous survey at PiHI (Blair, D. G. et al. (1992), MNRAS, 257, 105) with greater sensitivity, resolution, and coverage. We survey the nearest 94 main sequence stars in the HabCat catalog (Turnbull, M. C. and Tarter, J. C. (2003), ApJS, 145, 181) with spectral classes between F9 and G7 (max. radius 62 pc). The ATA's flexibility allows simultaneous measurements of targeted observations on stars (with beamformers) and 1° FOV "blind” observations of the areas around target stars (with imaging correlator). The targeted observations are carried out with a high resolution (0.7 Hz) spectrometer and integration times on the order of 200 s. The spectral imaging correlator measures a 50 x 50 grid of points with 3 kHz spectral resolution. This survey shows several signals of minor interest were discovered, though none of the signals reported are continuously "on,” which is an important characteristic for the positive identification of an ETI signal. The ATA has been funded through generous grants from the Paul G. Allen Family Foundation, the SETI Institute, UC Berkeley, the National Science Foundation (Grant No. 0540599), Sun Microsystems, Xilinx, Nathan Myhrvold, Greg Papadopoulos, and other corporations and individual donors.

Cascading ecohydrological transitions: Multiple changes in vegetation and hydrology over the past 500 years for a semiarid forest/woodland boundary zone in New Mexico, USA

NASA Astrophysics Data System (ADS)

Allen, Craig D.

2010-05-01

On decadal and centennial time scales, multiple drivers can cause substantial changes in vegetation cover, which can trigger associated changes in runoff and erosion patterns and processes, with consequent feedbacks to the vegetation - cumulatively this can lead to a cascading series of non-equilibrial ecosystem changes through time. The work reported here provides a relatively detailed 500-year perspective of such changes on the mesas the eastern Jemez Mountains in northern New Mexico (USA), which today exhibit vegetation transitions along an elevational gradient between semiarid ponderosa pine (Pinus ponderosa) forests, mixed woodlands dominated by piñon (Pinus edulis) and one-seed juniper (Juniperus monosperma), and juniper savannas. Using multiple lines of evidence, a history of major ecosystem changes since ca. 1500 A.D. is reconstructed for a dynamic transition zone on one such mesa (Frijolito Mesa). Evidence includes intensive archaeological surveys, dendrochronological reconstructions of the demographic and spatial patterns of establishment and mortality for these three main tree species, dendrochronological reconstructions of fire regimes and climate patterns, broad-scale mapping of vegetation changes from historic aerial photographs since 1935, monitoring of vegetation from permanent transects since 1991, detailed soil maps and interpretations, intensive ecohydrological studies since 1993 on portions of this mesa, and research on the ecosystem effects of an experimental tree-thinning experiment conducted in 1997. Frijolito Mesa was fully occupied by large numbers of Native American farmers from the A.D. 1200's until the late 1500's, when they left these mesas for settlements in the adjoining Rio Grande Valley. Archaeological evidence and tree ages indicate that the mesa was likely quite deforested when abandoned, followed by episodic tree establishment dominated by ponderosa pine during the Little Ice Age. By the late 1700's Frijolito Mesa included ponderosa pine in open stands maintained by frequent surface fires burning through herbaceous ground cover adequate to maintain ancient (>100,000 year old) soils, interspersed with young piñon-juniper savannas and woodlands on rockier fire-safe sites. Intensive livestock grazing from the late 1800's thru 1932 reduced the herbaceous ground cover, interrupting the surface fire regime, triggering massive establishment of fire-sensitive piñon and juniper throughout much of the 1900's. Severe drought in the 1950's killed all the ponderosa pine across an irregular ecotone shift zone up to 2 km wide, with no subsequent regeneration, leaving piñon-juniper woodland with accelerated, unsustainable erosion in desertified areas between tree clumps (averaging ~4 Mg/ha/year for the period 1995-2007 in a 1.09 ha study watershed). Warm drought in the early 2000's caused mass mortality of essentially all overstory piñon, leaving juniper as the only remaining tree dominant across huge areas. Ecohydrological processes are shifting again with declining runoff/erosion trends since 2003 as dead piñon skeletons fall and with increased abundances of shrubs and herbaceous surface cover, decreasing the connectivity of bare soil patches. The history of Frijolito Mesa illustrates multiple major transitions in vegetation since 1500 A.D., and substantial changes in runoff and erosion processes. This research has been used by the National Park Service since 2007 to implement an ecosystem restoration treatment (mechanical thinning of small trees with chainsaws and application of branch slash mulch) at a landscape scale of ~2000 ha. The treatments effectively conserve more water and soil onsite, increasing herbaceous ground cover and decreasing soil erosion rates 100-fold, stabilizing hundreds of archaeological sites and restoring the potential for natural surface fires. The ecohydrological history of this mesa also provides insight into how similar vegetation changes, such as episodes of widespread and intensive tree mortality that are now emerging with climate stress around the world, may significantly affect ecohydrological patterns and processes in other regions.

[Identification of a murderer on the basis of a biting pattern on body of the victim].

PubMed

Zaba, Czesław; Lorkiewicz-Muszyńska, Dorota; Glapiński, Mariusz; Smoluch, Krzysztof; Swiderski, Paweł

2010-01-01

The authors present a case of identification of a a murderer on the basis of his dentition pattern, reflected by a biting wound on the breast of the victim. The case is exceptional not only from the viewpoint of the authors, but also in view of very sporadic reports on this subject in forensic literature. Cases of biting by humans are not frequent in the forensic/ medical practice, and instances of identification of the perpetrator by his dental pattern reflected in the biting wound are very rare. In Poland, such problems have been the domain of mainly criminologists and only occasionally of forensic medics in collaboration with dentists and anthropologists. Due to the very low number of such cases in Poland, no experts in the matter are available. For this reason, we deemed it purposeful to present respective investigative principles and techniques for identification of a human perpetrator on the basis of the dental pattern reflected in a biting wound on the victim's body.

Inclusion probability for DNA mixtures is a subjective one-sided match statistic unrelated to identification information

PubMed Central

Perlin, Mark William

2015-01-01

Background: DNA mixtures of two or more people are a common type of forensic crime scene evidence. A match statistic that connects the evidence to a criminal defendant is usually needed for court. Jurors rely on this strength of match to help decide guilt or innocence. However, the reliability of unsophisticated match statistics for DNA mixtures has been questioned. Materials and Methods: The most prevalent match statistic for DNA mixtures is the combined probability of inclusion (CPI), used by crime labs for over 15 years. When testing 13 short tandem repeat (STR) genetic loci, the CPI-1 value is typically around a million, regardless of DNA mixture composition. However, actual identification information, as measured by a likelihood ratio (LR), spans a much broader range. This study examined probability of inclusion (PI) mixture statistics for 517 locus experiments drawn from 16 reported cases and compared them with LR locus information calculated independently on the same data. The log(PI-1) values were examined and compared with corresponding log(LR) values. Results: The LR and CPI methods were compared in case examples of false inclusion, false exclusion, a homicide, and criminal justice outcomes. Statistical analysis of crime laboratory STR data shows that inclusion match statistics exhibit a truncated normal distribution having zero center, with little correlation to actual identification information. By the law of large numbers (LLN), CPI-1 increases with the number of tested genetic loci, regardless of DNA mixture composition or match information. These statistical findings explain why CPI is relatively constant, with implications for DNA policy, criminal justice, cost of crime, and crime prevention. Conclusions: Forensic crime laboratories have generated CPI statistics on hundreds of thousands of DNA mixture evidence items. However, this commonly used match statistic behaves like a random generator of inclusionary values, following the LLN rather than measuring identification information. A quantitative CPI number adds little meaningful information beyond the analyst's initial qualitative assessment that a person's DNA is included in a mixture. Statistical methods for reporting on DNA mixture evidence should be scientifically validated before they are relied upon by criminal justice. PMID:26605124

Inclusion probability for DNA mixtures is a subjective one-sided match statistic unrelated to identification information.

PubMed

Perlin, Mark William

2015-01-01

DNA mixtures of two or more people are a common type of forensic crime scene evidence. A match statistic that connects the evidence to a criminal defendant is usually needed for court. Jurors rely on this strength of match to help decide guilt or innocence. However, the reliability of unsophisticated match statistics for DNA mixtures has been questioned. The most prevalent match statistic for DNA mixtures is the combined probability of inclusion (CPI), used by crime labs for over 15 years. When testing 13 short tandem repeat (STR) genetic loci, the CPI(-1) value is typically around a million, regardless of DNA mixture composition. However, actual identification information, as measured by a likelihood ratio (LR), spans a much broader range. This study examined probability of inclusion (PI) mixture statistics for 517 locus experiments drawn from 16 reported cases and compared them with LR locus information calculated independently on the same data. The log(PI(-1)) values were examined and compared with corresponding log(LR) values. The LR and CPI methods were compared in case examples of false inclusion, false exclusion, a homicide, and criminal justice outcomes. Statistical analysis of crime laboratory STR data shows that inclusion match statistics exhibit a truncated normal distribution having zero center, with little correlation to actual identification information. By the law of large numbers (LLN), CPI(-1) increases with the number of tested genetic loci, regardless of DNA mixture composition or match information. These statistical findings explain why CPI is relatively constant, with implications for DNA policy, criminal justice, cost of crime, and crime prevention. Forensic crime laboratories have generated CPI statistics on hundreds of thousands of DNA mixture evidence items. However, this commonly used match statistic behaves like a random generator of inclusionary values, following the LLN rather than measuring identification information. A quantitative CPI number adds little meaningful information beyond the analyst's initial qualitative assessment that a person's DNA is included in a mixture. Statistical methods for reporting on DNA mixture evidence should be scientifically validated before they are relied upon by criminal justice.

Study on the Characteristics of Contrast-Enhanced Ultrasound and Its Utility in Assessing the Microvessel Density in Ovarian Tumors or Tumor-Like Lesions

PubMed Central

Wang, Junyan; Lv, Faqin; Fei, Xiang; Cui, Qiuli; Wang, Longxia; Gao, Xuewen; Yuan, Zhixian; Lin, Qian; Lv, Yali; Liu, Aijun

2011-01-01

Angiogenesis is a critical factor in tumor growth and metastasis, and microvessel density (MVD) was an important parameter for assessing vessels in tumors. However, radiologic assessment of tumor vascularity is not yet well established. In our study, we aimed at investigating the efficacy of contrast-enhanced ultrasonography (CEUS) in exploring the vascularity of the ovarian tumors or tumor-like lesions to assess the relationship between the parameters of the peak intensity (PI) and area under curve (AUC) on CEUS and MVD in ovarian masses. Compared to the contrast-enhanced ultrasound technique, conventional ultrasound shows limitation in differentiating benign and malignant ovarian tumors. The former is promising in improving the sensitivity of detecting small vessels and blood flow in ovarian tumors. Our results showed clear differences in enhancement patterns between benign and malignant ovary tumors or tumor-like lesions. The PI and AUC in the malignant tumors were significantly higher than those in the benign tumors or tumor-like lesions (p=0.001 and =0.01, respectively). The MVD was 43.1 ± 20.4 in the benign tumors or tumor-like lesions and was 65.3 ± 22.3 in the malignant ones (p= 0.01). In both the benign and malignant groups, the PI and AUC were correlated significantly with the MVD (r=0.595, p = 0.001; r =0.533, p = 0.003, respectively). The PI and AUC in CEUS can reflect the MVD in ovarin tumors. The PI and AUC of the ovarian masses in the contrast transvaginal sonography show significant correlation with the angiogenesis and may help in assessing tumor vascularity in ovarian masses. PMID:21614152

PI3-kinase cascade has a differential role in acquisition and extinction of conditioned fear memory in juvenile and adult rats.

PubMed

Slouzkey, Ilana; Maroun, Mouna

2016-12-01

The basolateral amygdala (BLA), medial prefrontal cortex (mPFC) circuit, plays a crucial role in acquisition and extinction of fear memory. Extinction of aversive memories is mediated, at least in part, by the phosphoinositide-3 kinase (PI3K)/Akt pathway in adult rats. There is recent interest in the neural mechanisms that mediate fear and extinction in juvenile animals and whether these mechanisms are distinctive from those in adult animals. In the present study, we examined (1) changes in phosphorylation of Akt in the BLA and mPFC after fear conditioning and extinction in juvenile and adult rats and (2) the effect of BLA and mPFC localized inhibition of the PI3K following acquisition and extinction of contextual fear memory. Our results show that Akt phosphorylation is increased following acquisition of contextual fear learning in the BLA but not in the mPFC in adult and juvenile rats. Extinction learning was not associated with changes in Akt phosphorylation. Although there were no differences in the pattern of phosphorylation of Akt either in adult or juvenile rats, microinjection of the PI3K inhibitor, LY294002, into the BLA or mPFC elicited differential effects on fear memory acquisition and extinction, depending on the site and timing of the microinjection, as well as on the age of the animal. These results suggest that PI3K/Akt has a differential role in formation, retrieval, and extinction of contextual fear memory in juvenile and adult animals, and point to developmental differences between adult and juvenile rats in mechanisms of extinction. © 2016 Slouzkey and Maroun; Published by Cold Spring Harbor Laboratory Press.

Multitasking of the piRNA Silencing Machinery: Targeting Transposable Elements and Foreign Genes in the Bdelloid Rotifer Adineta vaga.

PubMed

Rodriguez, Fernando; Arkhipova, Irina R

2016-05-01

RNA-mediated silencing processes play a key role in silencing of transposable elements, especially in the germ line, where piwi-interacting RNAs (piRNAs) are responsible for suppressing transposon mobility and maintaining genome integrity. We previously reported that the genome of Adineta vaga, the first sequenced representative of the phylum Rotifera (class Bdelloidea), is characterized by massive levels of horizontal gene transfer, by unusually low transposon content, and by highly diversified RNA-mediated silencing machinery. Here, we investigate genome-wide distribution of pi-like small RNAs, which in A. vaga are 25-31 nucleotides in length and have a strong 5'-uridine bias, while lacking ping-pong amplification signatures. In agreement with expectations, 71% of mapped reads corresponded to annotated transposons, with 93% of these reads being in the antisense orientation. Unexpectedly, a significant fraction of piRNAs originate from predicted coding regions corresponding to genes of putatively foreign origin. The distribution of piRNAs across foreign genes is not biased toward 3'-UTRs, instead resembling transposons in uniform distribution pattern throughout the gene body, and in predominantly antisense orientation. We also find that genes with small RNA coverage, including a number of genes of metazoan origin, are characterized by higher occurrence of telomeric repeats in the surrounding genomic regions, and by higher density of transposons in the vicinity, which have the potential to promote antisense transcription. Our findings highlight the complex interplay between RNA-based silencing processes and acquisition of genes at the genome periphery, which can result either in their loss or eventual domestication and integration into the host genome. Copyright © 2016 by the Genetics Society of America.

Multitasking of the piRNA Silencing Machinery: Targeting Transposable Elements and Foreign Genes in the Bdelloid Rotifer Adineta vaga

PubMed Central

Rodriguez, Fernando; Arkhipova, Irina R.

