A Discrete-Time Average Model Based Predictive Control for Quasi-Z-Source Inverter

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

Liu, Yushan; Abu-Rub, Haitham; Xue, Yaosuo

A discrete-time average model-based predictive control (DTA-MPC) is proposed for a quasi-Z-source inverter (qZSI). As a single-stage inverter topology, the qZSI regulates the dc-link voltage and the ac output voltage through the shoot-through (ST) duty cycle and the modulation index. Several feedback strategies have been dedicated to produce these two control variables, among which the most popular are the proportional–integral (PI)-based control and the conventional model-predictive control (MPC). However, in the former, there are tradeoffs between fast response and stability; the latter is robust, but at the cost of high calculation burden and variable switching frequency. Moreover, they require anmore » elaborated design or fine tuning of controller parameters. The proposed DTA-MPC predicts future behaviors of the ST duty cycle and modulation signals, based on the established discrete-time average model of the quasi-Z-source (qZS) inductor current, the qZS capacitor voltage, and load currents. The prediction actions are applied to the qZSI modulator in the next sampling instant, without the need of other controller parameters’ design. A constant switching frequency and significantly reduced computations are achieved with high performance. Transient responses and steady-state accuracy of the qZSI system under the proposed DTA-MPC are investigated and compared with the PI-based control and the conventional MPC. Simulation and experimental results verify the effectiveness of the proposed approach for the qZSI.« less

A Discrete-Time Average Model Based Predictive Control for Quasi-Z-Source Inverter

DOE PAGES

Liu, Yushan; Abu-Rub, Haitham; Xue, Yaosuo; ...

2017-12-25

A discrete-time average model-based predictive control (DTA-MPC) is proposed for a quasi-Z-source inverter (qZSI). As a single-stage inverter topology, the qZSI regulates the dc-link voltage and the ac output voltage through the shoot-through (ST) duty cycle and the modulation index. Several feedback strategies have been dedicated to produce these two control variables, among which the most popular are the proportional–integral (PI)-based control and the conventional model-predictive control (MPC). However, in the former, there are tradeoffs between fast response and stability; the latter is robust, but at the cost of high calculation burden and variable switching frequency. Moreover, they require anmore » elaborated design or fine tuning of controller parameters. The proposed DTA-MPC predicts future behaviors of the ST duty cycle and modulation signals, based on the established discrete-time average model of the quasi-Z-source (qZS) inductor current, the qZS capacitor voltage, and load currents. The prediction actions are applied to the qZSI modulator in the next sampling instant, without the need of other controller parameters’ design. A constant switching frequency and significantly reduced computations are achieved with high performance. Transient responses and steady-state accuracy of the qZSI system under the proposed DTA-MPC are investigated and compared with the PI-based control and the conventional MPC. Simulation and experimental results verify the effectiveness of the proposed approach for the qZSI.« less

Periodontal inflamed surface area as a novel numerical variable describing periodontal conditions

PubMed Central

2017-01-01

Purpose A novel index, the periodontal inflamed surface area (PISA), represents the sum of the periodontal pocket depth of bleeding on probing (BOP)-positive sites. In the present study, we evaluated correlations between PISA and periodontal classifications, and examined PISA as an index integrating the discrete conventional periodontal indexes. Methods This study was a cross-sectional subgroup analysis of data from a prospective cohort study investigating the association between chronic periodontitis and the clinical features of ankylosing spondylitis. Data from 84 patients without systemic diseases (the control group in the previous study) were analyzed in the present study. Results PISA values were positively correlated with conventional periodontal classifications (Spearman correlation coefficient=0.52; P<0.01) and with periodontal indexes, such as BOP and the plaque index (PI) (r=0.94; P<0.01 and r=0.60; P<0.01, respectively; Pearson correlation test). Porphyromonas gingivalis (P. gingivalis) expression and the presence of serum P. gingivalis antibodies were significant factors affecting PISA values in a simple linear regression analysis, together with periodontal classification, PI, bleeding index, and smoking, but not in the multivariate analysis. In the multivariate linear regression analysis, PISA values were positively correlated with the quantity of current smoking, PI, and severity of periodontal disease. Conclusions PISA integrates multiple periodontal indexes, such as probing pocket depth, BOP, and PI into a numerical variable. PISA is advantageous for quantifying periodontal inflammation and plaque accumulation. PMID:29093989

Fractional order PID controller for improvement of PMSM speed control in aerospace applications

NASA Astrophysics Data System (ADS)

Saraji, Ali Motalebi; Ghanbari, Mahmood

2014-12-01

Because of the benefits reduced size, cost and maintenance, noise, CO2 emissions and increased control flexibility and precision, to meet these expectations, electrical equipment increasingly utilize in modern aircraft systems and aerospace industry rather than conventional mechanic, hydraulic, and pneumatic power systems. Electric motor drives are capable of converting electrical power to drive actuators, pumps, compressors, and other subsystems at variable speeds. In the past decades, permanent magnet synchronous motor (PMSM) and brushless dc (BLDC) motor were investigated for aerospace applications such as aircraft actuators. In this paper, the fractional-order PID controller is used in the design of speed loop of PMSM speed control system. Having more parameters for tuning fractional order PID controller lead to good performance ratio to integer order. This good performance is shown by comparison fractional order PID controller with the conventional PI and tuned PID controller by Genetic algorithm in MATLAB soft wear.

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.

Closed-loop control of a core free rolled EAP actuator

NASA Astrophysics Data System (ADS)

Sarban, Rahimullah; Oubaek, Jakob; Jones, Richard W.

2009-03-01

Tubular dielectric electro-active polymer actuators, also referred as tubular InLastors, have many possible applications. One of the most obvious is as a positioning push-type device. This work examines the feedback closed-loop control of a core-free tubular InLastor fabricated from sheets of PolyPowerTM, an EAP material developed by Danfoss PolyPower A/S, which uses a silicone elastomer in conjunction with smart compliant electrode technology. This is part of an ongoing study to develop a precision positioning feedback control system for this device. Initially proportional and integral (PI) control is considered to provide position control of the tubular InLastor. Control of the tubular Inlastors require more than conventional control, used for linear actuators, because the InLastors display highly nonlinear static voltage-strain and voltage-force characteristics as well as dynamic hysteresis and time-dependent strain behavior. In an attempt to overcome the nonlinear static voltage-strain characteristics of the Inlastors and for improving the dynamic performance of the controlled device, a gain scheduling algorithm is then integrated into the PI controlled system.

New down-converter for UV-stable perovskite solar cells: Phosphor-in-glass

NASA Astrophysics Data System (ADS)

Roh, Hee-Suk; Han, Gill Sang; Lee, Seongha; Kim, Sanghyun; Choi, Sungwoo; Yoon, Chulsoo; Lee, Jung-Kun

2018-06-01

Degradation of hybrid lead halide perovskite by UV light is a crucial issue that limits the commercialization of lead halide perovskite solar cells (PSCs). To address this problem, phosphor-in-glass (PiG) is used to convert UV to visible light. Down-conversion of UV light by PiG dramatically increases UV-stability of PSCs and enables PSCs to harvest UV light that is currently wasted. Performance of PSCs with PiG layer does not change significantly during 100 h-long UV-irradiation, while conventional PSCs degrade quickly by 1 h-long UV-irradiation. After 100 h long UV-irradiation, power conversion efficiency of PSCs with PiG is 440% larger than that of conventional PSCs. This result points a direction toward PSCs which are very stable and highly efficient under UV light.

The effect of a triclosan/copolymer/fluoride 
toothpaste on plaque formation, gingivitis, and 
dentin hypersensitivity: A single-blinded 
randomized clinical study.

PubMed

Al Habashneh, Rola; Farasin, Rawan; Khader, Yousef

2017-01-01

The daily removal of supragingival dental plaque is a key factor in the prevention of gingivitis. The aim of the study was to compare the gingival health benefits of a triclosan/copolymer/fluoride toothpaste (Colgate Total, a fluoride toothpaste containing an antiseptic) to a commercially available toothpaste containing 0.243% sodium fluoride in a silica base (Colgate Herbal, a conventional fluoride toothpaste with herbal extracts). A total of 50 patients with gingivitis and at least one sensitive tooth were included. The subjects were randomly stratified into two groups: Colgate Total toothpaste, and Colgate Herbal toothpaste. After a 4-week pre-experimental phase, baseline Plaque Index (Quigley-Hein Index) (PI), Gingival Index (GI), Gingival Bleeding Index (GBI), and Visual Analog Scale (VAS) were assessed. The PI, GI, GBI, and VAS were reexamined at weeks 4, 12, and 24 after the baseline. Fifty subjects complied with the protocol and completed the study. The conventional fluoride toothpaste with herbal extracts group and the fluoride toothpaste containing an antiseptic group exhibited significant reductions in PI, GI, GBI, and VAS over time. The amount of reduction after 6 months of the treatment was higher in the Total group compared to Herbal group (1.82 vs 1.39, P = .015 for PI; 0.67 vs 0.37, P < .005 for GI; and 56.64% vs 34.26%, P < .005 for GBI). No significant difference was seen for VAS. Twice daily brushing with a toothpaste containing 0.3% triclosan and polyvinyl methyl ether and maleic acid copolymer provides a more effective level of plaque control and gingival health with no effect on decreasing dentin hypersensitivity compared to conventional fluoride toothpaste. Toothpastes containing triclosan/copolymer, in addition to fluoride, result in a higher reduction in plaque, gingival inflammation, and gingival bleeding when compared with fluoride toothpastes without triclosan/copolymer.

An adaptive neuro fuzzy inference system controlled space cector pulse width modulation based HVDC light transmission system under AC fault conditions

NASA Astrophysics Data System (ADS)

Ajay Kumar, M.; Srikanth, N. V.

2014-03-01

In HVDC Light transmission systems, converter control is one of the major fields of present day research works. In this paper, fuzzy logic controller is utilized for controlling both the converters of the space vector pulse width modulation (SVPWM) based HVDC Light transmission systems. Due to its complexity in the rule base formation, an intelligent controller known as adaptive neuro fuzzy inference system (ANFIS) controller is also introduced in this paper. The proposed ANFIS controller changes the PI gains automatically for different operating conditions. A hybrid learning method which combines and exploits the best features of both the back propagation algorithm and least square estimation method is used to train the 5-layer ANFIS controller. The performance of the proposed ANFIS controller is compared and validated with the fuzzy logic controller and also with the fixed gain conventional PI controller. The simulations are carried out in the MATLAB/SIMULINK environment. The results reveal that the proposed ANFIS controller is reducing power fluctuations at both the converters. It also improves the dynamic performance of the test power system effectively when tested for various ac fault conditions.

Emotional Learning Based Intelligent Controllers for Rotor Flux Oriented Control of Induction Motor

NASA Astrophysics Data System (ADS)

Abdollahi, Rohollah; Farhangi, Reza; Yarahmadi, Ali

2014-08-01

This paper presents design and evaluation of a novel approach based on emotional learning to improve the speed control system of rotor flux oriented control of induction motor. The controller includes a neuro-fuzzy system with speed error and its derivative as inputs. A fuzzy critic evaluates the present situation, and provides the emotional signal (stress). The controller modifies its characteristics so that the critics stress is reduced. The comparative simulation results show that the proposed controller is more robust and hence found to be a suitable replacement of the conventional PI controller for the high performance industrial drive applications.

Design and application of discrete wavelet packet transform based multiresolution controller for liquid level system.

PubMed

Paul, Rimi; Sengupta, Anindita

2017-11-01

A new controller based on discrete wavelet packet transform (DWPT) for liquid level system (LLS) has been presented here. This controller generates control signal using node coefficients of the error signal which interprets many implicit phenomena such as process dynamics, measurement noise and effect of external disturbances. Through simulation results on LLS problem, this controller is shown to perform faster than both the discrete wavelet transform based controller and conventional proportional integral controller. Also, it is more efficient in terms of its ability to provide better noise rejection. To overcome the wind up phenomenon by considering the saturation due to presence of actuator, anti-wind up technique is applied to the conventional PI controller and compared to the wavelet packet transform based controller. In this case also, packet controller is found better than the other ones. This similar work has been extended for analogous first order RC plant as well as second order plant also. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Comparing near-infrared conventional diffuse reflectance spectroscopy and hyperspectral imaging for determination of the bulk properties of solid samples by multivariate regression: determination of Mooney viscosity and plasticity indices of natural rubber.

PubMed

Juliano da Silva, Carlos; Pasquini, Celio

2015-01-21

Conventional reflectance spectroscopy (NIRS) and hyperspectral imaging (HI) in the near-infrared region (1000-2500 nm) are evaluated and compared, using, as the case study, the determination of relevant properties related to the quality of natural rubber. Mooney viscosity (MV) and plasticity indices (PI) (PI0 - original plasticity, PI30 - plasticity after accelerated aging, and PRI - the plasticity retention index after accelerated aging) of rubber were determined using multivariate regression models. Two hundred and eighty six samples of rubber were measured using conventional and hyperspectral near-infrared imaging reflectance instruments in the range of 1000-2500 nm. The sample set was split into regression (n = 191) and external validation (n = 95) sub-sets. Three instruments were employed for data acquisition: a line scanning hyperspectral camera and two conventional FT-NIR spectrometers. Sample heterogeneity was evaluated using hyperspectral images obtained with a resolution of 150 × 150 μm and principal component analysis. The probed sample area (5 cm(2); 24,000 pixels) to achieve representativeness was found to be equivalent to the average of 6 spectra for a 1 cm diameter probing circular window of one FT-NIR instrument. The other spectrophotometer can probe the whole sample in only one measurement. The results show that the rubber properties can be determined with very similar accuracy and precision by Partial Least Square (PLS) regression models regardless of whether HI-NIR or conventional FT-NIR produce the spectral datasets. The best Root Mean Square Errors of Prediction (RMSEPs) of external validation for MV, PI0, PI30, and PRI were 4.3, 1.8, 3.4, and 5.3%, respectively. Though the quantitative results provided by the three instruments can be considered equivalent, the hyperspectral imaging instrument presents a number of advantages, being about 6 times faster than conventional bulk spectrometers, producing robust spectral data by ensuring sample representativeness, and minimizing the effect of the presence of contaminants.

Fractional order PID controller for improvement of PMSM speed control in aerospace applications

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

Saraji, Ali Motalebi; Ghanbari, Mahmood

Because of the benefits reduced size, cost and maintenance, noise, CO2 emissions and increased control flexibility and precision, to meet these expectations, electrical equipment increasingly utilize in modern aircraft systems and aerospace industry rather than conventional mechanic, hydraulic, and pneumatic power systems. Electric motor drives are capable of converting electrical power to drive actuators, pumps, compressors, and other subsystems at variable speeds. In the past decades, permanent magnet synchronous motor (PMSM) and brushless dc (BLDC) motor were investigated for aerospace applications such as aircraft actuators. In this paper, the fractional-order PID controller is used in the design of speed loopmore » of PMSM speed control system. Having more parameters for tuning fractional order PID controller lead to good performance ratio to integer order. This good performance is shown by comparison fractional order PID controller with the conventional PI and tuned PID controller by Genetic algorithm in MATLAB soft wear.« less

Fuzzy – PI controller to control the velocity parameter of Induction Motor

NASA Astrophysics Data System (ADS)

Malathy, R.; Balaji, V.

2018-04-01

The major application of Induction motor includes the usage of the same in industries because of its high robustness, reliability, low cost, highefficiency and good self-starting capability. Even though it has the above mentioned advantages, it also have some limitations: (1) the standard motor is not a true constant-speed machine, itsfull-load slip varies less than 1 % (in high-horsepower motors).And (2) it is not inherently capable of providing variable-speedoperation. In order to solve the above mentioned problem smart motor controls and variable speed controllers are used. Motor applications involve non linearity features, which can be controlled by Fuzzy logic controller as it is capable of handling those features with high efficiency and it act similar to human operator. This paper presents individuality of the plant modelling. The fuzzy logic controller (FLC)trusts on a set of linguistic if-then rules, a rule-based Mamdani for closed loop Induction Motor model. Themotor model is designed and membership functions are chosenaccording to the parameters of the motor model. Simulation results contains non linearity in induction motor model. A conventional PI controller iscompared practically to fuzzy logic controller using Simulink.

Potential-sensing electrochemical atomic force microscopy for in operando analysis of water-splitting catalysts and interfaces

NASA Astrophysics Data System (ADS)

Nellist, Michael R.; Laskowski, Forrest A. L.; Qiu, Jingjing; Hajibabaei, Hamed; Sivula, Kevin; Hamann, Thomas W.; Boettcher, Shannon W.

2018-01-01

Heterogeneous electrochemical phenomena, such as (photo)electrochemical water splitting to generate hydrogen using semiconductors and/or electrocatalysts, are driven by the accumulated charge carriers and thus the interfacial electrochemical potential gradients that promote charge transfer. However, measurements of the "surface" electrochemical potential during operation are not generally possible using conventional electrochemical techniques, which measure/control the potential of a conducting electrode substrate. Here we show that the nanoscale conducting tip of an atomic force microscope cantilever can sense the surface electrochemical potential of electrocatalysts in operando. To demonstrate utility, we measure the potential-dependent and thickness-dependent electronic properties of cobalt (oxy)hydroxide phosphate (CoPi). We then show that CoPi, when deposited on illuminated haematite (α-Fe2O3) photoelectrodes, acts as both a hole collector and an oxygen evolution catalyst. We demonstrate the versatility of the technique by comparing surface potentials of CoPi-decorated planar and mesoporous haematite and discuss viability for broader application in the study of electrochemical phenomena.

The effect of bracket ligation on the periodontal status of adolescents undergoing orthodontic treatment. A systematic review and meta-analysis.

PubMed

Arnold, Sina; Koletsi, Despina; Patcas, Raphael; Eliades, Theodore

2016-11-01

This systematic review aimed to critically appraise the evidence regarding the effect of bracket ligation type on the periodontal conditions of adolescents undergoing orthodontic treatment. Search terms included randomized controlled trial (RCTs), controlled clinical trials, ligation, bracket, periodontal, inflammation. Risk of bias assessment was made using the Cochrane risk of bias tool and the quality of evidence was assessed with GRADE. Electronic Database search of published and unpublished literature was performed without language restriction in May 25, 2016 (MEDLINE via Pubmed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Clinical Trials.gov and National Research Register). Of 140 articles initially retrieved, 8 were eligible for inclusion in the systematic review, while 4 RCTs with unclear risk of bias were included in the quantitative synthesis, all comparing self-ligating to conventional steel ligated brackets. Random effects meta-analyses were implemented. At 4-6 weeks after bracket placement there was no evidence to support the use of either type of bracket for achieving improved plaque- (PI) and gingival index (GI). At 3-6 months, there was scarce evidence of greater PI increase for conventional brackets. GI and pocket depth pooled estimates did not reveal significant differences between the two systems. The quality of the evidence was moderate according to GRADE for all outcomes. Overall, non-significant differences on the periodontal status of adolescents undergoing orthodontic treatment with either conventional or self-ligating brackets were detected. The periodontal status of adolescents undergoing orthodontic treatment is of considerable importance. The synthesis of the available evidence on oral hygiene related factors will provide insights to best clinical practice during the course of orthodontic treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

High-accuracy resolver-to-digital conversion via phase locked loop based on PID controller

NASA Astrophysics Data System (ADS)

Li, Yaoling; Wu, Zhong

2018-03-01

The problem of resolver-to-digital conversion (RDC) is transformed into the problem of angle tracking control, and a phase locked loop (PLL) method based on PID controller is proposed in this paper. This controller comprises a typical PI controller plus an incomplete differential which can avoid the amplification of higher-frequency noise components by filtering the phase detection error with a low-pass filter. Compared with conventional ones, the proposed PLL method makes the converter a system of type III and thus the conversion accuracy can be improved. Experimental results demonstrate the effectiveness of the proposed method.

Rapid activation of spleen dendritic cell subsets following lymphocytic choriomeningitis virus infection of mice: analysis of the involvement of type 1 IFN.

PubMed

Montoya, Maria; Edwards, Matthew J; Reid, Delyth M; Borrow, Persephone

2005-02-15

In this study, we report the dynamic changes in activation and functions that occur in spleen dendritic cell (sDC) subsets following infection of mice with a natural murine pathogen, lymphocytic choriomeningitis virus (LCMV). Within 24 h postinfection (pi), sDCs acquired the ability to stimulate naive LCMV-specific CD8+ T cells ex vivo. Conventional (CD11chigh CD8+ and CD4+) sDC subsets rapidly up-regulated expression of costimulatory molecules and began to produce proinflammatory cytokines. Their tendency to undergo apoptosis ex vivo simultaneously increased, and in vivo the number of conventional DCs in the spleen decreased markedly, dropping approximately 2-fold by day 3 pi. Conversely, the number of plasmacytoid (CD11clowB220+) DCs in the spleen increased, so that they constituted almost 40% of sDCs by day 3 pi. Type 1 IFN production was up-regulated in plasmacytoid DCs by 24 h pi. Analysis of DC activation and maturation in mice unable to respond to type 1 IFNs implicated these cytokines in driving infection-associated phenotypic activation of conventional DCs and their enhanced tendency to undergo apoptosis, but also indicated the existence of type 1 IFN-independent pathways for the functional maturation of DCs during LCMV infection.

Observation of an enhancement in e{sup +}e{sup -}{yields}{Upsilon}(1S){pi}{sup +}{pi}{sup -}, {Upsilon}(2S){pi}{sup +}{pi}{sup -}, and {Upsilon}(3S){pi}{sup +}{pi}{sup -} production near {radical}(s)=10.89 GeV

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

Chen, K.-F.; Hou, W.-S.; Chang, P.

2010-11-01

We measure the production cross sections for e{sup +}e{sup -}{yields}{Upsilon}(1S){pi}{sup +}{pi}{sup -}, {Upsilon}(2S){pi}{sup +}{pi}{sup -}, and {Upsilon}(3S){pi}{sup +}{pi}{sup -} as a function of {radical}(s) between 10.83 GeV and 11.02 GeV. The data consist of 8.1 fb{sup -1} collected with the Belle detector at the KEKB e{sup +}e{sup -} collider. We observe enhanced production in all three final states that does not agree well with the conventional {Upsilon}(10860) line shape. A fit using a Breit-Wigner resonance shape yields a peak mass of [10 888.4{sub -2.6}{sup +2.7}(stat){+-}1.2(syst)] MeV/c{sup 2} and a width of [30.7{sub -7.0}{sup +8.3}(stat){+-}3.1(syst)] MeV/c{sup 2}.

Design of static synchronous series compensator based damping controller employing invasive weed optimization algorithm.

PubMed

Ahmed, Ashik; Al-Amin, Rasheduzzaman; Amin, Ruhul

2014-01-01

This paper proposes designing of Static Synchronous Series Compensator (SSSC) based damping controller to enhance the stability of a Single Machine Infinite Bus (SMIB) system by means of Invasive Weed Optimization (IWO) technique. Conventional PI controller is used as the SSSC damping controller which takes rotor speed deviation as the input. The damping controller parameters are tuned based on time integral of absolute error based cost function using IWO. Performance of IWO based controller is compared to that of Particle Swarm Optimization (PSO) based controller. Time domain based simulation results are presented and performance of the controllers under different loading conditions and fault scenarios is studied in order to illustrate the effectiveness of the IWO based design approach.

Narrow Gap, High Mobility, and Stable Pi Conjugated Polymers

DTIC Science & Technology

2012-09-20

wide-angle X-ray scattering (2D-WAXS) of P5.1 (extruded at 210oC). This trend is reflected in conventional bulk- heterojunction OPV devices as shown...Additives in Molecular Bulk Heterojunction Solar Cells Using a bithiophene capped, isoindigo core, DAD molecule as the donor phase, and PCBM as the...PCE values of 3.7% as illustrated in Figure 11. Figure 11. Combining interface control using MoOx as an electron transport material and PDMS

A Pilot Study of Collective Parent Engagement and Children's Academic Achievement

ERIC Educational Resources Information Center

Alameda-Lawson, Tania

2014-01-01

Parent involvement (PI) programs typically represent an important improvement strategy for schools serving low-income children of color. This pilot study offers an alternative to conventional PI approaches, collective parent engagement (CPE). The study relied on a post hoc, quasiexperimental design, and data were collected from 32 low-income,…

Robust control of integrated motor-transmission powertrain system over controller area network for automotive applications

NASA Astrophysics Data System (ADS)

Zhu, Xiaoyuan; Zhang, Hui; Cao, Dongpu; Fang, Zongde

2015-06-01

Integrated motor-transmission (IMT) powertrain system with directly coupled motor and gearbox is a good choice for electric commercial vehicles (e.g., pure electric buses) due to its potential in motor size reduction and energy efficiency improvement. However, the controller design for powertrain oscillation damping becomes challenging due to the elimination of damping components. On the other hand, as controller area network (CAN) is commonly adopted in modern vehicle system, the network-induced time-varying delays that caused by bandwidth limitation will further lead to powertrain vibration or even destabilize the powertrain control system. Therefore, in this paper, a robust energy-to-peak controller is proposed for the IMT powertrain system to address the oscillation damping problem and also attenuate the external disturbance. The control law adopted here is based on a multivariable PI control, which ensures the applicability and performance of the proposed controller in engineering practice. With the linearized delay uncertainties characterized by polytopic inclusions, a delay-free closed-loop augmented system is established for the IMT powertrain system under discrete-time framework. The proposed controller design problem is then converted to a static output feedback (SOF) controller design problem where the feedback control gains are obtained by solving a set of linear matrix inequalities (LMIs). The effectiveness as well as robustness of the proposed controller is demonstrated by comparing its performance against that of a conventional PI controller.

Relation between scattering and production amplitude--Case of intermediate {sigma}-particle in {pi}{pi}-system--

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

Ishida, Muneyuki; Ishida, Shin; Ishida, Taku

1998-05-29

The relation between scattering and production amplitudes are investigated, using a simple field theoretical model, from the general viewpoint of unitarity and the applicability of final state interaction (FSI-) theorem. The IA-method and VMW-method, which are applied to our phenomenological analyses [2,3] suggesting the {sigma}-existence, are obtained as the physical state representations of scattering and production amplitudes, respectively. Moreover, the VMW-method is shown to be an effective method to obtain the resonance properties from general production processes, while the conventional analyses based on the 'universality' of {pi}{pi}-scattering amplitude are powerless for this purpose.

Relative equilibrium plot improves graphical analysis and allows bias correction of standardized uptake value ratio in quantitative 11C-PiB PET studies.

PubMed

Zhou, Yun; Sojkova, Jitka; Resnick, Susan M; Wong, Dean F

2012-04-01

Both the standardized uptake value ratio (SUVR) and the Logan plot result in biased distribution volume ratios (DVRs) in ligand-receptor dynamic PET studies. The objective of this study was to use a recently developed relative equilibrium-based graphical (RE) plot method to improve and simplify the 2 commonly used methods for quantification of (11)C-Pittsburgh compound B ((11)C-PiB) PET. The overestimation of DVR in SUVR was analyzed theoretically using the Logan and the RE plots. A bias-corrected SUVR (bcSUVR) was derived from the RE plot. Seventy-eight (11)C-PiB dynamic PET scans (66 from controls and 12 from participants with mild cognitive impaired [MCI] from the Baltimore Longitudinal Study of Aging) were acquired over 90 min. Regions of interest (ROIs) were defined on coregistered MR images. Both the ROI and the pixelwise time-activity curves were used to evaluate the estimates of DVR. DVRs obtained using the Logan plot applied to ROI time-activity curves were used as a reference for comparison of DVR estimates. Results from the theoretic analysis were confirmed by human studies. ROI estimates from the RE plot and the bcSUVR were nearly identical to those from the Logan plot with ROI time-activity curves. In contrast, ROI estimates from DVR images in frontal, temporal, parietal, and cingulate regions and the striatum were underestimated by the Logan plot (controls, 4%-12%; MCI, 9%-16%) and overestimated by the SUVR (controls, 8%-16%; MCI, 16%-24%). This bias was higher in the MCI group than in controls (P < 0.01) but was not present when data were analyzed using either the RE plot or the bcSUVR. The RE plot improves pixelwise quantification of (11)C-PiB dynamic PET, compared with the conventional Logan plot. The bcSUVR results in lower bias and higher consistency of DVR estimates than of SUVR. The RE plot and the bcSUVR are practical quantitative approaches that improve the analysis of (11)C-PiB studies.

Relative equilibrium plot improves graphical analysis and allows bias correction of SUVR in quantitative [11C]PiB PET studies

PubMed Central

Zhou, Yun; Sojkova, Jitka; Resnick, Susan M.; Wong, Dean F.

2012-01-01

Both the standardized uptake value ratio (SUVR) and the Logan plot result in biased distribution volume ratios (DVR) in ligand-receptor dynamic PET studies. The objective of this study is to use a recently developed relative equilibrium-based graphical plot (RE plot) method to improve and simplify the two commonly used methods for quantification of [11C]PiB PET. Methods The overestimation of DVR in SUVR was analyzed theoretically using the Logan and the RE plots. A bias-corrected SUVR (bcSUVR) was derived from the RE plot. Seventy-eight [11C]PiB dynamic PET scans (66 from controls and 12 from mildly cognitively impaired participants (MCI) from the Baltimore Longitudinal Study of Aging (BLSA)) were acquired over 90 minutes. Regions of interest (ROIs) were defined on coregistered MRIs. Both the ROI and pixelwise time activity curves (TACs) were used to evaluate the estimates of DVR. DVRs obtained using the Logan plot applied to ROI TACs were used as a reference for comparison of DVR estimates. Results Results from the theoretical analysis were confirmed by human studies. ROI estimates from the RE plot and the bcSUVR were nearly identical to those from the Logan plot with ROI TACs. In contrast, ROI estimates from DVR images in frontal, temporal, parietal, cingulate regions, and the striatum were underestimated by the Logan plot (controls 4 – 12%; MCI 9 – 16%) and overestimated by the SUVR (controls 8 – 16%; MCI 16 – 24%). This bias was higher in the MCI group than in controls (p < 0.01) but was not present when data were analyzed using either the RE plot or the bcSUVR. Conclusion The RE plot improves pixel-wise quantification of [11C]PiB dynamic PET compared to the conventional Logan plot. The bcSUVR results in lower bias and higher consistency of DVR estimates compared to SUVR. The RE plot and the bcSUVR are practical quantitative approaches that improve the analysis of [11C]PiB studies. PMID:22414634

Electron beam energy stabilization using a neural network hybrid controller at the Australian Synchrotron Linac.

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

Meier, E.; Morgan, M. J.; Biedron, S. G.

2009-01-01

This paper describes the implementation of a neural network hybrid controller for energy stabilization at the Australian Synchrotron Linac. The structure of the controller consists of a neural network (NNET) feed forward control, augmented by a conventional Proportional-Integral (PI) feedback controller to ensure stability of the system. The system is provided with past states of the machine in order to predict its future state, and therefore apply appropriate feed forward control. The NNET is able to cancel multiple frequency jitter in real-time. When it is not performing optimally due to jitter changes, the system can successfully be augmented by themore » PI controller to attenuate the remaining perturbations. With a view to control the energy and bunch length at the FERMI{at}Elettra Free Electron Laser (FEL), the present study considers a neural network hybrid feed forward-feedback type of control to rectify limitations related to feedback systems, such as poor response for high jitter frequencies or limited bandwidth, while ensuring robustness of control. The Australian Synchrotron Linac is equipped with a beam position monitor (BPM), that was provided by Sincrotrone Trieste from a former transport line thus allowing energy measurements and energy control experiments. The present study will consequently focus on correcting energy jitter induced by variations in klystron phase and voltage.« less

A brief motivational interviewing as an adjunct to periodontal therapy-A potential tool to reduce relapse in oral hygiene behaviours. A three-year study.

PubMed

Stenman, J; Wennström, J L; Abrahamsson, K H

2018-05-01

To evaluate (ii) whether inclusion of a single motivational interviewing (MI) session, as an adjunct to periodontal therapy, might be beneficial for preventing relapse in oral hygiene behaviours among patients treated for chronic periodontitis and (ii) whether individual and clinical characteristics can be of predictive value for retention of sufficient oral hygiene behaviours. This 3-year follow-up of a previously reported randomized controlled trial (RCT) study of 6-month duration included 26 patients. Patients in the test group had received one MI session by a clinical psychologist before initiation of the periodontal treatment. Otherwise, all patients followed the same treatment protocol for conventional educational intervention and non-surgical periodontal therapy. Efficacy variables assessed for evaluation of the standard of self-performed periodontal infection control were marginal bleeding index (MBI; primary efficacy variable) and plaque score (PI). The patterns of change in MBI and PI scores were similar for test and control groups over the observation period. At 3 years, both groups showed a desirable mean full-mouth MBI of 15%, a figure that was comparable to that at the short-term evaluation after active periodontal treatment. The post-treatment MBI was the only variable identified as a predictor of retained adequate oral hygiene behaviours. A single MI session as an adjunct to conventional periodontal therapy could not be proven to be of long-term beneficial additive effect with regard to prevention of relapse in oral hygiene behaviour. Desirable standard of self-performed infection control after active periodontal treatment predicted the retention of sufficient oral hygiene behaviour over time. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Speed tracking and synchronization of multiple motors using ring coupling control and adaptive sliding mode control.

PubMed

Li, Le-Bao; Sun, Ling-Ling; Zhang, Sheng-Zhou; Yang, Qing-Quan

2015-09-01

A new control approach for speed tracking and synchronization of multiple motors is developed, by incorporating an adaptive sliding mode control (ASMC) technique into a ring coupling synchronization control structure. This control approach can stabilize speed tracking of each motor and synchronize its motion with other motors' motion so that speed tracking errors and synchronization errors converge to zero. Moreover, an adaptive law is exploited to estimate the unknown bound of uncertainty, which is obtained in the sense of Lyapunov stability theorem to minimize the control effort and attenuate chattering. Performance comparisons with parallel control, relative coupling control and conventional PI control are investigated on a four-motor synchronization control system. Extensive simulation results show the effectiveness of the proposed control scheme. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

Deposition and thermal characterization of nano-structured aluminum nitride thin film on Cu-W substrate for high power light emitting diode package.

PubMed

Cho, Hyun Min; Kim, Min-Sun

2014-08-01

In this study, we developed AlN thick film on metal substrate for hybrid type LED package such as chip on board (COB) using metal printed circuit board (PCB). Conventional metal PCB uses ceramic-polymer composite as electrical insulating layer. Thermal conductivities of such type dielectric film are typically in the range of 1~4 W/m · K depending on the ceramic filler. Also, Al or Cu alloy are mainly used for metal base for high thermal conduction to dissipate heat from thermal source mounted on metal PCB. Here we used Cu-W alloy with low thermal expansion coefficient as metal substrate to reduce thermal stress between insulating layer and base metal. AlN with polyimide (PI) powder were used as starting materials for deposition. We could obtain very high thermal conductivity of 28.3 W/m · K from deposited AlN-PI thin film by AlN-3 wt% PI powder. We made hybrid type high power LED package using AlN-PI thin film. We tested thermal performance of this film by thermal transient measurement and compared with conventional metal PCB substrate.

Direct energy balance based active disturbance rejection control for coal-fired power plant.

PubMed

Sun, Li; Hua, Qingsong; Li, Donghai; Pan, Lei; Xue, Yali; Lee, Kwang Y

2017-09-01

The conventional direct energy balance (DEB) based PI control can fulfill the fundamental tracking requirements of the coal-fired power plant. However, it is challenging to deal with the cases when the coal quality variation is present. To this end, this paper introduces the active disturbance rejection control (ADRC) to the DEB structure, where the coal quality variation is deemed as a kind of unknown disturbance that can be estimated and mitigated promptly. Firstly, the nonlinearity of a recent power plant model is analyzed based on the gap metric, which provides guidance on how to set the pressure set-point in line with the power demand. Secondly, the approximate decoupling effect of the DEB structure is analyzed based on the relative gain analysis in frequency domain. Finally, the synthesis of the DEB based ADRC control system is carried out based on multi-objective optimization. The optimized ADRC results show that the integrated absolute error (IAE) indices of the tracking performances in both loops can be simultaneously improved, in comparison with the DEB based PI control and H ∞ control system. The regulation performance in the presence of the coal quality variation is significantly improved under the ADRC control scheme. Moreover, the robustness of the proposed strategy is shown comparable with the H ∞ control. Copyright © 2017. Published by Elsevier Ltd.

Microbead-based immunoassay using the outer membrane layer of Escherichia coli combined with autodisplayed Z-domains

NASA Astrophysics Data System (ADS)

Kim, Do-Hoon; Bong, Ji-Hong; Yoo, Gu; Chang, Seo-Yoon; Park, Min; Chang, Young Wook; Kang, Min-Jung; Jose, Joachim; Pyun, Jae-Chul

2016-01-01

The Z-domain has the potential to control the orientation of immobilized antibodies because of its binding affinity to the Fc regions of antibodies (IgGs). In this work, Z-domains were autodisplayed on the outer membrane (OM) of Escherichia coli. OM particles were isolated and coated onto microbeads with positive, neutral, or negative surface charges. Other conditions such as incubation time and initial OM concentration were also optimized for the OM coating to obtain maximum antibody-binding. Using three kinds of model proteins with different isoelectric points (pI), streptavidin (pI = 5, negative charge at pH 7), horseradish peroxidase (pI = 7, neutral charge at pH 7), and avidin (pI = 10, positive charge at pH 7), protein immobilization onto the microbeads was carried out through physical adsorption and electrostatic interactions. Using fluorescently labeled antibodies and fluorescence-activated cell sorting, it was determined that the neutral and the positively charged microbeads effectively bound antibodies while minimizing non-specific protein binding. The OM-coated microbeads with autodisplayed Z-domains were applied to C-reactive protein immunoassay. This immunoassay achieved 5-fold improved sensitivity compared to conventional immunoassay based on physical adsorption of antibodies at the cutoff concentration of medical diagnosis of inflammatory diseases (1000 ng/ml) and cardiovascular diseases (200 ng/ml).

Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations

PubMed Central

LoPiccolo, Jaclyn; Blumenthal, Gideon M.; Bernstein, Wendy B.; Dennis, Phillip A.

2008-01-01

The PI3K/Akt/mTOR pathway is a prototypic survival pathway that is constitutively activated in many types of cancer. Mechanisms for pathway activation include loss of tumor suppressor PTEN function, amplification or mutation of PI3K, amplification or mutation of Akt, activation of growth factor receptors, and exposure to carcinogens. Once activated, signaling through Akt can be propagated to a diverse array of substrates, including mTOR, a key regulator of protein translation. This pathway is an attractive therapeutic target in cancer because it serves as a convergence point for many growth stimuli, and through its downstream substrates, controls cellular processes that contribute to the initiation and maintenance of cancer. Moreover, activation of the Akt/mTOR pathway confers resistance to many types of cancer therapy, and is a poor prognostic factor for many types of cancers. This review will provide an update on the clinical progress of various agents that target the pathway, such as the Akt inhibitors perifosine and PX-866 and mTOR inhibitors (rapamycin, CCI-779, RAD-001) and discuss strategies to combine these pathway inhibitors with conventional chemotherapy, radiotherapy, as well as newer targeted agents. We will also discuss how the complex regulation of the PI3K/Akt/mTOR pathway poses practical issues concerning the design of clinical trials, potential toxicities and criteria for patient selection. PMID:18166498

Stable adaptive PI control for permanent magnet synchronous motor drive based on improved JITL technique.

PubMed

Zheng, Shiqi; Tang, Xiaoqi; Song, Bao; Lu, Shaowu; Ye, Bosheng

2013-07-01

In this paper, a stable adaptive PI control strategy based on the improved just-in-time learning (IJITL) technique is proposed for permanent magnet synchronous motor (PMSM) drive. Firstly, the traditional JITL technique is improved. The new IJITL technique has less computational burden and is more suitable for online identification of the PMSM drive system which is highly real-time compared to traditional JITL. In this way, the PMSM drive system is identified by IJITL technique, which provides information to an adaptive PI controller. Secondly, the adaptive PI controller is designed in discrete time domain which is composed of a PI controller and a supervisory controller. The PI controller is capable of automatically online tuning the control gains based on the gradient descent method and the supervisory controller is developed to eliminate the effect of the approximation error introduced by the PI controller upon the system stability in the Lyapunov sense. Finally, experimental results on the PMSM drive system show accurate identification and favorable tracking performance. Copyright © 2013 ISA. Published by Elsevier Ltd. All rights reserved.

Improved model reduction and tuning of fractional-order PI(λ)D(μ) controllers for analytical rule extraction with genetic programming.

PubMed

Das, Saptarshi; Pan, Indranil; Das, Shantanu; Gupta, Amitava

2012-03-01

Genetic algorithm (GA) has been used in this study for a new approach of suboptimal model reduction in the Nyquist plane and optimal time domain tuning of proportional-integral-derivative (PID) and fractional-order (FO) PI(λ)D(μ) controllers. Simulation studies show that the new Nyquist-based model reduction technique outperforms the conventional H(2)-norm-based reduced parameter modeling technique. With the tuned controller parameters and reduced-order model parameter dataset, optimum tuning rules have been developed with a test-bench of higher-order processes via genetic programming (GP). The GP performs a symbolic regression on the reduced process parameters to evolve a tuning rule which provides the best analytical expression to map the data. The tuning rules are developed for a minimum time domain integral performance index described by a weighted sum of error index and controller effort. From the reported Pareto optimal front of the GP-based optimal rule extraction technique, a trade-off can be made between the complexity of the tuning formulae and the control performance. The efficacy of the single-gene and multi-gene GP-based tuning rules has been compared with the original GA-based control performance for the PID and PI(λ)D(μ) controllers, handling four different classes of representative higher-order processes. These rules are very useful for process control engineers, as they inherit the power of the GA-based tuning methodology, but can be easily calculated without the requirement for running the computationally intensive GA every time. Three-dimensional plots of the required variation in PID/fractional-order PID (FOPID) controller parameters with reduced process parameters have been shown as a guideline for the operator. Parametric robustness of the reported GP-based tuning rules has also been shown with credible simulation examples. Copyright © 2011 ISA. Published by Elsevier Ltd. All rights reserved.

Control of photon storage time using phase locking.

PubMed

Ham, Byoung S

2010-01-18

A photon echo storage-time extension protocol is presented by using a phase locking method in a three-level backward propagation scheme, where phase locking serves as a conditional stopper of the rephasing process in conventional two-pulse photon echoes. The backward propagation scheme solves the critical problems of extremely low retrieval efficiency and pi rephasing pulse-caused spontaneous emission noise in photon echo based quantum memories. The physics of the storage time extension lies in the imminent population transfer from the excited state to an auxiliary spin state by a phase locking control pulse. We numerically demonstrate that the storage time is lengthened by spin dephasing time.

Constant Switching Frequency DTC for Matrix Converter Fed Speed Sensorless Induction Motor Drive

NASA Astrophysics Data System (ADS)

Mir, Tabish Nazir; Singh, Bhim; Bhat, Abdul Hamid

2018-05-01

The paper presents a constant switching frequency scheme for speed sensorless Direct Torque Control (DTC) of Matrix Converter fed Induction Motor Drive. The use of matrix converter facilitates improved power quality on input as well as motor side, along with Input Power Factor control, besides eliminating the need for heavy passive elements. Moreover, DTC through Space Vector Modulation helps in achieving a fast control over the torque and flux of the motor, with added benefit of constant switching frequency. A constant switching frequency aids in maintaining desired power quality of AC mains current even at low motor speeds, and simplifies input filter design of the matrix converter, as compared to conventional hysteresis based DTC. Further, stator voltage estimation from sensed input voltage, and subsequent stator (and rotor) flux estimation is done. For speed sensorless operation, a Model Reference Adaptive System is used, which emulates the speed dependent rotor flux equations of the induction motor. The error between conventionally estimated rotor flux (reference model) and the rotor flux estimated through the adaptive observer is processed through PI controller to generate the rotor speed estimate.

Survival in individuals with severe alpha 1-antitrypsin deficiency (PiZZ) in comparison to a general population with known smoking habits.

PubMed

Tanash, Hanan A; Ekström, Magnus; Rönmark, Eva; Lindberg, Anne; Piitulainen, Eeva

2017-09-01

Knowledge about the natural history of severe alpha 1-antitrypsin (AAT) deficiency (PiZZ) is limited. Our aim was to compare the survival of PiZZ individuals with randomly selected controls from the Swedish general population.The PiZZ subjects (n=1585) were selected from the Swedish National AATD Register. The controls (n=5999) were randomly selected from the Swedish population register. Smoking habits were known for all subjects.Median follow-up times for the PiZZ subjects (731 never-smokers) and controls (3179 never-smokers) were 12 and 17 years, respectively (p<0.001). During follow-up, 473 PiZZ subjects (30%), and 747 controls (12%) died. The PiZZ subjects had a significantly shorter survival time than the controls, p<0.001. After adjustment for gender, age, smoking habits and presence of respiratory symptoms, the risk of death was still significantly higher for the PiZZ individuals than for the controls, hazard ratio (HR) 3.2 (95% CI 2.8-3.6; p<0.001). By contrast, the risk of death was not increased in never-smoking PiZZ individuals identified by screening, compared to never-smoking controls, HR 1.2 (95% CI 0.6-2.2).The never-smoking PiZZ individuals identified by screening had a similar life expectancy to the never-smokers in the Swedish general population. Early diagnosis of AAT deficiency is of utmost importance. Copyright ©ERS 2017.

76 FR 16850 - 60-Day Notice of Proposed Information Collection: Agency Form DS-4127, NEA/PI Online Performance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-25

... Form DS- 4127, NEA/PI Online Performance Reporting System (PRS), OMB Control Number 1405-0183. ACTION... Collection: NEA/PI Online Performance Reporting System (PRS). OMB Control Number: 1405-0183. Type of Request: Renewal. Originating Office: NEA/PI. Form Number: DS-4127. Respondents: Recipients of NEA/PI grants...

Membrane permeabilization of mammalian cells using bursts of high magnetic field pulses

PubMed Central

Grainys, Audrius; Kranjc, Matej; Miklavčič, Damijan

2017-01-01

Background Cell membrane permeabilization by pulsed electromagnetic fields (PEMF) is a novel contactless method which results in effects similar to conventional electroporation. The non-invasiveness of the methodology, independence from the biological object homogeneity and electrical conductance introduce high flexibility and potential applicability of the PEMF in biomedicine, food processing, and biotechnology. The inferior effectiveness of the PEMF permeabilization compared to standard electroporation and the lack of clear description of the induced transmembrane transport are currently of major concern. Methods The PEMF permeabilization experiments have been performed using a 5.5 T, 1.2 J pulse generator with a multilayer inductor as an applicator. We investigated the feasibility to increase membrane permeability of Chinese Hamster Ovary (CHO) cells using short microsecond (15 µs) pulse bursts (100 or 200 pulses) at low frequency (1 Hz) and high dB/dt (>106 T/s). The effectiveness of the treatment was evaluated by fluorescence microscopy and flow cytometry using two different fluorescent dyes: propidium iodide (PI) and YO-PRO®-1 (YP). The results were compared to conventional electroporation (single pulse, 1.2 kV/cm, 100 µs), i.e., positive control. Results The proposed PEMF protocols (both for 100 and 200 pulses) resulted in increased number of permeable cells (70 ± 11% for PI and 67 ± 9% for YP). Both cell permeabilization assays also showed a significant (8 ± 2% for PI and 35 ± 14% for YP) increase in fluorescence intensity indicating membrane permeabilization. The survival was not affected. Discussion The obtained results demonstrate the potential of PEMF as a contactless treatment for achieving reversible permeabilization of biological cells. Similar to electroporation, the PEMF permeabilization efficacy is influenced by pulse parameters in a dose-dependent manner. PMID:28462057

Gingival crevicular fluid volume and periodontal parameters alterations after use of conventional and self-ligating brackets.

PubMed

Bergamo, Ana Zn; Nelson-Filho, Paulo; Romano, Fábio L; da Silva, Raquel Ab; Saraiva, Maria Cp; da Silva, Lea Ab; Matsumoto, Mirian An

2016-12-01

The aim of this study was to evaluate the alterations on plaque index (PI), gingival index (GI), gingival bleeding index (GBI), and gingival crevicular fluid (GCF) volume after use of three different brackets types for 60 days. Setting Participants: The sample comprised 20 patients of both sexes aged 11-15 years (mean age: 13.3 years), with permanent dentition, adequate oral hygiene, and mild tooth crowding, overjet, and overbite. A conventional metallic bracket Gemini™, and two different brands of self-ligating brackets - In-Ovation ® R and SmartClip™ - were bonded to the maxillary incisors and canines. PI, GI, GBI scores, and GCF volume were measured before and 30 and 60 days after bonding of the brackets. Data were analysed statistically using non-parametric tests coefficient at a 5% significance level. There was no statistically significant correlation (P > 0.05) between tooth crowding, overjet, and overbite and the PI, GI, GBI scores, and GCF volume before bonding, indicating no influence of malocclusion on the clinical parameters. Regardless of the bracket design, no statistically significant difference (P > 0.05) was found for GI, GBI scores. PI and GCF volume showed a significant difference among the brackets in different periods. In pairwise comparisons a significant difference was observed when compared before with 60 days after bonding, for the teeth bonded with SmartClip™ self-ligating bracket, (PI P = 0.009; GCF volume P = 0.001). There was an increase in PI score and GCF volume 60 days after bonding of SmartClip™ self-ligating brackets, indicating the influence of bracket design on these clinical parameters.

Design, implementation and application of distributed order PI control.

PubMed

Zhou, Fengyu; Zhao, Yang; Li, Yan; Chen, YangQuan

2013-05-01

In this paper, a series of distributed order PI controller design methods are derived and applied to the robust control of wheeled service robots, which can tolerate more structural and parametric uncertainties than the corresponding fractional order PI control. A practical discrete incremental distributed order PI control strategy is proposed basing on the discretization method and the frequency criterions, which can be commonly used in many fields of fractional order system, control and signal processing. Besides, an auto-tuning strategy and the genetic algorithm are applied to the distributed order PI control as well. A number of experimental results are provided to show the advantages and distinguished features of the discussed methods in fairways. Copyright © 2012 ISA. Published by Elsevier Ltd. All rights reserved.

A neural network controller for automated composite manufacturing

NASA Technical Reports Server (NTRS)

Lichtenwalner, Peter F.

1994-01-01

At McDonnell Douglas Aerospace (MDA), an artificial neural network based control system has been developed and implemented to control laser heating for the fiber placement composite manufacturing process. This neurocontroller learns an approximate inverse model of the process on-line to provide performance that improves with experience and exceeds that of conventional feedback control techniques. When untrained, the control system behaves as a proportional plus integral (PI) controller. However after learning from experience, the neural network feedforward control module provides control signals that greatly improve temperature tracking performance. Faster convergence to new temperature set points and reduced temperature deviation due to changing feed rate have been demonstrated on the machine. A Cerebellar Model Articulation Controller (CMAC) network is used for inverse modeling because of its rapid learning performance. This control system is implemented in an IBM compatible 386 PC with an A/D board interface to the machine.

Traditional Chinese medicine for stable angina pectoris via TCM pattern differentiation and TCM mechanism: study protocol of a randomized controlled trial.

PubMed

Zhang, Zhe; Zhang, Fan; Wang, Yang; Du, Yi; Zhang, Huiyong; Kong, Dezhao; Liu, Yue; Yang, Guanlin

2014-10-30

Stable angina pectoris is experienced as trans-sternal or retro-sternal pressure or pain that may radiate to the left arm, neck or back. Although available evidence relating to its effectiveness and mechanism are weak, traditional Chinese medicine is used as an alternative therapy for stable angina pectoris. We report a protocol of a randomized controlled trial using traditional Chinese medicine to investigate the effectiveness, mechanism and safety for patients with stable angina pectoris. This is a north-east Chinese, multi-center, multi-blinded, placebo-controlled and superiority randomized trail. A total of 240 patients with stable angina pectoris will be randomly assigned to three groups: two treatment groups and a control group. The treatment groups will receive Chinese herbal medicine consisting of Yi-Qi-Jian-Pi and Qu-Tan-Hua-Zhuo granule and Yi-Qi-Jian-Pi and Qu-Tan-Hua-Yu granule, respectively, and conventional medicine. The control group will receive placebo medicine in addition to conventional medicine. All 3 groups will undergo a 12-week treatment and 2-week follow-up. Four visits in sum will be scheduled for each subject: 1 visit each in week 0, week 4, week 12 and week 14. The primary outcomes include: the frequency of angina pectoris attack; the dosage of nitroglycerin; body limited dimension of Seattle Angina Questionnaire. The secondary outcomes include: except for the body limited dimension of SAQ, traditional Chinese medicine pattern questionnaire and so on. Therapeutic mechanism outcomes, safety outcomes and endpoint outcomes will be also assessed. The primary aim of this trial is to develop a standard protocol to utilize high-quality EBM evidence for assessing the effectiveness and safety of SAP via TCM pattern differentiation as well as exploring the efficacy mechanism and regulation with the molecular biology and systems biology. ChiCTR-TRC-13003608, registered 18 June 2013.

Constant voltage and constant current control implementation for electric vehicles (evs) wireless charger

NASA Astrophysics Data System (ADS)

Tampubolon, Marojahan; Pamungkas, Laskar; Hsieh, Yao Ching; Chiu, Huang Jen

2018-04-01

This paper presents the implementation of Constant Voltage (CV) and Constant Current (CC) control for a wireless charger system. A battery charging system needs these control modes to ensure the safety of the battery and the effectiveness of the charging system. Here, the wireless charger system does not employ any post-regulator stage to control the output voltage and output current of the charger. But, it uses a variable frequency control incorporated with a conventional PI control. As a result, the size and the weight of the system are reduced. This paper discusses the brief review of the SS-WPT, control strategy and implementation of the CV and CC control. Experimental hardware with 2kW output power has been performed and tested. The results show that the proposed CV and CC control method works well with the system.

Tuning fuzzy PD and PI controllers using reinforcement learning.

PubMed

Boubertakh, Hamid; Tadjine, Mohamed; Glorennec, Pierre-Yves; Labiod, Salim

2010-10-01

In this paper, we propose a new auto-tuning fuzzy PD and PI controllers using reinforcement Q-learning (QL) algorithm for SISO (single-input single-output) and TITO (two-input two-output) systems. We first, investigate the design parameters and settings of a typical class of Fuzzy PD (FPD) and Fuzzy PI (FPI) controllers: zero-order Takagi-Sugeno controllers with equidistant triangular membership functions for inputs, equidistant singleton membership functions for output, Larsen's implication method, and average sum defuzzification method. Secondly, the analytical structures of these typical fuzzy PD and PI controllers are compared to their classical counterpart PD and PI controllers. Finally, the effectiveness of the proposed method is proven through simulation examples. Copyright © 2010 ISA. Published by Elsevier Ltd. All rights reserved.

Adaptive Metropolis Sampling with Product Distributions

NASA Technical Reports Server (NTRS)

Wolpert, David H.; Lee, Chiu Fan

2005-01-01

The Metropolis-Hastings (MH) algorithm is a way to sample a provided target distribution pi(z). It works by repeatedly sampling a separate proposal distribution T(x,x') to generate a random walk {x(t)}. We consider a modification of the MH algorithm in which T is dynamically updated during the walk. The update at time t uses the {x(t' less than t)} to estimate the product distribution that has the least Kullback-Leibler distance to pi. That estimate is the information-theoretically optimal mean-field approximation to pi. We demonstrate through computer experiments that our algorithm produces samples that are superior to those of the conventional MH algorithm.

DSP-based adaptive backstepping using the tracking errors for high-performance sensorless speed control of induction motor drive.

PubMed

Zaafouri, Abderrahmen; Regaya, Chiheb Ben; Azza, Hechmi Ben; Châari, Abdelkader

2016-01-01

This paper presents a modified structure of the backstepping nonlinear control of the induction motor (IM) fitted with an adaptive backstepping speed observer. The control design is based on the backstepping technique complemented by the introduction of integral tracking errors action to improve its robustness. Unlike other research performed on backstepping control with integral action, the control law developed in this paper does not propose the increase of the number of system state so as not increase the complexity of differential equations resolution. The digital simulation and experimental results show the effectiveness of the proposed control compared to the conventional PI control. The results analysis shows the characteristic robustness of the adaptive control to disturbances of the load, the speed variation and low speed. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

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.

Femoral head retroposition as a potential compensatory mechanism in patients with a severe mismatch between pelvic incidence and lumbar lordosis.

PubMed

Cheng, Xiaofei; Zhang, Kai; Sun, Xiaojiang; Zhao, Changqing; Li, Hua; Zhao, Jie

2017-12-01

Severe mismatch between pelvic incidence (PI) and lumbar lordosis (LL) leads to extra anterior displacement of the gravity line. The objective of this study is to investigate whether femoral head retroposition is a separate compensatory mechanism responsible for the extra anterior displacement. Based on the values of PI and LL, 94 patients were divided into the PI-LL match group (PI-LL ≤ 0°), the mild PI-LL mismatch group (20°> PI-LL >0°), and the severe PI-LL mismatch group (PI-LL ≥ 20°). A series of parameters including PI, LL, PI-LL, thoracic kyphosis (TK), pelvic tilt (PT), sacral slope (SS), knee flexion angle (KFA), tibial obliquity angle (TOA), sagittal vertical axis (SVA), S1 overhang, femoral head shift (FHS), and pelvic shift (PS) were measured and compared among the three groups. The severe PI-LL mismatch group exhibited significantly greater PI, PI-LL, PT, KFA, SVA, PS, and FHS, and less LL and TK, compared with the control and mild PI-LL mismatch group. The mild PI-LL mismatch group had significantly greater PI-LL, PT, KFA, TOA, and S1 overhang, and less LL and SS than the control group. SS, TOA, and S1 overhang in the severe PI-LL mismatch group differed significantly from that in the control group, but did not differ significantly from that in the mild PI-LL mismatch group. Femoral head retroposition is an entirely separate compensatory mechanism and, in this study, participated in the compensation for the anterior displacement of the gravity line induced by extra-sagittal spinal malalignment in patients with severe PI-LL mismatch.

Diffusion control for a tempered anomalous diffusion system using fractional-order PI controllers.

PubMed

Juan Chen; Zhuang, Bo; Chen, YangQuan; Cui, Baotong

2017-05-09

This paper is concerned with diffusion control problem of a tempered anomalous diffusion system based on fractional-order PI controllers. The contribution of this paper is to introduce fractional-order PI controllers into the tempered anomalous diffusion system for mobile actuators motion and spraying control. For the proposed control force, convergence analysis of the system described by mobile actuator dynamical equations is presented based on Lyapunov stability arguments. Moreover, a new Centroidal Voronoi Tessellation (CVT) algorithm based on fractional-order PI controllers, henceforth called FOPI-based CVT algorithm, is provided together with a modified simulation platform called Fractional-Order Diffusion Mobile Actuator-Sensor 2-Dimension Fractional-Order Proportional Integral (FO-Diff-MAS2D-FOPI). Finally, extensive numerical simulations for the tempered anomalous diffusion process are presented to verify the effectiveness of our proposed fractional-order PI controllers. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Control design methods for floating wind turbines for optimal disturbance rejection

NASA Astrophysics Data System (ADS)

Lemmer, Frank; Schlipf, David; Cheng, Po Wen

2016-09-01

An analysis of the floating wind turbine as a multi-input-multi-output system investigating the effect of the control inputs on the system outputs is shown. These effects are compared to the ones of the disturbances from wind and waves in order to give insights for the selection of the control layout. The frequencies with the largest impact on the outputs due to limited effect of the controlled variables are identified. Finally, an optimal controller is designed as a benchmark and compared to a conventional PI-controller using only the rotor speed as input. Here, the previously found system properties, especially the difficulties to damp responses to wave excitation, are confirmed and verified through a spectral analysis with realistic environmental conditions. This comparison also assesses the quality of the employed simplified linear simulation model compared to the nonlinear model and shows that such an efficient frequency-domain evaluation for control design is feasible.

Nonlinear integral sliding mode control design of photovoltaic pumping system: Real time implementation.

PubMed

Chihi, Asma; Ben Azza, Hechmi; Jemli, Mohamed; Sellami, Anis

2017-09-01

The aim of this paper is to provide high performance control of pumping system. The proposed method is designed by an indirect field oriented control based on Sliding Mode (SM) technique. The first contribution of this work is to design modified switching surfaces which presented by adding an integral action to the considered controlled variables. Then, in order to prevent the chattering phenomenon, modified nonlinear component is developed. The SM concept and a Lyapunov function are combined to compute the Sliding Mode Control (SMC) gains. Besides, the motor performance is validated by numeric simulations and real time implementation using a dSpace system with DS1104 controller board. Also, to show the effectiveness of the proposed approach, the obtained results are compared with other techniques such as conventional PI, Proportional Sliding Mode (PSM) and backstepping controls. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

A Comparative study between MPC and PI controller to control vacuum distillation unit for producing LVGO, MVGO, and HVGO

NASA Astrophysics Data System (ADS)

Wahid, A.; Prasetyo, A. P.

2018-03-01

This study describes the selection of controllers in the vacuum distillation unit (VDU) between a model predictive control (MPC) and a proportional-integral (PI) controller by comparing the integral square error (ISE) values. Design of VDU in this simulation is based on modified Metso Automation Inc. scheme. Controlled variables in this study are feed flow rate, feed temperature, top stage pressure, condenser level, bottom stage temperature, LVGO (light vacuum gas oil), MVGO (medium vacuum gas oil), and HVGO (heavy vacuum gas oil) flow rate. As a result, control performance improvements occurred as using MPC compared to PI controllers, when testing a set-point change, of feed flow rate control, feed temperature, top-stage pressure, bottom-stage temperature and flow rate of LVGO, MVGO, and HVGO, respectively, 36%, 6%, 92%, 53%, 90%, 96% and 88%. Only on condenser level control PI performs much better than the MPC. So PI controller is used for level condenser control. While for the test of disturbance rejection, by changing feed flow rate by 10%, there is improvement of control performance using MPC compared to PI controller on feed temperature control, top-stage pressure, bottom-stage temperature and flow rate LVGO, MVGO and HVGO 0.3%, 0.7%, 14%, 2.7%, 10.6% and 4.3%, respectively.

Excited-state redox properties of ruthenium(II) phthalocyanine from electron-transfer quenching

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

Prasad, D.R.; Ferraudi, G.

1982-09-30

Electron-transfer reactions between the lowest-lying triplet state, /sup 3/..pi pi../sup */, of ruthenium (phthalocyanine)(pyridine)/sub 2/ and various nitroaromatic compounds have been studied by laser and conventional flash photolysis. Quenching rate constants determined for the oxidation of the excited state have been treated according to the Marcus-Hush theory. A self-exchange rate constant K approx. 10/sup 7/ M/sup -1/ x/sup -1/ was determined for the self-exchange reaction between the /sup 3/..pi pi../sup */ and radical cation, Ru(ph)(py)/sub 2//sup +/. Such a value indicates that the major component to the Franck-Condon reorganizational energy is the outer-sphere contribution. The photochemical properties of the phthalocyaninesmore » are discussed in terms of the redox potentials estimate for various excited states.« less

Measuring protein isoelectric points by AFM-based force spectroscopy using trace amounts of sample

NASA Astrophysics Data System (ADS)

Guo, Shifeng; Zhu, Xiaoying; Jańczewski, Dominik; Lee, Serina Siew Chen; He, Tao; Teo, Serena Lay Ming; Vancso, G. Julius

2016-09-01

Protein charge at various pH and isoelectric point (pI) values is important in understanding protein function. However, often only trace amounts of unknown proteins are available and pI measurements cannot be obtained using conventional methods. Here, we show a method based on the atomic force microscope (AFM) to determine pI using minute quantities of proteins. The protein of interest is immobilized on AFM colloidal probes and the adhesion force of the protein is measured against a positively and a negatively charged substrate made by layer-by-layer deposition of polyelectrolytes. From the AFM force-distance curves, pI values with an estimated accuracy of ±0.25 were obtained for bovine serum albumin, myoglobin, fibrinogen and ribonuclease A over a range of 4.7-9.8. Using this method, we show that the pI of the ‘footprint’ of the temporary adhesive proteins secreted by the barnacle cyprid larvae of Amphibalanus amphitrite is in the range 9.6-9.7.

Directional Charge Separation in Isolated Organic Semiconductor Crystalline Nanowires

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

Barnes, Michael; Labastide, Joelle; Bond-Thompson, Hilary

2017-03-01

In the conventional view of organic photovoltaics (OPV), localized electronic excitations (excitons) formed in the active layer are transported by random 3D diffusion to an interface where charge separation and extraction take place. Because radiative de-excitation is usually strongly allowed in organic semiconductors, efficient charge separation requires high exciton mobility, with much of the diffusive motion ‘wasted’ in directions that don’t result in an interface encounter. Our research efforts are focused on ways to enforce a preferred directionality in energy and/or charge transport using ordered crystalline nanowires in which the intermolecular interactions that facilitate transport along, for example, the pi-stackingmore » axis, can be made several orders of magnitude stronger than those in a transverse direction. The results presented in our recent work (Nature Communications) is a first step towards realizing the goal of directional control of both energy transport and charge separation, where excitons shared between adjacent molecules dissociate exclusively along the pi-stacking direction.« less

Anti-proliferative effect of biogenic gold nanoparticles against breast cancer cell lines (MDA-MB-231 & MCF-7)

NASA Astrophysics Data System (ADS)

K. S., Uma Suganya; Govindaraju, K.; Ganesh Kumar, V.; Prabhu, D.; Arulvasu, C.; Stalin Dhas, T.; Karthick, V.; Changmai, Niranjan

2016-05-01

Breast cancer is a major complication in women and numerous approaches are being developed to overcome this problem. In conventional treatments such as chemotherapy and radiotherapy the post side effects cause an unsuitable effect in treatment of cancer. Hence, it is essential to develop a novel strategy for the treatment of this disease. In the present investigation, a possible route for green synthesis of gold nanoparticles (AuNPs) using leaf extract of Mimosa pudica and its anticancer efficacy in the treatment of breast cancer cell lines is studied. The synthesized nanoparticles were found to be effective in killing cancer cells (MDA-MB-231 & MCF-7) which were studied using various anticancer assays (MTT assay, cell morphology determination, cell cycle analysis, comet assay, Annexin V-FITC/PI staining and DAPI staining). Cell morphological analysis showed the changes occurred in cancer cells during the treatment with AuNPs. Cell cycle analysis revealed apoptosis in G0/G1 to S phase. Similarly in Comet assay, there was an increase in tail length in treated cells in comparison with the control. Annexin V-FITC/PI staining assay showed prompt fluorescence in treated cells indicating the translocation of phosphatidylserine from the inner membrane. PI and DAPI staining showed the DNA damage in treated cells.

Adaptive Importance Sampling for Control and Inference

NASA Astrophysics Data System (ADS)

Kappen, H. J.; Ruiz, H. C.

2016-03-01

Path integral (PI) control problems are a restricted class of non-linear control problems that can be solved formally as a Feynman-Kac PI and can be estimated using Monte Carlo sampling. In this contribution we review PI control theory in the finite horizon case. We subsequently focus on the problem how to compute and represent control solutions. We review the most commonly used methods in robotics and control. Within the PI theory, the question of how to compute becomes the question of importance sampling. Efficient importance samplers are state feedback controllers and the use of these requires an efficient representation. Learning and representing effective state-feedback controllers for non-linear stochastic control problems is a very challenging, and largely unsolved, problem. We show how to learn and represent such controllers using ideas from the cross entropy method. We derive a gradient descent method that allows to learn feed-back controllers using an arbitrary parametrisation. We refer to this method as the path integral cross entropy method or PICE. We illustrate this method for some simple examples. The PI control methods can be used to estimate the posterior distribution in latent state models. In neuroscience these problems arise when estimating connectivity from neural recording data using EM. We demonstrate the PI control method as an accurate alternative to particle filtering.

Laboratory-based teaching and the Physics Innovations Centre for Excellence in Teaching and Learning

NASA Astrophysics Data System (ADS)

Lambourne, Robert

2007-05-01

Developments in the laboratory-based teaching of physics and astronomy are resulting from the collaboration between conventional and distance teaching universities. The collaboration, piCETL, is one of the Centres for Excellence in Teaching and Learning established as a result of a broad initiative by the Higher Education Funding Council for England. The initiative, the piCETL collaboration and some of its work on laboratory-based teaching are all described.

The quantitative assessment of peri-implant bone responses using histomorphometry and micro-computed tomography.

PubMed

Schouten, Corinne; Meijer, Gert J; van den Beucken, Jeroen J J P; Spauwen, Paul H M; Jansen, John A

2009-09-01

In the present study, the effects of implant design and surface properties on peri-implant bone response were evaluated with both conventional histomorphometry and micro-computed tomography (micro-CT), using two geometrically different dental implants (Screw type, St; Push-in, Pi) either or not surface-modified (non-coated, CaP-coated, or CaP-coated+TGF-beta1). After 12 weeks of implantation in a goat femoral condyle model, peri-implant bone response was evaluated in three different zones (inner: 0-500 microm; middle: 500-1000 microm; and outer: 1000-1500 microm) around the implant. Results indicated superiority of conventional histomorphometry over micro-CT, as the latter is hampered by deficits in the discrimination at the implant/tissue interface. Beyond this interface, both analysis techniques can be regarded as complementary. Histomorphometrical analysis showed an overall higher bone volume around St compared to Pi implants, but no effects of surface modification were observed. St implants showed lowest bone volumes in the outer zone, whereas inner zones were lowest for Pi implants. These results implicate that for Pi implants bone formation started from two different directions (contact- and distance osteogenesis). For St implants it was concluded that undersized implantation technique and loosening of bone fragments compress the zones for contact and distant osteogenesis, thereby improving bone volume at the interface significantly.

Using particle swarm optimization to enhance PI controller performances for active and reactive power control in wind energy conversion systems

NASA Astrophysics Data System (ADS)

Taleb, M.; Cherkaoui, M.; Hbib, M.

2018-05-01

Recently, renewable energy sources are impacting seriously power quality of the grids in term of frequency and voltage stability, due to their intermittence and less forecasting accuracy. Among these sources, wind energy conversion systems (WECS) received a great interest and especially the configuration with Doubly Fed Induction Generator. However, WECS strongly nonlinear, are making their control not easy by classical approaches such as a PI. In this paper, we continue deepen study of PI controller used in active and reactive power control of this kind of WECS. Particle Swarm Optimization (PSO) is suggested to improve its dynamic performances and its robustness against parameters variations. This work highlights the performances of PSO optimized PI control against classical PI tuned with poles compensation strategy. Simulations are carried out on MATLAB-SIMULINK software.

Phosphoinositide 5-phosphatase activities control cell motility in glioblastoma: Two phosphoinositides PI(4,5)P2 and PI(3,4)P2 are involved.

PubMed

Ramos, Ana Raquel; Elong Edimo, William's; Erneux, Christophe

2018-01-01

Inositol polyphosphate 5-phosphatases or phosphoinositide 5-phosphatases (PI 5-phosphatases) are enzymes that can act on soluble inositol phosphates and/or phosphoinositides (PIs). Several PI 5-phosphatases have been linked to human genetic diseases, in particular the Lowe protein or OCRL which is mutated in the Lowe syndrome. There are 10 different members of this family and 9 of them can use PIs as substrate. One of these substrates, PI(3,4,5)P3 binds to specific PH domains and recruits as effectors specific proteins to signaling complexes. Protein kinase B is one target protein and activation of the kinase will have a major impact on cell proliferation, survival and cell metabolism. Two other PIs, PI(4,5)P2 and PI(3,4)P2, are produced or used as substrates of PI 5-phosphatases (OCRL, INPP5B, SHIP1/2, SYNJ1/2, INPP5K, INPP5J, INPP5E). The inositol lipids may influence many aspects of cytoskeletal organization, lamellipodia formation and F-actin polymerization. PI 5-phosphatases have been reported to control cell migration, adhesion, polarity and cell invasion particularly in cancer cells. In glioblastoma, reducing SHIP2 expression can positively or negatively affect the speed of cell migration depending on the glioblastoma cell type. The two PI 5-phosphatases SHIP2 or SKIP could be localized at the plasma membrane and can reduce either PI(3,4,5)P3 or PI(4,5)P2 abundance. In the glioblastoma 1321 N1 cells, SHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Glutathione S-transferase Pi expression predicts response to adjuvant chemotherapy for stage C colon cancer: a matched historical control study

PubMed Central

2012-01-01

Background This study examined the association between overall survival and Glutathione S-transferase Pi (GST Pi) expression and genetic polymorphism in stage C colon cancer patients after resection alone versus resection plus 5-fluourouracil-based adjuvant chemotherapy. Methods Patients were drawn from a hospital registry of colorectal cancer resections. Those receiving chemotherapy after it was introduced in 1992 were compared with an age and sex matched control group from the preceding period. GST Pi expression was assessed by immunohistochemistry. Overall survival was analysed by the Kaplan-Meier method and Cox regression. Results From an initial 104 patients treated with chemotherapy and 104 matched controls, 26 were excluded because of non-informative immunohistochemistry, leaving 95 in the treated group and 87 controls. Survival did not differ significantly among patients with low GST Pi who did or did not receive chemotherapy and those with high GST Pi who received chemotherapy (lowest pair-wise p = 0.11) whereas patients with high GST Pi who did not receive chemotherapy experienced markedly poorer survival than any of the other three groups (all pair-wise p <0.01). This result was unaffected by GST Pi genotype. Conclusion Stage C colon cancer patients with low GST Pi did not benefit from 5-fluourouracil-based adjuvant chemotherapy whereas those with high GST Pi did. PMID:22639861

Glutathione S-transferase Pi expression predicts response to adjuvant chemotherapy for stage C colon cancer: a matched historical control study.

PubMed

Jankova, Lucy; Robertson, Graham; Chan, Charles; Tan, King L; Kohonen-Corish, Maija; Fung, Caroline L-S; Clarke, Candice; Lin, Betty P C; Molloy, Mark; Chapuis, Pierre H; Bokey, Les; Dent, Owen F; Clarke, Stephen J

2012-05-28

This study examined the association between overall survival and Glutathione S-transferase Pi (GST Pi) expression and genetic polymorphism in stage C colon cancer patients after resection alone versus resection plus 5-fluourouracil-based adjuvant chemotherapy. Patients were drawn from a hospital registry of colorectal cancer resections. Those receiving chemotherapy after it was introduced in 1992 were compared with an age and sex matched control group from the preceding period. GST Pi expression was assessed by immunohistochemistry. Overall survival was analysed by the Kaplan-Meier method and Cox regression. From an initial 104 patients treated with chemotherapy and 104 matched controls, 26 were excluded because of non-informative immunohistochemistry, leaving 95 in the treated group and 87 controls. Survival did not differ significantly among patients with low GST Pi who did or did not receive chemotherapy and those with high GST Pi who received chemotherapy (lowest pair-wise p = 0.11) whereas patients with high GST Pi who did not receive chemotherapy experienced markedly poorer survival than any of the other three groups (all pair-wise p <0.01). This result was unaffected by GST Pi genotype. Stage C colon cancer patients with low GST Pi did not benefit from 5-fluourouracil-based adjuvant chemotherapy whereas those with high GST Pi did.

In vivo body composition in autochthonous and conventional pig breeding groups by dual-energy X-ray absorptiometry and magnetic resonance imaging under special consideration of Cerdo Ibérico.

PubMed

Kremer, P V; Fernández-Fígares, I; Förster, M; Scholz, A M

2012-12-01

The improvement of carcass quality is one of the main breeding goals in pig production. To select appropriate breeding animals, it is of major concern to exactly and reliably analyze the body composition in vivo. Therefore, the objective of the study was to examine whether the combination of dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) offers the opportunity to reliably analyze quantitative and qualitative body composition characteristics of different pig breeding groups in vivo. In this study, a total of 77 pigs were studied by DXA and MRI at an average age of 154 days. The pigs originated from different autochthonous or conventional breeds or crossbreeds and were grouped into six breed types: Cerdo Ibérico (Ib); Duroc × Ib (Du_Ib); White Sow Lines (WSL, including German Landrace and German Large White); Hampshire/Pietrain (Pi_Ha, including Hampshire, Pietrain × Hampshire (PiHa) and Pietrain × PiHa); Pietrain/Duroc (Pi_Du, including Pietrain × Duroc (PiDu) and Pietrain × PiDu); crossbred WSL (PiDu_WSL, including Pietrain × WSL and PiDu × WSL). A whole-body scan was performed by DXA with a GE Lunar DPX-IQ in order to measure the amount and percentage of fat tissue (FM; %FM), lean tissue (LM; %LM) and bone mineral, whereas a Siemens Magnetom Open with a large body coil was used for MRI in the thorax region between 13th and 14th vertebrae in order to measure the area of the loin (LA) and the above back fat area (FA) of both body sides. A GLM procedure using SAS 9.2 was used to analyze the data. As expected, the native breed Ib followed by Du_Ib crossbreeds showed the highest %FM (27.2%, 25.0%) combined with the smallest LA (46.2 cm2, 73.6 cm2), whereas Ib had the lowest BW at an average age of 154 days. Pigs with Pi_Ha origin presented the least %FM (12.4%) and largest LA (99.5 cm2). The WSL and PiDu_WSL showed an intermediate body composition. Therefore, it could be concluded that DXA and MRI and especially their combination are very suitable methods to reliably identify differences in body composition and carcass traits among different pig lines in vivo.

Predicting successful supraclavicular brachial plexus block using pulse oximeter perfusion index.

PubMed

Abdelnasser, A; Abdelhamid, B; Elsonbaty, A; Hasanin, A; Rady, A

2017-08-01

Supraclavicular nerve block is a popular approach for anaesthesia for upper limb surgeries. Conventional methods for evaluation of block success are time consuming and need patient cooperation. The aim of this study was to evaluate whether the perfusion index (PI) can be used to predict and provide a cut-off value for ultrasound-guided supraclavicular nerve block success. The study included 77 patients undergoing elective orthopaedic procedures under ultrasound-guided supraclavicular nerve block. After local anaesthetic injection, sensory block success was assessed every 3 min by pinprick, and motor block success was assessed every 5 min by the ability to flex the elbow and the hand against resistance. The PI was recorded at baseline and at 10, 20, and 30 min after anaesthetic injection in both blocked and non-blocked limbs. The PI ratio was calculated as the PI after 10 min divided by the PI at the baseline. Receiver operating characteristic curves were constructed for the accuracy of the PI in detection of block success. The PI was higher in the blocked limb at all time points, and this was paralleled by a higher PI ratio compared with the unblocked limb. Both the PI and the PI ratio at 10 min after injection showed a sensitivity and specificity of 100% for block success at cut-off values of 3.3 and 1.4, respectively. The PI is a useful tool for evaluation of successful supraclavicular nerve block. A PI ratio of > 1.4 is a good predictor for block success. © The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Weaker cognitive control abilities of Pi (Spleen) qi-deficient individuals supported Chinese medicine diagnosis.

PubMed

Lin, Hui-Yan; Zhao, Yan-Ping; Xu, Gui-Ping; Li, Yun-Si; Xie, Wei-Yun; Bai, Li-Hua; Jin, Hua

2017-07-28

To investigate whether Pi (Spleen) qi-deficiency affected psychological and neural responses in relevance to cognitive control. Pi qi-deficient and balanced participants were asked to perform the Stroop task, a classical cognitive control paradigm. In this paradigm, participants had to judge the color of the prompted word. The word's meaning indicated the color (the consistent condition) or not (the inconsistent condition), or were unrelated to the color (the neutral condition). Electroencephalograph (EEG) was recorded during the task. Event-related potential (ERP) results showed that Pi qi-deficient individuals failed to exhibit a normal Stroop effect as Balanced individuals did, such as the accuracy differences between the consistent and the inconsistent conditions as well as the N450 effect (P>0.05). Meanwhile, Pi qi-deficient individuals displayed larger P2 and P3 amplitudes than balanced individuals did during performing the cognitive control task (P<0.05). Pi qi-deficiency had psychological and neural basis at least in cognitive control aspect.

A Closed-Loop Proportional-Integral (PI) Control Software for Fully Mechanically Controlled Automated Electron Microscopic Tomography

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

REN, GANG; LIU, JINXIN; LI, HONGCHANG

A closed-loop proportional-integral (PI) control software is provided for fully mechanically controlled automated electron microscopic tomography. The software is developed based on Gatan DigitalMicrograph, and is compatible with Zeiss LIBRA 120 transmission electron microscope. However, it can be expanded to other TEM instrument with modification. The software consists of a graphical user interface, a digital PI controller, an image analyzing unit, and other drive units (i.e.: image acquire unit and goniometer drive unit). During a tomography data collection process, the image analyzing unit analyzes both the accumulated shift and defocus value of the latest acquired image, and provides the resultsmore » to the digital PI controller. The digital PI control compares the results with the preset values and determines the optimum adjustments of the goniometer. The goniometer drive unit adjusts the spatial position of the specimen according to the instructions given by the digital PI controller for the next tilt angle and image acquisition. The goniometer drive unit achieves high precision positioning by using a backlash elimination method. The major benefits of the software are: 1) the goniometer drive unit keeps pre-aligned/optimized beam conditions unchanged and achieves position tracking solely through mechanical control; 2) the image analyzing unit relies on only historical data and therefore does not require additional images/exposures; 3) the PI controller enables the system to dynamically track the imaging target with extremely low system error.« less

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.

77 FR 57162 - Prudential Investment Portfolios 3, et al.; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-17

... Inc.'', together with PIP 3, the ``Trusts'') and Prudential Investments LLC (``PI'' or the ``Adviser... company or series thereof that (i) is advised by PI or by an entity controlling, controlled by or under common control with PI and (ii) invests in other registered open-end management investment companies in...

Diagnosis and Characterization of Patellofemoral Instability: Review of Available Imaging Modalities.

PubMed

Haj-Mirzaian, Arya; Thawait, Gaurav K; Tanaka, Miho J; Demehri, Shadpour

2017-06-01

Patellofemoral instability (PI) is defined as single or multiple episodes of patellar dislocation. Imaging modalities are useful for characterization of patellar malalignment, maltracking, underlying morphologic abnormalities, and stabilizing soft-tissue injuries. Using these findings, orthopedic surgeons can decide when to operate, determine the best operation, and measure degree of correction postoperatively in PI patients. Also, these methods assist with PI diagnosis in some suspicious cases. Magnetic resonance imaging is the preferred method especially in the setting of acute dislocations. Multidetector computed tomography allows a more accurate assessment for malalignment such as patellar tilt and lateral subluxation and secondary osteoarthritis. Dynamic magnetic resonance imaging and 4-dimensional computed tomography have been introduced for better kinematic assessment of the patellofemoral maltracking during extension-flexion motions. In this review article, we will discuss the currently available evidence regarding both the conventional and the novel imaging modalities that can be used for diagnosis and characterization of PI.

Design of PI Controlled Non Isolated Bidirectional DC to DC Converter for Electric Vehicle Application

NASA Astrophysics Data System (ADS)

Geetha, A.; Subramani, C.; Thamizh Thentral, T. M.; Krithika, V.; Usha, S.

2018-04-01

Non isolated Bidirectional DC-DC Converter (NIBDDC) is a good interface between DC source and inverter Fed induction motor drive. This paper deals with comparison between open loop and PI controlled Bidirectional DC to DC Converter Inverter System (BDDCIS). The modelling and control of BDDC is becomes an important issue. Open loop BDDCIS and closed loop PI controlled BDDCIS are designed, modelled and simulated using Matlab- simulink and their results are presented. The investigations indicate superior performance of PI controlled BDDCIS. The proposed BDDCIS has advantages like bidirectional power transfer ability, reduced hardware count and improved dynamic response.

Working memory in schizophrenia: behavioral and neural evidence for reduced susceptibility to item-specific proactive interference.

PubMed

Kaller, Christoph P; Loosli, Sandra V; Rahm, Benjamin; Gössel, Astrid; Schieting, Stephan; Hornig, Tobias; Hennig, Jürgen; Tebartz van Elst, Ludger; Weiller, Cornelius; Katzev, Michael

2014-09-15

Susceptibility to item-specific proactive interference (PI) contributes to interindividual differences in working memory (WM) capacity and complex cognition relying on WM. Although WM deficits are a well-recognized impairment in schizophrenia, the underlying pathophysiological effects on specific WM control functions, such as the ability to resist item-specific PI, remain unknown. Moreover, opposing hypotheses on increased versus reduced PI susceptibility in schizophrenia are both justifiable by the extant literature. To provide first insights into the behavioral and neural correlates of PI-related WM control in schizophrenia, a functional magnetic resonance imaging experiment was conducted in a sample of 20 patients and 20 well-matched control subjects. Demands on item-specific PI were experimentally manipulated in a recent-probes task (three runs, 64 trials each) requiring subjects to encode and maintain a set of four target items per trial. Compared with healthy control subjects, schizophrenia patients showed a significantly reduced PI susceptibility in both accuracy and latency measures. Notably, reduced PI susceptibility in schizophrenia was not associated with overall WM impairments and thus constituted an independent phenomenon. In addition, PI-related activations in inferior frontal gyrus and anterior insula, typically assumed to support PI resistance, were reduced in schizophrenia, thus ruling out increased neural efforts as a potential cause of the patients' reduced PI susceptibility. The present study provides first evidence for a diminished vulnerability of schizophrenia patients to item-specific PI, which is presumably a consequence of the patients' more efficient clearing of previously relevant WM traces and the accordingly reduced likelihood for item-specific PI to occur. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Organic materials and devices for detecting ionizing radiation

DOEpatents

Doty, F Patrick [Livermore, CA; Chinn, Douglas A [Livermore, CA

2007-03-06

A .pi.-conjugated organic material for detecting ionizing radiation, and particularly for detecting low energy fission neutrons. The .pi.-conjugated materials comprise a class of organic materials whose members are intrinsic semiconducting materials. Included in this class are .pi.-conjugated polymers, polyaromatic hydrocarbon molecules, and quinolates. Because of their high resistivities (.gtoreq.10.sup.9 ohmcm), these .pi.-conjugated organic materials exhibit very low leakage currents. A device for detecting and measuring ionizing radiation can be made by applying an electric field to a layer of the .pi.-conjugated polymer material to measure electron/hole pair formation. A layer of the .pi.-conjugated polymer material can be made by conventional polymer fabrication methods and can be cast into sheets capable of covering large areas. These sheets of polymer radiation detector material can be deposited between flexible electrodes and rolled up to form a radiation detector occupying a small volume but having a large surface area. The semiconducting polymer material can be easily fabricated in layers about 10 .mu.m to 100 .mu.m thick. These thin polymer layers and their associated electrodes can be stacked to form unique multi-layer detector arrangements that occupy small volume.

Ischemic preconditioning inhibits over-expression of arginyl-tRNA synthetase gene Rars in ischemia-injured neurons.

PubMed

Shen, Yin; Zhao, Hong-Yang; Wang, Hai-Jun; Wang, Wen-Liang; Zhang, Li-Zhi; Fu, Rong

2016-08-01

The expression changes of Rars gene in ischemia-injured neurons were investigated by detecting its translational product arginyl-tRNA synthetase (ArgRS), and the inhibitory effects of ischemic preconditioning (IPC) on Rars gene were explored. Both IPC model and prolonged ischemia (PI) model were established by using the classic oxygen glucose deprivation (OGD) method. The primary cultured neurons were assigned into the following groups: the experimental group (IPC+PI group), undergoing PI after a short period of IPC; the conditional control group (PI control group), subjected to PI without IPC; blank control group, the normally cultured neurons. The Rars transcriptional activities and ArgRS expression levels were measured at different time points after re-oxygenation (3 h/6 h/12 h/24 h). Data were collected and statistically analyzed. Compared to the blank control group, the Rars activities and ArgRS levels were significantly increased in PI control group, peaking at the time point of 6 h after re-oxygenation. Rars activities and ArgRS levels were significantly lower in the experimental group than in the PI control group at different time points after re-oxygenation. PI insult can induce an escalating activity of Rars and lead to ArgRS over-expression in primary cultured neurons. IPC can inhibit the increased Rars activity and down-regulate ArgRS expression of ischemia-insulted neurons. This mechanism may confer ischemic tolerance on neurons.

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

Oxidative stress mediates through apoptosis the anticancer effect of phospho-nonsteroidal anti-inflammatory drugs: implications for the role of oxidative stress in the action of anticancer agents.

PubMed

Sun, Yu; Huang, Liqun; Mackenzie, Gerardo G; Rigas, Basil

2011-09-01

We assessed the relationship between oxidative stress, cytokinetic parameters, and tumor growth in response to novel phospho-nonsteroidal anti-inflammatory drugs (NSAIDs), agents with significant anticancer effects in preclinical models. Compared with controls, in SW480 colon and MCF-7 breast cancer cells, phospho-sulindac, phospho-aspirin, phospho-flurbiprofen, and phospho-ibuprofen (P-I) increased the levels of reactive oxygen and nitrogen species (RONS) and decreased GSH levels and thioredoxin reductase activity, whereas the conventional chemotherapeutic drugs (CCDs), 5-fluorouracil (5-FU), irinotecan, oxaliplatin, chlorambucil, paclitaxel, and vincristine, did not. In both cell lines, phospho-NSAIDs induced apoptosis and inhibited cell proliferation much more potently than CCDs. We then treated nude mice bearing SW480 xenografts with P-I or 5-FU that had an opposite effect on RONS in vitro. Compared with controls, P-I markedly suppressed xenograft growth, induced apoptosis in the xenografts (8.9 ± 2.7 versus 19.5 ± 3.0), inhibited cell proliferation (52.6 ± 5.58 versus 25.8 ± 7.71), and increased urinary F2-isoprostane levels (10.7 ± 3.3 versus 17.9 ± 2.2 ng/mg creatinine, a marker of oxidative stress); all differences were statistically significant. 5-FU's effects on tumor growth, apoptosis, proliferation, and F2-isoprostane were not statistically significant. F2-isoprostane levels correlated with the induction of apoptosis and the inhibition of cell growth. P-I induced oxidative stress only in the tumors, and its apoptotic effect was restricted to xenografts. Our data show that phospho-NSAIDs act against cancer through a mechanism distinct from that of various CCDs, underscore the critical role of oxidative stress in their effect, and indicate that pathways leading to oxidative stress may be useful targets for anticancer strategies.

Correlation analysis between pulmonary function test parameters and CT image parameters of emphysema

NASA Astrophysics Data System (ADS)

Liu, Cheng-Pei; Li, Chia-Chen; Yu, Chong-Jen; Chang, Yeun-Chung; Wang, Cheng-Yi; Yu, Wen-Kuang; Chen, Chung-Ming

2016-03-01

Conventionally, diagnosis and severity classification of Chronic Obstructive Pulmonary Disease (COPD) are usually based on the pulmonary function tests (PFTs). To reduce the need of PFT for the diagnosis of COPD, this paper proposes a correlation model between the lung CT images and the crucial index of the PFT, FEV1/FVC, a severity index of COPD distinguishing a normal subject from a COPD patient. A new lung CT image index, Mirage Index (MI), has been developed to describe the severity of COPD primarily with emphysema disease. Unlike conventional Pixel Index (PI) which takes into account all voxels with HU values less than -950, the proposed approach modeled these voxels by different sizes of bullae balls and defines MI as a weighted sum of the percentages of the bullae balls of different size classes and locations in a lung. For evaluation of the efficacy of the proposed model, 45 emphysema subjects of different severity were involved in this study. In comparison with the conventional index, PI, the correlation between MI and FEV1/FVC is -0.75+/-0.08, which substantially outperforms the correlation between PI and FEV1/FVC, i.e., -0.63+/-0.11. Moreover, we have shown that the emphysematous lesion areas constituted by small bullae balls are basically irrelevant to FEV1/FVC. The statistical analysis and special case study results show that MI can offer better assessment in different analyses.

α1-Antitrypsin Protease Inhibitor MZ Heterozygosity Is Associated With Airflow Obstruction in Two Large Cohorts

PubMed Central

Sørheim, Inga-Cecilie; Bakke, Per; Gulsvik, Amund; Pillai, Sreekumar G.; Johannessen, Ane; Gaarder, Per I.; Campbell, Edward J.; Agustí, Alvar; Calverley, Peter M. A.; Donner, Claudio F.; Make, Barry J.; Rennard, Stephen I.; Vestbo, Jørgen; Wouters, Emiel F. M.; Paré, Peter D.; Levy, Robert D.; Coxson, Harvey O.; Lomas, David A.; Hersh, Craig P.

2010-01-01

Background: Severe α1-antitrypsin deficiency is a known genetic risk factor for COPD. Heterozygous (protease inhibitor [PI] MZ) individuals have moderately reduced serum levels of α1-antitrypsin, but whether they have an increased risk of COPD is uncertain. Methods: We compared PI MZ and PI MM individuals in two large populations: a case-control study from Norway (n = 1,669) and a multicenter family-based study from Europe and North America (n = 2,707). We sought to determine whether PI MZ was associated with the specific COPD-related phenotypes of lung function and quantitative CT scan measurements of emphysema and airway disease. Results: PI MZ was associated with a 3.5% lower FEV1/FVC ratio in the case-control study (P = .035) and 3.9% lower FEV1/vital capacity (VC) ratio in the family study (P = .009). In the case-control study, PI MZ also was associated with 3.7% more emphysema on quantitative analysis of chest CT scans (P = .003). The emphysema result was not replicated in the family study. PI MZ was not associated with airway wall thickness or COPD status in either population. Among subjects with low smoking exposure (< 20 pack-years), PI MZ individuals had more severe emphysema on chest CT scan than PI MM individuals in both studies. Conclusions: Compared with PI MM individuals, PI MZ heterozygotes had lower FEV1/(F)VC ratio in two independent studies. Our results suggest that PI MZ individuals may be slightly more susceptible to the development of airflow obstruction than PI MM individuals. PMID:20595457

Chromatic changes to artificial irises produced using different techniques

NASA Astrophysics Data System (ADS)

Bannwart, Lisiane Cristina; Goiato, Marcelo Coelho; dos Santos, Daniela Micheline; Moreno, Amália; Pesqueira, Aldiéris Alves; Haddad, Marcela Filié; Andreotti, Agda Marobo; de Medeiros, Rodrigo Antonio

2013-05-01

Ocular prostheses are important determinants of their users' aesthetic recovery and self-esteem. Because of use, ocular prostheses longevity is strongly affected by instability of the iris color due to polymerization. The goal of this study is to examine how the color of the artificial iris button is affected by different techniques of artificial wear and by the application of varnish following polymerization of the colorless acrylic resin that covers the colored paint. We produce 60 samples (n=10) according to the wear technique applied: conventional technique without varnish (PE); conventional technique with varnish (PEV); technique involving a prefabricated cap without varnish (CA); technique involving a prefabricated cap with varnish (CAV); technique involving inverted painting without varnish (PI); and technique involving inverted painting with varnish (PIV). Color readings using a spectrophotometer are taken before and after polymerization. We submitted the data obtained to analyses of variance and Tukey's test (P<0.05). The color test shows significant changes after polymerization in all groups. The PE and PI techniques have clinically acceptable values of ΔE, independent of whether we apply varnish to protect the paint. The PI technique produces the least color change, whereas the PE and CA techniques significantly improve color stability.

H2/H∞ control for grid-feeding converter considering system uncertainty

NASA Astrophysics Data System (ADS)

Li, Zhongwen; Zang, Chuanzhi; Zeng, Peng; Yu, Haibin; Li, Shuhui; Fu, Xingang

2017-05-01

Three-phase grid-feeding converters are key components to integrate distributed generation and renewable power sources to the power utility. Conventionally, proportional integral and proportional resonant-based control strategies are applied to control the output power or current of a GFC. But, those control strategies have poor transient performance and are not robust against uncertainties and volatilities in the system. This paper proposes a H2/H∞-based control strategy, which can mitigate the above restrictions. The uncertainty and disturbance are included to formulate the GFC system state-space model, making it more accurate to reflect the practical system conditions. The paper uses a convex optimisation method to design the H2/H∞-based optimal controller. Instead of using a guess-and-check method, the paper uses particle swarm optimisation to search a H2/H∞ optimal controller. Several case studies implemented by both simulation and experiment can verify the superiority of the proposed control strategy than the traditional PI control methods especially under dynamic and variable system conditions.

Moving from rational to normative ideologies of control over public involvement: A case of continued managerial dominance.

PubMed

Croft, Charlotte; Currie, Graeme; Staniszewska, Sophie

2016-08-01

Public Involvement (PI) is a strategic priority in global healthcare settings, yet can be seen as peripheral during decision making processes. Whilst extant research acknowledges variations in how policy is translated into practice, the majority attribute it to the limiting influence of professional hierarchies on the perceived 'legitimacy' of PI. Drawing on examples of three commissioning organisations within the English NHS, we outline how the variance in policy implementation for PI can be attributed to influence from the managers rather than professionals. In doing so we explore how rational ideologies of managerial control negatively impact PI. However, we also illustrate how PI alluded to in policy can be more successfully realised when organisational managers enact normative ideologies of control. Notwithstanding this assertion, we argue managerial domination exists even in the case of normative ideologies of control, to the detriment of more radical PI in service development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gingival response in orthodontic patients: Comparative study between self-ligating and conventional brackets.

PubMed

Folco, Alejandra A; Benítez-Rogé, Sandra C; Iglesias, Marina; Calabrese, Diana; Pelizardi, Cristina; Rosa, Alcira; Brusca, Marisa I; Hecht, Pedro; Mateu, María E

2014-01-01

Orthodontic brackets contribute to the accumulation of bacterial plaque on tooth surfaces because they hinder oral hygiene. In contrast to conventional brackets, self-ligating brackets do not require additional parts to support the arches, thus improving dental hygiene. The aim of this study was to compare the gingival response in orthodontic patients wearing self-ligating or conventional brackets. A sample of 22 patients aged 16 to 30 years was divided into two groups: Group A, treated with selfligating brackets (Damon system) and Group B, treated with conventional brackets (Roth technique). The following were assessed during the treatment: Plaque Index (PI), Gingival Index (GI) and Probing Depth (PD), and sub-gingival samples were taken from teeth 14/24 for microbiological observation. No statistically significant difference was found between Groups A and B; p>0.05 (sign-ranked) or between PI, GI and PD at the different times (Friedman's Analysis of Variance), even though the indices were found to increase at 14 days, particularly for self-ligating brackets. The quantity and quality of microorganisms present were compatible with health on days 0, 28 and 56. As from day 14 there is a predominance of microbiota compatible with gingivitis in both groups. In the samples studied, orthodontic treatment increases bacterial plaque and inflammatory gingival response, but gingival-periodontal health can be maintained with adequate basic therapy. Self-ligating and conventional brackets produced similar gingival response.

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.

Position control of twisted and coiled polymer actuator using a controlled fan for cooling

NASA Astrophysics Data System (ADS)

Takagi, Kentaro; Arakawa, Takeshi; Takeda, Jun; Masuya, Ken; Tahara, Kenji; Asaka, Kinji

2017-04-01

Recently, artificial muscles made of fishing lines or sewing threads, namely twisted and coiled polymer actuators (TCPAs), have been proposed by Haines et al. A TCPA contracts by applying heat and returns to its initial length by cooling. A TCPA can be driven by voltage if the TCPA is plated by metal or if conductive wire such as nichrome is wound around it. Compared with the conventional electroactive polymers, advantages of TCPAs are low cost, simple structure, large actuation strain, and large force. However, a big disadvantage of TCPAs is slow response due to heat transfer. The problem becomes apparent during cooling, although the response of heating can be improved by feedback control. This paper proposes a control method of switching heating and cooling. In the proposed method, a TCPA is cooled by an electric cooling fan. When the TCPA is heating, the cooling fan is stopped. In a previous report, the response speed can be improved by keeping cooling fan always on; however, unnecessary energy consumption is required even during heating. In the proposed method, energy consumption during heating does not increase and the response speed can be improved using fan only during cooling. The proposed control law is as follows. Firstly, the desired control input is determined by PI-D control with respect to the length of the actuator. Then, the control inputs to the heater and to the cooling fan are switched according to the sign of the PI-D controller output. The effectiveness of the proposed control method is demonstrated by comparing the cases with and without the cooling fan in the experiments.

Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate

PubMed Central

Gerber, Pehuén Pereyra; Cabrini, Mercedes; Jancic, Carolina; Paoletti, Luciana; Banchio, Claudia; von Bilderling, Catalina; Sigaut, Lorena; Pietrasanta, Lía I.; Duette, Gabriel; Freed, Eric O.; de Saint Basile, Genevieve; Moita, Catarina Ferreira; Moita, Luis Ferreira; Amigorena, Sebastian; Benaroch, Philippe; Geffner, Jorge

2015-01-01

During the late stages of the HIV-1 replication cycle, the viral polyprotein Pr55Gag is recruited to the plasma membrane (PM), where it binds phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and directs HIV-1 assembly. We show that Rab27a controls the trafficking of late endosomes carrying phosphatidylinositol 4-kinase type 2 α (PI4KIIα) toward the PM of CD4+ T cells. Hence, Rab27a promotes high levels of PM phosphatidylinositol 4-phosphate and the localized production of PI(4,5)P2, therefore controlling Pr55Gag membrane association. Rab27a also controls PI(4,5)P2 levels at the virus-containing compartments of macrophages. By screening Rab27a effectors, we identified that Slp2a, Slp3, and Slac2b are required for the association of Pr55Gag with the PM and that Slp2a cooperates with Rab27a in the recruitment of PI4KIIα to the PM. We conclude that by directing the trafficking of PI4KIIα-positive endosomes toward the PM, Rab27a controls PI(4,5)P2 production and, consequently, HIV-1 replication. PMID:25940347

Feedback linearization based control of a variable air volume air conditioning system for cooling applications.

PubMed

Thosar, Archana; Patra, Amit; Bhattacharyya, Souvik

2008-07-01

Design of a nonlinear control system for a Variable Air Volume Air Conditioning (VAVAC) plant through feedback linearization is presented in this article. VAVAC systems attempt to reduce building energy consumption while maintaining the primary role of air conditioning. The temperature of the space is maintained at a constant level by establishing a balance between the cooling load generated in the space and the air supply delivered to meet the load. The dynamic model of a VAVAC plant is derived and formulated as a MIMO bilinear system. Feedback linearization is applied for decoupling and linearization of the nonlinear model. Simulation results for a laboratory scale plant are presented to demonstrate the potential of keeping comfort and maintaining energy optimal performance by this methodology. Results obtained with a conventional PI controller and a feedback linearizing controller are compared and the superiority of the proposed approach is clearly established.

Analysis, control and design of a non-inverting buck-boost converter: A bump-less two-level T-S fuzzy PI control.

PubMed

Almasi, Omid Naghash; Fereshtehpoor, Vahid; Khooban, Mohammad Hassan; Blaabjerg, Frede

2017-03-01

In this paper, a new modified fuzzy Two-Level Control Scheme (TLCS) is proposed to control a non-inverting buck-boost converter. Each level of fuzzy TLCS consists of a tuned fuzzy PI controller. In addition, a Takagi-Sugeno-Kang (TSK) fuzzy switch proposed to transfer the fuzzy PI controllers to each other in the control system. The major difficulty in designing fuzzy TLCS which degrades its performance is emerging unwanted drastic oscillations in the converter output voltage during replacing the controllers. Thereby, the fuzzy PI controllers in each level of TLCS structure are modified to eliminate these oscillations and improve the system performance. Some simulations and digital signal processor based experiments are conducted on a non-inverting buck-boost converter to support the effectiveness of the proposed TLCS in controlling the converter output voltage. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

A combination of Raspberry Pi and SoftEther VPN for controlling research devices via the Internet.

PubMed

Kuroda, Toshikazu

2017-11-01

Remote control over devices for experiments may increase the efficiency of operant research and expand the area where behavior can be studied. This article introduces a combination of Raspberry Pi ® (Pi) and SoftEther VPN ® that allows for such remote control via the Internet. The Pi is a small Linux computer with a great degree of flexibility for customization. Test results indicate that a Pi-based interface meets the requirement for conducting operant research. SoftEther VPN ® allows for establishing an extensive private network on the Internet using a single private Wi-Fi router. Step-by-step instructions are provided in the present article for setting up the Pi along with SoftEther VPN ® . Their potential for improving the way of conducting research is discussed. © 2017 Society for the Experimental Analysis of Behavior.

Regulation of phosphate starvation responses in higher plants.

PubMed

Yang, Xiao Juan; Finnegan, Patrick M

2010-04-01

Phosphorus (P) is often a limiting mineral nutrient for plant growth. Many soils worldwide are deficient in soluble inorganic phosphate (P(i)), the form of P most readily absorbed and utilized by plants. A network of elaborate developmental and biochemical adaptations has evolved in plants to enhance P(i) acquisition and avoid starvation. Controlling the deployment of adaptations used by plants to avoid P(i) starvation requires a sophisticated sensing and regulatory system that can integrate external and internal information regarding P(i) availability. In this review, the current knowledge of the regulatory mechanisms that control P(i) starvation responses and the local and long-distance signals that may trigger P(i) starvation responses are discussed. Uncharacterized mutants that have P(i)-related phenotypes and their potential to give us additional insights into regulatory pathways and P(i) starvation-induced signalling are also highlighted and assessed. An impressive list of factors that regulate P(i) starvation responses is now available, as is a good deal of knowledge regarding the local and long-distance signals that allow a plant to sense and respond to P(i) availability. However, we are only beginning to understand how these factors and signals are integrated with one another in a regulatory web able to control the range of responses demonstrated by plants grown in low P(i) environments. Much more knowledge is needed in this agronomically important area before real gains can be made in improving P(i) acquisition in crop plants.

An activity index for geomagnetic paleosecular variation, excursions, and reversals

NASA Astrophysics Data System (ADS)

Panovska, S.; Constable, C. G.

2017-04-01

Magnetic indices provide quantitative measures of space weather phenomena that are widely used by researchers in geomagnetism. We introduce an index focused on the internally generated field that can be used to evaluate long term variations or climatology of modern and paleomagnetic secular variation, including geomagnetic excursions, polarity reversals, and changes in reversal rate. The paleosecular variation index, Pi, represents instantaneous or average deviation from a geocentric axial dipole field using normalized ratios of virtual geomagnetic pole colatitude and virtual dipole moment. The activity level of the index, σPi, provides a measure of field stability through the temporal standard deviation of Pi. Pi can be calculated on a global grid from geomagnetic field models to reveal large scale geographic variations in field structure. It can be determined for individual time series, or averaged at local, regional, and global scales to detect long term changes in geomagnetic activity, identify excursions, and transitional field behavior. For recent field models, Pi ranges from less than 0.05 to 0.30. Conventional definitions for geomagnetic excursions are characterized by Pi exceeding 0.5. Strong field intensities are associated with low Pi unless they are accompanied by large deviations from axial dipole field directions. σPi provides a measure of geomagnetic stability that is modulated by the level of PSV or frequency of excursional activity and reversal rate. We demonstrate uses of Pi for paleomagnetic observations and field models and show how it could be used to assess whether numerical simulations of the geodynamo exhibit Earth-like properties.

Functional Conservation of PISTILLATA Activity in a Pea Homolog Lacking the PI Motif1

PubMed Central

Berbel, Ana; Navarro, Cristina; Ferrándiz, Cristina; Cañas, Luis Antonio; Beltrán, José-Pío; Madueño, Francisco

2005-01-01

Current understanding of floral development is mainly based on what we know from Arabidopsis (Arabidopsis thaliana) and Antirrhinum majus. However, we can learn more by comparing developmental mechanisms that may explain morphological differences between species. A good example comes from the analysis of genes controlling flower development in pea (Pisum sativum), a plant with more complex leaves and inflorescences than Arabidopsis and Antirrhinum, and a different floral ontogeny. The analysis of UNIFOLIATA (UNI) and STAMINA PISTILLOIDA (STP), the pea orthologs of LEAFY and UNUSUAL FLORAL ORGANS, has revealed a common link in the regulation of flower and leaf development not apparent in Arabidopsis. While the Arabidopsis genes mainly behave as key regulators of flower development, where they control the expression of B-function genes, UNI and STP also contribute to the development of the pea compound leaf. Here, we describe the characterization of P. sativum PISTILLATA (PsPI), a pea MADS-box gene homologous to B-function genes like PI and GLOBOSA (GLO), from Arabidopsis and Antirrhinum, respectively. PsPI encodes for an atypical PI-type polypeptide that lacks the highly conserved C-terminal PI motif. Nevertheless, constitutive expression of PsPI in tobacco (Nicotiana tabacum) and Arabidopsis shows that it can specifically replace the function of PI, being able to complement the strong pi-1 mutant. Accordingly, PsPI expression in pea flowers, which is dependent on STP, is identical to PI and GLO. Interestingly, PsPI is also transiently expressed in young leaves, suggesting a role of PsPI in pea leaf development, a possibility that fits with the established role of UNI and STP in the control of this process. PMID:16113230

Design and implementation of adaptive PI control schemes for web tension control in roll-to-roll (R2R) manufacturing.

PubMed

Raul, Pramod R; Pagilla, Prabhakar R

2015-05-01

In this paper, two adaptive Proportional-Integral (PI) control schemes are designed and discussed for control of web tension in Roll-to-Roll (R2R) manufacturing systems. R2R systems are used to transport continuous materials (called webs) on rollers from the unwind roll to the rewind roll. Maintaining web tension at the desired value is critical to many R2R processes such as printing, coating, lamination, etc. Existing fixed gain PI tension control schemes currently used in industrial practice require extensive tuning and do not provide the desired performance for changing operating conditions and material properties. The first adaptive PI scheme utilizes the model reference approach where the controller gains are estimated based on matching of the actual closed-loop tension control systems with an appropriately chosen reference model. The second adaptive PI scheme utilizes the indirect adaptive control approach together with relay feedback technique to automatically initialize the adaptive PI gains. These adaptive tension control schemes can be implemented on any R2R manufacturing system. The key features of the two adaptive schemes is that their designs are simple for practicing engineers, easy to implement in real-time, and automate the tuning process. Extensive experiments are conducted on a large experimental R2R machine which mimics many features of an industrial R2R machine. These experiments include trials with two different polymer webs and a variety of operating conditions. Implementation guidelines are provided for both adaptive schemes. Experimental results comparing the two adaptive schemes and a fixed gain PI tension control scheme used in industrial practice are provided and discussed. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Regulation of flow through a T-Shaped open cavity by temperature dependent P, PI, and PID controllers

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

Saha, Sourav, E-mail: ssaha09@me.buet.ac.bd; Mojumder, Satyajit, E-mail: satyajit@me.buet.ac.bd; Saha, Sumon, E-mail: sumonsaha@me.buet.ac.bd

P (proportional), PI (proportional-integral), and PID (proportional-integral-derivative) controllers are popular means of controlling industrial processes. Due to superior response, accuracy, and stable performance, PID controllers are mostly used in control systems. This paper presents a mathematical model and subsequent response analysis regarding regulation of flow in mixed convection through a T-shaped open cavity by temperature dependent controllers. The T-shaped cavity has cold top and hot bottom walls, while air is flowing through the inlet at surrounding temperature. The inflow is regulated by a controlled gate which operates according to the signal received from the controller. Values of proportional gain (k{submore » p}), integral gain (k{sub i}), and derivative gain (k{sub d}) are varied to obtain the desired system response and to ensure a stable system with fastest response. At first, only P controller is used and eventually PI and finally PID control scheme is applied for controller tuning. Tuning of different controllers (P, PI, and PID) are carried out systematically based on the reference temperature which is continuously monitored at a certain location inside the cavity. It is found that PID controller performs better than P or PI controller.« less

Phosphoinositides play differential roles in regulating phototropin1- and phototropin2-mediated chloroplast movements in Arabidopsis.

PubMed

Aggarwal, Chhavi; Labuz, Justyna; Gabryś, Halina

2013-01-01

Phototropins are UVA/blue-light receptors involved in controlling the light-dependent physiological responses which serve to optimize the photosynthetic activity of plants and promote growth. The phototropin-induced phosphoinositide (PI) metabolism has been shown to be essential for stomatal opening and phototropism. However, the role of PIs in phototropin-induced chloroplast movements remains poorly understood. The aim of this work is to determine which PI species are involved in the control of chloroplast movements in Arabidopsis and the nature of their involvement. We present the effects of the inactivation of phospholipase C (PLC), PI3-kinase (PI3K) and PI4-kinase (PI4K) on chloroplast relocations in Arabidopsis. The inhibition of the phosphatidylinositol 4,5-bisphospahte [PI(4,5)P2]-PLC pathway, using neomycin and U73122, suppressed the phot2-mediated chloroplast accumulation and avoidance responses, without affecting movement responses controlled by phot1. On the other hand, PI3K and PI4K activities are more restricted to phot1- and phot2-induced weak-light responses. The inactivation of PI3K and PI4K by wortmannin and LY294002 severely affected the weak blue-light-activated accumulation response but had little effect on the strong blue-light-activated avoidance response. The inhibitory effect observed with PI metabolism inhibitors is, at least partly, due to a disturbance in Ca(2+) ((c)) signaling. Using the transgenic aequorin system, we show that the application of these inhibitors suppresses the blue-light-induced transient Ca(2+) ((c)) rise. These results demonstrate the importance of PIs in chloroplast movements, with the PI(4,5)P2-PLC pathway involved in phot2 signaling while PI3K and PI4K are required for the phot1- and phot2-induced accumulation response. Our results suggest that these PIs modulate cytosolic Ca(2+) signaling during movements.

Synchronization controller design of two coupling permanent magnet synchronous motors system with nonlinear constraints.

PubMed

Deng, Zhenhua; Shang, Jing; Nian, Xiaohong

2015-11-01

In this paper, two coupling permanent magnet synchronous motors system with nonlinear constraints is studied. First of all, the mathematical model of the system is established according to the engineering practices, in which the dynamic model of motor and the nonlinear coupling effect between two motors are considered. In order to keep the two motors synchronization, a synchronization controller based on load observer is designed via cross-coupling idea and interval matrix. Moreover, speed, position and current signals of two motor all are taken as self-feedback signal as well as cross-feedback signal in the proposed controller, which is conducive to improving the dynamical performance and the synchronization performance of the system. The proposed control strategy is verified by simulation via Matlab/Simulink program. The simulation results show that the proposed control method has a better control performance, especially synchronization performance, than that of the conventional PI controller. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

Multivariable model predictive control design of reactive distillation column for Dimethyl Ether production

NASA Astrophysics Data System (ADS)

Wahid, A.; Putra, I. G. E. P.

2018-03-01

Dimethyl ether (DME) as an alternative clean energy has attracted a growing attention in the recent years. DME production via reactive distillation has potential for capital cost and energy requirement savings. However, combination of reaction and distillation on a single column makes reactive distillation process a very complex multivariable system with high non-linearity of process and strong interaction between process variables. This study investigates a multivariable model predictive control (MPC) based on two-point temperature control strategy for the DME reactive distillation column to maintain the purities of both product streams. The process model is estimated by a first order plus dead time model. The DME and water purity is maintained by controlling a stage temperature in rectifying and stripping section, respectively. The result shows that the model predictive controller performed faster responses compared to conventional PI controller that are showed by the smaller ISE values. In addition, the MPC controller is able to handle the loop interactions well.

Study of biodegradable polymers for ``green'' devices

NASA Astrophysics Data System (ADS)

Perez, Carlos; Jiang, Xiaomei; Jiang Group Team

2015-03-01

Π - conjugated polymers such as polythiophenes are conventional picks for cost-effective organic solar cells. However, these organic semiconductors are not environment-friendly since the polymer back bones require temperature higher than 3000C to be decomposed, thus will cause potential environment problems upon disposal. In this work, the optical and electronic properties of biodegradable polymers, conjugated poly(disulfidediamine), were examined via continuous wave laser spectroscopy, FTIR spectroscopy and conductivity measurement. We found that the attachment of a side chain to aromatic ring increases both photo and thermal stability, as well as higher conductivity. Thermal annealing improved the film morphological, photophysical and electronic properties. Photo-Induced Absorption (PIA) reveals different features comparing with conventional pi-conjugated polymers. No observation of long-lived photoexcitations such as polarons or triplets which are common with pi-conjugated polymers. Instead, we found the formation of low energy species upon thermal annealing in these biodegradable polymers.

Inhibitory Control and Working Memory in Post-Institutionalized Children

PubMed Central

Merz, Emily C.; McCall, Robert B.; Wright, Amanda J.; Luna, Beatriz

2013-01-01

Inhibitory control and working memory were examined in post-institutionalized (PI) children adopted into United States families from Russian institutions. The PI sample originated from institutions that were less severely depriving than those represented in previous studies and approximated the level of psychosocial deprivation, which is characterized by adequate physical resources but a lack of consistent and responsive caregiving. PI children (N=75; 29 male) ranged in age from 8–17 years (M=12.97; SD=3.03) and were grouped according to whether they were adopted after 14 months or before 9 months. A non-adopted comparison group (N=133; 65 male) ranged in age from 8–17 years (M=12.26; SD=2.75). PI children adopted after 14 months of age displayed poorer performance on the stop-signal and spatial span tasks relative to PI children adopted before 9 months of age after controlling for age at assessment. The two PI groups did not differ in their performance on a spatial self-ordered search task. Older-adopted PI children also showed poorer spatial span task performance compared to non-adopted children, but younger-adopted PI children did not. Task performance was significantly associated with parent-rated hyperactive-impulsive behavior in everyday contexts. These findings suggest that exposure to prolonged early institutional deprivation may be linked with inhibitory control and working memory difficulties years after adoption. PMID:23519375

Baseband pulse shaping techniques for nonlinearly amplified pi/4-QPSK and QAM systems

NASA Technical Reports Server (NTRS)

Feher, Kamilo

1991-01-01

A new generation of multi-stage pi/4-shifted QPSK and of superposed quadrature-amplitude-modulated (SQAM) modulators-coherent demodulators (modems) and of continuous phase modulated (CPM)-gaussian premodulation filtered minimum-shift-keying (MGMSK) systems is proposed and studied. These modems will lead to bandwidth and power efficient satellite communications systems designs. As an illustrative application, a baseband processing technique pi/4-controlled transition PSK (pi/4-CTPSK) is described. To develop a cost and power efficient design strategy, we assume that nonlinear, fully saturated high power amplifiers (HPA) are utilized in the satellite earth station transmitter and in the satellite transponder. Modem structures which could lead to application specific integrated circuit (ASIC) satellite on-board processing universal modem applications are also considered. Multistate GMSK (i.e., MGMSK) signal generation methods by means of two or more RF combined nonlinearly amplified SQAM modems and by one multistate (in-phase and quadrature-baseband premodulation filtered-superposed) SQAM architecture and one RF nonlinear amplifier are studied. During the SQAM modem development phase we investigate the potential system advantages of the pi/4-shifted logic. The bandwidth efficiency of the proposed multistate GMSK and baseband filtered PAM-FM modulator (a new class in the CPM family) will be significantly higher than that of conventional G-MSK systems. To optimize the practical P(sub e) = f((E sub b)/(N sub o)) performance we consider improved coherent demodulation MGMSK structures such as deviated-frequency locking coherent demodulators. For relative low bit rate SATCOM applications, e.g., bit rates less than 300 kb/s, phase noise tracking cancellation (for fixed site earth station) and phase noise cancellation as well as Doppler compensation (for satellite to mobile earth station) applications may be required. We study digital channel sounding methods which could cancel the phase noise-caused degradations of CPM and GMSK modems.

Promoting healthy weight among elementary school children via a health report card approach.

PubMed

Chomitz, Virginia R; Collins, Jessica; Kim, Juhee; Kramer, Ellen; McGowan, Robert

2003-08-01

As overweight continues to rise among children, schools seek effective and sensitive ways to engage parents in promoting healthy weight. To evaluate a school-based health report card on the family awareness of and concern about the child weight status, plans for weight control, and preventive behaviors. Quasi-experimental field trial with a personalized weight and fitness health report card intervention (PI), a general-information intervention (GI), and a control group (CG). Outcomes were assessed using a postintervention telephone survey, including process and outcome measures. The intervention included 1396 ethnically diverse students at 4 elementary schools in an urban area. Telephone surveys were completed by 399 families from an evaluation sample of 793. Intervention Families were randomly assigned to the PI, GI, or CG and mailed intervention materials. The CG was mailed GI materials after the survey. Parent awareness of child weight status, concerns, weight-control plans, and preventive behaviors. Group effects were significantly different by the child's weight status, so results were stratified. Among overweight students, intervention parents were more likely to know their child's weight status (PI, 44%; GI, 41%; CG, 23%) (P =.02). The PI parents planned medical help (PI, 25%; GI, 7%; CG, 9%) (P =.004), dieting activities (PI, 19%; GI and CG, <5 cases) (P =.02) and physical activities (PI, 42%; GI, 27%; CG, 13%) (P<.001) for their overweight children. No group effect on concern or preventive behaviors was detected. Most parents of overweight children who read materials requested annual weight and health information on their child (PI, 91%; GI, 67%). Among overweight children, the PI was associated with increased parental awareness of their child's weight status. Although parents wanted PI for their children, more research is needed to test this approach on children's self-esteem and plans for weight control.

Hadronic decays of the X(3872) to {chi}{sub cJ} in effective field theory

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

Fleming, Sean; Mehen, Thomas

2008-11-01

The decays of the X(3872) to P-wave quarkonia are calculated under the assumption that it is a shallow bound state of neutral charmed mesons. The X(3872) is described using an effective theory of nonrelativistic D mesons and pions (X-EFT). We calculate X(3872) decays by first matching heavy hadron chiral perturbation theory (HH{chi}PT) amplitudes for D{sup 0}D*{sup 0}{yields}{chi}{sub cJ}({pi}{sup 0},{pi}{pi}) onto local operators in X-EFT, and then using these operators to calculate the X(3872) decays. This procedure reproduces the factorization theorems for X(3872) decays to conventional quarkonia previously derived using the operator product expansion. For single pion decays, we find nontrivialmore » dependence on the pion energy from HH{chi}PT diagrams with virtual D mesons. This nontrivial energy dependence can potentially modify heavy-quark symmetry predictions for the relative sizes of decay rates. At leading order, decays to final states with two pions are dominated by the final state {chi}{sub c1}{pi}{sup 0}{pi}{sup 0}, with a branching fraction just below that for the decay to {chi}{sub c1}{pi}{sup 0}. Decays to all other final states with two pions are highly suppressed.« less

On existence of the {sigma}(600) Its physical implications and related problems

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

Ishida, Shin

1998-05-29

We make a re-analysis of 1=0 {pi}{pi} scattering phase shift {delta}{sub 0}{sup 0} through a new method of S-matrix parametrization (IA; interfering amplitude method), and show a result suggesting strongly for the existence of {sigma}-particle-long-sought Chiral partner of {pi}-meson. Furthermore, through the phenomenological analyses of typical production processes of the 2{pi}-system, the pp-central collision and the J/{psi}{yields}{omega}{pi}{pi} decay, by applying an intuitive formula as sum of Breit-Wigner amplitudes, (VMW; variant mass and width method), the other evidences for the {sigma}-existence are given. The validity of the methods used in the above analyses is investigated, using a simple field theoretical model,more » from the general viewpoint of unitarity and the applicability of final state interaction (FSI-) theorem, especially in relation to the ''universality'' argument. It is shown that the IA and VMW are obtained as the physical state representations of scattering and production amplitudes, respectively. The VMW is shown to be an effective method to obtain the resonance properties from production processes, which generally have the unknown strong-phases. The conventional analyses based on the 'universality' seem to be powerless for this purpose.« less

Electron-transfer quenching vs. exciplex-mediated quenching of the low-lying excited states in phthalocyanines

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

Prasad, D.R.; Ferraudi, G.

1983-05-25

Oxidative electron-transfer quenching of the lowest ligand-centered /sup 3/..pi pi..* of ruthenium (RU) phthalocyanines (pc)L/sub 2/, L = dimethylformamide (dmf) or pyridine (py), by a series of nitroaromatic compounds, viologen salts, and metal complexes has been investigated by laser and conventional flash photolysis. The quenching rate constants, treated according to Marcus-Hush and Rehm-Weller equations, gave self-exchange rate constants, k/sub exch/ approx. 10/sup 7/ M/sup -1/ s/sup -1/, for the electron exchange between the /sup 3/..pi pi..* and the ruthenium(II) ligand radical. The excited states of a number of phthalocyanines, e.g. Ru(pc)(dimethyl sulfoxide(Me/sub 2/SO)/sub 2/), Ru(pc)(dmf)CO, Ru(pc)(py)CO, and Rh(pc)(methanol(CH/sub 3/OH)chloride), undergomore » quenching mediated by exciplex formation. The formation of exciplexes is discussed in terms of the related exciplexes of the porphyrins.« less

A new robust control scheme using second order sliding mode and fuzzy logic of a DFIM supplied by two five-level SVPWM inverters

NASA Astrophysics Data System (ADS)

Boudjema, Zinelaabidine; Taleb, Rachid; Bounadja, Elhadj

2017-02-01

Traditional filed oriented control strategy including proportional-integral (PI) regulator for the speed drive of the doubly fed induction motor (DFIM) have some drawbacks such as parameter tuning complications, mediocre dynamic performances and reduced robustness. Therefore, based on the analysis of the mathematical model of a DFIM supplied by two five-level SVPWM inverters, this paper proposes a new robust control scheme based on super twisting sliding mode and fuzzy logic. The conventional sliding mode control (SMC) has vast chattering effect on the electromagnetic torque developed by the DFIM. In order to resolve this problem, a second order sliding mode technique based on super twisting algorithm and fuzzy logic functions is employed. The validity of the employed approach was tested by using Matlab/Simulink software. Interesting simulation results were obtained and remarkable advantages of the proposed control scheme were exposed including simple design of the control system, reduced chattering as well as the other advantages.

Proportional-integral and proportional-integral-derivative-based cyclic sleep controllers with anti-windup technique for energy-efficient and delay-aware passive optical networks

NASA Astrophysics Data System (ADS)

Kikuchi, Takahiro; Kubo, Ryogo

2016-08-01

In energy-efficient passive optical network (PON) systems, the increase in the queuing delays caused by the power-saving mechanism of optical network units (ONUs) is an important issue. Some researchers have proposed quality-of-service (QoS)-aware ONU cyclic sleep controllers in PON systems. We have proposed proportional (P) and proportional-derivative (PD)-based controllers to maintain the average queuing delay at a constant level regardless of the amount of downstream traffic. However, sufficient performance has not been obtained because of the sleep period limitation. In this paper, proportional-integral (PI) and proportional-integral-derivative (PID)-based controllers considering the sleep period limitation, i.e., using an anti-windup (AW) technique, are proposed to improve both the QoS and power-saving performance. Simulations confirm that the proposed controllers provide better performance than conventional controllers in terms of the average downstream queuing delay and the time occupancy of ONU active periods.

Adaptive fuzzy logic controller with direct action type structures for InnoSAT attitude control system

NASA Astrophysics Data System (ADS)

Bakri, F. A.; Mashor, M. Y.; Sharun, S. M.; Bibi Sarpinah, S. N.; Abu Bakar, Z.

2016-10-01

This study proposes an adaptive fuzzy controller for attitude control system (ACS) of Innovative Satellite (InnoSAT) based on direct action type structure. In order to study new methods used in satellite attitude control, this paper presents three structures of controllers: Fuzzy PI, Fuzzy PD and conventional Fuzzy PID. The objective of this work is to compare the time response and tracking performance among the three different structures of controllers. The parameters of controller were tuned on-line by adjustment mechanism, which was an approach similar to a PID error that could minimize errors between actual and model reference output. This paper also presents a Model References Adaptive Control (MRAC) as a control scheme to control time varying systems where the performance specifications were given in terms of the reference model. All the controllers were tested using InnoSAT system under some operating conditions such as disturbance, varying gain, measurement noise and time delay. In conclusion, among all considered DA-type structures, AFPID controller was observed as the best structure since it outperformed other controllers in most conditions.

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.

Epilepsy increases vulnerability of long-term face recognition to proactive interference.

PubMed

Bengner, T; Malina, T; Lindenau, M; Voges, B; Goebell, E; Stodieck, S

2006-02-01

Proactive interference (PI) decreases short- and long-term memory in healthy subjects. Neurological patients exhibit a heightened PI effect on short-term memory. It is, however, not known if PI affects long-term memory in neurological patients. We analyzed whether epilepsy heightens the negative effect of PI on long-term face memory. PI was induced by a list of 20 faces learned 24 hours prior to a target list of 20 faces. We tested immediate and 24-hour recognition for both lists. Twelve healthy controls and 42 patients with generalized epilepsy or temporal lobe epilepsy (TLE) were studied. PI led to a decrease in 24-hour recognition in patients with generalized epilepsy and TLE but not in controls. Thus, PI may cause long-term memory disturbances in epilepsy patients. PI was also associated with decreased short-term memory, but only in right TLE. This confirms the dominant role of the right temporal lobe in short-term face memory.

Optimized statistical parametric mapping for partial-volume-corrected amyloid positron emission tomography in patients with Alzheimer's disease and Lewy body dementia

NASA Astrophysics Data System (ADS)

Oh, Jungsu S.; Kim, Jae Seung; Chae, Sun Young; Oh, Minyoung; Oh, Seung Jun; Cha, Seung Nam; Chang, Ho-Jong; Lee, Chong Sik; Lee, Jae Hong

2017-03-01

We present an optimized voxelwise statistical parametric mapping (SPM) of partial-volume (PV)-corrected positron emission tomography (PET) of 11C Pittsburgh Compound B (PiB), incorporating the anatomical precision of magnetic resonance image (MRI) and amyloid β (A β) burden-specificity of PiB PET. First, we applied region-based partial-volume correction (PVC), termed the geometric transfer matrix (GTM) method, to PiB PET, creating MRI-based lobar parcels filled with mean PiB uptakes. Then, we conducted a voxelwise PVC by multiplying the original PET by the ratio of a GTM-based PV-corrected PET to a 6-mm-smoothed PV-corrected PET. Finally, we conducted spatial normalizations of the PV-corrected PETs onto the study-specific template. As such, we increased the accuracy of the SPM normalization and the tissue specificity of SPM results. Moreover, lobar smoothing (instead of whole-brain smoothing) was applied to increase the signal-to-noise ratio in the image without degrading the tissue specificity. Thereby, we could optimize a voxelwise group comparison between subjects with high and normal A β burdens (from 10 patients with Alzheimer's disease, 30 patients with Lewy body dementia, and 9 normal controls). Our SPM framework outperformed than the conventional one in terms of the accuracy of the spatial normalization (85% of maximum likelihood tissue classification volume) and the tissue specificity (larger gray matter, and smaller cerebrospinal fluid volume fraction from the SPM results). Our SPM framework optimized the SPM of a PV-corrected A β PET in terms of anatomical precision, normalization accuracy, and tissue specificity, resulting in better detection and localization of A β burdens in patients with Alzheimer's disease and Lewy body dementia.

The relationship between VMT and economic activity.

DOT National Transportation Integrated Search

2011-11-01

"Vehicle miles traveled (VMT) in the U.S. have exhibited an upward trend over time similar to that observed : for gross domestic product (GDP) and personal income (PI). While conventional wisdom suggests that economic : growth leads to more driving a...

RBF neural network based PI pitch controller for a class of 5-MW wind turbines using particle swarm optimization algorithm.

PubMed

Poultangari, Iman; Shahnazi, Reza; Sheikhan, Mansour

2012-09-01

In order to control the pitch angle of blades in wind turbines, commonly the proportional and integral (PI) controller due to its simplicity and industrial usability is employed. The neural networks and evolutionary algorithms are tools that provide a suitable ground to determine the optimal PI gains. In this paper, a radial basis function (RBF) neural network based PI controller is proposed for collective pitch control (CPC) of a 5-MW wind turbine. In order to provide an optimal dataset to train the RBF neural network, particle swarm optimization (PSO) evolutionary algorithm is used. The proposed method does not need the complexities, nonlinearities and uncertainties of the system under control. The simulation results show that the proposed controller has satisfactory performance. Copyright © 2012 ISA. Published by Elsevier Ltd. All rights reserved.

Adaptive GSA-based optimal tuning of PI controlled servo systems with reduced process parametric sensitivity, robust stability and controller robustness.

PubMed

Precup, Radu-Emil; David, Radu-Codrut; Petriu, Emil M; Radac, Mircea-Bogdan; Preitl, Stefan

2014-11-01

This paper suggests a new generation of optimal PI controllers for a class of servo systems characterized by saturation and dead zone static nonlinearities and second-order models with an integral component. The objective functions are expressed as the integral of time multiplied by absolute error plus the weighted sum of the integrals of output sensitivity functions of the state sensitivity models with respect to two process parametric variations. The PI controller tuning conditions applied to a simplified linear process model involve a single design parameter specific to the extended symmetrical optimum (ESO) method which offers the desired tradeoff to several control system performance indices. An original back-calculation and tracking anti-windup scheme is proposed in order to prevent the integrator wind-up and to compensate for the dead zone nonlinearity of the process. The minimization of the objective functions is carried out in the framework of optimization problems with inequality constraints which guarantee the robust stability with respect to the process parametric variations and the controller robustness. An adaptive gravitational search algorithm (GSA) solves the optimization problems focused on the optimal tuning of the design parameter specific to the ESO method and of the anti-windup tracking gain. A tuning method for PI controllers is proposed as an efficient approach to the design of resilient control systems. The tuning method and the PI controllers are experimentally validated by the adaptive GSA-based tuning of PI controllers for the angular position control of a laboratory servo system.

Prenatal retinoic acid upregulates pulmonary gene expression of PI3K and AKT in nitrofen-induced pulmonary hypoplasia.

PubMed

Doi, Takashi; Sugimoto, Kaoru; Ruttenstock, Elke; Dingemann, Jens; Puri, Prem

2010-10-01

The precise mechanism of pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) still remains unclear. Recently, prenatal treatment with retinoic acid (RA) has been reported to stimulate alveologenesis in hypoplastic lungs in the nitrofen model of CDH. The serine/threonine protein kinase B (AKT) plays a key role in lung morphogenesis through epithelial-mesenchymal interaction in phosphatidylinositide 3-kinase (PI3K)-dependent manner. It has been reported that the lung morphogenesis in explants in mice is interfered by inhibitors of PI3K-AKT signaling pathway. Furthermore, we have recently shown that nitrofen inhibits PI3K-AKT signaling during mid-to-late lung morphogenesis in the nitrofen-induced hypoplastic lung. We hypothesized that prenatal administration of RA upregulates pulmonary gene expression of PI3K and AKT in the nitrofen-induced hypoplastic lung. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). 5 mg/kg of RA was given on D18, D19 and D20. The fetuses were harvested on D21, and fetal lungs were obtained and divided into four groups: control, control + RA, nitrofen, nitrofen + RA. The mRNA expression levels of PI3K and AKT were analyzed in each lung by real-time RT-PCR and statistically analyzed. Immunohistochemistry was also performed to evaluate protein expression of PI3K and AKT in the fetal lungs at D21. The pulmonary gene expression levels of PI3K and AKT were significantly upregulated in nitrofen + RA group compared to nitrofen group and control + RA group (p < 0.05), whereas there were no significant differences between controls and control + RA group. Immunoreactivity of PI3K and AKT was markedly increased in nitrofen + RA lungs compared to nitrofen-induced hypoplastic lungs. Upregulation of PI3K and AKT genes after prenatal treatment with RA in the nitrofen-induced hypoplastic lung suggests that RA may have a therapeutic potential in modulating lung alveologenesis by stimulating epithelial-mesenchymal interaction via PI3K-AKT signaling.

Is PiSS Alpha-1 Antitrypsin Deficiency Associated with Disease?

PubMed

McGee, Dawn; Schwarz, Laura; McClure, Rebecca; Peterka, Lauren; Rouhani, Farshid; Brantly, Mark; Strange, Charlie

2010-01-01

Background. Alpha-1 antitrypsin deficiency (AAT) is an inherited condition that predisposes to lung and/or liver disease. Objective. The current study examined the clinical features of the PiSS genotype. Methods. Nineteen study participants (PiSS) and 29 matched control participants (PiMM) were telephone interviewed using a standardized questionnaire. Demographic features, cigarette smoking, vocation, medication history, and clinical diagnoses were compared. Statistical analysis was performed. Finally, a comprehensive literature review was performed by two investigators. Results. 12/19 (63.2%) study participants reported the presence of lung and/or liver disease compared to 12/29 (41.4%) control participants. There trended toward having a higher frequency of medication allergies in the study population (42.11% versus 20.69%). Conclusions. The PiSS genotype was associated with a similar incidence of obstructive lung disease to controls. Selective bias intrinsic in testing for AAT deficiency and the rarity of the PiSS genotype will make future study of this association dependent on population-based tests.

Is PiSS Alpha-1 Antitrypsin Deficiency Associated with Disease?

PubMed Central

McGee, Dawn; Schwarz, Laura; McClure, Rebecca; Peterka, Lauren; Rouhani, Farshid; Brantly, Mark; Strange, Charlie

2010-01-01

Background. Alpha-1 antitrypsin deficiency (AAT) is an inherited condition that predisposes to lung and/or liver disease. Objective. The current study examined the clinical features of the PiSS genotype. Methods. Nineteen study participants (PiSS) and 29 matched control participants (PiMM) were telephone interviewed using a standardized questionnaire. Demographic features, cigarette smoking, vocation, medication history, and clinical diagnoses were compared. Statistical analysis was performed. Finally, a comprehensive literature review was performed by two investigators. Results. 12/19 (63.2%) study participants reported the presence of lung and/or liver disease compared to 12/29 (41.4%) control participants. There trended toward having a higher frequency of medication allergies in the study population (42.11% versus 20.69%). Conclusions. The PiSS genotype was associated with a similar incidence of obstructive lung disease to controls. Selective bias intrinsic in testing for AAT deficiency and the rarity of the PiSS genotype will make future study of this association dependent on population-based tests. PMID:21687342

Tooth movement using palatal implant supported anchorage compared to conventional dental anchorage.

PubMed

Borsos, Gabriella; Vokó, Zoltan; Gredes, Tomasz; Kunert-Keil, Christiane; Vegh, Andras

2012-11-01

Tooth stability is one of the most changing parameters in age. The aim of the present study has been to clarify the therapeutic benefit of the osseointegrated palatal implant (PI) supported anchorage in adolescents compared with conventional dental anchorage (DA) in extraction cases requiring 'maximum anchorage' in growing patients following the post pubertal growth spurt. Thirty patients (14.22±1.37 years) selected with homogeneous facial skeletal characteristics were divided in two groups. In the PI group, Orthosystem(®) implants were placed into the palate for anchorage and the transpalatal arch (TPA) was fixed to the implant and to the molar bands. In the DA group maximal anchorage was provided by a TPA and a utility arch. Super-elastic spring was used for canine- and contraction arch for incisor retraction. An insignificant difference was observed between the groups as to the duration of the canine retraction. In the PI group, the duration of the front retraction and the total treatment time was shorter compared to the DA group (P<0.05). No significant difference in molar mesial movement was found during canine retraction, but during front retraction, there was significantly less mesial molar movement in the PI group compared to the DA group (P<0.05). The use of palatal implant-based anchorage does not offer a shorter canine retraction period, but resulted in a significant shortening of the front-retraction phase and a total treatment time shortened by 5 months on average. The tooth stability in adolescent patients is adequate for tooth movements using both methods. Copyright © 2012 Elsevier GmbH. All rights reserved.

Simple system for measuring tritium Ad/absorption using a 2. pi. counter and thermal desorption spectrometer

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

Miyake, H.; Matsuyama, M.; Watanabe, K.

1992-03-01

In this paper, the authors develop a simple system using tritium tracer and thermal desorption techniques to measure the tritium adsorption and/or absorption on/in a material having typical surface conditions: namely, not cleaned surface. The tritium counting devices used were a 2{pi} counter and conventional proportional counter. With this system, the amounts of ad/absorption could be measured without exposing the samples to air after exposing them to tritium gas. The overall efficiency (F) of the 2{pi} counter was described at F = exp({minus}2.64h), where h is the distance from the sample to the detector. Ad/absorption measurements were carried out formore » several materials used for fabricating conventional vacuum systems. The results were, in the order of decreasing amounts of ad/absorption, as (fiber reinforced plastics(FRP)) {gt} (nickel(Ni), molybdenum disulfide(MoS{sub 2})) {gt} (stainless steel (SS304), iron(Fe), aluminum alloy(A2219)) {gt} (boron nitride(h-BN), silicon carbide (SiC), SS304 passivated by anodic oxidation layers(ASS) and that by boron nitride segregation layers (BSS)). The relative amounts were abut 100 for Ni and 0.1 for ASS and BSS, being normalized to Fe = 1.« less

Strong convergence and convergence rates of approximating solutions for algebraic Riccati equations in Hilbert spaces

NASA Technical Reports Server (NTRS)

Ito, Kazufumi

1987-01-01

The linear quadratic optimal control problem on infinite time interval for linear time-invariant systems defined on Hilbert spaces is considered. The optimal control is given by a feedback form in terms of solution pi to the associated algebraic Riccati equation (ARE). A Ritz type approximation is used to obtain a sequence pi sup N of finite dimensional approximations of the solution to ARE. A sufficient condition that shows pi sup N converges strongly to pi is obtained. Under this condition, a formula is derived which can be used to obtain a rate of convergence of pi sup N to pi. The results of the Galerkin approximation is demonstrated and applied for parabolic systems and the averaging approximation for hereditary differential systems.

Pathogen-free, plasma-poor platelet lysate and expansion of human mesenchymal stem cells.

PubMed

Iudicone, Paola; Fioravanti, Daniela; Bonanno, Giuseppina; Miceli, Michelina; Lavorino, Claudio; Totta, Pierangela; Frati, Luigi; Nuti, Marianna; Pierelli, Luca

2014-01-27

Supplements to support clinical-grade cultures of mesenchymal stem cells (MSC) are required to promote growth and expansion of these cells. Platelet lysate (PL) is a human blood component which may replace animal serum in MSC cultures being rich in various growth factors. Here, we describe a plasma poor pathogen-free platelet lysate obtained by pooling 12 platelet (PLT) units, to produce a standardized and safe supplement for clinical-grade expansion of MSC. PL lots were obtained by combining 2 6-unit PLT pools in additive solution (AS) following a transfusional-based procedure including pathogen inactivation (PI) by Intercept technology and 3 cycles of freezing/thawing, followed by membrane removal. Three PI-PL and 3 control PL lots were produced to compare their ability to sustain bone marrow derived MSC selection and expansion. Moreover, two further PL, subjected to PI or not, were also produced starting from the same initial PLT pools to evaluate the impact of PI on growth factor concentration and capacity to sustain cell growth. Additional PI-PL lots were used for comparison with fetal bovine serum (FBS) on MSC expansion. Immunoregulatory properties of PI-PL-generated MSC were documented in vitro by mixed lymphocyte culture (MLC) and peripheral blood mononuclear cells (PBMC) mitogen induced proliferation. PI-PL and PL control lots had similar concentrations of 4 well-described growth factors endowed with MSC stimulating ability. Initial growth and MSC expansion by PI-PL and PL controls were comparable either using different MSC populations or in head to head experiments. Moreover, PI-PL and PL control sustained similar MSC growth of frozen/thawed MSC. Multilineage differentiation of PI-derived and PI-PL-derived MSC were maintained in any MSC cultures as well as their immunoregulatory properties. Finally, no direct impact of PI on growth factor concentration and MSC growth support was observed, whereas the capacity of FBS to sustain MSC expansion in basic medium was irrelevant as compared to PL and PI-PL. The replacement of animal additives with human supplements is a basic issue in MSC ex vivo production. PI-PL represents a standardized, plasma-poor, human preparation which appears as a safe and good candidate to stimulate MSC growth in clinical-scale cultures.

Pathogen-free, plasma-poor platelet lysate and expansion of human mesenchymal stem cells

PubMed Central

2014-01-01

Background Supplements to support clinical-grade cultures of mesenchymal stem cells (MSC) are required to promote growth and expansion of these cells. Platelet lysate (PL) is a human blood component which may replace animal serum in MSC cultures being rich in various growth factors. Here, we describe a plasma poor pathogen-free platelet lysate obtained by pooling 12 platelet (PLT) units, to produce a standardized and safe supplement for clinical-grade expansion of MSC. Methods PL lots were obtained by combining 2 6-unit PLT pools in additive solution (AS) following a transfusional-based procedure including pathogen inactivation (PI) by Intercept technology and 3 cycles of freezing/thawing, followed by membrane removal. Three PI-PL and 3 control PL lots were produced to compare their ability to sustain bone marrow derived MSC selection and expansion. Moreover, two further PL, subjected to PI or not, were also produced starting from the same initial PLT pools to evaluate the impact of PI on growth factor concentration and capacity to sustain cell growth. Additional PI-PL lots were used for comparison with fetal bovine serum (FBS) on MSC expansion. Immunoregulatory properties of PI-PL-generated MSC were documented in vitro by mixed lymphocyte culture (MLC) and peripheral blood mononuclear cells (PBMC) mitogen induced proliferation. Results PI-PL and PL control lots had similar concentrations of 4 well-described growth factors endowed with MSC stimulating ability. Initial growth and MSC expansion by PI-PL and PL controls were comparable either using different MSC populations or in head to head experiments. Moreover, PI-PL and PL control sustained similar MSC growth of frozen/thawed MSC. Multilineage differentiation of PI-derived and PI-PL-derived MSC were maintained in any MSC cultures as well as their immunoregulatory properties. Finally, no direct impact of PI on growth factor concentration and MSC growth support was observed, whereas the capacity of FBS to sustain MSC expansion in basic medium was irrelevant as compared to PL and PI-PL. Conclusion The replacement of animal additives with human supplements is a basic issue in MSC ex vivo production. PI-PL represents a standardized, plasma-poor, human preparation which appears as a safe and good candidate to stimulate MSC growth in clinical-scale cultures. PMID:24467837

Optimal Design of MPPT Controllers for Grid Connected Photovoltaic Array System

NASA Astrophysics Data System (ADS)

Ebrahim, M. A.; AbdelHadi, H. A.; Mahmoud, H. M.; Saied, E. M.; Salama, M. M.

2016-10-01

Integrating photovoltaic (PV) plants into electric power system exhibits challenges to power system dynamic performance. These challenges stem primarily from the natural characteristics of PV plants, which differ in some respects from the conventional plants. The most significant challenge is how to extract and regulate the maximum power from the sun. This paper presents the optimal design for the most commonly used Maximum Power Point Tracking (MPPT) techniques based on Proportional Integral tuned by Particle Swarm Optimization (PI-PSO). These suggested techniques are, (1) the incremental conductance, (2) perturb and observe, (3) fractional short circuit current and (4) fractional open circuit voltage techniques. This research work provides a comprehensive comparative study with the energy availability ratio from photovoltaic panels. The simulation results proved that the proposed controllers have an impressive tracking response. The system dynamic performance improved greatly using the proposed controllers.

Embedded intelligent adaptive PI controller for an electromechanical system.

PubMed

El-Nagar, Ahmad M

2016-09-01

In this study, an intelligent adaptive controller approach using the interval type-2 fuzzy neural network (IT2FNN) is presented. The proposed controller consists of a lower level proportional - integral (PI) controller, which is the main controller and an upper level IT2FNN which tuning on-line the parameters of a PI controller. The proposed adaptive PI controller based on IT2FNN (API-IT2FNN) is implemented practically using the Arduino DUE kit for controlling the speed of a nonlinear DC motor-generator system. The parameters of the IT2FNN are tuned on-line using back-propagation algorithm. The Lyapunov theorem is used to derive the stability and convergence of the IT2FNN. The obtained experimental results, which are compared with other controllers, demonstrate that the proposed API-IT2FNN is able to improve the system response over a wide range of system uncertainties. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Programmable permanent data storage characteristics of nanoscale thin films of a thermally stable aromatic polyimide.

PubMed

Kim, Dong Min; Park, Samdae; Lee, Taek Joon; Hahm, Suk Gyu; Kim, Kyungtae; Kim, Jin Chul; Kwon, Wonsang; Ree, Moonhor

2009-10-06

We have synthesized a new thermally and dimensionally stable polyimide, poly(4,4'-amino(4-hydroxyphenyl)diphenylene hexafluoroisopropylidenediphthalimide) (6F-HTPA PI). 6F-HTPA PI is soluble in organic solvents and is thus easily processed with conventional solution coating techniques to produce good quality nanoscale thin films. Devices fabricated with nanoscale thin PI films with thicknesses less than 77 nm exhibit excellent unipolar write-once-read-many-times (WORM) memory behavior with a high ON/OFF current ratio of up to 10(6), a long retention time and low power consumption, less than +/-3.0 V. Furthermore, these WORM characteristics were found to persist even at high temperatures up to 150 degrees C. The WORM memory behavior was found to be governed by trap-limited space-charge limited conduction and local filament formation. The conduction processes are dominated by hole injection. Thus the hydroxytriphenylamine moieties of the PI polymer might play a key role as hole trapping sites in the observed WORM memory behavior. The properties of 6F-HTPA PI make it a promising material for high-density and very stable programmable permanent data storage devices with low power consumption.

Fuzzy decoupling controller based on multimode control algorithm of PI-single neuron and its application

NASA Astrophysics Data System (ADS)

Zhang, Xianxia; Wang, Jian; Qin, Tinggao

2003-09-01

Intelligent control algorithms are introduced into the control system of temperature and humidity. A multi-mode control algorithm of PI-Single Neuron is proposed for single loop control of temperature and humidity. In order to remove the coupling between temperature and humidity, a new decoupling method is presented, which is called fuzzy decoupling. The decoupling is achieved by using a fuzzy controller that dynamically modifies the static decoupling coefficient. Taking the control algorithm of PI-Single Neuron as the single loop control of temperature and humidity, the paper provides the simulated output response curves with no decoupling control, static decoupling control and fuzzy decoupling control. Those control algorithms are easily implemented in singlechip-based hardware systems.

Cytokine Response after Stimulation with Key Commensal Bacteria Differ in Post-Infectious Irritable Bowel Syndrome (PI-IBS) Patients Compared to Healthy Controls.

PubMed

Sundin, Johanna; Rangel, Ignacio; Repsilber, Dirk; Brummer, Robert-Jan

2015-01-01

Microbial dysbiosis and prolonged immune activation resulting in low-grade inflammation and intestinal barrier dysfunction have been suggested to be underlying causes of post-infectious irritable bowel syndrome (PI-IBS). The aim of this study was to evaluate the difference in cytokine response between mucosal specimens of PI-IBS patients and healthy controls (HC) after ex vivo stimulation with key anaerobic bacteria. Colonic biopsies from 11 PI-IBS patients and 10 HC were stimulated ex vivo with the commensal bacteria Bacteroides ovatus, Ruminococcus gnavus, Akkermansia muciniphila, Subdoligranulum variabile and Eubacterium limosum, respectively. The cytokine release (IL-1β, IL-2, IL-8, IL-10, IL-13, IL-17, TNF-α and IFN-γ) in stimulation supernatants was analyzed using the LUMINEX assay. Comparison of cytokine release between PI-IBS patients and healthy controls was performed taking both unstimulated and bacterially stimulated mucosal specimens into account. IL-13 release from mucosal specimens without bacterial stimulation was significantly lower in PI-IBS patients compared to HC (p < 0.05). After stimulation with Subdoligranulum variabile, IL-1β release from PI-IBS patients was significantly increased compared to HC (p < 0.05). Stimulation with Eubacterium limosum resulted in a significantly decreased IL-10 release in HC compared to PI-IBS patients (p < 0.05) and a tendency to decreased IL-13 release in HC compared to PI-IBS patients (p = 0.07). PI-IBS patients differ from HC with regard to cytokine release ex vivo after stimulation with selected commensal bacteria. Hence, our results support that the pathogenesis of PI-IBS comprises an altered immune response against commensal gut microbes.

Upregulation of Phosphatidylinositol 3-Kinase (PI3K) Enhances Ethylene Biosynthesis and Accelerates Flower Senescence in Transgenic Nicotiana tabacum L.

PubMed

Dek, Mohd Sabri Pak; Padmanabhan, Priya; Sherif, Sherif; Subramanian, Jayasankar; Paliyath, And Gopinadhan

2017-07-15

Phosphatidylinositol 3-kinase (PI3K) is a key enzyme that phosphorylates phosphatidylinositol at 3'-hydroxyl position of the inositol head group initiating the generation of several phosphorylated phosphatidylinositols, collectively referred to as phosphoinositides. The function of PI3K in plant senescence and ethylene signal transduction process was studied by expression of Solanum lycopersicum PI3K in transgenic Nicotiana tabacum , and delineating its effect on flower senescence. Detached flowers of transgenic tobacco plants with overexpressed Sl - PI3K (OX) displayed accelerated senescence and reduced longevity, when compared to the flowers of wild type plants. Flowers from PI3K-overexpressing plants showed enhanced ethylene production and upregulated expression of 1-aminocyclopropane-1-carboxylic acid oxidase 1 ( ACO1 ). Real time polymerase chain reaction (PCR) analysis showed that PI3K was expressed at a higher level in OX flowers than in the control. Seedlings of OX-lines also demonstrated a triple response phenotype with characteristic exaggerated apical hook, shorter hypocotyls and increased sensitivity to 1-aminocyclopropane-1-carboxylate than the control wild type seedlings. In floral tissue from OX-lines, Solanum lycopersicum phosphatidylinositol 3-kinase green fluorescent protein (PI3K-GFP) chimera protein was localized primarily in stomata, potentially in cytoplasm and membrane adjacent to stomatal pores in the guard cells. Immunoblot analysis of PI3K expression in OX lines demonstrated increased protein level compared to the control. Results of the present study suggest that PI3K plays a crucial role in senescence by enhancing ethylene biosynthesis and signaling.

Cognitive control of familiarity: directed forgetting reduces proactive interference in working memory.

PubMed

Festini, Sara B; Reuter-Lorenz, Patricia A

2014-03-01

Proactive interference (PI) occurs when previously learned information interferes with new learning. In a working memory task, PI induces longer response times and more errors to recent negative probes than to new probes, presumably because the recent probe's familiarity invites a "yes" response. Warnings, longer intertrial intervals, and the increased contextual salience of the probes can reduce but not eliminate PI, suggesting that cognitive control over PI is limited. Here we tested whether control exerted in the form of intentional forgetting performed during working memory can reduce the magnitude of PI. In two experiments, participants performed a working memory task with directed-forgetting instructions and the occasional presentation of recent probes. Surprise long-term memory testing indicated better memory for to-be-remembered than for to-be-forgotten items, documenting the classic directed-forgetting effect. Critically, in working memory, PI was virtually eliminated for recent probes from prior to-be-forgotten lists, as compared to recent probes from prior to-be-remembered lists. Thus cognitive control, when executed via directed forgetting, can reduce the adverse and otherwise persistent interference from familiarity, an effect that we attribute to attenuated memory representations of the to-be-forgotten items.

Greater numbers of nucleotide substitutions are introduced into the genomic RNA of bovine viral diarrhea virus during acute infections of pregnant cattle than of non-pregnant cattle.

PubMed

Neill, John D; Newcomer, Benjamin W; Marley, Shonda D; Ridpath, Julia F; Givens, M Daniel

2012-08-06

Bovine viral diarrhea virus (BVDV) strains circulating in livestock herds show significant sequence variation. Conventional wisdom states that most sequence variation arises during acute infections in response to immune or other environmental pressures. A recent study showed that more nucleotide changes were introduced into the BVDV genomic RNA during the establishment of a single fetal persistent infection than following a series of acute infections of naïve cattle. However, it was not known if nucleotide changes were introduce when the virus crossed the placenta and infected the fetus or during the acute infection of the dam. The sequence of the open reading frame (ORF) from viruses isolated from four acutely infected pregnant heifers following exposure to persistently infected (PI) calves was compared to the sequences of the virus from the progenitor PI calf and the virus from the resulting progeny PI calf to determine when genetic change was introduced. This was compared to genetic change found in viruses isolated from a pregnant PI cow and its PI calf, and in three viruses isolated from acutely infected, non-pregnant cattle exposed to PI calves. Most genetic changes previously identified between the progenitor and progeny PI viruses were in place in the acute phase viruses isolated from the dams six days post-exposure to the progenitor PI calf. Additionally, each progeny PI virus had two to three unique nucleotide substitutions that were introduced in crossing the placenta and infection of the fetus. The nucleotide sequence of two acute phase viruses isolated from steers exposed to PI calves revealed that six and seven nucleotide changes were introduced during the acute infection. The sequence of the BVDV-2 virus isolated from an acute infection of a PI calf (BVDV-1a) co-housed with a BVDV-2 PI calf had ten nucleotides that were different from the progenitor PI virus. Finally, twenty nucleotide changes were identified in the PI virus of a calf born to a PI dam. These results demonstrate that nucleotide changes are introduced into the BVDV infecting pregnant cattle at rates of 2.3 to 8 fold higher then during the acute infection of non-pregnant animals.

Global regulation by the seven-component Pi signaling system.

PubMed

Hsieh, Yi-Ju; Wanner, Barry L

2010-04-01

This review concerns how Escherichia coli detects environmental inorganic orthophosphate (P(i)) to regulate genes of the phosphate (Pho) regulon by the PhoR/PhoB two-component system (TCS). P(i) control by the PhoR/PhoB TCS is a paradigm of a bacterial signal transduction pathway in which occupancy of a cell surface receptor(s) controls gene expression in the cytoplasm. The P(i) signaling pathway requires seven proteins, all of which probably interact in a membrane-associated signaling complex. Our latest studies show that P(i) signaling involves three distinct processes, which appear to correspond to different states of the sensory histidine kinase PhoR: an inhibition state, an activation state, and a deactivation state. We describe a revised model for P(i) signal transduction of the E. coli Pho regulon. Copyright 2010 Elsevier Ltd. All rights reserved.

Mathematical models of the simplest fuzzy PI/PD controllers with skewed input and output fuzzy sets.

PubMed

Mohan, B M; Sinha, Arpita

2008-07-01

This paper unveils mathematical models for fuzzy PI/PD controllers which employ two skewed fuzzy sets for each of the two-input variables and three skewed fuzzy sets for the output variable. The basic constituents of these models are Gamma-type and L-type membership functions for each input, trapezoidal/triangular membership functions for output, intersection/algebraic product triangular norm, maximum/drastic sum triangular conorm, Mamdani minimum/Larsen product/drastic product inference method, and center of sums defuzzification method. The existing simplest fuzzy PI/PD controller structures derived via symmetrical fuzzy sets become special cases of the mathematical models revealed in this paper. Finally, a numerical example along with its simulation results are included to demonstrate the effectiveness of the simplest fuzzy PI controllers.

76 FR 34122 - 30-Day Notice of Proposed Information Collection: NEA/PI Online Performance Reporting System (PRS)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-10

... DEPARTMENT OF STATE [Public Notice 7499] 30-Day Notice of Proposed Information Collection: NEA/PI... of 1995. Title of Information Collection: NEA/PI Online Performance Reporting System (PRS). OMB Control Number: 1405-0183. Type of Request: Renewal. Originating Office: NEA/PI. Form Number: DS-4127...

48 CFR 1852.219-84 - Limitation of the principal investigator-STTR program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SBC/Contractor or RI. (b) The PI is considered to be key personnel in the performance of this contract. The SBC/Contractor, whether or not the employer of the PI, shall exercise primary management direction and control over the PI and be overall responsible for the PI's performance under this contract...

Prevalence of. cap alpha. /sub 1/-antitrypsin heterozygotes (Pi MZ) in patients with obstructive pulmonary disease

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

Shigeoka, J.W.; Hall, W.J.; Hyde, R.W.

1976-01-01

An increased incidence of intermediate deficiency of serum ..cap alpha../sub 1/-antitrypsin resulting from Pi phenotype MZ has been reported in patients with chronic obstructive pulmonary disease (COPD) by some laboratories but not confirmed by others. Prevalence of Pi MZ was determined in patients with COPD among 502 subjects referred to a pulmonary function testing laboratory in a region with low concentrations of air pollutants. Control prevalences were obtained from 930 randomly selected subjects in the same community as well as from patients without COPD referred to the laboratory. Depending on criteria used to define COPD, 155 to 306 subjects hadmore » COPD. Pi MZ prevalence in subjects with COPD varied from 1.5 to 4 times the prevalence in the community control group and in the patients without COPD. This difference approached significance or was significant. Because Pi MZ was present in only 3.5 to 4.5% of patients with COPD, Pi MZ is not a major factor in the etiology of COPD in this community. The higher incidence of Pi MZ in patients with COPD reported by other investigators may be explained by small sample size, bias in selection of study or control population groups, or the development of COPD from interaction between Pi MZ and air pollutants or other factors not present in this community.« less

Digital PI-PD controller design for arbitrary order systems: Dominant pole placement approach.