2016-01-01

RNA-mediated silencing processes play a key role in silencing of transposable elements, especially in the germ line, where piwi-interacting RNAs (piRNAs) are responsible for suppressing transposon mobility and maintaining genome integrity. We previously reported that the genome of Adineta vaga, the first sequenced representative of the phylum Rotifera (class Bdelloidea), is characterized by massive levels of horizontal gene transfer, by unusually low transposon content, and by highly diversified RNA-mediated silencing machinery. Here, we investigate genome-wide distribution of pi-like small RNAs, which in A. vaga are 25–31 nucleotides in length and have a strong 5′-uridine bias, while lacking ping-pong amplification signatures. In agreement with expectations, 71% of mapped reads corresponded to annotated transposons, with 93% of these reads being in the antisense orientation. Unexpectedly, a significant fraction of piRNAs originate from predicted coding regions corresponding to genes of putatively foreign origin. The distribution of piRNAs across foreign genes is not biased toward 3′-UTRs, instead resembling transposons in uniform distribution pattern throughout the gene body, and in predominantly antisense orientation. We also find that genes with small RNA coverage, including a number of genes of metazoan origin, are characterized by higher occurrence of telomeric repeats in the surrounding genomic regions, and by higher density of transposons in the vicinity, which have the potential to promote antisense transcription. Our findings highlight the complex interplay between RNA-based silencing processes and acquisition of genes at the genome periphery, which can result either in their loss or eventual domestication and integration into the host genome. PMID:27017627

Changing rates and patterns of drug resistance mutations in antiretroviral-experienced HIV-infected patients.

PubMed

de Mendoza, Carmen; Garrido, Carolina; Corral, Angelica; Ramírez-Olivencia, German; Jiménez-Nacher, Inmaculada; Zahonero, Natalia; Gonzalez-Lahoz, Juan; Soriano, Vincent

2007-07-01

Surveillance of drug resistance mutations in antiretroviral-experienced HIV(+) patients may provide useful information regarding options available for rescue interventions. All resistance tests performed from 1999 to 2005 on antiretroviral-experienced individuals at one reference laboratory in Madrid were examined. Only mutations associated with drug resistance recorded at the September 2006 IAS-USA list were considered. A total of 2137 specimens were analyzed. Overall, 71.1% showed resistance mutations to at least one drug class, 56.1% to at least two, and 21% to all three drug families. Resistance mutations were 65% for NRTI, 44.4% for NNRTI, and 42.5% for PI. Mutations T215Y/F, M184V, and M41L were the most frequent for NRTI. Their rate significantly declined since 1999. K65R significantly increased since 1999 (0.8%) to 2003 (7.3%) but declined up to 3.3% in 2005. For NNRTI, K103N significantly increased from 21.8% in 1999 to 29.5% in 2005 (p < 0.01). The most frequent PI resistance mutations were L90M (24.3%), V82X (19.9%), M46I/L (19.5%), and I54V (17.1%). The presence of five or more was 58.8% in 1999 but declined to 22.2% in 2005. The rate of drug resistance mutations causing NRTI and PI resistance has steadily declined in antiretroviral-experienced patients since 1999. The availability of a large number and/or more convenient NRTI as well as the wide use of ritonavir-boosted PI could explain these observations. However, broad PI cross-resistance was seen in nearly 25% of antiretroviral-experienced patients in 2005. Therefore, there is a still need for new antiretrovirals with different resistance profiles.

PepPat, a pattern-based oligopeptide homology search method and the identification of a novel tachykinin-like peptide.

PubMed

Jiang, Ying; Gao, Ge; Fang, Gang; Gustafson, Eric L; Laverty, Maureen; Yin, Yanbin; Zhang, Yong; Luo, Jingchu; Greene, Jonathan R; Bayne, Marvin L; Hedrick, Joseph A; Murgolo, Nicholas J

2003-05-01

PepPat, a hybrid method that combines pattern matching with similarity scoring, is described. We also report PepPat's application in the identification of a novel tachykinin-like peptide. PepPat takes as input a query peptide and a user-specified regular expression pattern within the peptide. It first performs a database pattern match and then ranks candidates on the basis of their similarity to the query peptide. PepPat calculates similarity over the pattern spanning region, enhancing PepPat's sensitivity for short query peptides. PepPat can also search for a user-specified number of occurrences of a repeated pattern within the target sequence. We illustrate PepPat's application in short peptide ligand mining. As a validation example, we report the identification of a novel tachykinin-like peptide, C14TKL-1, and show it is an NK1 (neuokinin receptor 1) agonist whose message is widely expressed in human periphery. PepPat is offered online at: http://peppat.cbi.pku.edu.cn.

Copernicus observations of interstellar matter toward the Orion OB1 association. I - Epsilon and Pi-5 Orionis

NASA Technical Reports Server (NTRS)

Shull, J. M.

1979-01-01

Copernicus UV data on interstellar lines toward Epsilon Ori and Pi-5 Ori are analyzed to study abundances and physical conditions in both low- and intermediate-velocity components. Clouds at -8 and +5 km/s (LSR) toward Epsilon Ori show typical depletions of Fe, Ti, Mg, and Si in dense (H number density about 100 per cu cm) gas. Low-column-density intermediate-velocity clouds toward both stars, with low densities (hydrogen number density less than 1 per cu cm) and near-cosmic Si abundances, are consistent with a widespread pattern of high-velocity gas over a 15-deg area surrounding the Orion region. Such activity may be attributed to the repeated action of supernovae in a patchy low-density region of interstellar gas.

Identification of 12/15-lipoxygenase as a suppressor of myeloproliferative disease

PubMed Central

Middleton, Melissa Kristine; Zukas, Alicia Marie; Rubinstein, Tanya; Jacob, Michele; Zhu, Peijuan; Zhao, Liang; Blair, Ian; Puré, Ellen

2006-01-01

Though Abl inhibitors are often successful therapies for the initial stages of chronic myelogenous leukemia (CML), refractory cases highlight the need for novel molecular insights. We demonstrate that mice deficient in the enzyme 12/15-lipoxygenase (12/15-LO) develop a myeloproliferative disorder (MPD) that progresses to transplantable leukemia. Although not associated with dysregulation of Abl, cells isolated from chronic stage 12/15-LO–deficient (Alox15) mice exhibit increased activation of the phosphatidylinositol 3–kinase (PI3-K) pathway, as indicated by enhanced phosphorylation of Akt. Furthermore, the transcription factor interferon consensus sequence binding protein (ICSBP) is hyperphosphorylated and displays decreased nuclear accumulation, translating into increased levels of expression of the oncoprotein Bcl-2. The ICSBP defect, exaggerated levels of Bcl-2, and prolonged leukemic cell survival associated with chronic stage Alox15 MPD are all reversible upon treatment with a PI3-K inhibitor. Remarkably, the evolution of Alox15 MPD to leukemia is associated with additional regulation of ICSBP on an RNA level, highlighting the potential usefulness of the Alox15 model for understanding the transition of CML to crisis. Finally, 12/15-LO expression suppresses the growth of a human CML–derived cell line. These data identify 12/15-LO as an important suppressor of MPD via its role as a critical upstream effector in the regulation of PI3-K–dependent ICSBP phosphorylation. PMID:17043146

Identification of the pI 4.6 extensin peroxidase from Lycopersicon esculentum using proteomics and reverse-genomics.

PubMed

Dong, Wen; Kieliszewski, Marcia; Held, Michael A

2015-04-01

The regulation of plant cell growth and early defense response involves the insolubilization of hydroxyproline-rich glycoproteins (HRGPs), such as extensin, in the primary cell wall. In tomato (Lycopersicon esculentum), insolubilization occurs by the formation of tyrosyl-crosslinks catalyzed specifically by the pI 4.6 extensin peroxidase (EP). To date, neither the gene encoding EP nor the protein itself has been identified. Here, we have identified tomato EP candidates using both proteomic and bioinformatic approaches. Bioinformatic screening of the tomato genome yielded eight EP candidates, which contained a putative signal sequence and a predicted pI near 4.6. Biochemical fractionation of tomato culture media followed by proteomic detection further refined our list of EP candidates to three, with the lead candidate designated (CG5). To test for EP crosslinking activity, we cloned into a bacterial expression vector the CG5 open-reading frame from tomato cDNA. The CG5 was expressed in Escherichia coli, fractionated from inclusion bodies, and folded in vitro. The peroxidase activity of CG5 was assayed and quantified by ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)) assay. Subsequent extensin crosslinking assays showed that CG5 can covalently crosslink authentic tomato P1 extensin and P3-type extensin analogs in vitro supporting our hypothesis that CG5 encodes a tomato EP. Copyright © 2014 Elsevier Ltd. All rights reserved.

Identification of the pI 4.6 extensin peroxidase from Lycopersicon esculentum using proteomics and reverse-genomics

PubMed Central

Dong, Wen; Kieliszewski, Marcia; Held, Michael A.

2014-01-01

The regulation of plant cell growth and early defense response involves the insolubilization of hydroxyproline-rich glycoproteins (HRGPs), such as extensin, in the primary cell wall. In tomato (Lycopersicon esculentum), insolublization occurs by the formation of tyrosyl-crosslinks catalyzed specifically by the pI 4.6 extensin peroxidase (EP). To date, neither the gene encoding EP nor the protein itself has been identified. Here, we’ve identified tomato EP candidates using both proteomic and bioinformatic approaches. Bioinformatic screening of the tomato genome yielded eight EP candidates, which contained a putative signal sequence and a predicted pI near 4.6. Biochemical fractionation of tomato culture media followed by proteomic detection further refined our list of EP candidates to three, with the lead candidate designated (CG5). To test for EP crosslinking activity, we cloned into a bacterial expression vector the CG5 open-reading frame from tomato cDNA. The CG5 was expressed in E. coli, fractionated from inclusion bodies, and folded in vitro. The peroxidase activity of CG5 was assayed and quantified by ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)) assay. Subsequent extensin crosslinking assays showed that CG5 can covalently crosslink authentic tomato P1 extensin and P3-type extensin analogs in vitro supporting our hypothesis that CG5 encodes a tomato EP. PMID:25446231

Different Bleeding Patterns with the Use of Levonorgestrel Intrauterine System: Are They Associated with Changes in Uterine Artery Blood Flow?

PubMed Central

Bastianelli, Carlo; Rapiti, Stefania; Bruno Vecchio, Roberta; Benagiano, Giuseppe

2014-01-01

Objective. Evaluate if different bleeding patterns associated with the use of the levonorgestrel intrauterine system (LNG-IUS) are associated with different uterine and endometrial vascularization patterns, as evidenced by ultrasound power Doppler analysis. Methodology. A longitudinal study, with each subject acting as its own control was conducted between January 2010 and December 2012. Healthy volunteers with a history of heavy but cyclic and regular menstrual cycles were enrolled in the study. Ultrasonographic examination was performed before and after six months of LNG-IUS placement: uterine volume, endometrial thickness, and subendometrial and myometrial Doppler blood flow patterns have been evaluated. Results. A total of 32 women were enrolled out of 186 initially screened. At six months of follow-up, all subjects showed a reduction in menstrual blood loss; for analysis, they were retrospectively divided into 3 groups: normal cycling women (Group I), amenorrheic women (Group II), and women with prolonged bleedings (Group III). Intergroup analysis documented a statistically significant difference in endometrial thickness among the three groups; in addition, mean pulsatility index (PI) and resistance index (RI) in the spiral arteries were significantly lower in Group I and Group III compared to Group II. This difference persisted also when comparing—within subjects of Group III—mean PI and RI mean values before and after insertion. Conclusions. The LNG-IUS not only altered endometrial thickness, but—in women with prolonged bleedings—also significantly changed uterine artery blood flow. Further studies are needed to confirm these results and enable gynecologists to properly counsel women, improving initial continuation rates. PMID:24868549

Individual Biometric Identification Using Multi-Cycle Electrocardiographic Waveform Patterns.

PubMed

Lee, Wonki; Kim, Seulgee; Kim, Daeeun

2018-03-28

The electrocardiogram (ECG) waveform conveys information regarding the electrical property of the heart. The patterns vary depending on the individual heart characteristics. ECG features can be potentially used for biometric recognition. This study presents a new method using the entire ECG waveform pattern for matching and demonstrates that the approach can potentially be employed for individual biometric identification. Multi-cycle ECG signals were assessed using an ECG measuring circuit, and three electrodes can be patched on the wrists or fingers for considering various measurements. For biometric identification, our-fold cross validation was used in the experiments for assessing how the results of a statistical analysis will generalize to an independent data set. Four different pattern matching algorithms, i.e., cosine similarity, cross correlation, city block distance, and Euclidean distances, were tested to compare the individual identification performances with a single channel of ECG signal (3-wire ECG). To evaluate the pattern matching for biometric identification, the ECG recordings for each subject were partitioned into training and test set. The suggested method obtained a maximum performance of 89.9% accuracy with two heartbeats of ECG signals measured on the wrist and 93.3% accuracy with three heartbeats for 55 subjects. The performance rate with ECG signals measured on the fingers improved up to 99.3% with two heartbeats and 100% with three heartbeats of signals for 20 subjects.

Analysis of enamel rod end patterns on tooth surface for personal identification--ameloglyphics.

PubMed

Manjunath, Krishnappa; Sivapathasundharam, Balasundharam; Saraswathi, Thillai R

2012-05-01

Ameloglyphics is the study of enamel rod end patterns on a tooth surface. Our aim was to study the in vivo analysis of enamel rod end patterns on tooth surfaces for personal identification. In this study, the maxillary left canine and 1st premolar of 30 men and 30 women were included. The cellulose acetate peel technique was used to record enamel rod endings on tooth surfaces. Photomicrographs of the acetate peel imprint were subjected to VeriFinger Standard SDK v5.0 software for obtaining enamel rod end patterns. All 120 enamel rod end patterns were subjected to visual analysis and biometric analysis. Biometric analysis revealed that the enamel rod end pattern is unique for each tooth in an individual. It shows both intra- and interindividual variation. Enamel rod end patterns were unique between the male and female subjects. Visual analysis showed that wavy branched subpattern was the predominant subpattern observed among examined teeth. Hence, ameloglyphics is a reliable technique for personal identification. © 2012 American Academy of Forensic Sciences.

Murine Polyomavirus Cell Surface Receptors Activate Distinct Signaling Pathways Required for Infection.

PubMed

O'Hara, Samantha D; Garcea, Robert L

2016-11-01

Virus binding to the cell surface triggers an array of host responses, including activation of specific signaling pathways that facilitate steps in virus entry. Using mouse polyomavirus (MuPyV), we identified host signaling pathways activated upon virus binding to mouse embryonic fibroblasts (MEFs). Pathways activated by MuPyV included the phosphatidylinositol 3-kinase (PI3K), FAK/SRC, and mitogen-activated protein kinase (MAPK) pathways. Gangliosides and α4-integrin are required receptors for MuPyV infection. MuPyV binding to both gangliosides and the α4-integrin receptors was required for activation of the PI3K pathway; however, either receptor interaction alone was sufficient for activation of the MAPK pathway. Using small-molecule inhibitors, we confirmed that the PI3K and FAK/SRC pathways were required for MuPyV infection, while the MAPK pathway was dispensable. Mechanistically, the PI3K pathway was required for MuPyV endocytosis, while the FAK/SRC pathway enabled trafficking of MuPyV along microtubules. Thus, MuPyV interactions with specific cell surface receptors facilitate activation of signaling pathways required for virus entry and trafficking. Understanding how different viruses manipulate cell signaling pathways through interactions with host receptors could lead to the identification of new therapeutic targets for viral infection. Virus binding to cell surface receptors initiates outside-in signaling that leads to virus endocytosis and subsequent virus trafficking. How different viruses manipulate cell signaling through interactions with host receptors remains unclear, and elucidation of the specific receptors and signaling pathways required for virus infection may lead to new therapeutic targets. In this study, we determined that gangliosides and α4-integrin mediate mouse polyomavirus (MuPyV) activation of host signaling pathways. Of these pathways, the PI3K and FAK/SRC pathways were required for MuPyV infection. Both the PI3K and FAK/SRC pathways have been implicated in human diseases, such as heart disease and cancer, and inhibitors directed against these pathways are currently being investigated as therapies. It is possible that these pathways play a role in human PyV infections and could be targeted to inhibit PyV infection in immunosuppressed patients. Copyright © 2016 O’Hara and Garcea.