PubMed

Dincel, Emre; Söylemez, Mehmet Turan

2018-05-02

In this paper, a digital PI-PD controller design method is proposed for arbitrary order systems with or without time-delay to achieve desired transient response in the closed-loop via dominant pole placement approach. The digital PI-PD controller design problem is solved by converting the original problem to the digital PID controller design problem. Firstly, parametrization of the digital PID controllers which assign dominant poles to desired location is done. After that the subset of digital PID controller parameters in which the remaining poles are located away from the dominant pole pair is found via Chebyshev polynomials. The obtained PID controller parameters are then transformed into the PI-PD controller parameters by considering the closed-loop controller zero and the design is completed. Success of the proposed design method is firstly demonstrated on an example transfer function and compared with the well-known PID controller methods from the literature through simulations. After that the design method is implemented on the fan and plate laboratory system in a real environment. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Changes in energy metabolism in the quadriceps femoris after a single bout of acute exhaustive swimming in rats: a ³¹P-magnetic resonance spectroscopy study.

PubMed

Sun, Yingwei; Pan, Shinong; Chen, Zhian; Zhao, Heng; Ma, Ying; Zheng, Liqiang; Li, Qi; Deng, Chunbo; Fu, Xihu; Lu, Zaiming; Guo, Qiyong

2014-01-01

Little is known about the value of (31)P-magnetic resonance spectroscopy ((31)P-MRS) in in vivo assessment of exhaustive exercise-induced injury in skeletal muscle. We aimed to evaluate the value of a (31)P-MRS study using the quadriceps femoris after a single bout of acute exhaustive swimming in rats, and the correlation between (31)P-MRS and histological changes. Sixty male Sprague-Dawley rats were randomly assigned to control, half-exhaustive, and exhaustive exercise groups. (31)P-MRS of the quadriceps femoris of the right lower limb was performed immediately after swimming exercise to detect Pi, PCr, and β-ATP. The Pi/PCr, Pi/β-ATP, PCr/β-ATP, and PCr/(PCr+Pi) were calculated and pH measured. Areas under the receiver operating characteristic curve (AUCs) were calculated to evaluate the diagnostic potential of (31)P-MRS in identifying and distinguishing the three groups. HE staining, electron microscopy and desmin immunostaining after imaging of the muscle were used as a reference standard. The correlation between (31)P-MRS and the mean absorbance (A value) of desmin staining were analyzed with the Pearson correlation test. Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) showed statistically significant intergroup differences (P < 0.05). AUCs of Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) were 0.905, 0.848, 0.930, and 0.930 for the control and half-exhaustive groups, while sensitivity and specificity were 90%/85%, 95%/55%, 95%/80%, and 90%/85%, respectively. The AUCs of Pi, PCr, Pi/PCr and PCr/(PCr+Pi) were 0.995, 0.980, 1.000, and 1.000 for the control and exhaustive groups, while sensitivity and specificity were 95%/90%, 100%/90%, 100%/95%, and 100%/95%, respectively. The AUCs of Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) were 0.735, 0.865, 0.903, and 0.903 for the half-exhaustive and exhaustive groups, while sensitivity and specificity were 80%/60%, 90%/75%, 95%/65%, and 95%/70%, respectively. In the half-exhaustive group, some muscle fibers exhibited edema in HE staining, and the unclear Z-discs and the mitochondria with vacuolar degeneration under electron microscopy. Compared with the half-exhaustive group, muscle fiber edema was increased in the exhaustive group, and the Z-discs were broken and the mitochondria exhibited marked vacuolar degeneration under electron microscopy. There were significant difference in A values of desmin staining in the right vastus lateralis among the control, half-exhaustive, and exhaustive groups with 0.58 ± 0.06, 0.30 ± 0.04, and 0.21 ± 0.02, respectively (P < 0.05). Histological examination also showed injury-induced changes in the vastus lateralis among the different intensities groups. Statistically a moderate correlation between (31)P-MRS and desmin was observed, the correlation coefficients of Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) were -0.706, 0.709, -0.726, and 0.791, respectively (P < 0.01). (31)P-MRS can effectively reflect the changes in energy metabolism in the skeletal muscle after a single bout of acute exhaustive swimming in rats. Based on the significant correlation between (31)P-MRS parameters and histological changes, the changes of Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) can indirectly reflect the degree of exercise-induced injury.

Gradient-free determination of isoelectric points of proteins on chip.

PubMed

Łapińska, Urszula; Saar, Kadi L; Yates, Emma V; Herling, Therese W; Müller, Thomas; Challa, Pavan K; Dobson, Christopher M; Knowles, Tuomas P J

2017-08-30

The isoelectric point (pI) of a protein is a key characteristic that influences its overall electrostatic behaviour. The majority of conventional methods for the determination of the isoelectric point of a molecule rely on the use of spatial gradients in pH, although significant practical challenges are associated with such techniques, notably the difficulty in generating a stable and well controlled pH gradient. Here, we introduce a gradient-free approach, exploiting a microfluidic platform which allows us to perform rapid pH change on chip and probe the electrophoretic mobility of species in a controlled field. In particular, in this approach, the pH of the electrolyte solution is modulated in time rather than in space, as in the case for conventional determinations of the isoelectric point. To demonstrate the general approachability of this platform, we have measured the isoelectric points of representative set of seven proteins, bovine serum albumin, β-lactoglobulin, ribonuclease A, ovalbumin, human transferrin, ubiquitin and myoglobin in microlitre sample volumes. The ability to conduct measurements in free solution thus provides the basis for the rapid determination of isoelectric points of proteins under a wide variety of solution conditions and in small volumes.

Targeting the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway: an emerging treatment strategy for squamous cell lung carcinoma.

PubMed

Beck, Joseph Thaddeus; Ismail, Amen; Tolomeo, Christina

2014-09-01

Squamous cell lung carcinoma accounts for approximately 30% of all non-small cell lung cancers (NSCLCs). Despite progress in the understanding of the biology of cancer, cytotoxic chemotherapy remains the standard of care for patients with squamous cell lung carcinoma, but the prognosis is generally poor. The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is one of the most commonly activated signaling pathways in cancer, leading to cell proliferation, survival, and differentiation. It has therefore become a major focus of clinical research. Various alterations in the PI3K/AKT/mTOR pathway have been identified in squamous cell lung carcinoma and a number of agents targeting these alterations are in clinical development for use as single agents and in combination with other targeted and conventional treatments. These include pan-PI3K inhibitors, isoform-specific PI3K inhibitors, AKT inhibitors, mTOR inhibitors, and dual PI3K/mTOR inhibitors. These agents have demonstrated antitumor activity in preclinical models of NSCLC and preliminary clinical evidence is also available for some agents. This review will discuss the role of the PI3K/AKT/mTOR pathway in cancer and how the discovery of genetic alterations in this pathway in patients with squamous cell lung carcinoma can inform the development of targeted therapies for this disease. An overview of ongoing clinical trials investigating PI3K/AKT/mTOR pathway inhibitors in squamous cell lung carcinoma will also be included. Copyright © 2014 Elsevier Ltd. All rights reserved.

PI Passivity-Based Control for Maximum Power Extraction of a Wind Energy System with Guaranteed Stability Properties

NASA Astrophysics Data System (ADS)

Cisneros, Rafael; Gao, Rui; Ortega, Romeo; Husain, Iqbal

2016-10-01

The present paper proposes a maximum power extraction control for a wind system consisting of a turbine, a permanent magnet synchronous generator, a rectifier, a load and one constant voltage source, which is used to form the DC bus. We propose a linear PI controller, based on passivity, whose stability is guaranteed under practically reasonable assumptions. PI structures are widely accepted in practice as they are easier to tune and simpler than other existing model-based methods. Real switching based simulations have been performed to assess the performance of the proposed controller.

Soft sensor based composition estimation and controller design for an ideal reactive distillation column.

PubMed

Vijaya Raghavan, S R; Radhakrishnan, T K; Srinivasan, K

2011-01-01

In this research work, the authors have presented the design and implementation of a recurrent neural network (RNN) based inferential state estimation scheme for an ideal reactive distillation column. Decentralized PI controllers are designed and implemented. The reactive distillation process is controlled by controlling the composition which has been estimated from the available temperature measurements using a type of RNN called Time Delayed Neural Network (TDNN). The performance of the RNN based state estimation scheme under both open loop and closed loop have been compared with a standard Extended Kalman filter (EKF) and a Feed forward Neural Network (FNN). The online training/correction has been done for both RNN and FNN schemes for every ten minutes whenever new un-trained measurements are available from a conventional composition analyzer. The performance of RNN shows better state estimation capability as compared to other state estimation schemes in terms of qualitative and quantitative performance indices. Copyright © 2010 ISA. Published by Elsevier Ltd. All rights reserved.

Mean deviation coupling synchronous control for multiple motors via second-order adaptive sliding mode control.

PubMed

Li, Lebao; Sun, Lingling; Zhang, Shengzhou

2016-05-01

A new mean deviation coupling synchronization control strategy is developed for multiple motor control systems, which can guarantee the synchronization performance of multiple motor control systems and reduce complexity of the control structure with the increasing number of motors. The mean deviation coupling synchronization control architecture combining second-order adaptive sliding mode control (SOASMC) approach is proposed, which can improve synchronization control precision of multiple motor control systems and make speed tracking errors, mean speed errors of each motor and speed synchronization errors converge to zero rapidly. The proposed control scheme is robustness to parameter variations and random external disturbances and can alleviate the chattering phenomena. Moreover, an adaptive law is employed to estimate the unknown bound of uncertainty, which is obtained in the sense of Lyapunov stability theorem to minimize the control effort. Performance comparisons with master-slave control, relative coupling control, ring coupling control, conventional PI control and SMC are investigated on a four-motor synchronization control system. Extensive comparative results are given to shown the good performance of the proposed control scheme. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Inorganic phosphorus (Pi) in CSF is a biomarker for SLC20A2-associated idiopathic basal ganglia calcification (IBGC1).

PubMed

Hozumi, Isao; Kurita, Hisaka; Ozawa, Kazuhiro; Furuta, Nobuyuki; Inden, Masatoshi; Sekine, Shin-Ichiro; Yamada, Megumi; Hayashi, Yuichi; Kimura, Akio; Inuzuka, Takashi; Seishima, Mitsuru

2018-05-15

Idiopathic basal ganglia calcification (IBGC), also called Fahr's disease or recently primary familial brain calcification (PFBC), is characterized by abnormal deposits of minerals including calcium mainly and phosphate in the brain. Mutations in SLC20A2 (IBGC1 (merged with former IBGC2 and IBGC3)), which encodes PiT-2, a phosphate transporter, is the major cause of IBGC. Recently, Slc20a2-KO mice have been showed to have elevated levels of inorganic phosphorus (Pi) in cerebrospinal fluid (CSF); however, CSF Pi levels in patients with IBGC have not been fully examined. We investigated the cases of 29 patients with IBGC including six patients with SLC20A2 mutation and three patients with PDGFB mutation, and 13 controls. The levels of sodium (Na), potassium (K), chloride (Cl), calcium (Ca), and Pi in sera and CSF were determined by potentiometry and colorimetry. Moreover, clinical manifestations were investigated in the IBGC patients with high Pi levels in CSF. The study revealed that the average level of Pi in the CSF of the total group of patients with IBGC is significantly higher than that of the control group, and the levels of Pi in CSF of the IBGC patients with SLC20A2 mutations are significantly higher than those of the IBGC patients with PDGFB mutations, the other IBGC patients and controls. Results of this study suggest that the levels of CSF Pi will be a good biomarker for IBGC1. Copyright © 2018 Elsevier B.V. All rights reserved.

Downregulation of RBO-PI4KIIIα Facilitates Aβ42 Secretion and Ameliorates Neural Deficits in Aβ42-Expressing Drosophila.

PubMed

Zhang, Xiao; Wang, Wen-An; Jiang, Li-Xiang; Liu, Hai-Yan; Zhang, Bao-Zhu; Lim, Nastasia; Li, Qing-Yi; Huang, Fu-De

2017-05-10

Phosphoinositides and their metabolizing enzymes are involved in Aβ 42 metabolism and Alzheimer's disease pathogenesis. In yeast and mammals, Eighty-five requiring 3 (EFR3), whose Drosophila homolog is Rolling Blackout (RBO), forms a plasma membrane-localized protein complex with phosphatidylinositol-4-kinase Type IIIα (PI4KIIIα) and a scaffold protein to tightly control the level of plasmalemmal phosphatidylinositol-4-phosphate (PI 4 P). Here, we report that RBO binds to Drosophila PI4KIIIα, and that in an Aβ 42 -expressing Drosophila model, separate genetic reduction of PI4KIIIα and RBO, or pharmacological inhibition of PI4KIIIα ameliorated synaptic transmission deficit, climbing ability decline, premature death, and reduced neuronal accumulation of Aβ 42 Moreover, we found that RBO-PI4KIIIa downregulation increased neuronal Aβ 42 release and that PI4P facilitated the assembly or oligomerization of Aβ 42 in/on liposomes. These results indicate that RBO-PI4KIIIa downregulation facilitates neuronal Aβ 42 release and consequently reduces neuronal Aβ 42 accumulation likely via decreasing Aβ 42 assembly in/on plasma membrane. This study suggests the RBO-PI4KIIIα complex as a potential therapeutic target and PI4KIIIα inhibitors as drug candidates for Alzheimer's disease treatment. SIGNIFICANCE STATEMENT Phosphoinositides and their metabolizing enzymes are involved in Aβ 42 metabolism and Alzheimer's disease pathogenesis. Here, in an Aβ 42 -expressing Drosophila model, we discovered and studied the beneficial role of downregulating RBO or its interacting protein PI4KIIIα-a protein that tightly controls the plasmalemmal level of PI 4 P-against the defects caused by Aβ 42 expression. Mechanistically, RBO-PI4KIIIα downregulation reduced neuronal Aβ 42 accumulation, and interestingly increased neuronal Aβ 42 release. This study suggests the RBO-PI4KIIIα complex as a novel therapeutic target, and PI4KIIIα inhibitors as new drug candidates. Copyright © 2017 the authors 0270-6474/17/374928-14$15.00/0.

Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance.

PubMed

Sheikh, Saba; Gudipaty, Lalitha; De Leon, Diva D; Hadjiliadis, Denis; Kubrak, Christina; Rosenfeld, Nora K; Nyirjesy, Sarah C; Peleckis, Amy J; Malik, Saloni; Stefanovski, Darko; Cuchel, Marina; Rubenstein, Ronald C; Kelly, Andrea; Rickels, Michael R

2017-01-01

Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased risk for developing diabetes. We determined β-cell secretory capacity and insulin secretory rates from glucose-potentiated arginine and mixed-meal tolerance tests (MMTTs), respectively, in pancreatic-sufficient cystic fibrosis (PS-CF), PI-CF, and normal control subjects, all with normal glucose tolerance, in order to identify early pathophysiologic defects. Acute islet cell secretory responses were determined under fasting, 230 mg/dL, and 340 mg/dL hyperglycemia clamp conditions. PI-CF subjects had lower acute insulin, C-peptide, and glucagon responses compared with PS-CF and normal control subjects, indicating reduced β-cell secretory capacity and α-cell function. Fasting proinsulin-to-C-peptide and proinsulin secretory ratios during glucose potentiation were higher in PI-CF, suggesting impaired proinsulin processing. In the first 30 min of the MMTT, insulin secretion was lower in PI-CF compared with PS-CF and normal control subjects, and glucagon-like peptide 1 and gastric inhibitory polypeptide were lower compared with PS-CF, and after 180 min, glucose was higher in PI-CF compared with normal control subjects. These findings indicate that despite "normal" glucose tolerance, adolescents and adults with PI-CF have impairments in functional islet mass and associated early-phase insulin secretion, which with decreased incretin responses likely leads to the early development of postprandial hyperglycemia in CF. © 2017 by the American Diabetes Association.

A postsynaptic PI3K-cII dependent signaling controller for presynaptic homeostatic plasticity

PubMed Central

Hauswirth, Anna G; Ford, Kevin J; Wang, Tingting; Fetter, Richard D; Tong, Amy

2018-01-01

Presynaptic homeostatic plasticity stabilizes information transfer at synaptic connections in organisms ranging from insect to human. By analogy with principles of engineering and control theory, the molecular implementation of PHP is thought to require postsynaptic signaling modules that encode homeostatic sensors, a set point, and a controller that regulates transsynaptic negative feedback. The molecular basis for these postsynaptic, homeostatic signaling elements remains unknown. Here, an electrophysiology-based screen of the Drosophila kinome and phosphatome defines a postsynaptic signaling platform that includes a required function for PI3K-cII, PI3K-cIII and the small GTPase Rab11 during the rapid and sustained expression of PHP. We present evidence that PI3K-cII localizes to Golgi-derived, clathrin-positive vesicles and is necessary to generate an endosomal pool of PI(3)P that recruits Rab11 to recycling endosomal membranes. A morphologically distinct subdivision of this platform concentrates postsynaptically where we propose it functions as a homeostatic controller for retrograde, trans-synaptic signaling. PMID:29303480

Effect of aniracetam on phosphatidylinositol transfer protein alpha in cytosolic and plasma membrane fractions of astrocytes subjected to simulated ischemia in vitro.

PubMed

Gabryel, Bozena; Chalimoniuk, Małgorzata; Małecki, Andrzej; Strosznajder, Joanna B

2005-01-01

Brain ischemia affects phosphoinositide metabolism and the level of lipid-derived second messengers. Phosphatidylinositol transfer proteins (PI-PTs) are responsible for the transport of phosphatidylinositol (PI) and other phospholipids through membranes. Isoform of PI-TPs (PI-TPalpha) is an essential component in ensuring substrate supply for phospholipase C (PLC). The current study was conducted to examine potential effect of aniracetam on PI-TPalpha expression and to characterize the PI-TPalpha isoform distribution between membrane and cytosol fractions of astrocytes exposed to simulated ischemia in vitro. After 8 h period of ischemia, the level of PI-TPalpha was significantly higher in cytosol (by about 28%) as well as in membrane fraction (by about 80%) in comparison with control. We have found that aniracetam treatment of astrocytes in normoxia significantly increased the level of PI-TPalpha in membrane fraction with a maximal effect at 0.1 microM concentration of aniracetam (by about 195% of control). In membrane fractions of ischemic cells, aniracetam increased PI-TPalpha expression in a concentration-dependent manner. In ischemic cells, aniracetam (10 microM) has elevated PI-TPalpha expression up to 155% and 428% in cytosolic and membrane fractions in comparison with ischemic untreated cells, respectively. The study has shown that aniracetam significantly activates PI-TPalpha in cell membrane fraction and this effect might be connected with previously described activation of MAP kinase cascade.

Control of actin polymerization via the coincidence of phosphoinositides and high membrane curvature

PubMed Central

Daste, Frederic; Walrant, Astrid; Mason, Julia; Lee, Ji-Eun; Brook, Daniel; Mettlen, Marcel; Larsson, Elin; Lee, Steven F.; Lundmark, Richard

2017-01-01

The conditional use of actin during clathrin-mediated endocytosis in mammalian cells suggests that the cell controls whether and how actin is used. Using a combination of biochemical reconstitution and mammalian cell culture, we elucidate a mechanism by which the coincidence of PI(4,5)P2 and PI(3)P in a curved vesicle triggers actin polymerization. At clathrin-coated pits, PI(3)P is produced by the INPP4A hydrolysis of PI(3,4)P2, and this is necessary for actin-driven endocytosis. Both Cdc42⋅guanosine triphosphate and SNX9 activate N-WASP–WIP- and Arp2/3-mediated actin nucleation. Membrane curvature, PI(4,5)P2, and PI(3)P signals are needed for SNX9 assembly via its PX–BAR domain, whereas signaling through Cdc42 is activated by PI(4,5)P2 alone. INPP4A activity is stimulated by high membrane curvature and synergizes with SNX9 BAR domain binding in a process we call curvature cascade amplification. We show that the SNX9-driven actin comets that arise on human disease–associated oculocerebrorenal syndrome of Lowe (OCRL) deficiencies are reduced by inhibiting PI(3)P production, suggesting PI(3)P kinase inhibitors as a therapeutic strategy in Lowe syndrome. PMID:28923975

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

Proinsulin slows retinal degeneration and vision loss in the P23H rat model of retinitis pigmentosa.

PubMed

Fernández-Sánchez, Laura; Lax, Pedro; Isiegas, Carolina; Ayuso, Eduard; Ruiz, José M; de la Villa, Pedro; Bosch, Fatima; de la Rosa, Enrique J; Cuenca, Nicolás

2012-12-01

Proinsulin has been characterized as a neuroprotective molecule. In this work we assess the therapeutic potential of proinsulin on photoreceptor degeneration, synaptic connectivity, and functional activity of the retina in the transgenic P23H rat, an animal model of autosomal dominant retinitis pigmentosa (RP). P23H homozygous rats received an intramuscular injection of an adeno-associated viral vector serotype 1 (AAV1) expressing human proinsulin (hPi+) or AAV1-null vector (hPi-) at P20. Levels of hPi in serum were determined by enzyme-linked immunosorbent assay (ELISA), and visual function was evaluated by electroretinographic (ERG) recording at P30, P60, P90, and P120. Preservation of retinal structure was assessed by immunohistochemistry at P120. Human proinsulin was detected in serum from rats injected with hPi+ at all times tested, with average hPi levels ranging from 1.1 nM (P30) to 1.4 nM (P120). ERG recordings showed an amelioration of vision loss in hPi+ animals. The scotopic b-waves were significantly higher in hPi+ animals than in control rats at P90 and P120. This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture. hPi+ animals had 48.7% more photoreceptors than control animals. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were preserved in hPi+ P23H rats. Furthermore, in hPi+ rat retinas the number of rod bipolar cell bodies was greater than in control rats. Our data demonstrate that hPi expression preserves cone and rod structure and function, together with their contacts with postsynaptic neurons, in the P23H rat. These data strongly support the further development of proinsulin-based therapy to counteract retinitis pigmentosa.

TEAMBLOCKS: HYBRID ABSTRACTIONS FOR PROVABLE MULTI-AGENT AUTONOMY

DTIC Science & Technology

2017-07-28

Raspberry Pi 23 can easily satisfy control loop periods on the order of 10−3s. Thus, we assume that the time to execute a piece of control code, ∆t...Release; Distribution Unlimited. 23 State Space The state space of the aircraft is X = R3 × SO(3) × R3 × R3; states consist of • pI ∈ R3, the...the tbdemo_ghaexecution script uses this operation to make feedback system out of the product of the linear system and PI controller. tbread

Microplasma device architectures with various diamond nanostructures

NASA Astrophysics Data System (ADS)

Kunuku, Srinivasu; Jothiramalingam Sankaran, Kamatchi; Leou, Keh-Chyang; Lin, I.-Nan

2017-02-01

Diamond nanostructures (DNSs) were fabricated from three different morphological diamonds, microcrystalline diamond (MCD), nanocrystalline diamond (NCD), and ultrananocrystalline diamond (UNCD) films, using a reactive ion etching method. The plasma illumination (PI) behavior of microplasma devices using the DNSs and the diamond films as cathode were investigated. The Paschen curve approach revealed that the secondary electron emission coefficient (γ value) of diamond materials is similar irrespective of the microstructure (MCD, NCD, and UNCD) and geometry of the materials (DNSs and diamond films). The diamond materials show markedly larger γ-coefficient than conventional metallic cathode materials such as Mo that resulted in markedly better PI behavior for the corresponding microplasma devices. Moreover, the PI behavior, i.e. the voltage dependence of plasma current density (J pl-V), plasma density (n e-V), and the robustness of the devices, varied markedly with the microstructure and geometry of the cathode materials that was closely correlated to the electron field emission (EFE) properties of the cathode materials. The UNCD nanopillars, possessing good EFE properties, resulted in superior PI behavior, whereas the MCD diamond films with insufficient EFE properties led to inferior PI behavior. Consequently, enhancement of plasma characteristics is the collective effects of EFE behavior and secondary electron emission characteristics of diamond-based cathode materials.

PI(3,5)P2 controls endosomal branched actin dynamics by regulating cortactin–actin interactions

PubMed Central

Hong, Nan Hyung; Qi, Aidong

2015-01-01

Branched actin critically contributes to membrane trafficking by regulating membrane curvature, dynamics, fission, and transport. However, how actin dynamics are controlled at membranes is poorly understood. Here, we identify the branched actin regulator cortactin as a direct binding partner of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) and demonstrate that their interaction promotes turnover of late endosomal actin. In vitro biochemical studies indicated that cortactin binds PI(3,5)P2 via its actin filament-binding region. Furthermore, PI(3,5)P2 competed with actin filaments for binding to cortactin, thereby antagonizing cortactin activity. These findings suggest that PI(3,5)P2 formation on endosomes may remove cortactin from endosome-associated branched actin. Indeed, inhibition of PI(3,5)P2 production led to cortactin accumulation and actin stabilization on Rab7+ endosomes. Conversely, inhibition of Arp2/3 complex activity greatly reduced cortactin localization to late endosomes. Knockdown of cortactin reversed PI(3,5)P2-inhibitor–induced actin accumulation and stabilization on endosomes. These data suggest a model in which PI(3,5)P2 binding removes cortactin from late endosomal branched actin networks and thereby promotes net actin turnover. PMID:26323691

Analytical design of an industrial two-term controller for optimal regulatory control of open-loop unstable processes under operational constraints.

PubMed

Tchamna, Rodrigue; Lee, Moonyong

2018-01-01

This paper proposes a novel optimization-based approach for the design of an industrial two-term proportional-integral (PI) controller for the optimal regulatory control of unstable processes subjected to three common operational constraints related to the process variable, manipulated variable and its rate of change. To derive analytical design relations, the constrained optimal control problem in the time domain was transformed into an unconstrained optimization problem in a new parameter space via an effective parameterization. The resulting optimal PI controller has been verified to yield optimal performance and stability of an open-loop unstable first-order process under operational constraints. The proposed analytical design method explicitly takes into account the operational constraints in the controller design stage and also provides useful insights into the optimal controller design. Practical procedures for designing optimal PI parameters and a feasible constraint set exclusive of complex optimization steps are also proposed. The proposed controller was compared with several other PI controllers to illustrate its performance. The robustness of the proposed controller against plant-model mismatch has also been investigated. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Insulin induces drug resistance in melanoma through activation of the PI3K/Akt pathway

PubMed Central

Chi, Mengna; Ye, Yan; Zhang, Xu Dong; Chen, Jiezhong

2014-01-01

Introduction There is currently no curative treatment for melanoma once the disease spreads beyond the original site. Although activation of the PI3K/Akt pathway resulting from genetic mutations and epigenetic deregulation of its major regulators is known to cause resistance of melanoma to therapeutic agents, including the conventional chemotherapeutic drug dacarbazine and the Food and Drug Administration-approved mutant BRAF inhibitors vemurafenib and dabrafenib, the role of extracellular stimuli of the pathway, such as insulin, in drug resistance of melanoma remains less understood. Objective To investigate the effect of insulin on the response of melanoma cells to dacarbazine, and in particular, the effect of insulin on the response of melanoma cells carrying the BRAFV600E mutation to mutant BRAF inhibitors. An additional aim was to define the role of the PI3K/Akt pathway in the insulin-triggered drug resistance. Methods The effect of insulin on cytotoxicity induced by dacarbazine or the mutant BRAF inhibitor PLX4720 was tested by pre-incubation of melanoma cells with insulin. Cytotoxicity was determined by the MTS assay. The role of the PI3K/Akt pathway in the insulin-triggered drug resistance was examined using the PI3K inhibitor LY294002 and the PI3K and mammalian target of rapamycin dual inhibitor BEZ-235. Activation of the PI3K/Akt pathway was monitored by Western blot analysis of phosphorylated levels of Akt. Results Recombinant insulin attenuated dacarbazine-induced cytotoxicity in both wild-type BRAF and BRAFV600E melanoma cells, whereas it also reduced killing of BRAFV600E melanoma cells by PLX4720. Nevertheless, the protective effect of insulin was abolished by the PI3K and mTOR dual inhibitor BEZ-235 or the PI3K inhibitor LY294002. Conclusion Insulin attenuates the therapeutic efficacy of dacarbazine and PLX4720 in melanoma cells, which is mediated by activation of the PI3K/Akt pathway and can be overcome by PI3K inhibitors. PMID:24600206

A Vision-Based Counting and Recognition System for Flying Insects in Intelligent Agriculture.

PubMed

Zhong, Yuanhong; Gao, Junyuan; Lei, Qilun; Zhou, Yao

2018-05-09

Rapid and accurate counting and recognition of flying insects are of great importance, especially for pest control. Traditional manual identification and counting of flying insects is labor intensive and inefficient. In this study, a vision-based counting and classification system for flying insects is designed and implemented. The system is constructed as follows: firstly, a yellow sticky trap is installed in the surveillance area to trap flying insects and a camera is set up to collect real-time images. Then the detection and coarse counting method based on You Only Look Once (YOLO) object detection, the classification method and fine counting based on Support Vector Machines (SVM) using global features are designed. Finally, the insect counting and recognition system is implemented on Raspberry PI. Six species of flying insects including bee, fly, mosquito, moth, chafer and fruit fly are selected to assess the effectiveness of the system. Compared with the conventional methods, the test results show promising performance. The average counting accuracy is 92.50% and average classifying accuracy is 90.18% on Raspberry PI. The proposed system is easy-to-use and provides efficient and accurate recognition data, therefore, it can be used for intelligent agriculture applications.

A Vision-Based Counting and Recognition System for Flying Insects in Intelligent Agriculture

PubMed Central

Zhong, Yuanhong; Gao, Junyuan; Lei, Qilun; Zhou, Yao

2018-01-01

Rapid and accurate counting and recognition of flying insects are of great importance, especially for pest control. Traditional manual identification and counting of flying insects is labor intensive and inefficient. In this study, a vision-based counting and classification system for flying insects is designed and implemented. The system is constructed as follows: firstly, a yellow sticky trap is installed in the surveillance area to trap flying insects and a camera is set up to collect real-time images. Then the detection and coarse counting method based on You Only Look Once (YOLO) object detection, the classification method and fine counting based on Support Vector Machines (SVM) using global features are designed. Finally, the insect counting and recognition system is implemented on Raspberry PI. Six species of flying insects including bee, fly, mosquito, moth, chafer and fruit fly are selected to assess the effectiveness of the system. Compared with the conventional methods, the test results show promising performance. The average counting accuracy is 92.50% and average classifying accuracy is 90.18% on Raspberry PI. The proposed system is easy-to-use and provides efficient and accurate recognition data, therefore, it can be used for intelligent agriculture applications. PMID:29747429

Tailless and Atrophin control Drosophila aggression by regulating neuropeptide signalling in the pars intercerebralis

NASA Astrophysics Data System (ADS)

Davis, Shaun M.; Thomas, Amanda L.; Nomie, Krystle J.; Huang, Longwen; Dierick, Herman A.

2014-02-01

Aggressive behaviour is widespread throughout the animal kingdom. However, its mechanisms are poorly understood, and the degree of molecular conservation between distantly related species is unknown. Here we show that knockdown of tailless (tll) increases aggression in Drosophila, similar to the effect of its mouse orthologue Nr2e1. Tll localizes to the adult pars intercerebralis (PI), which shows similarity to the mammalian hypothalamus. Knockdown of tll in the PI is sufficient to increase aggression and is rescued by co-expressing human NR2E1. Knockdown of Atrophin, a Tll co-repressor, also increases aggression, and both proteins physically interact in the PI. tll knockdown-induced aggression is fully suppressed by blocking neuropeptide processing or release from the PI. In addition, genetically activating PI neurons increases aggression, mimicking the aggression-inducing effect of hypothalamic stimulation. Together, our results suggest that a transcriptional control module regulates neuropeptide signalling from the neurosecretory cells of the brain to control aggressive behaviour.

Application of inorganic carrier-based formulations of fluorescent pseudomonads and Piriformospora indica on tomato plants and evaluation of their efficacy.

PubMed

Sarma, M V R K; Kumar, V; Saharan, K; Srivastava, R; Sharma, A K; Prakash, A; Sahai, V; Bisaria, V S

2011-08-01

Fluorescent pseudomonads are widely used as bioinoculants for improving plant growth and controlling phytopathogenic fungi. Piriformospora indica (Pi), a symbiotic root endophyte, also has beneficial effects on a number of plants. The present study focuses on the improvement of growth yields of tomato plants and control of Fusarium wilt using inorganic carrier-based formulations of two fluorescent pseudomonad strains (R62 and R81) and Pi. The inorganic carrier-based formulations of pseudomonad strains and Pi were tested for plant growth promotion of tomato plants under glass house and field conditions. In controlled glass house experiments, 8·8-fold increase in dry root weight and 8·6-fold increase in dry shoot weight were observed with talcum powder-based consortium formulation of R81 and Pi. Field trial experiments ascertained the glfass house results with a considerable amount of increase in plant growth responses, and amongst all the treatments, R81 + Pi treatment performed consistently well in field conditions with an increase of 2·6-, 3·1- and 3·9-fold increase in dry root weight, shoot weight and fruit yield, respectively. The fluorescent pseudomonad R81 and Pi also acted as biocontrol agents, as their treatments could control the incidence of wilt disease caused by Fusarium oxysporum f.sp. lycopersici in tomato plants under glass house conditions. The culture broths of pseudomonads R62, R81 and Pi were successfully used for development of talcum- and vermiculite-based bioinoculant formulations. In controlled glasshouse experiments, the talcum-based bioinoculant formulations performed significantly better over vermiculite-based formulations. In field experiments the talcum-based consortium formulation of pseudomonad R81 and Pi was most effective. This study suggests that the formulations of pseudomonad strains (R62 and R81) and Pi can be used as bioinoculants for improving the productivity of tomato plants. The application of such formulations is a step forward towards sustainable agriculture. © 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology.

Polymorphism of alpha-1-antitrypsin in hematological malignancies

PubMed Central

2009-01-01

Alpha-1-antitrypsin (AAT) or serine protease inhibitor A1 (SERPINA1) is an important serine protease inhibitor in humans. The main physiological role of AAT is to inhibit neutrophil elastase (NE) released from triggered neutrophils, with an additional lesser role in the defense against damage inflicted by other serine proteases, such as cathepsin G and proteinase 3. Although there is a reported association between AAT polymorphism and different types of cancer, this association with hematological malignancies (HM) is, as yet, unknown. We identified AAT phenotypes by isoelectric focusing (in the pH 4.2-4.9 range) in 151 serum samples from patients with HM (Hodgkins lymphomas, non-Hodgkins lymphomas and malignant monoclonal gammopathies). Healthy blood-donors constituted the control group (n = 272). The evaluated population of patients as well as the control group, were at Hardy-Weinberg equilibrium for the AAT gene (χ2 = 4.42, d.f.11, p = 0.96 and χ2 = 4.71, d.f.11, p = 0.97, respectively). There was no difference in the frequency of deficient AAT alleles (Pi Z and Pi S) between patients and control. However, we found a significantly higher frequency of PiM1M1 homozygote and PiM1 allele in HM patients than in control (for phenotype: f = 0.5166 and 0.4118 respectively, p = 0.037; for allele: f = 0.7020 and 0.6360 respectively, p = 0.05). In addition, PiM homozygotes in HM-patients were more numerous than in controls (59% and 48%, respectively, p = 0.044). PiM1 alleles and PiM1 homozygotes are both associated with hematological malignancies, although this is considered a functionally normal AAT variant. PMID:21637443

Effect of the PiAstra Benchtop Flash-Heating Pasteurizer on Immune Factors of Donor Human Milk.

PubMed

Daniels, Brodie; Reimers, Penny; King, Tracy; Schmidt, Stefan; Coutsoudis, Anna

2018-05-01

PiAstra is a simulated flash-heat (FH) pasteurization temperature monitoring system designed using Raspberry Pi technology for the pasteurization of human milk. This study analyzed the effect of the PiAstra FH method on human milk immune components (immunoglobulin A [IgA] and lactoferrin activity). Donor milk samples (N = 45) were obtained from a human milk bank, and pasteurized. Concentrations of IgA and lactoferrin activity were compared to their unpasteurized controls using the Student's t test. The PiAstra FH method retained 34.2% of IgA (p < 0.0001) and 40.4% of lactoferrin activity (p < 0.0001) when compared to unpasteurized controls. The retention of IgA by the PiAstra is similar to previous FH studies, while retention of lactoferrin activity was higher than previous FH studies. The high-technology, low-cost PiAstra system, which is able to retain vital immune components of human milk, provides safe donor milk for low-resourced settings. This enables the use of pasteurized donor milk when human milk is not available, potentially saving vulnerable infant lives.

The low-lying {pi}{sigma}* state and its role in the intramolecular charge transfer of aminobenzonitriles and aminobenzethyne

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

Lee, Jae-Kwang; Fujiwara, Takashige; Kofron, William G.

2008-04-28

Electronic absorption spectra of the low-lying {pi}{pi}* and {pi}{sigma}* states of several aminobenzonitriles and 4-dimethylaminobenzethyne have been studied by time-resolved transient absorption and time-dependent density functional theory calculation. In acetonitrile, the lifetime of the {pi}{sigma}*-state absorption is very short (picoseconds or subpicosecond) for molecules that exhibit intramolecular charge transfer (ICT), and very long (nanoseconds) for those that do not. Where direct comparison of the temporal characteristics of the {pi}{sigma}*-state and the ICT-state transients could be made, the formation rate of the ICT state is identical to the decay rate of the {pi}{sigma}* state within the experimental uncertainty. These results aremore » consistent with the {pi}{sigma}*-mediated ICT mechanism, L{sub a} ({pi}{pi}*){yields}{pi}{sigma}*{yields}ICT, in which the decay rate of the {pi}{sigma}* state is determined by the rate of the solvent-controlled {pi}{sigma}*{yields}ICT charge-shift reaction. The {pi}{pi}*{yields}{pi}{sigma}* state crossing does not occur in 3-dimethylaminobenzonitrile or 2-dimethylaminobenzonitrile, as predicted by the calculation, and 4-aminobenzonitrile and 4-dimethylaminobenzethyne does not exhibit the ICT reaction, consistent with the higher energy of the ICT state relative to the {pi}{sigma}* state.« less

The comparative evaluation of xanthan gel with chlorhexidine (Chlosite) in smokers and non-smokers: A clinical and microbiological assessment

PubMed Central

Chandra, Chetan; Valavalkar, Narayan; Vandana, K. L.

2011-01-01

Background and Objectives: Prevention of the periodontal disease progression is the primary goal of periodontal therapy. When conventional therapy is found inadequate to attain periodontal health in chronic periodontitis, local antimicrobial agents have been used as an adjunct with scaling and root planning (SRP) which has reproduced encouraging results. Hence, this study was undertaken to evaluate the new sustained released local drug Chlosite clinically and microbiologically in smokers and non-smokers. Materials and Methods: The patients were grouped into experimental group A treated with SRP plus Chlosite (SRP + CHL), experimental group B treated with Chlosite alone (CHL), and control group C treated only with SRP alone. A total number of 141 sites from six patients (67 sites from three non-smoker patients and 74 sites from three smoker patients) participated in this study. The clinical parameters, Plaque index (PI), Gingival index (GI), Bleeding index (BI), and Relative attachment level (RAL), were recorded and subgingival plaque samples were collected and subjected to microbiological analysis. Results: On comparison of smokers and non-smokers, in SRP group, non-smokers showed a higher reduction in BI and GI and smokers showed a higher reduction in PI. There was no significant gain in RAL of both smokers and non-smokers. In SRP + CHL group, non-smokers showed a higher reduction in relation to BI and GI and smokers showed a higher reduction in relation to PI. There was no significant gain in RAL of both smokers and non-smokers. In CHL group, both smokers and non-smokers showed a nonsignificant reduction in BI, GI, and RAL, but smokers showed a significant reduction in PI as compared with non-smokers. All the groups showed reduction in the microbial count of Fusobacterium nucleatum, Porphyromonas gingivalis, and Tannerella forsythia which were found to be statistically not significant when it was compared between non-smokers and smokers. Interpretation and Conclusion: In this study, all treatment groups were found to be efficacious in the treatment of periodontal disease as demonstrated by improvement in PI, GI, BI, and RAL. Combination of SRP and Chlosite resulted in added benefits compared with the two treatment groups. PMID:22028508

Targeting the PI3K/Akt pathway in murine MDS/MPN driven by hyperactive Ras.

PubMed

Akutagawa, J; Huang, T Q; Epstein, I; Chang, T; Quirindongo-Crespo, M; Cottonham, C L; Dail, M; Slusher, B S; Friedman, L S; Sampath, D; Braun, B S

2016-06-01

Chronic and juvenile myelomonocytic leukemias (CMML and JMML) are myelodysplastic/myeloproliferative neoplasia (MDS/MPN) overlap syndromes that respond poorly to conventional treatments. Aberrant Ras activation because of NRAS, KRAS, PTPN11, CBL and NF1 mutations is common in CMML and JMML. However, no mechanism-based treatments currently exist for cancers with any of these mutations. An alternative therapeutic strategy involves targeting Ras-regulated effector pathways that are aberrantly activated in CMML and JMML, which include the Raf/MEK/ERK and phosphoinositide-3'-OH kinase (PI3K)/Akt cascades. Mx1-Cre, Kras(D12) and Mx1-Cre, Nf1(flox/)(-) mice accurately model many aspects of CMML and JMML. Treating Mx1-Cre, Kras(D12) mice with GDC-0941 (also referred to as pictilisib), an orally bioavailable inhibitor of class I PI3K isoforms, reduced leukocytosis, anemia and splenomegaly while extending survival. However, GDC-0941 treatment attenuated activation of both PI3K/Akt and Raf/MEK/ERK pathways in primary hematopoietic cells, suggesting it could be acting through suppression of Raf/MEK/ERK signals. To interrogate the importance of the PI3K/Akt pathway specifically, we treated mice with the allosteric Akt inhibitor MK-2206. This compound had no effect on Raf/MEK/ERK signaling, yet it also induced robust hematologic responses in Kras and Nf1 mice with MPN. These data support investigating PI3K/Akt pathway inhibitors as a therapeutic strategy in JMML and CMML patients.

Assessment of intracranial vessels in association with carotid atherosclerosis and brain vascular lesions in rheumatoid arthritis.

PubMed

Oláh, Csaba; Kardos, Zsófia; Sepsi, Mariann; Sas, Attila; Kostyál, László; Bhattoa, Harjit Pal; Hodosi, Katalin; Kerekes, György; Tamási, László; Valikovics, Attila; Bereczki, Dániel; Szekanecz, Zoltán

2017-09-26

Stroke has been associated with rheumatoid arthritis (RA). We assessed patients with RA and healthy control subjects by transcranial Doppler (TCD), carotid ultrasonography and brain magnetic resonance imaging (MRI). Altogether, 41 female patients with RA undergoing methotrexate (MTX) or biologic treatment and 60 age-matched control subjects underwent TCD assessment of the middle cerebral artery (MCA) and basilar artery. Pulsatility index (PI), resistivity (resistance) index (RI) and circulatory reserve capacity (CRC) were determined at rest (r) and after apnoea (a) and hyperventilation (h). The presence of carotid plaques and carotid intima-media thickness (cIMT) were also determined. Intracerebral vascular lesions were investigated by brain MRI. MCA PI and RI values at rest and after apnoea were significantly increased in the total and MTX-treated RA populations vs control subjects. MCA CRC was also impaired, and basilar artery PI was higher in RA. More patients with RA had carotid plaques and increased cIMT. Linear regression analysis revealed that left PI(r) and RI(r) correlated with disease duration and that left PI(r), RI(r), PI(a), PI(h) and basilar PI correlated with disease activity. Right CRC inversely correlated with 28-joint Disease Activity Score. Disease activity was an independent determinant of left PI(a) and right CRC. Compared with long-term MTX treatment alone, the use of biologics in combination with MTX was associated with less impaired cerebral circulation. Impaired cerebral circulation was also associated with measures of carotid atherosclerosis. To our knowledge, this is the first study to show increased distal MCA and basilar artery occlusion in RA as determined by TCD. Patients with RA also had CRC defects. We also confirmed increased carotid plaque formation and increased cIMT. Biologics may beneficially influence some parameters in the intracranial vessels.

Reducing Dental Plaque and Gingivitis With 0.6% Cortex Ilicis Rotundae Toothpaste: A Randomized, Double-Masked Clinical Trial.

PubMed

Liu, Hongchun; Yin, Wei

2016-03-01

Cortex Ilicis Rotundae has antioxidant and anti-inflammatory properties. Few studies have evaluated the effects of toothpastes containing Cortex Ilicis Rotundae. This study evaluates the antiplaque and antigingivitis effects of a test toothpaste containing 0.6% Cortex Ilicis Rotundae extract in a calcium carbonate base compared with a control toothpaste without any active ingredient. One hundred adults with a mean plaque index (PI) ≥ 1.5 and a mean gingival index (GI) ≥ 1.0 were enrolled in this randomized, double-masked, placebo-controlled clinical trial. They were assigned randomly to use a test toothpaste or a control toothpaste. At baseline, 6 weeks, and 12 weeks, they received examinations of oral hard and soft tissues, using Löe-Silness GI for gingivitis and the Turesky modification of the Quigley-Hein PI for PI. Adverse events were monitored. When the study was completed, the test group reported lower mean GI than the control group (1.13 ± 0.22 versus 1.30 ± 0.23; P = 0.001) and lower mean PI than the control group (2.53 ± 0.5 versus 2.93 ± 0.44; P < 0.001). Compared to the baseline, the test group had reductions in GI and PI of 14.39% and 17.86%, respectively (both P < 0.001); the control group had reductions in GI and PI of 3.7% and 3.93%, respectively (both P < 0.001). No adverse events were reported during the course of the study. The toothpaste containing 0.6% Cortex Ilicis Rotundae was effective in reducing dental plaque and gingivitis after 12 weeks of use compared with a negative control toothpaste.

Pittsburgh compound-B PET white matter imaging and cognitive function in late multiple sclerosis.

PubMed

Zeydan, Burcu; Lowe, Val J; Schwarz, Christopher G; Przybelski, Scott A; Tosakulwong, Nirubol; Zuk, Samantha M; Senjem, Matthew L; Gunter, Jeffrey L; Roberts, Rosebud O; Mielke, Michelle M; Benarroch, Eduardo E; Rodriguez, Moses; Machulda, Mary M; Lesnick, Timothy G; Knopman, David S; Petersen, Ronald C; Jack, Clifford R; Kantarci, Kejal; Kantarci, Orhun H

2018-05-01

There is growing interest in white matter (WM) imaging with positron emission tomography (PET). We studied the association of cognitive function in late multiple sclerosis (MS) with cortical and WM Pittsburgh compound-B PET (PiB-PET) binding. In the population-based Mayo Clinic Study of Aging, 24 of 4869 participants had MS (12 underwent PiB-PET). Controls were age and sex matched (5:1). We used automated or semi-automated processing for quantitative image analyses and conditional logistic regression for group differences. MS patients had lower memory ( p = 0.03) and language ( p = 0.02) performance; smaller thalamic volumes ( p = 0.003); and thinner temporal ( p = 0.001) and frontal ( p = 0.045) cortices on magnetic resonance imaging (MRI) than controls. There was no difference in global cortical PiB standardized uptake value ratios between MS and controls ( p = 0.35). PiB uptake was lower in areas of WM hyperintensities compared to normal-appearing white matter (NAWM) in MS ( p = 0.0002). Reduced PiB uptake in both the areas of WM hyperintensities ( r = 0.65; p = 0.02) and NAWM ( r = 0.69; p = 0.01) was associated with decreased visuospatial performance in MS. PiB uptake in the cortex in late MS is not different from normal age-matched controls. PiB uptake in the WM in late MS may be a marker of the large network structures' integrity such as those involved in visuospatial performance.

Enhanced Tumor Growth and Invasiveness in Vivo by a Carboxyl-Terminal Fragment of α1-Proteinase Inhibitor Generated by Matrix Metalloproteinases

PubMed Central

Kataoka, Hiroaki; Uchino, Hirofumi; Iwamura, Takeshi; Seiki, Motoharu; Nabeshima, Kazuki; Koono, Masashi

1999-01-01

Matrix metalloproteinases (MMPs) are believed to contribute to the complex process of cancer progression. They also exhibit an α1-proteinase inhibitor (αPI)-degrading activity generating a carboxyl-terminal fragment of ∼5 kd (αPI-C). This study reports that overexpression of αPI-C in S2–020, a cloned subline derived from the human pancreas adenocarcinoma cell line SUIT-2, potentiates the growth capability of the cells in nude mice. After stable transfection of a vector containing a chimeric cDNA encoding a signal peptide sequence of tissue inhibitor of metalloproteinase-1 followed by cDNA for αPI-C into S2–020 cells, three clones that stably secrete αPI-C were obtained. The ectopic expression of αPI-C did not alter in vitro cellular growth. However, subcutaneous injection of the αPI-C-secreting clones resulted in tumors that were 1.5 to 3-fold larger than those of control clones with an increased tendency to invasiveness and lymph node metastasis. These effects could be a result of modulation of natural killer (NK) cell-mediated control of tumor growth in nude mice, as the growth advantage of αPI-C-secreting clones was not observed in NK-depleted mice, and αPI-C-secreting clones showed decreased NK sensitivity in vitro. In addition, production of αPI and generation of the cleaved form of αPI by MMP were observed in various human tumor cell lines and in a highly metastatic subline of SUIT-2 in vitro. These results provide experimental evidence that the αPI-degrading activity of MMPs may play a role in tumor progression not only via the inactivation of αPI but also via the generation of αPI-C. PMID:10027404

Improving atomic force microscopy imaging by a direct inverse asymmetric PI hysteresis model.

PubMed

Wang, Dong; Yu, Peng; Wang, Feifei; Chan, Ho-Yin; Zhou, Lei; Dong, Zaili; Liu, Lianqing; Li, Wen Jung

2015-02-03

A modified Prandtl-Ishlinskii (PI) model, referred to as a direct inverse asymmetric PI (DIAPI) model in this paper, was implemented to reduce the displacement error between a predicted model and the actual trajectory of a piezoelectric actuator which is commonly found in AFM systems. Due to the nonlinearity of the piezoelectric actuator, the standard symmetric PI model cannot precisely describe the asymmetric motion of the actuator. In order to improve the accuracy of AFM scans, two series of slope parameters were introduced in the PI model to describe both the voltage-increase-loop (trace) and voltage-decrease-loop (retrace). A feedforward controller based on the DIAPI model was implemented to compensate hysteresis. Performance of the DIAPI model and the feedforward controller were validated by scanning micro-lenses and standard silicon grating using a custom-built AFM.

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.

Improved FFT-based numerical inversion of Laplace transforms via fast Hartley transform algorithm

NASA Technical Reports Server (NTRS)

Hwang, Chyi; Lu, Ming-Jeng; Shieh, Leang S.

1991-01-01

The disadvantages of numerical inversion of the Laplace transform via the conventional fast Fourier transform (FFT) are identified and an improved method is presented to remedy them. The improved method is based on introducing a new integration step length Delta(omega) = pi/mT for trapezoidal-rule approximation of the Bromwich integral, in which a new parameter, m, is introduced for controlling the accuracy of the numerical integration. Naturally, this method leads to multiple sets of complex FFT computations. A new inversion formula is derived such that N equally spaced samples of the inverse Laplace transform function can be obtained by (m/2) + 1 sets of N-point complex FFT computations or by m sets of real fast Hartley transform (FHT) computations.

Fractional order PIλ controller synthesis for steam turbine speed governing systems.

PubMed

Chen, Kai; Tang, Rongnian; Li, Chuang; Lu, Junguo

2018-06-01

The current state of the art of fractional order stability theory is hardly to build connection between the time domain analysis and frequency domain synthesis. The existing tuning methodologies for fractional order PI λ D μ are not always satisfy the given gain crossover frequency and phase margin simultaneously. To overcome the drawbacks in the existing synthesis of fractional order controller, the synthesis of optimal fractional order PI λ controller for higher-order process is proposed. According to the specified phase margin, the corresponding upper boundary of gain crossover frequency and stability surface in parameter space are obtained. Sweeping the order parameter over λ∈(0,2), the complete set of stabilizing controller which guarantees both pre-specifying phase frequency characteristic can be collected. Whereafter, the optimal fractional order PI λ controller is applied to the speed governing systems of steam turbine generation units. The numerical simulation and hardware-in-the-loop simulation demonstrate the effectiveness and satisfactory closed-loop performance of obtained fractional order PI λ controller. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Polarization Imaging Apparatus with Auto-Calibration

NASA Technical Reports Server (NTRS)

Zou, Yingyin Kevin (Inventor); Zhao, Hongzhi (Inventor); Chen, Qiushui (Inventor)

2013-01-01

A polarization imaging apparatus measures the Stokes image of a sample. The apparatus consists of an optical lens set, a first variable phase retarder (VPR) with its optical axis aligned 22.5 deg, a second variable phase retarder with its optical axis aligned 45 deg, a linear polarizer, a imaging sensor for sensing the intensity images of the sample, a controller and a computer. Two variable phase retarders were controlled independently by a computer through a controller unit which generates a sequential of voltages to control the phase retardations of the first and second variable phase retarders. A auto-calibration procedure was incorporated into the polarization imaging apparatus to correct the misalignment of first and second VPRs, as well as the half-wave voltage of the VPRs. A set of four intensity images, I(sub 0), I(sub 1), I(sub 2) and I(sub 3) of the sample were captured by imaging sensor when the phase retardations of VPRs were set at (0,0), (pi,0), (pi,pi) and (pi/2,pi), respectively. Then four Stokes components of a Stokes image, S(sub 0), S(sub 1), S(sub 2) and S(sub 3) were calculated using the four intensity images.

Polarization imaging apparatus with auto-calibration

DOEpatents

Zou, Yingyin Kevin; Zhao, Hongzhi; Chen, Qiushui

2013-08-20

A polarization imaging apparatus measures the Stokes image of a sample. The apparatus consists of an optical lens set, a first variable phase retarder (VPR) with its optical axis aligned 22.5.degree., a second variable phase retarder with its optical axis aligned 45.degree., a linear polarizer, a imaging sensor for sensing the intensity images of the sample, a controller and a computer. Two variable phase retarders were controlled independently by a computer through a controller unit which generates a sequential of voltages to control the phase retardations of the first and second variable phase retarders. A auto-calibration procedure was incorporated into the polarization imaging apparatus to correct the misalignment of first and second VPRs, as well as the half-wave voltage of the VPRs. A set of four intensity images, I.sub.0, I.sub.1, I.sub.2 and I.sub.3 of the sample were captured by imaging sensor when the phase retardations of VPRs were set at (0,0), (.pi.,0), (.pi.,.pi.) and (.pi./2,.pi.), respectively. Then four Stokes components of a Stokes image, S.sub.0, S.sub.1, S.sub.2 and S.sub.3 were calculated using the four intensity images.

Polarization imaging apparatus

NASA Technical Reports Server (NTRS)

Zou, Yingyin Kevin (Inventor); Chen, Qiushui (Inventor); Zhao, Hongzhi (Inventor)

2010-01-01

A polarization imaging apparatus measures the Stokes image of a sample. The apparatus consists of an optical lens set 11, a linear polarizer 14 with its optical axis 18, a first variable phase retarder 12 with its optical axis 16 aligned 22.5.degree. to axis 18, a second variable phase retarder 13 with its optical axis 17 aligned 45.degree. to axis 18, a imaging sensor 15 for sensing the intensity images of the sample, a controller 101 and a computer 102. Two variable phase retarders 12 and 13 were controlled independently by a computer 102 through a controller unit 101 which generates a sequential of voltages to control the phase retardations of VPRs 12 and 13. A set of four intensity images, I.sub.0, I.sub.1, I.sub.2 and I.sub.3 of the sample were captured by imaging sensor 15 when the phase retardations of VPRs 12 and 13 were set at (0,0), (.pi.,0), (.pi.,.pi.) and (.pi./2,.pi.), respectively Then four Stokes components of a Stokes image, S.sub.0, S.sub.1, S.sub.2 and S.sub.3 were calculated using the four intensity images.

Fine mapping and characterization of candidate genes that control resistance to Cercospora Sojina K. Hara in two soybean germplasm accessions

USDA-ARS?s Scientific Manuscript database

In order to fine map the novel FLS resistance gene(s) in two PIs, PI 594891 and PI 594774, F2:3 seeds from the crosses Blackhawk (FLS susceptible genotype) ×PI 594891, and Blackhawk ×PI 594774 were genotyped with KASP markers that were designed based on the SoySNP 50k Infinium Chip data to identi...

Vulnerability Analysis of the MAVLink Protocol for Command and Control of Unmanned Aircraft

DTIC Science & Technology

2013-03-27

the cheapest computers currently on the market (the $35 Raspberry Pi [New13, Upt13]) to distribute the workload, a determined attacker would incur a...cCost of Brute-Force) for 6,318 Raspberry Pi systems (x) at $82 per 3DR-enabled Raspberry Pi (RPCost of RasPi) [3DR13, New13] to brute-force all 3,790,800...NIST, 2004. [New13] Newark. Order the Raspberry Pi , November 2013. last accessed: 19 Febru- ary 2014. URL: http://www.newark.com/jsp/search

Pharmaceuticals and the Environment (PiE): Evolution and impact of the published literature revealed by bibliometric analysis.

PubMed

Daughton, Christian G

2016-08-15

The evolution and impact of the published literature surrounding the transdisciplinary, multifaceted topic of pharmaceuticals as contaminants in the environment is examined for the first time in an historical context. The preponderance of literature cited in this examination represents the earlier works. As an historical chronology, the focus is on the emergence of key, specific aspects of the overall topic (often termed PiE) in the published literature and on the most highly cited works. This examination is not a conventional, technical review of the literature; as such, little attention was devoted to the more recent literature. The many dimensions involved with PiE span over 70years of published literature. Some articles began to appear in published works in the 1940s and earlier, while others only began to receive attention in the 1990s and later. Decades of early research on what at the time seemed to be disconnected topics eventually coalesced in the mid-to-late 1990s around a number of interconnected concerns and issues that now comprise PiE. Major objectives are to provide a new perspective to the topic, to facilitate more efficient and effective review of the literature by others, and to recognize the more significant, seminal contributions to the advancement of PiE as a field of research. Some of the most highly cited articles in all of environmental science now involve PiE. As of April 2015, a core group of 385 PiE articles had each received at least 200 citations; one had received 5424 citations. But hundreds of additional articles also played important roles in the evolution and advancement of the field. Published by Elsevier B.V.

CIEF separation, UV detection, and quantification of ampholytic antibiotics and bacteria from different matrices.

PubMed

Horká, Marie; Vykydalová, Marie; Růžička, Filip; Šalplachta, Jiří; Holá, Veronika; Dvořáčková, Milada; Kubesová, Anna; Šlais, Karel

2014-10-01

The effect of antibiotics on the microbial cells and concentration of antibiotics in the human body is essential for the effective use of antimicrobial therapy. The capillary isoelectric focusing is a suitable technique for the separation and the detection of bacteria, and amphoteric substances from nature. However, the determination of isoelectric points of ampholytic antibiotics by conventional techniques is time consuming. For this reason, capillary isoelectric focusing seems to be appropriate as a simple and reliable way for establishing them. The separation conditions for the capillary isoelectric focusing of selected ampholytic antibiotics with known isoelectric points and pK as, ampicillin (pI 4.9), ciprofloxacin (pI 7.4), ofloxacin (pI 7.1), tetracycline (pI 5.4), tigecycline (pI 9.7), and vancomycin (pI 8.1), were found and optimized in the suitable pH ranges pH 2.0-5.3, 2.0-9.6, and 9.0-10.4. The established values of isoelectric points correspond with those found in the literature except tigecycline. Its pI was not found in the literature. As an example of a possible procedure for direct detection of both ampholytic antibiotics and bacteria, Staphylococcus epidermidis, in the presence of culture media or whole human blood, was found. The changes of the bacterial cells after their treatment with tetracycline were confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Capillary isoelectric focusing allows the fast and simple determination of isoelectric points of relevant antibiotics, their quantification from the environment, as well as studying their effectiveness on microorganisms in biological samples.

Cationic ionene as an n-dopant agent of poly(3,4-ethylenedioxythiophene).

PubMed

Saborío, Maricruz G; Bertran, Oscar; Lanzalaco, Sonia; Häring, Marleen; Díaz Díaz, David; Estrany, Francesc; Alemán, Carlos

2018-04-18

We report the reduction of poly(3,4-ethylenedioxythiophene) (PEDOT) films with a cationic 1,4-diazabicyclo[2.2.2]octane-based ionene bearing N,N'-(meta-phenylene)dibenzamide linkages (mPI). Our main goal is to obtain n-doped PEDOT using a polymeric dopant agent rather than small conventional tetramethylammonium (TMA), as is usual. This has been achieved using a three-step process, which has been individually optimized: (1) preparation of p-doped (oxidized) PEDOT at a constant potential of +1.40 V in acetonitrile with LiClO4 as the electrolyte; (2) dedoping of oxidized PEDOT using a fixed potential of -1.30 V in water; and (3) redoping of dedoped PEDOT applying a reduction potential of -1.10 V in water with mPI. The resulting films display the globular appearance typically observed for PEDOT, with mPI being structured in separated phases forming nanospheres or ultrathin sheets. This organization, which has been supported by atomistic molecular dynamics simulations, resembles the nanosegregated phase distribution observed for PEDOT p-doped with poly(styrenesulfonate). Furthermore, the doping level achieved using mPI as the doping agent is comparable to that achieved using TMA, even though ionene provides distinctive properties to the conducting polymer. For example, films redoped with mPI exhibit much more hydrophilicity than the oxidized ones, whereas films redoped with TMA are hydrophobic. Similarly, films redoped with mPI exhibit the highest thermal stability, while those redoped with TMA show thermal stability that is intermediate between those of the latter and the dedoped PEDOT. Overall, the incorporation of an mPI polycation as the n-dopant into PEDOT has important advantages for modulating the properties of this emblematic conducting polymer.

Pain After Unilateral Total Knee Arthroplasty: A Prospective Randomized Controlled Trial Examining the Analgesic Effectiveness of a Combined Adductor Canal Peripheral Nerve Block with Periarticular Infiltration Versus Adductor Canal Nerve Block Alone Versus Periarticular Infiltration Alone.

PubMed

Sawhney, Monakshi; Mehdian, Hossein; Kashin, Brian; Ip, Gregory; Bent, Maurice; Choy, Joyce; McPherson, Mark; Bowry, Richard

2016-06-01

Total knee arthroplasty is a painful surgery that requires early mobilization for successful joint function. Multimodal analgesia, including spinal analgesia, nerve blocks, periarticular infiltration (PI), opioids, and coanalgesics, has been shown to effectively manage postoperative pain. Both adductor canal (AC) and PI have been shown to manage pain without significantly impairing motor function. However, it is unclear which technique is most effective. This 3-arm trial examined the effect of AC block with PI (AC + PI) versus AC block only (AC) versus PI only (PI). The primary outcome was pain on walking at postoperative day (POD) 1. One hundred fifty-one patients undergoing unilateral total knee arthroplasty were included. Patients received either AC block with 30 mL of 0.5% ropivacaine or sham block. PI was performed intraoperatively with a 110-mL normal saline solution containing 300 mg ropivacaine, 10 mg morphine, and 30 mg ketorolac. Those patients randomly assigned to AC only received normal saline knee infiltration. On POD 1, participants who received AC + PI reported significantly lower pain numeric rating scale scores on walking (3.3) compared with those who received AC (6.2) or PI (4.9) (P < 0.0001). Participants who received AC reported significantly higher pain scores at rest and knee bend compared with those who received AC + PI or PI (P < 0.0001). The difference in pain scores between participants who received AC + PI and those who received AC was 2.83 (95% confidence interval, 1.58-4.09) and the difference between those who received AC + PI and those who received PI was 1.61 (95% confidence interval, 0.37-2.86). On POD 2, participants who received AC + PI reported significantly less pain on walking (4.4) compared with those who received AC (5.6) or PI (5.6) (P = 0.006). On POD 2, there was no difference between the groups for pain at rest or knee bending. Participants who received AC used more IV patient-controlled analgesia on POD 0. There was no difference between the groups regarding distance walked. Participants who received AC + PI reported significantly less pain on walking on PODs 1 and 2 compared with those who received AC only or PI only.

Cu+ association to some Ph-X (X = OH, NH2, CHO, COOH, CF3) phenyl derivatives.: A comparison with Li+ complexes

NASA Astrophysics Data System (ADS)

Corral, Ines; Mo, Otilia; Yanez, Manuel

2006-09-01

The complexes of Cu+ with phenol, aniline, benzaldehyde, benzoic acid, and trifluromethyl-benzene were investigated through the use of MP2 and density functional theory (DFT) methods. Both harmonic vibrational frequencies and optimized geometries were obtained at the B3LYP/6-311G(d,p) and MP2(full)/6-311G(d,p) levels of theory. Final energies were obtained through single point B3LYP/6-311+G(3df,2p)//B3LYP/6-311G(d,p) calculations. The interactions of Cu+ with these aromatic compounds have a non-negligible covalent character, which clearly differentiate Cu+-complexes from the corresponding Li+-complexes. These dissimilarities are reflected in the geometries, binding energies and infrared spectra of the most stable adducts. For Li+ only conventional [pi]-complexes should be expected when interacting with aniline, while Cu+ attaches preferentially to the para carbon atom. For phenol, besides the conventional [pi]-complexes, a 12% of oxygen attached species are expected to be found upon Li+ association. Conversely, no oxygen attached species should be formed in reactions of phenol with Cu+. For benzoic acid and benzaldehyde, Li+ aligns with the dipole moment of the base, interacting exclusively with the carbonyl oxygen in the plane of the molecule. This is also the case in Cu+-benzoic acid complex, while in the Cu+-benzaldehyde complex the metal ion also interacts with the aromatic [pi]-system. Cu+ binding enthalpies (BEs) are systematically larger (about 1.3 times) than Li+ BEs. The covalent character of Cu+ interactions is associated with electron donations from bonding ([pi]) orbitals or lone-pairs of the base toward the 4s empty orbital of the metal and with back-donations from the occupied d orbitals of the metal toward antibonding ([pi]*) empty orbitals of the base. This non-negligible covalent character is also reflected in a rough correlation between the calculated Cu+ BEs and the available experimental proton affinities that does not exist for Li+ BEs.

The Economic and Risk Constraints in the Feasibility Analysis of Wireless Communications in Marine Corps Combat Operation Centers

DTIC Science & Technology

2013-09-01

attacker can acquire and use against a wireless infrastructure. Wireless attack tool kits such as the “ Raspberry – PI ” (shown in Figure 10), and...still use a tool such as the Raspberry – PI to perform attacks against a network from outside the controlled area or even inside the controlled area...when considering an insider attack. Figure 10. (From www.howtodocomputing.blogspot.com, n.d.) Wireless – PI is “a collection of pre-configured

Targeting the phosphatidylinositol 3-kinase/Akt/mechanistic target of rapamycin signaling pathway in B-lineage acute lymphoblastic leukemia: An update.

PubMed

Simioni, Carolina; Martelli, Alberto M; Zauli, Giorgio; Vitale, Marco; McCubrey, James A; Capitani, Silvano; Neri, Luca M

2018-04-18

Despite considerable progress in treatment protocols, B-lineage acute lymphoblastic leukemia (B-ALL) displays a poor prognosis in about 15-20% of pediatric cases and about 60% of adult patients. In addition, life-long irreversible late effects from chemo- and radiation therapy, including secondary malignancies, are a growing problem for leukemia survivors. Targeted therapy holds promising perspectives for cancer treatment as it may be more effective and have fewer side effects than conventional therapies. The phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway is a key regulatory cascade which controls proliferation, survival and drug-resistance of cancer cells, and it is frequently upregulated in the different subtypes of B-ALL, where it plays important roles in the pathophysiology, maintenance and progression of the disease. Moreover, activation of this signaling cascade portends a poorer prognosis in both pediatric and adult B-ALL patients. Promising preclinical data on PI3K/Akt/mTOR inhibitors have documented their anticancer activity in B-ALL and some of these novel drugs have entered clinical trials as they could lead to a longer event-free survival and reduce therapy-associated toxicity for patients with B-ALL. This review highlights the current status of PI3K/Akt/mTOR inhibitors in B-ALL, with an emphasis on emerging evidence of the superior efficacy of synergistic combinations involving the use of traditional chemotherapeutics or other novel, targeted agents. © 2018 Wiley Periodicals, Inc.

Multiplex bioimaging of piRNA molecular pathway-regulated theragnostic effects in a single breast cancer cell using a piRNA molecular beacon.

PubMed

Lee, Youn Jung; Moon, Sung Ung; Park, Min Geun; Jung, Woon Yong; Park, Yong Keun; Song, Sung Kyu; Ryu, Je Gyu; Lee, Yong Seung; Heo, Hye Jung; Gu, Ha Na; Cho, Su Jeong; Ali, Bahy A; Al-Khedhairy, Abdulaziz A; Lee, Ilkyun; Kim, Soonhag

2016-09-01

Recently, PIWI-interacting small non-coding RNAs (piRNAs) have emerged as novel cancer biomarkers candidate because of their high expression level in various cancer types and role in the control of tumor suppressor genes. In this study, a novel breast cancer theragnostics probe based on a single system targeting the piRNA-36026 (piR-36026) molecular pathway was developed using a piR-36026 molecular beacon (MB). The piR-36026 MB successfully visualized endogenous piR-36026 biogenesis, which is highly expressed in MCF7 cells (a human breast cancer cell line), and simultaneously inhibited piR-36026-mediated cancer progression in vitro and in vivo. We discovered two tumor suppressor proteins, SERPINA1 and LRAT, that were directly regulated as endogenous piR-36026 target genes in MCF7 cells. Furthermore, multiplex bioimaging of a single MCF7 cell following treatment with piR-36026 MB clearly visualized the direct molecular interaction of piRNA-36026 with SERPINA1 or LRAT and subsequent molecular therapeutic responses including caspase-3 and PI in the nucleus. Copyright © 2016 Elsevier Ltd. All rights reserved.

A novel FAD2-1 A allele in a soybean plant introduction offers an alternate means to produce soybean seed oil with 85% oleic acid content.

PubMed

Pham, Anh-Tung; Lee, Jeong-Dong; Shannon, J Grover; Bilyeu, Kristin D

2011-09-01

The alteration of fatty acid profiles in soybean to improve soybean oil quality has been a long-time goal of soybean researchers. Soybean oil with elevated oleic acid is desirable because this monounsaturated fatty acid improves the nutrition and oxidative stability of soybean oil compared to other oils. In the lipid biosynthetic pathway, the enzyme fatty acid desaturase 2 (FAD2) is responsible for the conversion of oleic acid precursors to linoleic acid precursors in developing soybean seeds. Two genes encoding FAD2-1A and FAD2-1B were identified to be expressed specifically in seeds during embryogenesis and have been considered to hold an important role in controlling the seed oleic acid content. A total of 22 soybean plant introduction (PI) lines identified to have an elevated oleic acid content were characterized for sequence mutations in the FAD 2-1A and FAD2-1B genes. PI 603452 was found to contain a deletion of a nucleotide in the second exon of FAD2-1A. These important SNPs were used in developing molecular marker genotyping assays. The assays appear to be a reliable and accurate tool to identify the FAD 2-1A and FAD2-1B genotype of wild-type and mutant plants. PI 603452 was subsequently crossed with PI 283327, a soybean line that has a mutation in FAD2-1B. Interestingly, soybean lines carrying both homozygous insertion/deletion mutation (indel) FAD2-1A alleles and mutant FAD2-1B alleles have an average of 82-86% oleic acid content, compared to 20% in conventional soybean, and low levels of linoleic and linolenic acids. The newly identified indel mutation in the FAD2-1A gene offers a simple method for the development of high oleic acid commercial soybean varieties.

Identification of a Pi9 containing rice germplasm with a newly developed robust marker

USDA-ARS?s Scientific Manuscript database

The Pi9 gene, originating from Oryza minuta, is an effective resistance gene for controlling rice blast disease (Magnaporthe oryzae). However, currently available linked DNA markers do not accurately identify the function of Pi9, thus hindering its efficient incorporation into new cultivars through...

Cellular Notch responsiveness is defined by phosphoinositide 3-kinase-dependent signals

PubMed Central

Mckenzie, Grahame; Ward, George; Stallwood, Yvette; Briend, Emmanuel; Papadia, Sofia; Lennard, Andrew; Turner, Martin; Champion, Brian; Hardingham, Giles E

2006-01-01

Background Notch plays a wide-ranging role in controlling cell fate, differentiation and development. The PI3K-Akt pathway is a similarly conserved signalling pathway which regulates processes such as differentiation, proliferation and survival. Mice with disrupted Notch and PI3K signalling show phenotypic similarities during haematopoietic cell development, suggesting functional interaction between these pathways. Results We show that cellular responsiveness to Notch signals depends on the activity of the PI3K-Akt pathway in cells as diverse as CHO cells, primary T-cells and hippocampal neurons. Induction of the endogenous PI3K-Akt pathway in CHO cells (by the insulin pathway), in T-cells (via TCR activation) or in neurons (via TrKB activation) potentiates Notch-dependent responses. We propose that the PI3K-Akt pathway exerts its influence on Notch primarily via inhibition of GSK3-beta, a kinase known to phosphorylate and regulate Notch signals. Conclusion The PI3K-Akt pathway acts as a "gain control" for Notch signal responses. Since physiological levels of intracellular Notch are often low, coincidence with PI3K-activation may be crucial for induction of Notch-dependent responses. PMID:16507111

A comparison between IMSC, PI and MIMSC methods in controlling the vibration of flexible systems

NASA Technical Reports Server (NTRS)

Baz, A.; Poh, S.

1987-01-01

A comparative study is presented between three active control algorithms which have proven to be successful in controlling the vibrations of large flexible systems. These algorithms are: the Independent Modal Space Control (IMSC), the Pseudo-inverse (PI), and the Modified Independent Modal Space Control (MIMSC). Emphasis is placed on demonstrating the effectiveness of the MIMSC method in controlling the vibration of large systems with small number of actuators by using an efficient time sharing strategy. Such a strategy favors the MIMSC over the IMSC method, which requires a large number of actuators to control equal number of modes, and also over the PI method which attempts to control large number of modes with smaller number of actuators through the use of an in-exact statistical realization of a modal controller. Numerical examples are presented to illustrate the main features of the three algorithms and the merits of the MIMSC method.

High-Speed Current dq PI Controller for Vector Controlled PMSM Drive

PubMed Central

Reaz, Mamun Bin Ibne; Rahman, Labonnah Farzana; Chang, Tae Gyu

2014-01-01

High-speed current controller for vector controlled permanent magnet synchronous motor (PMSM) is presented. The controller is developed based on modular design for faster calculation and uses fixed-point proportional-integral (PI) method for improved accuracy. Current dq controller is usually implemented in digital signal processor (DSP) based computer. However, DSP based solutions are reaching their physical limits, which are few microseconds. Besides, digital solutions suffer from high implementation cost. In this research, the overall controller is realizing in field programmable gate array (FPGA). FPGA implementation of the overall controlling algorithm will certainly trim down the execution time significantly to guarantee the steadiness of the motor. Agilent 16821A Logic Analyzer is employed to validate the result of the implemented design in FPGA. Experimental results indicate that the proposed current dq PI controller needs only 50 ns of execution time in 40 MHz clock, which is the lowest computational cycle for the era. PMID:24574913

Effects of Isoform-selective Phosphatidylinositol 3-Kinase Inhibitors on Osteoclasts

PubMed Central

Shugg, Ryan P. P.; Thomson, Ashley; Tanabe, Natsuko; Kashishian, Adam; Steiner, Bart H.; Puri, Kamal D.; Pereverzev, Alexey; Lannutti, Brian J.; Jirik, Frank R.; Dixon, S. Jeffrey; Sims, Stephen M.

2013-01-01

Phosphatidylinositol 3-kinases (PI3K) participate in numerous signaling pathways, and control distinct biological functions. Studies using pan-PI3K inhibitors suggest roles for PI3K in osteoclasts, but little is known about specific PI3K isoforms in these cells. Our objective was to determine effects of isoform-selective PI3K inhibitors on osteoclasts. The following inhibitors were investigated (targets in parentheses): wortmannin and LY294002 (pan-p110), PIK75 (α), GDC0941 (α, δ), TGX221 (β), AS252424 (γ), and IC87114 (δ). In addition, we characterized a new potent and selective PI3Kδ inhibitor, GS-9820, and explored roles of PI3K isoforms in regulating osteoclast function. Osteoclasts were isolated from long bones of neonatal rats and rabbits. Wortmannin, LY294002, GDC0941, IC87114, and GS-9820 induced a dramatic retraction of osteoclasts within 15–20 min to 65–75% of the initial area. In contrast, there was no significant retraction in response to vehicle, PIK75, TGX221, or AS252424. Moreover, wortmannin and GS-9820, but not PIK75 or TGX221, disrupted actin belts. We examined effects of PI3K inhibitors on osteoclast survival. Whereas PIK75, TGX221, and GS-9820 had no significant effect on basal survival, all blocked RANKL-stimulated survival. When studied on resorbable substrates, osteoclastic resorption was suppressed by wortmannin and inhibitors of PI3Kβ and PI3Kδ, but not other isoforms. These data are consistent with a critical role for PI3Kδ in regulating osteoclast cytoskeleton and resorptive activity. In contrast, multiple PI3K isoforms contribute to the control of osteoclast survival. Thus, the PI3Kδ isoform, which is predominantly expressed in cells of hematopoietic origin, is an attractive target for anti-resorptive therapeutics. PMID:24133210

Different mechanisms drive the performance of native and invasive woody species in response to leaf phosphorus supply during periods of drought stress and recovery.

PubMed

Oliveira, Marciel Teixeira; Medeiros, Camila Dias; Frosi, Gabriella; Santos, Mauro Guida

2014-09-01

The effects of drought stress and leaf phosphorus (Pi) supply on photosynthetic metabolism in woody tropical species are not known, and given the recent global environmental change models that forecast lower precipitation rates and periods of prolonged drought in tropical areas, this type of study is increasingly important. The effects of controlled drought stress and Pi supply on potted young plants of two woody species, Anadenanthera colubrina (native) and Prosopis juliflora (invasive), were determined by analyzing leaf photosynthetic metabolism, biochemical properties and water potential. In the maximum stress, both species showed higher leaf water potential (Ψl) in the treatment drought +Pi when compared with the respective control -Pi. The native species showed higher gas exchange under drought +Pi than under drought -Pi conditions, while the invasive species showed the same values between drought +Pi and -Pi. Drought affected the photochemical part of photosynthetic machinery more in the invasive species than in the native species. The invasive species showed higher leaf amino acid content and a lower leaf total protein content in both Pi treatments with drought. The two species showed different responses to the leaf Pi supply under water stress for several variables measured. In addition, the strong resilience of leaf gas exchange in the invasive species compared to the native species during the recovery period may be the result of higher efficiency of Pi use. The implications of this behavior for the success of this invasive species in semiarid environments are discussed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

The prevalence of PI*S and PI*Z SERPINA1 alleles in healthy individuals and COPD patients in Saudi Arabia: A case-control study.

PubMed

Al-Jameil, Noura; Hassan, Amina A; Hassanato, Rana; Isac, Sree R; Otaiby, Maram Al; Al-Shareef, Fadwa; Al-Maarik, Basmah; Ajeyan, Iman Al; Al-Bahloul, Khloud; Ghani, Samina; Al-Torbak, Dana

2017-10-01

Alpha-1 antitrypsin (AAT) is an acute phase protein produced in hepatocytes. Its deficiency affects the lungs and liver. A case-control study was carried out to determine the prevalence of 2 common deficiency alleles, PI*S and PI*Z, for alpha-1 antitrypsin deficiency (AATD) in both healthy and chronic obstructive pulmmonary disease (COPD)-affected Saudi populations and to clarify the importance of genetic tests in the screening of people at risk for COPD.One thousand blood samples from healthy individuals and 1000 from COPD-affected Saudi individuals were genotyped for the above-mentioned alleles, using real-time polymerase chain reaction (PCR), with the exclusion of any other nationalities. Data were analyzed by determining the allele and genotype frequencies through gene counting and its confidence intervals. The allele frequencies, derived by the Hardy-Weinberg equilibrium method, were analyzed by Pearson Chi-squared tests. The confidence intervals for genotype frequencies were calculated using exploratory software for confidence intervals.Of the 1000 COPD patients included in our study, the prevalence of PI*S and PI*Z was 21.8% and 7.7%, respectively, while within the 1000 normal samples, these alleles occurred in 8.9% of patients for PI*S and 1.6% for PI*Z. The AAT deficiency genotype frequencies (PI*ZZ, PI*SS, and PI*SZ) were 6.5 per 1000 and 87 per 1000 for normal and COPD-affected Saudi individuals.Our results indicated a high prevalence of AATD alleles in the normal Saudi population and an association between AAT deficiency and pulmonary disease development. Additionally, our research confirms the importance of genetic screening to achieve early and accurate diagnosis of AATD.

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.

PRMT8 Controls the Pluripotency and Mesodermal Fate of Human Embryonic Stem Cells By Enhancing the PI3K/AKT/SOX2 Axis.

PubMed

Jeong, Ho-Chang; Park, Soon-Jung; Choi, Jong-Jin; Go, Young-Hyun; Hong, Soon-Ki; Kwon, Ok-Seon; Shin, Joong-Gon; Kim, Rae-Kwon; Lee, Mi-Ok; Lee, Su-Jae; Shin, Hyoung Doo; Moon, Sung-Hwan; Cha, Hyuk-Jin

2017-09-01

Basic fibroblast growth factor (bFGF) supplementation is critical to maintain the pluripotency of human pluripotent stem cells (hPSCs) through activation of PI3K/AKT, rather than MEK/ERK pathway. Thus, elaborate molecular mechanisms that preserve PI3K/AKT signaling upon bFGF stimulation may exist in hPSCs. Protein arginine methyltransferase 8 (PRMT8) was expressed and then its level gradually decreased during spontaneous differentiation of human embryonic stem cells (hESCs). PRMT8 loss- or gain-of-function studies demonstrated that PRMT8 contributed to longer maintenance of hESC pluripotency, even under bFGF-deprived conditions. Direct interaction of membrane-localized PRMT8 with p85, a regulatory subunit of PI3K, was associated with accumulation of phosphoinositol 3-phosphate and consequently high AKT activity. Furthermore, the SOX2 induction, which was controlled by the PRMT8/PI3K/AKT axis, was linked to mesodermal lineage differentiation. Thus, we propose that PRMT8 in hESCs plays an important role not only in maintaining pluripotency but also in controlling mesodermal differentiation through bFGF signaling toward the PI3K/AKT/SOX2 axis. Stem Cells 2017;35:2037-2049. © 2017 AlphaMed Press.

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.

Improving Atomic Force Microscopy Imaging by a Direct Inverse Asymmetric PI Hysteresis Model

PubMed Central

Wang, Dong; Yu, Peng; Wang, Feifei; Chan, Ho-Yin; Zhou, Lei; Dong, Zaili; Liu, Lianqing; Li, Wen Jung

2015-01-01

A modified Prandtl–Ishlinskii (PI) model, referred to as a direct inverse asymmetric PI (DIAPI) model in this paper, was implemented to reduce the displacement error between a predicted model and the actual trajectory of a piezoelectric actuator which is commonly found in AFM systems. Due to the nonlinearity of the piezoelectric actuator, the standard symmetric PI model cannot precisely describe the asymmetric motion of the actuator. In order to improve the accuracy of AFM scans, two series of slope parameters were introduced in the PI model to describe both the voltage-increase-loop (trace) and voltage-decrease-loop (retrace). A feedforward controller based on the DIAPI model was implemented to compensate hysteresis. Performance of the DIAPI model and the feedforward controller were validated by scanning micro-lenses and standard silicon grating using a custom-built AFM. PMID:25654719

Molecular Basis for Association of PIPKIγ-p90 with Clathrin Adaptor AP-2*

PubMed Central

Kahlfeldt, Nina; Vahedi-Faridi, Ardeschir; Koo, Seong Joo; Schäfer, Johannes G.; Krainer, Georg; Keller, Sandro; Saenger, Wolfram; Krauss, Michael; Haucke, Volker

2010-01-01

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is an essential determinant in clathrin-mediated endocytosis (CME). In mammals three type I phosphatidylinositol-4-phosphate 5-kinase (PIPK) enzymes are expressed, with the Iγ-p90 isoform being highly expressed in the brain where it regulates synaptic vesicle (SV) exo-/endocytosis at nerve terminals. How precisely PI(4,5)P2 metabolism is controlled spatially and temporally is still uncertain, but recent data indicate that direct interactions between type I PIPK and components of the endocytic machinery, in particular the AP-2 adaptor complex, are involved. Here we demonstrated that PIPKIγ-p90 associates with both the μ and β2 subunits of AP-2 via multiple sites. Crystallographic data show that a peptide derived from the splice insert of the human PIPKIγ-p90 tail binds to a cognate recognition site on the sandwich subdomain of the β2 appendage. Partly overlapping aromatic and hydrophobic residues within the same peptide also can engage the C-terminal sorting signal binding domain of AP-2μ, thereby potentially competing with the sorting of conventional YXXØ motif-containing cargo. Biochemical and structure-based mutagenesis analysis revealed that association of the tail domain of PIPKIγ-p90 with AP-2 involves both of these sites. Accordingly the ability of overexpressed PIPKIγ tail to impair endocytosis of SVs in primary neurons largely depends on its association with AP-2β and AP-2μ. Our data also suggest that interactions between AP-2 and the tail domain of PIPKIγ-p90 may serve to regulate complex formation and enzymatic activity. We postulate a model according to which multiple interactions between PIPKIγ-p90 and AP-2 lead to spatiotemporally controlled PI(4,5)P2 synthesis during clathrin-mediated SV endocytosis. PMID:19903820

HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK.

PubMed

El Bouzidi, Kate; White, Ellen; Mbisa, Jean L; Sabin, Caroline A; Phillips, Andrew N; Mackie, Nicola; Pozniak, Anton L; Tostevin, Anna; Pillay, Deenan; Dunn, David T

2016-12-01

Darunavir is considered to have a high genetic barrier to resistance. Most darunavir-associated drug resistance mutations (DRMs) have been identified through correlation of baseline genotype with virological response in clinical trials. However, there is little information on DRMs that are directly selected by darunavir in clinical settings. We examined darunavir DRMs emerging in clinical practice in the UK. Baseline and post-exposure protease genotypes were compared for individuals in the UK Collaborative HIV Cohort Study who had received darunavir; analyses were stratified for PI history. A selection analysis was used to compare the evolution of subtype B proteases in darunavir recipients and matched PI-naive controls. Of 6918 people who had received darunavir, 386 had resistance tests pre- and post-exposure. Overall, 2.8% (11/386) of these participants developed emergent darunavir DRMs. The prevalence of baseline DRMs was 1.0% (2/198) among PI-naive participants and 13.8% (26/188) among PI-experienced participants. Emergent DRMs developed in 2.0% of the PI-naive group (4 mutations) and 3.7% of the PI-experienced group (12 mutations). Codon 77 was positively selected in the PI-naive darunavir cases, but not in the control group. Our findings suggest that although emergent darunavir resistance is rare, it may be more common among PI-experienced patients than those who are PI-naive. Further investigation is required to explore whether codon 77 is a novel site involved in darunavir susceptibility. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Analysis of compensatory mechanisms in the pelvis and lower extremities in patients with pelvic incidence and lumbar lordosis mismatch.

PubMed

Cheng, Xiaofei; Zhang, Kai; Sun, Xiaojiang; Zhao, Changqing; Li, Hua; Zhao, Jie

2017-07-01

The objective was to analyze the compensatory effect of the pelvis and lower extremities on sagittal spinal malalignment in patients with pelvic incidence (PI) and lumbar lordosis (LL) mismatch. A series of parameters including PI, LL, PI-LL, thoracic kyphosis (TK), pelvic tilt (PT), sacral slope (SS), knee flexion angle (KFA), tibial obliquity angle (TOA), femoral obliquity angle (FOA), femur pelvis angle (FPA) and pelvic shift (PS) were measured. Patients with PI-LL mismatch were divided into pelvic retroversion group and pelvic retroposition group based on their PT and PS, and then the parameters were compared within the two groups and with the control group. All variables were significantly different when comparing the pelvic retroversion and retroposition group with the control group except for PI, FOA and PS in the pelvic retroversion group. The pelvic retroposition group had significantly greater value of PI-LL, PI, PT, KFA, FOA and PS and contribution ratio of FOA and PS, and smaller value of LL, TK and FPA and contribution ratio of PT, TOA and FPA compared with the pelvic retroversion group. Patients with lesser PI-LL mismatch rely more on hip extension to increase pelvic retroversion while those with greater PI-LL mismatch tend to add extra femoral obliquity. When compensating for larger PI-LL mismatch, the importance of hip extension is decreased and the effect of the knee and ankle joint becomes more important by providing greater femoral incline and relatively lesser ankle dorsiflexion respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

Time-resolved, single-cell analysis of induced and programmed cell death via non-invasive propidium iodide and counterstain perfusion.

PubMed

Krämer, Christina E M; Wiechert, Wolfgang; Kohlheyer, Dietrich

2016-09-01

Conventional propidium iodide (PI) staining requires the execution of multiple steps prior to analysis, potentially affecting assay results as well as cell vitality. In this study, this multistep analysis method has been transformed into a single-step, non-toxic, real-time method via live-cell imaging during perfusion with 0.1 μM PI inside a microfluidic cultivation device. Dynamic PI staining was an effective live/dead analytical tool and demonstrated consistent results for single-cell death initiated by direct or indirect triggers. Application of this method for the first time revealed the apparent antibiotic tolerance of wild-type Corynebacterium glutamicum cells, as indicated by the conversion of violet fluorogenic calcein acetoxymethyl ester (CvAM). Additional implementation of this method provided insight into the induced cell lysis of Escherichia coli cells expressing a lytic toxin-antitoxin module, providing evidence for non-lytic cell death and cell resistance to toxin production. Finally, our dynamic PI staining method distinguished necrotic-like and apoptotic-like cell death phenotypes in Saccharomyces cerevisiae among predisposed descendants of nutrient-deprived ancestor cells using PO-PRO-1 or green fluorogenic calcein acetoxymethyl ester (CgAM) as counterstains. The combination of single-cell cultivation, fluorescent time-lapse imaging, and PI perfusion facilitates spatiotemporally resolved observations that deliver new insights into the dynamics of cellular behaviour.

A feature-based approach to modeling protein-protein interaction hot spots.

PubMed

Cho, Kyu-il; Kim, Dongsup; Lee, Doheon

2009-05-01

Identifying features that effectively represent the energetic contribution of an individual interface residue to the interactions between proteins remains problematic. Here, we present several new features and show that they are more effective than conventional features. By combining the proposed features with conventional features, we develop a predictive model for interaction hot spots. Initially, 54 multifaceted features, composed of different levels of information including structure, sequence and molecular interaction information, are quantified. Then, to identify the best subset of features for predicting hot spots, feature selection is performed using a decision tree. Based on the selected features, a predictive model for hot spots is created using support vector machine (SVM) and tested on an independent test set. Our model shows better overall predictive accuracy than previous methods such as the alanine scanning methods Robetta and FOLDEF, and the knowledge-based method KFC. Subsequent analysis yields several findings about hot spots. As expected, hot spots have a larger relative surface area burial and are more hydrophobic than other residues. Unexpectedly, however, residue conservation displays a rather complicated tendency depending on the types of protein complexes, indicating that this feature is not good for identifying hot spots. Of the selected features, the weighted atomic packing density, relative surface area burial and weighted hydrophobicity are the top 3, with the weighted atomic packing density proving to be the most effective feature for predicting hot spots. Notably, we find that hot spots are closely related to pi-related interactions, especially pi . . . pi interactions.

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.

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.

Reynolds stress of localized toroidal modes

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

Zhang, Y.Z.; Mahajan, S.M.

1995-02-01

An investigation of the 2D toroidal eigenmode problem reveals the possibility of a new consistent 2D structure, the dissipative BM-II mode. In contrast to the conventional ballooning mode, the new mode is poloidally localized at {pi}/2 (or -{pi}/2), and possesses significant radial asymmetry. The radial asymmetry, in turn, allows the dissipative BM-II to generate considerably larger Reynolds stress as compared to the standard slab drift type modes. It is also shown that a wide class of localized dissipative toroidal modes are likely to be of the dissipative BM-II nature, suggesting that at the tokamak edge, the fluctuation generated Reynolds stressmore » (a possible source of poloidal flow) can be significant.« less

Some Background Considerations to the Establishment of an External Studies Programme.

ERIC Educational Resources Information Center

Gordon, Hopeton L. A.

A study was made of how conventional, face-to-face teaching methods might be used in conjunction with correspondence study (CS), programed instruction (PI), educational television (ETV) and radio broadcasts, and other approaches to make higher education more widely available throughout the region served by the University of the West Indies. These…

Finite element analysis of ultra-high performance concrete : modeling structural performance of an AASHTO type II girder and a 2nd generation pi-girder

DOT National Transportation Integrated Search

2010-10-01

Ultra-high performance concrete (UHPC) is an advanced cementitious composite material which has been developed in recent decades. When compared to more conventional cement-based concrete materials, UHPC tends to exhibit superior properties such as in...

Registration of TN09-008 soybean cyst nematode resistant cultivar

USDA-ARS?s Scientific Manuscript database

The conventional soybean line TN09-008 (Reg. No. CV- , PI ) was released by University of Tennessee Agricultural Research in 2017 as a cultivar, based on high seed yield potential in Tennessee and the southern region. Soybean cultivar TN09-008 is resistant to HG types 1.2.5.7, 5.7, a...

Registration of conventional soybean germplasm JTN-4307 with resistance to nematodes and fungal diseases

USDA-ARS?s Scientific Manuscript database

JTN-4307 soybean [Glycine max (L.) Merr.] (Reg. No. XX-XXX, PI 670017) was developed by USDA-ARS in collaboration with the University of Missouri and the University of Tennessee, and released in 2013, for its broad resistance to soybean cyst nematode (Heterodera glycines Ichinohe), reniform nematode...

Cerebral Metabolic Alterations in Rats With Diabetic Ketoacidosis

PubMed Central

Glaser, Nicole; Yuen, Natalie; Anderson, Steven E.; Tancredi, Daniel J.; O'Donnell, Martha E.

2010-01-01

OBJECTIVE Cerebral edema is a life-threatening complication of diabetic ketoacidosis (DKA) in children. Recent data suggest that cerebral hypoperfusion and activation of cerebral ion transporters may be involved, but data describing cerebral metabolic alterations during DKA are lacking. RESEARCH DESIGN AND METHODS We evaluated 50 juvenile rats with DKA and 21 normal control rats using proton and phosphorus magnetic resonance spectroscopy (MRS). MRS measured cerebral intracellular pH and ratios of metabolites including ATP/inorganic phosphate (Pi), phosphocreatine (PCr)/Pi, N-acetyl aspartate (NAA)/creatine (Cr), and lactate/Cr before and during DKA treatment. We determined the effects of treatment with insulin and intravenous saline with or without bumetanide, an inhibitor of Na-K-2Cl cotransport, using ANCOVA with a 2 × 2 factorial study design. RESULTS Cerebral intracellular pH was decreased during DKA compared with control (mean ± SE difference −0.13 ± 0.03; P < 0.001), and lactate/Cr was elevated (0.09 ± 0.02; P < 0.001). DKA rats had lower ATP/Pi and NAA/Cr (−0.32 ± 0.10, P = 0.003, and −0.14 ± 0.04, P < 0.001, respectively) compared with controls, but PCr/Pi was not significantly decreased. During 2-h treatment with insulin/saline, ATP/Pi, PCr/Pi, and NAA/Cr declined significantly despite an increase in intracellular pH. Bumetanide treatment increased ATP/Pi and PCr/Pi and ameliorated the declines in these values with insulin/saline treatment. CONCLUSIONS These data demonstrate that cerebral metabolism is significantly compromised during DKA and that further deterioration occurs during early DKA treatment—consistent with possible effects of cerebral hypoperfusion and reperfusion injury. Treatment with bumetanide may help diminish the adverse effects of initial treatment with insulin/saline. PMID:20028943

Targeting the PI3K/Akt pathway in murine MDS/MPN driven by hyperactive Ras

PubMed Central

Akutagawa, Jon; Huang, Tannie Q.; Epstein, Inbal; Chang, Tiffany; Quirindongo-Crespo, Maricel; Cottonham, Charisa L.; Dail, Monique; Slusher, Barbara S.; Friedman, Lori S.; Sampath, Deepak; Braun, Benjamin S.

2016-01-01

Chronic and juvenile myelomonocytic leukemias (CMML and JMML) are myelodysplastic/myeloproliferative neoplasia (MDS/MPN) overlap syndromes that respond poorly to conventional treatments. Aberrant Ras activation due to NRAS, KRAS, PTPN11, CBL, and NF1 mutations is common in CMML and JMML. However, no mechanism-based treatments currently exist for cancers with any of these mutations. An alternative therapeutic strategy involves targeting Ras-regulated effector pathways that are aberrantly activated in CMML and JMML, which include the Raf/MEK/ERK and phosphoinositide-3´-OH kinase (PI3K)/Akt cascades. Mx1-Cre, KrasD12 and Mx1-Cre, Nf1flox/− mice accurately model many aspects of CMML and JMML. Treating Mx1-Cre, KrasD12 mice with GDC-0941 (also referred to as pictilisib), an orally bioavailable inhibitor of class I PI3K isoforms, reduced leukocytosis, anemia, and splenomegaly while extending survival. However, GDC-0941 treatment attenuated activation of both PI3K/Akt and Raf/MEK/ERK pathways in primary hematopoietic cells, suggesting it could be acting through suppression of Raf/MEK/ERK signals. To interrogate the importance of the PI3K/Akt pathway specifically, we treated mice with the allosteric Akt inhibitor MK-2206. This compound had no effect on Raf/MEK/ERK signaling, yet it also induced robust hematologic responses in Kras and Nf1 mice with MPN. These data support investigating PI3K/Akt pathway inhibitors as a therapeutic strategy in JMML and CMML patients. PMID:26965285

Degradation of phosphor-in-glass encapsulants with various phosphor types for high power LEDs

NASA Astrophysics Data System (ADS)

Iqbal, Fauzia; Kim, Sunil; Kim, Hyungsun

2017-10-01

In order to replace conventional silicone-based phosphor light emitting diodes (LEDs), inorganic color converters with high thermal stabilities and transparencies, i.e., phosphors-in-glass (PiGs), have been investigated as encapsulants for high-power LEDs. In this paper, the effect of various types of phosphors, i.e., LuAG (green, Lu3Al5O12:Ce3+), silicate (yellow, Sr2SiO4:Eu2+), CASN (red, CaAlSiN3:Eu2+), and oxynitride (yellow, (Sr,Ba) Si2O2N2:Eu2+), on the reliability/degradation of the remote PiG encapsulants is explored for high power LEDs. For this purpose, a glass composition (SiO2-B2O3-ZnO-Na2O) was separately mixed with each type of phosphor and then sintered at appropriate temperatures to make the corresponding PiG. The reliabilities of the formed PiGs were evaluated by standard accelerated-aging tests (85 °C/85% RH) for 1000 h. Luminosity losses and shifts in the Commission Internationale de l'Eclairage (CIE) coordinates of the PiGs were measured before and after aging. Thermal, and moisture-induced quenching behavior was also analyzed. The surface of PiGs with different phosphors degraded differently, possibly because of structural incompatibilities between the glass matrix and phosphor type. Determining the compatibility of the glass composition with the type of phosphor used is therefore important in order to ensure the long-term stabilities of encapsulants for use in commercial LEDs.

76 FR 55109 - In the Matter of Certain DC-DC Controllers and Products Containing Same; Notice of Institution of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-06

... named the following respondents: VisionTek Products LLC (``VisionTek'') of Inverness, Illinois; uPI Semiconductor Corp. (``uPI'') of Taiwan; Sapphire Technology Limited (``Sapphire'') of Hong Kong; Advanced Micro...'') initial determination (``ID'') granting uPI's and Sapphire's joint motion to terminate the investigation...

Statistical inference of selection and divergence of rice blast resistance gene Pi-ta

USDA-ARS?s Scientific Manuscript database

The resistance gene Pi-ta has been effectively used to control rice blast disease worldwide. A few recent studies have described the possible evolution of Pi-ta in cultivated and weedy rice. However, evolutionary statistics used for the studies are too limited to precisely understand selection and d...

The €100 lab: A 3D-printable open-source platform for fluorescence microscopy, optogenetics, and accurate temperature control during behaviour of zebrafish, Drosophila, and Caenorhabditis elegans.

PubMed

Maia Chagas, Andre; Prieto-Godino, Lucia L; Arrenberg, Aristides B; Baden, Tom

2017-07-01

Small, genetically tractable species such as larval zebrafish, Drosophila, or Caenorhabditis elegans have become key model organisms in modern neuroscience. In addition to their low maintenance costs and easy sharing of strains across labs, one key appeal is the possibility to monitor single or groups of animals in a behavioural arena while controlling the activity of select neurons using optogenetic or thermogenetic tools. However, the purchase of a commercial solution for these types of experiments, including an appropriate camera system as well as a controlled behavioural arena, can be costly. Here, we present a low-cost and modular open-source alternative called 'FlyPi'. Our design is based on a 3D-printed mainframe, a Raspberry Pi computer, and high-definition camera system as well as Arduino-based optical and thermal control circuits. Depending on the configuration, FlyPi can be assembled for well under €100 and features optional modules for light-emitting diode (LED)-based fluorescence microscopy and optogenetic stimulation as well as a Peltier-based temperature stimulator for thermogenetics. The complete version with all modules costs approximately €200 or substantially less if the user is prepared to 'shop around'. All functions of FlyPi can be controlled through a custom-written graphical user interface. To demonstrate FlyPi's capabilities, we present its use in a series of state-of-the-art neurogenetics experiments. In addition, we demonstrate FlyPi's utility as a medical diagnostic tool as well as a teaching aid at Neurogenetics courses held at several African universities. Taken together, the low cost and modular nature as well as fully open design of FlyPi make it a highly versatile tool in a range of applications, including the classroom, diagnostic centres, and research labs.

The p85α regulatory subunit of PI3K mediates cAMP-PKA and retinoic acid biological effects on MCF7 cell growth and migration.

PubMed

Donini, Caterina F; Di Zazzo, Erika; Zuchegna, Candida; Di Domenico, Marina; D'Inzeo, Sonia; Nicolussi, Arianna; Avvedimento, Enrico V; Coppa, Anna; Porcellini, Antonio

2012-05-01

Phosphoinositide-3-OH kinase (PI3K) signalling regulates various cellular processes, including cell survival, growth, proliferation and motility, and is among the most frequently mutated pathways in cancer. Although the involvement of p85αPI3K SH2 domain in signal transduction has been extensively studied, the function of the SH3 domain at the N-terminus remains elusive. A serine (at codon 83) adjacent to the N-terminal SH3 domain in the PI3K regulatory subunit p85αPI3K that is phosphorylated by protein kinase A (PKA) in vivo and in vitro has been identified. Virtually all receptors binding p85αPI3K can cooperate with cAMP-PKA signals via phosphorylation of p85αPI3KSer83. To analyse the role of p85αPI3KSer83 in retinoic acid (RA) and cAMP signalling, in MCF7 cells, we used p85αPI3K mutated forms, in which Ser83 has been substituted with alanine (p85A) to prevent phosphorylation or with aspartic acid (p85D) to mimic the phosphorylated residue. We demonstrated that p85αPI3KSer83 is crucial for the synergistic enhancement of RARα/p85αPI3K binding induced by cAMP/RA co-treatment in MCF7 cells. Growth curves, colorimetric MTT assay and cell cycle analysis demonstrated that phosphorylation of p85αPI3KSer83 plays an important role in the control of MCF7 cell proliferation and in RA-induced inhibition of proliferation. Wound healing and transwell experiments demonstrated that p85αPI3KSer83 was also essential both for the control of migratory behaviour and for the reduction of motility induced by RA. This study points to p85αPI3KSer83 as the physical link between different pathways (cAMP-PKA, RA and FAK), and as an important regulator of MCF7 cell proliferation and migration.

Effect of lingual gauze swab placement on pulse oximeter readings in anaesthetised dogs and cats.

PubMed

Mair, A; Martinez-Taboada, F; Nitzan, M

2017-01-14

This study aimed to evaluate the effect of lingual gauze swab placement on pulse oximeter readings in anaesthetised dogs and cats. Following anaesthetic induction, the following pulse oximeter probe configurations were performed: no gauze swab (control), placement of a gauze swab between the tongue and the probe, placement of different thicknesses of gauze swab, placement of red cotton fabric, placement of a sheet of white paper and placement of the probe and gauze swab on different locations on the tongue. Oxygen saturation (SpO 2 ) and peripheral perfusion index (PI) were recorded. Placement of a gauze swab between the pulse oximeter probe and the tongue in anaesthetised dogs and cats resulted in significantly higher SpO 2 values compared with the control group. In dogs, PI values were significantly higher than the control in all groups except the quarter thickness swab group. In cats, PI was significantly higher in the double thickness swab and white paper groups compared with the control. Cats had significantly higher SpO 2 and lower PI values than dogs. The authors propose that increased contact pressure is responsible for significantly higher SpO 2 and PI readings with the use of a lingual gauze swab resulting from changes in transmural pressure and arterial compliance. British Veterinary Association.

Homeostatic Regulation of the PI(4,5)P2-Ca2+ Signaling System at ER-PM Junctions

PubMed Central

Chang, Chi-Lun; Liou, Jen

2016-01-01

The phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-Ca2+ signaling system is important for cell activation in response to various extracellular stimuli. This signaling system is initiated by receptor-induced hydrolysis of PI(4,5)P2 in the plasma membrane (PM) to generate the soluble second messenger inositol 1,4,5-trisphosphate (IP3). IP3 subsequently triggers the release of Ca2+ from the endoplasmic reticulum (ER) store to the cytosol to activate Ca2+-mediated responses, such as secretion and proliferation. The consumed PM PI(4,5)P2 and ER Ca2+ must be quickly restored to sustain signaling responses, and to maintain the homeostasis of PI(4,5)P2 and Ca2+. Since phosphatidylinositol (PI), the precursor lipid for PM PI(4,5)P2, is synthesized in the ER membrane, and a Ca2+ influx across the PM is required to refill the ER Ca2+ store, efficient communications between the ER and the PM are critical for the homeostatic regulation of the PI(4,5)P2-Ca2+ signaling system. This review describes the major findings that established the framework of the PI(4,5)P2-Ca2+ signaling system, and recent discoveries on feedback control mechanisms at ER-PM junctions that sustain the PI(4,5)P2-Ca2+ signaling system. Particular emphasis is placed on the characterization of ER-PM junctions where efficient communications between the ER and the PM occurs, and the activation mechanisms of proteins that dynamically localize to ER-PM junctions to provide the feedback control during PI(4,5)P2-Ca2+ signaling, including the ER Ca2+ sensor STIM1, the extended synaptotagmin E-Syt1, and the PI transfer protein Nir2. This review is part of a Special Issue entitled The Cellular Lipid Landscape. PMID:26924250

Effect of inorganic phosphate on the force and number of myosin cross-bridges during the isometric contraction of permeabilized muscle fibers from rabbit psoas.

PubMed

Caremani, Marco; Dantzig, Jody; Goldman, Yale E; Lombardi, Vincenzo; Linari, Marco

2008-12-15

The relation between the chemical and mechanical steps of the myosin-actin ATPase reaction that leads to generation of isometric force in fast skeletal muscle was investigated in demembranated fibers of rabbit psoas muscle by determining the effect of the concentration of inorganic phosphate (Pi) on the stiffness of the half-sarcomere (hs) during transient and steady-state conditions of the isometric contraction (temperature 12 degrees C, sarcomere length 2.5 mum). Changes in the hs strain were measured by imposing length steps or small 4 kHz oscillations on the fibers in control solution (without added Pi) and in solution with 3-20 mM added Pi. At the plateau of the isometric contraction in control solution, the hs stiffness is 22.8 +/- 1.1 kPa nm(-1). Taking the filament compliance into account, the total stiffness of the array of myosin cross-bridges in the hs (e) is 40.7 +/- 3.7 kPa nm(-1). An increase in [Pi] decreases the stiffness of the cross-bridge array in proportion to the isometric force, indicating that the force of the cross-bridge remains constant independently of [Pi]. The rate constant of isometric force development after a period of unloaded shortening (r(F)) is 23.5 +/- 1.0 s(-1) in control solution and increases monotonically with [Pi], attaining a maximum value of 48.6 +/- 0.9 s(-1) at 20 mM [Pi], in agreement with the idea that Pi release is a relatively fast step after force generation by the myosin cross-bridge. During isometric force development at any [Pi], e and thus the number of attached cross-bridges increase in proportion to the force, indicating that, independently of the speed of the process that leads to myosin attachment to actin, there is no significant (>1 ms) delay between generation of stiffness and generation of force by the cross-bridges.

A biomolecular proportional integral controller based on feedback regulations of protein level and activity.

PubMed

Mairet, Francis

2018-02-01

Homeostasis is the capacity of living organisms to keep internal conditions regulated at a constant level, despite environmental fluctuations. Integral feedback control is known to play a key role in this behaviour. Here, I show that a feedback system involving transcriptional and post-translational regulations of the same executor protein acts as a proportional integral (PI) controller, leading to enhanced transient performances in comparison with a classical integral loop. Such a biomolecular controller-which I call a level and activity-PI controller (LA-PI)-is involved in the regulation of ammonium uptake by Escherichia coli through the transporter AmtB. The P II molecules, which reflect the nitrogen status of the cell, inhibit both the production of AmtB and its activity (via the NtrB-NtrC system and the formation of a complex with GlnK, respectively). Other examples of LA-PI controller include copper and zinc transporters, and the redox regulation in photosynthesis. This scheme has thus emerged through evolution in many biological systems, surely because of the benefits it offers in terms of performances (rapid and perfect adaptation) and economy (protein production according to needs).

Influence of Polymer-Clay Interfacial Interactions on the Ignition Time of Polymer/Clay Nanocomposites

PubMed Central

Zope, Indraneel S.; Yu, Zhong-Zhen

2017-01-01

Metal ions present on smectite clay (montmorillonite) platelets have preferential reactivity towards peroxy/alkoxy groups during polyamide 6 (PA6) thermal decomposition. This changes the decomposition pathway and negatively affects the ignition response of PA6. To restrict these interfacial interactions, high-temperature-resistant polymers such as polyetherimide (PEI) and polyimide (PI) were used to coat clay layers. PEI was deposited on clay by solution-precipitation, whereas PI was deposited through a solution-imidization-precipitation technique before melt blending with PA6. The absence of polymer-clay interfacial interactions has resulted in a similar time-to-ignition of PA6/PEI-clay (133 s) and PA6/PI-clay (139 s) composites as neat PA6 (140 s). On the contrary, PA6 with conventional ammonium-based surfactant modified clay has showed a huge drop in time-to-ignition (81 s), as expected. The experimental evidences provided herein reveal the role of the catalytic activity of clay during the early stages of polymer decomposition. PMID:28800095

Influence of Polymer-Clay Interfacial Interactions on the Ignition Time of Polymer/Clay Nanocomposites.

PubMed

Zope, Indraneel S; Dasari, Aravind; Yu, Zhong-Zhen

2017-08-11

Metal ions present on smectite clay (montmorillonite) platelets have preferential reactivity towards peroxy/alkoxy groups during polyamide 6 (PA6) thermal decomposition. This changes the decomposition pathway and negatively affects the ignition response of PA6. To restrict these interfacial interactions, high-temperature-resistant polymers such as polyetherimide (PEI) and polyimide (PI) were used to coat clay layers. PEI was deposited on clay by solution-precipitation, whereas PI was deposited through a solution-imidization-precipitation technique before melt blending with PA6. The absence of polymer-clay interfacial interactions has resulted in a similar time-to-ignition of PA6/PEI-clay (133 s) and PA6/PI-clay (139 s) composites as neat PA6 (140 s). On the contrary, PA6 with conventional ammonium-based surfactant modified clay has showed a huge drop in time-to-ignition (81 s), as expected. The experimental evidences provided herein reveal the role of the catalytic activity of clay during the early stages of polymer decomposition.

The machinery at endoplasmic reticulum-plasma membrane contact sites contributes to spatial regulation of multiple Legionella effector proteins.

PubMed

Hubber, Andree; Arasaki, Kohei; Nakatsu, Fubito; Hardiman, Camille; Lambright, David; De Camilli, Pietro; Nagai, Hiroki; Roy, Craig R

2014-07-01

The Dot/Icm system of the intracellular pathogen Legionella pneumophila has the capacity to deliver over 270 effector proteins into host cells during infection. Important questions remain as to spatial and temporal mechanisms used to regulate such a large array of virulence determinants after they have been delivered into host cells. Here we investigated several L. pneumophila effector proteins that contain a conserved phosphatidylinositol-4-phosphate (PI4P)-binding domain first described in the effector DrrA (SidM). This PI4P binding domain was essential for the localization of effectors to the early L. pneumophila-containing vacuole (LCV), and DrrA-mediated recruitment of Rab1 to the LCV required PI4P-binding activity. It was found that the host cell machinery that regulates sites of contact between the plasma membrane (PM) and the endoplasmic reticulum (ER) modulates PI4P dynamics on the LCV to control localization of these effectors. Specifically, phosphatidylinositol-4-kinase IIIα (PI4KIIIα) was important for generating a PI4P signature that enabled L. pneumophila effectors to localize to the PM-derived vacuole, and the ER-associated phosphatase Sac1 was involved in metabolizing the PI4P on the vacuole to promote the dissociation of effectors. A defect in L. pneumophila replication in macrophages deficient in PI4KIIIα was observed, highlighting that a PM-derived PI4P signature is critical for biogenesis of a vacuole that supports intracellular multiplication of L. pneumophila. These data indicate that PI4P metabolism by enzymes controlling PM-ER contact sites regulate the association of L. pneumophila effectors to coordinate early stages of vacuole biogenesis.

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

Biologically inspired design of feedback control systems implemented using DNA strand displacement reactions.

PubMed

Foo, Mathias; Sawlekar, Rucha; Kulkarni, Vishwesh V; Bates, Declan G

2016-08-01

The use of abstract chemical reaction networks (CRNs) as a modelling and design framework for the implementation of computing and control circuits using enzyme-free, entropy driven DNA strand displacement (DSD) reactions is starting to garner widespread attention in the area of synthetic biology. Previous work in this area has demonstrated the theoretical plausibility of using this approach to design biomolecular feedback control systems based on classical proportional-integral (PI) controllers, which may be constructed from CRNs implementing gain, summation and integrator operators. Here, we propose an alternative design approach that utilises the abstract chemical reactions involved in cellular signalling cycles to implement a biomolecular controller - termed a signalling-cycle (SC) controller. We compare the performance of the PI and SC controllers in closed-loop with a nonlinear second-order chemical process. Our results show that the SC controller outperforms the PI controller in terms of both performance and robustness, and also requires fewer abstract chemical reactions to implement, highlighting its potential usefulness in the construction of biomolecular control circuits.

Histone-derived piRNA biogenesis depends on the ping-pong partners Piwi5 and Ago3 in Aedes aegypti

PubMed Central

Girardi, Erika; Miesen, Pascal; Pennings, Bas; Frangeul, Lionel; Saleh, Maria-Carla

2017-01-01

Abstract The piRNA pathway is of key importance in controlling transposable elements in most animal species. In the vector mosquito Aedes aegypti, the presence of eight PIWI proteins and the accumulation of viral piRNAs upon arbovirus infection suggest additional functions of the piRNA pathway beyond genome defense. To better understand the regulatory potential of this pathway, we analyzed in detail host-derived piRNAs in A. aegypti Aag2 cells. We show that a large repertoire of protein-coding genes and non-retroviral integrated RNA virus elements are processed into genic piRNAs by different combinations of PIWI proteins. Among these, we identify a class of genes that produces piRNAs from coding sequences in an Ago3- and Piwi5-dependent fashion. We demonstrate that the replication-dependent histone gene family is a genic source of ping-pong dependent piRNAs and that histone-derived piRNAs are dynamically expressed throughout the cell cycle, suggesting a role for the piRNA pathway in the regulation of histone gene expression. Moreover, our results establish the Aag2 cell line as an accessible experimental model to study gene-derived piRNAs. PMID:28115625

Protein synthesis controls phosphate homeostasis.

PubMed

Pontes, Mauricio H; Groisman, Eduardo A

2018-01-01

Phosphorus is an essential element assimilated largely as orthophosphate (Pi). Cells respond to Pi starvation by importing Pi from their surroundings. We now report that impaired protein synthesis alone triggers a Pi starvation response even when Pi is plentiful in the extracellular milieu. In the bacterium Salmonella enterica serovar Typhimurium , this response entails phosphorylation of the regulatory protein PhoB and transcription of PhoB-dependent Pi transporter genes and is eliminated upon stimulation of adenosine triphosphate (ATP) hydrolysis. When protein synthesis is impaired due to low cytoplasmic magnesium (Mg 2+ ), Salmonella triggers the Pi starvation response because ribosomes are destabilized, which reduces ATP consumption and thus free cytoplasmic Pi. This response is transient because low cytoplasmic Mg 2+ promotes an uptake in Mg 2+ and a decrease in ATP levels, which stabilizes ribosomes, resulting in ATP consumption and Pi increase, thus ending the response. Notably, pharmacological inhibition of protein synthesis also elicited a Pi starvation response in the bacterium Escherichia coli and the yeast Saccharomyces cerevisiae Our findings identify a regulatory connection between protein synthesis and Pi homeostasis that is widespread in nature. © 2018 Pontes and Groisman; Published by Cold Spring Harbor Laboratory Press.

Analysis of Proportional Integral and Optimized Proportional Integral Controllers for Resistance Spot Welding System (RSWS) - A Performance Perspective

NASA Astrophysics Data System (ADS)

Rama Subbanna, S.; Suryakalavathi, M., Dr.

2017-08-01

This paper is an attempt to accomplish a performance analysis of the different control techniques on spikes reduction method applied on the medium frequency transformer based DC spot welding system. Spike reduction is an important factor to be considered while spot welding systems are concerned. During normal RSWS operation welding transformer’s magnetic core can become saturated due to the unbalanced resistances of both transformer secondary windings and different characteristics of output rectifier diodes, which causes current spikes and over-current protection switch-off of the entire system. The current control technique is a piecewise linear control technique that is inspired from the DC-DC converter control algorithms to register a novel spike reduction method in the MFDC spot welding applications. Two controllers that were used for the spike reduction portion of the overall applications involve the traditional PI controller and Optimized PI controller. Care is taken such that the current control technique would maintain a reduced spikes in the primary current of the transformer while it reduces the Total Harmonic Distortion. The performance parameter that is involved in the spikes reduction technique is the THD, Percentage of current spike reduction for both techniques. Matlab/SimulinkTM based simulation is carried out for the MFDC RSWS with KW and results are tabulated for the PI and Optimized PI controllers and a tradeoff analysis is carried out.

Switches from pi- to sigma-bonding complexes controlled by gate voltages.

PubMed

Matsui, Eriko; Harnack, Oliver; Matsuzawa, Nobuyuki N; Yasuda, Akio

2005-10-01

A conjugated polymer/metal ion/liquid-crystal molecular system was set between source and drain electrodes with a 100 nm gap. When gate voltage (Vg) increases, the current between source and drain electrodes increases. Infrared spectra show this system to be composed of pi and sigma complexes. At Vg = 0, the pi complex dominates the sigma complex, whereas the sigma complex becomes dominant when Vg is switched on. Calculations found that the pi complex has lower conductivity than the sigma complex.

Assessment of riverine load of contaminants to European seas under policy implementation scenarios: an example with 3 pilot substances.

PubMed

Marinov, Dimitar; Pistocchi, Alberto; Trombetti, Marco; Bidoglio, Giovanni

2014-01-01

An evaluation of conventional emission scenarios is carried out targeting a possible impact of European Union (EU) policies on riverine loads to the European seas for 3 pilot pollutants: lindane, trifluralin, and perfluorooctane sulfonate (PFOS). The policy scenarios are investigated to the time horizon of year 2020 starting from chemical-specific reference conditions and considering different types of regulatory measures including business as usual (BAU), current trend (CT), partial implementation (PI), or complete ban (PI ban) of emissions. The scenario analyses show that the model-estimated lindane load of 745 t to European seas in 1995, based on the official emission data, would be reduced by 98.3% to approximately 12.5 t in 2005 (BAU scenario), 10 years after the start of the EU regulation of this chemical. The CT and PI ban scenarios indicate a reduction of sea loads of lindane in 2020 by 74% and 95%, respectively, when compared to the BAU estimate. For trifluralin, an annual load of approximately 61.7 t is estimated for the baseline year 2003 (BAU scenario), although the applied conservative assumptions related to pesticide use data availability in Europe. Under the PI (ban) scenario, assuming only small residual emissions of trifluralin, we estimate a sea loading of approximately 0.07 t/y. For PFOS, the total sea load from all European countries is estimated at approximately 5.8 t/y referred to 2007 (BAU scenario). Reducing the total load of PFOS below 1 t/y requires emissions to be reduced by 84%. The analysis of conventional scenarios or scenario typologies for emissions of contaminants using simple spatially explicit GIS-based models is suggested as a viable, affordable exercise that may support the assessment of implementation of policies and the identification or negotiation of emission reduction targets. © 2013 SETAC.

Exploring inhibitory potential of Curcumin against various cancer targets by in silico virtual screening.

PubMed

Mahajanakatti, Arpitha Badarinath; Murthy, Geetha; Sharma, Narasimha; Skariyachan, Sinosh

2014-03-01

Various types of cancer accounts for 10% of total death worldwide which necessitates better therapeutic strategies. Curcumin, a curcuminoid present in Curcuma longa, shown to exhibit antioxidant, anti-inflammatory and anticarcinogenic properties. Present study, we aimed to analyze inhibitory properties of curcumin towards virulent proteins for various cancers by computer aided virtual screening. Based on literature studies, twenty two receptors were selected which have critical virulent functions in various cancer. The binding efficiencies of curcumin towards selected targets were studied by molecular docking. Out of all, curcumin showed best results towards epidermal growth factor (EGF), virulent protein of gastric cancer; glutathione-S-transferase Pi gene (GST-PI), virulent protein for prostate cancer; platelet-derived growth factor alpha (PDGFA), virulent protein for mesothelioma and glioma compared with their natural ligands. The calculated binding energies of their docked conformations with curcumin found to be -7.59 kcal/mol, -7.98 kcal/mol and -7.93 kcal/mol respectively. Further, a comparative study was performed to screen binding efficiency of curcumin with two conventional antitumor agents, litreol and triterpene. Docking studies revealed that calculated binding energies of docked complex of litreol and EGF, GST-PI and PDGFA were found to be -5.08 kcal/mol, -3.69 kcal/mol and -1.86 kcal/mol respectively. The calculated binding energies of triterpene with EGF and PDGFA were found to be -4.02 kcal/mol and -3.11 kcal/mol respectively, whereas GST-PI showed +6.07 kcal/mol, indicate poor binding. The predicted pharmacological features of curcumin found to be better than litreol and triterpene. Our study concluded that curcumin has better interacting properties towards these cancer targets than their normal ligands and conventional antitumor agents. Our data pave insight for designing of curcumin as novel inhibitors against various types of cancer.

Proactive interference in a semantic short-term memory deficit: role of semantic and phonological relatedness.

PubMed

Hamilton, A Cris; Martin, Randi C

2007-01-01

Previous research has indicated that patients with semantic short-term memory (STM) deficits demonstrate unusual intrusions of previously presented material during serial recall tasks (Martin and Lesch, 1996). These intrusions suggest excessive proactive interference (PI) from previous lists. Here, we explore one such patient's susceptibility to PI. Experiment 1 demonstrated patient M.L.'s extreme susceptibility to PI using a probe recognition task that manipulates the recency of negative probes (the recent negatives task). When stimuli consisted of letters, M.L. showed greatly exaggerated effects of PI, well outside of the range of healthy control participants. Experiment 2 used a variation of the recent negatives task to examine the relative contribution of semantic and phonological relatedness in PI. This task manipulated semantic and phonological relatedness of probes and recently presented list items. Relative to healthy control participants, patient M.L. showed exaggerated interference effects for both phonological and semantically related probes, both for probes related to the current list and for probes related to the previous list. These data have important implications for theories of semantic STM deficits. Specifically, these data suggest that it is not the rapid decay of semantic representations that is responsible for difficulties in short-term recall, but rather the abnormal persistence of previously presented material. We propose that this susceptibility to PI is the result of a deficit in control processes acting on STM.

Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: Redundant roles for PiT-1 and PiT-2

PubMed Central

Crouthamel, Matthew H.; Lau, Wei Ling; Leaf, Elizabeth M.; Chavkin, Nick; Wallingford, Mary C.; Peterson, Danielle F.; Li, Xianwu; Liu, Yonggang; Chin, Michael T.; Levi, Moshe; Giachelli, Cecilia M.

2014-01-01

Objective Elevated serum phosphate has emerged as a major risk factor for vascular calcification. The sodium-dependent phosphate cotransporter, PiT-1, was previously shown to be required for phosphate-induced osteogenic differentiation and calcification of cultured human VSMCs, but its importance in vascular calcification in vivo, as well as the potential role of its homologue, PiT-2, have not been determined. We investigated the in vivo requirement for PiT-1 in vascular calcification using a mouse model of chronic kidney disease, and the potential compensatory role of PiT-2 using in vitro knockdown and over-expression strategies. Approach and Results Mice with targeted deletion of PiT-1 in VSMCs were generated (PiT-1Δsm). PiT-1 mRNA levels were undetectable whereas PiT-2 mRNA levels were increased 2 fold in the vascular aortic media of PiT-1Δsm compared to PiT-1flox/flox control. When arterial medial calcification was induced in PiT-1Δsm and PiT-1flox/flox by chronic kidney disease followed by dietary phosphate loading, the degree of aortic calcification was not different between genotypes, suggesting compensation by PiT-2. Consistent with this possibility, VSMCs isolated from PiT-1Δsm mice had no PiT-1 mRNA expression, increased PiT-2 mRNA levels, and no difference in sodium-dependent phosphate uptake or phosphate-induced matrix calcification compared to PiT-1flox/flox VSMCs. Knockdown of PiT-2 decreased phosphate uptake and phosphate-induced calcification of PiT-1Δsm VSMCs. Furthermore, over-expression of PiT-2 restored these parameters in human PiT-1-deficient VSMCs. Conclusions PiT-2 can mediate phosphate uptake and calcification of VSMCs in the absence of PiT-1. Mechanistically, PiT-1 and PiT-2 appear to serve redundant roles in phosphate-induced calcification of vascular smooth muscle cells. PMID:23968976

Robust set-point regulation for ecological models with multiple management goals.

PubMed

Guiver, Chris; Mueller, Markus; Hodgson, Dave; Townley, Stuart

2016-05-01

Population managers will often have to deal with problems of meeting multiple goals, for example, keeping at specific levels both the total population and population abundances in given stage-classes of a stratified population. In control engineering, such set-point regulation problems are commonly tackled using multi-input, multi-output proportional and integral (PI) feedback controllers. Building on our recent results for population management with single goals, we develop a PI control approach in a context of multi-objective population management. We show that robust set-point regulation is achieved by using a modified PI controller with saturation and anti-windup elements, both described in the paper, and illustrate the theory with examples. Our results apply more generally to linear control systems with positive state variables, including a class of infinite-dimensional systems, and thus have broader appeal.

Improvement of the grid-connect current quality using novel proportional-integral controller for photovoltaic inverters.

PubMed

Cheng, Yuhua; Chen, Kai; Bai, Libing; Yang, Jing

2014-02-01

Precise control of the grid-connected current is a challenge in photovoltaic inverter research. Traditional Proportional-Integral (PI) control technology cannot eliminate steady-state error when tracking the sinusoidal signal from the grid, which results in a very high total harmonic distortion in the grid-connected current. A novel PI controller has been developed in this paper, in which the sinusoidal wave is discretized into an N-step input signal that is decided by the control frequency to eliminate the steady state error of the system. The effect of periodical error caused by the dead zone of the power switch and conduction voltage drop can be avoided; the current tracking accuracy and current harmonic content can also be improved. Based on the proposed PI controller, a 700 W photovoltaic grid-connected inverter is developed and validated. The improvement has been demonstrated through experimental results.

Regulation of Head and Neck Squamous Cancer Stem Cells by PI3K and SOX2

PubMed Central

Keysar, Stephen B.; Le, Phuong N.; Miller, Bettina; Jackson, Brian C.; Eagles, Justin R.; Nieto, Cera; Kim, Jihye; Tang, Binwu; Glogowska, Magdalena J.; Morton, J. Jason; Padilla-Just, Nuria; Gomez, Karina; Warnock, Emily; Reisinger, Julie; Arcaroli, John J.; Messersmith, Wells A.; Wakefield, Lalage M.; Gao, Dexiang; Tan, Aik-Choon; Serracino, Hilary

2017-01-01

Background: We have an incomplete understanding of the differences between cancer stem cells (CSCs) in human papillomavirus–positive (HPV-positive) and –negative (HPV-negative) head and neck squamous cell cancer (HNSCC). The PI3K pathway has the most frequent activating genetic events in HNSCC (especially HPV-positive driven), but the differential signaling between CSCs and non-CSCs is also unknown. Methods: We addressed these unresolved questions using CSCs identified from 10 HNSCC patient-derived xenografts (PDXs). Sored populations were serially passaged in nude mice to evaluate tumorigenicity and tumor recapitulation. The transcription profile of HNSCC CSCs was characterized by mRNA sequencing, and the susceptibility of CSCs to therapy was investigated using an in vivo model. SOX2 transcriptional activity was used to follow the asymmetric division of PDX-derived CSCs. All statistical tests were two-sided. Results: CSCs were enriched by high aldehyde dehydrogenase (ALDH) activity and CD44 expression and were similar between HPV-positive and HPV-negative cases (percent tumor formation injecting ≤ 1x103 cells: ALDH+CD44high = 65.8%, ALDH-CD44high = 33.1%, ALDH+CD44high = 20.0%; and injecting 1x105 cells: ALDH-CD44low = 4.4%). CSCs were resistant to conventional therapy and had PI3K/mTOR pathway overexpression (GSEA pathway enrichment, P < .001), and PI3K inhibition in vivo decreased their tumorigenicity (40.0%–100.0% across cases). PI3K/mTOR directly regulated SOX2 protein levels, and SOX2 in turn activated ALDH1A1 (P < .001 013C and 067C) expression and ALDH activity (ALDH+ [%] empty-control vs SOX2, 0.4% ± 0.4% vs 14.5% ± 9.8%, P = .03 for 013C and 1.7% ± 1.3% vs 3.6% ± 3.4%, P = .04 for 067C) in 013C and 067 cells. SOX2 enhanced sphere and tumor growth (spheres/well, 013C P < .001 and 067C P = .04) and therapy resistance. SOX2 expression prompted mesenchymal-to-epithelial transition (MET) by inducing CDH1 (013C P = .002, 067C P = .01), followed by asymmetric division and proliferation, which contributed to tumor formation. Conclusions: The molecular link between PI3K activation and CSC properties found in this study provides insights into therapeutic strategies for HNSCC. Constitutive expression of SOX2 in HNSCC cells generates a CSC-like population that enables CSC studies. PMID:27634934

Application of neural models as controllers in mobile robot velocity control loop

NASA Astrophysics Data System (ADS)

Cerkala, Jakub; Jadlovska, Anna

2017-01-01

This paper presents the application of an inverse neural models used as controllers in comparison to classical PI controllers for velocity tracking control task used in two-wheel, differentially driven mobile robot. The PI controller synthesis is based on linear approximation of actuators with equivalent load. In order to obtain relevant datasets for training of feed-forward multi-layer perceptron based neural network used as neural model, the mathematical model of mobile robot, that combines its kinematic and dynamic properties such as chassis dimensions, center of gravity offset, friction and actuator parameters is used. Neural models are trained off-line to act as an inverse dynamics of DC motors with particular load using data collected in simulation experiment for motor input voltage step changes within bounded operating area. The performances of PI controllers versus inverse neural models in mobile robot internal velocity control loops are demonstrated and compared in simulation experiment of navigation control task for line segment motion in plane.

Proactive interference and item similarity in working memory.

PubMed

Bunting, Michael

2006-03-01

Proactive interference (PI) may influence the predictive utility of working memory span tasks. Participants in one experiment (N=70) completed Ravens Advanced Progressive Matrices (RAPM) and multiple versions of operation span and probed recall, modified for the type of memoranda (digits or words). Changing memoranda within- or across-trials released PI, but not doing so permitted PI buildup. Scores from PI-build trials, but not PI-release trials, correlated with RAPM and accounted for as much variance in RAPM as unmodified tasks. These results are consistent with controlled attention and inhibition accounts of working memory, and they elucidate a fundamental component of working memory span tasks.

Theoretical studies on beta and delta isoform-specific binding mechanisms of phosphoinositide 3-kinase inhibitors.

PubMed

Zhu, Jingyu; Pan, Peichen; Li, Youyong; Wang, Man; Li, Dan; Cao, Biyin; Mao, Xinliang; Hou, Tingjun

2014-03-04

Phosphoinositide 3-kinase (PI3K) is known to be closely related to tumorigenesis and cell proliferation, and controls a variety of cellular processes, including proliferation, growth, apoptosis, migration, metabolism, etc. The PI3K family comprises eight catalytic isoforms, which are subdivided into three classes. Recently, the discovery of inhibitors that block a single isoform of PI3K has continued to attract special attention because they may have higher selectivity for certain tumors and less toxicity for healthy cells. The PI3Kβ and PI3Kδ share fewer studies than α/γ, and therefore, in this work, the combination of molecular dynamics simulations and free energy calculations was employed to explore the binding of three isoform-specific PI3K inhibitors (COM8, IC87114, and GDC-0941) to PI3Kβ or PI3Kδ. The isoform specificities of the studied inhibitors derived from the predicted binding free energies are in good agreement with the experimental data. In addition, the key residues critical for PI3Kβ or PI3Kδ selectivity were highlighted by decomposing the binding free energies into the contributions from individual residues. It was observed that although PI3Kβ and PI3Kδ share the conserved ATP-binding pockets, individual residues do behave differently, particularly the residues critical for PI3Kβ or PI3Kδ selectivity. It can be concluded that the inhibitor specificity between PI3Kβ and PI3Kδ is determined by the additive contributions from multiple residues, not just a single one. This study provides valuable information for understanding the isoform-specific binding mechanisms of PI3K inhibitors, and should be useful for the rational design of novel and selective PI3K inhibitors.

Effects of small interfering RNA inhibit Class I phosphoinositide 3-kinase on human gastric cancer cells

PubMed Central

Zhu, Bao-Song; Yu, Li-Yan; Zhao, Kui; Wu, Yong-You; Cheng, Xiao-Li; Wu, Yong; Zhong, Feng-Yun; Gong, Wei; Chen, Qiang; Xing, Chun-Gen

2013-01-01

AIM: To investigate the effects of small interfering RNA (siRNA)-mediated inhibition of Class I phosphoinositide 3-kinase (Class I PI3K) signal transduction on the proliferation, apoptosis, and autophagy of gastric cancer SGC7901 and MGC803 cells. METHODS: We constructed the recombinant replication adenovirus PI3K(I)-RNA interference (RNAi)-green fluorescent protein (GFP) and control adenovirus NC-RNAi-GFP, and infected it into human gastric cancer cells. MTT assay was used to determine the growth rate of the gastric cancer cells. Activation of autophagy was monitored with monodansylcadaverine (MDC) staining after adenovirus PI3K(I)-RNAi-GFP and control adenovirus NC-RNAi-GFP treatment. Immunofluorescence staining was used to detect the expression of microtubule-associated protein 1 light chain 3 (LC3). Mitochondrial membrane potential was measured using the fluorescent probe JC-1. The expression of autophagy was monitored with MDC, LC3 staining, and transmission electron microscopy. Western blotting was used to detect p53, Beclin-1, Bcl-2, and LC3 protein expression in the culture supernatant. RESULTS: The viability of gastric cancer cells was inhibited after siRNA targeting to the Class I PI3K blocked Class I PI3K signal pathway. MTT assays revealed that, after SGC7901 cancer cells were treated with adenovirus PI3K(I)-RNAi-GFP, the rate of inhibition reached 27.48% ± 2.71% at 24 h, 41.92% ± 2.02% at 48 h, and 50.85% ± 0.91% at 72 h. After MGC803 cancer cells were treated with adenovirus PI3K(I)-RNAi-GFP, the rate of inhibition reached 24.39% ± 0.93% at 24 h, 47.00% ± 0.87% at 48 h, and 70.30% ± 0.86% at 72 h (P < 0.05 compared to control group). It was determined that when 50 MOI, the transfection efficiency was 95% ± 2.4%. Adenovirus PI3K(I)-RNAi-GFP (50 MOI) induced mitochondrial dysfunction and activated cell apoptosis in SGC7901 cells, and the results described here prove that RNAi of Class I PI3K induced apoptosis in SGC7901 cells. The results showed that adenovirus PI3K(I)-RNAi-GFP transfection induced punctate distribution of LC3 immunoreactivity, indicating increased formation of autophagosomes. The results showed that the basal level of Beclin-1 and LC3 protein in SGC7901 cells was low. After incubating with adenovirus PI3K(I)-RNAi-GFP (50 MOI), Beclin-1, LC3, and p53 protein expression was significantly increased from 24 to 72 h. We also found that Bcl-2 protein expression down-regulated with the treatment of adenovirus PI3K(I)-RNAi-GFP (50 MOI). A number of isolated membranes, possibly derived from ribosome-free endoplasmic reticulum, were seen. These isolated membranes were elongated and curved to engulf a cytoplasmic fraction and organelles. We used transmission electron microscopy to identify ultrastructural changes in SGC7901 cells after adenovirus PI3K(I)-RNAi-GFP (50 MOI) treatment. Control cells showed a round shape and contained normal-looking organelles, nucleus, and chromatin, while adenovirus PI3K(I)-RNAi-GFP (50 MOI)-treated cells exhibited the typical signs of autophagy. CONCLUSION: After the Class I PI3K signaling pathway has been blocked by siRNA, the proliferation of cells was inhibited and the apoptosis of gastric cancer cells was enhanced. PMID:23555164

Immunophenotyping in post-giardiasis functional gastrointestinal disease and chronic fatigue syndrome.

PubMed

Hanevik, Kurt; Kristoffersen, Einar K; Sørnes, Steinar; Mørch, Kristine; Næss, Halvor; Rivenes, Ann C; Bødtker, Jørn E; Hausken, Trygve; Langeland, Nina

2012-10-14

A Giardia outbreak was associated with development of post-infectious functional gastrointestinal disorders (PI-FGID) and chronic fatigue syndrome (PI-CFS). Markers of immune dysfunction have given conflicting results in CFS and FGID patient populations. The aim of this study was to evaluate a wide selection of markers of immune dysfunction in these two co-occurring post-infectious syndromes. 48 patients, reporting chronic fatigue in a questionnaire study, were clinically evaluated five years after the outbreak and grouped according to Fukuda criteria for CFS (n=19) and idiopathic chronic fatigue (n=5) and Rome II criteria for FGIDs (n=54). 22 Giardia exposed non-fatigued individuals and 10 healthy unexposed individuals were recruited as controls. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. In peripheral blood we found significantly higher CD8 T-cell levels in PI-FGID, and significantly lower NK-cell levels in PI-CFS patients. Severity of abdominal and fatigue symptoms correlated negatively with NK-cell levels. A tendency towards lower T-cell CD26 expression in FGID was seen. Patients with PI-CFS and/or PI-FGID 5 years after Giardia lamblia infection showed alterations in NK-cell and CD8-cell populations suggesting a possible immunological abnormality in these conditions. We found no significant changes in other markers examined in this well-defined group of PI-CFS and PI-FGID elicited by a gastrointestinal infection. Controlling for co-morbid conditions is important in evaluation of CFS-biomarkers.

PI3K/AKT signaling inhibits NOTCH1 lysosome-mediated degradation.

PubMed

Platonova, Natalia; Manzo, Teresa; Mirandola, Leonardo; Colombo, Michela; Calzavara, Elisabetta; Vigolo, Emilia; Cermisoni, Greta Chiara; De Simone, Daria; Garavelli, Silvia; Cecchinato, Valentina; Lazzari, Elisa; Neri, Antonino; Chiaramonte, Raffaella

2015-06-06

The pathways of NOTCH and PI3K/AKT are dysregulated in about 60% and 48% of T-cell acute lymphoblastic leukemia (T-ALL) patients, respectively. In this context, they interact and cooperate in controlling tumor cell biology. Here, we propose a novel mechanism by which the PI3K/AKT pathway regulates NOTCH1 in T-ALL, starting from the evidence that the inhibition of PI3K/AKT signaling induced by treatment with LY294002 or transient transfection with a dominant negative AKT mutant downregulates NOTCH1 protein levels and activity, without affecting NOTCH1 transcription. We showed that the withdrawal of PI3K/AKT signaling was associated to NOTCH1 phosphorylation in tyrosine residues and monoubiquitination of NOTCH1 detected by Ubiquitin capture assay. Co-immunoprecipitation assay and colocalization analysis further showed that the E3 ubiquitin ligase c-Cbl interacts and monoubiquitinates NOTCH1, activating its lysosomal degradation. These results suggest that the degradation of NOTCH1 could represent a mechanism of control by which NOTCH1 receptors are actively removed from the cell surface. This mechanism is finely regulated by the PI3K/AKT pathway in physiological conditions. In pathological conditions characterized by PI3K/AKT hyperactivation, such as T-ALL, the excessive AKT signaling could lead to NOTCH1 signaling dysregulation. Therefore, a therapeutic strategy directed to PI3K/AKT in T-ALL could contemporaneously inhibit the dysregulated NOTCH1 signaling. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

A biomolecular proportional integral controller based on feedback regulations of protein level and activity

PubMed Central

2018-01-01

Homeostasis is the capacity of living organisms to keep internal conditions regulated at a constant level, despite environmental fluctuations. Integral feedback control is known to play a key role in this behaviour. Here, I show that a feedback system involving transcriptional and post-translational regulations of the same executor protein acts as a proportional integral (PI) controller, leading to enhanced transient performances in comparison with a classical integral loop. Such a biomolecular controller—which I call a level and activity-PI controller (LA-PI)—is involved in the regulation of ammonium uptake by Escherichia coli through the transporter AmtB. The PII molecules, which reflect the nitrogen status of the cell, inhibit both the production of AmtB and its activity (via the NtrB-NtrC system and the formation of a complex with GlnK, respectively). Other examples of LA-PI controller include copper and zinc transporters, and the redox regulation in photosynthesis. This scheme has thus emerged through evolution in many biological systems, surely because of the benefits it offers in terms of performances (rapid and perfect adaptation) and economy (protein production according to needs). PMID:29515895

A review of phosphate mineral nucleation in biology and geobiology.

PubMed

Omelon, Sidney; Ariganello, Marianne; Bonucci, Ermanno; Grynpas, Marc; Nanci, Antonio

2013-10-01

Relationships between geological phosphorite deposition and biological apatite nucleation have often been overlooked. However, similarities in biological apatite and phosphorite mineralogy suggest that their chemical formation mechanisms may be similar. This review serves to draw parallels between two newly described phosphorite mineralization processes, and proposes a similar novel mechanism for biologically controlled apatite mineral nucleation. This mechanism integrates polyphosphate biochemistry with crystal nucleation theory. Recently, the roles of polyphosphates in the nucleation of marine phosphorites were discovered. Marine bacteria and diatoms have been shown to store and concentrate inorganic phosphate (Pi) as amorphous, polyphosphate granules. Subsequent release of these P reserves into the local marine environment as Pi results in biologically induced phosphorite nucleation. Pi storage and release through an intracellular polyphosphate intermediate may also occur in mineralizing oral bacteria. Polyphosphates may be associated with biologically controlled apatite nucleation within vertebrates and invertebrates. Historically, biological apatite nucleation has been attributed to either a biochemical increase in local Pi concentration or matrix-mediated apatite nucleation control. This review proposes a mechanism that integrates both theories. Intracellular and extracellular amorphous granules, rich in both calcium and phosphorus, have been observed in apatite-biomineralizing vertebrates, protists, and atremate brachiopods. These granules may represent stores of calcium-polyphosphate. Not unlike phosphorite nucleation by bacteria and diatoms, polyphosphate depolymerization to Pi would be controlled by phosphatase activity. Enzymatic polyphosphate depolymerization would increase apatite saturation to the level required for mineral nucleation, while matrix proteins would simultaneously control the progression of new biological apatite formation.

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

Spermatozoa Expression of piR-31704, piR-39888, and piR-40349 and Their Correlation to Sperm Concentration and Fertilization Rate After ICSI.

PubMed

Cui, Long; Fang, Li; Shi, Biwei; Qiu, Sunquan; Ye, Yinghui

2018-05-01

To investigate the relationship between spermatozoa PIWI-interacting RNAs (piRNAs) levels and semen parameters and to evaluate the role of expression of piRNAs on fertilization and embryo development after intracytoplasmic sperm injection (ICSI) treatment. One hundred and eighty-six patients with idiopathic male infertility who had undergone first ICSI cycles were enrolled in our study. The levels of piRNAs in spermatozoa were measured by real-time polymerase chain reaction. Semen parameters, including sperm concentration, motility, and morphology, were evaluated. The rates of fertilization, early cleavage, and day 3 good-quality embryo were calculated to assess embryo development potential. Spermatozoa levels of piR-31704 and piR-39888 were decreased in male factor infertility group as compared with control group (for piR-31704, P = .027 and for piR-39888, P = .041, respectively). And these 2 piRNAs were expressed at higher levels in patients with normal sperm concentration compared with subnormal sperm concentration group (for piR-31704, P = .042; for piR-39888, P = .047, respectively), while there were no correlation between the 3 piRNAs expression levels in spermatozoa and the rates of sperm progressive motility and normal sperm morphology. There were significant increases in the levels of all 3 piRNAs in spermatozoa from the group with higher 2PN rates (for piR-31704, P = .002; for piR-39888, P < .001; for piR-40349, P < .001; respectively), but there was no correlation between spermatozoa levels of these 3 piRNAs and the rates of embryo early cleavage, day 3 good-quality embryos and pregnancy. Spermatozoa piRNA levels correlate with sperm concentration and fertilization rate after ICSI. Paternal piRNAs may play a role in fertilization process.

Electrocardiographic findings in patients with polycythemia vera.

PubMed

Kayrak, Mehmet; Acar, Kadir; Gul, Enes Elvin; Abdulhalikov, Turyan; Bağlıcaklıoğlu, Murat; Sonmez, Osman; Kaya, Zeynettin; Arı, Hatem

2012-01-01

The 12-lead surface electrocardiogram (ECG) is a useful tool to predict both atrial and ventricular arrhythmias via P-wave and QT measurements and its derivatives. Polycythemia vera (PV) is a chronic myeloproliferative disorder associated with cardiovascular events. The aim of this study was to assess ECG findings of patients with PV. Sixty patients with PV (34 male, mean age 58±11 years) and 60 age and gender-matched healthy volunteers were enrolled into the study. From the 12-lead surface ECG, P-wave and both conventional QT measurements and transmyocardial repolarization parameters (T(peak)-T(end) interval (T(p)-T(e)) and derivatives) were evaluated digitally by two experienced cardiologists. In addition, a novel parameter, Pi was calculated digitally as the standard deviation of the P-wave duration across the 12 ECG leads. QT duration and corrected QT interval were significantly longer in the PV group compared to healthy controls (p<0.01 and p<0.01, respectively). The T(p)-T(e) was longer and the T(p)-T(e)/QT ratio was significantly higher in the PV group compared to the controls. P-wave analyses showed that all P-wave parameters including Pmax, Pmin, P dispersion, and Pi were significantly prolonged in PV patients compared to the controls. The increase of both T(p)-T(e )and P max in the PV group was independent of age, BMI, diabetes and hypertension, gender, systolic blood pressure, hemoglobin, hematocrit, left atrial dimension, left ventricular end-diastolic diameter and early deceleration time in a univariate analysis of co-variance model (F=11.097, p=0.001 and F=31.537, p=0.0001, respectively). The present study demonstrated that PV may be associated with electrocardiographic abnormalities of both atrium and ventricle.

PI3K and MEK1/2 molecular pathways are involved in the erythropoietin-mediated regulation of the central respiratory command.

PubMed

Caravagna, Céline; Soliz, Jorge

2015-01-15

Erythropoietin stimulation modulates the central respiratory command in newborn mice. Specifically, the central respiratory depression induced by hypoxia is attenuated by acute (1h) or abolished by chronic erythropoietin stimulation. However, the underlying mechanisms remain unknown. As MEK and PI3K pathways are commonly involved in Epo-mediated effects of neuroprotection and erythropoiesis, we investigated here the implication of PI3K and MEK1/2 in the Epo-mediated regulation of the central respiratory command. To this end, in vitro brainstem-spinal cord preparations from 3 days old transgenic (Tg21; constitutively overexpressing erythropoietin in the brain specifically) and control mice were used. Our results show that blockade of PI3K or MEK1/2 stimulates normoxic bursts frequency in Tg21 preparations and abolish hypoxia-induced frequency depression in control preparations. These results show that MEK1/2 and PI3K pathways are involved in the Epo-mediated regulation of the central respiratory command. Moreover, this is the first demonstration that MEK1/2 and PI3K are involved in the brainstem central respiratory command. Copyright © 2014 Elsevier B.V. All rights reserved.

Load and Pi control flux through the branched kinetic cycle of myosin V.

PubMed

Kad, Neil M; Trybus, Kathleen M; Warshaw, David M

2008-06-20

Myosin V is a processive actin-based motor protein that takes multiple 36-nm steps to deliver intracellular cargo to its destination. In the laser trap, applied load slows myosin V heavy meromyosin stepping and increases the probability of backsteps. In the presence of 40 mm phosphate (P(i)), both forward and backward steps become less load-dependent. From these data, we infer that P(i) release commits myosin V to undergo a highly load-dependent transition from a state in which ADP is bound to both heads and its lead head trapped in a pre-powerstroke conformation. Increasing the residence time in this state by applying load increases the probability of backstepping or detachment. The kinetics of detachment indicate that myosin V can detach from actin at two distinct points in the cycle, one of which is turned off by the presence of P(i). We propose a branched kinetic model to explain these data. Our model includes P(i) release prior to the most load-dependent step in the cycle, implying that P(i) release and load both act as checkpoints that control the flux through two parallel pathways.

Antibody to fibroblast growth factor 23-peptide reduces excreta phosphorus of laying hens.

PubMed

Ren, Zhouzheng; Ebrahimi, Marziyeh; Bütz, Daniel E; Sand, Jordan M; Zhang, Keying; Cook, Mark E

2017-01-01

Novel strategies to minimize the excretion of phosphorus in swine and poultry are critical in minimizing environmental degradation. We have developed a synthetic peptide vaccine to produce autoantibodies to fibroblast growth factor 23 (FGF-23), a bone-derived hormone that blocks kidney phosphate resorption and indirectly reduces intestinal phosphate absorption. Single Comb White Leghorn laying hens, fed a standard diet (inorganic phosphorus, Pi = 0.4%), were immunized over the course of 4 weeks with either a FGF-23 peptide vaccine or adjuvant control (without FGF-23 peptide). At peak antibody titer to the peptide (week 5), 24-h excreta were collected and hens were blood sampled (represents 0.4% Pi treatment). Hens were then fed a 0.8% Pi diet and blood was sampled at 24 and 72 h and 24-h excreta were collected at 12 to 36 and 60 to 84 h (represents 0.8% Pi treatment). Increasing Pi from 0.4 to 0.8% increased (P < 0.05) percent excreta phosphorus, total 24-h phosphorus excretion, and plasma levels of FGF-23 and phosphate in either control or FGF-23 peptide vaccinated hens as early as the first sampling period. FGF-23 peptide vaccinated hens fed 0.4% Pi had reduced (P < 0.05) percent excreta phosphorus, total 24 h phosphorus excretion, and plasma levels of FGF-23 and iPTH, and increased (P < 0.05) plasma levels of phosphate and 1,25(OH) 2 D 3 when compared to control vaccinated hens fed 0.4% Pi. In the first collection period post 0.8% Pi feeding, FGF-23 peptide vaccinated hens had reduced (P < 0.05) plasma levels of FGF-23 and iPTH, and increased (P < 0.05) plasma levels of phosphate and 1,25(OH) 2 D 3 , and tended to have reduced percent excreta phosphorus (P = 0.085) and total 24 h phosphorus excretion (P = 0.078) when compared to control vaccinated hens. Results during the second collection period post 0.8% Pi feeding were similar to that at the first collection period. These results are the first to show that the inhibition of FGF-23 action by a peptide vaccine (via neutralizing antibody) reduced phosphorus excretion. The approach presented provides new information on phosphorus metabolism in the laying hen. © 2016 Poultry Science Association Inc.

[Effect of Buzhong Yiqi decoction on PI3K and AKT in spleen, stomach and lung of nude mice with lung adenocarcinoma transplantation tumor].

PubMed

Liu, Ya-Li; Wang, Ying; Yi, Jia-Li; Jing, Huan; Liu, Chun-Ying

2014-05-01

To explore the effect of Buzhong Yiqi decoction on PI3K/AKT signaling pathway in spleen, stomach and lung of nude mice with lung adenocarcinoma transplantation tumor. Totally 60 nude mice were randomly divided into the blank control group, the tumor-bearing control group, the cisplatin group, the low-dose Buzhong Yiqi decoction group, the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group. After the corresponding interventions, efforts were made to measure the transplanted tumor volume and calculate the tumor inhibiting rate. The immunohistochemical method and real time PCR were used to detect the expression of PI3K and AKT level in nude mice spleen, stomach and lung. Buzhong Yiqi decoction of different concentrations combined with cisplatin could inhibit the growth of the transplanted tumor, with the strongest inhibitory effect in the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group. All of the expressions of PI3K and AKT protein and gene in the spleen, stomach and lung increased, with the most significant increase in the tumor-bearing group. Along with the increase of the concentration of cisplatin and Buzhong Yiqi decoction, the expressions of PI3K and AKT gradually reduced. Compared with the tumor-bearing control group, there were statistical differences in spleen and stomach tissues (P < 0.05). Compared with the cisplatin group, the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group showed statistical differences (P < 0.05), but without statistical difference compared with the blank control group. Among nude mice with lung adenocarcinoma transplantation tumor, the PI3K and AKT protein and gene expressions in spleen, stomach and lung tissues increased, which might indicated the effect of cisplatin and Buzhong Yiqi decoction in reducing PI3K and AKT expressions and the relations between the reduction degree and the concentrations of Buzhong Yiqi decoction. Cisplatin combined with Buzhong Yiqi decoction could decrease the PI3K and AKT protein and gene expression in spleen, stomach and lung, and make the pathway closer to normal, so as to protect the functions of spleen, stomach and lung, there may be target spots of Buzhong Yiqi decoction in PI3K/AKT signal pathway.

The fractional Fourier transform and applications

NASA Technical Reports Server (NTRS)

Bailey, David H.; Swarztrauber, Paul N.

1991-01-01

This paper describes the 'fractional Fourier transform', which admits computation by an algorithm that has complexity proportional to the fast Fourier transform algorithm. Whereas the discrete Fourier transform (DFT) is based on integral roots of unity e exp -2(pi)i/n, the fractional Fourier transform is based on fractional roots of unity e exp -2(pi)i(alpha), where alpha is arbitrary. The fractional Fourier transform and the corresponding fast algorithm are useful for such applications as computing DFTs of sequences with prime lengths, computing DFTs of sparse sequences, analyzing sequences with noninteger periodicities, performing high-resolution trigonometric interpolation, detecting lines in noisy images, and detecting signals with linearly drifting frequencies. In many cases, the resulting algorithms are faster by arbitrarily large factors than conventional techniques.

Low Emittance, High Brilliance Relativistic Electron Beams from a Laser-Plasma Accelerator

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

Brunetti, E.; Shanks, R. P.; Manahan, G. G.

2010-11-19

Progress in laser wakefield accelerators indicates their suitability as a driver of compact free-electron lasers (FELs). High brightness is defined by the normalized transverse emittance, which should be less than 1{pi} mm mrad for an x-ray FEL. We report high-resolution measurements of the emittance of 125 MeV, monoenergetic beams from a wakefield accelerator. An emittance as low as 1.1{+-}0.1{pi} mm mrad is measured using a pepper-pot mask. This sets an upper limit on the emittance, which is comparable with conventional linear accelerators. A peak transverse brightness of 5x10{sup 15} A m{sup -1} rad{sup -1} makes it suitable for compact XUVmore » FELs.« less

POLI-mix functional food enhances steady-state bioenergetic status independently of age: an experimental study.

PubMed

Rastmanesh, Reza; Marotta, Francesco; Kantah, Makoto Keiichi; Nagpal, Ravinder; Lorenzetti, Aldo; Takadanohara, Hiroshi; Mashizume, Hiroshi; Kobayashi, Riyichi; Chui, De Hua

2012-04-01

BALB/c mice were divided into young, middle-aged, and aged groups, and each group was given 3 weeks of oral treatments: (1) 1 mL of VBC1-99 (a mixture of 42 fruits and vegetables extracts) or (2) 1 mL of same amount of antioxidant vitamins as control. Steady-state hepatic adenosine triphosphate (ATP) was assessed by phosphorus-31 nuclear magnetic resonance ((31)P-NMR) spectroscopy as: β-ATP/reference peak, inorganic phosphorus (Pi)/peak and β-ATP/Pi. As compared to untreated control, VBC1-99 significantly enhanced β-ATP/peak and β-ATP/Pi ratios (p<0.01) in all age groups and throughout the observation period (p<0.05) together with a significant decrease of Pi/ref peak ratio (p<0.05). However, this value in middle-aged and aged mice was comparable to antioxidant control mice. These NMR data demonstrate that VBC1-99 has a beneficial effect on hepatic energy metabolism, irrespective of age.

Α₁-antitrypsin PiMZ heterozygosity has an independent aggravating effect on liver fibrosis in alcoholic liver disease.

PubMed

Goltz, Diane; Hittetiya, Kanishka; Vössing, Lena Marie; Kirfel, Jutta; Spengler, Ulrich; Fischer, Hans-Peter

2014-11-01

Heterozygous α1-antitrypsin deficiency type PiZ (PiMZ) results in chronic liver injury and predisposes to hepatocellular carcinoma. Gene frequency of the PiZ allele ranges from 0.005 to 0.027 in Western and Central Europe; therefore, there is a substantial risk of coincidence with chronic alcohol abuse. This retrospective case-control study evaluates the impact of PiMZ genotype on the development of chronic liver disease in alcohol consuming patients. Six thousand eight hundred eighty-six consecutive liver specimens were immunohistochemically tested for PiZ-deposits. From 254 PiZ-positive patients, the liver biopsies of 30 PiMZ adults without concomitant liver disease other than alcoholic liver disease (ALD) were selected and matched to PiMM (wild type) patients with respect to age, gender and lifetime daily alcohol ingestion (LDAI). Histomorphological changes were assessed using the SAF score and by digital image analysis. Liver cirrhosis was significantly more frequent in PIMZ patients than in matched PiMM patients (PiMM 9/30 vs. PiMZ 14/30, p = 0.04). Comparison of the extent of fibrosis in PiMZ and PiMM livers by two-way ANOVA indicated that the amount of LDAI has a major effect in PiMZ and PiMM patients (30.04 % of total variation, p < 0.0001), whereas PIMZ genotype has a minor but independent effect on liver fibrosis as assessed by digital planimetric evaluation (9.27 % of total variation, p = 0.005). Semiquantitative assessment was in agreement with this finding. Histomorphological findings support that PiMZ heterozygosity has an independent aggravating effect on liver fibrosis, even though the pathogenic effect of alcohol consumption is much stronger.

Effect of saw palmetto extract on PI3K cell signaling transduction in human glioma.