Examining relations of entertainment with social interaction motives and team identification.

PubMed

Gau, Li-Shiue; Wann, Daniel L; James, Jeffrey D

2010-10-01

The goal was to investigate a potential causal pattern between the motives of sport spectators and team identification by using a cross-lagged panel design. Questionnaires were completed by 229 participants at the beginning and end of one NCAA (National Collegiate Athletic Association) college football season for 4 mo. in the USA. The questionnaire included three items for each motive (Social Interaction and Entertainment), three items measuring team identification, and demographic items. The relation of Entertainment at Time 1 to team identification at Time 2 was larger than the relation of team identification at Time 1 to Entertainment at Time 2. This suggests that the motivation of Entertainment may lead to the formation of team identification more than team identification leads to Entertainment. However, the motive of Social Interaction did not show the same pattern. As results of this study suggested some spectator sport motives might lead to identification with a team, the hypothesis that all motives would be the basis of team identification might not be correct.

Nurses' Behaviors and Visual Scanning Patterns May Reduce Patient Identification Errors

ERIC Educational Resources Information Center

Marquard, Jenna L.; Henneman, Philip L.; He, Ze; Jo, Junghee; Fisher, Donald L.; Henneman, Elizabeth A.

2011-01-01

Patient identification (ID) errors occurring during the medication administration process can be fatal. The aim of this study is to determine whether differences in nurses' behaviors and visual scanning patterns during the medication administration process influence their capacities to identify patient ID errors. Nurse participants (n = 20)…

Personological evaluation of Clance's Imposter Phenomenon Scale in a Korean sample.

PubMed

Chae, J H; Piedmont, R L; Estadt, B K; Wicks, R J

1995-12-01

The purpose of this study was both to determine if the Impostor Phenomenon (IP) can be reliably and validly assessed in a Korean context and if so, evaluate the construct within the context of Jungian typology and the 5-factor model of personality. A sample of 654 Korean men and women were selected from 4 major Korean cities and administered the Clance Impostor Phenomenon Scale (CIPS; Clance & Imes, 1978) along with the Myers-Briggs Type Indicator (MBTI, Form G; Myers & McCaulley, 1985) and NEO Personality Inventory-Revised (NEO-PI-R; Costa & McCrae, 1992). Results indicated that the CIPS was very reliable, and the pattern of correlates suggested impostors to be introverted types on the MBTI. Results with the NEO-PI-R showed impostors to be very high on neuroticism and low on conscientiousness. This pattern of correlates is similar to other performance-inhibiting constructs such as fear of success and fear of failure. It was argued that IP be construed more as a motivational style than as a distinct clinical syndrome. The IP seems to be less pervasive in Korea than America and these cross-cultural implications were discussed.

Monitoring Doppler patterns and clinical parameters may predict feeding tolerance in intrauterine growth-restricted infants.

PubMed

Bozzetti, Valentina; Paterlini, Giuseppe; Gazzolo, Diego; Van Bel, Frank; Visser, Gerard H A; Roncaglia, Nadia; Tagliabue, Paolo E

2013-11-01

To detect predictors of feeding tolerance in intrauterine growth restriction (IUGR) infants with or without brain-sparing effect (BS). We conducted a case-control study in 70 IUGR infants (35 IUGR with BS, matched for gestational age with 35 IUGR infants with no BS). BS was classified as pulsatility index (PI) ratio [umbilical artery (UAPI) to middle cerebral artery (MCAPI) (U/C ratio)] > 1. Clinical parameters of feeding tolerance - days to achieve full enteral feeding (FEF) - were compared between the IUGR with BS and IUGR without BS infants. Age at the start of minimal enteral feeding (MEF) was analysed. Achievement of FEF was significantly shorter in IUGR infants without BS than in IUGR with BS. IUGR with BS started MEF later than IUGR without BS infants. Significant correlation of MEF and FEF with UA PI, U/C ratio and CRIB score was found. Multiple linear regression analysis showed significant correlations with CRIB score and caffeine administration (MEF only), and sepsis (FEF only) and U/C ratio (for both). Impaired gut function can be early detected by monitoring Doppler patterns and clinical parameters. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Disinhibited social engagement in postinstitutionalized children: differentiating normal from atypical behavior.

PubMed

Lawler, Jamie M; Hostinar, Camelia E; Mliner, Shanna B; Gunnar, Megan R

2014-05-01

The most commonly reported socially aberrant behavior in postinstitutionalized (PI) children is disinhibited social engagement (DSE; also known as indiscriminate friendliness). There is no gold standard for measurement of this phenomenon nor agreement on how to differentiate it from normative behavior. We adopted a developmental psychopathology approach (Cicchetti, 1984) to study this phenomenon by comparing it to normative social development and by studying its patterns over time in 50 newly adopted PI children (16-36 months at adoption) compared with 41 children adopted early from foster care overseas and 47 nonadopted (NA) controls. Using coded behavioral observations of the child's interaction with an unfamiliar adult, atypical behaviors were differentiated from normative behaviors. Principal components analysis identified two dimensions of social disinhibition. The nonphysical social dimension (e.g., initiations, proximity) showed wide variation in NA children and is therefore considered a typical form of sociability. Displays of physical contact and intimacy were rare in NA children, suggesting that they represent an atypical pattern of behavior. Both adopted groups demonstrated more physical DSE behavior than NA children. There were no group differences on the nonphysical factor, and it increased over time in all groups. Implications for understanding the etiology of DSE and future directions are discussed.

Integrating microarray analysis and the soybean genome to understand the soybeans iron deficiency response

PubMed Central

2009-01-01

Background Soybeans grown in the upper Midwestern United States often suffer from iron deficiency chlorosis, which results in yield loss at the end of the season. To better understand the effect of iron availability on soybean yield, we identified genes in two near isogenic lines with changes in expression patterns when plants were grown in iron sufficient and iron deficient conditions. Results Transcriptional profiles of soybean (Glycine max, L. Merr) near isogenic lines Clark (PI548553, iron efficient) and IsoClark (PI547430, iron inefficient) grown under Fe-sufficient and Fe-limited conditions were analyzed and compared using the Affymetrix® GeneChip® Soybean Genome Array. There were 835 candidate genes in the Clark (PI548553) genotype and 200 candidate genes in the IsoClark (PI547430) genotype putatively involved in soybean's iron stress response. Of these candidate genes, fifty-eight genes in the Clark genotype were identified with a genetic location within known iron efficiency QTL and 21 in the IsoClark genotype. The arrays also identified 170 single feature polymorphisms (SFPs) specific to either Clark or IsoClark. A sliding window analysis of the microarray data and the 7X genome assembly coupled with an iterative model of the data showed the candidate genes are clustered in the genome. An analysis of 5' untranslated regions in the promoter of candidate genes identified 11 conserved motifs in 248 differentially expressed genes, all from the Clark genotype, representing 129 clusters identified earlier, confirming the cluster analysis results. Conclusion These analyses have identified the first genes with expression patterns that are affected by iron stress and are located within QTL specific to iron deficiency stress. The genetic location and promoter motif analysis results support the hypothesis that the differentially expressed genes are co-regulated. The combined results of all analyses lead us to postulate iron inefficiency in soybean is a result of a mutation in a transcription factor(s), which controls the expression of genes required in inducing an iron stress response. PMID:19678937

Diurnal variations of summer precipitation over the regions east to Tibetan Plateau

NASA Astrophysics Data System (ADS)

Wu, Yang; Huang, Anning; Huang, Danqing; Chen, Fei; Yang, Ben; Zhou, Yang; Fang, Dexian; Zhang, Lujun; Wen, Lijuan

2017-12-01

Based on the hourly gauge-satellite merged precipitation product with the horizontal resolution of 0.1° latitude/longitude during 2008-2014, diurnal variations of the summer precipitation amount (PA), frequency (PF), and intensity (PI) with different duration time over the regions east to Tibetan Plateau have been systematically revealed in this study. Results indicate that the eight typical precipitation diurnal patterns identified by the cluster analysis display pronounced regional features among the plateaus, basins, plains, hilly and coastal areas. The precipitation diurnal cycles are significantly affected by the sub-grid terrain fluctuations. The PA, PF and PI of the total rainfall show much more pronounced double diurnal peaks with the sub-grid topography standard deviation (SD) decreased. Meanwhile, the diurnal peaks of PA and PF (PI) strengthen (weaken) with the sub-grid topography SD enhanced. Over the elevated mountain ranges, southeastern hilly and coastal regions, the PA and PF diurnal patterns of the total rainfall generally show predominant late-afternoon peaks, which are closely associated with the short-duration (≤slant 3 h) rainfall. Along the Tibetan Plateau to its downstream, the diurnal peaks of PA, PF and PI for the total rainfall all exhibit obvious eastward phase time delay mainly due to the diurnal evolutions of long-duration (> 6 h) rainfall. However, the 4-6 h rainfall leads to the eastward phase time delay of the total rainfall along the Taihang Mountains to its downstream. Further mechanism analysis suggests that the midnight to morning diurnal evolution of the long-duration rainfall is closely associated with the diurnal variations of the upward branches of thermally driven mountain-plain solenoids and the water vapor transport associated with the accelerated nocturnal southwesterly winds. The late-afternoon peak of the short-duration PA over the southeastern hilly and coastal regions is ascribed to the strong local thermal convections due to the solar heating in afternoon, while the early-evening peak of the short-duration PA over the elevated mountain ranges is significantly contributed by the upward warm-moist wind from the surrounding low-lying basins or plains.

[Spatial distribution pattern and fractal analysis of Larix chinensis populations in Qinling Mountain].

PubMed

Guo, Hua; Wang, Xiaoan; Xiao, Yaping

2005-02-01

In this paper, the fractal characters of Larix chinensis populations in Qinling Mountain were studied by contiguous grid quadrate sampling method and by boxing-counting dimension and information dimension. The results showed that the high boxing-counting dimension (1.8087) and information dimension (1.7931) reflected a higher spatial occupational degree of L. chinensis populations. Judged by the dispersal index and Morisita's pattern index, L. chinensis populations clumped at three different age stages (0-25, 25-50 and over 50 years). From Greig-Smiths' mean variance analysis, the figure of pattern scale showed that L. chinensis populations clumped in 128 m2 and 512 m2, and the different age groups clumped in different scales. The pattern intensities decreased with increasing age, and tended to reduce with increasing area when detected by Kershaw's PI index. The spatial pattern characters of L. chinensis populations may be their responses to environmental factors.

Dalitz Plot Analyses of B- to D+ Pi- Pi-, B+ to Pi+ Pi- Pi+ and D(S)+ to Pi+ Pi- Pi+ at BaBar

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

Dong, Liaoyuan; /Iowa State U.

We report on the Dalitz plot analyses of B{sup -} {yields} D{sup +}{pi}{sup -}{pi}{sup -}, B{sup +} {yields} {pi}{sup +}{pi}{sup -}{pi}{sup +} and D{sub s}{sup +} {yields} {pi}{sup +}{pi}{sup -}{sup +}. The Dalitz plot method and the most recent BABAR results are discussed.

CO 2 Capture by Cold Membrane Operation with Actual Power Plant Flue Gas

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

Chaubey, Trapti; Kulkarni, Sudhir; Hasse, David

The main objective of the project was to develop a post-combustion CO 2 capture process based on the hybrid cold temperature membrane operation. The CO 2 in the flue gas from coal fired power plant is pre-concentrated to >60% CO 2 in the first stage membrane operation followed by further liquefaction of permeate stream to achieve >99% CO 2 purity. The aim of the project was based on DOE program goal of 90% CO 2 capture with >95% CO 2 purity from Pulverized Coal (PC) fired power plants with $40/tonne of carbon capture cost by 2025. The project moves themore » technology from TRL 4 to TRL 5. The project involved optimization of Air Liquide commercial 12” PI-1 bundle to improve the bundle productivity by >30% compared to the previous baseline (DE-FE0004278) using computational fluid dynamics (CFD) modeling and bundle testing with synthetic flue gas at 0.1 MWe bench scale skid located at Delaware Research and Technology Center (DRTC). In parallel, the next generation polyimide based novel PI-2 membrane was developed with 10 times CO 2 permeance compared to the commercial PI-1 membrane. The novel PI-2 membrane was scaled from mini-permeator to 1” permeator and 1” bundle for testing. Bundle development was conducted with a Development Spin Unit (DSU) installed at MEDAL. Air Liquide’s cold membrane technology was demonstrated with real coal fired flue gas at the National Carbon Capture Center (NCCC) with a 0.3 MWe field-test unit (FTU). The FTU was designed to incorporate testing of two PI-1 commercial membrane bundles (12” or 6” diameter) in parallel or series. A slip stream was sent to the next generation PI-2 membrane for testing with real flue gas. The system exceeded performance targets with stable PI-1 membrane operation for over 500 hours of single bundle, steady state testing. The 12” PI-1 bundle exceeded the productivity target by achieving ~600 Nm3/hr, where the target was set at ~455 Nm3/hr at 90% capture rate. The cost of 90% CO 2 capture from a 550 MWe net coal power plant was estimated between 40 and $45/tonne. A 6” PI-1 bundle exhibited superior bundle performance compared to the 12” PI-1 bundle. However, the carbon capture cost was not lower with the 6” PI-1 bundle due to the higher bundle installed cost. A 1” PI-1 bundle was tested to compare bundles with different length / diameter ratios. This bundle exhibited the lowest performance due to the different fiber winding pattern and increased bundle non-ideality. Several long-term and parametric tests were conducted with 3,200 hours of total run-time at NCCC. Finally, the new PI-2 membrane fiber was tested at a small scale (1” modules) in real flue gas and exhibited up to 10 times the CO 2 permeance and slightly lower CO 2/N 2 selectivity as the commercial PI-1 fiber. This corresponded to a projected 4 - 5 times increase in the productivity per bundle and a potential cost reduction of $3/tonne for CO2 capture, as compared with PI-1. An analytical campaign was conducted to trace different impurities such as NOx, mercury, Arsenic, Selenium in gas and liquid samples through the carbon capture system. An Environmental, Health and Safety (EH&S) analysis was completed to estimate emissions from a 550 MWe net power plant with carbon capture using cold membrane. A preliminary design and cost analysis was completed for 550 tpd (~25 MWe) plant to assess the capital investment and carbon capture cost for PI-1 and PI-2 membrane solutions from coal fired flue gas. A comparison was made with an amine based solution with significant cost advantage for the membrane at this scale. Additional preliminary design and cost analysis was completed between coal, natural gas and SMR flue gas for carbon capture at 550 tpd (~25 MWe) plant.« less

Investigation of Novel Molecular Targets for Pleckstrin Homology (PH) Domains Found in Oncogenes Implicated in Breast Cancer

DTIC Science & Technology

2007-03-01

protein’s PI3K-dependent roles as a positive regulator of IL- 2 gene induction in T cells (Deckert et al, 1998), NK cell-mediated cytotoxicity...82. Fournier, MV, Guimaraes da Costa, F, Paschoal, ME, Ronco, LV, Carvalho, MG, and Pardee, AB. (1999) Identification of a gene encoding a human...Ipl and Tih1. J Biol Chem. 277(51), 49935-44. Scanlan, MJ, Gout , I, Gordon, CM, Williamson, B, Stockert, E, Gure, AO, Jager, D, Chen, YT, Mackay, A

Identification and Targeting of Upstream Tyrosine Kinases Mediating PI3 Kinase Activation in PTEN Deficient Prostate Cancer

DTIC Science & Technology

2011-06-01

tyrosine phosphorylated proteins, but they were not recognized by an anti-pYxxM motif antibody and were not found in PTEN deficient PC3 PCa cells. LC/MS/MS...immunoblotted the p85 immunoprecipitates with a pYxxM motif specific antibody . This antibody weakly detected several discrete p85 associated proteins...anti-pYxxM antibody after EGF or heregulin-1 stimulation, with the band after heregulin- 1 being consistent with ErbB3 (which contains 6 pYxxM motifs

Context Dependence of Protein Misfolding and Structural Strains in Neurodegenerative Diseases

PubMed Central

Mehta, Anil K.; Rosen, Rebecca F.; Childers, W. Seth; Gehman, John D.; Walker, Lary C.; Lynn, David G.