PubMed

Yang, Yang; Hui, Lv; Yuqin, Che; Jie, Li; Shuai, Hou; Tiezhu, Zhou; Wei, Wang

2014-08-01

Saw palmetto extract can induce the apoptosis of prostate cancer cells. The aim of the present study was to investigate the effect of saw palmetto extract on the phosphatidylinositol 3-kinase (PI3K)/Akt signaling transduction pathway in human glioma U87 and U251 cell lines. Suspensions of U87 and U251 cells in a logarithmic growth phase were seeded into six-well plates at a density of 10 4 cells/well. In the experimental group, 1 μl/ml saw palmetto extract was added, while the control group was cultured without a drug for 24 h. The expression levels of PI3K, B-cell lymphoma-extra large (Bcl-xL) and p53 were evaluated through western blot analysis. In the experimental group, the U87 and U251 cells exhibited a lower expression level of PI3K protein as compared with the control group (t=6.849; P<0.001). In addition, the two cell lines had a higher expression level of p53 protein in the experimental group as compared with the control group (t=40.810; P<0.001). Protein expression levels of Bcl-xL decreased significantly in the experimental group as compared with the control group (t=19.640; P=0.000). Therefore, saw palmetto extract induces glioma cell growth arrest and apoptosis via decreasing PI3K/Akt signal transduction.

Nucleon form factors in dispersively improved chiral effective field theory: Scalar form factor

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

Alarcon Soriano, Jose Manuel; Weiss, Christian

We propose a method for calculating the nucleon form factors (FFs) ofmore » $G$-parity-even operators by combining Chiral Effective Field Theory ($$\\chi$$EFT) and dispersion analysis. The FFs are expressed as dispersive integrals over the two-pion cut at $$t > 4 M_\\pi^2$$. The spectral functions are obtained from the elastic unitarity condition and expressed as products of the complex $$\\pi\\pi \\rightarrow N\\bar N$$ partial-wave amplitudes and the timelike pion FF. $$\\chi$$EFT is used to calculate the ratio of the partial-wave amplitudes and the pion FF, which is real and free of $$\\pi\\pi$$ rescattering in the $t$-channel ($N/D$ method). The rescattering effects are then incorporated by multiplying with the squared modulus of the empirical pion FF. The procedure results in a marked improvement compared to conventional $$\\chi$$EFT calculations of the spectral functions. We apply the method to the nucleon scalar FF and compute the scalar spectral function, the scalar radius, the $t$-dependent FF, and the Cheng-Dashen discrepancy. Higher-order chiral corrections are estimated through the $$\\pi N$$ low-energy constants. Results are in excellent agreement with dispersion-theoretical calculations. We elaborate several other interesting aspects of our method. The results show proper scaling behavior in the large-$$N_c$$ limit of QCD because the $$\\chi$$EFT includes $N$ and $$\\Delta$$ intermediate states. The squared modulus of the timelike pion FF required by our method can be extracted from Lattice QCD calculations of vacuum correlation functions of the operator at large Euclidean distances. Our method can be applied to the nucleon FFs of other operators of interest, such as the isovector-vector current, the energy-momentum tensor, and twist-2 QCD operators (moments of generalized parton distributions).« less

Nucleon form factors in dispersively improved chiral effective field theory: Scalar form factor

DOE PAGES

Alarcon Soriano, Jose Manuel; Weiss, Christian

2017-11-20

We propose a method for calculating the nucleon form factors (FFs) ofmore » $G$-parity-even operators by combining Chiral Effective Field Theory ($$\\chi$$EFT) and dispersion analysis. The FFs are expressed as dispersive integrals over the two-pion cut at $$t > 4 M_\\pi^2$$. The spectral functions are obtained from the elastic unitarity condition and expressed as products of the complex $$\\pi\\pi \\rightarrow N\\bar N$$ partial-wave amplitudes and the timelike pion FF. $$\\chi$$EFT is used to calculate the ratio of the partial-wave amplitudes and the pion FF, which is real and free of $$\\pi\\pi$$ rescattering in the $t$-channel ($N/D$ method). The rescattering effects are then incorporated by multiplying with the squared modulus of the empirical pion FF. The procedure results in a marked improvement compared to conventional $$\\chi$$EFT calculations of the spectral functions. We apply the method to the nucleon scalar FF and compute the scalar spectral function, the scalar radius, the $t$-dependent FF, and the Cheng-Dashen discrepancy. Higher-order chiral corrections are estimated through the $$\\pi N$$ low-energy constants. Results are in excellent agreement with dispersion-theoretical calculations. We elaborate several other interesting aspects of our method. The results show proper scaling behavior in the large-$$N_c$$ limit of QCD because the $$\\chi$$EFT includes $N$ and $$\\Delta$$ intermediate states. The squared modulus of the timelike pion FF required by our method can be extracted from Lattice QCD calculations of vacuum correlation functions of the operator at large Euclidean distances. Our method can be applied to the nucleon FFs of other operators of interest, such as the isovector-vector current, the energy-momentum tensor, and twist-2 QCD operators (moments of generalized parton distributions).« less

Splicing-independent loading of TREX on nascent RNA is required for efficient expression of dual-strand piRNA clusters in Drosophila

PubMed Central

Hur, Junho K.; Luo, Yicheng; Moon, Sungjin; Ninova, Maria; Marinov, Georgi K.; Chung, Yun D.; Aravin, Alexei A.

2016-01-01

The conserved THO/TREX (transcription/export) complex is critical for pre-mRNA processing and mRNA nuclear export. In metazoa, TREX is loaded on nascent RNA transcribed by RNA polymerase II in a splicing-dependent fashion; however, how TREX functions is poorly understood. Here we show that Thoc5 and other TREX components are essential for the biogenesis of piRNA, a distinct class of small noncoding RNAs that control expression of transposable elements (TEs) in the Drosophila germline. Mutations in TREX lead to defects in piRNA biogenesis, resulting in derepression of multiple TE families, gametogenesis defects, and sterility. TREX components are enriched on piRNA precursors transcribed from dual-strand piRNA clusters and colocalize in distinct nuclear foci that overlap with sites of piRNA transcription. The localization of TREX in nuclear foci and its loading on piRNA precursor transcripts depend on Cutoff, a protein associated with chromatin of piRNA clusters. Finally, we show that TREX is required for accumulation of nascent piRNA precursors. Our study reveals a novel splicing-independent mechanism for TREX loading on nascent RNA and its importance in piRNA biogenesis. PMID:27036967

Reduced Warburg Effect in Cancer Cells Undergoing Autophagy: Steady- State 1H-MRS and Real-Time Hyperpolarized 13C-MRS Studies

PubMed Central

Wong Te Fong, Anne-Christine; Hill, Deborah K.; Orton, Matthew R.; Parkes, Harry G.; Koh, Dow-Mu; Robinson, Simon P.; Leach, Martin O.; Eykyn, Thomas R.; Chung, Yuen-Li

2014-01-01

Autophagy is a highly regulated, energy dependent cellular process where proteins, organelles and cytoplasm are sequestered in autophagosomes and digested to sustain cellular homeostasis. We hypothesized that during autophagy induced in cancer cells by i) starvation through serum and amino acid deprivation or ii) treatment with PI-103, a class I PI3K/mTOR inhibitor, glycolytic metabolism would be affected, reducing flux to lactate, and that this effect may be reversible. We probed metabolism during autophagy in colorectal HT29 and HCT116 Bax knock-out cells using hyperpolarized 13C-magnetic resonance spectroscopy (MRS) and steady-state 1H-MRS. 24 hr PI103-treatment or starvation caused significant reduction in the apparent forward rate constant (kPL) for pyruvate to lactate exchange compared with controls in HT29 (100 μM PI-103: 82%, p = 0.05) and HCT116 Bax-ko cells (10 μM PI-103: 53%, p = 0.05; 20 μM PI-103: 42%, p<0.0001; starvation: 52%, p<0.001), associated with reduced lactate excretion and intracellular lactate in all cases, and unchanged lactate dehydrogenase (LDH) activity and increased NAD+/NADH ratio following PI103 treatment or decreased LDH activity and unchanged NAD+/NADH ratio following starvation. After 48 hr recovery from PI103 treatment, kPL remained below control levels in HT29 cells (74%, p = 0.02), and increased above treated values, but remained below 24 hr vehicle-treated control levels in HCT116 Bax-ko cells (65%, p = 0.004) both were accompanied by sustained reduction in lactate excretion, recovery of NAD+/NADH ratio and intracellular lactate. Following recovery from starvation, kPL was significantly higher than 24 hr vehicle-treated controls (140%, p = 0.05), associated with increased LDH activity and total cellular NAD(H). Changes in kPL and cellular and excreted lactate provided measureable indicators of the major metabolic processes accompanying starvation- and drug-induced autophagy. The changes are reversible, returning towards and exceeding control values on cellular recovery, which potentially identifies resistance. kPL (hyperpolarized 13C-MRS) and lactate (1H-MRS) provide useful biomarkers for the autophagic process, enabling non-invasive monitoring of the Warburg effect. PMID:24667972

PI and repetitive control for single phase inverter based on virtual rotating coordinate system

NASA Astrophysics Data System (ADS)

Li, Mengqi; Tong, Yibin; Jiang, Jiuchun; Liang, Jiangang

2018-03-01

Microgrid technology developed rapidly and nonlinear loads were connected increasingly. A new control strategy was proposed for single phase inverter when connected nonlinear loads under island condition. PI and repetitive compound controller was realized under synchronous rotating coordinate system and acquired high quality sinusoidal voltage output without voltage spike when loads step changed. Validity and correctness were verified by simulation using MATLAB/Simulink.

Role of PDZK1 Protein in Apical Membrane Expression of Renal Sodium-coupled Phosphate Transporters*

PubMed Central

Giral, Hector; Lanzano, Luca; Caldas, Yupanqui; Blaine, Judith; Verlander, Jill W.; Lei, Tim; Gratton, Enrico; Levi, Moshe

2011-01-01

The sodium-dependent phosphate (Na/Pi) transporters NaPi-2a and NaPi-2c play a major role in the renal reabsorption of Pi. The functional need for several transporters accomplishing the same role is still not clear. However, the fact that these transporters show differential regulation under dietary and hormonal stimuli suggests different roles in Pi reabsorption. The pathways controlling this differential regulation are still unknown, but one of the candidates involved is the NHERF family of scaffolding PDZ proteins. We propose that differences in the molecular interaction with PDZ proteins are related with the differential adaptation of Na/Pi transporters. Pdzk1−/− mice adapted to chronic low Pi diets showed an increased expression of NaPi-2a protein in the apical membrane of proximal tubules but impaired up-regulation of NaPi-2c. These results suggest an important role for PDZK1 in the stabilization of NaPi-2c in the apical membrane. We studied the specific protein-protein interactions of Na/Pi transporters with NHERF-1 and PDZK1 by FRET. FRET measurements showed a much stronger interaction of NHERF-1 with NaPi-2a than with NaPi-2c. However, both Na/Pi transporters showed similar FRET efficiencies with PDZK1. Interestingly, in cells adapted to low Pi concentrations, there were increases in NaPi-2c/PDZK1 and NaPi-2a/NHERF-1 interactions. The differential affinity of the Na/Pi transporters for NHERF-1 and PDZK1 proteins could partially explain their differential regulation and/or stability in the apical membrane. In this regard, direct interaction between NaPi-2c and PDZK1 seems to play an important role in the physiological regulation of NaPi-2c. PMID:21388960

Artificial “ping-pong” cascade of PIWI-interacting RNA in silkworm cells

PubMed Central

Shoji, Keisuke; Suzuki, Yutaka; Sugano, Sumio; Shimada, Toru; Katsuma, Susumu

2017-01-01

PIWI-interacting RNAs (piRNAs) play essential roles in the defense system against selfish elements in animal germline cells by cooperating with PIWI proteins. A subset of piRNAs is predicted to be generated via the “ping-pong” cascade, which is mainly controlled by two different PIWI proteins. Here we established a cell-based artificial piRNA production system using a silkworm ovarian cultured cell line that is believed to possess a complete piRNA pathway. In addition, we took advantage of a unique silkworm sex-determining one-to-one ping-pong piRNA pair, which enabled us to precisely monitor the behavior of individual artificial piRNAs. With this novel strategy, we successfully generated artificial piRNAs against endogenous protein-coding genes via the expected back-and-forth traveling mechanism. Furthermore, we detected “primary” piRNAs from the upstream region of the artificial “ping-pong” site in the endogenous gene. This artificial piRNA production system experimentally confirms the existence of the “ping-pong” cascade of piRNAs. Also, this system will enable us to identify the factors involved in both, or each, of the “ping” and “pong” cascades and the sequence features that are required for efficient piRNA production. PMID:27777367

Induction motor speed control using varied duty cycle terminal voltage via PI controller

NASA Astrophysics Data System (ADS)

Azwin, A.; Ahmed, S.

2018-03-01

This paper deals with the PI speed controller for the three-phase induction motor using PWM technique. The PWM generated signal is utilized for voltage source inverter with an optimal duty cycle on a simplified induction motor model. A control algorithm for generating PWM control signal is developed. Obtained results shows that the steady state error and overshoot of the developed system is in the limit under different speed and load condition. The robustness of the control performance would be potential for induction motor performance improvement.

Correction of hypophosphatasia (HPP) associated mineralization deficiencies in vitro by phosphate/pyrophosphate modulation in periodontal ligament cells

PubMed Central

Rodrigues, Thaisângela L.; Foster, Brian L.; Silverio, Karina G.; Martins, Luciane; Casati, Marcio Z.; Sallum, Enilson A.; Somerman, Martha J.; Nociti, Francisco H.

2013-01-01

Background Mutations in the Alpl gene in hypophosphatasia (HPP) reduce the function of tissue nonspecific alkaline phosphatase (TNAP), resulting in increased pyrophosphate (PPi) and a severe deficiency in acellular cementum. We hypothesized that exogenous phosphate (Pi) would rescue the in vitro mineralization capacity of periodontal ligament (PDL) cells harvested from HPP-diagnosed subjects, by correcting Pi/PPi ratio and modulating expression of genes involved with Pi/PPi metabolism. Methods Ex vivo and in vitro analyses were employed to identify mechanisms involved in HPP-associated PDL/tooth root deficiencies. Constitutive expression of PPi-associated genes was contrasted in PDL versus pulp tissues obtained from healthy subjects. Primary PDL cell cultures from HPP subjects (monozygotic twin males) were established to assay alkaline phosphatase activity (ALP), in vitro mineralization, and gene expression. Exogenous Pi was provided to correct Pi/PPi ratio. Results PDL tissues obtained from healthy individuals featured higher basal expression of key PPi regulators, genes Alpl, progressive ankylosis protein (Ankh) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1), versus paired pulp tissues. A novel Alpl mutation was identified in the twin HPP subjects enrolled in this study. Compared to controls, HPP-PDL cells exhibited significantly reduced ALP and mineralizing capacity, which were rescued by addition of 1mM Pi. Dysregulated expression of PPi regulatory genes Alpl, Ankh, and Enpp1 was also corrected by adding Pi, though other matrix markers evaluated in our study remained down-regulated. Conclusions These findings underscore the importance of controlling Pi/PPi ratio toward development of a functional periodontal apparatus, and support Pi/PPi imbalance as the etiology of HPP-associated cementum defects. PMID:22014174

Online intelligent controllers for an enzyme recovery plant: design methodology and performance.

PubMed

Leite, M S; Fujiki, T L; Silva, F V; Fileti, A M F

2010-12-27

This paper focuses on the development of intelligent controllers for use in a process of enzyme recovery from pineapple rind. The proteolytic enzyme bromelain (EC 3.4.22.4) is precipitated with alcohol at low temperature in a fed-batch jacketed tank. Temperature control is crucial to avoid irreversible protein denaturation. Fuzzy or neural controllers offer a way of implementing solutions that cover dynamic and nonlinear processes. The design methodology and a comparative study on the performance of fuzzy-PI, neurofuzzy, and neural network intelligent controllers are presented. To tune the fuzzy PI Mamdani controller, various universes of discourse, rule bases, and membership function support sets were tested. A neurofuzzy inference system (ANFIS), based on Takagi-Sugeno rules, and a model predictive controller, based on neural modeling, were developed and tested as well. Using a Fieldbus network architecture, a coolant variable speed pump was driven by the controllers. The experimental results show the effectiveness of fuzzy controllers in comparison to the neural predictive control. The fuzzy PI controller exhibited a reduced error parameter (ITAE), lower power consumption, and better recovery of enzyme activity.

Online Intelligent Controllers for an Enzyme Recovery Plant: Design Methodology and Performance

PubMed Central

Leite, M. S.; Fujiki, T. L.; Silva, F. V.; Fileti, A. M. F.

2010-01-01

This paper focuses on the development of intelligent controllers for use in a process of enzyme recovery from pineapple rind. The proteolytic enzyme bromelain (EC 3.4.22.4) is precipitated with alcohol at low temperature in a fed-batch jacketed tank. Temperature control is crucial to avoid irreversible protein denaturation. Fuzzy or neural controllers offer a way of implementing solutions that cover dynamic and nonlinear processes. The design methodology and a comparative study on the performance of fuzzy-PI, neurofuzzy, and neural network intelligent controllers are presented. To tune the fuzzy PI Mamdani controller, various universes of discourse, rule bases, and membership function support sets were tested. A neurofuzzy inference system (ANFIS), based on Takagi-Sugeno rules, and a model predictive controller, based on neural modeling, were developed and tested as well. Using a Fieldbus network architecture, a coolant variable speed pump was driven by the controllers. The experimental results show the effectiveness of fuzzy controllers in comparison to the neural predictive control. The fuzzy PI controller exhibited a reduced error parameter (ITAE), lower power consumption, and better recovery of enzyme activity. PMID:21234106

Cbp80 is needed for the expression of piRNA components and piRNAs

PubMed Central

Colombo, Martino; Hernandez, Greco; Beuchle, Dirk; Berger, Fabienne; Peischl, Stephan; Bruggmann, Rémy

2017-01-01

Cap binding protein 80 (Cbp80) is the larger subunit of the nuclear cap-binding complex (nCBC), which is known to play important roles in nuclear mRNA processing, export, stability and quality control events. Reducing Cbp80 mRNA levels in the female germline revealed that Cbp80 is also involved in defending the germline against transposable elements. Combining such knockdown experiments with large scale sequencing of small RNAs further showed that Cbp80 is involved in the initial biogenesis of piRNAs as well as in the secondary biogenesis pathway, the ping-pong amplification cycle. We further found that Cbp80 knockdown not only led to the upregulation of transposons, but also to delocalization of Piwi, Aub and Ago3, key factors in the piRNA biosynthesis pathway. Furthermore, compared to controls, levels of Piwi and Aub were also reduced upon knock down of Cbp80. On the other hand, with the same treatment we could not detect significant changes in levels or subcellular distribution (nuage localization) of piRNA precursor transcripts. This shows that Cbp80 plays an important role in the production and localization of the protein components of the piRNA pathway and it seems to be less important for the production and export of the piRNA precursor transcripts. PMID:28746365

Effects of upright weight bearing and the knee flexion angle on patellofemoral indices using magnetic resonance imaging in patients with patellofemoral instability.

PubMed

Becher, Christoph; Fleischer, Benjamin; Rase, Marten; Schumacher, Thees; Ettinger, Max; Ostermeier, Sven; Smith, Tomas

2017-08-01

This study analysed the effects of upright weight bearing and the knee flexion angle on patellofemoral indices, determined using magnetic resonance imaging (MRI), in patients with patellofemoral instability (PI). Healthy volunteers (control group, n = 9) and PI patients (PI group, n = 16) were scanned in an open-configuration MRI scanner during upright weight bearing and supine non-weight bearing positions at full extension (0° flexion) and at 15°, 30°, and 45° flexion. Patellofemoral indices included the Insall-Salvati Index, Caton-Deschamp Index, and Patellotrochlear Index (PTI) to determine patellar height and the patellar tilt angle (PTA), bisect offset (BO), and the tibial tubercle-trochlear groove (TT-TG) distance to assess patellar rotation and translation with respect to the femur and alignment of the extensor mechanism. A significant interaction effect of weight bearing by flexion angle was observed for the PTI, PTA, and BO for subjects with PI. At full extension, post hoc pairwise comparisons revealed a significant effect of weight bearing on the indices, with increased patellar height and increased PTA and BO in the PI group. Except for the BO, no such changes were seen in the control group. Independent of weight bearing, flexing the knee caused the PTA, BO, and TT-TG distance to be significantly reduced. Upright weight bearing and the knee flexion angle affected patellofemoral MRI indices in PI patients, with significantly increased values at full extension. The observations of this study provide a caution to be considered by professionals when treating PI patients. These patients should be evaluated clinically and radiographically at full extension and various flexion angles in context with quadriceps engagement. Explorative case-control study, Level III.

Apoptosis regulator through modulating IAP expression (ARIA) controls the PI3K/Akt pathway in endothelial and endothelial progenitor cells.

PubMed

Koide, Masahiro; Ikeda, Koji; Akakabe, Yoshiki; Kitamura, Youhei; Ueyama, Tomomi; Matoba, Satoaki; Yamada, Hiroyuki; Okigaki, Mitsuhiko; Matsubara, Hiroaki

2011-06-07

Endothelial and endothelial progenitor cells (ECs and EPCs) play a fundamental role in angiogenesis that is essential for numerous physiological and pathological processes. The phosphatase and tensin homolog (PTEN)/ phosphoinositide 3-kinase (PI3K) pathway has been implicated in angiogenesis, but the mechanism in the regulation of this pathway in ECs and EPCs is poorly understood. Here we show that ARIA (apoptosis regulator through modulating IAP expression), a transmembrane protein that we recently identified, regulates the PTEN/PI3K pathway in ECs and EPCs and controls developmental and postnatal angiogenesis in vivo. We found that ARIA is abundantly expressed in EPCs and regulates their angiogenic functions by modulating PI3K/Akt/endothelial nitric oxide synthase (eNOS) signaling. Genetic deletion of ARIA caused nonfatal bleeding during embryogenesis, in association with increased small vessel density and altered expression of various vascular growth factors including angiopoietins and VEGF receptors. Postnatal neovascularization induced by critical limb ischemia was substantially enhanced in ARIA-null mice, in conjunction with more bone marrow (BM)-derived ECs detected in ischemic muscles. Administration of PI3K or NO synthase inhibitor completely abolished the enhanced neovascularization in ARIA(-/-) mice. Mechanistically, we identified that ARIA interacts with PTEN at the intracellular domain independently of the PTEN phosphorylation in its C-terminal tail. Overexpressed ARIA increased PTEN in the membrane fraction, whereas ARIA-silencing reduced the membrane-associated PTEN, resulting in modified PI3K/Akt signaling. Taken together, our findings establish a previously undescribed mode of regulation of the PTEN/PI3K/Akt pathway by ARIA, and reveal a unique mechanism in the control of angiogenesis. These functions of ARIA might offer a unique therapeutic potential.

Drug Hypersensitivity: How Drugs Stimulate T Cells via Pharmacological Interaction with Immune Receptors.

PubMed

Pichler, Werner J; Adam, Jacqueline; Watkins, Stephen; Wuillemin, Natascha; Yun, James; Yerly, Daniel

2015-01-01

Small chemicals like drugs tend to bind to proteins via noncovalent bonds, e.g. hydrogen bonds, salt bridges or electrostatic interactions. Some chemicals interact with other molecules than the actual target ligand, representing so-called 'off-target' activities of drugs. Such interactions are a main cause of adverse side effects to drugs and are normally classified as predictable type A reactions. Detailed analysis of drug-induced immune reactions revealed that off-target activities also affect immune receptors, such as highly polymorphic human leukocyte antigens (HLA) or T cell receptors (TCR). Such drug interactions with immune receptors may lead to T cell stimulation, resulting in clinical symptoms of delayed-type hypersensitivity. They are assigned the 'pharmacological interaction with immune receptors' (p-i) concept. Analysis of p-i has revealed that drugs bind preferentially or exclusively to distinct HLA molecules (p-i HLA) or to distinct TCR (p-i TCR). P-i reactions differ from 'conventional' off-target drug reactions as the outcome is not due to the effect on the drug-modified cells themselves, but is the consequence of reactive T cells. Hence, the complex and diverse clinical manifestations of delayed-type hypersensitivity are caused by the functional heterogeneity of T cells. In the abacavir model of p-i HLA, the drug binding to HLA may result in alteration of the presenting peptides. More importantly, the drug binding to HLA generates a drug-modified HLA, which stimulates T cells directly, like an allo-HLA. In the sulfamethoxazole model of p-i TCR, responsive T cells likely require costimulation for full T cell activation. These findings may explain the similarity of delayed-type hypersensitivity reactions to graft-versus-host disease, and how systemic viral infections increase the risk of delayed-type hypersensitivity reactions. © 2015 The Author(s) Published by S. Karger AG, Basel.

Targeting Phosphoinositide 3-Kinase γ in Airway Smooth Muscle Cells to Suppress Interleukin-13-Induced Mouse Airway Hyperresponsiveness

PubMed Central

Jiang, Haihong; Xie, Yan; Abel, Peter W.; Toews, Myron L.; Townley, Robert G.; Casale, Thomas B.

2012-01-01

We recently reported that phosphoinositide 3-kinase γ (PI3Kγ) directly regulates airway smooth muscle (ASM) contraction by modulating Ca2+ oscillations. Because ASM contraction plays a critical role in airway hyperresponsiveness (AHR) of asthma, the aim of the present study was to determine whether targeting PI3Kγ in ASM cells could suppress AHR in vitro and in vivo. Intranasal administration into mice of interleukin-13 (IL-13; 10 μg per mouse), a key pathophysiologic cytokine in asthma, induced AHR after 48 h, as assessed by invasive tracheostomy. Intranasal administration of a broad-spectrum PI3K inhibitor or a PI3Kγ-specific inhibitor 1 h before AHR assessment attenuated IL-13 effects. Airway responsiveness to bronchoconstrictor agonists was also examined in precision-cut mouse lung slices pretreated without or with IL-13 for 24 h. Acetylcholine and serotonin dose-response curves indicated that IL-13-treated lung slices had a 40 to 50% larger maximal airway constriction compared with controls. Furthermore, acetylcholine induced a larger initial Ca2+ transient and increased Ca2+ oscillations in IL-13-treated primary mouse ASM cells compared with control cells, correlating with increased cell contraction. As expected, PI3Kγ inhibitor treatment attenuated IL-13-augmented airway contractility of lung slices and ASM cell contraction. In both control and IL-13-treated ASM cells, small interfering RNA-mediated knockdown of PI3Kγ by 70% only reduced the initial Ca2+ transient by 20 to 30% but markedly attenuated Ca2+ oscillations and contractility of ASM cells by 50 to 60%. This report is the first to demonstrate that PI3Kγ in ASM cells is important for IL-13-induced AHR and that acute treatment with a PI3Kγ inhibitor can ameliorate AHR in a murine model of asthma. PMID:22543031

Mycorrhizal phosphate uptake pathway in maize: vital for growth and cob development on nutrient poor agricultural and greenhouse soils

PubMed Central

Willmann, Martin; Gerlach, Nina; Buer, Benjamin; Polatajko, Aleksandra; Nagy, Réka; Koebke, Eva; Jansa, Jan; Flisch, René; Bucher, Marcel

2013-01-01

Arbuscular mycorrhizal fungi (AMF) form a mutually beneficial symbiosis with plant roots providing predominantly phosphorus in the form of orthophosphate (Pi) in exchange for plant carbohydrates on low P soils. The goal of this work was to generate molecular-genetic evidence in support of a major impact of the mycorrhizal Pi uptake (MPU) pathway on the productivity of the major crop plant maize under field and controlled conditions. Here we show, that a loss-of-function mutation in the mycorrhiza-specific Pi transporter gene Pht1;6 correlates with a dramatic reduction of above-ground biomass and cob production in agro-ecosystems with low P soils. In parallel mutant pht1;6 plants exhibited an altered fingerprint of chemical elements in shoots dependent on soil P availability. In controlled environments mycorrhiza development was impaired in mutant plants when grown alone. The presence of neighboring mycorrhizal nurse plants enhanced the reduced mycorrhiza formation in pht1;6 roots. Uptake of 33P-labeled orthophosphate via the MPU pathway was strongly impaired in colonized mutant plants. Moreover, repression of the MPU pathway resulted in a redirection of Pi to neighboring plants. In line with previous results, our data highlight the relevance of the MPU pathway in Pi allocation within plant communities and in particular the role of Pht1;6 for the establishment of symbiotic Pi uptake and for maize productivity and nutritional value in low-input agricultural systems. In a first attempt to identify cellular pathways which are affected by Pht1;6 activity, gene expression profiling via RNA-Seq was performed and revealed a set of maize genes involved in cellular signaling which exhibited differential regulation in mycorrhizal pht1;6 and control plants. The RNA data provided support for the hypothesis that fungal supply of Pi and/or Pi transport across Pht1;6 affects cell wall biosynthesis and hormone metabolism in colonized root cells. PMID:24409191

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

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

External force/velocity control for an autonomous rehabilitation robot

NASA Astrophysics Data System (ADS)

Saekow, Peerayuth; Neranon, Paramin; Smithmaitrie, Pruittikorn

2018-01-01

Stroke is a primary cause of death and the leading cause of permanent disability in adults. There are many stroke survivors, who live with a variety of levels of disability and always need rehabilitation activities on daily basis. Several studies have reported that usage of rehabilitation robotic devices shows the better improvement outcomes in upper-limb stroke patients than the conventional therapy-nurses or therapists actively help patients with exercise-based rehabilitation. This research focuses on the development of an autonomous robotic trainer designed to guide a stroke patient through an upper-limb rehabilitation task. The robotic device was designed and developed to automate the reaching exercise as mentioned. The designed robotic system is made up of a four-wheel omni-directional mobile robot, an ATI Gamma multi-axis force/torque sensor used to measure contact force and a microcontroller real-time operating system. Proportional plus Integral control was adapted to control the overall performance and stability of the autonomous assistive robot. External force control was successfully implemented to establish the behavioral control strategy for the robot force and velocity control scheme. In summary, the experimental results indicated satisfactorily stable performance of the robot force and velocity control can be considered acceptable. The gain tuning for proportional integral (PI) velocity control algorithms was suitably estimated using the Ziegler-Nichols method in which the optimized proportional and integral gains are 0.45 and 0.11, respectively. Additionally, the PI external force control gains were experimentally tuned using the trial and error method based on a set of experiments which allow a human participant moves the robot along the constrained circular path whilst attempting to minimize the radial force. The performance was analyzed based on the root mean square error (E_RMS) of the radial forces, in which the lower the variation in radial forces, the better the performance of the system. The outstanding performance of the tests as specified by the E_RMS of the radial force was observed with proportional and integral gains of Kp = 0.7 and Ki = 0.75, respectively.

Novel Formulation of Adaptive MPC as EKF Using ANN Model: Multiproduct Semibatch Polymerization Reactor Case Study.

PubMed

Kamesh, Reddi; Rani, Kalipatnapu Yamuna

2017-12-01

In this paper, a novel formulation for nonlinear model predictive control (MPC) has been proposed incorporating the extended Kalman filter (EKF) control concept using a purely data-driven artificial neural network (ANN) model based on measurements for supervisory control. The proposed scheme consists of two modules focusing on online parameter estimation based on past measurements and control estimation over control horizon based on minimizing the deviation of model output predictions from set points along the prediction horizon. An industrial case study for temperature control of a multiproduct semibatch polymerization reactor posed as a challenge problem has been considered as a test bed to apply the proposed ANN-EKFMPC strategy at supervisory level as a cascade control configuration along with proportional integral controller [ANN-EKFMPC with PI (ANN-EKFMPC-PI)]. The proposed approach is formulated incorporating all aspects of MPC including move suppression factor for control effort minimization and constraint-handling capability including terminal constraints. The nominal stability analysis and offset-free tracking capabilities of the proposed controller are proved. Its performance is evaluated by comparison with a standard MPC-based cascade control approach using the same adaptive ANN model. The ANN-EKFMPC-PI control configuration has shown better controller performance in terms of temperature tracking, smoother input profiles, as well as constraint-handling ability compared with the ANN-MPC with PI approach for two products in summer and winter. The proposed scheme is found to be versatile although it is based on a purely data-driven model with online parameter estimation.

Effect of Npt2b deletion on intestinal and renal inorganic phosphate (Pi) handling.

PubMed

Ikuta, Kayo; Segawa, Hiroko; Sasaki, Shohei; Hanazaki, Ai; Fujii, Toru; Kushi, Aoi; Kawabata, Yuka; Kirino, Ruri; Sasaki, Sumire; Noguchi, Miwa; Kaneko, Ichiro; Tatsumi, Sawako; Ueda, Otoya; Wada, Naoko A; Tateishi, Hiromi; Kakefuda, Mami; Kawase, Yosuke; Ohtomo, Shuichi; Ichida, Yasuhiro; Maeda, Akira; Jishage, Kou-Ichi; Horiba, Naoshi; Miyamoto, Ken-Ichi

2018-06-01

Hyperphosphatemia is common in chronic kidney disease and is associated with morbidity and mortality. The intestinal Na + -dependent phosphate transporter Npt2b is thought to be an important molecular target for the prevention of hyperphosphatemia. The role of Npt2b in the net absorption of inorganic phosphate (Pi), however, is controversial. In the present study, we made tamoxifen-inducible Npt2b conditional knockout (CKO) mice to analyze systemic Pi metabolism, including intestinal Pi absorption. Although the Na + -dependent Pi transport in brush-border membrane vesicle uptake levels was significantly decreased in the distal intestine of Npt2b CKO mice compared with control mice, plasma Pi and fecal Pi excretion levels were not significantly different. Data obtained using the intestinal loop technique showed that Pi uptake in Npt2b CKO mice was not affected at a Pi concentration of 4 mM, which is considered the typical luminal Pi concentration after meals in mice. Claudin, which may be involved in paracellular pathways, as well as claudin-2, 12, and 15 protein levels were significantly decreased in the Npt2b CKO mice. Thus, Npt2b deficiency did not affect Pi absorption within the range of Pi concentrations that normally occurs after meals. These findings indicate that abnormal Pi metabolism may also be involved in tight junction molecules such as Cldns that are affected by Npt2b deficiency.

The effect of higher ATP cost of contraction on the metabolic response to graded exercise in patients with chronic obstructive pulmonary disease.

PubMed

Layec, Gwenael; Haseler, Luke J; Richardson, Russell S

2012-03-01

To better understand the metabolic implications of a higher ATP cost of contraction in chronic obstructive pulmonary disease (COPD), we used (31)P-magnetic resonance spectroscopy ((31)P-MRS) to examine muscle energetics and pH in response to graded exercise. Specifically, in six patients and six well-matched healthy controls, we determined the intracellular threshold for pH (T(pH)) and inorganic phosphate-to-phosphocreatine ratio (T(Pi/PCr)) during progressive dynamic plantar flexion exercise with work rate expressed as both absolute and relative intensity. Patients with COPD displayed a lower peak power output (WRmax) compared with controls (controls 25 ± 4 W, COPD 15 ± 5 W, P = 0.01) while end-exercise pH (controls 6.79 ± 0.15, COPD 6.76 ± 0.21, P = 0.87) and PCr consumption (controls 82 ± 10%, COPD 70 ± 18%, P = 0.26) were similar between groups. Both T(pH) and T(Pi/PCr) occurred at a significantly lower absolute work rate in patients with COPD compared with controls (controls: 14.7 ± 2.4 W for T(pH) and 15.3 ± 2.4 W for T(Pi/PCr); COPD: 9.7 ± 4.5 W for T(pH) and 10.0 ± 4.6 W for T(Pi/PCr), P < 0.05), but these thresholds occurred at the same percentage of WRmax (controls: 63 ± 11% WRmax for T(pH) and 67 ± 18% WRmax for T(Pi/PCr); COPD: 59 ± 9% WRmax for T(pH) and 61 ± 12% WRmax for T(Pi/PCr), P > 0.05). Indexes of mitochondrial function, the PCr recovery time constant (controls 42 ± 7 s, COPD 45 ± 11 s, P = 0.66) and the PCr resynthesis rate (controls 105 ± 21%/min, COPD 91 ± 31%/min, P = 0.43) were similar between groups. In combination, these results reveal that when energy demand is normalized to WRmax, as a consequence of higher ATP cost of contraction, patients with COPD display the same metabolic pattern as healthy subjects, suggesting that skeletal muscle energy production is well preserved in these patients.

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

Influence of a high vacuum on the precise positioning using an ultrasonic linear motor.

PubMed

Kim, Wan-Soo; Lee, Dong-Jin; Lee, Sun-Kyu

2011-01-01

This paper presents an investigation of the ultrasonic linear motor stage for use in a high vacuum environment. The slider table is driven by the hybrid bolt-clamped Langevin-type ultrasonic linear motor, which is excited with its different modes of natural frequencies in both lateral and longitudinal directions. In general, the friction behavior in a vacuum environment becomes different from that in an environment of atmospheric pressure and this difference significantly affects the performance of the ultrasonic linear motor. In this paper, to consistently provide stable and high power of output in a high vacuum, frequency matching was conducted. Moreover, to achieve the fine control performance in the vacuum environment, a modified nominal characteristic trajectory following control method was adopted. Finally, the stage was operated under high vacuum condition, and the operating performances were investigated compared with that of a conventional PI compensator. As a result, robustness of positioning was accomplished in a high vacuum condition with nanometer-level accuracy.

Early-Phase 11C-PiB PET in Amyloid Angiopathy-Related Symptomatic Cerebral Hemorrhage: Potential Diagnostic Value?

PubMed Central

Aigbirhio, Franklin I.; Fryer, Tim D.; Menon, David K.; Warburton, Elizabeth A.; Baron, Jean-Claude

2015-01-01

Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently high uptake in healthy aged subjects. By detecting perfusion-like abnormalities, early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1–6min) 11C-PiB-PET was obtained in 11 non-demented patients with probable CAA-related symptomatic lobar intracerebral haemorrhage (70±7yrs), 9 age-matched healthy controls (HCs) and 10 HCs <55yrs. There was a significant decrease in early-phase atrophy-corrected whole-cortex SUV relative to cerebellar vermis (SUVR) in the CAA vs age-matched HC group. None of the age-matched controls fell below the lower 95% confidence limit derived from the young HCs, while 6/11 CAA patients did (sensitivity = 55%, specificity = 100%). Combining both early- and late-phase 11C-PiB data did not change the sensitivity and specificity of late-phase PiB, but combined early- and late-phase positivity entails a very high suspicion of underlying Aβ-related clinical disorder, i.e., CAA or Alzheimer disease (AD). In order to clarify this ambiguity, we then show that the occipital/posterior cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with respect to the unclear situation of late-phase positivity, but also help differentiate CAA from AD. PMID:26439113

The 20-hydroxyecdysone-induced signalling pathway in G2/M arrest of Plodia interpunctella imaginal wing cells.

PubMed

Siaussat, David; Bozzolan, Françoise; Porcheron, Patrick; Debernard, Stéphane

2008-05-01

The mechanisms involved in the control of cellular proliferation by the steroid hormone 20-hydroxyecdysone (20E) in insects are not known. We dissected the 20E signalling pathway responsible for G2/M arrest of imaginal cells from the IAL-PID2 cells of the Indian meal moth Plodia interpunctella. We first used a 5'-3' RACE-based strategy to clone a 4479bp cDNA encoding a putative P. interpunctella HR3 transcription factor named PiHR3. The deduced amino acid sequence of PiHR3 was highly similar to those of HR3 proteins from other lepidopterans, e.g. Manduca sexta and Bombyx mori. Using double-stranded RNA-mediated interference (dsRNAi), we then succeeded in blocking the ability of 20E to induce the expression of PiEcR-B1, PiUSP-2 and PiHR3 genes that encode the P. interpunctella ecdysone receptor B1-isoform, Ultraspiracle-2 isoform, the insect homologue of the vertebrate retinoid X receptor, and the HR3 transcription factor. We showed that inhibiting the 20E induction of PiEcR-B1, PiUSP-2 and PiHR3 mRNAs prevented the decreased expression of B cyclin and consequently the G2/M arrest of IAL-PID2 cells. Using this functional approach, we revealed the participation of EcR, USP and HR3 in a 20E signalling pathway that controls the proliferation of imaginal cells by regulating the expression of B cyclin.

Helicopter Controllability

DTIC Science & Technology

1989-09-01

106 3. Program CC Systems Technology, Inc. (STI) of Hawthorne, CA., develops and markets PC control system analysis and design software including...is marketed in Palo Alto, Ca., by Applied i and can be used for both linear and non- linear control system analysis. Using TUTSIM involves developing...gravity centroid ( ucg ) can be calculated as 112 n m pi - 2 zi acg n i (7-5) where pi = poles zi = zeroes n = number of poles m = number of zeroes If K

PI3K/AKT/mTOR Pathway in Ovarian Cancer Treatment: Are We on the Right Track?

PubMed Central

Gasparri, Maria Luisa; Bardhi, Erlisa; Ruscito, Ilary; Papadia, Andrea; Farooqi, Ammad Ahmad; Marchetti, Claudia; Bogani, Giorgio; Ceccacci, Irene; Mueller, Michael D.; Benedetti Panici, Pierluigi

2017-01-01

The high recurrence rate and the low overall survival in ovarian cancer suggest that a more specific therapeutic approach in addition to conventional treatment is required. Translational and clinical research is investigating new molecular targets in order to find an alternative way to affect tumor growth and to minimize the overlap of toxicity of antiblastic agents. Given its implication in many cellular activities including regulation of cell growth, motility, survival, proliferation, protein synthesis, autophagy, transcription, as well as angiogenesis, PI3K/AKT/mTOR is one of the most investigated intracellular signaling pathways. A dis-regulation of this pathway has been shown in several tumors, including ovarian cancer. In this setting, mTor proteins represent a potential target for inhibitors, which could ultimately play a pivotal role in counteracting cellular proliferation. Recently, mTor inhibitors have been approved in the treatment of pancreatic neuroendocrine tumors, mantle cell lymphoma and renal cancer. Clinical trials have assessed the safety of these drugs in ovarian cancer patients. Ongoing phase I and II studies are evaluating the oncologic outcome of mTor inhibitor treatment and its effect in combination with conventional chemotherapy and target agents. PMID:29093603

PI3K/AKT/mTOR Pathway in Ovarian Cancer Treatment: Are We on the Right Track?

PubMed

Gasparri, Maria Luisa; Bardhi, Erlisa; Ruscito, Ilary; Papadia, Andrea; Farooqi, Ammad Ahmad; Marchetti, Claudia; Bogani, Giorgio; Ceccacci, Irene; Mueller, Michael D; Benedetti Panici, Pierluigi

2017-10-01

The high recurrence rate and the low overall survival in ovarian cancer suggest that a more specific therapeutic approach in addition to conventional treatment is required. Translational and clinical research is investigating new molecular targets in order to find an alternative way to affect tumor growth and to minimize the overlap of toxicity of antiblastic agents. Given its implication in many cellular activities including regulation of cell growth, motility, survival, proliferation, protein synthesis, autophagy, transcription, as well as angiogenesis, PI3K/AKT/mTOR is one of the most investigated intracellular signaling pathways. A dis-regulation of this pathway has been shown in several tumors, including ovarian cancer. In this setting, mTor proteins represent a potential target for inhibitors, which could ultimately play a pivotal role in counteracting cellular proliferation. Recently, mTor inhibitors have been approved in the treatment of pancreatic neuroendocrine tumors, mantle cell lymphoma and renal cancer. Clinical trials have assessed the safety of these drugs in ovarian cancer patients. Ongoing phase I and II studies are evaluating the oncologic outcome of mTor inhibitor treatment and its effect in combination with conventional chemotherapy and target agents.

[An analysis for the clinical difference between post infectious irritable bowel syndrome and non post infectious irritable bowel syndrome].

PubMed

Shi, Hui; Wan, Jun; Liu, Wenhui; Su, Binbin

2015-04-01

To study the clinical discrepancy between patients with post infectious irritable bowel syndrome (PI-IBS) and non post infectious irritable bowel syndrome (NPI-IBS) , and assess the value of serum intestinal fatty acid binding protein (I-FABP) for differential diagnosis. A total of 117 patients with PI-IBS, 201 patients with NPI-IBS and 31 healthy controls were prospectively recruited in General Liberation Army Hospital from 2010 to 2013. Plasma samples and clinical data were collected. Serum I-FABP level was measured by an enzyme-linked immunosorbent assay. The median age of patients with PI-IBS was 36 years. The median time to diagnosis in PI-IBS group was significantly longer than that in NPI-IBS group [(19.7 ± 10.3)months vs (11.4 ± 5.3) months, P < 0.05]. Similarly, the proportion of anxiety [58.1%(68/117) vs 28.9%(58/201), P < 0.05] and the value of I-FABP [(42.6 ± 14.8) µg/L vs (17.3 ± 11.5) µg/L, P < 0.05] in PI-IBS group were significant higher than NPI-IBS patients. The level of I-FABP of healthy controls [(10.6 ± 8.2) µg/L] was also significantly lower than that of PI-IBS patients (P < 0.05), yet no difference from that of NPI-IBS group. The I-FABP value of subgroup PI-IBS patients with diarrhoea (IBS-D) was significant higher than that of NPI-IBS group [(54.8 ± 9.3)µg/L vs (12.3 ± 6.2) µg/L, P < 0.05]. However, other parameters including gender, age, GSRS score, and I-FABP value of subgroup constipation (IBS-C) and mix (IBS-M), were not different between PI-IBS group and NPI-IBS group (all P > 0.05). PI-IBS is an occult intestinal inflammation disease with mucosa injury. I-FABP might be a potential testing marker for the diagnosis of PI-IBS.

High phosphorus diet-induced changes in NaPi-IIb phosphate transporter expression in the rat kidney: DNA microarray analysis.

PubMed

Suyama, Tatsuya; Okada, Shinji; Ishijima, Tomoko; Iida, Kota; Abe, Keiko; Nakai, Yuji

2012-01-01

The mechanism by which phosphorus levels are maintained in the body was investigated by analyzing changes in gene expression in the rat kidney following administration of a high phosphorus (HP) diet. Male Wistar rats were divided into two groups and fed a diet containing 0.3% (control) or 1.2% (HP) phosphorous for 24 days. Phosphorous retention was not significantly increased in HP rats, but fractional excretion of phosphorus was significantly increased in the HP group compared to controls, with an excessive amount of the ingested phosphorus being passed through the body. DNA microarray analysis of kidney tissue from both groups revealed changes in gene expression profile induced by a HP diet. Among the genes that were upregulated, Gene Ontology (GO) terms related to ossification, collagen fibril organization, and inflammation and immune response were significantly enriched. In particular, there was significant upregulation of type IIb sodium-dependent phosphate transporter (NaPi-IIb) in the HP rat kidney compared to control rats. This upregulation was confirmed by in situ hybridization. Distinct signals for NaPi-IIb in both the cortex and medulla of the kidney were apparent in the HP group, while the corresponding signals were much weaker in the control group. Immunohistochemical analysis showed that NaPi-IIb localized to the basolateral side of kidney epithelial cells surrounding the urinary duct in HP rats but not in control animals. These data suggest that NaPi-IIb is upregulated in the kidney in response to the active excretion of phosphate in HP diet-fed rats.

Preliminary analysis of the PreFlexMS molten salt once-through steam generator dynamics and control strategy

NASA Astrophysics Data System (ADS)

Trabucchi, Stefano; Casella, Francesco; Maioli, Tommaso; Elsido, Cristina; Franzini, Davide; Ramond, Mathieu

2017-06-01

Concentrated Solar Power plants (CSP) coupled with thermal storage have the potential to guarantee both flexible and continuous energy production, thus being competitive with conventional fossil fuel and hydro power plants, in terms of dispatchability and provision of ancillary services. Hence, the plant equipment and control design have to be focused on flexible operation on one hand, and on plant safety concerning the molten salt freezing on the other hand. The PreFlexMS European project aims to introduce a molten salt Once-Through Steam Generator (OTSG) within a Rankine cycle based power unit, a technology that has greater flexibility potential if compared to steam drum boilers, currently used in CSP plants. The dynamic modelling and simulation from the early design stages is, thus, of paramount importance, to assess the plant dynamic behavior and controllability, and to predict the achievable closed-loop dynamic performance, potentially saving money and time during the detailed design, construction and commissioning phases. The present paper reports the main results of the analysis carried out during the first part of the project, regarding the system analysis and control design. In particular, two different control systems have been studied and tested with the plant dynamic model: a decentralized control strategy based on PI controllers and a Linear Model Predictive Control (LMPC).

Impact of Performance Improvement Continuing Medical Education on Cardiometabolic Risk Factor Control: The COSEHC Initiative

PubMed Central

Joyner, JaNae; Moore, Michael A.; Simmons, Debra R.; Forrest, Brian; Yu-Isenberg, Kristina; Piccione, Ron; Caton, Kirt; Lackland, Daniel T.; Ferrario, Carlos M.

2016-01-01

Introduction The Consortium for Southeastern Hypertension Control (COSEHC) implemented a study to assess benefits of a performance improvement continuing medical education (PI CME) activity focused on cardiometabolic risk factor management in primary care patients. Methods Using the plan-do-study-act (PDSA) model as the foundation, this PI CME activity aimed at improving practice gaps by integrating evidence-based clinical interventions, physician-patient education, processes of care, performance metrics, and patient outcomes. The PI CME intervention was implemented in a group of South Carolina physician practices, while a comparable physician practice group served as a control. Performance outcomes at 6 months included changes in patients’ cardiometabolic risk factor values and control rates from baseline. We also compared changes in diabetic, African American, the elderly (> 65 years), and female patient subpopulations and in patients with uncontrolled risk factors at baseline. Results Only women receiving health care by intervention physicians showed a statistical improvement in their cardiometabolic risk factors as evidenced by a −3.0 mg/dL and a −3.5 mg/dL decrease in mean LDL cholesterol and non-HDL cholesterol, respectively, and a −7.0 mg/dL decrease in LDL cholesterol among females with uncontrolled baseline LDL cholesterol values. No other statistical differences were found. Discussion These data demonstrate that our PI CME activity is a useful strategy in assisting physicians to improve their management of cardiometabolic control rates in female patients with abnormal cholesterol control. Other studies that extend across longer PI CME PDSA periods may be needed to demonstrate statistical improvements in overall cardiometabolic treatment goals in men, women, and various subpopulations. PMID:24648361

Adaptive two-degree-of-freedom PI for speed control of permanent magnet synchronous motor based on fractional order GPC.

PubMed

Qiao, Wenjun; Tang, Xiaoqi; Zheng, Shiqi; Xie, Yuanlong; Song, Bao

2016-09-01

In this paper, an adaptive two-degree-of-freedom (2Dof) proportional-integral (PI) controller is proposed for the speed control of permanent magnet synchronous motor (PMSM). Firstly, an enhanced just-in-time learning technique consisting of two novel searching engines is presented to identify the model of the speed control system in a real-time manner. Secondly, a general formula is given to predict the future speed reference which is unavailable at the interval of two bus-communication cycles. Thirdly, the fractional order generalized predictive control (FOGPC) is introduced to improve the control performance of the servo drive system. Based on the identified model parameters and predicted speed reference, the optimal control law of FOGPC is derived. Finally, the designed 2Dof PI controller is auto-tuned by matching with the optimal control law. Simulations and real-time experimental results on the servo drive system of PMSM are provided to illustrate the effectiveness of the proposed strategy. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Distinctive Resting State Network Disruptions Among Alzheimer's Disease, Subcortical Vascular Dementia, and Mixed Dementia Patients.

PubMed

Kim, Hee Jin; Cha, Jungho; Lee, Jong-Min; Shin, Ji Soo; Jung, Na-Yeon; Kim, Yeo Jin; Choe, Yearn Seong; Lee, Kyung Han; Kim, Sung Tae; Kim, Jae Seung; Lee, Jae Hong; Na, Duk L; Seo, Sang Won

2016-01-01

Recent advances in resting-state functional MRI have revealed altered functional networks in Alzheimer's disease (AD), especially those of the default mode network (DMN) and central executive network (CEN). However, few studies have evaluated whether small vessel disease (SVD) or combined amyloid and SVD burdens affect the DMN or CEN. The aim of this study was to evaluate whether SVD or combined amyloid and SVD burdens affect the DMN or CEN. In this cross-sectional study, we investigated the resting-state functional connectivity within DMN and CEN in 37 Pittsburgh compound-B (PiB)(+) AD, 37 PiB(-) subcortical vascular dementia (SVaD), 13 mixed dementia patients, and 65 normal controls. When the resting-state DMN of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(+) AD patients displayed lower functional connectivity in the inferior parietal lobule while the PiB(-) SVaD patients displayed lower functional connectivity in the medial frontal and superior frontal gyri. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the DMN in the posterior cingulate gyrus. When the resting-state CEN connectivity of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(-) SVaD patients displayed lower functional connectivity in the anterior insular region. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the CEN in the inferior frontal gyrus. Our findings suggest that in PiB(+) AD and PiB(-) SVaD, there is divergent disruptions in resting-state DMN and CEN. Furthermore, patients with combined amyloid and SVD burdens exhibited more disrupted resting-state DMN and CEN than patients with only amyloid or SVD burden.

Adaptation of the symbiotic Mesorhizobium-chickpea relationship to phosphate deficiency relies on reprogramming of whole-plant metabolism.

PubMed

Nasr Esfahani, Maryam; Kusano, Miyako; Nguyen, Kien Huu; Watanabe, Yasuko; Ha, Chien Van; Saito, Kazuki; Sulieman, Saad; Herrera-Estrella, Luis; Tran, L S

2016-08-09

Low inorganic phosphate (Pi) availability is a major constraint for efficient nitrogen fixation in legumes, including chickpea. To elucidate the mechanisms involved in nodule acclimation to low Pi availability, two Mesorhizobium-chickpea associations exhibiting differential symbiotic performances, Mesorhizobium ciceri CP-31 (McCP-31)-chickpea and Mesorhizobium mediterranum SWRI9 (MmSWRI9)-chickpea, were comprehensively studied under both control and low Pi conditions. MmSWRI9-chickpea showed a lower symbiotic efficiency under low Pi availability than McCP-31-chickpea as evidenced by reduced growth parameters and down-regulation of nifD and nifK These differences can be attributed to decline in Pi level in MmSWRI9-induced nodules under low Pi stress, which coincided with up-regulation of several key Pi starvation-responsive genes, and accumulation of asparagine in nodules and the levels of identified amino acids in Pi-deficient leaves of MmSWRI9-inoculated plants exceeding the shoot nitrogen requirement during Pi starvation, indicative of nitrogen feedback inhibition. Conversely, Pi levels increased in nodules of Pi-stressed McCP-31-inoculated plants, because these plants evolved various metabolic and biochemical strategies to maintain nodular Pi homeostasis under Pi deficiency. These adaptations involve the activation of alternative pathways of carbon metabolism, enhanced production and exudation of organic acids from roots into the rhizosphere, and the ability to protect nodule metabolism against Pi deficiency-induced oxidative stress. Collectively, the adaptation of symbiotic efficiency under Pi deficiency resulted from highly coordinated processes with an extensive reprogramming of whole-plant metabolism. The findings of this study will enable us to design effective breeding and genetic engineering strategies to enhance symbiotic efficiency in legume crops.

Fetal cardiac function in late-onset intrauterine growth restriction vs small-for-gestational age, as defined by estimated fetal weight, cerebroplacental ratio and uterine artery Doppler.

PubMed

Pérez-Cruz, M; Cruz-Lemini, M; Fernández, M T; Parra, J A; Bartrons, J; Gómez-Roig, M D; Crispi, F; Gratacós, E

2015-10-01

Among late-onset small fetuses, a combination of estimated fetal weight (EFW), cerebroplacental ratio (CPR) and mean uterine artery (UtA) pulsatility index (PI) can predict a subgroup of fetuses with poor perinatal outcome; however, the association of these criteria with fetal cardiac structure and function is unknown. Our aim was to determine the presence and severity of signs indicating cardiac dysfunction in small fetuses, classified as intrauterine growth-restricted (IUGR) or small-for-gestational age (SGA), according to EFW, CPR and UtA-PI. A cohort of 209 late-onset small fetuses that were delivered > 34 weeks of gestation was divided in two categories: SGA (n = 59) if EFW was between the 3(rd) and 9(th) centiles with normal CPR and UtA-PI; and IUGR (n = 150) if EFW was < 3(rd) centile, or < 10(th) centile with a CPR < 5(th) centile and/or UtA-PI > 95(th) centile. The small population was compared with 150 appropriately grown fetuses (controls). Fetal cardiac morphometry and function were assessed by echocardiography using two-dimensional M-mode, conventional and tissue Doppler. Compared with controls, both IUGR and SGA fetuses showed larger and more globular hearts (mean left sphericity index ± SD: controls, 1.8 ± 0.3; SGA, 1.5 ± 0.2; and IUGR, 1.6 ± 0.3; P < 0.01) and showed signs of systolic and diastolic dysfunction, including decreased tricuspid annular plane systolic excursion (mean ± SD: controls, 8.2 ± 1.1; SGA, 7.4 ± 1.2; and IUGR, 6.9 ± 1.1; P < 0.001) and increased left myocardial performance index (mean ± SD: controls, 0.45 ± 0.14; SGA, 0.51 ± 0.08; and IUGR, 0.57 ± 0.1; P < 0.001). Despite a perinatal outcome comparable to that of normal fetuses, the population of so-defined SGA fetuses showed signs of prenatal cardiac dysfunction. This supports the concept that at least a proportion of them are not 'constitutionally small' and that further research is needed. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

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.

On the effect of local barrier height in scanning tunneling microscopy: Measurement methods and control implications

NASA Astrophysics Data System (ADS)

Tajaddodianfar, Farid; Moheimani, S. O. Reza; Owen, James; Randall, John N.

2018-01-01

A common cause of tip-sample crashes in a Scanning Tunneling Microscope (STM) operating in constant current mode is the poor performance of its feedback control system. We show that there is a direct link between the Local Barrier Height (LBH) and robustness of the feedback control loop. A method known as the "gap modulation method" was proposed in the early STM studies for estimating the LBH. We show that the obtained measurements are affected by controller parameters and propose an alternative method which we prove to produce LBH measurements independent of the controller dynamics. We use the obtained LBH estimation to continuously update the gains of a STM proportional-integral (PI) controller and show that while tuning the PI gains, the closed-loop system tolerates larger variations of LBH without experiencing instability. We report experimental results, conducted on two STM scanners, to establish the efficiency of the proposed PI tuning approach. Improved feedback stability is believed to help in avoiding the tip/sample crash in STMs.

Influence of Chronic Social Defeat Stress on Digestive System Functioning in Rats.

PubMed

Toyoda, Atsushi; Iio, Wataru; Matsukawa, Noriko; Tsukahara, Takamitsu

2015-01-01

Mental disorders are caused by chronic psychosocial stress, and can cause various symptoms related to the digestive system. We focused on the conjugation of intestinal absorptive and enzymatic mechanisms between chronic social defeat stress (CSDS) model rats and healthy controls to obtain general biochemical data about the intestine of the model in this study. The small intestine was divided into three regions: proximal (PI), middle (MI), and distal (DI); mRNA expression associated with a nutrient absorption, glucose absorption activity, and activities of the digestive enzymes such as maltase, sucrase and lactase was measured. Expression of both sodium-dependent glucose transporter 1 (Sglt1) and glucose transporter 2 gene tended to be higher in the stress group compared to the control group in PI. Glucose absorption was also higher in PI of the CSDS group. Sglt1 and peptide transporter 1 gene expressions in the CSDS group were significantly higher than those in the control group in DI. Furthermore, in PI, expression of the aquaporin 1 gene was significantly higher in the CSDS group compared to the control group. Thus, absorption of some nutrients might be higher in the small intestine of the CSDS rat.

A PI4P-driven electrostatic field controls cell membrane identity and signaling in plants

PubMed Central

Simon, Mathilde Laetitia Audrey; Platre, Matthieu Pierre; Marquès-Bueno, Maria Mar; Armengot, Laia; Stanislas, Thomas; Bayle, Vincent; Caillaud, Marie-Cécile; Jaillais, Yvon

2016-01-01

Many signaling proteins permanently or transiently localize to specific organelles for function. It is well established that certain lipids act as biochemical landmarks to specify compartment identity. However, they also influence membrane biophysical properties, which emerge as important features in specifying cellular territories. Such parameters include the membrane inner surface potential, which varies according to the lipid composition of each organelle. Here, we found that the plant plasma membrane (PM) and the cell plate of dividing cells have a unique electrostatic signature controlled by phosphatidylinositol-4-phosphate (PI4P). Our results further reveal that, contrarily to other eukaryotes, PI4P massively accumulates at the PM, establishing it as a critical hallmark of this membrane in plants. Membrane surface charges control the PM localization and function of the polar auxin transport regulator PINOID, as well as proteins from the BRI1 KINASE INHIBITOR1 (BKI1)/MEMBRANE ASSOCIATED KINASE REGULATORs (MAKRs) family, which are involved in brassinosteroid and receptor-like kinase signaling. We anticipate that this PI4P-driven physical membrane property will control the localization and function of many proteins involved in development, reproduction, immunity and nutrition. PMID:27322096

Phosphate Starvation Inducible Metabolism in Lycopersicon esculentum1

PubMed Central

Goldstein, Alan H.; Baertlein, Dawn A.; McDaniel, Robert G.

1988-01-01

Both tomato (Lycopersicon esculentum cv VF 36) plants and suspension cultured cells show phosphate starvation inducible (psi) excretion of acid phosphatase (Apase). Apase excretion in vitro was proportional to the level of exogenous orthophosphate (Pi). Intracellular Apase activity remained the same in both Pi-starved and sufficient cells, while Apase excreted by the starved cells increased by as much as six times over unstressed control cells on a dry weight basis. At peak induction, 50% of total Apase was excreted. Ten day old tomato seedlings grown without Pi showed slight growth reduction versus unstressed control plants. The Pi-depleted roots showed psi enhancement of Apase activity. Severely starved seedlings (17 days) reached only one-third of the biomass of unstressed control plants but, because of a combination of psi Apase excretion by roots and a shift in biomass to this organ, they excreted 5.5 times the Apase activity of the unstressed control. Observed psi Apase excretion may be part of a phosphate starvation rescue system in plants. The utility of the visible indicator dye 5-bromo-4-chloro-3-indolyl-phosphate-p-toluidine as a phenotypic marker for plant Apase excretion is demonstrated. Images Fig. 5 PMID:16666212

Hemodynamic adaptation to suboptimal fetal growth in patients with single ventricle physiology.

PubMed

Alsaied, Tarek; Tseng, Stephanie; King, Eileen; Hahn, Eunice; Divanovic, Allison; Habli, Mounira; Cnota, James

2018-06-10

In fetuses with structurally normal heart and suboptimal fetal growth (SFG), umbilical artery vascular resistance increases as measured by umbilical artery pulsatility index (UA-PI). The objective of this study is to compare hemodynamic responses to SFG in fetuses with single ventricle (SV) and controls with structurally normal heart. Fetal echocardiograms around 30 weeks of gestation were reviewed. UA-PI and middle cerebral artery pulsatility index (MCA-PI) were calculated. SFG was defined as a birth weight below 25th percentile for gestational age. Studies from 92 fetuses were reviewed-SV (n = 50) and controls (n = 42). The prevalence of SFG was higher in SV compared to controls (46% vs 21%, P = .02). In patients with normal heart and SFG, UAPI was significantly higher than normal controls (P = .003) suggesting increased placental vascular resistance. In SV with SFG there was no difference in UAPI compared to SV without SFG. There was no difference in MCA-PI between the groups. The hemodynamic response to SFG in SV varies from fetuses with structurally normal heart. The mechanism of SFG and the placental pathology may be distinct in SV. © 2018 Wiley Periodicals, Inc.

A fuzzy controller with nonlinear control rules is the sum of a global nonlinear controller and a local nonlinear PI-like controller

NASA Technical Reports Server (NTRS)

Ying, Hao

1993-01-01

The fuzzy controllers studied in this paper are the ones that employ N trapezoidal-shaped members for input fuzzy sets, Zadeh fuzzy logic and a centroid defuzzification algorithm for output fuzzy set. The author analytically proves that the structure of the fuzzy controllers is the sum of a global nonlinear controller and a local nonlinear proportional-integral-like controller. If N approaches infinity, the global controller becomes a nonlinear controller while the local controller disappears. If linear control rules are used, the global controller becomes a global two-dimensional multilevel relay which approaches a global linear proportional-integral (PI) controller as N approaches infinity.

Two-component duality and flavoring in the P+f model

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

Dash, J.W.; Jones, S.T.; Martin, A.

We show that modern Regge fits to rising ..pi..N total cross sections sigma/sub piN/ using the Harari-Freund P+f model of diffraction are not consistent with two-component duality. If a conventional Pomeron is chosen (dominant j-plane pole plus weak cuts), the resulting f is ''dual'' to the resonances plus one-half the background. Conversely, constraining the f-pole amplitude by duality does not allow a reasonable fit to sigma/sub piN/. In contrast, the P-f identity model of diffraction is shown to satisfy a modified form of two-component duality. We show that by incorporating flavoring renormalization, the P+f picture can be made consistent withmore » duality. The unflavored P intercept is 0.91 and the flavored P intercept is 1.1. Significant absorptive j-plane cuts are also required, though these are small enough to be consistent with dominant short-range order. Thus flavoring, which is so essential in P-f identity phenomenology, seems to play a positive role in diffraction scattering generally.« less

Abnormal Neural Network of Primary Insomnia: Evidence from Spatial Working Memory Task fMRI.

PubMed

Li, Yongli; Liu, Liya; Wang, Enfeng; Zhang, Hongju; Dou, Shewei; Tong, Li; Cheng, Jingliang; Chen, Chuanliang; Shi, Dapeng

2016-01-01

Contemporary functional MRI (fMRI) methods can provide a wealth of information about the neural mechanisms associated with primary insomnia (PI), which centrally involve neural network circuits related to spatial working memory. A total of 30 participants diagnosed with PI and without atypical brain anatomy were selected along with 30 age- and gender-matched healthy controls. Subjects were administered the Pittsburgh Sleep Quality Index (PSQI), Hamilton Rating Scale for Depression and clinical assessments of spatial working memory, followed by an MRI scan and fMRI in spatial memory task state. Statistically significant differences between PSQI and spatial working memory were observed between PI patients and controls (p < 0.01). Activation of neural networks related to spatial memory task state in the PI group was observed at the left temporal lobe, left occipital lobe and right frontal lobe. Lower levels of activation were observed in the left parahippocampal gyrus, right parahippocampal gyrus, bilateral temporal cortex, frontal cortex and superior parietal lobule. Participants with PI exhibited characteristic abnormalities in the neural network connectivity related to spatial working memory. These results may be indicative of an underlying pathological mechanism related to spatial working memory deterioration in PI, analogous to recently described mechanisms in other mental health disorders. © 2016 S. Karger AG, Basel.

PI3Kδ promotes CD4(+) T-cell interactions with antigen-presenting cells by increasing LFA-1 binding to ICAM-1.

PubMed

Garçon, Fabien; Okkenhaug, Klaus

2016-05-01

Activation of T lymphocytes by peptide/major histocompatibility complex on antigen-presenting cells (APCs) involves dynamic contacts between the two cells, during which T cells undergo marked morphological changes. These interactions are facilitated by integrins. Activation of the T cells increases the binding of the integrin lymphocyte function-associated antigen 1 (LFA-1) expressed by T cells to intercellular adhesion molecule (ICAM)-1 and ICAM-2 expressed by APCs. The signalling pathways that control integrin affinities are incompletely defined. The phosphoinositide 3-kinases (PI3Ks) generate second-messenger signalling molecules that control cell growth, proliferation, differentiation and trafficking. Here we show that in T cells, PI3Kδ attenuates the activation of Rac1, but sustains the activation of Rap1. Consequently, PI3Kδ increases LFA-1-dependent adhesion to form stable conjugates with APCs. Increased Rap1 activity and LFA-1 adhesion were only in part mediated by the downstream kinase Akt, suggesting the involvement of additional phosphatidylinositol(3,4,5)P3-binding proteins. These results establish a link between PI3K activity, cytoskeletal changes and integrin binding and help explain the impaired T-cell-dependent immune responses in PI3Kδ-deficient mice.

Effect of saw palmetto extract on PI3K cell signaling transduction in human glioma

PubMed Central

YANG, YANG; HUI, LV; YUQIN, CHE; JIE, LI; SHUAI, HOU; TIEZHU, ZHOU; WEI, WANG

2014-01-01

Saw palmetto extract can induce the apoptosis of prostate cancer cells. The aim of the present study was to investigate the effect of saw palmetto extract on the phosphatidylinositol 3-kinase (PI3K)/Akt signaling transduction pathway in human glioma U87 and U251 cell lines. Suspensions of U87 and U251 cells in a logarithmic growth phase were seeded into six-well plates at a density of 104 cells/well. In the experimental group, 1 μl/ml saw palmetto extract was added, while the control group was cultured without a drug for 24 h. The expression levels of PI3K, B-cell lymphoma-extra large (Bcl-xL) and p53 were evaluated through western blot analysis. In the experimental group, the U87 and U251 cells exhibited a lower expression level of PI3K protein as compared with the control group (t=6.849; P<0.001). In addition, the two cell lines had a higher expression level of p53 protein in the experimental group as compared with the control group (t=40.810; P<0.001). Protein expression levels of Bcl-xL decreased significantly in the experimental group as compared with the control group (t=19.640; P=0.000). Therefore, saw palmetto extract induces glioma cell growth arrest and apoptosis via decreasing PI3K/Akt signal transduction. PMID:25009620

Consumer purchase intention towards environmentally friendly vehicles: an empirical investigation in Kuala Lumpur, Malaysia.

PubMed

Afroz, Rafia; Masud, Muhammad Mehedi; Akhtar, Rulia; Islam, Md Ashraful; Duasa, Jarita Bt

2015-10-01

This paper examines whether attitudes towards electric vehicles (ATEVs), subjective norms (SNs) and perceived behavioural control (PBC) have significant associations with consumer purchase intention (PI) and the purchase behaviour of environmentally friendly vehicles (EFVs). The results from the survey questionnaires are analysed using confirmatory factor analysis (CFA) and structural equation modelling (SEM). The findings of this paper indicate that ATEV, SN and PBC significantly influence PI. This finding also indicates that environmental consequence and individual preferences do not influence the PI of the respondents. We found that Malaysian car owners are largely unaware of the greenhouse effects on the environment or attach to it little importance, which is reflected in their PI towards EFVs. The outcomes of this study could help policymakers design programmes to influence attitudes, subjective norms, perceived behavioural control and purchase behaviour to prevent further air pollution and reduce CO2 emissions from the transportation sector.

Distributed Control of Robotic Networks: A Mathematical Approach to Motion Coordination Algorithms

DTIC Science & Technology

2008-10-27

centered at y. The open lune associated to x, y ∈ S is B(x,dist(x, y))∩B(y,dist(x, y)). These notions are illustrated in Figure 1.1 for the Euclidean...version: October 27, 2008 DCRN October 27, 2008 Figure 1.1 Open balls (dashed lines), closed ball (solid line), and open lune for the Eu- clidean...their associated open lune (cf. Section 1.1.3) does not contain any point in P, that is, (pi, pj) ∈ EGRN(P) if pk 6∈ B(pi,dist(pi, pj))∩B(pj ,dist(pi

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.

Design of set-point weighting PI{sup λ} + D{sup μ} controller for vertical magnetic flux controller in Damavand tokamak

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

Rasouli, H.; Fatehi, A.

2014-12-15

In this paper, a simple method is presented for tuning weighted PI{sup λ} + D{sup μ} controller parameters based on the pole placement controller of pseudo-second-order fractional systems. One of the advantages of this controller is capability of reducing the disturbance effects and improving response to input, simultaneously. In the following sections, the performance of this controller is evaluated experimentally to control the vertical magnetic flux in Damavand tokamak. For this work, at first a fractional order model is identified using output-error technique in time domain. For various practical experiments, having desired time responses for magnetic flux in Damavand tokamak,more » is vital. To approach this, at first the desired closed loop reference models are obtained based on generalized characteristic ratio assignment method in fractional order systems. After that, for the identified model, a set-point weighting PI{sup λ} + D{sup μ} controller is designed and simulated. Finally, this controller is implemented on digital signal processor control system of the plant to fast/slow control of magnetic flux. The practical results show appropriate performance of this controller.« less

Digitally controlled analog proportional-integral-derivative (PID) controller for high-speed scanning probe microscopy

NASA Astrophysics Data System (ADS)

Dukic, Maja; Todorov, Vencislav; Andany, Santiago; Nievergelt, Adrian P.; Yang, Chen; Hosseini, Nahid; Fantner, Georg E.

2017-12-01

Nearly all scanning probe microscopes (SPMs) contain a feedback controller, which is used to move the scanner in the direction of the z-axis in order to maintain a constant setpoint based on the tip-sample interaction. The most frequently used feedback controller in SPMs is the proportional-integral (PI) controller. The bandwidth of the PI controller presents one of the speed limiting factors in high-speed SPMs, where higher bandwidths enable faster scanning speeds and higher imaging resolution. Most SPM systems use digital signal processor-based PI feedback controllers, which require analog-to-digital and digital-to-analog converters. These converters introduce additional feedback delays which limit the achievable imaging speed and resolution. In this paper, we present a digitally controlled analog proportional-integral-derivative (PID) controller. The controller implementation allows tunability of the PID gains over a large amplification and frequency range, while also providing precise control of the system and reproducibility of the gain parameters. By using the analog PID controller, we were able to perform successful atomic force microscopy imaging of a standard silicon calibration grating at line rates up to several kHz.

Digitally controlled analog proportional-integral-derivative (PID) controller for high-speed scanning probe microscopy.

PubMed

Dukic, Maja; Todorov, Vencislav; Andany, Santiago; Nievergelt, Adrian P; Yang, Chen; Hosseini, Nahid; Fantner, Georg E

2017-12-01

Nearly all scanning probe microscopes (SPMs) contain a feedback controller, which is used to move the scanner in the direction of the z-axis in order to maintain a constant setpoint based on the tip-sample interaction. The most frequently used feedback controller in SPMs is the proportional-integral (PI) controller. The bandwidth of the PI controller presents one of the speed limiting factors in high-speed SPMs, where higher bandwidths enable faster scanning speeds and higher imaging resolution. Most SPM systems use digital signal processor-based PI feedback controllers, which require analog-to-digital and digital-to-analog converters. These converters introduce additional feedback delays which limit the achievable imaging speed and resolution. In this paper, we present a digitally controlled analog proportional-integral-derivative (PID) controller. The controller implementation allows tunability of the PID gains over a large amplification and frequency range, while also providing precise control of the system and reproducibility of the gain parameters. By using the analog PID controller, we were able to perform successful atomic force microscopy imaging of a standard silicon calibration grating at line rates up to several kHz.

Digital quadrature phase detection

DOEpatents

Smith, James A.; Johnson, John A.

1992-01-01

A system for detecting the phase of a frequency of phase modulated signal that includes digital quadrature sampling of the frequency or phase modulated signal at two times that are one quarter of a cycle of a reference signal apart, determination of the arctangent of the ratio of a first sampling of the frequency or phase modulated signal to the second sampling of the frequency or phase modulated signal, and a determination of quadrant in which the phase determination is increased by 2.pi. when the quadrant changes from the first quadrant to the fourth quadrant and decreased by 2.pi. when the quadrant changes from the fourth quadrant to the first quadrant whereby the absolute phase of the frequency or phase modulated signal can be determined using an arbitrary reference convention.

Digital quadrature phase detection

DOEpatents

Smith, J.A.; Johnson, J.A.

1992-05-26

A system for detecting the phase of a frequency or phase modulated signal that includes digital quadrature sampling of the frequency or phase modulated signal at two times that are one quarter of a cycle of a reference signal apart, determination of the arctangent of the ratio of a first sampling of the frequency or phase modulated signal to the second sampling of the frequency or phase modulated signal, and a determination of quadrant in which the phase determination is increased by 2[pi] when the quadrant changes from the first quadrant to the fourth quadrant and decreased by 2[pi] when the quadrant changes from the fourth quadrant to the first quadrant whereby the absolute phase of the frequency or phase modulated signal can be determined using an arbitrary reference convention. 6 figs.

Mycorrhiza Symbiosis Increases the Surface for Sunlight Capture in Medicago truncatula for Better Photosynthetic Production

PubMed Central

Adolfsson, Lisa; Keresztes, Áron; Uddling, Johan; Schoefs, Benoît; Spetea, Cornelia

2015-01-01

Arbuscular mycorrhizal (AM) fungi play a prominent role in plant nutrition by supplying mineral nutrients, particularly inorganic phosphate (Pi), and also constitute an important carbon sink. AM stimulates plant growth and development, but the underlying mechanisms are not well understood. In this study, Medicago truncatula plants were grown with Rhizophagus irregularis BEG141 inoculum (AM), mock inoculum (control) or with Pi fertilization. We hypothesized that AM stimulates plant growth through either modifications of leaf anatomy or photosynthetic activity per leaf area. We investigated whether these effects are shared with Pi fertilization, and also assessed the relationship between levels of AM colonization and these effects. We found that increased Pi supply by either mycorrhization or fertilization led to improved shoot growth associated with increased nitrogen uptake and carbon assimilation. Both mycorrhized and Pi-fertilized plants had more and longer branches with larger and thicker leaves than the control plants, resulting in an increased photosynthetically active area. AM-specific effects were earlier appearance of the first growth axes and increased number of chloroplasts per cell section, since they were not induced by Pi fertilization. Photosynthetic activity per leaf area remained the same regardless of type of treatment. In conclusion, the increase in growth of mycorrhized and Pi-fertilized Medicago truncatula plants is linked to an increase in the surface for sunlight capture, hence increasing their photosynthetic production, rather than to an increase in the photosynthetic activity per leaf area. PMID:25615871

Low-molecular-weight color pI markers to monitor on-line the peptide focusing process in OFFGEL fractionation.

PubMed

Michelland, Sylvie; Bourgoin-Voillard, Sandrine; Cunin, Valérie; Tollance, Axel; Bertolino, Pascal; Slais, Karel; Seve, Michel

2017-08-01

High-throughput mass spectrometry-based proteomic analysis requires peptide fractionation to simplify complex biological samples and increase proteome coverage. OFFGEL fractionation technology became a common method to separate peptides or proteins using isoelectric focusing in an immobilized pH gradient. However, the OFFGEL focusing process may be further optimized and controlled in terms of separation time and pI resolution. Here we evaluated OFFGEL technology to separate peptides from different samples in the presence of low-molecular-weight (LMW) color pI markers to visualize the focusing process. LMW color pI markers covering a large pH range were added to the peptide mixture before OFFGEL fractionation using a 24-wells device encompassing the pH range 3-10. We also explored the impact of LMW color pI markers on peptide fractionation labeled previously for iTRAQ. Then, fractionated peptides were separated by RP_HPLC prior to MS analysis using MALDI-TOF/TOF mass spectrometry in MS and MS/MS modes. Here we report the performance of the peptide focusing process in the presence of LMW color pI markers as on-line trackers during the OFFGEL process and the possibility to use them as pI controls for peptide focusing. This method improves the workflow for peptide fractionation in a bottom-up proteomic approach with or without iTRAQ labeling. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transitioning EEG experiments away from the laboratory using a Raspberry Pi 2.

PubMed

Kuziek, Jonathan W P; Shienh, Axita; Mathewson, Kyle E

2017-02-01

Electroencephalography (EEG) experiments are typically performed in controlled laboratory settings to minimise noise and produce reliable measurements. These controlled conditions also reduce the applicability of the obtained results to more varied environments and may limit their relevance to everyday situations. Advances in computer portability may increase the mobility and applicability of EEG results while decreasing costs. In this experiment we show that stimulus presentation using a Raspberry Pi 2 computer provides a low cost, reliable alternative to a traditional desktop PC in the administration of EEG experimental tasks. Significant and reliable MMN and P3 activity, typical event-related potentials (ERPs) associated with an auditory oddball paradigm, were measured while experiments were administered using the Raspberry Pi 2. While latency differences in ERP triggering were observed between systems, these differences reduced power only marginally, likely due to the reduced processing power of the Raspberry Pi 2. An auditory oddball task administered using the Raspberry Pi 2 produced similar ERPs to those derived from a desktop PC in a laboratory setting. Despite temporal differences and slight increases in trials needed for similar statistical power, the Raspberry Pi 2 can be used to design and present auditory experiments comparable to a PC. Our results show that the Raspberry Pi 2 is a low cost alternative to the desktop PC when administering EEG experiments and, due to its small size and low power consumption, will enable mobile EEG experiments unconstrained by a traditional laboratory setting. Copyright © 2016 Elsevier B.V. All rights reserved.

Adaptive control paradigm for photovoltaic and solid oxide fuel cell in a grid-integrated hybrid renewable energy system.

PubMed

Mumtaz, Sidra; Khan, Laiq

2017-01-01

The hybrid power system (HPS) is an emerging power generation scheme due to the plentiful availability of renewable energy sources. Renewable energy sources are characterized as highly intermittent in nature due to meteorological conditions, while the domestic load also behaves in a quite uncertain manner. In this scenario, to maintain the balance between generation and load, the development of an intelligent and adaptive control algorithm has preoccupied power engineers and researchers. This paper proposes a Hermite wavelet embedded NeuroFuzzy indirect adaptive MPPT (maximum power point tracking) control of photovoltaic (PV) systems to extract maximum power and a Hermite wavelet incorporated NeuroFuzzy indirect adaptive control of Solid Oxide Fuel Cells (SOFC) to obtain a swift response in a grid-connected hybrid power system. A comprehensive simulation testbed for a grid-connected hybrid power system (wind turbine, PV cells, SOFC, electrolyzer, battery storage system, supercapacitor (SC), micro-turbine (MT) and domestic load) is developed in Matlab/Simulink. The robustness and superiority of the proposed indirect adaptive control paradigm are evaluated through simulation results in a grid-connected hybrid power system testbed by comparison with a conventional PI (proportional and integral) control system. The simulation results verify the effectiveness of the proposed control paradigm.

Adaptive control paradigm for photovoltaic and solid oxide fuel cell in a grid-integrated hybrid renewable energy system

PubMed Central

Khan, Laiq

2017-01-01

The hybrid power system (HPS) is an emerging power generation scheme due to the plentiful availability of renewable energy sources. Renewable energy sources are characterized as highly intermittent in nature due to meteorological conditions, while the domestic load also behaves in a quite uncertain manner. In this scenario, to maintain the balance between generation and load, the development of an intelligent and adaptive control algorithm has preoccupied power engineers and researchers. This paper proposes a Hermite wavelet embedded NeuroFuzzy indirect adaptive MPPT (maximum power point tracking) control of photovoltaic (PV) systems to extract maximum power and a Hermite wavelet incorporated NeuroFuzzy indirect adaptive control of Solid Oxide Fuel Cells (SOFC) to obtain a swift response in a grid-connected hybrid power system. A comprehensive simulation testbed for a grid-connected hybrid power system (wind turbine, PV cells, SOFC, electrolyzer, battery storage system, supercapacitor (SC), micro-turbine (MT) and domestic load) is developed in Matlab/Simulink. The robustness and superiority of the proposed indirect adaptive control paradigm are evaluated through simulation results in a grid-connected hybrid power system testbed by comparison with a conventional PI (proportional and integral) control system. The simulation results verify the effectiveness of the proposed control paradigm. PMID:28329015

Untangling the Web: The Diverse Functions of the PIWI/piRNA Pathway

PubMed Central

Mani, Sneha Ramesh; Juliano, Celina E.

2014-01-01

SUMMARY Small RNAs impact several cellular processes through gene regulation. Argonaute proteins bind small RNAs to form effector complexes that control transcriptional and post-transcriptional gene expression. PIWI proteins belong to the Argonaute protein family, and bind PIWI-interacting RNAs (piRNAs). They are highly abundant in the germline, but are also expressed in some somatic tissues. The PIWI/piRNA pathway has a role in transposon repression in Drosophila, which occurs both by epigenetic regulation and post-transcriptional degradation of transposon mRNAs. These functions are conserved, but clear differences in the extent and mechanism of transposon repression exist between species. Mutations in piwi genes lead to the upregulation of transposon mRNAs. It is hypothesized that this increased transposon mobilization leads to genomic instability and thus sterility, although no causal link has been established between transposon upregulation and genome instability. An alternative scenario could be that piwi mutations directly affect genomic instability, and thus lead to increased transposon expression. We propose that the PIWI/piRNA pathway controls genome stability in several ways: suppression of transposons, direct regulation of chromatin architecture and regulation of genes that control important biological processes related to genome stability. The PIWI/piRNA pathway also regulates at least some, if not many, protein-coding genes, which further lends support to the idea that piwi genes may have broader functions beyond transposon repression. An intriguing possibility is that the PIWI/piRNA pathway is using transposon sequences to coordinate the expression of large groups of genes to regulate cellular function. PMID:23712694

Evaluation of Relationship between Obsessive-compulsive Disorder and Dissociative Experiences.

PubMed

Tatlı, Mustafa; Cetinkaya, Ozlem; Maner, Fulya

2018-05-31

The aim of the study is to evaluate the relationship between obsessive-compulsive disorder (OCD) symptoms and dissociative experiences and the effect of childhood traumatic experiences on this relationship in OCD patients. Fifty consecutive OCD patients and 50 healthy controls are enrolled for this study. Sociodemographic and Clinical Data Form, Dissociative Experiences Scale (DES), Padua Inventory (PI) and Childhood Trauma Questionnaire (CTQ) are applied to participants. Average DES total score in the patient group is 20.58 and in the control group it is 4.87. In the patient group, when we evaluate the relation strengths of DES total and subscale scores with PI total score, we found out that amnesia subscale has r=0.361 ( p <0.01), absorption subscale has r=0.611 ( p <0.01), depersonalization/derealization subscale has r=0.574 ( p <0.01), and DES total score has r=0.55 ( p <0.01) relation strengths with PI total score. In patient group both DES total score and CTQ total score have influence on PI total score independently from each other. In addition to this, the level of the influence of DES total scores on PI total scores is, R²=0.399 ( p <0.01) and the level of the influence of CTQ total scores on PI total scores is R²=0.343 ( p <0.01). Dissociative experiences are seen more frequently in OCD patients than healthy controls. Among dissociative experiences, absorption has stronger relation with OCD symptoms. The relation between OCD and dissociation is independent from and stronger than the relation between childhood traumatic experiences and OCD.

Relationship between dietary protein intake and the changes in creatinine clearance and glomerular cross-sectional area in patients with IgA nephropathy.

PubMed

Wada, Toshikazu; Nakao, Toshiyuki; Matsumoto, Hiroshi; Okada, Tomonari; Nagaoka, Yume; Iwasawa, Hideaki; Gondo, Asako; Niwata, Ami; Kanno, Yoshihiko

2015-08-01

Dietary protein intake (PI) induces glomerular hyperfiltration and reduced dietary PI can be effective in preserving kidney function. However, there is limited information regarding the relationship between dietary PI and glomerular histological changes in chronic kidney disease. We investigated the relationship between changes in dietary PI and both the changes in creatinine clearance and glomerular histomorphometry in adult patients with IgA nephropathy (IgAN). A total of 24 consecutive adult patients with biopsy-confirmed IgAN were enrolled and glomerular histomorphometric variables and clinical variables were investigated. The main clinical variables were differences in creatinine clearance (Ccr) (dCcr) and in PI (dPI) which were calculated by subtracting PI and Ccr values in patients on a controlled diet during hospitalization for kidney biopsy from the respective values in patients on daily diets as outpatients. These values of PI were estimated from urinary urea excretion measured by 24-h urine collection. The main renal histomorphometric variable was glomerular tuft area (GTA) (μm(2)). dCcr positively correlated with dPI (r = 0.726, P < 0.001). GTA correlated positively with dPI (r = 0.556, P = 0.013). Multiple regression analysis showed that dPI was independently associated with both dCcr and GTA. Additionally, GTA positively correlated with dietary PI as outpatients (r = 0.457, P = 0.043). Changes in dietary PI were associated with the changes in glomerular filtration rate. Furthermore, histomorphometric findings suggested that a greater dietary PI can affect the glomerular size at the time of the initial diagnostic biopsy for IgAN.

Effect of Bovine Viral Diarrhea Virus on the ovarian functionality and in vitro reproductive performance of persistently infected heifers.

PubMed

González Altamiranda, E A; Kaiser, G G; Mucci, N C; Verna, A E; Campero, C M; Odeón, A C

2013-08-30

The aim of this study was to study the effect of Bovine Viral Diarrhea Virus on the reproductive female tract by means of analyzing the ovarian follicular population of persistently infected (PI) heifers, and evaluating the performance of oocytes procured form those heifers in in vitro fertilization procedures. Seven BVDV PI Aberdeen Angus and British crossbred heifers ranging from 18 to 36 months of age were spayed and their ovaries used for viral isolation, microscopic examination, and in vitro fertilization procedures. Bovine Viral Diarrhea Virus was detected from the follicular fluid and sera of all PI heifers. Microscopic examination of the ovaries from PI heifers showed a significant drop in the number of follicles cortical regions, compared with controls. A comparative analysis of the stages of follicular development showed a significant decrease in the number of primordial and tertiary follicles in the cortical regions of ovaries from PI heifers. Viral antigen was detected by immunohistochemistry, and was widely distributed throughout the ovarian tissues. There were differences in the rate of cleavage and embryo development between oocytes obtained from the ovaries of control animals and PI heifers. Furthermore, two developed embryos obtained from oocytes from one of the PI heifers were positive to BVDV, as well as two media from in vitro fertilization (IVF) procedures. The results of this study demonstrate that BVDV PI heifers exhibit alterations in follicular population through of the early interaction between the virus and germ cell line affecting directly the mechanisms involved in the ontogenesis of the ovary. Copyright © 2013 Elsevier B.V. All rights reserved.

Motility Response to Colonic Distention is Increased in Post-infectious Irritable Bowel Syndrome (PI-IBS)

PubMed Central

Kanazawa, Motoyori; Palsson, Olafur S.; van Tilburg, Miranda A.L.; Gangarosa, Lisa M.; Fukudo, Shin; Whitehead., William E.

2015-01-01

Background Acute intestinal infection leads to persistent intestinal smooth muscle hypercontractility and pain hypersensitivity after resolution of the infection in animal models. We investigated whether post-infectious irritable bowel syndrome (PI-IBS) is associated with abnormalities in phasic contractions of the colon, smooth muscle tone and pain sensitivity compared to non-PI-IBS (NI-IBS) or healthy controls (HC). Methods 218 Rome III positive IBS patients and 43 healthy controls participated. IBS patients were designated PI-IBS if their IBS symptoms began following an episode of gastroenteritis characterized by 2 or more of: fever, vomiting, or diarrhea. Pain threshold to phasic distentions of the descending colon was assessed using a barostat. Colonic motility was assessed with the barostat bag minimally inflated to the individual operating pressure (IOP), at 20 mmHg above the IOP, and following a test meal. IBS symptom severity and psychological symptoms were assessed by the IBS Severity Scale (IBS-SS) and the Brief Symptom Inventory-18 (BSI-18). Key Results Twenty-two (10.1%) met criteria for PI-IBS. Both IBS and HC groups showed a significant increase in motility index during intraluminal distention and following meals. The magnitude of the response to distention above (orad to) the balloon was significantly greater in PI-IBS compared with NI-IBS (p<0.05) or HC (p<0.01). Differences between PI-IBS and NI-IBS were not significant for IBS symptom severity, pain threshold, barostat bag volumes, or any psychological score on the BSI-18. Conclusions & Inferences Patients with PI-IBS have greater colonic hypercontractility than NI-IBS. We speculate that sustained mild mucosal inflammation may cause this colonic irritability. PMID:24602083

Carbon-ion radiation enhances migration ability and invasiveness of the pancreatic cancer cell, PANC-1, in vitro.

PubMed

Fujita, Mayumi; Otsuka, Yoshimi; Imadome, Kaori; Endo, Satoshi; Yamada, Shigeru; Imai, Takashi

2012-04-01

Pancreatic cancer is an aggressive disease that responds poorly to conventional photon radiotherapy. Carbon-ion (C-ion) radiation has advantages compared with conventional radiotherapy, because it enables more accurate dose distribution and more efficient tumor cell killing. To elucidate the effects of local radiotherapy on the characteristics of metastatic tumors, it is necessary to understand the nature of motility in irradiated tumor cells; this will, in turn, facilitate the development of effective strategies to counter tumor cell motility, which can be used in combination with radiotherapy. The aim of the present study was to examine the invasiveness of pancreatic cancer cells exposed to C-ion irradiation. We found that C-ion irradiation suppressed the migration of MIAPaCa-2, BxPC-3 and AsPC-1; diminished the invasiveness of MIAPaCa-2; and tended to reduce the invasion of BxPC-3 and AsPC-1. However, C-ion irradiation increased the invasiveness of PANC-1 through the activation of plasmin and urokinase-type plasiminogen activator. Administration of serine protease inhibitor (SerPI) alone failed to reduce C-ion-induced PANC-1 invasiveness, whereas the combination of SerPI and Rho-associated coiled-coil forming protein kinase (ROCK) inhibitor suppressed it. Furthermore, PANC-1 showed mesenchymal-amoeboid transition when we treated with SerPI alone. In conclusion, C-ion irradiation is effective in suppressing the invasive potential of several pancreatic tumor cell lines, but not PANC-1; this is the first study showing that C-ion irradiation induces the invasive potential of a tumor cell line. Further in vivo studies are required to examine the therapeutic effectiveness of radiotherapy combined with inhibitors of both mesenchymal and amoeboid modes of tumor cell motility. © 2011 Japanese Cancer Association.

Preference test of sound among multiple alternatives in rats.

PubMed

Soga, Ryo; Shiramatsu, Tomoyo Isoguchi; Takahashi, Hirokazu

2018-01-01

Conditioned place preference (CPP) tests in rodents have been well established to measure preference induced by secondary reinforcing properties, but conventional assays are not sensitive enough to measure innate, weak preference, or the primary reinforcing property of a conditioned stimulus. We designed a novel CPP assay with better sensitivity and efficiency in quantifying and ranking preference of particular sounds among multiple alternatives. Each test tone was presented according to the location of free-moving rats in the arena, where assignment of location to each tone changed in every 20-s session. We demonstrated that our assay was able to rank tone preference among 4 alternatives within 12.5 min (125 s (habituation) + 25 s/sessions × 25 sessions). In order to measure and rank sound preference, we attempted to use sojourn times with each test sound ([Formula: see text]), and a preference index (PI) based on transition matrices of initial and end sounds in every session. Both [Formula: see text] and PI revealed similar trends of innate preference in which rats preferred test conditions in the following order: silence, 40-, 20-, then 10-kHz tones. Further, rats exhibited a change in preference after an classical conditioning of the 20-kHz tone with a rewarding microstimulation of the dopaminergic system. We also demonstrated that PI was a more robust and sensitive indicator than [Formula: see text] when the locomotion activity level of rats became low due to habituation to the assay repeated over sessions. Thus, our assay offers a novel method of evaluating auditory preference that is superior to conventional CPP assays, offering promising prospects in the field of sensory neuroscience.

Novel agents for advanced pancreatic cancer

PubMed Central

Akinleye, Akintunde; Iragavarapu, Chaitanya; Furqan, Muhammad; Cang, Shundong; Liu, Delong

2015-01-01

Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer. PMID:26369833

Operator control systems and methods for swing-free gantry-style cranes

DOEpatents

Feddema, J.T.; Petterson, B.J.; Robinett, R.D. III

1998-07-28

A system and method are disclosed for eliminating swing motions in gantry-style cranes while subject to operator control. The present invention comprises an infinite impulse response (IIR) filter and a proportional-integral (PI) feedback controller. The IIR filter receives input signals (commanded velocity or acceleration) from an operator input device and transforms them into output signals in such a fashion that the resulting motion is swing free (i.e., end-point swinging prevented). The parameters of the IIR filter are updated in real time using measurements from a hoist cable length encoder. The PI feedback controller compensates for modeling errors and external disturbances, such as wind or perturbations caused by collision with objects. The PI feedback controller operates on cable swing angle measurements provided by a cable angle sensor. The present invention adjusts acceleration and deceleration to eliminate oscillations. An especially important feature of the present invention is that it compensates for variable-length cable motions from multiple cables attached to a suspended payload. 10 figs.

Operator control systems and methods for swing-free gantry-style cranes

DOEpatents

Feddema, John T.; Petterson, Ben J.; Robinett, III, Rush D.

1998-01-01

A system and method for eliminating swing motions in gantry-style cranes while subject to operator control is presented. The present invention comprises an infinite impulse response ("IIR") filter and a proportional-integral ("PI") feedback controller (50). The IIR filter receives input signals (46) (commanded velocity or acceleration) from an operator input device (45) and transforms them into output signals (47) in such a fashion that the resulting motion is swing free (i.e., end-point swinging prevented). The parameters of the IIR filter are updated in real time using measurements from a hoist cable length encoder (25). The PI feedback controller compensates for modeling errors and external disturbances, such as wind or perturbations caused by collision with objects. The PI feedback controller operates on cable swing angle measurements provided by a cable angle sensor (27). The present invention adjusts acceleration and deceleration to eliminate oscillations. An especially important feature of the present invention is that it compensates for variable-length cable motions from multiple cables attached to a suspended payload.

[Research on magnetic coupling centrifugal blood pump control based on a self-tuning fuzzy PI algorithm].

PubMed

Yang, Lei; Yang, Ming; Xu, Zihao; Zhuang, Xiaoqi; Wang, Wei; Zhang, Haibo; Han, Lu; Xu, Liang

2014-10-01

The purpose of this paper is to report the research and design of control system of magnetic coupling centrifugal blood pump in our laboratory, and to briefly describe the structure of the magnetic coupling centrifugal blood pump and principles of the body circulation model. The performance of blood pump is not only related to materials and structure, but also depends on the control algorithm. We studied the algorithm about motor current double-loop control for brushless DC motor. In order to make the algorithm adjust parameter change in different situations, we used the self-tuning fuzzy PI control algorithm and gave the details about how to design fuzzy rules. We mainly used Matlab Simulink to simulate the motor control system to test the performance of algorithm, and briefly introduced how to implement these algorithms in hardware system. Finally, by building the platform and conducting experiments, we proved that self-tuning fuzzy PI control algorithm could greatly improve both dynamic and static performance of blood pump and make the motor speed and the blood pump flow stable and adjustable.

piRNAs and their diverse roles: a transposable element-driven tactic for gene regulation?

PubMed

Sarkar, Arpita; Volff, Jean-Nicolas; Vaury, Chantal

2017-02-01

P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are small, noncoding RNAs known for silencing transposable elements (TEs) in the germline of animals. Most genomes host TEs, which are notorious for mobilizing themselves and endangering survival of the host if not controlled. By silencing TEs in the germline, piRNAs prevent harmful mutations from being passed on to the next generation. How piRNAs are generated and how they silence TEs were the focus of researchers ever since their discovery. Now a spate of recent papers are beginning to tell us that piRNAs can play roles beyond TE silencing and are involved in diverse cellular processes from mRNA regulation to development or genome rearrangement. In this review, we discuss some of these recently reported roles. Data on these new roles are often rudimentary, and the involvement of piRNAs in these processes is yet to be definitely established. What is interesting is that the reports are on animals widely separated on the phylogenetic tree of life and that piRNAs were also found outside the gonadal tissues. Some of these piRNAs map to TE sequences, prompting us to hypothesize that genomes may have co-opted the TE-derived piRNA system for their own regulation.-Sarkar, A., Volff, J.-N., Vaury, C. piRNAs and their diverse roles: a transposable element-driven tactic for gene regulation? © FASEB.

Statistical Study of the Characteristics of Isolated Bursts of Midlatitude Pi2 Geomagnetic Pulsations

NASA Astrophysics Data System (ADS)

Kurazhkovskaya, N. A.; Klain, B. I.

2018-03-01

The characteristics and interplanetary excitation conditions of isolated bursts of Pi2 geomagnetic pulsations observed during the development of magnetospheric substorms (substorm Pi2) and in its absence (nonsubstorm Pi2) on the night side of the Earth are comparatively analyzed. It is shown that, regardless of the local time and season, the amplitude of isolated Pi2 substorm bursts is always higher than that of the nonsubstorm ones, and the periods and duration of the wave packets of substorm Pi2 bursts are less than those of nonsubstorms. Diurnal and seasonal variations in the characteristics of the two groups of Pi2 bursts differ in the form and position of maxima and minima. It is found that the start of excitation of isolated Pi2 bursts, during substorms and in its absence, is controlled by the preferred direction of the interplanetary magnetic field (IMF) vector perpendicular to the Sun-Earth line (angle θxB = arccos( B x/B) → 90°). It is assumed that isolated Pi2 bursts of both groups are triggered by reorientation of the IMF vector in the ecliptic plane and the plane perpendicular to it 15 min before their onset. The most likely source of midlatitude isolated Pi2 bursts during substorm development and in its absence are bursty bulk flows (BBFs) in the plasma sheet of the magnetospheric tail, the regularities of which coincide in many respects with the observed features of Pi2 bursts.

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.

Euchromatic Transposon Insertions Trigger Production of Novel Pi- and Endo-siRNAs at the Target Sites in the Drosophila Germline

PubMed Central

Olovnikov, Ivan; Abramov, Yuri; Kalmykova, Alla

2014-01-01

The control of transposable element (TE) activity in germ cells provides genome integrity over generations. A distinct small RNA–mediated pathway utilizing Piwi-interacting RNAs (piRNAs) suppresses TE expression in gonads of metazoans. In the fly, primary piRNAs derive from so-called piRNA clusters, which are enriched in damaged repeated sequences. These piRNAs launch a cycle of TE and piRNA cluster transcript cleavages resulting in the amplification of piRNA and TE silencing. Using genome-wide comparison of TE insertions and ovarian small RNA libraries from two Drosophila strains, we found that individual TEs inserted into euchromatic loci form novel dual-stranded piRNA clusters. Formation of the piRNA-generating loci by active individual TEs provides a more potent silencing response to the TE expansion. Like all piRNA clusters, individual TEs are also capable of triggering the production of endogenous small interfering (endo-si) RNAs. Small RNA production by individual TEs spreads into the flanking genomic regions including coding cellular genes. We show that formation of TE-associated small RNA clusters can down-regulate expression of nearby genes in ovaries. Integration of TEs into the 3′ untranslated region of actively transcribed genes induces piRNA production towards the 3′-end of transcripts, causing the appearance of genic piRNA clusters, a phenomenon that has been reported in different organisms. These data suggest a significant role of TE-associated small RNAs in the evolution of regulatory networks in the germline. PMID:24516406

Combined adductor canal block with periarticular infiltration versus periarticular infiltration for analgesia after total knee arthroplasty.

PubMed

Ma, Jinhui; Gao, Fuqiang; Sun, Wei; Guo, Wanshou; Li, Zirong; Wang, Weiguo

2016-12-01

Both adductor canal block (ACB) and periarticular infiltration (PI) have been shown to reduce pain after total knee arthroplasty (TKA) without the motor blockade. However, the efficacy and safety of combined ACB with PI (ACB + PI) as compared to PI alone for analgesia after TKA remains controversial. We therefore performed a meta-analysis to compare the effects of ACB + PI with PI alone on pain controll after TKA. PubMed, Medline, Embase, Web of Science, and the Cochrane Library were searched to identify studies comparing ACB + PI with PI alone for TKA patients. The primary outcomes included pain score with rest or activity and morphine consumption. Secondary outcomes were distance walked, length of hospital stay, and postoperative complications. Relevant data were analyzed using RevMan v5.3. Three studies involving 337 patients were included. Combined ACB with PI was associated with longer distances walked than PI alone (MD = 7.27, 95% CI: 0.43-14.12, P = 0.04) on postoperative day 1. The outcomes of pain, morphine consumption, length of hospital stay, and postoperative complications were not statistically different between the 2 groups (P > 0.05). Our meta-analysis suggests that combined ACB with PI may achieve earlier ambulation for patients after TKA without a reduction in analgesia when compared to PI alone in the early postoperative period. There were no significant differences in morphine consumption, length of hospital stay, and postoperative complications between the 2 groups. However, owing to the variation of included studies, no firm conclusions can be drawn.

Artemether as adjuvant therapy to praziquantel in murine Egyptian schistosomiasis mansoni.

PubMed

Mahmoud, M R; Botros, S S

2005-02-01

We investigated the activity of artemether (ART) against different developmental stages of schistosomes alone and in addition to praziquantel (PZQ). ART was administered orally (400 mg/kg) 4 and 6 wk postinfection (PI), 4 and 5 wk PI, or 4 or 6 wk PI alone and in addition to oral PZQ (500 x 2 mg/kg) 6 wk PI. Mice were killed in parallel to infected untreated controls 8 wk PI. Parasitological parameters and histological changes in the liver were studied. ART given 4 and 6 wk PI reduced worm burdens by 59 and 55% and tissue egg load by 96 and 90%, respectively. Moreover, eggs in different developmental stages were not found. The reduction in worm and egg burden (63 and 58%, and 96 and 99%, respectively) in mice treated with ART 4 and 5 wk or 4 and 6 wk PI was comparable with that in ART-treated mice at 4 or 6 wk PI. Compared with PZQ alone, combined treatment of PZQ and ART (4 and 5 wk or 4 and 6 wk PI) did not enhance worm eradication, but there was a complete absence of parasite eggs. Livers revealed no granulomata when ART was given 4 and 5 wk or 4 and 6 wk PI, with minimal central necrosis in those treated 4 and 6 wk PI. In conclusion, combined treatment of ART (4 and 6 wk PI) and PZQ resulted in >90% worm eradication and amelioration of Schistosoma mansoni eggs from the tissues, with minor histological changes in the liver.

Design and synthesis of imidazopyridine analogues as inhibitors of phosphoinositide 3-kinase signaling and angiogenesis.

PubMed

Kim, Okseon; Jeong, Yujeong; Lee, Hyunseung; Hong, Sun-Sun; Hong, Sungwoo

2011-04-14

Phosphatidylinositol 3-kinase α (PI3Kα) is an important regulator of intracellular signaling pathways, controlling remarkably diverse arrays of physiological processes. Because the PI3K pathway is frequently up-regulated in human cancers, the inhibition of PI3Kα can be a promising approach to cancer therapy. In this study, we have designed and synthesized a new series of imidazo[1,2-a]pyridine derivatives as PI3Kα inhibitors through the fragment-growing strategy. By varying groups at the 3- and 6-positions of imidazo[1,2-a]pyridines, we studied the structure-activity relationships (SAR) profiles and identified a series of potent PI3Kα inhibitors. Representative derivatives showed good activity in cellular proliferation and apoptosis assays. Moreover, these inhibitors exhibited noteworthy antiangiogenic activity.

[Expression of mRNA and protein of p38, Osx, PI3K and Akt1 in rat bone with chronic fluorosis].

PubMed

Yu, Yan-ni; Yang, Dan; Zhu, Hai-zhen; Deng, Chao-nan; Guan, Zhi-zhong

2012-09-01

To investigate the expressions of mRNA and protein of p38, Osx, PI3K, Akt1 in the rats bone with chronic fluorosis. Dental fluorosis were observed and the fluoride contents in the urine and bone were detected by fluorin-ion selective electrode. The morphologic changes and ultrastructure of rats' bone were observed by light and electronic microscopy. The expressions of protein and mRNA of p38, Osx, PI3K and Akt1 were detected by immunohistochemistry and real-time PCR, respectively. The contents of BALP and BGP in serum were detected by ELISA. The rates of dental fluorosis in the fluorosis rats were increased, and the fluoride contents in bone and urine of the fluorosis rats were increased compared to the control group, the difference was statistically significant (P < 0.05). The bone trabeculae thickness and density and the thickness of bone cortex in fluorosis rats were remarkably increased, the space of bone trabeculae was reduced, and in accordance with the matching morphometrical indices, the difference was statistically significant (P < 0.05) as compared with the control rats. The contents of BALP [(54.61 ± 2.27) U/L] and BGP [(2.38 ± 0.16) µg/L]in the fluoride groups were higher than those in the control group, the difference was statistically significant (P < 0.05). Ultrastructurally, the broadening of the osseouslacuna was observed. The reduced protuberances of the osteocytes, the unclear organelle structure, pyknosis, karyotheca increasation and edged chromatin were also observed. Compared to the control group, the expressions of protein and its mRNA of p38, Osx, PI3K and Akt1 were higher in the fluorosis rats than those in the control rats, and the difference was statistically significant (P < 0.05). There is no any expression of p38, Osx, PI3K and Akt1 in the osteocytes in fluorosis rats. The over-expression of p38, Osx, PI3K and Akt1 in bone tissue of fluorosis rats may relate to the accumulation of fluorine in the body. The bone injury mainly occur in the stage of the differentiation and proliferation. The upregulation of P38MARK signal path and PI3K/Akt1 signal path may be involved in the pathogenesis of bone injury caused by fluoride.

Asymptotic sideslip angle and yaw rate decoupling control in four-wheel steering vehicles

NASA Astrophysics Data System (ADS)

Marino, Riccardo; Scalzi, Stefano

2010-09-01

This paper shows that, for a four-wheel steering vehicle, a proportional-integral (PI) active front steering control and a PI active rear steering control from the yaw rate error together with an additive feedforward reference signal for the vehicle sideslip angle can asymptotically decouple the lateral velocity and the yaw rate dynamics; that is the control can set arbitrary steady state values for lateral speed and yaw rate at any longitudinal speed. Moreover, the PI controls can suppress oscillatory behaviours by assigning real stable eigenvalues to a widely used linearised model of the vehicle steering dynamics for any value of longitudinal speed in understeering vehicles. In particular, the four PI control parameters are explicitly expressed in terms of the three real eigenvalues to be assigned. No lateral acceleration and no lateral speed measurements are required. The controlled system maintains the well-known advantages of both front and rear active steering controls: higher controllability, enlarged bandwidth for the yaw rate dynamics, suppressed resonances, new stable cornering manoeuvres and improved manoeuvrability. In particular, zero lateral speed may be asymptotically achieved while controlling the yaw rate: in this case comfort is improved since the phase lag between lateral acceleration and yaw rate is reduced. Also zero yaw rate can be asymptotically achieved: in this case additional stable manoeuvres are obtained in obstacle avoidance. Several simulations, including step references and moose tests, are carried out on a standard small SUV CarSim model to explore the robustness with respect to unmodelled effects such as combined lateral and longitudinal tyre forces, pitch, roll and driver dynamics. The simulations confirm the decoupling between the lateral velocity and the yaw rate and show the advantages obtained by the proposed control: reduced lateral speed or reduced yaw rate, suppressed oscillations and new stable manoeuvres.

Targeting phosphoinositide 3-kinase: moving towards therapy.

PubMed

Marone, Romina; Cmiljanovic, Vladimir; Giese, Bernd; Wymann, Matthias P

2008-01-01

Phosphoinositide 3-kinases (PI3K) orchestrate cell responses including mitogenic signaling, cell survival and growth, metabolic control, vesicular trafficking, degranulation, cytoskeletal rearrangement and migration. Deregulation of the PI3K pathway occurs by activating mutations in growth factor receptors or the PIK3CA locus coding for PI3Kalpha, by loss of function of the lipid phosphatase and tensin homolog deleted in chromosome ten (PTEN/MMAC/TEP1), by the up-regulation of protein kinase B (PKB/Akt), or the impairment of the tuberous sclerosis complex (TSC1/2). All these events are linked to growth and proliferation, and have thus prompted a significant interest in the pharmaceutical targeting of the PI3K pathway in cancer. Genetic targeting of PI3Kgamma (p110gamma) and PI3Kdelta (p110delta) in mice has underlined a central role of these PI3K isoforms in inflammation and allergy, as they modulate chemotaxis of leukocytes and degranulation in mast cells. Proof-of-concept molecules selective for PI3Kgamma have already successfully alleviated disease progress in murine models of rheumatoid arthritis and lupus erythematosus. As targeting PI3K moves forward to therapy of chronic, non-fatal disease, safety concerns for PI3K inhibitors increase. Many of the present inhibitor series interfere with target of rapamycin (TOR), DNA-dependent protein kinase (DNA-PK(cs)) and activity of the ataxia telangiectasia mutated gene product (ATM). Here we review the current disease-relevant knowledge for isoform-specific PI3K function in the above mentioned diseases, and review the progress of >400 recent patents covering pharmaceutical targeting of PI3K. Currently, several drugs targeting the PI3K pathway have entered clinical trials (phase I) for solid tumors and suppression of tissue damage after myocardial infarction (phases I,II).

Oxysterol-binding Protein Activation at Endoplasmic Reticulum-Golgi Contact Sites Reorganizes Phosphatidylinositol 4-Phosphate Pools*

PubMed Central

Goto, Asako; Charman, Mark; Ridgway, Neale D.

2016-01-01

Oxysterol-binding protein (OSBP) exchanges cholesterol and phosphatidylinositol 4-phosphate (PI-4P) at contact sites between the endoplasmic reticulum (ER) and the trans-Golgi/trans-Golgi network. 25-Hydroxycholesterol (25OH) competitively inhibits this exchange reaction in vitro and causes the constitutive localization of OSBP at the ER/Golgi interface and PI-4P-dependent recruitment of ceramide transfer protein (CERT) for sphingomyelin synthesis. We used PI-4P probes and mass analysis to determine how OSBP controls the availability of PI-4P for this metabolic pathway. Treatment of fibroblasts or Chinese hamster ovary (CHO) cells with 25OH caused a 50–70% reduction in Golgi-associated immunoreactive PI-4P that correlated with Golgi localization of OSBP. In contrast, 25OH caused an OSBP-dependent enrichment in Golgi PI-4P that was detected with a pleckstrin homology domain probe. The cellular mass of phosphatidylinositol monophosphates and Golgi PI-4P measured with an unbiased PI-4P probe (P4M) was unaffected by 25OH and OSBP silencing, indicating that OSBP shifts the distribution of PI-4P upon localization to ER-Golgi contact sites. The PI-4P and sterol binding activities of OSBP were both required for 25OH activation of sphingomyelin synthesis, suggesting that 25OH must be exchanged for PI-4P to be concentrated at contact sites. We propose a model wherein 25OH activation of OSBP promotes the binding and retention of PI-4P at ER-Golgi contact sites. This pool of PI-4P specifically recruits pleckstrin homology domain-containing proteins involved in lipid transfer and metabolism, such as CERT. PMID:26601944

Oxysterol-binding Protein Activation at Endoplasmic Reticulum-Golgi Contact Sites Reorganizes Phosphatidylinositol 4-Phosphate Pools.

PubMed

Goto, Asako; Charman, Mark; Ridgway, Neale D

2016-01-15

Oxysterol-binding protein (OSBP) exchanges cholesterol and phosphatidylinositol 4-phosphate (PI-4P) at contact sites between the endoplasmic reticulum (ER) and the trans-Golgi/trans-Golgi network. 25-Hydroxycholesterol (25OH) competitively inhibits this exchange reaction in vitro and causes the constitutive localization of OSBP at the ER/Golgi interface and PI-4P-dependent recruitment of ceramide transfer protein (CERT) for sphingomyelin synthesis. We used PI-4P probes and mass analysis to determine how OSBP controls the availability of PI-4P for this metabolic pathway. Treatment of fibroblasts or Chinese hamster ovary (CHO) cells with 25OH caused a 50-70% reduction in Golgi-associated immunoreactive PI-4P that correlated with Golgi localization of OSBP. In contrast, 25OH caused an OSBP-dependent enrichment in Golgi PI-4P that was detected with a pleckstrin homology domain probe. The cellular mass of phosphatidylinositol monophosphates and Golgi PI-4P measured with an unbiased PI-4P probe (P4M) was unaffected by 25OH and OSBP silencing, indicating that OSBP shifts the distribution of PI-4P upon localization to ER-Golgi contact sites. The PI-4P and sterol binding activities of OSBP were both required for 25OH activation of sphingomyelin synthesis, suggesting that 25OH must be exchanged for PI-4P to be concentrated at contact sites. We propose a model wherein 25OH activation of OSBP promotes the binding and retention of PI-4P at ER-Golgi contact sites. This pool of PI-4P specifically recruits pleckstrin homology domain-containing proteins involved in lipid transfer and metabolism, such as CERT. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Serum alpha1 -proteinase inhibitor concentrations in dogs with systemic inflammatory response syndrome or sepsis.

PubMed

Heilmann, Romy M; Grützner, Niels; Thames, Brittany E; Steiner, Jörg M; Barr, James W

2017-11-01

To determine whether the concentration of serum canine alpha 1 -proteinase inhibitor (cα 1 -PI) has diagnostic or prognostic utility in dogs with sepsis or noninfectious systemic inflammatory response syndrome (SIRS). Prospective, observational study from May to December 2010. University teaching hospital ICU. Sixty-nine client-owned dogs: 19 dogs with SIRS or sepsis and 50 healthy control dogs. None. Serum and plasma samples were collected from dogs with SIRS or sepsis on the day of hospital admission and once on the following 2 days, and on a single day in healthy controls. Patients were assessed using the 10-parameter Acute Patient Physiologic and Laboratory Evaluation (APPLE full ) and 5-parameter (APPLE fast ) score. Serum cα 1 -PI concentrations were measured, compared among groups of dogs, and evaluated for a correlation with the concentration of serum C-reactive protein, plasma interleukin-6, tumor necrosis factor-α, the APPLE scores, and survival to discharge. Serum cα 1 -PI concentrations were significantly lower in dogs with SIRS/sepsis (P < 0.001) than in healthy controls. While day 1 serum cα 1 -PI concentrations did not differ between dogs with SIRS and those with sepsis (P = 0.592), septic dogs had significantly lower serum cα 1 -PI concentrations on days 2 (P = 0.017) and 3 (P = 0.036) than dogs with SIRS. Serum cα 1 -PI concentrations did not differ between survivors and nonsurvivors (P = 1.000), but were inversely correlated with the APPLE full score (ρ = -0.48; P = 0.040) and plasma interleukin-6 concentrations (ρ = -0.50; P = 0.037). These results suggest a role of cα 1 -PI as a negative acute phase protein in dogs. The concentration of serum cα 1 -PI at the time of hospital admission does not have utility to identify dogs with sepsis from those with noninfectious SIRS, but may be a useful surrogate marker for early stratification of illness severity. © Veterinary Emergency and Critical Care Society 2017.

Leptin and insulin stimulation of signalling pathways in arcuate nucleus neurones: PI3K dependent actin reorganization and KATP channel activation

PubMed Central

Mirshamsi, Shirin; Laidlaw, Hilary A; Ning, Ke; Anderson, Erin; Burgess, Laura A; Gray, Alexander; Sutherland, Calum; Ashford, Michael LJ

2004-01-01

Background Leptin and insulin are long-term regulators of body weight. They act in hypothalamic centres to modulate the function of specific neuronal subtypes, by altering transcriptional control of releasable peptides and by modifying neuronal electrical activity. A key cellular signalling intermediate, implicated in control of food intake by these hormones, is the enzyme phosphoinositide 3-kinase. In this study we have explored further the linkage between this enzyme and other cellular mediators of leptin and insulin action on rat arcuate nucleus neurones and the mouse hypothalamic cell line, GT1-7. Results Leptin and insulin increased the levels of various phosphorylated signalling intermediates, associated with the JAK2-STAT3, MAPK and PI3K cascades in the arcuate nucleus. Inhibitors of PI3K were shown to reduce the hormone driven phosphorylation through the PI3K and MAPK pathways. Using isolated arcuate neurones, leptin and insulin were demonstrated to increase the activity of KATP channels in a PI3K dependent manner, and to increase levels of PtdIns(3,4,5)P3. KATP activation by these hormones in arcuate neurones was also sensitive to the presence of the actin filament stabilising toxin, jasplakinolide. Using confocal imaging of fluorescently labelled actin and direct analysis of G- and F-actin concentration in GT1-7 cells, leptin was demonstrated directly to induce a re-organization of cellular actin, by increasing levels of globular actin at the expense of filamentous actin in a PI3-kinase dependent manner. Leptin stimulated PI3-kinase activity in GT1-7 cells and an increase in PtdIns(3,4,5)P3 could be detected, which was prevented by PI3K inhibitors. Conclusions Leptin and insulin mediated phosphorylation of cellular signalling intermediates and of KATP channel activation in arcuate neurones is sensitive to PI3K inhibition, thus strengthening further the likely importance of this enzyme in leptin and insulin mediated energy homeostasis control. The sensitivity of leptin and insulin stimulation of KATP channel opening in arcuate neurones to jasplakinolide indicates that cytoskeletal remodelling may be an important contributor to the cellular signalling mechanisms of these hormones in hypothalamic neurones. This hypothesis is reinforced by the finding that leptin induces actin filament depolymerization, in a PI3K dependent manner in a mouse hypothalamic cell line. PMID:15581426

Resistance Training Augments Cerebral Blood Flow Pulsatility: Cross-Sectional Study.

PubMed

Nakamura, Nobuhiro; Muraoka, Isao

2018-06-11

Increased central arterial stiffness and/or decreased compliance reduces buffer function and increases cerebral blood flow (CBF) pulsatility, which leads to increased cerebral microvascular damage, resulting in the augmentation of the risk of cerebrovascular diseases. Resistance-trained men showed higher central arterial stiffness and lower arterial compliance than age-matched, sedentary men. This study examined the effect of increased central arterial stiffness and/or decreased arterial compliance on CBF pulsatility. The study participants included 31 young healthy men (15 resistance-trained men, aged 21 ± 1 years; and 16 controls, aged 23 ± 1 years). β-Stiffness index and arterial compliance were measured in the right carotid artery as index of central arterial stiffness and compliance, respectively. The pulsatility index (PI) was measured in the middle cerebral artery as index of CBF pulsatility. β-Stiffness index and PI were significantly higher in the resistance-trained group than in the control group (β-stiffness index: 5.3 ± 0.3 vs. 3.5 ± 0.3 a.u., P < 0.05, PI: 0.80 ± 0.02 vs. 0.70 ± 0.02, P < 0.05). The resistance-trained group showed significantly lower arterial compliance than the control group (0.16 ± 0.01 vs. 0.23 ± 0.01 mm2/mm Hg, P < 0.05). Positive and negative correlations were observed between β-stiffness index and PI (r = 0.39, P < 0.05), and between arterial compliance and PI (r = -0.59, P < 0.05), respectively. The resistance-trained group showed higher central arterial stiffness and PI and lower arterial compliance. Central arterial stiffness and arterial compliance were associated with PI. Increased arterial stiffness and decreased arterial compliance with resistance training impair buffer function, resulting in increased CBF pulsatility. Trial Number UMIN000023816 URL: http://www.umin.ac.jp/icdr/index.html Official scientific title of the study: effect of increase arterial stiffness by resistance training on cerebral hemodynamic.

Autonomic arterial neuropathy in lower limbs.

PubMed

Ener, B K; Uçankale, H

2015-06-01

This prospective and controlled study was carried out to show the role of hyperperfusion due to decreased arterial resistance in patients with arterial neuropathy of lower limbs. Arterial Duplex color scanning and magnetic resonance imaging (MRI) angiography were made in 54 patients with lower limb venous stasis in which Pulsatility Index (PI) from pedal arteries by using CW Doppler was below cut off value of 5 as a confirmatory evidence of autonomic neuropathy and in 24 healthy subjects. PI was mean 2.79 ranged from 4.87 to 0.82 in patients. It was mean 9.38 between 5.43 and 15.25 in control subjects. PSV was found mean 44.52 cm/sec ranged from 26 to 74 cm/s in patients. It was found between 10 and 23 cm/sec with average 16.08 cm/s in healthy ones. In addition to venous duplex scanning findings, MRI angiography demonstrates arterial contrast enhancement, vascular blush, early venous filling and permanent venous dilatation in 16 patients (group 2) having PI below 3 with severe degrees of hyperperfusion. In this group, PI was mean 1.70 ranged from 2.46 to 0.82 and PSV was mean 61.19 cm/s, between 53 to 74 cm/s. Out of patients, 38 (group 1) had no pathological findings in MRI angiography and had PI>3 and <5. In this group, PI was mean 3.26, ranged from 4.87 to 2.55 and PSV was mean 37.5 cm/s, between 26 to 47 cm/s. In this trial, we observed that patients with arterial neuropathy in the leg (groups 1 and 2) had a significant increase in PSV and a decrease in PI values from foot arteries compared with that of the control group (P=0.001). A remarkable difference was found in parameters between patient groups (P=0.001). Finally, it can be said that lower limb hyperperfusion owing to arterial neuropathy in various degrees produce venous stasis and is also responsible for some venous abnormalities.

Sagittal plane analysis of the spine and pelvis in degenerative lumbar scoliosis.

PubMed

Han, Fei; Weishi, Li; Zhuoran, Sun; Qingwei, Ma; Zhongqiang, Chen

2017-01-01

Previous studies have reported the normative values of pelvic sagittal parameters, but no study has analyzed the sagittal spino-pelvic alignment in degenerative lumbar scoliosis (DLS) and its role in the pathogenesis. Retrospective analysis was applied to 104 patients with DLS, together with 100 cases of asymptomatic young adults as a control group and another control group consisting of 145 cases with cervical spondylosis. The coronal and sagittal parameters were measured on the anteroposterior and lateral radiograph of the whole spine in the DLS group as well as in the two control groups. Statistical analysis showed that the DLS group had a higher pelvic incidence (PI) value (50.5° ± 10.2°), than the normal control group (with PI 47.2° ± 8.8°) and the cervical spondylosis group (46.9° ± 9.1°). In DLS group, there were 38 cases (36.5%) complicated with degenerative lumbar spondylolisthesis, who had higher PI values than patients without it. Besides, the lumbar lordosis (LL) and sacral slope (SS) of DLS group were lower; the scoliosis Cobb's angle was correlated with pelvic tilt (PT); thoracic kyphosis was correlated with LL, SS, and PT; and LL was correlated with other sagittal parameters. Patients with DLS may have a higher PI, which may impact the pathogenesis of DLS. A high PI value is probably associated with the high prevalence of degenerative lumbar spondylolisthesis among DLS patients. In DLS patients, the lumbar spine maintains the ability of regulating the sagittal balance, and the regulation depends more on thoracic curve.

Differential roles of resistance to proactive interference and suppression of prepotent responses in overgeneral memory.

PubMed

Comas, Michelle; Valentino, Kristin; Johnson, Anne F; Gibson, Bradley S; Taylor, Courtney

2018-06-12

Overgeneral memory (OGM), difficulty in retrieving specific autobiographical memories, is a robust phenomenon related to the onset and course of depressive and posttraumatic stress disorders. Inhibitory mechanisms are theorized to underlie OGM; however, empirical support for this link is equivocal. The current study examines the differential roles of two aspects of inhibitory control in association with OGM: suppression of prepotent responses and resistance to proactive interference (PI). Only resistance to PI was expected to be negatively related to OGM, whereby individuals with greater ability to resist PI would have reduced OGM. Participants (n = 49) completed a self-report measure of depressive symptoms and engaged in two tasks aimed at assessing resistance to PI and suppression of prepotent responses. Participants also completed a task assessing overgeneral autobiographical memory. As hypothesized, resistance to PI, but not suppression of prepotent responses negatively predicted OGM above and beyond the influence of depressive symptoms. Because a double dissociation was not examined, we cannot address the potential independence of the submechanisms of inhibitory control that we assessed. Results exemplify the differential associations of two components of inhibition and OGM, suggesting that resistance to PI, in particular, may contribute to the development and/or maintenance of OGM and associated depressive disorders. Directions for future research are discussed. Copyright © 2018. Published by Elsevier Ltd.

Integral reinforcement learning for continuous-time input-affine nonlinear systems with simultaneous invariant explorations.

PubMed

Lee, Jae Young; Park, Jin Bae; Choi, Yoon Ho

2015-05-01

This paper focuses on a class of reinforcement learning (RL) algorithms, named integral RL (I-RL), that solve continuous-time (CT) nonlinear optimal control problems with input-affine system dynamics. First, we extend the concepts of exploration, integral temporal difference, and invariant admissibility to the target CT nonlinear system that is governed by a control policy plus a probing signal called an exploration. Then, we show input-to-state stability (ISS) and invariant admissibility of the closed-loop systems with the policies generated by integral policy iteration (I-PI) or invariantly admissible PI (IA-PI) method. Based on these, three online I-RL algorithms named explorized I-PI and integral Q -learning I, II are proposed, all of which generate the same convergent sequences as I-PI and IA-PI under the required excitation condition on the exploration. All the proposed methods are partially or completely model free, and can simultaneously explore the state space in a stable manner during the online learning processes. ISS, invariant admissibility, and convergence properties of the proposed methods are also investigated, and related with these, we show the design principles of the exploration for safe learning. Neural-network-based implementation methods for the proposed schemes are also presented in this paper. Finally, several numerical simulations are carried out to verify the effectiveness of the proposed methods.

M-RNA Gene Expression of INF-Γ and IL-10 during Intestinal Phase of Trichinella spiralis after Myrrh and Albendazole Treatment.

PubMed

Bakir, Hanaa Y; Ah Attia, Rasha; Mahmoud, Abeer E; Ibraheim, Zedan

2017-01-01

The protective response developed against Trichinella spiralis infection provokes immune and inflammatory responses mediated by cytokines released from T helper cells. We aimed to evaluate the effect of albendazole or myrrh on the expression of IFN-γ and IL-10 in BALB/c mice infected with T. spiralis . This study was done at the Animal House of Faculty of Medicine, Assiut University (Assiut, Egypt) from April to December 2015. Mice were infected with 300 T. spiralis larvae and treated with albendazole (50 mg/kg per day) or myrrh (500 mg/kg per day) for 3 consecutive days post-infection (pi). The expression of INF-γ and IL-10 was detected in the intestinal tissue by reverse transcription (RT) PCR. The expression of IFN-γ in mice treated with albendazole and myrrh was detected on days 3 and 15 pi respectively. In the control group, it was found on days 5, 10, 15 and 20 pi with the highest expression on day 15 pi. The expression of IL-10 was detected on days 3, 20 pi in the albendazole and myrrh treated groups, respectively. In the control group, IL-10 expression appeared on days 5 and day 20 pi. The target of albendazole and myrrh on the profile of IFN-γ and IL-10 on these cytokines were encouraging to reinforce their therapeutic use against trichinellosis.

Abnormal amygdala connectivity in patients with primary insomnia: evidence from resting state fMRI.

PubMed

Huang, Zhaoyang; Liang, Peipeng; Jia, Xiuqin; Zhan, Shuqin; Li, Ning; Ding, Yan; Lu, Jie; Wang, Yuping; Li, Kuncheng

2012-06-01

Neurobiological mechanisms underlying insomnia are poorly understood. Previous findings indicated that dysfunction of the emotional circuit might contribute to the neurobiological mechanisms underlying insomnia. The present study will test this hypothesis by examining alterations in functional connectivity of the amygdala in patients with primary insomnia (PI). Resting-state functional connectivity analysis was used to examine the temporal correlation between the amygdala and whole-brain regions in 10 medication-naive PI patients and 10 age- and sex-matched healthy controls. Additionally, the relationship between the abnormal functional connectivity and insomnia severity was investigated. We found decreased functional connectivity mainly between the amygdala and insula, striatum and thalamus, and increased functional connectivity mainly between the amygdala and premotor cortex, sensorimotor cortex in PI patients as compared to healthy controls. The connectivity of the amygdala with the premotor cortex in PI patients showed significant positive correlation with the total score of the Pittsburgh Sleep Quality Index (PSQI). The decreased functional connectivity between the amygdala and insula, striatum, and thalamus suggests that dysfunction in the emotional circuit might contribute to the neurobiological mechanisms underlying PI. The increased functional connectivity of the amygdala with the premotor and sensorimotor cortex demonstrates a compensatory mechanism to overcome the negative effects of sleep deficits and maintain the psychomotor performances in PI patients. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Impacts of long-term precipitation manipulation on hydraulic architecture and xylem anatomy of piñon and juniper in Southwest USA.

PubMed

Hudson, P J; Limousin, J M; Krofcheck, D J; Boutz, A L; Pangle, R E; Gehres, N; McDowell, N G; Pockman, W T

2018-02-01

Hydraulic architecture imposes a fundamental control on water transport, underpinning plant productivity, and survival. The extent to which hydraulic architecture of mature trees acclimates to chronic drought is poorly understood, limiting accuracy in predictions of forest responses to future droughts. We measured seasonal shoot hydraulic performance for multiple years to assess xylem acclimation in mature piñon (Pinus edulis) and juniper (Juniperus monosperma) after 3+ years of precipitation manipulation. Our treatments consisted of water addition (+20% ambient precipitation), partial precipitation-exclusion (-45% ambient precipitation), and exclusion-structure control. Supplemental watering elevated leaf water potential, sapwood-area specific hydraulic conductivity, and leaf-area specific hydraulic conductivity relative to precipitation exclusion. Shifts in allocation of leaf area to sapwood area enhanced differences between irrigated and droughted K L in piñon but not juniper. Piñon and juniper achieved similar K L under ambient conditions, but juniper matched or outperformed piñon in all physiological measurements under both increased and decreased precipitation treatments. Embolism vulnerability and xylem anatomy were unaffected by treatments in either species. Absence of significant acclimation combined with inferior performance for both hydraulic transport and safety suggests piñon has greater risk of local extirpation if aridity increases as predicted in the southwestern USA. © 2017 John Wiley & Sons Ltd.

Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941.

PubMed

Raynaud, Florence I; Eccles, Suzanne A; Patel, Sonal; Alix, Sonia; Box, Gary; Chuckowree, Irina; Folkes, Adrian; Gowan, Sharon; De Haven Brandon, Alexis; Di Stefano, Francesca; Hayes, Angela; Henley, Alan T; Lensun, Letitia; Pergl-Wilson, Giles; Robson, Anthony; Saghir, Nahid; Zhyvoloup, Alexander; McDonald, Edward; Sheldrake, Peter; Shuttleworth, Stephen; Valenti, Melanie; Wan, Nan Chi; Clarke, Paul A; Workman, Paul

2009-07-01

The phosphatidylinositide 3-kinase pathway is frequently deregulated in human cancers and inhibitors offer considerable therapeutic potential. We previously described the promising tricyclic pyridofuropyrimidine lead and chemical tool compound PI-103. We now report the properties of the pharmaceutically optimized bicyclic thienopyrimidine derivatives PI-540 and PI-620 and the resulting clinical development candidate GDC-0941. All four compounds inhibited phosphatidylinositide 3-kinase p110alpha with IC(50) < or = 10 nmol/L. Despite some differences in isoform selectivity, these agents exhibited similar in vitro antiproliferative properties to PI-103 in a panel of human cancer cell lines, with submicromolar potency in PTEN-negative U87MG human glioblastoma cells and comparable phosphatidylinositide 3-kinase pathway modulation. PI-540 and PI-620 exhibited improvements in solubility and metabolism with high tissue distribution in mice. Both compounds gave improved antitumor efficacy over PI-103, following i.p. dosing in U87MG glioblastoma tumor xenografts in athymic mice, with treated/control values of 34% (66% inhibition) and 27% (73% inhibition) for PI-540 (50 mg/kg b.i.d.) and PI-620 (25 mg/kg b.i.d.), respectively. GDC-0941 showed comparable in vitro antitumor activity to PI-103, PI-540, and PI-620 and exhibited 78% oral bioavailability in mice, with tumor exposure above 50% antiproliferative concentrations for >8 hours following 150 mg/kg p.o. and sustained phosphatidylinositide 3-kinase pathway inhibition. These properties led to excellent dose-dependent oral antitumor activity, with daily p.o. dosing at 150 mg/kg achieving 98% and 80% growth inhibition of U87MG glioblastoma and IGROV-1 ovarian cancer xenografts, respectively. Together, these data support the development of GDC-0941 as a potent, orally bioavailable inhibitor of phosphatidylinositide 3-kinase. GDC-0941 has recently entered phase I clinical trials.

Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941

PubMed Central

Raynaud, Florence I.; Eccles, Suzanne A.; Patel, Sonal; Alix, Sonia; Box, Gary; Chuckowree, Irina; Folkes, Adrian; Gowan, Sharon; De Haven Brandon, Alexis; Di Stefano, Francesca; Hayes, Angela; Henley, Alan T.; Lensun, Letitia; Pergl-Wilson, Giles; Robson, Anthony; Saghir, Nahid; Zhyvoloup, Alexander; McDonald, Edward; Sheldrake, Peter; Shuttleworth, Stephen; Valenti, Melanie; Wan, Nan Chi; Clarke, Paul A.; Workman, Paul

2009-01-01

The phosphatidylinositide 3-kinase pathway is frequently deregulated in human cancers and inhibitors offer considerable therapeutic potential. We previously described the promising tricyclic pyridofuropyrimidine lead and chemical tool compound PI-103. We now report the properties of the pharmaceutically optimized bicyclic thienopyrimidine derivatives PI-540 and PI-620 and the resulting clinical development candidate GDC-0941. All four compounds inhibited phosphatidylinositide 3-kinase p110α with IC50 ≤ 10 nmol/L. Despite some differences in isoform selectivity, these agents exhibited similar in vitro antiproliferative properties to PI-103 in a panel of human cancer cell lines, with submicromolar potency in PTEN-negative U87MG human glioblastoma cells and comparable phosphatidylinositide 3-kinase pathway modulation. PI-540 and PI-620 exhibited improvements in solubility and metabolism with high tissue distribution in mice. Both compounds gave improved antitumor efficacy over PI-103, following i.p. dosing in U87MG glioblastoma tumor xenografts in athymic mice, with treated/control values of 34% (66% inhibition) and 27% (73% inhibition) for PI-540 (50 mg/kg b.i.d.) and PI-620 (25 mg/kg b.i.d.), respectively. GDC-0941 showed comparable in vitro antitumor activity to PI-103, PI-540, and PI-620 and exhibited 78% oral bioavailability in mice, with tumor exposure above 50% anti-proliferative concentrations for >8 hours following 150 mg/kg p.o. and sustained phosphatidylinositide 3-kinase pathway inhibition. These properties led to excellent dose-dependent oral antitumor activity, with daily p.o. dosing at 150 mg/kg achieving 98% and 80% growth inhibition of U87MG glioblastoma and IGROV-1 ovarian cancer xenografts, respectively. Together, these data support the development of GDC-0941 as a potent, orally bioavailable inhibitor of phosphatidylinositide 3-kinase. GDC-0941 has recently entered phase I clinical trials. PMID:19584227

Hydrodynamic Controls on Acoustical and Optical Water Properties in Tropical Reefs

DTIC Science & Technology

2013-09-30

the dominant hydrodynamic controls across different reef environments? Tropical coral health can be significantly affected by sedimentation that can...collaborative field work by the PIs, carried out in collaboration with UCSD SIO (PI: Terrill) and the Coral Reef Research Foundation in Koror (PI...bed stress in coral reef environments, using observations from Oahu, Palau and Guam. The project is providing partial support for a postdoctoral

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.

Type II PI4-kinases control Weibel-Palade body biogenesis and von Willebrand factor structure in human endothelial cells.

PubMed

Lopes da Silva, Mafalda; O'Connor, Marie N; Kriston-Vizi, Janos; White, Ian J; Al-Shawi, Raya; Simons, J Paul; Mössinger, Julia; Haucke, Volker; Cutler, Daniel F

2016-05-15

Weibel-Palade bodies (WPBs) are endothelial storage organelles that mediate the release of molecules involved in thrombosis, inflammation and angiogenesis, including the pro-thrombotic glycoprotein von Willebrand factor (VWF). Although many protein components required for WPB formation and function have been identified, the role of lipids is almost unknown. We examined two key phosphatidylinositol kinases that control phosphatidylinositol 4-phosphate levels at the trans-Golgi network, the site of WPB biogenesis. RNA interference of the type II phosphatidylinositol 4-kinases PI4KIIα and PI4KIIβ in primary human endothelial cells leads to formation of an increased proportion of short WPB with perturbed packing of VWF, as exemplified by increased exposure of antibody-binding sites. When stimulated with histamine, these cells release normal levels of VWF yet, under flow, form very few platelet-catching VWF strings. In PI4KIIα-deficient mice, immuno-microscopy revealed that VWF packaging is also perturbed and these mice exhibit increased blood loss after tail cut compared to controls. This is the first demonstration that lipid kinases can control the biosynthesis of VWF and the formation of WPBs that are capable of full haemostatic function. © 2016. Published by The Company of Biologists Ltd.

Myotubularin related protein-2 and its phospholipid substrate PIP2 control Piezo2-mediated mechanotransduction in peripheral sensory neurons

PubMed Central

Narayanan, Pratibha; Hütte, Meike; Kudryasheva, Galina; Taberner, Francisco J; Lechner, Stefan G; Rehfeldt, Florian; Gomez-Varela, David

2018-01-01

Piezo2 ion channels are critical determinants of the sense of light touch in vertebrates. Yet, their regulation is only incompletely understood. We recently identified myotubularin related protein-2 (Mtmr2), a phosphoinositide (PI) phosphatase, in the native Piezo2 interactome of murine dorsal root ganglia (DRG). Here, we demonstrate that Mtmr2 attenuates Piezo2-mediated rapidly adapting mechanically activated (RA-MA) currents. Interestingly, heterologous Piezo1 and other known MA current subtypes in DRG appeared largely unaffected by Mtmr2. Experiments with catalytically inactive Mtmr2, pharmacological blockers of PI(3,5)P2 synthesis, and osmotic stress suggest that Mtmr2-dependent Piezo2 inhibition involves depletion of PI(3,5)P2. Further, we identified a PI(3,5)P2 binding region in Piezo2, but not Piezo1, that confers sensitivity to Mtmr2 as indicated by functional analysis of a domain-swapped Piezo2 mutant. Altogether, our results propose local PI(3,5)P2 modulation via Mtmr2 in the vicinity of Piezo2 as a novel mechanism to dynamically control Piezo2-dependent mechanotransduction in peripheral sensory neurons. PMID:29521261

Experimental use of new absorbable tracheal stent.

PubMed

Schopf, Luciano F; Fraga, José Carlos; Porto, Rodrigo; Santos, Luis A; Marques, Douglas R; Sanchez, Paulo R; Meyer, Fabíola S; Ulbrich, Jane M

2017-11-16

Silicone and metallic stents are not effective in children with tracheobronchial stenosis or tracheomalacia. Herein, we aimed to evaluate the clinical manifestations and histological reaction of rabbit trachea to the presence of a new poly(lactic-co-glycolic acid) with polyisoprene (PLGA/PI) polymer absorbable stent. Fourteen adult white rabbits (weight, 3.0-3.5kg) were randomly assigned to three groups: Group I (n=6): PLGA/PI spiral stent; Group II (n=6): PLGA/PI fragment; and Group III (n=2): controls. After a longitudinal incision on three cervical tracheal rings, the stents and fragments were inserted into the trachea and fixed onto the lateral wall with nonabsorbable sutures. The stented group showed significantly more stridor at rest (p=0.0041), agitation (p=0.014), and use of accessory muscles (p=0.0002) and required more emergency endoscopies than the fragment group. Further, it showed significantly more remarkable histological inflammatory damage than the fragment and control groups (p=0.002). The new PLGA/PI polymeric stent implanted into the trachea of rabbits caused more clinical manifestations and histologically verified inflammatory reaction than the PLGA/PI polymeric fragment. Future studies should be aimed at reducing the stent-wall thickness. Copyright © 2017 Elsevier Inc. All rights reserved.

Control of plant phosphate homeostasis by inositol pyrophosphates and the SPX domain.

PubMed

Jung, Ji-Yul; Ried, Martina K; Hothorn, Michael; Poirier, Yves

2018-02-01

Proteins containing a SPX domain are involved in phosphate (Pi) homeostasis, including Pi transport and adaptation to Pi deficiency. The SPX domain harbors a basic surface binding Pi at low affinity and inositol pyrophosphates (PP-InsPs) at high affinity. Genetic and biochemical studies revealed that PP-InsPs serve as ligands for the SPX domain. Residues in the PHO1 SPX domain involved in PP-InsPs binding are critical for its Pi export activity, and the interaction between SPX proteins and the PHR1 transcription factor, which results in PHR1 inactivation, is promoted by PP-InsPs. Changes in PP-InsPs levels in response to Pi deficiency may thus contribute to the adaptation of plants to stress via the modulation of the activity of SPX-containing proteins and their interactors. Modulating PP-InsP levels or the affinity/specificity of the SPX domain for PP-InsP could potentially be used to engineer crops to maintain high yield under reduced Pi fertilizer input. Copyright © 2017 Elsevier Ltd. All rights reserved.

Baseband pulse shaping for pi /4 FQPSK in nonlinearly amplified mobile channels

NASA Astrophysics Data System (ADS)

Subasinghe-Dias, Dileeka; Feher, Kamilo

1994-10-01

We apply baseband pulse shaping techniques for pi /4 QPSK in order to reduce the spectral regeneration of the bandlimited carrier after nonlinear amplification. These Feher's patented techniques, namely, pi /4 FQPSK (superposed QPSK) and pi /4 CTPSK (controlled transition PSK), may also be noncoherently demodulated. Application of these techniques is in fast fading, power efficient channels, typical of the mobile radio environment. Patents related to FQPSK are described. Computer simulation and experimental studies demonstrate that with these baseband waveshaping techniques, carrier envelope fluctuations are significantly reduced, and the out-of-band power after nonlinear amplification is suppressed by up to 20 dB compared to pi /4 QPSK. In frequency noninterleaved land or satellite mobile radio systems operating in a nonlinear, fading and ACI (adjacent channel interference) environment, these techniques may achieve 20%-50% higher spectral efficiency compared to pi /4 QPSK. In mobile cellular systems using pi /4 QPSK, such as the new North American and the Japanese digital cellular systems, the application of these baseband pulse shapes may allow more convenient and less costly amplifier linearization.

Phosphorus cycling in natural and low input soil/plant systems: the role of soil microorganisms

NASA Astrophysics Data System (ADS)

Tamburini, F.; Bünemann, E. K.; Oberson, A.; Bernasconi, S. M.; Frossard, E.

2011-12-01

Availability of phosphorus (as orthophosphate, Pi) limits biological production in many terrestrial ecosystems. During the first phase of soil development, weathering of minerals and leaching of Pi are the processes controlling Pi concentrations in the soil solution, while in mature soils, Pi is made available by desorption of mineral Pi and mineralization of organic compounds. In agricultural soils additional Pi is supplied by fertilization, either with mineral P and/or organic inputs (animal manure or plant residues). Soil microorganisms (bacteria and fungi) mediate several processes, which are central to the availability of Pi to plants. They play a role in the initial release of Pi from the mineral phase, and through extracellular phosphatase enzymes, they decompose and mineralize organic compounds, releasing Pi. On the other hand, microbial immobilization and internal turnover of Pi can decrease the soil available Pi pool, competing in this way with plants. Using radio- and stable isotopic approaches, we show evidence from different soil/plant systems which points to the central role of the microbial activity. In the presented case studies, P contained in the soil microbial biomass is a larger pool than available Pi. In a soil chronosequence after deglaciation, stable isotopes of oxygen associated to phosphate showed that even in the youngest soils microbial activity highly impacted the isotopic signature of available Pi. These results suggested that microorganisms were rapidly taking up and cycling Pi, using it to sustain their community. Microbial P turnover time was faster in the young (about 20 days) than in older soils (about 120 days), reflecting a different functioning of the microbial community. Microbial community crashes, caused by drying/rewetting and freezing/thawing cycles, were most likely responsible for microbial P release to the available P pool. In grassland fertilization experiments with mineral NK and NPK amendments, microbial P turnover was faster in the P-free treatment. Laboratory incubation also showed a more rapid P uptake by microbial biomass in the NK than in the NPK treatment (37% and 6% of added 33P recovered in microbial P after 100 minutes in NK and NPK, respectively). The seasonal microbial P flux in both treatments was 1.5-4 times larger than the annual plant P uptake. In field studies carried out on highly weathered low P soils in Colombia, the comparison between grass-legume and grass-only pastures showed that the presence of legumes had an impact on the overall biological activity. In fact, microbial biomass and phosphatase activity were significantly larger in grass-legume pastures than in the legume-free experiments. Larger release of Pi from the organic P pool improved P availability to plants and pointed at a modified C:N:P stoichiometry along pathways of the nutrient cycle in the soil/plant system. All these data are evidence of a highly dynamic microbial P pool, which controls Pi concentration and, hence, availability for plants in natural and low input agricultural ecosystems.

MLCK-mediated intestinal permeability promotes immune activation and visceral hypersensitivity in PI-IBS mice.

PubMed

Long, Y; Du, L; Kim, J J; Chen, B; Zhu, Y; Zhang, Y; Yao, S; He, H; Zheng, X; Huang, Z; Dai, N

2018-04-11

Alterations in intestinal permeability regulated by tight junctions (TJs) are associated with immune activation and visceral hypersensitivity in irritable bowel syndrome (IBS). Myosin light chain kinase (MLCK) is an important mediator of epithelial TJ. The aim of this study is to investigate the role of MLCK in the pathogenesis of IBS using a post infectious IBS (PI-IBS) mouse model. Trichinella spiralis-infected PI-IBS mouse model was used. Urine lactulose/mannitol ratio was measured to assess intestinal epithelial permeability. Western blotting was used to evaluate intestinal TJ protein (zonula occludens-1) and MLCK-associated protein expressions. Immune profile was assessed by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was determined by abdominal withdrawal reflex in response to colorectal distension. Eight weeks after inoculation with T. spiralis, PI-IBS mice developed decreased pain and volume thresholds during colorectal distention, increased urine lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and decreased zonula occludens-1 expression compared to the control mice. MLCK expression was dramatically elevated in the colonic mucosa of PI-IBS mice compared to the control mice, alongside increased pMLC/MLC and decreased MLCP expression. Administration of MLCK inhibitor and TJ blocker both reversed the increased intestinal permeability, visceral hypersensitivity, and Th1-dominant immune profile in PI-IBS mice. MLCK is a pivotal step in inducing increased intestinal permeability promoting low-grade intestinal immune activation and visceral hypersensitivity in PI-IBS mice. MLCK inhibitor may provide a potential therapeutic option in the treatment of IBS. © 2018 John Wiley & Sons Ltd.

Electronic tuning of the lability of Pt(II) complexes through pi-acceptor effects. Correlations between thermodynamic, kinetic, and theoretical parameters.

PubMed

Hofmann, Andreas; Jaganyi, Deogratius; Munro, Orde Q; Liehr, Günter; van Eldik, Rudi

2003-03-10

pi-Acceptor effects are often used to account for the unusual high lability of [Pt(terpy)L]((2)(-)(n)+) (terpy = 2,2':6',2' '-terpyridine) complexes. To gain further insight into this phenomenon, the pi-acceptor effect was varied systematically by studying the lability of [Pt(diethylenetriamine)OH(2)](2+) (aaa), [Pt(2,6-bis-aminomethylpyridine)OH(2)](2+) (apa), [Pt(N-(pyridyl-2-methyl)-1,2-diamino-ethane)OH(2)](2+) (aap), [Pt(bis(2-pyridylmethyl)amine)OH(2)](2+) (pap), [Pt(2,2'-bipyridine)(NH(3))(OH(2))](2+) (app), and [Pt(terpy)OH(2)](2+) (ppp). The crystal structure of the apa precursor [Pt(2,6-bis-aminomethylpyridine)Cl]Cl.H(2)O was determined. The substitution of water by a series of nucleophiles, viz. thiourea, N,N-dimethylthiourea, N,N,N',N'-tetramethylthiourea, I(-), and SCN(-), was studied under pseudo-first-order conditions as a function of concentration, pH, temperature, and pressure, using stopped-flow techniques. The data enable an overall comparison of the substitution behavior of these complexes, emphasizing the role played by the kinetic cis and trans pi-acceptor effects. The results indicate that the cis pi-acceptor effect is larger than the trans pi-acceptor effect, and that the pi-acceptor effects are multiplicative. DFT calculations at the B3LYP/LACVP level of theory show that, by the addition of pi-acceptor ligands to the metal, the positive charge on the metal center increases, and the energy separation of the frontier molecular orbitals (E(LUMO) - E(HOMO)) of the ground state Pt(II) complexes decreases. The calculations collectively support the experimentally observed additional increase in reactivity when two pi-accepting rings are adjacent to each other (app and ppp), which is ascribed to "electronic communication" between the pyridine rings. The results furthermore indicate that the pK(a) value of the platinum bound water molecule is controlled by the pi-accepting nature of the chelate system and reflects the electron density around the metal center. This in turn controls the rate of the associative substitution reaction and was analyzed using the Hammett equation.

Foliar carbon dynamics of piñon and juniper in response to experimental drought and heat

NASA Astrophysics Data System (ADS)

Collins, A.; Ryan, M. G.; Adams, H. D.; Dickman, L. T.; Garcia-Forner, N.; Grossiord, C.; Powers, H. H.; Sevanto, S.; McDowell, N. G.

2015-12-01

Plant respiration (R) is generally well-coupled with temperature and in the absence of thermal acclimation, respiration is expected to increase as climate change brings higher temperatures. Increased drought is also predicted for future climate, which could drive respiration higher if the carbon (C) cost to maintain tissues (Rm) or grow increases, or lower if substrate or other factors become limiting. We examined the effects of temperature and drought on R as well as photosynthesis, growth, and carbohydrate storage of mature individuals of two co-dominant tree species. Three mature, in-situ piñon (Pinus edulis) and juniper (Juniperus monosperma) trees were assigned to each of the following treatments: +4.8 °C; 45% reduced precipitation; a combination of both (heat + drought); along with ambient control and treatment controls. Rm measured prior to foliar and twig growth was far more sensitive to drought in piñon, and heat in juniper. Total respiration (Rt, R not partitioned) acclimated to temperature in piñon such that elevated temperature had minimal impacts on Rt; however, juniper exhibited higher Rt with elevated temperature, thus juniper did not display any thermal acclimation. Rt in both species was weakly associated with temperature, but strongly correlated with pre-dawn water potential, photosynthetic assimilation (A) rates, and in piñon, foliar carbohydrates. For both species, heat caused far more days where A-R was negative than did drought. The consequences of drought alone and heat alone in piñon included higher Rt per unit growth, indicating that each abiotic stress forces a greater allocation of Rt to maintenance costs, and both drought + heat in combination results in far fewer days that foliar carbohydrates could sustain R in both species. Notably, the much higher A and R of juniper than piñon is consistent with predicted superior carbon budget regulation of juniper than piñon during drought; however, juniper's lack of temperature acclimation in contrast to piñon suggests climate warming may have a greater deleterious impact on juniper carbon balance than piñon.

Respiratory muscle weakness and respiratory muscle training in severely disabled multiple sclerosis patients.

PubMed

Gosselink, R; Kovacs, L; Ketelaer, P; Carton, H; Decramer, M

2000-06-01

To evaluate the contribution of respiratory muscle weakness (part 1) and respiratory muscle training (part 2) to pulmonary function, cough efficacy, and functional status in patients with advanced multiple sclerosis (MS). Survey (part 1) and randomized controlled trial (part 2). Rehabilitation center for MS. Twenty-eight bedridden or wheelchair-bound MS patients (part 1); 18 patients were randomly assigned to a training group (n = 9) or a control group (n = 9) (part 2). The training group (part 2) performed three series of 15 contractions against an expiratory resistance (60% maximum expiratory pressure [PEmax]) two times a day, whereas the control group performed breathing exercises to enhance maximal inspirations. Forced vital capacity (FVC), inspiratory, and expiratory muscle strength (PImax and PEmax), neck flexion force (NFF), cough efficacy by means of the Pulmonary Index (PI), and functional status by means of the Extended Disability Status Scale (EDSS). Part 1 revealed a significantly reduced FVC (43% +/- 26% predicted), PEmax (18% +/- 8% predicted), and PImax (27% +/- 11% predicted), whereas NFF was only mildly reduced (93% +/- 26% predicted). The PI (median score, 10) and EDSS (median score, 8.5) were severely reduced. PEmax was significantly correlated to FVC, EDSS, and PI (r = .77, -.79, and -.47, respectively). In stepwise multiple regression analysis. PEmax was the only factor contributing to the explained variance in FVC (R2 = .60), whereas body weight (R2 = .41) was the only factor for the PI. In part 2, changes in PImax and PEmax tended to be higher in the training group (p = .06 and p = .07, respectively). The PI was significantly improved after 3 months of training compared with the control group (p < .05). After 6 months, the PI remained significantly better in the training group. Expiratory muscle strength was significantly reduced and related to FVC, cough efficacy, and functional status. Expiratory muscle training tended to enhance inspiratory and expiratory muscle strength. In addition, subjectively and objectively rated cough efficacy improved significantly and lasted for 3 months after training cessation.

Voltage control in Z-source inverter using low cost microcontroller for undergraduate approach

NASA Astrophysics Data System (ADS)

Zulkifli, Shamsul Aizam; Sewang, Mohd Rizal; Salimin, Suriana; Shah, Noor Mazliza Badrul

2017-09-01

This paper is focussing on controlling the output voltage of Z-Source Inverter (ZSI) using a low cost microcontroller with MATLAB-Simulink that has been used for interfacing the voltage control at the output of ZSI. The key advantage of this system is the ability of a low cost microcontroller to process the voltage control blocks based on the mathematical equations created in MATLAB-Simulink. The Proportional Integral (PI) control equations are been applied and then, been downloaded to the microcontroller for observing the changes on the voltage output regarding to the changes on the reference on the PI. The system has been simulated in MATLAB and been verified with the hardware setup. As the results, the Raspberry Pi and Arduino that have been used in this work are able to respond well when there is a change of ZSI output. It proofed that, by applying/introducing this method to student in undergraduate level, it will help the student to understand more on the process of the power converter combine with a control feedback function that can be applied at low cost microcontroller.

Comparison of conventional medicine, TCM treatment, and combination of both conventional medicine and TCM treatment for patients with chronic obstructive pulmonary disease: study protocol of a randomized comparative effectiveness research trial.

PubMed

Li, Jian-Sheng; Xie, Yang; Li, Su-Yun; Yu, Xue-Qing

2014-05-01

Chronic obstructive pulmonary disease (COPD) affects millions worldwide. Although many therapies exist and are being developed to relieve symptoms and reduce mortality, few data are available to understand which of the therapeutic alternatives is the most cost-effective for COPD patients in everyday clinical practice, especially for traditional Chinese medicine (TCM). Comparative effectiveness research can help patients, clinicians, and decision-makers make best informed treatment decisions where such evidence was previously lacking. This study aims to compare the effectiveness and economic evaluation of three treatments: (1) conventional Western medicine; (2) TCM treatments, which have been evaluated and have certain effect; and (3) a combination of both conventional Western medicine and TCM treatments, and then determine which treatment is the most suitable for COPD patients. A multicenter, pragmatic, randomized, controlled trial is adopted. A total of 360 patients will be recruited and randomly assigned to one of the three treatments group, with 120 in each group. Patients in the conventional Western medicine group will be given Salbutamol, Formoterol, Salmeterol/fluticasone, respectively, according to the guidelines. For the TCM group, patients will be given Bufei granule, Bu-Fei Jian-Pi granule, Bu-Fei Yi-Shen granule, and Yi-Qi Zi-Shen granule based on their corresponding TCM syndrome patterns, respectively. For the combination of conventional medicine and TCM treatments group, patients will be given a combination of conventional Western medicine and TCM granules. Treatments in each group are recognized as a whole comprehensive intervention. After the 26-week treatment, another 26 weeks will be followed up. The outcome measures including the frequency and duration of acute exacerbations, lung function, dyspnea, exercise capacity, quality of life, and economic evaluation will be assessed. It is hypothesized that each of the three treatments will have beneficial effects in reducing the frequency and duration of acute exacerbations, improving exercise capacity and psychosocial function of COPD patients. In addition, the combination of conventional medicine and TCM treatments may be most suitable for COPD patients with better effectiveness and economic evaluation. ClinicalTrials.gov NCT01836016.

DREAM plays an important role in platelet activation and thrombogenesis

PubMed Central

Kim, Kyungho; Tseng, Alan; Barazia, Andrew; Italiano, Joseph E.