2014-01-01

Vast arrays of structural forms are accessible to simple amyloid peptides and environmental conditions can direct assembly into single phases. These insights are now being applied to the aggregation of the Aβ peptide of Alzheimer’s disease (AD) and the identification of causative phases. We extend use of the imaging agent Pittsburgh compound B (PiB) to discriminate among Aβ phases and begin to define conditions of relevance to the disease state. And we specifically highlight the development of methods for defining the structures of these more complex phases. PMID:23893572

Contraceptive efficacy and safety of estradiol valerate/dienogest in a healthy female population: a multicenter, open-label, uncontrolled Phase III study.

PubMed

Yu, Qi; Huang, Zirong; Ren, Mulan; Chang, Qing; Zhang, Zhongqi; Parke, Susanne

2018-01-01

To investigate the efficacy and safety of a combined oral contraceptive containing estradiol valerate and dienogest (EV/DNG) in healthy Asian women. In this multicenter Phase III study, women received oral EV/DNG in a 28-day regimen for 13 cycles. The primary efficacy endpoint was the number of unintended pregnancies, measured by the Pearl Index (PI); secondary efficacy endpoints included bleeding pattern and cycle control parameters. Adverse events were monitored during the study and overall satisfaction with treatment was determined on completion of the study. A total of 954 Asian women (97.7% of subjects assigned to study medication; mean age 33.4 years) were treated. Five pregnancies were reported during EV/DNG treatment over 796.34 relevant woman-years of exposure, giving an unadjusted PI of 0.63 and a cumulative failure rate of 0.0049; 3 pregnancies during EV/DNG treatment over 760.35 relevant woman-years of exposure gave an adjusted PI of 0.39. The bleeding pattern improved during the reporting periods within the study. The proportion of women who experienced withdrawal bleeding decreased with treatment (84.9% of women during Cycle 1 vs 79.3% in Cycle 13), and the mean length of withdrawal bleeding decreased with treatment (4.2 vs 3.4 days). The number and maximum length of intracyclic bleeding/spotting episodes also decreased with EV/DNG. EV/DNG was well tolerated, and 92% of women included in the study were very satisfied or somewhat satisfied with EV/DNG. EV/DNG showed high contraceptive efficacy, was well tolerated in Asian women, and may be effectively used in this population. ClinicalTrials.gov identifier: NCT01638910.

Vibrational and chiroptical spectroscopic characterization of gamma-turn model cyclic tetrapeptides containing two beta-Ala residues.

PubMed

Vass, Elemér; Majer, Zsuzsa; Kohalmy, Krisztina; Hollósi, Miklós

2010-08-01

The optical spectroscopic characterization of gamma-turns in solution is uncertain and their distinction from beta-turns is often difficult. This work reports systematic ECD and vibrational circular dichroism (VCD) spectroscopic studies on gamma-turn model cyclic tetrapeptides cyclo(Ala-beta-Ala-Pro-beta-Ala) (1), cyclo(Pro-beta-Ala-Pro-beta-Ala) (2) and cyclo(Ala-beta-Ala-Ala-beta-Ala) (3). Conformational analysis performed at the 6-31G(d)/B3LYP level of theory using an adequate PCM solvent model predicted one predominant conformer for 1-3, featuring two inverse gamma-turns. The ECD spectra in ACN of 1 and 2 are characterized by a negative n-->pi* band near 230 nm and a positive pi-->pi* band below 200 nm with a long wavelength shoulder. The ECD spectra in TFE of 1-3 show similar spectra with blue-shifted bands. The VCD spectra in ACN-d(3) of 1 and 2 show a +/-/+/- amide I sign pattern resulting from four uncoupled vibrations in the case of 1 and a sequence of two positive couplets in the case of 2. A -/+/+/- amide I VCD pattern was measured for 3 in TFE-d(2). All three peptides give a positive couplet or couplet-like feature (+/-) in the amide II region. VCD spectroscopy, in agreement with theoretical calculations revealed that low frequency amide I vibrations (at approximately 1630 cm(-1) or below) are indicative of a C(7) H-bonded inverse gamma-turns with Pro in position 2, while gamma-turns encompassing Ala absorb at higher frequency (above 1645 cm(-1)). Copyright 2010 Wiley-Liss, Inc.

Dynamics of virus shedding and antibody responses in influenza A virus-infected feral swine.

PubMed

Sun, Hailiang; Cunningham, Fred L; Harris, Jillian; Xu, Yifei; Long, Li-Ping; Hanson-Dorr, Katie; Baroch, John A; Fioranelli, Paul; Lutman, Mark W; Li, Tao; Pedersen, Kerri; Schmit, Brandon S; Cooley, Jim; Lin, Xiaoxu; Jarman, Richard G; DeLiberto, Thomas J; Wan, Xiu-Feng

2015-09-01

Given their free-ranging habits, feral swine could serve as reservoirs or spatially dynamic 'mixing vessels' for influenza A virus (IAV). To better understand virus shedding patterns and antibody response dynamics in the context of IAV surveillance amongst feral swine, we used IAV of feral swine origin to perform infection experiments. The virus was highly infectious and transmissible in feral swine, and virus shedding patterns and antibody response dynamics were similar to those in domestic swine. In the virus-inoculated and sentinel groups, virus shedding lasted ≤ 6 and ≤ 9 days, respectively. Antibody titres in inoculated swine peaked at 1 : 840 on day 11 post-inoculation (p.i.), remained there until 21 days p.i. and dropped to < 1 : 220 at 42 days p.i. Genomic sequencing identified changes in wildtype (WT) viruses and isolates from sentinel swine, most notably an amino acid divergence in nucleoprotein position 473. Using data from cell culture as a benchmark, sensitivity and specificity of a matrix gene-based quantitative reverse transcription-PCR method using nasal swab samples for detection of IAV in feral swine were 78.9 and 78.1 %, respectively. Using data from haemagglutination inhibition assays as a benchmark, sensitivity and specificity of an ELISA for detection of IAV-specific antibody were 95.4 and 95.0 %, respectively. Serological surveillance from 2009 to 2014 showed that ∼7.58 % of feral swine in the USA were positive for IAV. Our findings confirm the susceptibility of IAV infection and the high transmission ability of IAV amongst feral swine, and also suggest the need for continued surveillance of IAVs in feral swine populations.

Frequency and patterns of protease gene resistance mutations in HIV-infected patients treated with lopinavir/ritonavir as their first protease inhibitor.

PubMed

Barber, Tristan J; Harrison, Linda; Asboe, David; Williams, Ian; Kirk, Stuart; Gilson, Richard; Bansi, Loveleen; Pillay, Deenan; Dunn, David

2012-04-01

Selection of protease mutations on antiretroviral therapy (ART) including a ritonavir-boosted protease inhibitor (PI) has been reported infrequently. Scarce data exist from long-term cohorts on resistance incidence or mutational patterns emerging to different PIs. We studied UK patients receiving lopinavir/ritonavir as their first PI, either while naive to ART or having previously received non-PI-based ART. Virological failure was defined as viral load ≥ 400 copies/mL after previous suppression <400 copies/mL, or failure to achieve <400 copies/mL during the first 6 months. pol sequences whilst failing lopinavir or within 30 days after stopping were analysed. Major and minor mutations (IAS-USA 2008-after exclusion of polymorphisms) were considered. Predicted susceptibility was determined using the Stanford HIVdb algorithm. Three thousand and fifty-six patients were followed for a median (IQR) of 14 (6-30) months, of whom 811 (27%) experienced virological failure. Of these, resistance test results were available on 291 (36%). One or more protease mutations were detected in 32 (11%) patients; the most frequent were I54V (n = 12), M46I (n = 11), V82A (n = 7) and L76V (n = 3). No association with viral subtype was evident. Many patients retained virus predicted to be susceptible to lopinavir (14, 44%), tipranavir (26, 81%) and darunavir (27, 84%). This study reflects the experience of patients in routine care. Selection of protease gene mutations by lopinavir/ritonavir occurred at a much higher rate than in clinical trials. The mutations observed showed only partial overlap with those previously identified by structural chemistry models, serial cell culture passage and genotype-phenotype analyses. There remained a low degree of predicted cross-resistance to other widely used PIs.

Dynamics of virus shedding and antibody responses in influenza A virus-infected feral swine

PubMed Central

Sun, Hailiang; Cunningham, Fred L.; Harris, Jillian; Xu, Yifei; Long, Li-Ping; Hanson-Dorr, Katie; Baroch, John A.; Fioranelli, Paul; Lutman, Mark W.; Li, Tao; Pedersen, Kerri; Schmit, Brandon S.; Cooley, Jim; Lin, Xiaoxu; Jarman, Richard G.; DeLiberto, Thomas J.

2015-01-01

Given their free-ranging habits, feral swine could serve as reservoirs or spatially dynamic ‘mixing vessels’ for influenza A virus (IAV). To better understand virus shedding patterns and antibody response dynamics in the context of IAV surveillance amongst feral swine, we used IAV of feral swine origin to perform infection experiments. The virus was highly infectious and transmissible in feral swine, and virus shedding patterns and antibody response dynamics were similar to those in domestic swine. In the virus-inoculated and sentinel groups, virus shedding lasted ≤ 6 and ≤ 9 days, respectively. Antibody titres in inoculated swine peaked at 1 : 840 on day 11 post-inoculation (p.i.), remained there until 21 days p.i. and dropped to < 1 : 220 at 42 days p.i. Genomic sequencing identified changes in wildtype (WT) viruses and isolates from sentinel swine, most notably an amino acid divergence in nucleoprotein position 473. Using data from cell culture as a benchmark, sensitivity and specificity of a matrix gene-based quantitative reverse transcription-PCR method using nasal swab samples for detection of IAV in feral swine were 78.9 and 78.1 %, respectively. Using data from haemagglutination inhibition assays as a benchmark, sensitivity and specificity of an ELISA for detection of IAV-specific antibody were 95.4 and 95.0 %, respectively. Serological surveillance from 2009 to 2014 showed that ∼7.58 % of feral swine in the USA were positive for IAV. Our findings confirm the susceptibility of IAV infection and the high transmission ability of IAV amongst feral swine, and also suggest the need for continued surveillance of IAVs in feral swine populations. PMID:26297148

Current pattern of Ponderal Indices of term small-for-gestational age in a population of Nigerian babies

PubMed Central

2013-01-01

Background Small-for-gestational age (SGA) newborns constitute a special group of neonates who may have suffered varying degrees of intrauterine insults and deprivation. Variations in birth weight, length and Ponderal Index (PI) depend on the type and degree of intrauterine insults the babies were exposed to. The objective of the study was to determine the current prevalence of term SGA births in a Nigerian Tertiary Hospital and the current pattern of Ponderal Indices among term SGA in a population of Nigerian babies. Methods Subjects comprised of consecutive term singleton mother-baby pairs in the first 24 hours of life. It was a cross sectional study. The anthropometric parameters of each baby were recorded and the PI was also determined. Results Out of 1,052 live births during the study period (September to December, 2009), 825 were term, singleton babies. Five hundred and eight-one babies (70.4%) fall into the upper socio-economic classes 1 and II, 193 (23.4%) in the middle class and 51 (6.2%) were of the lower classes IV and V. None of the mothers indicated ingestion of alcohol or smoking of cigarette. Fifty-nine babies (7.2%) were small-for gestational age (SGA). Of the 59 SGA subjects, 26 (44.1%) were symmetrical SGA while 33 (55.9%) were asymmetrical SGA. There was no significant sex or socioeconomic predilection for either symmetrical or asymmetrical growth (p = 0.59, 0.73 respectively). Conclusion The findings showed that proportionality in SGA fetuses is a continuum, with the PI depending on the duration of intrauterine insult and the extent of its effects on weight and length before delivery. PMID:23875695

Summary of tracking and identification methods

NASA Astrophysics Data System (ADS)

Blasch, Erik; Yang, Chun; Kadar, Ivan

2014-06-01

Over the last two decades, many solutions have arisen to combine target tracking estimation with classification methods. Target tracking includes developments from linear to non-linear and Gaussian to non-Gaussian processing. Pattern recognition includes detection, classification, recognition, and identification methods. Integrating tracking and pattern recognition has resulted in numerous approaches and this paper seeks to organize the various approaches. We discuss the terminology so as to have a common framework for various standards such as the NATO STANAG 4162 - Identification Data Combining Process. In a use case, we provide a comparative example highlighting that location information (as an example) with additional mission objectives from geographical, human, social, cultural, and behavioral modeling is needed to determine identification as classification alone does not allow determining identification or intent.

Frontal sinus recognition for human identification

NASA Astrophysics Data System (ADS)

Falguera, Juan Rogelio; Falguera, Fernanda Pereira Sartori; Marana, Aparecido Nilceu

2008-03-01

Many methods based on biometrics such as fingerprint, face, iris, and retina have been proposed for person identification. However, for deceased individuals, such biometric measurements are not available. In such cases, parts of the human skeleton can be used for identification, such as dental records, thorax, vertebrae, shoulder, and frontal sinus. It has been established in prior investigations that the radiographic pattern of frontal sinus is highly variable and unique for every individual. This has stimulated the proposition of measurements of the frontal sinus pattern, obtained from x-ray films, for skeletal identification. This paper presents a frontal sinus recognition method for human identification based on Image Foresting Transform and shape context. Experimental results (ERR = 5,82%) have shown the effectiveness of the proposed method.