2017-01-01

Downstream regulatory element antagonist modulator (DREAM), a transcriptional repressor, is known to modulate pain responses. However, it is unknown whether DREAM is expressed in anucleate platelets and plays a role in thrombogenesis. By using intravital microscopy with DREAM-null mice and their bone marrow chimeras, we demonstrated that both hematopoietic and nonhematopoietic cell DREAMs are required for platelet thrombus formation following laser-induced arteriolar injury. In a FeCl3-induced thrombosis model, we found that compared with wild-type (WT) control and nonhematopoietic DREAM knockout (KO) mice, DREAM KO control and hematopoietic DREAM KO mice showed a significant delay in time to occlusion. Tail bleeding time was prolonged in DREAM KO control mice, but not in WT or DREAM bone marrow chimeric mice. In vivo adoptive transfer experiments further indicated the importance of platelet DREAM in thrombogenesis. We found that DREAM deletion does not alter the ultrastructural features of platelets but significantly impairs platelet aggregation and adenosine triphosphate secretion induced by numerous agonists (collagen-related peptide, adenosine 5′-diphosphate, A23187, thrombin, or U46619). Biochemical studies revealed that platelet DREAM positively regulates phosphoinositide 3-kinase (PI3K) activity during platelet activation. Using DREAM-null platelets and PI3K isoform-specific inhibitors, we observed that platelet DREAM is important for α-granule secretion, Ca2+ mobilization, and aggregation through PI3K class Iβ (PI3K-Iβ). Genetic and pharmacological studies in human megakaryoblastic MEG-01 cells showed that DREAM is important for A23187-induced Ca2+ mobilization and its regulatory function requires Ca2+ binding and PI3K-Iβ activation. These results suggest that platelet DREAM regulates PI3K-Iβ activity and plays an important role during thrombus formation. PMID:27903531

Evaluation of Relationship between Obsessive-compulsive Disorder and Dissociative Experiences

PubMed Central

Cetinkaya, Ozlem; Maner, Fulya

2018-01-01

Objective The aim of the study is to evaluate the relationship between obsessive-compulsive disorder (OCD) symptoms and dissociative experiences and the effect of childhood traumatic experiences on this relationship in OCD patients. Methods Fifty consecutive OCD patients and 50 healthy controls are enrolled for this study. Sociodemographic and Clinical Data Form, Dissociative Experiences Scale (DES), Padua Inventory (PI) and Childhood Trauma Questionnaire (CTQ) are applied to participants. Results Average DES total score in the patient group is 20.58 and in the control group it is 4.87. In the patient group, when we evaluate the relation strengths of DES total and subscale scores with PI total score, we found out that amnesia subscale has r=0.361 (p<0.01), absorption subscale has r=0.611 (p<0.01), depersonalization/derealization subscale has r=0.574 (p<0.01), and DES total score has r=0.55 (p<0.01) relation strengths with PI total score. In patient group both DES total score and CTQ total score have influence on PI total score independently from each other. In addition to this, the level of the influence of DES total scores on PI total scores is, R2=0.399 (p<0.01) and the level of the influence of CTQ total scores on PI total scores is R2=0.343 (p<0.01). Conclusion Dissociative experiences are seen more frequently in OCD patients than healthy controls. Among dissociative experiences, absorption has stronger relation with OCD symptoms. The relation between OCD and dissociation is independent from and stronger than the relation between childhood traumatic experiences and OCD. PMID:29739129

Development of a constant surface pressure penetration langmuir balance based on axisymmetric drop shape analysis.

PubMed

Wege, H A; Holgado-Terriza, J A; Cabrerizo-Vílchez, M A

2002-05-15

A new constant pressure pendant-drop penetration surface balance has been developed combining a pendant-drop surface balance, a rapid-subphase-exchange technique, and a fuzzy logic control algorithm. Beside the determination of insoluble monolayer compression-expansion isotherms, it allows performance of noninvasive kinetic studies of the adsorption of surfactants added to the new subphase onto the free surface and of the adsorption/penetration/reaction of the former onto/into/with surface layers, respectively. The interfacial pressure pi is a fundamental parameter in these studies: by working at constant pi one controls the height of the energy barrier to adsorption/penetration and can select different regimes and steps of the adsorption/penetration process. In our device a solution drop is formed at the tip of a coaxial double capillary, connected to a double microinjector. Drop profiles are extracted from digital drop micrographs and fitted to the equation of capillarity, yielding pi, the drop volume V, and the interfacial area A. pi is varied changing V (and hence A) with the microinjector. Control is based on a case-adaptable modulated fuzzy-logic PID algorithm able to maintain constant pi (or A) under a wide range of experimental conditions. The drop subphase liquid can be exchanged quantitatively by the coaxial capillaries. The adsorption/penetration/reaction kinetics at constant pi are then studied monitoring A(t), i.e., determining the relative area change necessary at each instant to compensate the pressure variation due to the interaction of the surfactant in the subsurface with the surface layer. A fully Windows-integrated program manages the whole setup. Examples of experimental protein adsorption and monolayer penetration kinetics are presented.

Periapical inflammation subsequent to coronal inoculation of dog teeth root filled with resilon/epiphany in 1 or 2 treatment sessions with chlorhexidine medication.

PubMed

Santos, João M; Palma, Paulo J; Ramos, João C; Cabrita, António S; Friedman, Shimon

2014-06-01

Therapeutic methods that inhibit microbial ingress into filled root canals are desirable. This in vivo study assessed the inhibition of periapical inflammation subsequent to coronal inoculation in canals medicated with 2% chlorhexidine gel and filled with Resilon/Epiphany (Pentron Clinical Technologies, Wallingford, CT). Six Beagle dogs each had 10 two-rooted premolars treated. In group 1 (n = 36 roots), 1 root/tooth had the canal conditioned with Primer Epiphany, filled with Epiphany sealer and Resilon core in 1 session, and coronally sealed with PhotacFil. In group 2 (n = 36 roots), the second root/tooth had the canal medicated with 2% chlorhexidine gel for 1 week and then filled and coronally sealed as in group 1. After 3 weeks, canals were exposed to the oral environment for 7 days, inoculated with isologous plaque, and coronally sealed. Negative controls treated as groups 1 and 2 remained sealed. Positive controls had canals unfilled and exposed. Seven months after inoculation, dogs were euthanized; jaw blocks processed for histologic examination; and periapical inflammation (PI) recorded as none, mild, or severe. In groups 1 and 2, severe PI occurred in 5 of 65 roots (8%) and mild PI in 18 of 65 roots (28%) with a significantly higher (P = .031) PI incidence in group 2 than in group 1. Negative controls had only mild PI in 9 of 29 roots (31%). Roots medicated with 2% chlorhexidine gel had mild PI significantly more (P = .009) than roots filled in 1 session (more than 2-fold). Intracanal medication with 2% chlorhexidine gel and root filling with Resilon/Epiphany did not effectively inhibit apical periodontitis subsequent to coronal inoculation. Copyright © 2014 American Association of Endodontists. All rights reserved.

Systematic review and cost-effectiveness evaluation of 'pill-in-the-pocket' strategy for paroxysmal atrial fibrillation compared to episodic in-hospital treatment or continuous antiarrhythmic drug therapy.

PubMed

Saborido, C Martin; Hockenhull, J; Bagust, A; Boland, A; Dickson, R; Todd, D

2010-06-01

Atrial fibrillation (AF) is a tachyarrhythmia characterised by uncoordinated atrial activation with consequent deterioration of impairment of atrial function and a rapid, irregular heartbeat. The annual incidence rate of paroxysmal AF (PAF) has been estimated at 1.0 per 1000 person-years (95% confidence interval 0.9 to 1.1), and reported prevalence rates show wide variations depending on age and country. Conventional treatment strategies for PAF focus on the suppression of paroxysms of AF and return to normal sinus rhythm. To summarise the results of the rapid reviews of the clinical effectiveness and cost-effectiveness literature describing the pill-in-the-pocket (PiP) approach for the treatment of patients with PAF; and to develop an economic model to assess the cost-effectiveness of PiP compared with in-hospital treatment (IHT) or continuous antiarrhythmic drugs (AADs) for the treatment of patients with PAF. Ovid MEDLINE and Ovid OLDMEDLINE 1950 to present with Daily Update were searched. The following electronic databases were searched for ongoing trials: Health Services Research Projects in Progress, ClinicalTrials.gov, metaRegister of Current Controlled Trials, BioMed Central, World Health Organization International Clinical Trials Registry Platform, ClinicalStudyResults.org and the National Library of Medicine Gateway. Inclusion criteria, which included patients suffering from PAF, were independently applied to all identified references by two reviewers (JH and CMS). Electronic searches were conducted to identify clinical effectiveness and cost-effectiveness evidence describing the use of a PiP strategy for the treatment of PAF, published since the release of the Royal College of Physicians' national guidelines on AF in June 2006. A Markov model was constructed to examine differences between three PAF strategies (PiP, AAD and IHT) in terms of cost per quality-adjusted life-year (QALY). A Markov model structure was chosen because it is assumed that PAF is a condition that causes patients to move between a limited number of relevant health states during their lives. The search strategies for clinical studies identified 201 randomised controlled trials (RCTs). Of the 201 RCTs identified, 12 were deemed to be relevant to the decision problem as they included drugs used to treat PAF; summary data were abstracted from these studies in order to inform the development of the economic model only. The model results indicate that the PiP strategy is slightly less effective than the other two strategies, but also less costly (incremental cost-effectiveness ratio of 45,916 pounds per QALY when compared to AAD, and 12,424 pounds per QALY when compared to IHT). The one-way sensitivity analyses performed do not show substantial changes in relative cost-effectiveness except in relation to the age of patients, where PiP dominates AAD in men over 65 years and in women over 70 years. At a threshold of 25,000 pounds per QALY, IHT has the maximum probability of being cost-effective at this threshold. For threshold values between 0 pounds and 9266 pounds per QALY, PiP is the option exhibiting the maximum probability of being cost-effective. The AAD strategy has a very poor probability of being cost-effective under any threshold. However, none of the strategies considered has more than a 40% probability of being cost-effective at a threshold of 25,000 pounds per QALY at any threshold level. This demonstrates the uncertainty around the parameters and its effect on the decision to choose any one strategy over the others. Most of the data used to populate the model have been taken from studies with populations that do not match the patient population specified in the decision problem. Populating the model in this way was unavoidable as there was a paucity of published clinical effectiveness and cost-effectiveness data describing a PiP strategy for this highly specific group of patients. Overall, a PiP strategy seems to be slightly less effective (i.e. fewer QALYs gained) than AAD and IHT, but is associated with cost savings. A PiP strategy seems to be more efficacious and cost-effective than an AAD strategy in men over 65 years and women over 70 years, but this is principally due to a very slight difference in QALY gained by the PiP strategy. A change in clinical practice that includes the introduction of PiP may save costs, but also involves a reduction in clinical effectiveness compared to existing approaches used to treat patients with PAF. Uncertainty in the available clinical data means there was insufficient evidence to support a recommendation for the use of PiP strategy in patients with PAF. Further research should identify outcomes of interest such as adverse events and recurrent AF episodes in an RCT setting because the only clinical study addressing these issues, even partially, is not an RCT but a descriptive analysis. Patient preferences also need to be considered in any future research designs.

All 17 S-locus F-box proteins of the S2 - and S3 -haplotypes of Petunia inflata are assembled into similar SCF complexes with a specific function in self-incompatibility.

PubMed

Li, Shu; Williams, Justin S; Sun, Penglin; Kao, Teh-Hui

2016-09-01

The collaborative non-self-recognition model for S-RNase-based self-incompatibility predicts that multiple S-locus F-box proteins (SLFs) produced by pollen of a given S-haplotype collectively mediate ubiquitination and degradation of all non-self S-RNases, but not self S-RNases, in the pollen tube, thereby resulting in cross-compatible pollination but self-incompatible pollination. We had previously used pollen extracts containing GFP-fused S2 -SLF1 (SLF1 with an S2 -haplotype) of Petunia inflata for co-immunoprecipitation (Co-IP) and mass spectrometry (MS), and identified PiCUL1-P (a pollen-specific Cullin1), PiSSK1 (a pollen-specific Skp1-like protein) and PiRBX1 (a conventional Rbx1) as components of the SCF(S) (2-) (SLF) (1) complex. Using pollen extracts containing PiSSK1:FLAG:GFP for Co-IP/MS, we identified two additional SLFs (SLF4 and SLF13) that were assembled into SCF(SLF) complexes. As 17 SLF genes (SLF1 to SLF17) have been identified in S2 and S3 pollen, here we examined whether all 17 SLFs are assembled into similar complexes and, if so, whether these complexes are unique to SLFs. We modified the previous Co-IP/MS procedure, including the addition of style extracts from four different S-genotypes to pollen extracts containing PiSSK1:FLAG:GFP, to perform four separate experiments. The results taken together show that all 17 SLFs and an SLF-like protein, SLFLike1 (encoded by an S-locus-linked gene), co-immunoprecipitated with PiSSK1:FLAG:GFP. Moreover, of the 179 other F-box proteins predicted by S2 and S3 pollen transcriptomes, only a pair with 94.9% identity and another pair with 99.7% identity co-immunoprecipitated with PiSSK1:FLAG:GFP. These results suggest that SCF(SLF) complexes have evolved specifically to function in self-incompatibility. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

VS-5584 as a PI3K/mTOR inhibitor enhances apoptotic effects of subtoxic dose arsenic trioxide via inhibition of NF-κB activity in B cell precursor-acute lymphoblastic leukemia.

PubMed

Toosi, Bahareh; Zaker, Farhad; Alikarami, Fatemeh; Kazemi, Ahmad; Teremmahi Ardestanii, Majid

2018-06-01

Activation of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway as a survival signaling cascade is a prominent feature of cancers such as acute lymphoblastic leukemia (ALL). In patients with B-cell precursor-ALL (BCP-ALL), the high activity of the pathway correlates with the weak response to anti-leukemic drugs and relapse as a result of downstream prosurvival pathway activation, such as nuclear factor kappa B (NF-κB). Recent targeted therapy (PI3K/mTOR inhibitors) in combination with a multifunctional conventional chemotherapeutic drug may be useful for treatment of BCP-ALL patients. In the current study, the potential of a subtoxic dose (0.2 μM) of arsenic trioxide (ATO) in combination with VS-5584 (a highly potent PI3K/mTOR dual inhibitor) was tested for blocking of the PI3K/Akt/mTOR pathway, inhibition of NF-κB activation and induction of apoptosis and cell-cycle arrest. The data indicate that VS-5584 as a PI3K/mTOR inhibitor inhibited cell proliferation and induced apoptosis in NALM-6 cells by means of NF-κB transcriptional activity suppression. This apoptotic process markedly increased 72 h after administration of the subtoxic dose of ATO. We also showed that concomitant treatment of VS-5584 and the subtoxic dose of ATO significantly inhibited phosphorylation of NF-κB inhibitor alpha (IκBα) and S6 ribosomal protein (S6) as the downstream proteins of the PI3K/Akt/mTOR pathway. Combining VS-5584 and a subtoxic dose of ATO also resulted in down expression of the NF-κB target genes involved in cell proliferation and survival. These results indicate that incorporation of VS-5584/ATO combination into BCP-ALL therapeutic protocols can improve treatment and the survival of patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

LPCAT1 controls phosphate homeostasis in a zinc-dependent manner

PubMed Central

Kisko, Mushtak; Bouain, Nadia; Safi, Alaeddine; Medici, Anna; Akkers, Robert C; Secco, David; Fouret, Gilles; Krouk, Gabriel; Aarts, Mark GM; Busch, Wolfgang

2018-01-01

All living organisms require a variety of essential elements for their basic biological functions. While the homeostasis of nutrients is highly intertwined, the molecular and genetic mechanisms of these dependencies remain poorly understood. Here, we report a discovery of a molecular pathway that controls phosphate (Pi) accumulation in plants under Zn deficiency. Using genome-wide association studies, we first identified allelic variation of the Lyso-PhosphatidylCholine (PC) AcylTransferase 1 (LPCAT1) gene as the key determinant of shoot Pi accumulation under Zn deficiency. We then show that regulatory variation at the LPCAT1 locus contributes significantly to this natural variation and we further demonstrate that the regulation of LPCAT1 expression involves bZIP23 TF, for which we identified a new binding site sequence. Finally, we show that in Zn deficient conditions loss of function of LPCAT1 increases the phospholipid Lyso-PhosphatidylCholine/PhosphatidylCholine ratio, the expression of the Pi transporter PHT1;1, and that this leads to shoot Pi accumulation. PMID:29453864

Impaired acid neutralization in the duodenum in pancreatic insufficiency.

PubMed

Dutta, S K; Russell, R M; Iber, F L

1979-10-01

The influence of severe exocrine pancreatic disease on the acid-neutralizing capacity of the duodenum was studied in five patients with pancreatic insufficiency (PI) and six control subjects using duodenal perfusion-marker technique. Hydrochloric acid (0.1 N containing 1% PEG) was infused at constant rates (1.2, 4.5 and 7.0 ml/min) into the duodenum just distal to the duodenal bulb. Samples were aspirated from the tip of the duodenal perfusion tube located at the ligament of Treitz. All samples were analyzed for volume, pH, titrable acidity, PEG and [14C]PEG (gastric marker) determination. Patients with PI demonstrated significantly diminished ability to neutralize various acid loads as compared to controls who virtually completely neutralized acid loads in the range of maximal gastric acid secretion. Exogenous secretin did not significantly improve percent acid neutralized in PI. These data clearly indicate that patients with PI have significantly impaired ability to neutralize even small loads of acid in the duodenum.

Effect of tillage and crop residue management on nematode densities on corn.

PubMed

McSorley, R; Gallaher, R N

1994-12-01

Effects of winter cover crop management on nematode densities associated with a subsequent corn (Zea mays) crop were examined in five sites in north Florida. Two sites had received winter cover crops of lupine (Lupinus angustifolius), and one site each had rye (Secale cereale), hairy vetch (Vicia villosa), and crimson clover (Trifolium incarnatum). In each site, five different management regimes were compared: 1) conventional tillage after the cover crop was removed for forage; 2) conventional tillage with the cover crop retained as green manure; 3) no-till with the cover crop mowed and used as a mulch; 4) no-till with the cover crop removed as forage; and 5) fallow. Sites were sampled at corn planting and harvest for estimates of initial (Pi) and final (Pf) nematode population densities, respectively. Whether the cover crop was removed as forage or retained as green manure or mulch had no effect (P > 0.10) on population densities of any plant-parasitic nematode before or after corn at any site. Differences between conventional-till and no-till treatments were significant (P

Exercise activates the phosphatidylinositol 3-kinase pathway.

PubMed

Chen, Michael J; Russo-Neustadt, Amelia A

2005-04-27

Physical exercise is known to enhance psychological well-being and coping capacity. Voluntary physical exercise in rats also robustly and rapidly up-regulates hippocampal brain-derived neurotrophic factor (BDNF) mRNA levels, which are potentiated following a regimen of chronic antidepressant treatment. Increased BDNF levels are associated with enhanced activity of cyclic AMP response element binding protein (CREB). So far, relatively little is known about the intracellular signaling mechanisms mediating this effect of exercise. We wished to explore the possibility that exercise and/or antidepressant treatment activate the hippocampal phosphatidylinositol-3 (PI-3) kinase pathway, which mediates cellular survival. In young male Sprague-Dawley rats, we examined the effects of 2 weeks of daily voluntary wheel-running activity and/or tranylcypromine (n = 7 per group) on the levels of the active forms of protein-dependent kinase-1 (PDK-1), PI-3 kinase, phospho-thr308-Akt, phospho-ser473-Akt, and phospho-glycogen synthase kinase-3beta (GSK3beta; inactive form), as well as BDNF, activated CREB, and the phospho-Trk receptor, in the rat hippocampus, and compared these with sedentary saline-treated controls. Immunoblotting analyses revealed that in exercising rats, there was a significant increase in PI-3 kinase expression (4.61 times that of controls, P = 0.0161) and phosphorylation of PDK-1 (2.73 times that of controls, P = 0.0454), thr308-Akt (2.857 times that of controls, P = 0.0082), CREB (60.27 times that of controls, P = 0.05), and Trk (35.3 times that of controls, P < 0.0001) in the hippocampi of exercising animals; BDNF was also increased (3.2 times that of controls), but this was not statistically significant. In rats receiving both exercise and tranylcypromine, BDNF (4.51 times that of controls, P = 0.0068) and PI-3 kinase (4.88 times that of controls, P = 0.0103), and the phospho- forms of Trk (13.67 times that of controls, P = 0.0278), thr308-Akt (3.644 times that of controls, P = 0.0004), GSK-3beta (2.93 times that of controls, P = 0.026), and CREB (88.97 times that of controls, P = 0.0053) were significantly increased. These results suggest that the exercise-induced expression of BDNF is associated with the increased expression of several key intermediates of the PI-3 kinase/Akt pathway, which is known for its role in enhancing neuronal survival.

Empowerment of personal injury victims through the internet: design of a randomized controlled trial.

PubMed

Elbers, Nieke A; Akkermans, Arno J; Cuijpers, Pim; Bruinvels, David J

2011-02-02

Research has shown that current claims settlement process can have a negative impact on psychological and physical recovery of personal injury (PI) victims. One of the explanations for the negative impact on health is that the claims settlement process is a stressful experience and victims suffer from renewed victimization caused by the claims settlement process. PI victims can experience a lack of information, lack of involvement, lack of 'voice', and poor communication. We present the first study that aims to empower PI victims with respect to the negative impact of the claims settlement process by means of an internet intervention. The study is a two armed, randomized controlled trial (RCT), in which 170 PI victims are randomized to either the intervention or control group. The intervention group will get access to a website providing 1) an information module, so participants learn what is happening and what to expect during the claims settlement process, and 2) an e-coach module, so participants learn to cope with problems they experience during the claims settlement process. The control group will get access to a website with hyperlinks to commonly available information only. Participants will be recruited via a PI claims settlement office. Participants are included if they have been involved in a traffic accident which happened less than two years ago, and are at least 18 years old.The main study parameter is the increase of empowerment within the intervention group compared to the control group. Empowerment will be measured by the mastery scale and a self-efficacy scale. The secondary outcomes are perceived justice, burden, well being, work ability, knowledge, amount of damages, and lawyer-client communication. Data are collected at baseline (T0 measurement before randomization), at three months, six months, and twelve months after baseline. Analyses will be conducted according to the intention-to-treat principle. This study evaluates the effectiveness of an internet intervention aimed at empowerment of PI victims. The results will give more insight into the impact of compensation proceedings on health over time, and they can have important consequences for legal claims settlement. Strengths and limitations of this study are discussed. Netherlands Trial Register NTR2360.

Increased production of piRNAs from euchromatic clusters and genes in Anopheles gambiae compared with Drosophila melanogaster.

PubMed

George, Phillip; Jensen, Silke; Pogorelcnik, Romain; Lee, Jiyoung; Xing, Yi; Brasset, Emilie; Vaury, Chantal; Sharakhov, Igor V

2015-01-01

Specific genomic loci, termed Piwi-interacting RNA (piRNA) clusters, manufacture piRNAs that serve as guides for the inactivation of complementary transposable elements (TEs). The piRNA pathway has been accurately detailed in Drosophila melanogaster, while it remains poorly examined in other insects. This pathway is increasingly recognized as critical for germline development and reproduction. Understanding of the piRNA functions in mosquitoes could offer an opportunity for disease vector control by the reduction of their reproductive potential. To analyze the similarities and differences in this pathway between Drosophila and mosquito, we performed an in-depth analysis of the genomic loci producing piRNAs and their targets in the African malaria vector Anopheles gambiae. We identified 187 piRNA clusters in the An. gambiae genome and 155 piRNA clusters in the D. melanogaster genome. We demonstrate that many more piRNA clusters in the mosquito compared with the fruit fly are uni-directionally transcribed and are located outside pericentromeric heterochromatin. About 11 % of the An. gambiae piRNA population map to gene transcripts. This is a noticeable increase compared with the ~6 % of the piRNA population mapped to genes in D. melanogaster. A subset of the piRNA-enriched genes in An. gambiae has functions related to reproduction and development. At least 24 and 65 % of the mapped piRNAs correspond to genomic TE sequences in An. gambiae and D. melanogaster, respectively. DNA transposons and non-LTR retrotransposons are more abundant in An. gambiae, while LTR retrotransposons are more abundant in D. melanogaster. Yet, piRNAs predominantly target LTR retrotransposons in both species, which may point to a distinct feature of these elements compared to the other classes of TEs concerning their silencing by the piRNA pathway. Here, we demonstrate that piRNA-producing loci have more ubiquitous distribution in the An. gambiae genome than in the genome of D. melanogaster. Also, protein-coding genes have an increased role in production of piRNAs in the germline of this mosquito. Genes involved in germline and embryonic development of An. gambiae generate a substantial portion of piRNAs, suggesting a role of the piRNA pathway in the epigenetic regulation of the reproductive processes in the African malaria vector.

Star-PAP Control of BIK Expression and Apoptosis Is Regulated by Nuclear PIPKIα and PKCδ Signaling

PubMed Central

Li, Weimin; Laishram, Rakesh S.; Ji, Zhe; Barlow, Christy A.; Tian, Bin; Anderson, Richard A.

2012-01-01

SUMMARY BIK protein is an initiator of mitochondrial apoptosis and BIK expression is induced by pro-apoptotic signals including DNA damage. Here we demonstrate that 3′-end processing and expression of BIK mRNA are controlled by the nuclear PI4,5P2-regulated poly(A) polymerase Star-PAP downstream of DNA damage. Nuclear PKCδ is a key mediator of apoptosis and DNA damage stimulates PKCδ association with the Star-PAP complex where PKCδ is required for Star-PAP-dependent BIK expression. PKCδ binds the PI4,5P2-generating enzyme PIPKIα, which is essential for PKCδ interaction with the Star-PAP complex and PKCδ activity is directly stimulated by PI4,5P2. Features in the BIK 3′-UTR uniquely define Star-PAP specificity and may block canonical PAP activity toward BIK mRNA. This reveals a nuclear phosphoinositide signaling nexus where PIPKIα, PI4,5P2 and PKCδ regulate Star-PAP control of BIK expression and induction of apoptosis. This pathway is distinct from the Star-PAP-mediated oxidative stress pathway indicating signal-specific regulation of mRNA 3′-end processing. PMID:22244330

MMP13, TIMP2 and TGFB3 Gene Polymorphisms in Brazilian Chronic Periodontitis and Periimplantitis Subjects.

PubMed

Gonçalves Junior, Roberto; Pinheiro, Aristides da Rosa; Schoichet, José Jorge; Nunes, Carlos Henrique Ramirez; Gonçalves, Rackel; Bonato, Leticia Ladeira; Quinelato, Valquiria; Antunes, Leonardo Santos; Küchler, Erika Calvano; Lobo, Julie; Villas-Bôas, Ricardo de Mello; Vieira, Alexandre Rezende; Granjeiro, José Mauro; Casado, Priscila Ladeira

2016-01-01

Subjects susceptible to chronic periodontitis (CP) show a high risk for the development of periimplantitis (PI). Both diseases are multifactorial, presenting similarities in their pathophysiology and polygenic profile. MMP-13 (matrix metalloproteinases 13/ collagenase 3) is a collagenolytic enzyme, which expression is induced by TGF beta 3 (transforming growth factor type 3) in human gingival fibroblasts and inhibited by TIMP-2 (tissue inhibitor of metalloproteinase type 2). The aim of this study was to investigate the occurrence of periimplantitis (PI) in subjects with history of chronic periodontitis (CP) and polymorphisms frequency in MMP13, TIMP2 and TGFB3 genes. One hundred and sixty-three volunteers received dental implant placement were submitted to oral and radiographic examination in order to identify past history of CP or presence of PI. Volunteers were divided into 4 groups: Control (without PI and CP, n=72), CP (with CP and without PI, n=28), PI (with PI and without CP, n=28) and diseased (with CP and PI, n=35). The chi-square test correlated genotypes in specific regions of MMP13 (rs2252070), TIMP2 (rs7501477) and TGFB3 (rs2268626) genes, considering the interaction between CP and PI. The results showed that volunteers with CP had 3.2 times more susceptibility to develop PI (p=0.0004) compared to those without CP. No significant association was observed in MMP13, TIMP2 and TGFB3 genes with CP or PI. CP is a risk factor to develop PI, however, there is no association of both diseases with polymorphisms in the MMP13, TIMP2 and TGFB3 genes.

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

Purification of Glutathione S-Transferase pi from Erythrocytes and Evaluation of the Inhibitory Effect of Hypericin.

PubMed

Turk, Seyhan; Kulaksiz Erkmen, Gulnihal; Dalmizrak, Ozlem; Ogus, I Hamdi; Ozer, Nazmi

2015-12-01

Hypericin is a photosensitizer compound used in the photodynamic therapy (PDT). PDT is an alternative cancer treatment strategy whose function is dependent on the photosensitizers accumulating selectively in tumor cells and following visible or infra-red light induced activation lead to the apoptosis/necrosis of the tumor cells via the formation of reactive oxygen species. Thus, the cellular redox balance is essential for the efficacy of PDT. Among the protective enzyme systems glutathione S-transferases (GST, E.C.2.5.1.18) function in detoxification, protection against oxidative stress and intracellular transport of molecules. It is known that isoenzymes of GST and especially GST-pi is increased in cancer cells and it plays very important functions in the development of resistance to anticancer drugs. Since photosensitizers are used intravenously, it is important to elucidate the effects of photosensitizers on the erythrocyte enzymes. The aim of the present study was to investigate the impact of hypericin on human erythrocyte GST-pi (heGST-pi). Purification yield of 71% and purification fold of 2550 were achieved by using conventional chromatographic methods. The specific activity of the enzyme is found as 51 U/mg protein. Hypericin inhibited heGST-pi in a dose dependent manner and inhibition was biphasic. Noncompetitive type of inhibition was observed with both substrates, GSH and CDNB. The inhibitory constant (K i ) values obtained from Lineweaver-Burk, Dixon, secondary plots; slope and y-intercept versus 1/S (substrate) and from non-linear regression analysis were in good correlation: K i (GSH) was calculated as 0.19 ± 0.01 μM and K i (CDNB) as 0.26 ± 0.03 μM.

Suboptimal Scheduling in Switched Systems With Continuous-Time Dynamics: A Least Squares Approach.

PubMed

Sardarmehni, Tohid; Heydari, Ali

2018-06-01

Two approximate solutions for optimal control of switched systems with autonomous subsystems and continuous-time dynamics are presented. The first solution formulates a policy iteration (PI) algorithm for the switched systems with recursive least squares. To reduce the computational burden imposed by the PI algorithm, a second solution, called single loop PI, is presented. Online and concurrent training algorithms are discussed for implementing each solution. At last, effectiveness of the presented algorithms is evaluated through numerical simulations.

Tracking and disturbance rejection of MIMO nonlinear systems with PI controller

NASA Technical Reports Server (NTRS)

Desoer, C. A.; Lin, C. A.

1985-01-01

The tracking and disturbance rejection of a class of MIMO nonlinear systems with a linear proportional plus integral (PI) compensator is studied. Roughly speaking, it is shown that if the given nonlinear plant is exponentially stable and has a strictly increasing dc steady-state I/O map, then a simple PI compensator can be used to yield a stable unity-feedback closed-loop system which asymptotically tracks reference inputs that tend to constant vectors and asymptotically rejects disturbances that tend to constant vectors.

Tracking and disturbance rejection of MIMO nonlinear systems with PI controller

NASA Technical Reports Server (NTRS)

Desoer, C. A.; Lin, C.-A.

1985-01-01

The tracking and disturbance rejection of a class of MIMO nonlinear systems with linear proportional plus integral (PI) compensator is studied. Roughly speaking, it is shown that if the given nonlinear plant is exponentially stable and has a strictly increasing dc steady-state I/O map, then a simple PI compensator can be used to yield a stable unity-feedback closed-loop system which asymptotically tracks reference inputs that tend to constant vectors and asymptotically rejects disturbances that tend to constant vectors.

Persistent infections after natural transmission of bovine viral diarrhoea virus from cattle to goats and among goats

PubMed Central

2013-01-01

Bovine viral diarrhoea virus (BVDV) is an economically important pathogen of cattle worldwide. Infection of a pregnant animal may lead to persistent infection of the foetus and birth of a persistently infected (PI) calf that sheds the virus throughout its life. However, BVD viruses are not strictly species specific. BVDV has been isolated from many domesticated and wild ruminants. This is of practical importance as virus reservoirs in non-bovine hosts may hamper BVDV control in cattle. A goat given as a social companion to a BVDV PI calf gave birth to a PI goat kid. In order to test if goat to goat infections were possible, seronegative pregnant goats were exposed to the PI goat. In parallel, seronegative pregnant goats were kept together with the PI calf. Only the goat to goat transmission resulted in the birth of a next generation of BVDV PI kids whereas all goats kept together with the PI calf aborted. To our knowledge, this is the first report which shows that a PI goat cannot only transmit BVD virus to other goats but that such transmission may indeed lead to the birth of a second generation of PI goats. Genetic analyses indicated that establishment in the new host species may be associated with step-wise adaptations in the viral genome. Thus, goats have the potential to be a reservoir for BVDV. However, the PI goats showed growth retardation and anaemia and their survival under natural conditions remains questionable. PMID:23675947

Persistent infections after natural transmission of bovine viral diarrhoea virus from cattle to goats and among goats.

PubMed

Bachofen, Claudia; Vogt, Hans-Rudolf; Stalder, Hanspeter; Mathys, Tanja; Zanoni, Reto; Hilbe, Monika; Schweizer, Matthias; Peterhans, Ernst

2013-05-15

Bovine viral diarrhoea virus (BVDV) is an economically important pathogen of cattle worldwide. Infection of a pregnant animal may lead to persistent infection of the foetus and birth of a persistently infected (PI) calf that sheds the virus throughout its life. However, BVD viruses are not strictly species specific. BVDV has been isolated from many domesticated and wild ruminants. This is of practical importance as virus reservoirs in non-bovine hosts may hamper BVDV control in cattle. A goat given as a social companion to a BVDV PI calf gave birth to a PI goat kid. In order to test if goat to goat infections were possible, seronegative pregnant goats were exposed to the PI goat. In parallel, seronegative pregnant goats were kept together with the PI calf. Only the goat to goat transmission resulted in the birth of a next generation of BVDV PI kids whereas all goats kept together with the PI calf aborted. To our knowledge, this is the first report which shows that a PI goat cannot only transmit BVD virus to other goats but that such transmission may indeed lead to the birth of a second generation of PI goats. Genetic analyses indicated that establishment in the new host species may be associated with step-wise adaptations in the viral genome. Thus, goats have the potential to be a reservoir for BVDV. However, the PI goats showed growth retardation and anaemia and their survival under natural conditions remains questionable.

The cell wall-targeted purple acid phosphatase AtPAP25 is critical for acclimation of Arabidopsis thaliana to nutritional phosphorus deprivation.

PubMed

Del Vecchio, Hernan A; Ying, Sheng; Park, Joonho; Knowles, Vicki L; Kanno, Satomi; Tanoi, Keitaro; She, Yi-Min; Plaxton, William C

2014-11-01

Plant purple acid phosphatases (PAPs) belong to a relatively large gene family whose individual functions are poorly understood. Three PAP isozymes that are up-regulated in the cell walls of phosphate (Pi)-starved (-Pi) Arabidopsis thaliana suspension cells were purified and identified by MS as AtPAP12 (At2g27190), AtPAP25 (At4g36350) and AtPAP26 (At5g34850). AtPAP12 and AtPAP26 were previously isolated from the culture medium of -Pi cell cultures, and shown to be secreted by roots of Arabidopsis seedlings to facilitate Pi scavenging from soil-localized organophosphates. AtPAP25 exists as a 55 kDa monomer containing complex NX(S/T) glycosylation motifs at Asn172, Asn367 and Asn424. Transcript profiling and immunoblotting with anti-AtPAP25 immune serum indicated that AtPAP25 is exclusively synthesized under -Pi conditions. Coupled with potent mixed-type inhibition of AtPAP25 by Pi (I50 = 50 μm), this indicates a tight feedback control by Pi that prevents AtPAP25 from being synthesized or functioning as a phosphatase except when Pi levels are quite low. Promoter-GUS reporter assays revealed AtPAP25 expression in shoot vascular tissue of -Pi plants. Development of an atpap25 T-DNA insertion mutant was arrested during cultivation on soil lacking soluble Pi, but rescued upon Pi fertilization or complementation with AtPAP25. Transcript profiling by quantitative RT-PCR indicated that Pi starvation signaling was attenuated in the atpap25 mutant. AtPAP25 exhibited near-optimal phosphatase activity with several phosphoproteins and phosphoamino acids as substrates. We hypothesize that AtPAP25 plays a key signaling role during Pi deprivation by functioning as a phosphoprotein phosphatase rather than as a non-specific scavenger of Pi from extracellular P-monoesters. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Control Improvement for Jump-Diffusion Processes with Applications to Finance

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

Baeuerle, Nicole, E-mail: nicole.baeuerle@kit.edu; Rieder, Ulrich, E-mail: ulrich.rieder@uni-ulm.de

2012-02-15

We consider stochastic control problems with jump-diffusion processes and formulate an algorithm which produces, starting from a given admissible control {pi}, a new control with a better value. If no improvement is possible, then {pi} is optimal. Such an algorithm is well-known for discrete-time Markov Decision Problems under the name Howard's policy improvement algorithm. The idea can be traced back to Bellman. Here we show with the help of martingale techniques that such an algorithm can also be formulated for stochastic control problems with jump-diffusion processes. As an application we derive some interesting results in financial portfolio optimization.

Designing of smart home automation system based on Raspberry Pi

NASA Astrophysics Data System (ADS)

Saini, Ravi Prakash; Singh, Bhanu Pratap; Sharma, Mahesh Kumar; Wattanawisuth, Nattapol; Leeprechanon, Nopbhorn

2016-03-01

Locally networked or remotely controlled home automation system becomes a popular paradigm because of the numerous advantages and is suitable for academic research. This paper proposes a method for an implementation of Raspberry Pi based home automation system presented with an android phone access interface. The power consumption profile across the connected load is measured accurately through programming. Users can access the graph of total power consumption with respect to time worldwide using their Dropbox account. An android application has been developed to channelize the monitoring and controlling operation of home appliances remotely. This application facilitates controlling of operating pins of Raspberry Pi by pressing the corresponding key for turning "on" and "off" of any desired appliance. Systems can range from the simple room lighting control to smart microcontroller based hybrid systems incorporating several other additional features. Smart home automation systems are being adopted to achieve flexibility, scalability, security in the sense of data protection through the cloud-based data storage protocol, reliability, energy efficiency, etc.

Designing of smart home automation system based on Raspberry Pi

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

Saini, Ravi Prakash; Singh, Bhanu Pratap; Sharma, Mahesh Kumar

Locally networked or remotely controlled home automation system becomes a popular paradigm because of the numerous advantages and is suitable for academic research. This paper proposes a method for an implementation of Raspberry Pi based home automation system presented with an android phone access interface. The power consumption profile across the connected load is measured accurately through programming. Users can access the graph of total power consumption with respect to time worldwide using their Dropbox account. An android application has been developed to channelize the monitoring and controlling operation of home appliances remotely. This application facilitates controlling of operating pinsmore » of Raspberry Pi by pressing the corresponding key for turning “on” and “off” of any desired appliance. Systems can range from the simple room lighting control to smart microcontroller based hybrid systems incorporating several other additional features. Smart home automation systems are being adopted to achieve flexibility, scalability, security in the sense of data protection through the cloud-based data storage protocol, reliability, energy efficiency, etc.« less

Relationship between pelvic incidence and osteoarthritis of the hip

PubMed Central

Weinberg, D. S.; Bohl, M. S.; Liu, R. W.

2016-01-01

Objectives Sagittal alignment of the lumbosacral spine, and specifically pelvic incidence (PI), has been implicated in the development of spine pathology, but generally ignored with regards to diseases of the hip. We aimed to determine if increased PI is correlated with higher rates of hip osteoarthritis (HOA). The effect of PI on the development of knee osteoarthritis (KOA) was used as a negative control. Methods We studied 400 well-preserved cadaveric skeletons ranging from 50 to 79 years of age at death. Each specimen’s OA of the hip and knee were graded using a previously described method. PI was measured from standardised lateral photographs of reconstructed pelvises. Multiple regression analysis was performed to determine the relationship between age and PI with HOA and KOA. Results The mean age was 60.2 years (standard deviation (sd) 8.1), and the mean PI was 46.7° (sd 10.7°). Multiple regression analysis demonstrated a significant correlation between increased PI and HOA (standardised beta = 0.103, p = 0.017). There was no correlation between PI and KOA (standardised beta = 0.003, p = 0.912). Conclusion Higher PI in the younger individual may contribute to the development of HOA in later life. Cite this article: Dr J. J. Gebhart. Relationship between pelvic incidence and osteoarthritis of the hip. Bone Joint Res 2016;5:66–72. DOI: 10.1302/2046-3758.52.2000552. PMID:26912384

Hydraulic limits preceding mortality in a piñon-juniper woodland under experimental drought.

PubMed

Plaut, Jennifer A; Yepez, Enrico A; Hill, Judson; Pangle, Robert; Sperry, John S; Pockman, William T; McDowell, Nate G

2012-09-01

Drought-related tree mortality occurs globally and may increase in the future, but we lack sufficient mechanistic understanding to accurately predict it. Here we present the first field assessment of the physiological mechanisms leading to mortality in an ecosystem-scale rainfall manipulation of a piñon-juniper (Pinus edulis-Juniperus monosperma) woodland. We measured transpiration (E) and modelled the transpiration rate initiating hydraulic failure (E(crit) ). We predicted that isohydric piñon would experience mortality after prolonged periods of severely limited gas exchange as required to avoid hydraulic failure; anisohydric juniper would also avoid hydraulic failure, but sustain gas exchange due to its greater cavitation resistance. After 1 year of treatment, 67% of droughted mature piñon died with concomitant infestation by bark beetles (Ips confusus) and bluestain fungus (Ophiostoma spp.); no mortality occurred in juniper or in control piñon. As predicted, both species avoided hydraulic failure, but safety margins from E(crit) were much smaller in piñon, especially droughted piñon, which also experienced chronically low hydraulic conductance. The defining characteristic of trees that died was a 7 month period of near-zero gas exchange, versus 2 months for surviving piñon. Hydraulic limits to gas exchange, not hydraulic failure per se, promoted drought-related mortality in piñon pine. © 2012 Blackwell Publishing Ltd.

Automatic monitoring of ecosystem structure and functions using integrated low-cost near surface sensors

NASA Astrophysics Data System (ADS)

Kim, J.; Ryu, Y.; Jiang, C.; Hwang, Y.

2016-12-01

Near surface sensors are able to acquire more reliable and detailed information with higher temporal resolution than satellite observations. Conventional near surface sensors usually work individually, and thus they require considerable manpower from data collection through information extraction and sharing. Recent advances of Internet of Things (IoT) provides unprecedented opportunities to integrate various low-cost sensors as an intelligent near surface observation system for monitoring ecosystem structure and functions. In this study, we developed a Smart Surface Sensing System (4S), which can automatically collect, transfer, process and analyze data, and then publish time series results on public-available website. The system is composed of micro-computer Raspberry pi, micro-controller Arduino, multi-spectral spectrometers made from Light Emitting Diode (LED), visible and near infrared cameras, and Internet module. All components are connected with each other and Raspberry pi intelligently controls the automatic data production chain. We did intensive tests and calibrations in-lab. Then, we conducted in-situ observations at a rice paddy field and a deciduous broadleaf forest. During the whole growth season, 4S obtained landscape images, spectral reflectance in red, green, blue, and near infrared, normalized difference vegetation index (NDVI), fraction of photosynthetically active radiation (fPAR), and leaf area index (LAI) continuously. Also We compared 4S data with other independent measurements. NDVI obtained from 4S agreed well with Jaz hyperspectrometer at both diurnal and seasonal scales (R2 = 0.92, RMSE = 0.059), and 4S derived fPAR and LAI were comparable to LAI-2200 and destructive measurements in both magnitude and seasonal trajectory. We believe that the integrated low-cost near surface sensor could help research community monitoring ecosystem structure and functions closer and easier through a network system.

Loss of PiT-1 Results in Abnormal Endocytosis in the Yolk Sac Visceral Endoderm

PubMed Central

Wallingford, Mary C.; Giachelli, Cecilia M.

2014-01-01

PiT-1 protein is a transmembrane sodium-dependent phosphate (Pi) transporter. PiT-1 knock out (KO) embryos die from largely unknown causes by embryonic day (E) 12.5. We tested the hypothesis that PiT-1 is required for endocytosis in the embryonic yolk sac (YS) visceral endoderm (VE). Here we present data supporting that PiT-1 KO results in a YS remodeling defect and decreased endocytosis in the YS VE. The remodeling defect is not due to an upstream cardiomyocyte requirement for PiT-1, as SM22αCre-specific KO of PiT-1 in the developing heart and the YS mesodermal layer (ME) does not recapitulate the PiT-1 global KO phenotype. Furthermore, we find that high levels of PiT-1 protein localize to the YS VE apical membrane. Together these data support that PiT-1 is likely required in YS VE. During normal development maternal immunoglobulin (IgG) is endocytosed into YS VE and accumulates in the apical side of the VE in a specialized lysosome termed the apical vacuole (AV). We have identified a reduction in PiT-1 KO VE cell height and a striking loss of IgG accumulation in the PiT-1 KO VE. The endocytosis genes Tfeb, Lamtor2 and Snx2 are increased at the RNA level. Lysotracker Red staining reveals a loss of distinct AVs, and yolk sacs incubated ex vivo with phRODO Green Dextran for Endocytosis demonstrate a functional loss of endocytosis. As yolk sac endocytosis is controlled in part by microautophagy, but expression of LC3 had not been examined, we investigated LC3 expression during yolk sac development and found stage-specific LC3 RNA expression that is predominantly from the YS VE layer at E9.5. Normalized LC3-II protein levels are decreased in the PiT-1 KO YS, supporting a requirement for PiT-1 in autophagy in the YS. Therefore, we propose the novel idea that PiT-1 is central to the regulation of endocytosis and autophagy in the YS VE. PMID:25138534

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.

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.

Hysteresis compensation of piezoelectric deformable mirror based on Prandtl-Ishlinskii model

NASA Astrophysics Data System (ADS)

Ma, Jianqiang; Tian, Lei; Li, Yan; Yang, Zongfeng; Cui, Yuguo; Chu, Jiaru

2018-06-01

Hysteresis of piezoelectric deformable mirror (DM) reduces the closed-loop bandwidth and the open-loop correction accuracy of adaptive optics (AO) systems. In this work, a classical Prandtl-Ishlinskii (PI) model is employed to model the hysteresis behavior of a unimorph DM with 20 actuators. A modified control algorithm combined with the inverse PI model is developed for piezoelectric DMs. With the help of PI model, the hysteresis of the DM was reduced effectively from about 9% to 1%. Furthermore, open-loop regenerations of low-order aberrations with or without hysteresis compensation were carried out. The experimental results demonstrate that the regeneration accuracy with PI model compensation is significantly improved.

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

Classical and adaptive control of ex vivo skeletal muscle contractions using Functional Electrical Stimulation (FES)

PubMed Central

Shoemaker, Adam; Grange, Robert W.; Abaid, Nicole; Leonessa, Alexander

2017-01-01

Functional Electrical Stimulation is a promising approach to treat patients by stimulating the peripheral nerves and their corresponding motor neurons using electrical current. This technique helps maintain muscle mass and promote blood flow in the absence of a functioning nervous system. The goal of this work is to control muscle contractions from FES via three different algorithms and assess the most appropriate controller providing effective stimulation of the muscle. An open-loop system and a closed-loop system with three types of model-free feedback controllers were assessed for tracking control of skeletal muscle contractions: a Proportional-Integral (PI) controller, a Model Reference Adaptive Control algorithm, and an Adaptive Augmented PI system. Furthermore, a mathematical model of a muscle-mass-spring system was implemented in simulation to test the open-loop case and closed-loop controllers. These simulations were carried out and then validated through experiments ex vivo. The experiments included muscle contractions following four distinct trajectories: a step, sine, ramp, and square wave. Overall, the closed-loop controllers followed the stimulation trajectories set for all the simulated and tested muscles. When comparing the experimental outcomes of each controller, we concluded that the Adaptive Augmented PI algorithm provided the best closed-loop performance for speed of convergence and disturbance rejection. PMID:28273101

Disturbance rejection control for vibration suppression of piezoelectric laminated thin-walled structures

NASA Astrophysics Data System (ADS)

Zhang, S. Q.; Li, H. N.; Schmidt, R.; Müller, P. C.

2014-02-01

Thin-walled piezoelectric integrated smart structures are easily excited to vibrate by unknown disturbances. In order to design and simulate a control strategy, firstly, an electro-mechanically coupled dynamic finite element (FE) model of smart structures is developed based on first-order shear deformation (FOSD) hypothesis. Linear piezoelectric constitutive equations and the assumption of constant electric field through the thickness are considered. Based on the dynamic FE model, a disturbance rejection (DR) control with proportional-integral (PI) observer using step functions as the fictitious model of disturbances is developed for vibration suppression of smart structures. In order to achieve a better dynamic behavior of the fictitious model of disturbances, the PI observer is extended to generalized proportional-integral (GPI) observer, in which sine or polynomial functions can be used to represent disturbances resulting in better dynamics. Therefore the disturbances can be estimated either by PI or GPI observer, and then the estimated signals are fed back to the controller. The DR control is validated by various kinds of unknown disturbances, and compared with linear-quadratic regulator (LQR) control. The results illustrate that the vibrations are better suppressed by the proposed DR control.

The Moderating Effects of Perceived Intentionality: Exploring the Relationships Between Ideas of Reference, Paranoia, and Social Anxiety in Schizotypy

PubMed Central

Morrison, Sean C.; Cohen, Alex S.

2014-01-01

Introduction Ideas of reference (IOR), paranoia, and social anxiety are features of schizophrenia-spectrum disorders, which appear to be conceptually related; however, the precise nature of these relationships is unclear. These relationships may be partially explained by perceived intentionality (PI), a social-cognitive bias for perceiving other people’s actions during unpleasant situations as being directed at oneself in an intentionally malicious manner. Our primary aim was to examine the moderating role of PI on the relationships between IOR and paranoia, and between IOR and social anxiety amongst individuals with psychometrically-defined schizotypy. Methods We assessed IOR, paranoia, and social anxiety amongst individuals with psychometrically-defined schizotypy (n = 44) and controls (n = 36), and examined the moderating effects of PI within each group. Results As hypothesized, PI moderated the relationship between IOR and paranoia such that higher PI predicted higher levels of paranoia as IOR increased. Additionally, we found that PI moderated the relationship between IOR and social anxiety such that higher PI predicted lower levels of social anxiety as IOR increased. Discussion Theoretical and practical implications are discussed including the potential for assessing PI as a proxy for paranoia when clinicians suspect a client is underreporting paranoia due to positive impression management. PMID:24987988

Complications of hyperglycaemia with PI3K–AKT–mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials

PubMed Central

Geuna, E; Roda, D; Rafii, S; Jimenez, B; Capelan, M; Rihawi, K; Montemurro, F; Yap, T A; Kaye, S B; De Bono, J S; Molife, L R; Banerji, U

2015-01-01

Background: PI3K–AKT–mTOR inhibitors (PAMi) are promising anticancer treatments. Hyperglycaemia is a mechanism-based toxicity of these agents and is becoming increasingly important with their use in larger numbers of patients. Methods: Retrospective case-control study comparing incidence and severity of hyperglycaemia (all grades) between a case group of 387 patients treated on 18 phase I clinical trials with PAMi (78 patients with PI3Ki, 138 with mTORi, 144 with AKTi and 27 with PI3K/mTORi) and a control group of 109 patients treated on 10 phase I clinical trials with agents not directly targeting the PAM pathway. Diabetic patients were excluded in both groups. Results: The incidence of hyperglycaemia was not significantly different between cases and controls (86.6% vs 80.7%, respectively, P=0.129). However, high grade (grade 3–4) hyperglycaemia was more frequent in the PAMi group than in controls (6.7% vs 0%, respectively, P=0.005). The incidence of grade 3–4 hyperglycaemia was greater with AKT and multikinase inhibitors compared with other PAMi (P<0.001). All patients with high-grade hyperglycaemia received antihyperglycemic treatment and none developed severe metabolic complications (diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic state). High-grade hyperglycaemia was the cause of permanent PAMi discontinuation in nine patients. Conclusions: PI3K–AKT–mTOR inhibitors are associated with small (6.7%) but statistically significant increased risk of high-grade hyperglycaemia compared with non-PAM targeting agents. However, PAMi-induced hyperglycaemia was not found to be associated with severe metabolic complications in this non-diabetic population of patients with advanced cancers. PMID:26554652

Complications of hyperglycaemia with PI3K-AKT-mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials.

PubMed

Geuna, E; Roda, D; Rafii, S; Jimenez, B; Capelan, M; Rihawi, K; Montemurro, F; Yap, T A; Kaye, S B; De Bono, J S; Molife, L R; Banerji, U

2015-12-01

PI3K-AKT-mTOR inhibitors (PAMi) are promising anticancer treatments. Hyperglycaemia is a mechanism-based toxicity of these agents and is becoming increasingly important with their use in larger numbers of patients. Retrospective case-control study comparing incidence and severity of hyperglycaemia (all grades) between a case group of 387 patients treated on 18 phase I clinical trials with PAMi (78 patients with PI3Ki, 138 with mTORi, 144 with AKTi and 27 with PI3K/mTORi) and a control group of 109 patients treated on 10 phase I clinical trials with agents not directly targeting the PAM pathway. Diabetic patients were excluded in both groups. The incidence of hyperglycaemia was not significantly different between cases and controls (86.6% vs 80.7%, respectively, P=0.129). However, high grade (grade 3-4) hyperglycaemia was more frequent in the PAMi group than in controls (6.7% vs 0%, respectively, P=0.005). The incidence of grade 3-4 hyperglycaemia was greater with AKT and multikinase inhibitors compared with other PAMi (P<0.001). All patients with high-grade hyperglycaemia received antihyperglycemic treatment and none developed severe metabolic complications (diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic state). High-grade hyperglycaemia was the cause of permanent PAMi discontinuation in nine patients. PI3K-AKT-mTOR inhibitors are associated with small (6.7%) but statistically significant increased risk of high-grade hyperglycaemia compared with non-PAM targeting agents. However, PAMi-induced hyperglycaemia was not found to be associated with severe metabolic complications in this non-diabetic population of patients with advanced cancers.

Enhanced Frontoparietal Synchronized Activation During the Wake-Sleep Transition in Patients with Primary Insomnia

PubMed Central

Corsi-Cabrera, María; Figueredo-Rodríguez, Pedro; del Río-Portilla, Yolanda; Sánchez-Romero, Jorge; Galán, Lídice; Bosch-Bayard, Jorge

2012-01-01

Introduction: Cognitive and brain hyperactivation have been associated with trouble falling asleep and sleep misperception in patients with primary insomnia (PI). Activation and synchronization/temporal coupling in frontal and frontoparietal regions involved in executive control and endogenous attention might be implicated in these symptoms. Methods: Standard polysomnography (PSG) and electroencephalogram (EEG) were recorded in 10 unmedicated young patients (age 19-34 yr) with PI with no other sleep/medical condition, and in 10 matched control subjects. Absolute power, temporal coupling, and topographic source distribution (variable resolution electromagnetic tomography or VARETA) were obtained for all time spent in waking, Stage 1 and Stage 2 of the wake-sleep transition period (WSTP), and the first 3 consecutive min of N3. Subjective sleep quality and continuity were evaluated. Results: In comparison with control subjects, patients with PI exhibited significantly higher frontal beta power and current density, and beta and gamma frontoparietal temporal coupling during waking and Stage 1. Conclusion: These findings suggest that frontal deactivation and disengagement of brain regions involved in executive control, attention, and self-awareness are impaired in patients with PI. The persistence of this activated and coherent network during the wake-sleep transition period (WSTP) may contribute to a better understanding of underlying mechanisms involved in difficulty in falling asleep, in sleep misperception, and in the lighter, poorer, and nonrefreshing sleep experienced by some patients with PI. Citation: Corsi-Cabrera M; Figueredo-Roríguez P; del Río-Portilla Y; Sánchez-Romero J; Galán L; Bosch-Bayard J. Enhanced frontoparietal synchronized activation during the wake-sleep transition in patients with primary insomnia. SLEEP 2012;35(4):501-511. PMID:22467988

The Dynamics of Treg/Th17 and the Imbalance of Treg/Th17 in Clonorchis sinensis-Infected Mice

PubMed Central

Hua, Hui; Li, Bo; Zhang, Bo; Yu, Qian; Li, Xiang-Yang; Liu, Ying; Pan, Wei; Liu, Xiang-Ye; Tang, Ren-Xian; Zheng, Kui-Yang

2015-01-01

Clonorchiasis, caused by the liver fluke Clonorchis sinensis, is a chronic parasitic infection regulated by T cell subsets. An imbalance of CD4+CD25+ Foxp3+regulatory T (Treg) and interleukin (IL)-17-secreting T cells (Th17) may control inflammation and play an important role in the pathogenesis of immune evasion. In the present study, we assessed the dynamics of Treg/Th17 and determined whether the Treg/Th17 ratio is altered in C. sinensis-infected mice. The results showed that the percentages of splenic Treg cells in CD4+ T cells were suppressed on day 14 post-infection (PI) but increased on day 56 PI, while Th17 cells were increased on day 56 PI compared with normal control (NC) mice. The Treg/Th17 ratio steadily increased from day 28 to day 56 PI. The hepatic levels of their specific transcription factors (Foxp3 for Treg and RORγt for Th17) were increased in C. sinensis-infected mice from day 14 to 56 PI, and significantly higher than those in NC mice. Meanwhile, serum levels of IL-2 and IL-17 were profoundly increased in C. sinensis-infected mice throughout the experiment; while the concentrations of IL-6 and transforming growth factor β1 (TGF-β1) peaked on day 14 PI, but then decreased on day 28 and 56 PI. Our results provide the first evidence of an increased Treg/Th17 ratio in C. sinensis-infected mice, suggesting that a Treg/Th17 imbalance may play a role in disease outcomes of clonorchiasis. PMID:26599407

Effect of dolutegravir in combination with Nucleoside Reverse Transcriptase Inhibitors (NRTIs) on people living with HIV who have pre-existing NRTI mutations.

PubMed

Sörstedt, Erik; Carlander, Christina; Flamholc, Leo; Hejdeman, Bo; Svedhem, Veronica; Sönnerborg, Anders; Gisslén, Magnus; Yilmaz, Aylin

2018-05-01

Until the introduction of dolutegravir (DTG), people living with HIV (PLWH) who have developed nucleoside reverse transcriptase inhibitor (NRTI) mutations have had few other treatment options outside of regimens based on ritonavir-boosted protease inhibitors (PI/r). Here we report treatment results among PLWH in Sweden with pre-existing NRTI mutations on antiretroviral treatment (ART) with DTG and one to two NRTIs. All PLWH on ART with DTG and one to two NRTIs with pre-existing NRTI mutations were retrospectively identified from the National InfCare HIV database. As controls, PLWH on PI/r and one to two NRTIs, matched according to Genotypic Susceptibility Score and observation time, were included. Data were collected as long as the study population was on treatment with DTG; controls were monitored for the same interval. Outcome was classified as either treatment success or failure. In total, 244 participants (122 individuals treated with DTG and 122 individuals treated with PI/r) were included. Median observation time was 78 weeks (interquartile range 50-98 weeks) for participants on DTG and 75 weeks (50-101 weeks) for individuals on PI/r. Viral failure was detected in four individuals treated with DTG and three individuals treated with PI/r, resulting in similar success rates of 96.7% and 97.5%, respectively. No new mutations were found among participants with treatment failure. DTG in combination with one to two NRTIs was as efficient as PI/r in individuals with pre-existing NRTI mutations in this setting. It may be considered an alternative to PI/r-based ART even in the presence of NRTI resistance. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Sensitivity of single-domain versus multiple-domain outcome measures to identify responders in chronic low-back pain: pooled analysis of 2 placebo-controlled trials of etoricoxib.

PubMed

Jensen, Mark P; Schnitzer, Thomas J; Wang, Hongwei; Smugar, Steven S; Peloso, Paul M; Gammaitoni, Arnold

2012-01-01

A composite responder index for chronic low-back pain (CLBP) has recently been proposed to evaluate the efficacy of CLBP treatments in clinical trials. We compared the responsiveness of this composite measure with a number of single-item responder definitions. We pooled data from 2 placebo-controlled studies of etoricoxib in CLBP to evaluate 5 response criteria: 30% pain intensity (PI) reduction; 50% PI reduction; 20 mm absolute reduction (100 mm PI visual analog scale); patient global assessment of response to therapy (PGART); and the composite criteria of 30% reduction in PI+30% improvement in PGART of disease status+no worsening in function. We used bootstrap analysis and logistic regression to assess the ability to differentiate etoricoxib and placebo, and the κ coefficient to assess agreement among the responder criteria. The criterion of a 20 mm improvement in PI resulted in the greatest proportion (71.5%) of patients being classified as responders and all criteria separated etoricoxib from placebo (P≤0.0001). PGART had the highest discriminant ability (odds ratio 5.90), and was significantly (P<0.05) more discriminant than the 20 mm and ≥30% improvements and the composite criteria. After adjusting for all other measures, only PGART continued to show a significant treatment effect for etoricoxib versus placebo (P=0.0003). Kappa values contrasting the composite criteria and the single-item measures ranged from 0.59 to 0.85. These findings do not support the superiority of a composite index over single-item ratings of PI and PGART ratings, but do suggest that PGART ratings may be more responsive to treatment, perhaps because they measure something in addition to change in PI.

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.

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

Probing Combustion Chemistry in a Miniature Shock Tube with Synchrotron VUV Photo Ionization Mass Spectrometry

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

Lynch, Patrick T.; Troy, Tyler P.; Ahmed, Musahid

2015-01-29

Tunable synchrotron-sourced photoionization time-of-flight mass spectrometry (PI-TOF-MS) is an important technique in combustion chemistry, complementing lab-scale electron impact and laser photoionization studies for a wide variety of reactors, typically at low pressure. For high-temperature and high-pressure chemical kinetics studies, the shock tube is the reactor of choice. Extending the benefits of shock tube/TOF-MS research to include synchrotron sourced PI-TOF-MS required a radical reconception of the shock tube. An automated, miniature, high-repetition-rate shock tube was developed and can be used to study high-pressure reactive systems (T > 600 K, P < 100 bar) behind reflected shock waves. In this paper, wemore » present results of a PI-TOF-MS study at the Advanced Light Source at Lawrence Berkeley National Laboratory. Dimethyl ether pyrolysis (2% CH3OCH3/Ar) was observed behind the reflected shock (1400 < T-5 < 1700 K, 3 < P-5 < 16 bar) with ionization energies between 10 and 13 eV. Individual experiments have extremely low signal levels. However, product species and radical intermediates are well-resolved when averaging over hundreds of shots, which is ordinarily impractical in conventional shock tube studies. The signal levels attained and data throughput rates with this technique are comparable to those with other synchrotron-based PI-TOF-MS reactors, and it is anticipated that this high pressure technique will greatly complement those lower pressure techniques.« less

A novel TFC forward osmosis (FO) membrane supported by polyimide (PI) microporous nanofiber membrane

NASA Astrophysics Data System (ADS)

Chi, Xiang-Yu; Zhang, Ping-Yun; Guo, Xue-Jiao; Xu, Zhen-Liang

2018-01-01

A novel interfacial polymerization (IP) procedure on polyimide (PI) microporous nanofiber membrane support with mean pore size 1.27 μm was reported. Using m-phenylenediamine (MPD) as aqueous phase monomer, trimesoyl chloride (TMC) as organic phase monomer, ethanol as aqueous phase co-solvent, thin-film composite (TFC) forward osmosis (FO) membrane was fabricated by two IP procedures. The first IP procedure with the unconventional order (ie, the membrane was immersed in the TMC organic phase first, then in the co-solvent ethanol-water MPD aqueous phase) was used to diminish the pore size of PI microporous nanofiber membrane support for the formation of the polyamide layer. The secondary IP procedure was employed to form the relatively dense polyamide layer with conventional order (ie, the membrane was immersed in the co-solvent ethanol-water MPD aqueous phase first, then in the TMC organic phase). The experimental results showed that higher ethanol concentration led to the relatively higher pure water permeability in RO process and osmotic water flux in FO process, whereas NaCl rejection in RO process decreased and reverse salt flux increased. The specific salt flux (Js/Jv) of TFC FO PI nanofiber membrane (PIN-2-4) could be as low as 0.095 g/L in FO mode. These results could be attributed to influence of the addition of ethanol into aqueous phase on the surface morphology, hydrophilicity and polyamide layer structure.

Wire rope tension control of hoisting systems using a robust nonlinear adaptive backstepping control scheme.

PubMed

Zhu, Zhen-Cai; Li, Xiang; Shen, Gang; Zhu, Wei-Dong

2018-01-01

This paper concerns wire rope tension control of a double-rope winding hoisting system (DRWHS), which consists of a hoisting system employed to realize a transportation function and an electro-hydraulic servo system utilized to adjust wire rope tensions. A dynamic model of the DRWHS is developed in which parameter uncertainties and external disturbances are considered. A comparison between simulation results using the dynamic model and experimental results using a double-rope winding hoisting experimental system is given in order to demonstrate accuracy of the dynamic model. In order to improve the wire rope tension coordination control performance of the DRWHS, a robust nonlinear adaptive backstepping controller (RNABC) combined with a nonlinear disturbance observer (NDO) is proposed. Main features of the proposed combined controller are: (1) using the RNABC to adjust wire rope tensions with consideration of parameter uncertainties, whose parameters are designed online by adaptive laws derived from Lyapunov stability theory to guarantee the control performance and stability of the closed-loop system; and (2) introducing the NDO to deal with uncertain external disturbances. In order to demonstrate feasibility and effectiveness of the proposed controller, experimental studies have been conducted on the DRWHS controlled by an xPC rapid prototyping system. Experimental results verify that the proposed controller exhibits excellent performance on wire rope tension coordination control compared with a conventional proportional-integral (PI) controller and adaptive backstepping controller. Copyright © 2017 ISA. All rights reserved.

PI3Kδ inhibition reduces TNF secretion and neuroinflammation in a mouse cerebral stroke model.

PubMed

Low, Pei Ching; Manzanero, Silvia; Mohannak, Nika; Narayana, Vinod K; Nguyen, Tam H; Kvaskoff, David; Brennan, Faith H; Ruitenberg, Marc J; Gelderblom, Mathias; Magnus, Tim; Kim, Hyun Ah; Broughton, Brad R S; Sobey, Christopher G; Vanhaesebroeck, Bart; Stow, Jennifer L; Arumugam, Thiruma V; Meunier, Frédéric A

2014-03-14

Stroke is a major cause of death worldwide and the leading cause of permanent disability. Although reperfusion is currently used as treatment, the restoration of blood flow following ischaemia elicits a profound inflammatory response mediated by proinflammatory cytokines such as tumour necrosis factor (TNF), exacerbating tissue damage and worsening the outcomes for stroke patients. Phosphoinositide 3-kinase delta (PI3Kδ) controls intracellular TNF trafficking in macrophages and therefore represents a prospective target to limit neuroinflammation. Here we show that PI3Kδ inhibition confers protection in ischaemia/reperfusion models of stroke. In vitro, restoration of glucose supply following an episode of glucose deprivation potentiates TNF secretion from primary microglia-an effect that is sensitive to PI3Kδ inhibition. In vivo, transient middle cerebral artery occlusion and reperfusion in kinase-dead PI3Kδ (p110δ(D910A/D910A)) or wild-type mice pre- or post-treated with the PI3Kδ inhibitor CAL-101, leads to reduced TNF levels, decreased leukocyte infiltration, reduced infarct size and improved functional outcome. These data identify PI3Kδ as a potential therapeutic target in ischaemic stroke.

AGO3 Slicer activity regulates mitochondria-nuage localization of Armitage and piRNA amplification.

PubMed

Huang, Haidong; Li, Yujing; Szulwach, Keith E; Zhang, Guoqiang; Jin, Peng; Chen, Dahua

2014-07-21

In Drosophila melanogaster the reciprocal "Ping-Pong" cycle of PIWI-interacting RNA (piRNA)-directed RNA cleavage catalyzed by the endonuclease (or "Slicer") activities of the PIWI proteins Aubergine (Aub) and Argonaute3 (AGO3) has been proposed to expand the secondary piRNA population. However, the role of AGO3/Aub Slicer activity in piRNA amplification remains to be explored. We show that AGO3 Slicer activity is essential for piRNA amplification and that AGO3 inhibits the homotypic Aub:Aub Ping-Pong process in a Slicer-independent manner. We also find that expression of an AGO3 Slicer mutant causes ectopic accumulation of Armitage, a key component in the primary piRNA pathway, in the Drosophila melanogaster germline granules known as nuage. AGO3 also coexists and interacts with Armitage in the mitochondrial fraction. Furthermore, AGO3 acts in conjunction with the mitochondria-associated protein Zucchini to control the dynamic subcellular localization of Armitage between mitochondria and nuage in a Slicer-dependent fashion. Collectively, our findings uncover a new mechanism that couples mitochondria with nuage to regulate secondary piRNA amplification. © 2014 Huang et al.

Reduced autobiographical memory specificity relates to weak resistance to proactive interference.

PubMed

Smets, Jorien; Wessel, Ineke; Raes, Filip

2014-06-01

Reduced autobiographical memory specificity (rAMS), experiencing intrusive memories, and rumination appear to be risk factors for depression and depressive relapse. The aim of the current study was to investigate whether a weak resistance to proactive interference (PI) might underlie this trio of cognitive risk factors. Resistance to PI refers to being able to ignore cognitive distracters that were previously relevant but became irrelevant for current task goals. Students (N = 65) and depressed patients (N = 37) completed tasks measuring resistance to PI and AMS, and completed questionnaires on intrusive memories and rumination. In both samples, weaker resistance to PI was associated with rAMS. There was no evidence for a relationship between resistance to PI and intrusive memories or rumination. As we did not assess other measures of executive functioning, we cannot conclude whether the observed relationship between rumination and PI is due to unique qualities of PI. Difficulties to deliberately recall specific, rather than general or categoric autobiographical memories appear to be related to more general problems with the inhibition of interference of mental distracters. The results are in line with the executive control account of rAMS. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

Two-photon or higher-order absorbing optical materials and methods of use

NASA Technical Reports Server (NTRS)

Marder, Seth (Inventor); Perry, Joseph (Inventor)

2012-01-01

Compositions capable of simultaneous two-photon absorption and higher order absorptivities are provided. Compounds having a donor-pi-donor or acceptor-pi-acceptor structure are of particular interest, where the donor is an electron donating group, acceptor is an electron accepting group, and pi is a pi bridge linking the donor and/or acceptor groups. The pi bridge may additionally be substituted with electron donating or withdrawing groups to alter the absorptive wavelength of the structure. Also disclosed are methods of generating an excited state of such compounds through optical stimulation with light using simultaneous absorption of photons of energies individually insufficient to achieve an excited state of the compound, but capable of doing so upon simultaneous absorption of two or more such photons. Applications employing such methods are also provided, including controlled polymerization achieved through focusing of the light source(s) used.

Use of the PiCCO system in critically ill patients with septic shock and acute respiratory distress syndrome: a study protocol for a randomized controlled trial.

PubMed

Zhang, Zhongheng; Xu, Xiao; Yao, Min; Chen, Huilan; Ni, Hongying; Fan, Haozhe

2013-02-01

Hemodynamic monitoring is very important in critically ill patients with shock or acute respiratory distress syndrome(ARDS). The PiCCO (Pulse index Contour Continuous Cardiac Output, Pulsion Medical Systems, Germany) system has been developed and used in critical care settings for several years. However, its impact on clinical outcomes remains unknown. The study is a randomized controlled multi-center trial. A total of 708 patients with ARDS, septic shock or both will be included from January 2012 to January 2014. Subjects will be randomized to receive PiCCO monitoring or not. Our primary end point is 30-day mortality, and secondary outcome measures include ICU length of stay, days on mechanical ventilation, days of vasoactive agent support, ICU-free survival days during a 30-day period, mechanical-ventilation-free survival days during a 30-day period, and maximum SOFA score during the first 7 days. We investigate whether the use of PiCCO monitoring will improve patient outcomes in critically ill patients with ARDS or septic shock. This will provide additional data on hemodynamic monitoring and help clinicians to make decisions on the use of PiCCO. http://www.clinicaltrials.gov NCT01526382.

Phosphoinositide 3-kinase gamma regulates airway smooth muscle contraction by modulating calcium oscillations.

PubMed

Jiang, Haihong; Abel, Peter W; Toews, Myron L; Deng, Caishu; Casale, Thomas B; Xie, Yan; Tu, Yaping

2010-09-01

Phosphoinositide 3-kinase gamma (PI3Kgamma) has been implicated in the pathogenesis of asthma, but its mechanism has been considered indirect, through release of inflammatory cell mediators. Because airway smooth muscle (ASM) contractile hyper-responsiveness plays a critical role in asthma, the aim of the present study was to determine whether PI3Kgamma can directly regulate contractility of ASM. Immunohistochemistry staining indicated expression of PI3Kgamma protein in ASM cells of mouse trachea and lung, which was confirmed by Western blot analysis in isolated mouse tracheal ASM cells. PI3Kgamma inhibitor II inhibited acetylcholine (ACh)-stimulated airway contraction of cultured precision-cut mouse lung slices in a dose-dependent manner with 75% inhibition at 10 muM. In contrast, inhibitors of PI3Kalpha, PI3Kbeta, or PI3Kdelta, at concentrations 40-fold higher than their reported IC(50) values for their primary targets, had no effect. It is noteworthy that airways in lung slices pretreated with PI3Kgamma inhibitor II still exhibited an ACh-induced initial contraction, but the sustained contraction was significantly reduced. Furthermore, the PI3Kgamma-selective inhibitor had a small inhibitory effect on the ACh-stimulated initial Ca(2+) transient in ASM cells of mouse lung slices or isolated mouse ASM cells but significantly attenuated the sustained Ca(2+) oscillations that are critical for sustained airway contraction. This report is the first to show that PI3Kgamma directly controls contractility of airways through regulation of Ca(2+) oscillations in ASM cells. Thus, in addition to effects on airway inflammation, PI3Kgamma inhibitors may also exert direct effects on the airway contraction that contribute to pathologic airway hyper-responsiveness.

Phosphoinositide 3-Kinase γ Regulates Airway Smooth Muscle Contraction by Modulating Calcium Oscillations

PubMed Central

Jiang, Haihong; Abel, Peter W.; Toews, Myron L.; Deng, Caishu; Casale, Thomas B.; Xie, Yan

2010-01-01

Phosphoinositide 3-kinase γ (PI3Kγ) has been implicated in the pathogenesis of asthma, but its mechanism has been considered indirect, through release of inflammatory cell mediators. Because airway smooth muscle (ASM) contractile hyper-responsiveness plays a critical role in asthma, the aim of the present study was to determine whether PI3Kγ can directly regulate contractility of ASM. Immunohistochemistry staining indicated expression of PI3Kγ protein in ASM cells of mouse trachea and lung, which was confirmed by Western blot analysis in isolated mouse tracheal ASM cells. PI3Kγ inhibitor II inhibited acetylcholine (ACh)-stimulated airway contraction of cultured precision-cut mouse lung slices in a dose-dependent manner with 75% inhibition at 10 μM. In contrast, inhibitors of PI3Kα, PI3Kβ, or PI3Kδ, at concentrations 40-fold higher than their reported IC50 values for their primary targets, had no effect. It is noteworthy that airways in lung slices pretreated with PI3Kγ inhibitor II still exhibited an ACh-induced initial contraction, but the sustained contraction was significantly reduced. Furthermore, the PI3Kγ-selective inhibitor had a small inhibitory effect on the ACh-stimulated initial Ca2+ transient in ASM cells of mouse lung slices or isolated mouse ASM cells but significantly attenuated the sustained Ca2+ oscillations that are critical for sustained airway contraction. This report is the first to show that PI3Kγ directly controls contractility of airways through regulation of Ca2+ oscillations in ASM cells. Thus, in addition to effects on airway inflammation, PI3Kγ inhibitors may also exert direct effects on the airway contraction that contribute to pathologic airway hyper-responsiveness. PMID:20501633

Repeat, Low Altitude Measurements of Vegetation Status and Biomass Using Manned Aerial and UAS Imagery in a Piñon-Juniper Woodland

NASA Astrophysics Data System (ADS)

Krofcheck, D. J.; Lippitt, C.; Loerch, A.; Litvak, M. E.

2015-12-01

Measuring the above ground biomass of vegetation is a critical component of any ecological monitoring campaign. Traditionally, biomass of vegetation was measured with allometric-based approach. However, it is also time-consuming, labor-intensive, and extremely expensive to conduct over large scales and consequently is cost-prohibitive at the landscape scale. Furthermore, in semi-arid ecosystems characterized by vegetation with inconsistent growth morphologies (e.g., piñon-juniper woodlands), even ground-based conventional allometric approaches are often challenging to execute consistently across individuals and through time, increasing the difficulty of the required measurements and consequently the accuracy of the resulting products. To constrain the uncertainty associated with these campaigns, and to expand the extent of our measurement capability, we made repeat measurements of vegetation biomass in a semi-arid piñon-juniper woodland using structure-from-motion (SfM) techniques. We used high-spatial resolution overlapping aerial images and high-accuracy ground control points collected from both manned aircraft and multi-rotor UAS platforms, to generate digital surface model (DSM) for our experimental region. We extracted high-precision canopy volumes from the DSM and compared these to the vegetation allometric data, s to generate high precision canopy volume models. We used these models to predict the drivers of allometric equations for Pinus edulis and Juniperous monosperma (canopy height, diameter at breast height, and root collar diameter). Using this approach, we successfully accounted for the carbon stocks in standing live and standing dead vegetation across a 9 ha region, which contained 12.6 Mg / ha of standing dead biomass, with good agreement to our field plots. Here we present the initial results from an object oriented workflow which aims to automate the biomass estimation process of tree crown delineation and volume calculation, and partition standing biomass into live and dead pools, in a change detection context.

Participation in sport in persons with spinal cord injury in Switzerland.

PubMed

Rauch, A; Fekete, C; Oberhauser, C; Marti, A; Cieza, A

2014-09-01

Secondary data analysis of a questionnaire-based, cross-sectional survey in persons with spinal cord injury (SCI) in Switzerland. To describe the frequency of participation in sport (PiS) and to identify correlates for PiS in persons with SCI in Switzerland. Community sampleMethods:Frequency of PiS was assessed retrospectively for the time before the onset of SCI and the time of the survey using a single-item question. A comprehensive set of independent variables was selected from the original questionnaire. Descriptive statistics, bivariate analyses and ordinal regressions were carried out. Data from 505 participants were analyzed. Twenty independent variables were selected for analyses. PiS decreased significantly from the time before the onset of SCI to the time of the survey (P<0.001). Sport levels were significantly lower in women than men for the time of the survey (P<0.001), whereas no difference was observed before onset of SCI (P=0.446). Persons with tetraplegia participated significantly less often in sport than persons with paraplegia (P<0.001). Lesion level, active membership in a club, frequency of PiS before the onset of SCI and the subjective evaluation of the importance of sport correlate with PiS. When controlling for gender differences, only the subjective importance of sport for persons with SCI determines PiS, particularly among women. Persons with tetraplegia and women need special attention when planning interventions to improve PiS. Furthermore, the subjective importance of sport is important for PiS, particularly among women, whereas most other factors were only weakly associated with PiS.

[A correlation study between diarrhea-predominant irritable bowel syndrome complicated functional dyspepsia patients of Gan-stagnation Pi-deficiency syndrome and gastrointestinal hormones].