Molecular self-assembly approaches for supramolecular electronic and organic electronic devices

NASA Astrophysics Data System (ADS)

Yip, Hin-Lap

Molecular self-assembly represents an efficient bottom-up strategy to generate structurally well-defined aggregates of semiconducting pi-conjugated materials. The capability of tuning the chemical structures, intermolecular interactions and nanostructures through molecular engineering and novel materials processing renders it possible to tailor a large number of unprecedented properties such as charge transport, energy transfer and light harvesting. This approach does not only benefit traditional electronic devices based on bulk materials, but also generate a new research area so called "supramolecular electronics" in which electronic devices are built up with individual supramolecular nanostructures with size in the sub-hundred nanometers range. My work combined molecular self-assembly together with several novel materials processing techniques to control the nucleation and growth of organic semiconducting nanostructures from different type of pi-conjugated materials. By tailoring the interactions between the molecules using hydrogen bonds and pi-pi stacking, semiconducting nanoplatelets and nanowires with tunable sizes can be fabricated in solution. These supramolecular nanostructures were further patterned and aligned on solid substrates through printing and chemical templating methods. The capability to control the different hierarchies of organization on surface provides an important platform to study their structural-induced electronic properties. In addition to using molecular self-assembly to create different organic nanostructures, functional self-assembled monolayer (SAM) formed by spontaneous chemisorption on surfaces was used to tune the interfacial property in organic solar cells. Devices showed dramatically improved performance when appropriate SAMs were applied to optimize the contact property for efficiency charge collection.

The effect of early deprivation on executive attention in middle childhood.

PubMed

Loman, Michelle M; Johnson, Anna E; Westerlund, Alissa; Pollak, Seth D; Nelson, Charles A; Gunnar, Megan R

2013-01-01

Children reared in deprived environments, such as institutions for the care of orphaned or abandoned children, are at increased risk for attention and behavior regulation difficulties. This study examined the neurobehavioral correlates of executive attention in post institutionalized (PI) children. The performance and event-related potentials (ERPs) of 10- and 11-year-old internationally adopted PI children on two executive attention tasks, go/no-go and Flanker, were compared with two groups: children internationally adopted early from foster care (PF) and nonadopted children (NA). Behavioral measures suggested problems with sustained attention, with PIs performing more poorly on go trials and not on no-go trials of the go/no-go and made more errors on both congruent and incongruent trials on the Flanker. ERPs suggested differences in inhibitory control and error monitoring, as PIs had smaller N2 amplitude on go/no-go and smaller error-related negativity on Flanker. This pattern of results raises questions regarding the nature of attention difficulties for PI children. The behavioral errors are not specific to executive attention and instead likely reflect difficulties in overall sustained attention. The ERP results are consistent with neural activity related to deficits in inhibitory control (N2) and error monitoring (error-related negativity). Questions emerge regarding the similarity of attention regulatory difficulties in PIs to those experienced by non-PI children with ADHD. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

Changes in nerve conduction and Pi/PCr ratio during denervation-reinnervation of the gastrocsoleus muscles of rats

NASA Technical Reports Server (NTRS)

Lai, K. S.; Jaweed, M. M.; Seestead, R.; Herbison, G. J.; Ditunno, J. F. Jr; McCully, K.; Chance, B.

1992-01-01

The purpose of this investigation was to study the changes in nerve conduction and phosphate metabolites of the gastrocsoleus muscles of rats during denervation-reinnervation. Sixteen male Sprague-Dawley rats underwent unilateral crush-denervation of the left sciatic nerves at the sciatic notch. Six rats were used for measurement of motor conduction latency and action potential amplitude of the gastrocsoleus muscle by stimulating the sciatic nerve at one, two and eight weeks after nerve crush. The other ten rats were designated for evaluation of the ratio of inorganic phosphorous (Pi) to phosphocreatine (PCr) by a 31P-phosphoenergetic spectrometer at two weeks and eight weeks after nerve crush. None of the sciatic nerves showed conduction to the gastrocsoleus at one or two weeks after nerve crush. At eight weeks postcrush, the motor conduction latency returned to within normal limits, whereas the action potential amplitude was only 55% of the normal. For the eight-week period of study, the Pi/PCr ratio of the normal control muscles ranged between 0.09 +/- 0.02 and 0.11 +/- 0.02 (mean +/- SD). The denervated muscles showed an increase of Pi/PCr ratio by 54% at two weeks postcrush, compared to the respective contralateral control sides. The ratios returned to the normal value by eight weeks postcrush. In summary, these data suggested that the metabolic recovery of the crush-denervated muscle followed the same pattern as the parameters of nerve conduction.

Symbolic dynamic filtering and language measure for behavior identification of mobile robots.

PubMed

Mallapragada, Goutham; Ray, Asok; Jin, Xin

2012-06-01

This paper presents a procedure for behavior identification of mobile robots, which requires limited or no domain knowledge of the underlying process. While the features of robot behavior are extracted by symbolic dynamic filtering of the observed time series, the behavior patterns are classified based on language measure theory. The behavior identification procedure has been experimentally validated on a networked robotic test bed by comparison with commonly used tools, namely, principal component analysis for feature extraction and Bayesian risk analysis for pattern classification.

Observation of {eta}{sup '} Decays to {pi}{sup +}{pi}{sup -}{pi}{sup 0} and {pi}{sup +}{pi}{sup -}e{sup +}e{sup -}

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

Naik, P.; Rademacker, J.; Asner, D. M.

Using {psi}(2S){yields}{pi}{sup +}{pi}{sup -}J/{psi}, J/{psi}{yields}{gamma}{eta}{sup '} events acquired with the CLEO-c detector at the CESR e{sup +}e{sup -} collider, we make the first observations of the decays {eta}{sup '}{yields}{pi}{sup +}{pi}{sup -}{pi}{sup 0} and {eta}{sup '}{yields}{pi}{sup +}{pi}{sup -}e{sup +}e{sup -}, measuring absolute branching fractions (37{sub -9}{sup +11}{+-}4)x10{sup -4} and (25{sub -9}{sup +12}{+-}5)x10{sup -4}, respectively. For {eta}{sup '}{yields}{pi}{sup +}{pi}{sup -}{pi}{sup 0}, this result probes the mechanism of isospin violation and the roles of {pi}{sup 0}/{eta}/{eta}{sup '}-mixing and final state rescattering in strong decays. We also set upper limits on branching fractions for {eta}{sup '} decays to {pi}{sup +}{pi}{sup -}{mu}{sup +}{mu}{sup -}, 2({pi}{supmore » +}{pi}{sup -}), {pi}{sup +}{pi}{sup -}2{pi}{sup 0}, 2({pi}{sup +}{pi}{sup -}){pi}{sup 0}, 3({pi}{sup +}{pi}{sup -}), and invisible final states.« less

Direct mapping of symbolic DNA sequence into frequency domain in global repeat map algorithm

PubMed Central

Glunčić, Matko; Paar, Vladimir

2013-01-01

The main feature of global repeat map (GRM) algorithm (www.hazu.hr/grm/software/win/grm2012.exe) is its ability to identify a broad variety of repeats of unbounded length that can be arbitrarily distant in sequences as large as human chromosomes. The efficacy is due to the use of complete set of a K-string ensemble which enables a new method of direct mapping of symbolic DNA sequence into frequency domain, with straightforward identification of repeats as peaks in GRM diagram. In this way, we obtain very fast, efficient and highly automatized repeat finding tool. The method is robust to substitutions and insertions/deletions, as well as to various complexities of the sequence pattern. We present several case studies of GRM use, in order to illustrate its capabilities: identification of α-satellite tandem repeats and higher order repeats (HORs), identification of Alu dispersed repeats and of Alu tandems, identification of Period 3 pattern in exons, implementation of ‘magnifying glass’ effect, identification of complex HOR pattern, identification of inter-tandem transitional dispersed repeat sequences and identification of long segmental duplications. GRM algorithm is convenient for use, in particular, in cases of large repeat units, of highly mutated and/or complex repeats, and of global repeat maps for large genomic sequences (chromosomes and genomes). PMID:22977183

New measurements of Cabibbo-suppressed decays of mesons with the CLEO-c detector.

PubMed

Rubin, P; Cawlfield, C; Eisenstein, B I; Karliner, I; Kim, D; Lowrey, N; Naik, P; Sedlack, C; Selen, M; White, E J; Wiss, J; Shepherd, M R; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Gong, D T; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Smith, A; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Zweber, P; Ernst, J; Severini, H; Dytman, S A; Love, W; Mehrabyan, S; Savinov, V; Aquines, O; Li, Z; Lopez, A; Mendez, H; Ramirez, J; Xin, B; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shipsey, I P J; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Napolitano, J; He, Q; Insler, J; Muramatsu, H; Park, C S; Thorndike, E H; Coan, T E; Gao, Y S; Liu, F; Stroynowski, R; Artuso, M; Blusk, S; Butt, J; Li, J; Menaa, N; Mountain, R; Nisar, S; Randrianarivony, K; Redjimi, R; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Zhang, K; Csorna, S E; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Asner, D M; Edwards, K W; Briere, R A; Brock, I; Chen, J; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Adam, N E; Alexander, J P; Berkelman, K; Cassel, D G; Duboscq, J E; Ecklund, K M; Ehrlich, R; Fields, L; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Meyer, T O; Onyisi, P U E; Patterson, J R; Peterson, D; Phillips, E A; Pivarski, J; Riley, D; Ryd, A; Sadoff, A J; Schwarthoff, H; Shi, X; Stroiney, S; Sun, W M; Wilksen, T; Weinberger, M; Athar, S B; Avery, P; Breva-Newell, L; Patel, R; Potlia, V; Stoeck, H; Yelton, J

2006-03-03

Using of data collected with the CLEO-c detector, we report on first observations and measurements of Cabibbo-suppressed decays of D mesons in the following six decay modes: pi+ pi- pi0 pi0, pi+ pi+ pi- pi- pi0, pi+ pi0 pi0, pi+ pi+ pi- pi0, eta pi0, and omega pi+ pi-. Improved branching fraction measurements in eight other multipion decay modes are also presented. The measured D --> pi pi rates allow us to extract the ratio of isospin amplitudes A(DeltaI = (3/2) / A(DeltaI = (1/2)) = 0.420 +/- 0.014(stat) +/- 0.016(syst) and the strong phase shift of delta1 = (86.4 +/- 2.8 +/- 3.3) degrees, which is quite large and now more precisely determined.

Pattern identification in time-course gene expression data with the CoGAPS matrix factorization.

PubMed

Fertig, Elana J; Stein-O'Brien, Genevieve; Jaffe, Andrew; Colantuoni, Carlo

2014-01-01

Patterns in time-course gene expression data can represent the biological processes that are active over the measured time period. However, the orthogonality constraint in standard pattern-finding algorithms, including notably principal components analysis (PCA), confounds expression changes resulting from simultaneous, non-orthogonal biological processes. Previously, we have shown that Markov chain Monte Carlo nonnegative matrix factorization algorithms are particularly adept at distinguishing such concurrent patterns. One such matrix factorization is implemented in the software package CoGAPS. We describe the application of this software and several technical considerations for identification of age-related patterns in a public, prefrontal cortex gene expression dataset.

Dynamical coupled-channels study of pi N --> pi pi N reactions

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

Kamano, Hiroyuki; Julia Diaz, Bruno; Lee, Tsung-Shung

2009-01-01

As a step toward performing a complete coupled-channels analysis of the world data of pi N, gamma^* N --> pi N, eta N, pi pi N reactions, the pi N --> pi pi N reactions are investigated starting with the dynamical coupled-channels model developed in Phys. Rev. C76, 065201 (2007). The channels included are pi N, eta N, and pi pi N which has pi Delta, rho N, and sigma N resonant components. The non-resonant amplitudes are generated from solving a set of coupled-channels equations with the meson-baryon potentials defined by effective Lagrangians. The resonant amplitudes are generated from 16more » bare excited nucleon (N^*) states which are dressed by the non-resonant interactions as constrained by the unitarity condition. The available total cross section data of pi^+ p --> pi^+ pi^+ n, pi^+ pi^0 and pi^- p --> pi^+ pi^- n, pi^- pi^0 n, pi^0 pi^0 n can be reproduced to a very large extent both in magnitudes and energy-dependence. Possible improvements of the model are investigated, in p« less

Alzheimer disease identification using amyloid imaging and reserve variables

PubMed Central

Roe, C.M.; Mintun, M.A.; Ghoshal, N.; Williams, M.M.; Grant, E.A.; Marcus, D.S.; Morris, J.C.

2010-01-01

Objective: Several factors may influence the relationship between Alzheimer disease (AD) lesions and the expression of dementia, including those related to brain and cognitive reserve. Other factors may confound the association between AD pathology and dementia. We tested whether factors thought to influence the association of AD pathology and dementia help to accurately identify dementia of the Alzheimer type (DAT) when considered together with amyloid imaging. Methods: Participants with normal cognition (n = 180) and with DAT (n = 25), aged 50 years or older, took part in clinical, neurologic, and psychometric assessments. PET with the Pittsburgh compound B (PiB) tracer was used to measure brain amyloid, yielding a mean cortical binding potential (MCBP) reflecting PiB uptake. Logistic regression was used to generate receiver operating characteristic curves, and the areas under those curves (AUC), to compare the predictive accuracy of using MCBP alone vs MCBP together with other variables selected using a stepwise selection procedure to identify participants with DAT vs normal cognition. Results: The AUC resulting from MCBP alone was 0.84 (95% confidence interval [CI] = 0.73–0.94; cross-validated AUC = 0.80, 95% CI = 0.68–0.92). The AUC for the predictive equation generated by a stepwise model including education, normalized whole brain volume, physical health rating, gender, and use of medications that may interfere with cognition was 0.94 (95% CI = 0.90–0.98; cross-validated AUC = 0.91, 95% CI = 0.85–0.96), an improvement (p = 0.025) over that yielded using MCBP alone. Conclusion: Results suggest that factors reported to influence associations between AD pathology and dementia can improve the predictive accuracy of amyloid imaging for the identification of symptomatic AD. GLOSSARY A β = amyloid-β; AD = Alzheimer disease; AUC = area under receiver operating characteristic curve; BP = binding potential; CDR = Clinical Dementia Rating; CI = confidence interval; DAT = dementia of the Alzheimer type; DV = distribution volume; MCBP = mean cortical binding potential; nWBV = normalized whole brain volume; OR = odds ratio; PiB = Pittsburgh compound B; ROC = receiver operating characteristic curve; ROI = region of interest. PMID:20603484

Activation of phosphatidylinositol-3 kinase by nerve growth factor involves indirect coupling of the trk proto-oncogene with src homology 2 domains.

PubMed

Ohmichi, M; Decker, S J; Saltiel, A R

1992-10-01

Growth factor receptor tyrosine kinases can form stable associations with intracellular proteins that contain src homology (SH) 2 domains, including the p85 regulatory subunit of phosphatidylinositol (PI)-3 kinase. The activation of this enzyme by growth factors is evaluated in PC12 pheochromocytoma cells and NIH 3T3 fibroblasts expressing the pp140c-trk nerve growth factor (NGF) receptor (3T3-c-trk). NGF causes the rapid stimulation of PI-3 kinase activity detected in anti-phosphotyrosine, but not in anti-trk, immunoprecipitates. This effect coincides with the tyrosine phosphorylation of two proteins, with molecular masses of of 100 kd and 110 kd, that coimmunoprecipitate with p85. Similar phosphorylation patterns are induced when an immobilized fusion protein containing the amino-terminal SH2 domain of p85 is used to precipitate tyrosine-phosphorylated proteins. Thus, although NGF produces the rapid activation of PI-3 kinase through a mechanism that involves tyrosine phosphorylation, there is no evidence for tyrosine phosphorylation of p85, or for its ligand-dependent association with the NGF receptor. Perhaps another phosphoprotein may link the NGF receptor to this enzyme.

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

Lazaris, Andreas; Hwang, Kristy S.; Goukasian, Naira

Objective: We investigated the association between apoE protein plasma levels and brain amyloidosis and the effect of the top 10 Alzheimer disease (AD) risk genes on this association. Methods: Our dataset consisted of 18 AD, 52 mild cognitive impairment, and 3 cognitively normal Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) participants with available [ 11C]-Pittsburgh compound B (PiB) and peripheral blood protein data. We used cortical pattern matching to study associations between plasma apoE and cortical PiB binding and the effect of carrier status for the top 10 AD risk genes. Results: Low plasma apoE was significantly associated with high PiBmore » SUVR, except in the sensorimotor and entorhinal cortex. For BIN1 rs744373, the association was observed only in minor allele carriers. For CD2AP rs9349407 and CR1 rs3818361, the association was preserved only in minor allele noncarriers. We did not find evidence for modulation by CLU, PICALM, ABCA7, BIN1, and MS4A6A. Conclusions: Our data show that BIN1 rs744373, CD2AP rs9349407, and CR1 rs3818361 genotypes modulate the association between apoE protein plasma levels and brain amyloidosis, implying a potential epigenetic/downstream interaction.« less

Time course of the MAPK and PI3-kinase response within 24 h of skeletal muscle overload

NASA Technical Reports Server (NTRS)

Carlson, C. J.; Fan, Z.; Gordon, S. E.; Booth, F. W.

2001-01-01

Knowledge of the molecular mechanisms by which skeletal muscle hypertrophies in response to increased mechanical loading may lead to the discovery of novel treatment strategies for muscle wasting and frailty. To gain insight into potential early signaling mechanisms associated with skeletal muscle hypertrophy, the temporal pattern of mitogen-activated protein kinase (MAPK) phosphorylation and phosphatidylinositol 3-kinase (PI3-kinase) activity during the first 24 h of muscle overload was determined in the rat slow-twitch soleus and fast-twitch plantaris muscles after ablation of the gastrocnemius muscle. p38alpha MAPK phosphorylation was elevated for the entire 24-h overload period in both muscles. In contrast, Erk 2 and p54 JNK phosphorylation were transiently increased by overload, returning to the levels of sham-operated controls by 24 h. PI3-kinase activity was increased by muscle overload only at 12 h of overload and only in the plantaris muscle. In summary, sustained elevation of p38alpha MAPK phosphorylation occurred early in response to muscle overload, identifying this pathway as a potential candidate for mediating early hypertrophic signals in response to skeletal muscle overload.

PTEN and PI-3 kinase inhibitors control LPS signaling and the lymphoproliferative response in the CD19+ B cell compartment

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

Singh, Alok R.; Peirce, Susan K.; Joshi, Shweta

Pattern recognition receptors (PRRs), e.g. toll receptors (TLRs) that bind ligands within the microbiome have been implicated in the pathogenesis of cancer. LPS is a ligand for two TLR family members, TLR4 and RP105 which mediate LPS signaling in B cell proliferation and migration. Although LPS/TLR/RP105 signaling is well-studied; our understanding of the underlying molecular mechanisms controlling these PRR signaling pathways remains incomplete. Previous studies have demonstrated a role for PTEN/PI-3K signaling in B cell selection and survival, however a role for PTEN/PI-3K in TLR4/RP105/LPS signaling in the B cell compartment has not been reported. Herein, we crossed a CD19cremore » and PTEN{sup fl/fl} mouse to generate a conditional PTEN knockout mouse in the CD19+ B cell compartment. These mice were further crossed with an IL-14α transgenic mouse to study the combined effect of PTEN deletion, PI-3K inhibition and expression of IL-14α (a cytokine originally identified as a B cell growth factor) in CD19+ B cell lymphoproliferation and response to LPS stimulation. Targeted deletion of PTEN and directed expression of IL-14α in the CD19+ B cell compartment (IL-14+PTEN-/-) lead to marked splenomegaly and altered spleen morphology at baseline due to expansion of marginal zone B cells, a phenotype that was exaggerated by treatment with the B cell mitogen and TLR4/RP105 ligand, LPS. Moreover, LPS stimulation of CD19+ cells isolated from these mice display increased proliferation, augmented AKT and NFκB activation as well as increased expression of c-myc and cyclinD1. Interestingly, treatment of LPS treated IL-14+PTEN-/- mice with a pan PI-3K inhibitor, SF1126, reduced splenomegaly, cell proliferation, c-myc and cyclin D1 expression in the CD19+ B cell compartment and normalized the splenic histopathologic architecture. These findings provide the direct evidence that PTEN and PI-3K inhibitors control TLR4/RP105/LPS signaling in the CD19+ B cell compartment and that pan PI-3 kinase inhibitors reverse the lymphoproliferative phenotype in vivo. - Highlights: • First genetic evidence that PTEN controls LPS/TLR4 signaling in B lymphocytes. • Evidence that PTEN regulates LPS induced lymphoproliferation in vivo. • PI-3 kinase inhibitors block LPS induced lymphoproliferation in vivo.« less

ArcAtlas in the Classroom: Pattern Identification, Description, and Explanation

ERIC Educational Resources Information Center

DeMers, Michael N.; Vincent, Jeffrey S.

2007-01-01

The use of geographic information systems (GIS) in the classroom provides a robust and effective method of teaching the primary spatial skills of identification, description, and explanation of spatial pattern. A major handicap for the development of GIS-based learning experiences, especially for non-GIS specialist educators, is the availability…

Dynamical coupled-channels study of {pi}N {right arrow} {pi pi}N reactions.

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

Kamano, H.; Julia-Diaz, B.; Lee, T.-S. H.

As a step toward performing a complete coupled-channels analysis of the world data of {pi}N,{gamma}*N {yields} {pi}N,{eta}N,{pi}{pi}N reactions, the {pi}N {yields} {pi}{pi}N reactions are investigated starting with the dynamical coupled-channels model developed in Phys. Rev. C 76, 065201 (2007). The channels included are {pi}N,{eta}N, and {pi}{pi}N which has {pi}{Delta},{rho}N, and {sigma}N resonant components. The nonresonant amplitudes are generated from solving a set of coupled-channels equations with the meson-baryon potentials defined by effective Lagrangians. The resonant amplitudes are generated from 16 bare excited nucleon (N*) states that are dressed by the nonresonant interactions as constrained by the unitarity condition. The datamore » of total cross sections and {pi}N and {pi}{pi} invariant mass distributions of {pi} + p {yields} {pi} + {pi} + n, {pi} + {pi}0p and {pi} - p {yields} {pi} + {pi} - n, {pi} - {pi}0p,{pi}0{pi}0n reactions from threshold to the invariant mass W = 2 GeV can be described to a very large extent. We show the importance of the coupled-channels effects and the strong interference among the contributions from the {pi}{Delta},{sigma}N, and {rho}N channels. The large interference between the resonant and nonresonant amplitudes is also demonstrated. Possible future developments are discussed.« less

Identification of critical amino acids in the proximal C-terminal of TREK-2 K+ channel for activation by acidic pHi and ATP-dependent inhibition.

PubMed

Woo, Joohan; Jun, Young Keul; Zhang, Yin-Hua; Nam, Joo Hyun; Shin, Dong Hoon; Kim, Sung Joon

2018-02-01

TWIK-related two-pore domain K + channels (TREKs) are regulated by intracellular pH (pH i ) and Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 ). Previously, Glu 306 in proximal C-terminal (pCt) of mouse TREK-1 was identified as the pH i -sensing residue. The direction of PI(4,5)P 2 sensitivity is controversial, and we have recently shown that TREKs are inhibited by intracellular ATP via endogenous PI(4,5)P 2 formation. Here we investigate the anionic and cationic residues of pCt for the pH i and ATP-sensitivity in human TREK-2 (hTREK-2). In inside-out patch clamp recordings (I TREK-2,i-o ), acidic pH i -induced activation was absent in E332A and was partly attenuated in E335A. Neutralization of cationic Lys (K330A) also eliminated the acidic pH i sensitivity of I TREK-2,i-o . Unlike the inhibition of wild-type (WT) I TREK-2,i-o by intracellular ATP, neither E332A nor K330A was sensitive to ATP. Nevertheless, exogenous PI(4,5)P 2 (10 μM) abolished I TREK-2 i-o in all the above mutants as well as in WT, indicating unspecific inhibition by exogenous PI(4,5)P 2 . In whole-cell recordings of TREK-2 (I TREK-2,w-c ), K330A and E332A showed higher or fully active basal activity, showing attenuated or insignificant activation by 2-APB, arachidonic acid, or acidic pH e 6.9. I TREK-1,w-c of WT is largely suppressed by pH e 6.9, and the inhibition is slightly attenuated in K312A and E315A. The results show concerted roles of the oppositely charged Lys and Glu in pCt for the ATP-dependent low basal activity and pH i sensitivity.

A Novel fry1 Allele Reveals the Existence of a Mutant Phenotype Unrelated to 5′->3′ Exoribonuclease (XRN) Activities in Arabidopsis thaliana Roots

PubMed Central

Hirsch, Judith; Estavillo, Gonzalo M.; Javot, Hélène; Chiarenza, Serge; Mallory, Allison C.; Maizel, Alexis; Declerck, Marie; Pogson, Barry J.; Vaucheret, Hervé; Crespi, Martin; Desnos, Thierry; Thibaud, Marie-Christine; Nussaume, Laurent; Marin, Elena

2011-01-01

Background Mutations in the FRY1/SAL1 Arabidopsis locus are highly pleiotropic, affecting drought tolerance, leaf shape and root growth. FRY1 encodes a nucleotide phosphatase that in vitro has inositol polyphosphate 1-phosphatase and 3′,(2′),5′-bisphosphate nucleotide phosphatase activities. It is not clear which activity mediates each of the diverse biological functions of FRY1 in planta. Principal Findings A fry1 mutant was identified in a genetic screen for Arabidopsis mutants deregulated in the expression of Pi High affinity Transporter 1;4 (PHT1;4). Histological analysis revealed that, in roots, FRY1 expression was restricted to the stele and meristems. The fry1 mutant displayed an altered root architecture phenotype and an increased drought tolerance. All of the phenotypes analyzed were complemented with the AHL gene encoding a protein that converts 3′-polyadenosine 5′-phosphate (PAP) into AMP and Pi. PAP is known to inhibit exoribonucleases (XRN) in vitro. Accordingly, an xrn triple mutant with mutations in all three XRNs shared the fry1 drought tolerance and root architecture phenotypes. Interestingly these two traits were also complemented by grafting, revealing that drought tolerance was primarily conferred by the rosette and that the root architecture can be complemented by long-distance regulation derived from leaves. By contrast, PHT1 expression was not altered in xrn mutants or in grafting experiments. Thus, PHT1 up-regulation probably resulted from a local depletion of Pi in the fry1 stele. This hypothesis is supported by the identification of other genes modulated by Pi deficiency in the stele, which are found induced in a fry1 background. Conclusions/Significance Our results indicate that the 3′,(2′),5′-bisphosphate nucleotide phosphatase activity of FRY1 is involved in long-distance as well as local regulatory activities in roots. The local up-regulation of PHT1 genes transcription in roots likely results from local depletion of Pi and is independent of the XRNs. PMID:21304819

Measurement of the ratios of branching fractions B(B0s --> Ds- pi+ pi+ pi-)/B(B0-->D- pi+ pi+ pi-) and B(B0s --> Ds- pi+)/B(B0-->D- pi+).

PubMed

Abulencia, A; Adelman, J; Affolder, T; Akimoto, T; Albrow, M G; Ambrose, D; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arguin, J-F; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Bedeschi, F; Behari, S; Belforte, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Budroni, S; Burkett, K; Busetto, G; Bussey, P; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carillo, S; Carlsmith, D; Carosi, R; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciljak, M; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Coca, M; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Cyr, D; DaRonco, S; D'Auria, S; Davies, T; D'Onofrio, M; Dagenhart, D; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; Dell'Orso, M; Delli Paoli, F; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; Dituro, P; Dörr, C; Donati, S; Donega, M; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, I; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Foland, A; Forrester, S; Foster, G W; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Garberson, F; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D; Giagu, S; Giannetti, P; Gibson, A; Gibson, K; Gimmell, J L; Ginsburg, C; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, J; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Griffiths, M; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Holloway, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ishizawa, Y; Ivanov, A; Iyutin, B; James, E; Jang, D; Jayatilaka, B; Jeans, D; Jensen, H; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Karchin, P E; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kovalev, A; Kraan, A C; Kraus, J; Kravchenko, I; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Loverre, P; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Manca, G; Margaroli, F; Marginean, R; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Maruyama, T; Mastrandrea, P; Masubuchi, T; Matsunaga, H; Mattson, M E; Mazini, R; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyamoto, A; Moed, S; Moggi, N; Mohr, B; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Nachtman, J; Nagano, A; Naganoma, J; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nigmanov, T; Nodulman, L; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagliarone, C; Palencia, E; Papadimitriou, V; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ranjan, N; Rappoccio, S; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Sabik, S; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Saltzberg, D; Sánchez, C; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savard, P; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Sjolin, J; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; Staveris-Polykalas, A; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Takikawa, K; Tanaka, M; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tsuchiya, R; Tsuno, S; Turini, N; Ukegawa, F; Unverhau, T; Uozumi, S; Usynin, D; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Veramendi, G; Veszpremi, V; Vidal, R; Vila, I; Vilar, R; Vine, T; Vollrath, I; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner, J; Wagner, W; Wallny, R; Wang, S M; Warburton, A; Waschke, S; Waters, D; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zhou, J; Zucchelli, S

2007-02-09

Using 355 pb;{-1} of data collected by the CDF II detector in pp[over ] collisions at sqrt[s]=1.96 TeV at the Fermilab Tevatron, we study the fully reconstructed hadronic decays B_{(s)};{0}-->D_{(s)};{-}pi;{+} and B_{(s)};{0}-->D_{(s)};{-}pi;{+}pi;{+}pi;{-}. We present the first measurement of the ratio of branching fractions B(B_{s};{0}-->D_{s};{-}pi;{+}pi;{+}pi;{-})/B(B;{0}-->D;{-}pi;{+}pi;{+}pi;{-})=1.05+/-0.10(stat)+/-0.22(syst). We also update our measurement of B(B_{s};{0}-->D_{s};{-}pi;{+})/B(B;{0}-->D;{-}pi;{+}) to 1.13+/-0.08(stat)+/-0.23(syst), improving the statistical uncertainty by more than a factor of 2. We find B(B_{s};{0}-->D_{s};{-}pi;{+})=[3.8+/-0.3(stat)+/-1.3(syst)]x10;{-3} and B(B_{s};{0}-->D_{s};{-}pi;{+}pi;{+}pi;{-})=[8.4+/-0.8(stat)+/-3.2(syst)]x10;{-3}.