PubMed

Zhao, Liang; Song, Wen; Zhu, Ping; Zhang, Yu; Bu, Ping

2014-10-01

To investigate the correlation between the pathogeneses of diarrhea-pre- dominant irritable bowel syndrome (D-IBS) complicated functional dyspepsia (FD) patients of Gan-stagnation Pi-deficiency Syndrome (GSPDS) and symptoms, psychological states, and gastrointestinal hormones. A total of 111 patients with confirmed D-IBS complicated FD of GSPDS were recruited as the treated group by using Rome III standard and Chinese medical syndrome standard. And 30 healthy volunteers were recruited as the control group. The general condition, scoring for digestive symptoms, and the distribution of GSPDS subtype of all subjects were recorded by a questionnaire, and assessed by Symptom Checklist (SCL-90; a software for psychological test developed by Beijing Huicheng Adult Cor- poration). Meanwhile, plasma levels of 5-hydroxytryptamine (5-HT), somatostatin (SS), vasoactive intestinal peptide (VIP), endothelin (ET), interleukin 10 (IL-10), and interleukin 12 (IL-12) were measured in all subjects. (1) The subtype of D-IBS complicated FD of GSPDS was dominant in Pi-qi deficiency type (51/111,45.9%),Pi yang deficiency type (34/111,30.6%), and GSPDS. There was no statistical difference in the scoring of digestive symptoms among the 3 subtypes (P >0.05). (2) Compared with the control group, the anxiety factor score and the total score significantly increased in all three subtypes of D-IBS complicated FD of GSPDS, and the depression score of Pi yang deficiency type and Gan-depression type also significantly increased (P <0.05, P <0.01); the depression score of Gan-depression type was significantly higher than that of the Pi-qi deficiency type (P <0.01). Plasma 5-HT levels were obviously lower in D-IBS complicated FD patients of GSPDS accompanied with anxiety or depression than in those with no obvious psychological abnormalities, and VIP and IL-10 levels were significantly lower than those in the control group (P <0.05). Plasma VIP levels were also obviously lower in D-IBS complicated FD patients of GSPDS accompanied with anxiety or depression than in those with no obvious psychological abnormalities (P <0.01), and SS levels were significantly lower than those in the control group (P <0.05). There was no statistical difference in plasma ET or IL-12 levels in each patient group, when compared with the control group (P >0.05). (3) Compared with the.control group, plasma 5-HT levels significantly increased, plasma VIP and IL-10 levels significantly decreased in ach subtype of D-IBS complicated FD patients of GSPDS (P <0.05, P <0.01), and no significant change of SS, ET, or IL-12 occurred (P >0.05). Besides, plasma 5-HT levels were significantly higher in Gan-depression type than in Pi yang deficiency type, VIP levels were lower in Gan-depression type than in Pi-qi deficiency type (all P <0.05). Gan stagnation and Pi deficiency were dominant in D-IBS complicated FD patients of GSPDS. Psychological abnormalities, increased plasma 5-HT levels, and decreased plasma VIP levels were closely correlated with Gan stagnation subtype, which provided some reference for looking for objective indicators of Chinese medical syndromes in treating D-IBS complicated FD patients of GSPDS.

Robust decentralized power system controller design: Integrated approach

NASA Astrophysics Data System (ADS)

Veselý, Vojtech

2017-09-01

A unique approach to the design of gain scheduled controller (GSC) is presented. The proposed design procedure is based on the Bellman-Lyapunov equation, guaranteed cost and robust stability conditions using the parameter dependent quadratic stability approach. The obtained feasible design procedures for robust GSC design are in the form of BMI with guaranteed convex stability conditions. The obtained design results and their properties are illustrated in the simultaneously design of controllers for simple model (6-order) turbogenerator. The results of the obtained design procedure are a PI automatic voltage regulator (AVR) for synchronous generator, a PI governor controller and a power system stabilizer for excitation system.

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

Fast helicity switching of x-ray circular polarization at beamline P09 at PETRA III

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

Strempfer, J., E-mail: Joerg.Strempfer@desy.de; Mardegan, J. R. L.; Francoual, S.

At the resonant scattering and diffraction beamline P09 at PETRA III/DESY, polarization manipulation in the X-ray energy range 3-13 keV is possible using wave-plates. Recently, fast flipping of circular polarization helicity using the Raspberry Pi controlled FPGA (PiLC) device developed at DESY and dedicated piezo-electric flippers has been commissioned. Functionality of the PiLC for XMCD and first XMCD measurements at the Fe K-and Dy-L{sub 3} absorption edges are presented.

Wind Turbine Power Generation Emulation Via Doubly Fed Induction Generator Control

DTIC Science & Technology

2009-12-01

vde thetas vqs_pu vds_pu synchronous...to stationary 0 ide_ref 200 Vdc_ref I_ref I_meas vqe PI iq I_ref I_meas vde PI id v_ref v_meas iqs PI Vdc 4 theta_s 3 ide 2 iqe 1 Vdc 21 between...1-1 x(-1)- a b a + b+ Sy stem Generator Variac P/S 60V 60HzVariac P/S 60V 60Hz 70 Vabc_s THETA CALCULATION 5 vde 4 vqe 3 Vas 2 Vdc_out 1

The PI3K Pathway Balances Self-Renewal and Differentiation of Nephron Progenitor Cells through β-Catenin Signaling

PubMed Central

Lindström, Nils Olof; Carragher, Neil Oliver; Hohenstein, Peter

2015-01-01

Summary Nephron progenitor cells differentiate to form nephrons during embryonic kidney development. In contrast, self-renewal maintains progenitor numbers and premature depletion leads to impaired kidney function. Here we analyze the PI3K pathway as a point of convergence for the multiple pathways that are known to control self-renewal in the kidney. We demonstrate that a reduction in PI3K signaling triggers premature differentiation of the progenitors and activates a differentiation program that precedes the mesenchymal-to-epithelial transition through ectopic activation of the β-catenin pathway. Therefore, the combined output of PI3K and other pathways fine-tunes the balance between self-renewal and differentiation in nephron progenitors. PMID:25754203

Phosphate homeostasis in the yeast Saccharomyces cerevisiae, the key role of the SPX domain-containing proteins.

PubMed

Secco, David; Wang, Chuang; Shou, Huixia; Whelan, James

2012-02-17

In the yeast Saccharomyces cerevisiae, a working model for nutrient homeostasis in eukaryotes, inorganic phosphate (Pi) homeostasis is regulated by the PHO pathway, a set of phosphate starvation induced genes, acting to optimize Pi uptake and utilization. Among these, a subset of proteins containing the SPX domain has been shown to be key regulators of Pi homeostasis. In this review, we summarize the recent progresses in elucidating the mechanisms controlling Pi homeostasis in yeast, focusing on the key roles of the SPX domain-containing proteins in these processes, as well as describing the future challenges and opportunities in this fast-moving field. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Model based PI power system stabilizer design for damping low frequency oscillations in power systems.

PubMed

Salgotra, Aprajita; Pan, Somnath

2018-05-01

This paper explores a two-level control strategy by blending local controller with centralized controller for the low frequency oscillations in a power system. The proposed control scheme provides stabilization of local modes using a local controller and minimizes the effect of inter-connection of sub-systems performance through a centralized control. For designing the local controllers in the form of proportional-integral power system stabilizer (PI-PSS), a simple and straight forward frequency domain direct synthesis method is considered that works on use of a suitable reference model which is based on the desired requirements. Several examples both on one machine infinite bus and multi-machine systems taken from the literature are illustrated to show the efficacy of the proposed PI-PSS. The effective damping of the systems is found to be increased remarkably which is reflected in the time-responses; even unstable operation has been stabilized with improved damping after applying the proposed controller. The proposed controllers give remarkable improvement in damping the oscillations in all the illustrations considered here and as for example, the value of damping factor has been increased from 0.0217 to 0.666 in Example 1. The simulation results obtained by the proposed control strategy are favourably compared with some controllers prevalent in the literature. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

The Price of Fame: The Impact of Stimulus Familiarity on Proactive Interference Resolution

PubMed Central

Prabhakaran, Ranjani; Thompson-Schill, Sharon L.

2013-01-01

Interference from previously learned information, known as proactive interference (PI), limits our memory retrieval abilities. Previous studies of PI resolution have focused on the role of short-term familiarity, or recency, in causing PI. In the present study, we investigated the impact of long-term stimulus familiarity on PI resolution processes. In two behavioral experiments and one event-related fMRI experiment, long-term familiarity was manipulated through the use of famous and nonfamous stimuli, and short-term familiarity was manipulated through the use of recent and nonrecent probe items in an item recognition task. The right middle frontal gyrus demonstrated greater sensitivity to famous stimuli, suggesting that long-term stimulus familiarity plays a role in influencing PI resolution processes. Further examination of the effect of long-term stimulus familiarity on PI resolution revealed a larger behavioral interference effect for famous stimuli, but only under speeded response conditions. Thus, models of memory retrieval—and of the cognitive control mechanisms that guide retrieval processes—should consider the impact of and interactions among sources of familiarity on multiple time scales. PMID:20429858

The price of fame: the impact of stimulus familiarity on proactive interference resolution.

PubMed

Prabhakaran, Ranjani; Thompson-Schill, Sharon L

2011-04-01

Interference from previously learned information, known as proactive interference (PI), limits our memory retrieval abilities. Previous studies of PI resolution have focused on the role of short-term familiarity, or recency, in causing PI. In the present study, we investigated the impact of long-term stimulus familiarity on PI resolution processes. In two behavioral experiments and one event-related fMRI experiment, long-term familiarity was manipulated through the use of famous and nonfamous stimuli, and short-term familiarity was manipulated through the use of recent and nonrecent probe items in an item recognition task. The right middle frontal gyrus demonstrated greater sensitivity to famous stimuli, suggesting that long-term stimulus familiarity plays a role in influencing PI resolution processes. Further examination of the effect of long-term stimulus familiarity on PI resolution revealed a larger behavioral interference effect for famous stimuli, but only under speeded response conditions. Thus, models of memory retrieval--and of the cognitive control mechanisms that guide retrieval processes--should consider the impact of and interactions among sources of familiarity on multiple time scales.

Statistical Inference of Selection and Divergence of the Rice Blast Resistance Gene Pi-ta

PubMed Central

Amei, Amei; Lee, Seonghee; Mysore, Kirankumar S.; Jia, Yulin

2014-01-01

The resistance gene Pi-ta has been effectively used to control rice blast disease, but some populations of cultivated and wild rice have evolved resistance. Insights into the evolutionary processes that led to this resistance during crop domestication may be inferred from the population history of domesticated and wild rice strains. In this study, we applied a recently developed statistical method, time-dependent Poisson random field model, to examine the evolution of the Pi-ta gene in cultivated and weedy rice. Our study suggests that the Pi-ta gene may have more recently introgressed into cultivated rice, indica and japonica, and U.S. weedy rice from the wild species, O. rufipogon. In addition, the Pi-ta gene is under positive selection in japonica, tropical japonica, U.S. cultivars and U.S. weedy rice. We also found that sequences of two domains of the Pi-ta gene, the nucleotide binding site and leucine-rich repeat domain, are highly conserved among all rice accessions examined. Our results provide a valuable analytical tool for understanding the evolution of disease resistance genes in crop plants. PMID:25335927

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.

Method of preparing a tunable-focus liquid-crystal (LC) lens

NASA Astrophysics Data System (ADS)

Li, Xiaolong; Zhou, Zuowei; Ren, Hongwen

2018-02-01

A liquid crystal (LC) lens is prepared by controlling the alignment of a LC using a homogeneous polyimide (PI) layer and a homeotropic PI layer. The rubbed homogeneous PI layer has a concave surface and the homeotropic PI layer is flat. The LC sandwiched between the two PI layers obtains a hybrid alignment which has the largest gradient of refractive index (GRIN) distribution. The LC layer exhibits a lens character because of its convex shape. Since the effective refractive index of the LC is larger than that of the homogeneous PI, the LC lens can focus a light with the shortest focal length in the voltage-off state. By applying an external voltage, the LC molecules can be reoriented along the electric field. As a result, the focal length of the LC lens is reduced. The focal length of the LC lens can be tuned from 30 to 120 μm when the voltage is changed from 0 to 7 Vrms. This LC lens has the advantages of no threshold, low operating voltage, and simple fabrication.

Alpha-1-antitrypsin phenotypes in adult liver disease patients

PubMed Central

Alempijevic, Tamara; Milutinovic, Aleksandra Sokic; Kovacevic, Nada

2009-01-01

Alpha-1-antitrypsin (AAT) is an important serine protease inhibitor in humans. Hereditary alpha-1-antitrypsin deficiency (AATD) affects lungs and liver. Liver disease caused by AATD in paediatric patients has been previously well documented. However, the association of liver disease with alpha-1-antitrypsin gene polymorphisms in adults is less clear. Therefore, we aimed to study AAT polymorphisms in adults with liver disease. We performed a case-control study. AAT polymorphisms were investigated by isoelectric focusing in 61 patients with liver cirrhosis and 9 patients with hepatocellular carcinoma. The control group consisted of 218 healthy blood donors. A significant deviation of observed and expected frequency of AAT phenotypes from Hardy-Weinberg equilibrium (chi-square = 34.77, df 11, P = 0.000) in the patient group was caused by a higher than expected frequency of Pi ZZ homozygotes (f = 0.0143 and f = 0.0005, respectively, P = 0.000). In addition, Pi M homozygotes were more frequent in patients than in controls (63% and 46%, respectively, P = 0.025). Our study results show that Pi ZZ homozygosity in adults could be associated with severe liver disease. Presence of Pi M homozygosity could be associated with liver disease via some mechanism different from Z allele-induced liver damage through accumulation of AAT polymers. PMID:19961268

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.

Laboratory plasma interactions experiments: Results and implications to future space systems

NASA Technical Reports Server (NTRS)

Leung, Philip

1986-01-01

The experimental results discussed show the significance of the effects caused by spacecraft plasma interactions, in particular the generation of Electromagnetic Interference. As the experimental results show, the magnitude of the adverse effects induced by Plasma Interactions (PI) will be more significant for spacecraft of the next century. Therefore, research is needed to control possible adverse effects. Several techniques to control the selected PI effects are discussed. Tests, in the form of flight experiments, are needed to validate these proposed ideas.

Controlling coherence using the internal structure of hard pi pulses.

PubMed

Dong, Yanqun; Ramos, R G; Li, Dale; Barrett, S E

2008-06-20

The tiny difference between hard pi pulses and their delta-function approximation can be exploited to control coherence. Variants on the magic echo that work despite a large spread in resonance offsets are demonstrated using the zeroth- and first-order average Hamiltonian terms, for 13C NMR in 60C. The 29Si NMR linewidth of silicon has been reduced by a factor of about 70,00 using this approach, which also has potential applications in magnetic resonance microscopy and imaging of solids.

X-linked hypophosphatemia: the mutant gene is expressed in teeth as well as in kidney.

PubMed Central

Shields, E D; Scriver, C R; Reade, T; Fujiwara, T M; Morgan, K; Ciampi, A; Schwartz, S

1990-01-01

Mutation at a locus (HPDR) on the X chromosome (McKusick 30780 [HPDR1]; 30781 [HPDR2]) causes impaired renal phosphate transport, hypophosphatemia, and an associated impairment in the process of mineralization in bone and teeth (X-linked hypophosphatemia [XLH]). We measured the dental pulp profile area (PRATIO [= pulp area/tooth area]) and serum phosphorus (Pi) values in uniformly treated XLH patients (six males, 81 teeth, 1,457 Pi values; 11 females, 129 teeth, 1,439 Pi values). Serum Pi values, reflecting the metabolic environment of tooth development, were obtained by repeated measurement between 1 mo and 26 years of age during treatment. PRATIO values calculated from standardized Rinn radiographs were used as outcome measurements of tooth development in XLH patients and in age-matched controls (12 males, 100 teeth; 27 females, 275 teeth). Age-dependent serum Pi values were not different in the treated XLH males and females. In teeth forming primary dentin there was no gene dosage effect on PRATIO values apparent in subjects below 15 years of age. However, in teeth forming secondary dentin a gene dosage was found in the subjects aged 15 to 25 years: XLH male teeth (n = 65) mean +/- SD = 0.163 +/- 0.046; XLH female teeth (n = 75) mean +/- SD = 0.137 +/- 0.039; control teeth (n = 209) mean +/- SD = 0.116 +/- 0.023; (higher PRATIO values mean less development or mineralization of secondary dentin); differences in these PRATIO values (males vs. female and XLH vs. control) were significant by mixed-model analysis of variance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2155529

Chemotactic cell trapping in controlled alternating gradient fields

PubMed Central

Meier, Börn; Zielinski, Alejandro; Weber, Christoph; Arcizet, Delphine; Youssef, Simon; Franosch, Thomas; Rädler, Joachim O.; Heinrich, Doris

2011-01-01

Directed cell migration toward spatio-temporally varying chemotactic stimuli requires rapid cytoskeletal reorganization. Numerous studies provide evidence that actin reorganization is controlled by intracellular redistribution of signaling molecules, such as the PI4,5P2/PI3,4,5P3 gradient. However, exploring underlying mechanisms is difficult and requires careful spatio-temporal control of external chemotactic stimuli. We designed a microfluidic setup to generate alternating chemotactic gradient fields for simultaneous multicell exposure, greatly facilitating statistical analysis. For a quantitative description of intracellular response dynamics, we apply alternating time sequences of spatially homogeneous concentration gradients across 300 μm, reorienting on timescales down to a few seconds. Dictyostelium discoideum amoebae respond to gradient switching rates below 0.02 Hz by readapting their migration direction. For faster switching, cellular repolarization ceases and is completely stalled at 0.1 Hz. In this “chemotactically trapped” cell state, external stimuli alternate faster than intracellular feedback is capable to respond by onset of directed migration. To investigate intracellular actin cortex rearrangement during gradient switching, we correlate migratory cell response with actin repolymerization dynamics, quantified by a fluorescence distribution moment of the GFP fusion protein LimEΔcc. We find two fundamentally different cell polarization types and we could reveal the role of PI3-Kinase for cellular repolarization. In the early aggregation phase, PI3-Kinase enhances the capability of D. discoideum cells to readjust their polarity in response to spatially alternating gradient fields, whereas in aggregation competent cells the effect of PI3-Kinase perturbation becomes less relevant. PMID:21709255

75 FR 1589 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-12

... Census Coverage Measurement Recall Bias Panel Study has been added. Two previous notices were published... Reinterview, and Recall Bias Panel Study. OMB Control Number: None. Form Number(s): All data will be collected... different PI enumerator. In addition to the CCM PI Operation, CCM will conduct a Recall Bias Panel Study...

Impact of the Shodan Computer Search Engine on Internet-facing Industrial Control System Devices

DTIC Science & Technology

2014-03-27

bridge implementation. The transparent bridge is designed using a Raspberry Pi configured with Linux IPtables and bridge-utils to bridge the on board...Ethernet card and a second USB Ethernet adapter. A Raspberry Pi is a credit-card-sized single-board computer running a version of Debian Linux. There

Sage-grouse groceries: forb response to pinon-juniper treatments

USDA-ARS?s Scientific Manuscript database

In the past 150 years, juniper (Juniperus spp. L.) and piñon (Pinus spp. L.) coniferous woodlands have increased 2 to 10-fold in 9 ecoregions spanning the Intermountain area of the western United States. Control of piñon-juniper woodlands by mechanical treatments and prescribed fire have been appli...

Aubergine and piRNAs promote germline stem cell self-renewal by repressing the proto-oncogene Cbl.

PubMed

Rojas-Ríos, Patricia; Chartier, Aymeric; Pierson, Stéphanie; Simonelig, Martine

2017-11-02

PIWI proteins play essential roles in germ cells and stem cell lineages. In Drosophila , Piwi is required in somatic niche cells and germline stem cells (GSCs) to support GSC self-renewal and differentiation. Whether and how other PIWI proteins are involved in GSC biology remains unknown. Here, we show that Aubergine (Aub), another PIWI protein, is intrinsically required in GSCs for their self-renewal and differentiation. Aub needs to be loaded with piRNAs to control GSC self-renewal and acts through direct mRNA regulation. We identify the Cbl proto-oncogene, a regulator of mammalian hematopoietic stem cells, as a novel GSC differentiation factor. Aub stimulates GSC self-renewal by repressing Cbl mRNA translation and does so in part through recruitment of the CCR4-NOT complex. This study reveals the role of piRNAs and PIWI proteins in controlling stem cell homeostasis via translational repression and highlights piRNAs as major post-transcriptional regulators in key developmental decisions. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Performance analysis of electronic power transformer based on neuro-fuzzy controller.

PubMed

Acikgoz, Hakan; Kececioglu, O Fatih; Yildiz, Ceyhun; Gani, Ahmet; Sekkeli, Mustafa

2016-01-01

In recent years, electronic power transformer (EPT), which is also called solid state transformer, has attracted great interest and has been used in place of the conventional power transformers. These transformers have many important functions as high unity power factor, low harmonic distortion, constant DC bus voltage, regulated output voltage and compensation capability. In this study, proposed EPT structure contains a three-phase pulse width modulation rectifier that converts 800 Vrms AC to 2000 V DC bus at input stage, a dual active bridge converter that provides 400 V DC bus with 5:1 high frequency transformer at isolation stage and a three-phase two level inverter that is used to obtain AC output at output stage. In order to enhance dynamic performance of EPT structure, neuro fuzzy controllers which have durable and nonlinear nature are used in input and isolation stages instead of PI controllers. The main aim of EPT structure with the proposed controller is to improve the stability of power system and to provide faster response against disturbances. Moreover, a number of simulation results are carried out to verify EPT structure designed in MATLAB/Simulink environment and to analyze compensation ability for voltage harmonics, voltage flicker and voltage sag/swell conditions.

Effects of nominally selective inhibitors of the kinases PI3K, SGK1 and PKB on the insulin-dependent control of epithelial Na+ absorption.

PubMed

Mansley, Morag K; Wilson, Stuart M

2010-10-01

Insulin-induced Na(+) retention in the distal nephron may contribute to the development of oedema/hypertension in patients with type 2 diabetes. This response to insulin is usually attributed to phosphatidylinositol-3-kinase (PI3K)/serum and glucocorticoid-inducible kinase 1 (SGK1) but a role for protein kinase B (PKB) has been proposed. The present study therefore aimed to clarify the way in which insulin can evoke Na(+) retention. We examined the effects of nominally selective inhibitors of PI3K (wortmannin, PI103, GDC-0941), SGK1 (GSK650394A) and PKB (Akti-1/2) on Na(+) transport in hormone-deprived and insulin-stimulated cortical collecting duct (mpkCCD) cells, while PI3K, SGK1 and PKB activities were assayed by monitoring the phosphorylation of endogenous proteins. Wortmannin substantially inhibited basal Na(+) transport whereas PI103 and GDC-0941 had only very small effects. However, these PI3K inhibitors all abolished insulin-induced Na(+) absorption and inactivated PI3K, SGK1 and PKB fully. GSK650394A and Akti-1/2 also inhibited insulin-evoked Na(+) absorption and while GSK650394A inhibited SGK1 without affecting PKB, Akti-1/2 inactivated both kinases. While studies undertaken using PI103 and GDC-0941 show that hormone-deprived cells can absorb Na(+) independently of PI3K, PI3K seems to be essential for insulin induced Na(+) transport. Akti-1/2 does not act as a selective inhibitor of PKB and data obtained using this compound must therefore be treated with caution. GSK650394A, on the other hand, selectively inhibits SGK1 and the finding that GSK650394A suppressed insulin-induced Na(+) absorption suggests that this response is dependent upon signalling via PI3K/SGK1.

Gene Expression Changes in Phosphorus Deficient Potato (Solanum tuberosum L.) Leaves and the Potential for Diagnostic Gene Expression Markers

PubMed Central

Hammond, John P.; Broadley, Martin R.; Bowen, Helen C.; Spracklen, William P.; Hayden, Rory M.; White, Philip J.

2011-01-01

Background There are compelling economic and environmental reasons to reduce our reliance on inorganic phosphate (Pi) fertilisers. Better management of Pi fertiliser applications is one option to improve the efficiency of Pi fertiliser use, whilst maintaining crop yields. Application rates of Pi fertilisers are traditionally determined from analyses of soil or plant tissues. Alternatively, diagnostic genes with altered expression under Pi limiting conditions that suggest a physiological requirement for Pi fertilisation, could be used to manage Pifertiliser applications, and might be more precise than indirect measurements of soil or tissue samples. Results We grew potato (Solanum tuberosum L.) plants hydroponically, under glasshouse conditions, to control their nutrient status accurately. Samples of total leaf RNA taken periodically after Pi was removed from the nutrient solution were labelled and hybridised to potato oligonucleotide arrays. A total of 1,659 genes were significantly differentially expressed following Pi withdrawal. These included genes that encode proteins involved in lipid, protein, and carbohydrate metabolism, characteristic of Pi deficient leaves and included potential novel roles for genes encoding patatin like proteins in potatoes. The array data were analysed using a support vector machine algorithm to identify groups of genes that could predict the Pi status of the crop. These groups of diagnostic genes were tested using field grown potatoes that had either been fertilised or unfertilised. A group of 200 genes could correctly predict the Pi status of field grown potatoes. Conclusions This paper provides a proof-of-concept demonstration for using microarrays and class prediction tools to predict the Pi status of a field grown potato crop. There is potential to develop this technology for other biotic and abiotic stresses in field grown crops. Ultimately, a better understanding of crop stresses may improve our management of the crop, improving the sustainability of agriculture. PMID:21935429

Role of SiNx Barrier Layer on the Performances of Polyimide Ga2O3-doped ZnO p-i-n Hydrogenated Amorphous Silicon Thin Film Solar Cells

PubMed Central

Wang, Fang-Hsing; Kuo, Hsin-Hui; Yang, Cheng-Fu; Liu, Min-Chu

2014-01-01

In this study, silicon nitride (SiNx) thin films were deposited on polyimide (PI) substrates as barrier layers by a plasma enhanced chemical vapor deposition (PECVD) system. The gallium-doped zinc oxide (GZO) thin films were deposited on PI and SiNx/PI substrates at room temperature (RT), 100 and 200 °C by radio frequency (RF) magnetron sputtering. The thicknesses of the GZO and SiNx thin films were controlled at around 160 ± 12 nm and 150 ± 10 nm, respectively. The optimal deposition parameters for the SiNx thin films were a working pressure of 800 × 10−3 Torr, a deposition power of 20 W, a deposition temperature of 200 °C, and gas flowing rates of SiH4 = 20 sccm and NH3 = 210 sccm, respectively. For the GZO/PI and GZO-SiNx/PI structures we had found that the GZO thin films deposited at 100 and 200 °C had higher crystallinity, higher electron mobility, larger carrier concentration, smaller resistivity, and higher optical transmittance ratio. For that, the GZO thin films deposited at 100 and 200 °C on PI and SiNx/PI substrates with thickness of ~000 nm were used to fabricate p-i-n hydrogenated amorphous silicon (α-Si) thin film solar cells. 0.5% HCl solution was used to etch the surfaces of the GZO/PI and GZO-SiNx/PI substrates. Finally, PECVD system was used to deposit α-Si thin film onto the etched surfaces of the GZO/PI and GZO-SiNx/PI substrates to fabricate α-Si thin film solar cells, and the solar cells’ properties were also investigated. We had found that substrates to get the optimally solar cells’ efficiency were 200 °C-deposited GZO-SiNx/PI. PMID:28788494

High-resolution confocal imaging of wall ingrowth deposition in plant transfer cells: Semi-quantitative analysis of phloem parenchyma transfer cell development in leaf minor veins of Arabidopsis.

PubMed

Nguyen, Suong T T; McCurdy, David W

2015-04-23

Transfer cells (TCs) are trans-differentiated versions of existing cell types designed to facilitate enhanced membrane transport of nutrients at symplasmic/apoplasmic interfaces. This transport capacity is conferred by intricate wall ingrowths deposited secondarily on the inner face of the primary cell wall, hence promoting the potential trans-membrane flux of solutes and consequently assigning TCs as having key roles in plant growth and productivity. However, TCs are typically positioned deep within tissues and have been studied mostly by electron microscopy. Recent advances in fluorophore labelling of plant cell walls using a modified pseudo-Schiff-propidium iodide (mPS-PI) staining procedure in combination with high-resolution confocal microscopy have allowed visualization of cellular details of individual tissue layers in whole mounts, hence enabling study of tissue and cellular architecture without the need for tissue sectioning. Here we apply a simplified version of the mPS-PI procedure for confocal imaging of cellulose-enriched wall ingrowths in vascular TCs at the whole tissue level. The simplified mPS-PI staining procedure produced high-resolution three-dimensional images of individual cell types in vascular bundles and, importantly, wall ingrowths in phloem parenchyma (PP) TCs in minor veins of Arabidopsis leaves and companion cell TCs in pea. More efficient staining of tissues was obtained by replacing complex clearing procedures with a simple post-fixation bleaching step. We used this modified procedure to survey the presence of PP TCs in other tissues of Arabidopsis including cotyledons, cauline leaves and sepals. This high-resolution imaging enabled us to classify different stages of wall ingrowth development in Arabidopsis leaves, hence enabling semi-quantitative assessment of the extent of wall ingrowth deposition in PP TCs at the whole leaf level. Finally, we conducted a defoliation experiment as an example of using this approach to statistically analyze responses of PP TC development to leaf ablation. Use of a modified mPS-PI staining technique resulted in high-resolution confocal imaging of polarized wall ingrowth deposition in TCs. This technique can be used in place of conventional electron microscopy and opens new possibilities to study mechanisms determining polarized deposition of wall ingrowths and use reverse genetics to identify regulatory genes controlling TC trans-differentiation.

Explicit analytical tuning rules for digital PID controllers via the magnitude optimum criterion.

PubMed

Papadopoulos, Konstantinos G; Yadav, Praveen K; Margaris, Nikolaos I

2017-09-01

Analytical tuning rules for digital PID type-I controllers are presented regardless of the process complexity. This explicit solution allows control engineers 1) to make an accurate examination of the effect of the controller's sampling time to the control loop's performance both in the time and frequency domain 2) to decide when the control has to be I, PI and when the derivative, D, term has to be added or omitted 3) apply this control action to a series of stable benchmark processes regardless of their complexity. The former advantages are considered critical in industry applications, since 1) most of the times the choice of the digital controller's sampling time is based on heuristics and past criteria, 2) there is little a-priori knowledge of the controlled process making the choice of the type of the controller a trial and error exercise 3) model parameters change often depending on the control loop's operating point making in this way, the problem of retuning the controller's parameter a much challenging issue. Basis of the proposed control law is the principle of the PID tuning via the Magnitude Optimum criterion. The final control law involves the controller's sampling time T s within the explicit solution of the controller's parameters. Finally, the potential of the proposed method is justified by comparing its performance with the conventional PID tuning when controlling the same process. Further investigation regarding the choice of the controller's sampling time T s is also presented and useful conclusions for control engineers are derived. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Empowerment of personal injury victims through the internet: design of a randomized controlled trial

PubMed Central

2011-01-01

Background Research has shown that current claims settlement process can have a negative impact on psychological and physical recovery of personal injury (PI) victims. One of the explanations for the negative impact on health is that the claims settlement process is a stressful experience and victims suffer from renewed victimization caused by the claims settlement process. PI victims can experience a lack of information, lack of involvement, lack of 'voice', and poor communication. We present the first study that aims to empower PI victims with respect to the negative impact of the claims settlement process by means of an internet intervention. Methods/design The study is a two armed, randomized controlled trial (RCT), in which 170 PI victims are randomized to either the intervention or control group. The intervention group will get access to a website providing 1) an information module, so participants learn what is happening and what to expect during the claims settlement process, and 2) an e-coach module, so participants learn to cope with problems they experience during the claims settlement process. The control group will get access to a website with hyperlinks to commonly available information only. Participants will be recruited via a PI claims settlement office. Participants are included if they have been involved in a traffic accident which happened less than two years ago, and are at least 18 years old. The main study parameter is the increase of empowerment within the intervention group compared to the control group. Empowerment will be measured by the mastery scale and a self-efficacy scale. The secondary outcomes are perceived justice, burden, well being, work ability, knowledge, amount of damages, and lawyer-client communication. Data are collected at baseline (T0 measurement before randomization), at three months, six months, and twelve months after baseline. Analyses will be conducted according to the intention-to-treat principle. Discussion This study evaluates the effectiveness of an internet intervention aimed at empowerment of PI victims. The results will give more insight into the impact of compensation proceedings on health over time, and they can have important consequences for legal claims settlement. Strengths and limitations of this study are discussed. Trial registration Netherlands Trial Register NTR2360 PMID:21288346

Apatite mineralization in elasmobranch skeletons via a polyphosphate intermediate

NASA Astrophysics Data System (ADS)

Omelon, Sidney; Lacroix, Nicolas; Lildhar, Levannia; Variola, Fabio; Dean, Mason

2014-05-01

All vertebrate skeletons are stiffened with apatite, a calcium phosphate mineral. Control of apatite mineralization is essential to the growth and repair of the biology of these skeletons, ensuring that apatite is deposited in the correct tissue location at the desired time. The mechanism of this biochemical control remains debated, but must involve increasing the localized apatite saturation state. It was theorized in 1923 that alkaline phosphatase (ALP) activity provides this control mechanism by increasing the inorganic phosphate (Pi) concentration via dephosphorylation of phosphorylated molecules. The ALP substrate for biological apatite is not known. We propose that polyphosphates (polyPs) produced by mitochondria may be the substrate for biological apatite formation by ALP activity. PolyPs (PO3-)n, also known as condensed phosphates, represent a concentrated, bioavailable Pi-storage strategy. Mitochondria import Pi and synthesize phosphate polymers through an unknown biochemical mechanism. When chelated with calcium and/or other cations, the effective P-concentration of these neutrally charged, amorphous, polyP species can be very high (~ 0.5 M), without inducing phosphate mineral crystallization. This P-concentration in the low Pi-concentration biological environment offers a method of concentrating P well above an apatite supersaturation required for nucleation. Bone is the most studied mineralized skeletal tissue. However, locating and analyzing active mineralizing areas is challenging. We studied calcified cartilage skeletons of elasmobranch fishes (sharks, stingrays and relatives) to analyse the phosphate chemistry in this continually mineralizing skeleton. Although the majority of the elasmobranch skeleton is unmineralized cartilage, it is wrapped in an outer layer of mineralized tissue comprised of small tiles called tesserae. These calcified tesserae continually grow through the formation of new mineral on their borders. Co-localization of ALP and polyPs were identified at the mineralizing tessera borders using Raman spectroscopy, fluorescence microscopy and histological methods. Application of exogenous ALP to skeletal tissue cross-sections resulted in polyP disappearance, and Pi production. It is proposed that elasmobranch skeletal cells produce polyP-containing granules as a concentrated P-source, while ALP activity controls when and where Pi is cleaved from polyP, increasing the apatite supersaturation to nucleate apatite minerals in the skeleton. These data support not only interaction of polyP and ALP as a cell-mediated apatite mineralization control mechanism, but also suggest that this mechanism arose millions of years ago and is common to both bony and cartilaginous skeletal systems.

Closed-loop analysis and control of a non-inverting buck-boost converter

NASA Astrophysics Data System (ADS)

Chen, Zengshi; Hu, Jiangang; Gao, Wenzhong

2010-11-01

In this article, a cascade controller is designed and analysed for a non-inverting buck-boost converter. The fast inner current loop uses sliding mode control. The slow outer voltage loop uses the proportional-integral (PI) control. Stability analysis and selection of PI gains are based on the nonlinear closed-loop error dynamics incorporating both the inner and outer loop controllers. The closed-loop system is proven to have a nonminimum phase structure. The voltage transient due to step changes of input voltage or resistance is predictable. The operating range of the reference voltage is discussed. The controller is validated by a simulation circuit. The simulation results show that the reference output voltage is well-tracked under system uncertainties or disturbances, confirming the validity of the proposed controller.

Stabilizing detached Bridgman melt crystal growth: Model-based nonlinear feedback control

NASA Astrophysics Data System (ADS)

Yeckel, Andrew; Daoutidis, Prodromos; Derby, Jeffrey J.

2012-12-01

The dynamics and operability limits of a nonlinear-proportional-integral controller designed to stabilize detached vertical Bridgman crystal growth are studied. The manipulated variable is the pressure difference between upper and lower vapor spaces, and the controlled variable is the gap width at the triple-phase line. The controller consists of a model-based nonlinear component coupled with a standard proportional-integral controller. The nonlinear component is based on a capillary model of shape stability. Perturbations to gap width, pressure difference, wetting angle, and growth angle are studied under both shape stable and shape unstable conditions. The nonlinear-PI controller allows a wider operating range of gain than a standard PI controller used alone, is easier to tune, and eliminates solution multiplicity from closed-loop operation.

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

Snow, Dr., Joel

This final report is presented by Langston University (LU) for the project entitled "Langston University High Energy Physics" (LUHEP) under the direction of principal investigator (PI) and project director Professor Joel Snow. The project encompassed high energy physics research performed at hadron colliders. The PI is a collaborator on the DZero experiment at Fermi National Accelerator Laboratory in Batavia, IL, USA and the ATLAS experiment at CERN in Geneva, Switzerland and was during the entire project period from April 1, 1999 until May 14, 2012. Both experiments seek to understand the fundamental constituents of the physical universe and the forcesmore » that govern their interactions. In 1999 as member of the Online Systems group for Run 2 the PI developed a cross-platform Python-based, Graphical User Interface (GUI) application for monitoring and control of EPICS based devices for control room use. This served as a model for other developers to enhance and build on for further monitoring and control tasks written in Python. Subsequently the PI created and developed a cross-platform C++ GUI utilizing a networked client-server paradigm and based on ROOT, the object oriented analysis framework from CERN. The GUI served as a user interface to the Examine tasks running in the D\\O\\ control room which monitored the status and integrity of data taking for Run 2. The PI developed the histogram server/control interface to the GUI client for the EXAMINE processes. The histogram server was built from the ROOT framework and was integrated into the D\\O\\ framework used for online monitoring programs and offline analysis. The PI developed the first implementation of displaying histograms dynamically generated by ROOT in a Web Browser. The PI's work resulted in several talks and papers at international conferences and workshops. The PI established computing software infrastructure at LU and U. Oklahoma (OU) to do analysis of DZero production data and produce simulation data for the experiment. Eventually this included the FNAL SAM data grid system, the SAMGrid (SG) infrastructure, and the Open Science Grid software stacks for computing and storage elements. At the end of 2003 Snow took on the role of global Monte Carlo production coordinator for the DØ experiment. A role which continues til this day. In January of 2004 Snow started working with the SAMGrid development team to help debug, deploy, and integrate SAMGrid with DØ Monte Carlo production. Snow installed and configured SG execution and client sites at LUHEP and OUHEP, and a SG scheduler site at LUHEP. The PI developed a python based GUI (DAJ) that acts as a front end for job submission to SAMGrid. The GUI interfaces to the DZero Mone Carlo (MC) request system that uses SAM to manage MC requests by the physics analysis groups. DAJ significantly simplified SG job submission and was deployed in DZero in an effort to increase the user base of SG. The following year was the advent of SAMGrid job submission to the Open Science Grid (OSG) and LHC Computing Grid (LCG) through a forwarding mechanism. The PI oversaw the integration of these grids into the existing production infrastructure. The PI developed an automatic MC (Automc) request processing system capable of operating without user intervention (other than getting grid credentials), and able to submit to any number of sites on various grids. The system manages production at all but 2 sites. The system was deployed at Fermilab and remains operating there today. The PI's work in distributed computing resulted in several talks at international conferences. UTA, OU, and LU were chosen as the collaborating institutions that form the Southwest Tier 2 Center (SWT2) for ATLAS. During the project period the PI contributed to the online and offline software infrastructure through his work with the Run 2 online group, and played a major role in Monte Carlo production for DZero. During the part of the project period in which the PI served as MC production coordinator MC production increased very significantly. In the first year of the PI's tenure as production coordinator production was 159M events and 6.7~TB of data. During the last year of the project period production was 2,342~M events and 262~TB of data. That is a factor of 15 increase in events and 39 in data volume. The increase occurred with improvements in computer hardware and networks, through the use of grid technology on diverse resources, and through increased automation and efficiency of the production process. LU HEP developed and deployed the automatic MC request processing system in use at FNAL. The complementary strategies of automation and grid production served DZero well. Fermilab has recognized LU HEP's contribution to DZero by allowing the PI to devote full time to research activities by appointing him a guest scientist for the last six years of the project period.« less

Differential Acclimation of Enzymatic Antioxidant Metabolism and Photosystem II Photochemistry in Tall Fescue under Drought and Heat and the Combined Stresses

PubMed Central

Bi, Aoyue; Fan, Jibiao; Hu, Zhengrong; Wang, Guangyang; Amombo, Erick; Fu, Jinmin; Hu, Tao

2016-01-01

Quality inferiority in cool-season turfgrass due to drought, heat, and a combination of both stresses is predicted to be more prevalent in the future. Understanding the various response to heat and drought stress will assist in the selection and breeding of tolerant grass varieties. The objective of this study was to investigate the behavior of antioxidant metabolism and photosystem II (PSII) photochemistry in two tall fescue genotypes (PI 234881 and PI 578718) with various thermotolerance capacities. Wide variations were found between heat-tolerant PI 578718 and heat-sensitive PI 234881 for leaf relative water content, malondialdehyde and electrolyte leakage under drought, high-temperature or a combination of both stresses. The sensitivity of PI 234881 exposed to combined stresses was associated with lower superoxide dismutase activity and higher H2O2 accumulation than that in PI 578718. Various antioxidant enzymes displayed positive correlation with chlorophyll content, but negative with membrane injury index at most of the stages in both tall fescue genotypes. The JIP-test analysis in PI 578718 indicated a significant improvement in ABS/RC, TR0/RC, RE0/RC, RE0/ABS values as compared to the control regime, which indicated that PI 578718 had a high potential to protect the PSII system under drought and high temperature stress. And the PS II photochemistry in PI 234881 was damaged significantly compared with PI578718. Moreover, quantitative RT-PCR revealed that heat and drought stresses deduced the gene expression of psbB and psbC, but induced the expression of psbA. These findings to some extent confirmed that the various adaptations of physiological traits may contribute to breeding in cold-season turfgrass in response to drought, high-temperature, and a combination of both stresses. PMID:27148288

A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria

PubMed Central

Mbengue, Alassane; Bhattacharjee, Souvik; Pandharkar, Trupti; Liu, Haining; Estiu, Guillermina; Stahelin, Robert V.; Rizk, Shahir; Njimoh, Dieudonne L.; Ryan, Yana; Chotivanich, Kesinee; Nguon, Chea; Ghorbal, Mehdi; Lopez-Rubio, Jose-Juan; Pfrender, Michael; Emrich, Scott; Mohandas, Narla; Dondorp, Arjen M.; Wiest, Olaf; Haldar, Kasturi

2015-01-01

Artemisinins are the corner stone of anti-malarial drugs1. Emergence and spread of resistance to them2–4 raises risk of wiping out recent gains achieved in reducing world-wide malaria burden and threatens future malaria control and elimination on a global level. Genome wide association studies (GWAS) have revealed parasite genetic loci associated with artemisinin resistance5–10. However, there is no consensus on biochemical targets of artemisinin. Whether and how these targets interact with genes identified by GWAS, remains unknown. Here we provide biochemical and cellular evidence that artemisinins are potent inhibitors of Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an unexpected mechanism of action. In resistant clinical strains, increased PfPI3K was associated with the C580Y mutation in P. falciparum Kelch13 (PfKelch13), a primary marker of artemisinin resistance. Polyubiquitination of PfPI3K and its binding to PfKelch13 were reduced by PfKelch13 mutation, which limited proteolysis of PfPI3K and thus increased levels of the kinase as well as its lipid product phosphatidylinositol 3-phosphate (PI3P). We find PI3P levels to be predictive of artemisinin resistance in both clinical and engineered laboratory parasites as well as across non-isogenic strains. Elevated PI3P induced artemisinin resistance in absence of PfKelch13 mutations, but remained responsive to regulation by PfKelch13. Evidence is presented for PI3P-dependent signaling, where transgenic expression of an additional kinase confers resistance. Together these data present PI3P as the key mediator of artemisinin resistance and the sole PfPI3K as an important target for malaria elimination. PMID:25874676

A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria.

PubMed

Mbengue, Alassane; Bhattacharjee, Souvik; Pandharkar, Trupti; Liu, Haining; Estiu, Guillermina; Stahelin, Robert V; Rizk, Shahir S; Njimoh, Dieudonne L; Ryan, Yana; Chotivanich, Kesinee; Nguon, Chea; Ghorbal, Mehdi; Lopez-Rubio, Jose-Juan; Pfrender, Michael; Emrich, Scott; Mohandas, Narla; Dondorp, Arjen M; Wiest, Olaf; Haldar, Kasturi

2015-04-30

Artemisinins are the cornerstone of anti-malarial drugs. Emergence and spread of resistance to them raises risk of wiping out recent gains achieved in reducing worldwide malaria burden and threatens future malaria control and elimination on a global level. Genome-wide association studies (GWAS) have revealed parasite genetic loci associated with artemisinin resistance. However, there is no consensus on biochemical targets of artemisinin. Whether and how these targets interact with genes identified by GWAS, remains unknown. Here we provide biochemical and cellular evidence that artemisinins are potent inhibitors of Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an unexpected mechanism of action. In resistant clinical strains, increased PfPI3K was associated with the C580Y mutation in P. falciparum Kelch13 (PfKelch13), a primary marker of artemisinin resistance. Polyubiquitination of PfPI3K and its binding to PfKelch13 were reduced by the PfKelch13 mutation, which limited proteolysis of PfPI3K and thus increased levels of the kinase, as well as its lipid product phosphatidylinositol-3-phosphate (PI3P). We find PI3P levels to be predictive of artemisinin resistance in both clinical and engineered laboratory parasites as well as across non-isogenic strains. Elevated PI3P induced artemisinin resistance in absence of PfKelch13 mutations, but remained responsive to regulation by PfKelch13. Evidence is presented for PI3P-dependent signalling in which transgenic expression of an additional kinase confers resistance. Together these data present PI3P as the key mediator of artemisinin resistance and the sole PfPI3K as an important target for malaria elimination.

Hypophosphatemia promotes lower rates of muscle ATP synthesis

PubMed Central

Pesta, Dominik H.; Tsirigotis, Dimitrios N.; Befroy, Douglas E.; Caballero, Daniel; Jurczak, Michael J.; Rahimi, Yasmeen; Cline, Gary W.; Dufour, Sylvie; Birkenfeld, Andreas L.; Rothman, Douglas L.; Carpenter, Thomas O.; Insogna, Karl; Petersen, Kitt Falk; Bergwitz, Clemens; Shulman, Gerald I.

2016-01-01

Hypophosphatemia can lead to muscle weakness and respiratory and heart failure, but the mechanism is unknown. To address this question, we noninvasively assessed rates of muscle ATP synthesis in hypophosphatemic mice by using in vivo saturation transfer [31P]-magnetic resonance spectroscopy. By using this approach, we found that basal and insulin-stimulated rates of muscle ATP synthetic flux (VATP) and plasma inorganic phosphate (Pi) were reduced by 50% in mice with diet-induced hypophosphatemia as well as in sodium-dependent Pi transporter solute carrier family 34, member 1 (NaPi2a)-knockout (NaPi2a−/−) mice compared with their wild-type littermate controls. Rates of VATP normalized in both hypophosphatemic groups after restoring plasma Pi concentrations. Furthermore, VATP was directly related to cellular and mitochondrial Pi uptake in L6 and RC13 rodent myocytes and isolated muscle mitochondria. Similar findings were observed in a patient with chronic hypophosphatemia as a result of a mutation in SLC34A3 who had a 50% reduction in both serum Pi content and muscle VATP. After oral Pi repletion and normalization of serum Pi levels, muscle VATP completely normalized in the patient. Taken together, these data support the hypothesis that decreased muscle ATP synthesis, in part, may be caused by low blood Pi concentrations, which may explain some aspects of muscle weakness observed in patients with hypophosphatemia.—Pesta, D. H., Tsirigotis, D. N., Befroy, D. E., Caballero, D., Jurczak, M. J., Rahimi, Y., Cline, G. W., Dufour, S., Birkenfeld, A. L., Rothman, D. L., Carpenter, T. O., Insogna, K., Petersen, K. F., Bergwitz, C., Shulman, G. I. Hypophosphatemia promotes lower rates of muscle ATP synthesis. PMID:27338702

Breeding of commercially acceptable allelopathic rice cultivars in China.

PubMed

Kong, Chui-Hua; Chen, Xiong-Hui; Hu, Fei; Zhang, Song-Zhu

2011-09-01

One promising area of paddy weed control is the potential for exploiting the weed-suppressing ability of rice. This study was conducted to develop commercially acceptable allelopathic rice cultivars using crosses between allelopathic rice variety PI312777 and commercial Chinese cultivars (N2S, N9S, Huahui354, Peiai64S and Tehuazhan35), and to assess their weed suppression and grain yield in paddy fields in relation to their parents. There was a positive dominance in the crosses Huahui354 × PI312777 and N2S × PI312777 but recessive or negative dominance in N9S × PI312777, Peiai64S × PI312777 and Tehuazhan35 × PI312777. Huahui354 × PI312777 and N2S × PI312777 showed stronger weed suppression than their parents and other crosses. Finally, an F8 line with an appearance close to Huahui354 and a magnitude of weed suppression close to PI312777 was obtained from Huahui354 × PI312777. This line, named Huagan-3, was released as a first commercially acceptable allelopathic rice cultivar in China. The grain yield and quality of Huagan-3 met the commercial standard of the local rice industry. Huagan-3 greatly suppressed paddy weeds, although suppression was influenced by year-to-year variation and plant density. There was no certain yield reduction in Huagan-3 even under a slight infestation of barnyard grass in paddy fields. The successful breeding of Huagan-3 with high yield and strong weed suppression may be incorporated into present rice production systems to minimise the amount of herbicide used. Copyright © 2011 Society of Chemical Industry.

Ablation of Phosphoinositide 3-Kinase-γ Reduces the Severity of Acute Pancreatitis

PubMed Central

Lupia, Enrico; Goffi, Alberto; De Giuli, Paolo; Azzolino, Ornella; Bosco, Ornella; Patrucco, Enrico; Vivaldo, Maria Cristina; Ricca, Marco; Wymann, Matthias P.; Hirsch, Emilio; Montrucchio, Giuseppe; Emanuelli, Giorgio

2004-01-01

In pancreatic acini, the G-protein-activated phosphoinositide 3-kinase-γ (PI3Kγ) regulates several key pathological responses to cholecystokinin hyperstimulation in vitro. Thus, using mice lacking PI3Kγ, we studied the function of this enzyme in vivo in two different models of acute pancreatitis. The disease was induced by supramaximal concentrations of cerulein and by feeding mice a choline-deficient/ethionine-supplemented diet. Although the secretive function of isolated pancreatic acini was identical in mutant and control samples, in both models, genetic ablation of PI3Kγ significantly reduced the extent of acinar cell injury/necrosis. In agreement with a protective role of apoptosis in pancreatitis, PI3Kγ-deficient pancreata showed an increased number of apoptotic acinar cells, as determined by terminal dUTP nick-end labeling and caspase-3 activity. In addition, neutrophil infiltration within the pancreatic tissue was also reduced, suggesting a dual action of PI3Kγ, both in the triggering events within acinar cells and in the subsequent neutrophil recruitment and activation. Finally, the lethality of the choline-deficient/ethionine-supplemented diet-induced pancreatitis was significantly reduced in mice lacking PI3Kγ. Our results thus suggest that inhibition of PI3Kγ may be of therapeutic value in acute pancreatitis. PMID:15579443

Ablation of phosphoinositide 3-kinase-gamma reduces the severity of acute pancreatitis.

PubMed

Lupia, Enrico; Goffi, Alberto; De Giuli, Paolo; Azzolino, Ornella; Bosco, Ornella; Patrucco, Enrico; Vivaldo, Maria Cristina; Ricca, Marco; Wymann, Matthias P; Hirsch, Emilio; Montrucchio, Giuseppe; Emanuelli, Giorgio

2004-12-01

In pancreatic acini, the G-protein-activated phosphoinositide 3-kinase-gamma (PI3K gamma) regulates several key pathological responses to cholecystokinin hyperstimulation in vitro. Thus, using mice lacking PI3K gamma, we studied the function of this enzyme in vivo in two different models of acute pancreatitis. The disease was induced by supramaximal concentrations of cerulein and by feeding mice a choline-deficient/ethionine-supplemented diet. Although the secretive function of isolated pancreatic acini was identical in mutant and control samples, in both models, genetic ablation of PI3K gamma significantly reduced the extent of acinar cell injury/necrosis. In agreement with a protective role of apoptosis in pancreatitis, PI3K gamma-deficient pancreata showed an increased number of apoptotic acinar cells, as determined by terminal dUTP nick-end labeling and caspase-3 activity. In addition, neutrophil infiltration within the pancreatic tissue was also reduced, suggesting a dual action of PI3K gamma, both in the triggering events within acinar cells and in the subsequent neutrophil recruitment and activation. Finally, the lethality of the choline-deficient/ethionine-supplemented diet-induced pancreatitis was significantly reduced in mice lacking PI3K gamma. Our results thus suggest that inhibition of PI3K gamma may be of therapeutic value in acute pancreatitis.

Increased susceptibility to proactive interference in adults with dyslexia?

PubMed

Bogaerts, Louisa; Szmalec, Arnaud; Hachmann, Wibke M; Page, Mike P A; Woumans, Evy; Duyck, Wouter

2015-01-01

Recent findings show that people with dyslexia have an impairment in serial-order memory. Based on these findings, the present study aimed to test the hypothesis that people with dyslexia have difficulties dealing with proactive interference (PI) in recognition memory. A group of 25 adults with dyslexia and a group of matched controls were subjected to a 2-back recognition task, which required participants to indicate whether an item (mis)matched the item that had been presented 2 trials before. PI was elicited using lure trials in which the item matched the item in the 3-back position instead of the targeted 2-back position. Our results demonstrate that the introduction of lure trials affected 2-back recognition performance more severely in the dyslexic group than in the control group, suggesting greater difficulty in resisting PI in dyslexia.

Modulation of gut microbiota dysbioses in type 2 diabetic patients by macrobiotic Ma-Pi 2 diet.

PubMed

Candela, Marco; Biagi, Elena; Soverini, Matteo; Consolandi, Clarissa; Quercia, Sara; Severgnini, Marco; Peano, Clelia; Turroni, Silvia; Rampelli, Simone; Pozzilli, Paolo; Pianesi, Mario; Fallucca, Francesco; Brigidi, Patrizia

2016-07-01

The gut microbiota exerts a role in type 2 diabetes (T2D), and deviations from a mutualistic ecosystem layout are considered a key environmental factor contributing to the disease. Thus, the possibility of improving metabolic control in T2D by correcting gut microbiome dysbioses through diet has been evaluated. Here, we explore the potential of two different energy-restricted dietary approaches - the fibre-rich macrobiotic Ma-Pi 2 diet or a control diet recommended by Italian professional societies for T2D treatment - to correct gut microbiota dysbioses in T2D patients. In a previous 21-d open-label MADIAB trial, fifty-six overweight T2D patients were randomised to the Ma-Pi 2 or the control diet. For the present study, stools were collected before and after intervention from a subset of forty MADIAB participants, allowing us to characterise the gut microbiota by 16S rRNA sequencing and imputed metagenomics. To highlight microbiota dysbioses in T2D, the gut microbiota of thirteen normal-weight healthy controls were characterised. According to our findings, both diets were effective in modulating gut microbiome dysbioses in T2D, resulting in an increase of the ecosystem diversity and supporting the recovery of a balanced community of health-promoting SCFA producers, such as Faecalibacterium, Roseburia, Lachnospira, Bacteroides and Akkermansia. The Ma-Pi 2 diet, but not the control diet, was also effective in counteracting the increase of possible pro-inflammatory groups, such as Collinsella and Streptococcus, in the gut ecosystem, showing the potential to reverse pro-inflammatory dysbioses in T2D, and possibly explaining the greater efficacy in improving the metabolic control.

Metabolomics study on model rats of chronic obstructive pulmonary disease treated with Bu‑Fei Jian‑Pi.

PubMed

Li, Jiansheng; Yang, Liping; Li, Ya; Tian, Yange; Li, Suyun; Jiang, Suli; Wang, Ying; Li, Xinmin

2015-02-01

The therapeutic effect of Traditional Chinese Medicine (TCM) on chronic obstructive pulmonary disease (COPD) has been know for numerous years; however, the mechanism of action of the beneficial effects of TCM remains to be elucidated. The present study aimed to investigate the molecular mechanisms of COPD through metabolomic analysis as well as explore the targets and intervention mechanisms of TCM therapy using the common TCM granules Bu‑Fei Jian‑Pi. COPD rat models were established using smoke inhalations and recurrent bacterial infections. Rats were then divided into three groups as follows: A1, control healthy rats; B1, COPD model; and D1, Bu‑Fei Jian‑Pi‑treated COPD rats. Following administration of the medicine, the metabolomic profile of the lung tissue of rats in each group was assessed using high‑performance liquid chromatography/quadrupole‑time‑of‑flight mass spectrometry. The results demonstrated that there was a significanlty different spectrum of metabolites in the lung tissue of the model group compared to that of the control group as well as the Bu‑Fei Jian‑Pi‑treated COPD group; in addition, following treatment with Bu‑Fei Jian‑Pi, the metabolites of COPD rats were comparable with those of the control. Notable changes were observed in 31 metabolites between the Bu‑Fei Jian‑Pi‑treated group and the model group; however, there were 13 comparable metabolites between the Bu‑Fei Jian‑Pi and control groups as well as the model and control groups. Eleven metabolites showed a negative fold change in the Bu‑Fei Jian‑Pi‑treated groups compared to concentrations in the model group; however, minimal changes were observed in phenylpyruvic acid and α‑D‑fucose expression. In conclusion, the results of the present study demonstrated that Bu‑Fei Jian‑Pi granules had beneficial effects on measured outcomes in a rat model of stable COPD, indicated by a significantly different spectrum of metabolites. This therefore indicated that the metabolites which had significantly altered expression in the model group compared with that of the control and Bu‑Fei Jian‑Pi‑treated groups may be potential biomarkers of COPD.

Practical controller design for ultra-precision positioning of stages with a pneumatic artificial muscle actuator

NASA Astrophysics Data System (ADS)

Tang, T. F.; Chong, S. H.

2017-06-01

This paper presents a practical controller design method for ultra-precision positioning of pneumatic artificial muscle actuator stages. Pneumatic artificial muscle (PAM) actuators are safe to use and have numerous advantages which have brought these actuators to wide applications. However, PAM exhibits strong non-linear characteristics, and these limitations lead to low controllability and limit its application. In practice, the non-linear characteristics of PAM mechanism are difficult to be precisely modeled, and time consuming to model them accurately. The purpose of the present study is to clarify a practical controller design method that emphasizes a simple design procedure that does not acquire plants parameters modeling, and yet is able to demonstrate ultra-precision positioning performance for a PAM driven stage. The practical control approach adopts continuous motion nominal characteristic trajectory following (CM NCTF) control as the feedback controller. The constructed PAM driven stage is in low damping characteristic and causes severe residual vibration that deteriorates motion accuracy of the system. Therefore, the idea to increase the damping characteristic by having an acceleration feedback compensation to the plant has been proposed. The effectiveness of the proposed controller was verified experimentally and compared with a classical PI controller in point-to-point motion. The experiment results proved that the CM NCTF controller demonstrates better positioning performance in smaller motion error than the PI controller. Overall, the CM NCTF controller has successfully to reduce motion error to 3µm, which is 88.7% smaller than the PI controller.

Specification/Verification of Temporal Properties for Distributed Systems: Issues and Approaches. Volume 1

DTIC Science & Technology

1990-02-01

copies Pl ,...,P. of a multiple module fp resolve nondeterminism (local or global) in an identical manner. 5. The copies PI,...,P, axe physically...recovery block. A recovery block consists of a conventional block (like in ALGOL or PL /I) which is provided with a means of error detection, called an...improved failures model for communicating processes. In Proceeding. NSF- SERC Seminar on Concurrency, volume 197 of Lecture Notes in Computer Science

Src kinases in chondrosarcoma chemoresistance and migration: dasatinib sensitises to doxorubicin in TP53 mutant cells

PubMed Central

van Oosterwijk, J G; van Ruler, M A J H; Briaire-de Bruijn, I H; Herpers, B; Gelderblom, H; van de Water, B; Bovée, J V M G

2013-01-01

Background: Chondrosarcomas are malignant cartilage-forming tumours of bone. Because of their resistance to conventional chemotherapy and radiotherapy, currently no treatment strategies exist for unresectable and metastatic chondrosarcoma. Previously, PI3K/AKT/GSK3β and Src kinase pathways were shown to be activated in chondrosarcoma cell lines. Our aim was to investigate the role of these kinases in chemoresistance and migration in chondrosarcoma in relation to TP53 mutation status. Methods: We used five conventional and three dedifferentiated chondrosarcoma cell lines and investigated the effect of PI3K/AKT/GSK3β pathway inhibition (enzastaurin) and Src pathway inhibition (dasatinib) in chemoresistance using WST assay and live cell imaging with AnnexinV staining. Immunohistochemistry on tissue microarrays (TMAs) containing 157 cartilaginous tumours was performed for Src family members. Migration assays were performed with the RTCA xCelligence System. Results: Src inhibition was found to overcome chemoresistance, to induce apoptosis and to inhibit migration. Cell lines with TP53 mutations responded better to combination therapy than wild-type cell lines (P=0.002). Tissue microarray immunohistochemistry confirmed active Src (pSrc) signalling, with Fyn being most abundantly expressed (76.1%). Conclusion: These results strongly indicate Src family kinases, in particular Fyn, as a potential target for the treatment of inoperable and metastatic chondrosarcomas, and to sensitise for doxorubicin especially in the presence of TP53 mutations. PMID:23922104

An Ethylene-Protected Achilles’ Heel of Etiolated Seedlings for Arthropod Deterrence

PubMed Central

Boex-Fontvieille, Edouard; Rustgi, Sachin; von Wettstein, Diter; Pollmann, Stephan; Reinbothe, Steffen; Reinbothe, Christiane

2016-01-01

A small family of Kunitz protease inhibitors exists in Arabidopsis thaliana, a member of which (encoded by At1g72290) accomplishes highly specific roles during plant development. Arabidopsis Kunitz-protease inhibitor 1 (Kunitz-PI;1), as we dubbed this protein here, is operative as cysteine PI. Activity measurements revealed that despite the presence of the conserved Kunitz-motif the bacterially expressed Kunitz-PI;1 was unable to inhibit serine proteases such as trypsin and chymotrypsin, but very efficiently inhibited the cysteine protease RESPONSIVE TO DESICCATION 21. Western blotting and cytolocalization studies using mono-specific antibodies recalled Kunitz-PI;1 protein expression in flowers, young siliques and etiolated seedlings. In dark-grown seedlings, maximum Kunitz-PI;1 promoter activity was detected in the apical hook region and apical parts of the hypocotyls. Immunolocalization confirmed Kunitz-PI;1 expression in these organs and tissues. No transmitting tract (NTT) and HECATE 1 (HEC1), two transcription factors previously implicated in the formation of the female reproductive tract in flowers of Arabidopsis, were identified to regulate Kunitz-PI;1 expression in the dark and during greening, with NTT acting negatively and HEC1 acting positively. Laboratory feeding experiments with isopod crustaceans such as Porcellio scaber (woodlouse) and Armadillidium vulgare (pillbug) pinpointed the apical hook as ethylene-protected Achilles’ heel of etiolated seedlings. Because exogenous application of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) and mechanical stress (wounding) strongly up-regulated HEC1-dependent Kunitz-PI;1 gene expression, our results identify a new circuit controlling herbivore deterrence of etiolated plants in which Kunitz-PI;1 is involved. PMID:27625656

EEG spectral analysis in primary insomnia: NREM period effects and sex differences.

PubMed

Buysse, Daniel J; Germain, Anne; Hall, Martica L; Moul, Douglas E; Nofzinger, Eric A; Begley, Amy; Ehlers, Cindy L; Thompson, Wesley; Kupfer, David J

2008-12-01

To compare NREM EEG power in primary insomnia (PI) and good sleeper controls (GSC), examining both sex and NREM period effects; to examine relationships between EEG power, clinical characteristics, and self-reports of sleep. Overnight polysomnographic study. Sleep laboratory. PI (n=48; 29 women) and GSC (n=25; 15 women). None. EEG power from 1-50 Hz was computed for artifact-free sleep epochs across four NREM periods. Repeated measures mixed effect models contrasted differences between groups, EEG frequency bands, and NREM periods. EEG power-frequency curves were modeled using regressions with fixed knot splines. Mixed models showed no significant group (PI vs. GSC) differences; marginal sex differences (delta and theta bands); significant differences across NREM periods; and group*sex and group*NREM period interactions, particularly in beta and gamma bands. Modeled power-frequency curves showed no group difference in whole-night NREM, but PI had higher power than GSC from 18-40 Hz in the first NREM period. Among women, PI had higher 16 to 44-Hz power than GSC in the first 3 NREM periods, and higher 3 to 5-Hz power across all NREM periods. PI and GSC men showed no consistent differences in EEG power. High-frequency EEG power was not related to clinical or subjective sleep ratings in PI. Women with PI, but not men, showed increased high-frequency and low-frequency EEG activity during NREM sleep compared to GSC, particularly in early NREM periods. Sex and NREM period may moderate quantitative EEG differences between PI and GSC.

Enterovirus 3A Facilitates Viral Replication by Promoting Phosphatidylinositol 4-Kinase IIIβ–ACBD3 Interaction

PubMed Central

Xiao, Xia; Lei, Xiaobo; Zhang, Zhenzhen; Ma, Yijie; Qi, Jianli; Wu, Chao; Xiao, Yan; Li, Li

2017-01-01

ABSTRACT Like other enteroviruses, enterovirus 71 (EV71) relies on phosphatidylinositol 4-kinase IIIβ (PI4KB) for genome RNA replication. However, how PI4KB is recruited to the genome replication sites of EV71 remains elusive. Recently, we reported that a host factor, ACBD3, is needed for EV71 replication by interacting with viral 3A protein. Here, we show that ACBD3 is required for the recruitment of PI4KB to RNA replication sites. Overexpression of viral 3A or EV71 infection stimulates the interaction of PI4KB and ACBD3. Consistently, EV71 infection induces the production of phosphatidylinositol-4-phosphate (PI4P). Furthermore, PI4KB, ACBD3, and 3A are all localized to the viral-RNA replication sites. Accordingly, PI4KB or ACBD3 depletion by small interfering RNA (siRNA) leads to a reduction in PI4P production after EV71 infection. I44A or H54Y substitution in 3A interrupts the stimulation of PI4KB and ACBD3. Further analysis suggests that stimulation of ACBD3-PI4KB interaction is also important for the replication of enterovirus 68 but disadvantageous to human rhinovirus 16. These results reveal a mechanism of enterovirus replication that involves a selective strategy for recruitment of PI4KB to the RNA replication sites. IMPORTANCE Enterovirus 71, like other human enteroviruses, replicates its genome within host cells, where viral proteins efficiently utilize cellular machineries. While multiple factors are involved, it is largely unclear how viral replication is controlled. We show that the 3A protein of enterovirus 71 recruits an enzyme, phosphatidylinositol 4-kinase IIIβ, by interacting with ACBD3, which alters cellular membranes through the production of a lipid, PI4P. Consequently, the viral and host proteins form a large complex that is necessary for RNA synthesis at replication sites. Notably, PI4KB-ACBD3 interaction also differentially mediates the replication of enterovirus 68 and rhinovirus 16. These results provide new insight into the molecular network of enterovirus replication. PMID:28701404

Detection and quantification of pestivirus in experimentally infected pregnant ewes and their progeny.

PubMed

Hurtado, Ana; Sanchez, Isbene; Bastida, Felix; Minguijón, Esmeralda; Juste, Ramón A; García-Pérez, Ana L

2009-11-05

Border disease virus (BDV) causes important reproductive losses, and eradication strategies focus on the identification and removal of persistently infected animals arising after in uterine infection. BDV infection dynamics were studied in 13 ewes experimentally infected with BDV-4 genotype at 3 phases of pregnancy [days 108 (group A), 76 (group B) and 55 (group C)] by quantification of viral RNA in blood collected on days -1 to parturition using quantitative real-time RT-PCR (qRT-PCR). Viral RNA loads were also measured in blood/foetal fluid and tissue samples from their offspring at lambing (3 foetuses, 7 stillborns, 15 lambs). qRT-PCR results were compared with those obtained by conventional RT-PCR and used to predict persistent infections. Viral RNA was detected in the ewes between days 2-15 p.i. The viraemia reached its highest peak between days 6-7 p.i. with a second peak at days 11-12 p.i. qRT-PCR was significantly faster to perform (less than 1 h) than conventional RT-PCR and detected BDV RNA in more ewes, being detection more continuous and prolonged in time. The virus was detected in peripheral blood in a higher percentage of lambs than in tissues, where differences in viral genome copies were more marked. Skin and cerebral cortex showed the highest viral RNA loads, and spleen and spinal cord the lowest. High viral RNA loads were observed in several animals in group B and all in group C, infected during middle and early foetal development, respectively, but also in one lamb from group A, infected during late foetal development. Serology and viral genome copy number estimates in blood and tissues were used to establish a quantitative cut-off threshold for transient viraemia. Viral RNA quantification showed potential for the discrimination between persistent infections and transient viraemia using single-time point blood sampling and raised questions regarding foetal immune system development and the occurrence of persistent infections.

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...

Maraviroc, as a Switch Option, in HIV-1–infected Individuals With Stable, Well-controlled HIV Replication and R5-tropic Virus on Their First Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Plus Ritonavir-boosted Protease Inhibitor Regimen: Week 48 Results of the Randomized, Multicenter MARCH Study

PubMed Central

Pett, Sarah Lilian; Amin, Janaki; Horban, Andrejz; Andrade-Villanueva, Jaime; Losso, Marcelo; Porteiro, Norma; Sierra Madero, Juan; Belloso, Waldo; Tu, Elise; Silk, David; Kelleher, Anthony; Harrigan, Richard; Clark, Andrew; Sugiura, Wataru; Wolff, Marcelo; Gill, John; Gatell, Jose; Fisher, Martin; Clarke, Amanda; Ruxrungtham, Kiat; Prazuck, Thierry; Kaiser, Rolf; Woolley, Ian; Arnaiz, Juan Alberto; Cooper, David; Rockstroh, Jürgen K.; Mallon, Patrick; Emery, Sean; Kelleher, Anthony; Merlin, Kate; Yeung, Julie; Fsadni, Bertha; Marks, Kat; Suzuki, Kazuo; Rismanto, Nick; Salomon, Horacio; Rubio, Andrea E.; Chibo, Doris; Birch, Chris; Harrigan, Richard; Swenson, Luke; Chan, Dennison; Berg, Thomas; Obermeier, Martin; Kaiser, Rolf; Schuelter, Eugen; Sierra Aragon, Saleta; Luebke, Nadine; Coughlan, Suzie; Dean, Jonathan; Sugiura, Wataru; Iwatani, Yasumasa; Reyes Teran, Gustavo; Avila, Santiago; Ruxrungtham, Kiat; Sirivichayakul, Sunee; Naphassanant, May; Ubolyam, Sasiwimol; Kaye, Steve; Land, Sally; Walker, Sarah; Haubrich, Richard; DeJesus, Edwin; Emery, Sean; Pett, Sarah L.; Tu, Elise; Silk, David; Berthon-Jones, Nisha; Amin, Janaki; Espinosa, Natalie; Courtney-Vega, Kymme; Absar, Noorul; Haskelberg, Hila; Robson, Rose; Donaldson, Anna; Losso, Marcelo; Belloso, Waldo; Guelman, Daniel; Gambardella, Luciana; Valdovinos, Mariana; Gatell, Jose; Arnaiz, Juan; Beleta, Helena; Ramos, Nuria; Targa, Marta; Rockstroh, Jurgen; Späth, Brigitta; Boesecke, Christoph; Engelhardt, Angelika; Fisher, Martin; Perry, Nicky; Clarke, Amanda; Gill, John; Beckthold, Brenda; Clark, Andrew; Drummond, Fraser; Lefevre, Eric; Corr, Sharon; Grant, Carol; Lupo, Sergio; Peroni, Luciana; Italiano, Hospital; Sanchez, Marisa; De Paz Sierra, Mariana; Mejia, Ramos; Losso, Marcelo; Viloria, Guillermo; Parlante, Angel; Bissio, Emiliano; Luchetti, Pablo; Warley, Eduardo; Vieni, Ines; Porteiro, Norma; Vilas, Cecilia; Zarate, Abel; Mayer, Gabriela; Elliot, Julian; Hagenauer, Michelle; Kelley, Mark; Rowling, Diane; Gibson, Abby; Latch, Ngaire; Tabrett, Chantal; Warzywoda, Elizabeth; Cooper, David; Pett, Sarah; MacRae, Karen; Sinclair, Brett; Sinn, Kate; Bloch, Mark; Franic, Teo; Vincent, Trina; Stewart, Natasha; Jayewardene, Avindra; Dwyer, Dominic; Kok, Jennifer; Assam, Delene; Taylor, Janette; King, Patricia; Orth, David; Youds, David; Sowden, David; Johnston, Colleen; Murray, Suzanne; Hehir, Jennifer; Wadham, Samantha; Donohue, William; Thompson, Jill; Garsia, Roger; Turnham, Geoffrey; Madden, Tracey; Woolley, Ian; Gillies, Ainsley; Bryant, Mellissa; Gill, John; Beckthold, Brenda; Walmsley, Sharon; Chan, Warmond; LeBlanc, Roger; Lanteigne, Francois; Mouawad, Rima; Rahal, Ines; Guber, Sergio; Ozturk, Sefika; Smith, Graham; Halpenny, Roberta; Reko, Tatjana; Robinette Hills, Jennifer; Wolff, Marcelo; Prazuck, Thierry; Laurent Hocqueloux, Francois; Wolfgang, Johann; Stephan, Christoph; Ebeling, Franziska; Rockstroh, Juergen; Boesecke, Christoph; Spath, Brigitta; Engelhardt, Angelika; Ole Jensen, Bjorn-Erik; Feind, Cecilie; Meyer-Olson, Dirk; Stoll, Matthias; Hoeper, Kirsten; Beider, Renata; Faetkenheur, Gerd; Thomas Baumgarten, Ellen; Baumgarten, Axel; Ingiliz, Patrick; Wienbreyer, Andreas; Behrendt, Daniela; Nienkarken, Tanja; Stein, Jessen; Jessen, Heiko; Zedlack, Carmen; Mallon, Paddy; Simelane, Sibongile; Assmann, Jennifer; Ghavami-Kia, Bijan; Sugiura, Wataru; Imahashi, Mayumi; Tanabe, Kazue; Yokomaku, Yoshiyuki; Imamura, Junji; Andrade-Villanueva, Jaime; Montes de Oca, Melva; Gonzalez, Lucero; Ponce, David; Mendoza, Andrea; Sierra-Madero, Juan; Sanchez Hernandez, Jesus Eduardo; Jaime Ruiz Ballesteros, Eduardo; del Moral Ponce, Sergio; Mosqueda, Luis; Lopez, Monica; Horban, Andrzej; Ignatowska, Anna; Bakowska, Elzbieta; Pulik, Piotr; Sanz-Moreno, Jose; Paredes, Roger; Puig, Jordi; Domingo, Pere; Gutierrez, Mar; Gatell, Jose; González-Cordón, Ana; Callau, Pili; Lopez Aldeguer, Jose; Cuellar Tovar, Sandra; Leal Noval, Manuel; Rivas, Inmaculada; Delgado-Fernandez, Marcial; Ramon Arribas, Jose; Miguel Castro, Juan; Ruxrungtham, Kiat; Avihingsanon, Anchalee; Maek-a-nantawat, Wirach; Intasan, Jintana; Charoenporn, Walairat; Cuprasitrut, Thidarat; Jaisomkom, Pachuen; Pruksakaew, Kanchana; Winston, Alan; Mullaney, Scott; Fisher, Martin; Clarke, Amanda; Barbour, Lisa; Perry, Nicky; Richardson, Celia; Fox, Julie; Murray, Tammy; Leen, Clifford; Morris, Shelia; Satyajit, Das; Sandhu, Rumun; Tucker, James

2016-01-01

Abstract Background. Alternative combination antiretroviral therapies in virologically suppressed human immunodeficiency virus (HIV)–infected patients experiencing side effects and/or at ongoing risk of important comorbidities from current therapy are needed. Maraviroc (MVC), a chemokine receptor 5 antagonist, is a potential alternative component of therapy in those with R5-tropic virus. Methods. The Maraviroc Switch Study is a randomized, multicenter, 96-week, open-label switch study in HIV type 1–infected adults with R5-tropic virus, virologically suppressed on a ritonavir-boosted protease inhibitor (PI/r) plus double nucleoside/nucleotide reverse transcriptase inhibitor (2 N(t)RTI) backbone. Participants were randomized 1:2:2 to current combination antiretroviral therapy (control), or replacing the protease inhibitor (MVC + 2 N(t)RTI arm) or the nucleoside reverse transcriptase inhibitor backbone (MVC + PI/r arm) with twice-daily MVC. The primary endpoint was the difference (switch minus control) in proportion with plasma viral load (VL) <200 copies/mL at 48 weeks. The switch arms were judged noninferior if the lower limit of the 95% confidence interval (CI) for the difference in the primary endpoint was < −12% in the intention-to-treat (ITT) population. Results. The ITT population comprised 395 participants (control, n = 82; MVC + 2 N(t)RTI, n = 156; MVC + PI/r, n = 157). Baseline characteristics were well matched. At week 48, noninferior rates of virological suppression were observed in those switching away from a PI/r (93.6% [95% CI, −9.0% to 2.2%] and 91.7% [95% CI, −9.6% to 3.8%] with VL <200 and <50 copies/mL, respectively) compared to the control arm (97.6% and 95.1% with VL <200 and <50 copies/mL, respectively). In contrast, MVC + PI/r did not meet noninferiority bounds and was significantly inferior (84.1% [95% CI, −19.8% to −5.8%] and 77.7% [95% CI, −24.9% to −8.4%] with VL <200 and <50 copies/mL, respectively) to the control arm in the ITT analysis. Conclusions. These data support MVC as a switch option for ritonavir-boosted PIs when partnered with a 2-N(t)RTI backbone, but not as part of N(t)RTI-sparing regimens comprising MVC with PI/r. Clinical Trials Registration. NCT01384682. PMID:27048747

Increasing contextual demand modulates anterior and lateral prefrontal brain regions associated with proactive interference.

PubMed

Wolf, Robert Christian; Walter, Henrik; Vasic, Nenad

2010-01-01

Using a parametric version of a modified item-recognition paradigm with three different load levels and by means of event-related functional magnetic resonance imaging, this study tested the hypothesis that cerebral activation associated with intratrial proactive interference (PI) during working memory retrieval is influenced by increased context processing. We found activation of left BA 45 during interference trials across all levels of cognitive processing, and left lateralized activation of the dorsolateral prefrontal cortex (DLPFC, BA 9/46) and the frontopolar cortex (FPC, BA 10) with increasing contextual load. Compared with high susceptibility to PI, low susceptibility was associated with activation of the left DLPFC. These results suggest that an intratrial PI effect can be modulated by increasing context processing of a transiently relevant stimulus set. Moreover, PI resolution associated with increasing context load involves multiple prefrontal regions including the ventro- and dorsolateral prefrontal cortex as well as frontopolar brain areas. Furthermore, low susceptibility to PI might be influenced by increased executive control exerted by the DLPFC.

Pirating conserved phage mechanisms promotes promiscuous staphylococcal pathogenicity island transfer.

PubMed

Bowring, Janine; Neamah, Maan M; Donderis, Jorge; Mir-Sanchis, Ignacio; Alite, Christian; Ciges-Tomas, J Rafael; Maiques, Elisa; Medmedov, Iltyar; Marina, Alberto; Penadés, José R

2017-08-08

Targeting conserved and essential processes is a successful strategy to combat enemies. Remarkably, the clinically important Staphylococcus aureus pathogenicity islands (SaPIs) use this tactic to spread in nature. SaPIs reside passively in the host chromosome, under the control of the SaPI-encoded master repressor, Stl. It has been assumed that SaPI de-repression is effected by specific phage proteins that bind to Stl, initiating the SaPI cycle. Different SaPIs encode different Stl repressors, so each targets a specific phage protein for its de-repression. Broadening this narrow vision, we report here that SaPIs ensure their promiscuous transfer by targeting conserved phage mechanisms. This is accomplished because the SaPI Stl repressors have acquired different domains to interact with unrelated proteins, encoded by different phages, but in all cases performing the same conserved function. This elegant strategy allows intra- and inter-generic SaPI transfer, highlighting these elements as one of nature's most fascinating subcellular parasites.