Dynamical coupled-channels study of {pi}N{yields}{pi}{pi}N reactions

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

Kamano, H.; Julia-Diaz, B.; Department d'Estructura i Constituents de la Materia and Institut de Ciencies del Cosmos, Universitat de Barcelona E-08028 Barcelona

As a step toward performing a complete coupled-channels analysis of the world data of {pi}N,{gamma}*N{yields}{pi}N,{eta}N,{pi}{pi}N reactions, the {pi}N{yields}{pi}{pi}N reactions are investigated starting with the dynamical coupled-channels model developed in Phys. Rev. C 76, 065201 (2007). The channels included are {pi}N,{eta}N, and {pi}{pi}N which has {pi}{delta},{rho}N, and {sigma}N resonant components. The nonresonant amplitudes are generated from solving a set of coupled-channels equations with the meson-baryon potentials defined by effective Lagrangians. The resonant amplitudes are generated from 16 bare excited nucleon (N*) states that are dressed by the nonresonant interactions as constrained by the unitarity condition. The data of total cross sectionsmore » and {pi}N and {pi}{pi} invariant mass distributions of {pi}{sup +}p{yields}{pi}{sup +}{pi}{sup +}n,{pi}{sup +}{pi}{sup 0}p and {pi}{sup -}p{yields}{pi}{sup +}{pi}{sup -}n,{pi}{sup -}{pi}{sup 0}p,{pi}{sup 0}{pi}{sup 0}n reactions from threshold to the invariant mass W=2 GeV can be described to a very large extent. We show the importance of the coupled-channels effects and the strong interference among the contributions from the {pi}{delta},{sigma}N, and {rho}N channels. The large interference between the resonant and nonresonant amplitudes is also demonstrated. Possible future developments are discussed.« less

Patterns of Cognitive Strengths and Weaknesses: Identification Rates, Agreement, and Validity for Learning Disabilities Identification

PubMed Central

Miciak, Jeremy; Fletcher, Jack M.; Stuebing, Karla; Vaughn, Sharon; Tolar, Tammy D.

2014-01-01

Purpose Few empirical investigations have evaluated LD identification methods based on a pattern of cognitive strengths and weaknesses (PSW). This study investigated the reliability and validity of two proposed PSW methods: the concordance/discordance method (C/DM) and cross battery assessment (XBA) method. Methods Cognitive assessment data for 139 adolescents demonstrating inadequate response to intervention was utilized to empirically classify participants as meeting or not meeting PSW LD identification criteria using the two approaches, permitting an analysis of: (1) LD identification rates; (2) agreement between methods; and (3) external validity. Results LD identification rates varied between the two methods depending upon the cut point for low achievement, with low agreement for LD identification decisions. Comparisons of groups that met and did not meet LD identification criteria on external academic variables were largely null, raising questions of external validity. Conclusions This study found low agreement and little evidence of validity for LD identification decisions based on PSW methods. An alternative may be to use multiple measures of academic achievement to guide intervention. PMID:24274155

The connecting link! Lip prints and fingerprints.

PubMed

Negi, Amita; Negi, Anurag

2016-01-01

Lip prints and fingerprints are considered to be unique to each individual. The study of fingerprints and lip prints is very popular in personal identification of the deceased and in criminal investigations. This study was done to find the predominant lip and fingerprint patterns in males and females in the North Indian population and also to find any correlation between lip print and fingerprint patterns within a gender. Two hundred students (100 males, 100 females) were included in the study. Lip prints were recorded for each individual using a dark-colored lipstick and the right thumb impression was recorded using an ink pad. The lip prints and fingerprints were analyzed using a magnifying glass. The Chi-square test was used for statistical analysis. The branched pattern in males and the vertical pattern in females were the predominant lip print patterns. The predominant fingerprint pattern in both males and females was found to be the loop pattern, followed by the whorl pattern and then the arch pattern. No statistically significant correlation was found between lip prints and fingeprints. However, the arch type of fingerprint was found to be associated with different lip print patterns in males and females. Lip prints and fingerprints can be used for personal identification in a forensic scenario. Further correlative studies between lip prints and fingerprints could be useful in forensic science for gender identification.

Optical DC overlay measurement in the 2nd level process of 65 nm alternating phase shift mask

NASA Astrophysics Data System (ADS)

Ma, Jian; Han, Ke; Lee, Kyung; Korobko, Yulia; Silva, Mary; Chavez, Joas; Irvine, Brian; Henrichs, Sven; Chakravorty, Kishore; Olshausen, Robert; Chandramouli, Mahesh; Mammen, Bobby; Padmanaban, Ramaswamy

2005-11-01

Alternating phase shift mask (APSM) techniques help bridge the significant gap between the lithography wavelength and the patterning of minimum features, specifically, the poly line of 35 nm gate length (1x) in Intel's 65 nm technology. One of key steps in making APSM mask is to pattern to within the design tolerances the 2nd level resist so that the zero-phase apertures will be protected by the resist and the pi-phase apertures will be wide open for quartz etch. The ability to align the 2nd level to the 1st level binary pattern, i.e. the 2nd level overlay capability is very important, so is the capability of measuring the overlay accurately. Poor overlay could cause so-called the encroachment after quartz etch, producing undesired quartz bumps in the pi-apertures or quartz pits in the zero-apertures. In this paper, a simple, low-cost optical setup for the 2nd level DC (develop check) overlay measurements in the high volume manufacturing (HVM) of APSM masks is presented. By removing systematic errors in overlay associated with TIS and MIS (tool-induced shift and Mask-process induced shift), it is shown that this setup is capable of supporting the measurement of DC overlay with a tolerance as small as +/- 25 nm. The outstanding issues, such as DC overlay error component analysis, DC - FC (final check) overlay correlation and the overlay linearity (periphery vs. indie), are discussed.

First observation of the decays {chi}{sub cJ}{yields}{pi}{sup 0}{pi}{sup 0}{pi}{sup 0}{pi}{sup 0}

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

Ablikim, M.; An, Z. H.; Bai, J. Z.

We present a study of the P-wave spin-triplet charmonium {chi}{sub cJ} decays (J=0, 1, 2) into {pi}{sup 0}{pi}{sup 0}{pi}{sup 0}{pi}{sup 0}. The analysis is based on 106x10{sup 6} {psi}{sup '} decays recorded with the BESIII detector at the BEPCII electron positron collider. The decay into the {pi}{sup 0}{pi}{sup 0}{pi}{sup 0}{pi}{sup 0} hadronic final state is observed for the first time. We measure the branching fractions B({chi}{sub c0}{yields}{pi}{sup 0}{pi}{sup 0}{pi}{sup 0}{pi}{sup 0})=(3.34{+-}0.06{+-}0.44)x10{sup -3}, B({chi}{sub c1}{yields}{pi}{sup 0}{pi}{sup 0}{pi}{sup 0}{pi}{sup 0})=(0.57{+-}0.03{+-}0.08)x10{sup -3}, and B({chi}{sub c2}{yields}{pi}{sup 0}{pi}{sup 0}{pi}{sup 0}{pi}{sup 0})=(1.21{+-}0.05{+-}0.16)x10{sup -3}, where the uncertainties are statistical and systematical, respectively.

First observation and measurement of the resonant structure of the lambda_b->lambda_c pi-pi+pi- decay mode

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

Azzurri, P.; Barria, P.; Ciocci, M.A.

The authors present the first observation of the {Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -} decay using data from an integrated luminosity of approximately 2.4 fb{sup -1} of p{bar p} collisions at {radical}s = 1.96 TeV, collected with the CDF II detector at the Fermilab Tevatron. They also present the first observation of the resonant decays {Lambda}{sub b}{sup 0} {yields} {Sigma}{sub c}(2455){sup 0} {pi}{sup +}{pi}{sup -} {yields} {Lambda}{sub c}{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -}, {Lambda}{sub b}{sup 0} {yields} {Sigma}{sub c}(2455){sup ++}{pi}{sup -}{pi}{sup -} {yields} {Lambda}{sub c}{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -}, {Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}(2595){sup +}{pi}{sup -}more » {yields} {Lambda}{sub c}{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -} and {Lambda}{sub b}{sup 0} {yields} {Lambda}{sub c}(2625){sup +}{pi}{sup -} {yields} {Lambda}{sub c}{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -}, and measure their relative branching ratios.« less

Maximum likelihood estimation of label imperfections and its use in the identification of mislabeled patterns

NASA Technical Reports Server (NTRS)

Chittineni, C. B.

1979-01-01

The problem of estimating label imperfections and the use of the estimation in identifying mislabeled patterns is presented. Expressions for the maximum likelihood estimates of classification errors and a priori probabilities are derived from the classification of a set of labeled patterns. Expressions also are given for the asymptotic variances of probability of correct classification and proportions. Simple models are developed for imperfections in the labels and for classification errors and are used in the formulation of a maximum likelihood estimation scheme. Schemes are presented for the identification of mislabeled patterns in terms of threshold on the discriminant functions for both two-class and multiclass cases. Expressions are derived for the probability that the imperfect label identification scheme will result in a wrong decision and are used in computing thresholds. The results of practical applications of these techniques in the processing of remotely sensed multispectral data are presented.

Pion Elastic Scattering and the (pion Pion' Proton) Reaction on HELIUM-4 in the DELTA(3,3) Region

NASA Astrophysics Data System (ADS)

Jones, Mark Kevin

This dissertation presents measurements and analyses of pi^+ and pi ^{-} elastic scattering, and ( pi^{+}, pi^ {+^'}p) and ( pi^{-},pi^{-^ '}p) reactions on ^4 He. Both experiments were done at the Los Alamos Meson Physics Facility using the Energetic Pion Channel and Spectrometer. The ^4He( pi,pi) elastic scattering cross sections were measured for pi^{+} scattering at scattering angles theta _{lab} = 110^circ -170^circ and five incident energies between T_{pi } = 90 and 180 MeV. Elastic pi ^{-} cross sections were measured only at T_{pi} = 180 MeV. The ^4He(pi, pi' p) angular correlation functions were measured for pi^{+} and pi^{-} at T_{pi} = 180 and theta_{pi^' } = 30^circ, 40 ^circ, 60^circ , 80^circ and at T _pi = 140 MeV and theta_{pi^'} = 40^circ. Using scintillators at eight angles the protons were detected in coincidence with the inelastically scattered pions. In the ^4He(pi, pi^' p) experiment unexpectedly large ratios R_{pi p} = {sigma(pi^{+}, pi^{+} p)}over{sigma( pi^{-},pi^{-} p)} of up to 50 were observed near the quasi -free angle in the angular correlation functions summed over 30.5 to 39.5 MeV in ^4He excitation energy. The (pi,pi' p) data were analyzed by a distorted wave impulse approximation code 3DEE (Ch 82), (Re 82). 3DEE models the ( pi,pi' p) reaction as a pion -induced proton knock-out and includes distortions in the incident pion, the outgoing pion, and the emitted proton waves. The calculations give R_{pi p} between 6 and 9 at all proton and pion angles. The pi^{+} calculations reproduce the absolute pi^ {+} cross sections fairly well. The pi^{-} calculations have a peak in the angular correlation function near the quasi-free angle, in contrast to the pi^ {-} data which displays a flat distribution. At proton angles near 180^circ in the center of mass of the struck mass 4 system, the measured pi^{-} cross sections are larger than the pi^ {+} cross section which is the reverse of the ratio at 0^circ. These features of the measured pi^- cross sections indicate that interference between a quasi -free process and another process is important in the ( pi,pi^' p) reaction. The measurement of ^4He( pi,pi) elastic scattering data at theta_pi = 110 ^circ-170^circ extends the angular range of previous ^4He(pi,pi) data measured at EPICS. The experiment provides high quality elastic scattering data at backward angles. The pi^{-} elastic cross section at T_pi = 180 MeV measured for this dissertation when extrapolated to theta _{cm} = 180^circ is about a factor of two smaller than the cross section measured previously at CERN (Ref. (Bi 78)). The data were analyzed using a microscopic optical model and by a phase shift fit.

Chiral discrimination in diastereomeric salts of chlorine-substituted mandelic acid and phenylethylamine.

PubMed

He, Quan; Gomaa, Hassan; Rohani, Sohrab; Zhu, Jesse; Jennings, Michael

2010-08-01

The crystal structures of diastereomeric salts of chloromandelic acid and phenylethylamine were determined and are presented herein. The structure comparison between less soluble salts and more soluble salts shows that weak interactions such as CH/pi interactions and van der Waals gain importance and contribute to chiral recognition when the hydrogen bonding patterns are very similar. Copyright 2010 Wiley-Liss, Inc.

Global Emerging Infection Surveillance and Response (GEIS)- Avian Influenza Pandemic Influenza (AI/PI) Program

DTIC Science & Technology

2010-10-01

work in Nairobi, Kericho, and Kisumu, including the National Influenza Center (NIC), the arbovirus reference laboratory, the antimalarial resistance...and establish the pattern of antimalarial resistance across Kenya. Outbreak investigation and response continues. AFI expanded into regions around...important scientific activity since it aids in the detection of viral antigenic shift and drift which are responsible for pandemics and epidemics

Resting bold fMRI differentiates dementia with Lewy bodies vs Alzheimer disease

PubMed Central

Price, J.L.; Yan, Z.; Morris, J.C.; Sheline, Y.I.

2011-01-01

Objective: Clinicopathologic phenotypes of dementia with Lewy bodies (DLB) and Alzheimer disease (AD) often overlap, making discrimination difficult. We performed resting state blood oxygen level–dependent (BOLD) functional connectivity MRI (fcMRI) to determine whether there were differences between AD and DLB. Methods: Participants (n = 88) enrolled in a longitudinal study of memory and aging underwent 3-T fcMRI. Clinical diagnoses of probable DLB (n = 15) were made according to published criteria. Cognitively normal control participants (n = 38) were selected for the absence of cerebral amyloid burden as imaged with Pittsburgh compound B (PiB). Probable AD cases (n = 35) met published criteria and had appreciable amyloid deposits with PiB imaging. Functional images were collected using a gradient spin-echo sequence sensitive to BOLD contrast (T2* weighting). Correlation maps selected a seed region in the combined bilateral precuneus. Results: Participants with DLB had a functional connectivity pattern for the precuneus seed region that was distinct from AD; both the DLB and AD groups had functional connectivity patterns that differed from the cognitively normal group. In the DLB group, we found increased connectivity between the precuneus and regions in the dorsal attention network and the putamen. In contrast, we found decreased connectivity between the precuneus and other task-negative default regions and visual cortices. There was also a reversal of connectivity in the right hippocampus. Conclusions: Changes in functional connectivity in DLB indicate patterns of activation that are distinct from those seen in AD and may improve discrimination of DLB from AD and cognitively normal individuals. Since patterns of connectivity differ between AD and DLB groups, measurements of BOLD functional connectivity can shed further light on neuroanatomic connections that distinguish DLB from AD. PMID:21525427

Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil.

PubMed

Lei, Zhengdeng; Tan, Iain Beehuat; Das, Kakoli; Deng, Niantao; Zouridis, Hermioni; Pattison, Sharon; Chua, Clarinda; Feng, Zhu; Guan, Yeoh Khay; Ooi, Chia Huey; Ivanova, Tatiana; Zhang, Shenli; Lee, Minghui; Wu, Jeanie; Ngo, Anna; Manesh, Sravanthy; Tan, Elisabeth; Teh, Bin Tean; So, Jimmy Bok Yan; Goh, Liang Kee; Boussioutas, Alex; Lim, Tony Kiat Hon; Flotow, Horst; Tan, Patrick; Rozen, Steven G

2013-09-01

Almost all gastric cancers are adenocarcinomas, which have considerable heterogeneity among patients. We sought to identify subtypes of gastric adenocarcinomas with particular biological properties and responses to chemotherapy and targeted agents. We compared gene expression patterns among 248 gastric tumors; using a robust method of unsupervised clustering, consensus hierarchical clustering with iterative feature selection, we identified 3 major subtypes. We developed a classifier for these subtypes and validated it in 70 tumors from a different population. We identified distinct genomic and epigenomic properties of the subtypes. We determined drug sensitivities of the subtypes in primary tumors using clinical survival data, and in cell lines through high-throughput drug screening. We identified 3 subtypes of gastric adenocarcinoma: proliferative, metabolic, and mesenchymal. Tumors of the proliferative subtype had high levels of genomic instability, TP53 mutations, and DNA hypomethylation. Cancer cells of the metabolic subtype were more sensitive to 5-fluorouracil than the other subtypes. Furthermore, in 2 independent groups of patients, those with tumors of the metabolic subtype appeared to have greater benefits with 5-fluorouracil treatment. Tumors of the mesenchymal subtype contain cells with features of cancer stem cells, and cell lines of this subtype are particularly sensitive to phosphatidylinositol 3-kinase-AKT-mTOR inhibitors in vitro. Based on gene expression patterns, we classified gastric cancers into 3 subtypes, and validated these in an independent set of tumors. The subgroups have differences in molecular and genetic features and response to therapy; this information might be used to select specific treatment approaches for patients with gastric cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

The Effect of Achievement Test Selection on Identification of Learning Disabilities within a Patterns of Strengths and Weaknesses Framework

ERIC Educational Resources Information Center

Miciak, Jeremy; Taylor, W. Pat; Denton, Carolyn A.; Fletcher, Jack M.

2015-01-01

Few empirical investigations have evaluated learning disabilities (LD) identification methods based on a pattern of cognitive strengths and weaknesses (PSW). This study investigated the reliability of LD classification decisions of the concordance/discordance method (C/DM) across different psychoeducational assessment batteries. C/DM criteria were…

Patterns in the Identification of and Outcomes for Children and Youth with Disabilities. Final Report. NCEE 2010-4005

ERIC Educational Resources Information Center

Blackorby, Jose; Schiller, Ellen; Mallik, Sangeeta; Hebbeler, Kathleen; Huang, Tracy; Javitz, Harold; Marder, Camille; Nagle, Katherine; Shaver, Debra; Wagner, Mary; Williamson, Cyndi

2010-01-01

Reported here are the results of analyses to describe the patterns of identification and academic and developmental outcomes for children with disabilities, conducted as part of the 2004 National Assessment of the implementation of the Individuals with Disabilities Education Act (IDEA). This report provides background context for National…

Observation of thirteen new exclusive multibody hadronic decays of the psi(2S).

PubMed

Briere, R A; Chen, G P; Chen, J; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Adam, N E; Alexander, J P; Berkelman, K; Cassel, D G; Crede, V; Duboscq, J E; Ecklund, K M; Ehrlich, R; Fields, L; Gibbons, L; Gittelman, B; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Meyer, T O; Onyisi, P U E; Patterson, J R; Peterson, D; Phillips, E A; Pivarski, J; Riley, D; Ryd, A; Sadoff, A J; Schwarthoff, H; Shi, X; Shepherd, M R; Stroiney, S; Sun, W M; Urner, D; Wilksen, T; Weaver, K M; Weinberger, M; Athar, S B; Avery, P; Breva-Newell, L; Patel, R; Potlia, V; Stoeck, H; Yelton, J; Rubin, P; Cawlfield, C; Eisenstein, B I; Gollin, G D; Karliner, I; Kim, D; Lowrey, N; Naik, P; Sedlack, C; Selen, M; White, E J; Williams, J; Wiss, J; Edwards, K W; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Gong, D T; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Li, S Z; Poling, R; Scott, A W; Smith, A; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Zweber, P; Ernst, J; Mahmood, A H; Severini, H; Asner, D M; Dytman, S A; Love, W; Mehrabyan, S; Mueller, J A; Savinov, V; Li, Z; Lopez, A; Mendez, H; Ramirez, J; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shipsey, I P J; Adams, G S; Cravey, M; Cummings, J P; Danko, I; Napolitano, J; He, Q; Muramatsu, H; Park, C S; Park, W; Thorndike, E H; Coan, T E; Gao, Y S; Liu, F; Artuso, M; Boulahouache, C; Blusk, S; Butt, J; Dorjkhaidav, O; Li, J; Menaa, N; Mountain, R; Nandakumar, R; Randrianarivony, K; Redjimi, R; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Zhang, K; Csorna, S E; Bonvicini, G; Cinabro, D; Dubrovin, M

2005-08-05

Using data accumulated with the CLEO detector corresponding to an integrated luminosity of [symbol: see text] = 5.63 pb(-1) on the peak of the psi(2S) [3.08 x 10(6) psi(2S) decays] and 20.70 pb(-1) at square root of[s] = 3.67 GeV, we report first measurements of the branching fractions for the following 13 decay modes of the psi(2S): eta3pi, &eta'3pi, rhoK+K-, K+K-pi+pi-pi0, 2(K+K-), 2(K+K-)pi0, rhopp, pppi+pi-pi0, etapp, ppK+K-, lambdalambdapi+pi-, lambdapK+, and lambdapK+pi+pi-, and more precise measurements of 8 previously measured modes: 2(pi+pi-), rhopi+pi-, 2(pi+pi-)pi0, omegapi+pi-, K+K-pi+pi-, omegaK+K-, phiK+K-, and pppi+pi-. We also report new branching fraction measurements of phipi+pi- and omegapp and upper limits for etapi+pi-, etaK+K-, and phivpp. Results are compared, where possible, with the corresponding J/psi branching ratios to provide new tests of the 12% rule.

Load compensation in a lean burn natural gas vehicle

NASA Astrophysics Data System (ADS)

Gangopadhyay, Anupam

A new multivariable PI tuning technique is developed in this research that is primarily developed for regulation purposes. Design guidelines are developed based on closed-loop stability. The new multivariable design is applied in a natural gas vehicle to combine idle and A/F ratio control loops. This results in better recovery during low idle operation of a vehicle under external step torques. A powertrain model of a natural gas engine is developed and validated for steady-state and transient operation. The nonlinear model has three states: engine speed, intake manifold pressure and fuel fraction in the intake manifold. The model includes the effect of fuel partial pressure in the intake manifold filling and emptying dynamics. Due to the inclusion of fuel fraction as a state, fuel flow rate into the cylinders is also accurately modeled. A linear system identification is performed on the nonlinear model. The linear model structure is predicted analytically from the nonlinear model and the coefficients of the predicted transfer function are shown to be functions of key physical parameters in the plant. Simulations of linear system and model parameter identification is shown to converge to the predicted values of the model coefficients. The multivariable controller developed in this research could be designed in an algebraic fashion once the plant model is known. It is thus possible to implement the multivariable PI design in an adaptive fashion combining the controller with identified plant model on-line. This will result in a self-tuning regulator (STR) type controller where the underlying design criteria is the multivariable tuning technique designed in this research.

First observation of exclusive {chi}{sub cJ} decays to two charged and two neutral hadrons

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

He, Q.; Insler, J.; Muramatsu, H.

2008-11-01

We study exclusive {chi}{sub c0,1,2} decays to four-hadron final states involving two charged and two neutral hadrons: {pi}{sup +}{pi}{sup -}{pi}{sup 0}{pi}{sup 0}, K{sup +}K{sup -}{pi}{sup 0}{pi}{sup 0}, pp{pi}{sup 0}{pi}{sup 0}, K{sup +}K{sup -}{eta}{pi}{sup 0}, and K{sup {+-}}{pi}{sup {+-}}K{sup 0}{pi}{sup 0}. The {chi}{sub c} states are produced in radiative decays of 3.08x10{sup 6} {psi}(2S) resonance decays and observed in the CLEO detector. We also measure the largest substructure contributions to the modes {pi}{sup +}{pi}{sup -}{pi}{sup 0}{pi}{sup 0} and K{sup {+-}}{pi}{sup {+-}}K{sup 0}{pi}{sup 0}.

The e{sup +}e{sup -}{yields}2({pi}{sup +}{pi}{sup -}){pi}{sup 0}, 2({pi}{sup +}{pi}{sup -}){eta}, K{sup +}K{sup -}{pi}{sup +}{pi}{sup -}{pi}{sup 0} and K{sup +}K{sup -}{pi}{sup +}{pi}{sup -}{eta} cross sections measured with initial-state radiation

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

Aubert, B.; Bona, M.; Boutigny, D.

We study the processes e{sup +}e{sup -}{yields}2({pi}{sup +}{pi}{sup -}){pi}{sup 0}{gamma}, 2({pi}{sup +}{pi}{sup -}){eta}{gamma}, K{sup +}K{sup -}{pi}{sup +}{pi}{sup -}{pi}{sup 0}{gamma} and K{sup +}K{sup -}{pi}{sup +}{pi}{sup -}{eta}{gamma} with the hard photon radiated from the initial state. About 20 000, 4300, 5500, and 375 fully reconstructed events, respectively, are selected from 232 fb{sup -1} of BABAR data. The invariant mass of the hadronic final state defines the effective e{sup +}e{sup -} center-of-mass energy, so that the obtained cross sections from the threshold to about 5 GeV can be compared with corresponding direct e{sup +}e{sup -} measurements, currently available only for the {eta}{pi}{sup +}{pi}{supmore » -} and {omega}{pi}{sup +}{pi}{sup -} submodes of the e{sup +}e{sup -}{yields}2({pi}{sup +}{pi}{sup -}){pi}{sup 0} channel. Studying the structure of these events, we find contributions from a number of intermediate states, and we extract their cross sections where possible. In particular, we isolate the contribution from e{sup +}e{sup -}{yields}{omega}(782){pi}{sup +}{pi}{sup -} and study the {omega}(1420) and {omega}(1650) resonances. In the charmonium region, we observe the J/{psi} in all these final states and several intermediate states, as well as the {psi}(2S) in some modes, and we measure the corresponding branching fractions.« less

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

Patterson, Ryan; Backhouse, Christopher; Bays, Kirk

The NOvA long-baseline neutrino experiment uses a fine-grained, low-Z, fully active detector that offers unprecedented electron neutrino identification capabilities for a detector of its scale. In this award’s proposal, the PI outlined the development and implementation of novel techniques for channel readout, detector calibration, and event reconstruction that make full use of the strengths of the NOvA detector technology. In particular, this included designing custom event reconstruction algorithms that utilize the rich information available in the substructure of hadronic and electromagnetic showers. Exploiting this information provides not only substantial improvement in background rejection for the electron neutrino search but alsomore » better shower energy resolution (improving the precision on measured oscillation parameters) and a high-energy electromagnetic calibration source (through neutral pion events). The PI further proposed developing and deploying a new electronics readout scheme compatible with the existing hardware that can reduce near detector event pile-up and can offer powerful timing information to the reconstruction, allowing for cosmic ray muon tagging via track direction determination, among other things. In conjunction with the above, the PI proposed leading the calibration of the NOvA detectors, including characterizing individual electronics channels, correcting for spatial variations across the detector, and establishing absolute event energy scales. All three of these lines of effort have been successfully completed, feeding directly into the NOvA’s recent exciting neutrino oscillation results. The techniques developed under this award are detailed in this final technical report.« less

A novel snapshot polarimetric imager

NASA Astrophysics Data System (ADS)

Wong, Gerald; McMaster, Ciaran; Struthers, Robert; Gorman, Alistair; Sinclair, Peter; Lamb, Robert; Harvey, Andrew R.

2012-10-01

Polarimetric imaging (PI) is of increasing importance in determining additional scene information beyond that of conventional images. For very long-range surveillance, image quality is degraded due to turbulence. Furthermore, the high magnification required to create images with sufficient spatial resolution suitable for object recognition and identification require long focal length optical systems. These are incompatible with the size and weight restrictions for aircraft. Techniques which allow detection and recognition of an object at the single pixel level are therefore likely to provide advance warning of approaching threats or long-range object cueing. PI is a technique that has the potential to detect object signatures at the pixel level. Early attempts to develop PI used rotating polarisers (and spectral filters) which recorded sequential polarized images from which the complete Stokes matrix could be derived. This approach has built-in latency between frames and requires accurate registration of consecutive frames to analyze real-time video of moving objects. Alternatively, multiple optical systems and cameras have been demonstrated to remove latency, but this approach increases cost and bulk of the imaging system. In our investigation we present a simplified imaging system that divides an image into two orthogonal polarimetric components which are then simultaneously projected onto a single detector array. Thus polarimetric data is recorded without latency on a single snapshot. We further show that, for pixel-level objects, the data derived from only two orthogonal states (H and V) is sufficient to increase the probability of detection whilst reducing false alarms compared to conventional unpolarised imaging.

Routine use of PCR-restriction fragment length polymorphism analysis for identification of mycobacteria growing in liquid media.

PubMed Central

Taylor, T B; Patterson, C; Hale, Y; Safranek, W W

1997-01-01

A PCR-restriction fragment length polymorphism (PCR-RFLP) procedure capable of rapidly identifying 28 species of clinically encountered mycobacteria was evaluated for use in the routine identification of acid-fast isolates growing in BACTEC 12B and 13A liquid media. PCR-RFLP identified 100 of 103 acid-fast isolates recovered from 610 patient specimens submitted for culture during the study. The three isolates unidentifiable by PCR-RFLP produced restriction patterns not included in the PCR-RFLP algorithm and could therefore not be assigned to a species. These isolates were characterized by their morphologic and biochemical characteristics. Two of the isolates were identified as M. terrae complex and M. gordonae. The third isolate could not be definitively identified and could only be characterized as a Mycobacterium sp. most closely resembling M. chelonae. PCR-RFLP identifications agreed with the conventional identifications for 96 of the 100 isolates identified by PCR-RFLP. Subsequent identification of the four discordant isolates by gas chromatography analysis supported the PCR-RFLP identification of each isolate. Amplification products were also obtained from isolates of Streptococcus albus and Rhodococcus equi recovered from patient specimens; however, the restriction patterns of these nonmycobacterial species did not resemble the patterns of any mycobacterial species included in the PCR-RFLP algorithm. PCR-RFLP seems to be a reliable procedure for the routine identification of mycobacteria and has the potential for providing identifications of mycobacterial isolates which are more accurate than conventional identification techniques based on morphologic and biochemical characteristics. PMID:8968884

Basic concepts and architectural details of the Delphi trigger system

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

Bocci, V.; Booth, P.S.L.; Bozzo, M.

1995-08-01

Delphi (DEtector with Lepton, Photon and Hadron Identification) is one of the four experiments of the LEP (Large Electron Positron) collider at CERN. The detector is laid out to provide a nearly 4 {pi} coverage for charged particle tracking, electromagnetic, hadronic calorimetry and extended particle identification. The trigger system consists of four levels. The first two are synchronous with the BCO (Beam Cross Over) and rely on hardwired control units, while the last two are performed asynchronously with respect to the BCO and are driven by the Delphi host computers. The aim of this paper is to give a comprehensivemore » global view of the trigger system architecture, presenting in detail the first two levels, their various hardware components and the latest modifications introduced in order to improve their performance and make more user friendly the whole software user interface.« less