Ground-based telescope pointing and tracking optimization using a neural controller.

PubMed

Mancini, D; Brescia, M; Schipani, P

2003-01-01

Neural network models (NN) have emerged as important components for applications of adaptive control theories. Their basic generalization capability, based on acquired knowledge, together with execution rapidity and correlation ability between input stimula, are basic attributes to consider NN as an extremely powerful tool for on-line control of complex systems. By a control system point of view, not only accuracy and speed, but also, in some cases, a high level of adaptation capability is required in order to match all working phases of the whole system during its lifetime. This is particularly remarkable for a new generation ground-based telescope control system. Infact, strong changes in terms of system speed and instantaneous position error tolerance are necessary, especially in case of trajectory disturb induced by wind shake. The classical control scheme adopted in such a system is based on the proportional integral (PI) filter, already applied and implemented on a large amount of new generation telescopes, considered as a standard in this technological environment. In this paper we introduce the concept of a new approach, the neural variable structure proportional integral, (NVSPI), related to the implementation of a standard multi layer perceptron network in new generation ground-based Alt-Az telescope control systems. Its main purpose is to improve adaptive capability of the Variable structure proportional integral model, an already innovative control scheme recently introduced by authors [Proc SPIE (1997)], based on a modified version of classical PI control model, in terms of flexibility and accuracy of the dynamic response range also in presence of wind noise effects. The realization of a powerful well tested and validated telescope model simulation system allowed the possibility to directly compare performances of the two control schemes on simulated tracking trajectories, revealing extremely encouraging results in terms of NVSPI control robustness and reliability.

African swine fever virus infection in Classical swine fever subclinically infected wild boars.

PubMed

Cabezón, Oscar; Muñoz-González, Sara; Colom-Cadena, Andreu; Pérez-Simó, Marta; Rosell, Rosa; Lavín, Santiago; Marco, Ignasi; Fraile, Lorenzo; de la Riva, Paloma Martínez; Rodríguez, Fernando; Domínguez, Javier; Ganges, Llilianne

2017-08-01

Recently moderate-virulence classical swine fever virus (CSFV) strains have been proven capable of generating postnatal persistent infection (PI), defined by the maintenance of viremia and the inability to generate CSFV-specific immune responses in animals. These animals also showed a type I interferon blockade in the absence of clinical signs. In this study, we assessed the infection generated in 7-week-old CSFV PI wild boars after infection with the African swine fever virus (ASFV). The wild boars were divided in two groups and were infected with ASFV. Group A comprised boars who were CSFV PI in a subclinical form and Group B comprised pestivirus-free wild boars. Some relevant parameters related to CSFV replication and the immune response of CSFV PI animals were studied. Additionally, serum soluble factors such as IFN-α, TNF-α, IL-6, IL-10, IFN-γ and sCD163 were analysed before and after ASFV infection to assess their role in disease progression. After ASFV infection, only the CSFV PI wild boars showed progressive acute haemorrhagic disease; however, the survival rates following ASFV infection was similar in both experimental groups. Notwithstanding, the CSFV RNA load of CSFV PI animals remained unaltered over the study; likewise, the ASFV DNA load detected after infection was similar between groups. Interestingly, systemic type I FN-α and IL-10 levels in sera were almost undetectable in CSFV PI animals, yet detectable in Group B, while detectable levels of IFN-γ were found in both groups. Finally, the flow cytometry analysis showed an increase in myelomonocytic cells (CD172a + ) and a decrease in CD4 + T cells in the PBMCs from CSFV PI animals after ASFV infection. Our results showed that the immune response plays a role in the progression of disease in CSFV subclinically infected wild boars after ASFV infection, and the immune response comprised the systemic type I interferon blockade. ASFV does not produce any interference with CSFV replication, or vice versa. ASFV infection could be a trigger factor for the disease progression in CSFV PI animals, as their survival after ASFV was similar to that of the pestivirus-free ASFV-infected group. This fact suggests a high resistance in CSFV PI animals even against a virus like ASFV; this may mean that there are relevant implications for CSF control in endemic countries. The diagnosis of ASFV and CSFV co-infection in endemic countries cannot be ruled out and need to be studied in greater depth.

Load Frequency Control of AC Microgrid Interconnected Thermal Power System

NASA Astrophysics Data System (ADS)

Lal, Deepak Kumar; Barisal, Ajit Kumar

2017-08-01

In this paper, a microgrid (MG) power generation system is interconnected with a single area reheat thermal power system for load frequency control study. A new meta-heuristic optimization algorithm i.e. Moth-Flame Optimization (MFO) algorithm is applied to evaluate optimal gains of the fuzzy based proportional, integral and derivative (PID) controllers. The system dynamic performance is studied by comparing the results with MFO optimized classical PI/PID controllers. Also the system performance is investigated with fuzzy PID controller optimized by recently developed grey wolf optimizer (GWO) algorithm, which has proven its superiority over other previously developed algorithm in many interconnected power systems.

Cell permeability and nuclear DNA staining by propidium iodide in basidiomycetous yeasts.

PubMed

Zhang, Ning; Fan, Yuxuan; Li, Chen; Wang, Qiming; Leksawasdi, Noppol; Li, Fuli; Wang, Shi'an

2018-05-01

Non-model yeasts within basidiomycetes have considerable importance in agriculture, industry, and environment, but they are not as well studied as ascomycetous yeasts. Serving as a basic technique, nuclear DNA staining is widely used in physiology, ecology, cell biology, and genetics. However, it is unclear whether the classical nuclear DNA staining method for ascomycetous yeasts is applicable to basidiomycetous yeasts. In this study, 5 yeasts ineffectively stained by the classical propidium iodide (PI) staining method were identified from 23 representative basidiomycetous yeasts. Pretreatment of cells using dimethyl sulfoxide (DMSO) or snailase markedly improved cell penetration to PI and thus enabled DNA content determination by flow cytometry on the recalcitrant yeasts. The pretreatments are efficient, simple, and fast, avoiding tedious mutagenesis or genetic engineering used in previous reports. The heterogeneity of cell penetration to PI among basidiomycetous yeasts was attributed to the discrepancy in cell wall polysaccharides instead of capsule or plasma membrane. This study also indicated that care must be taken in attributing PI-negative staining as viable cells when studying non-model microorganisms.

Enzymatic Kinetic Isotope Effects from Path-Integral Free Energy Perturbation Theory.

PubMed

Gao, J

2016-01-01

Path-integral free energy perturbation (PI-FEP) theory is presented to directly determine the ratio of quantum mechanical partition functions of different isotopologs in a single simulation. Furthermore, a double averaging strategy is used to carry out the practical simulation, separating the quantum mechanical path integral exactly into two separate calculations, one corresponding to a classical molecular dynamics simulation of the centroid coordinates, and another involving free-particle path-integral sampling over the classical, centroid positions. An integrated centroid path-integral free energy perturbation and umbrella sampling (PI-FEP/UM, or simply, PI-FEP) method along with bisection sampling was summarized, which provides an accurate and fast convergent method for computing kinetic isotope effects for chemical reactions in solution and in enzymes. The PI-FEP method is illustrated by a number of applications, to highlight the computational precision and accuracy, the rule of geometrical mean in kinetic isotope effects, enhanced nuclear quantum effects in enzyme catalysis, and protein dynamics on temperature dependence of kinetic isotope effects. © 2016 Elsevier Inc. All rights reserved.

Classical and quantum analysis of repulsive singularities in four-dimensional extended supergravity

NASA Astrophysics Data System (ADS)

Gaida, I.; Hollmann, H. R.; Stewart, J. M.

1999-07-01

Non-minimal repulsive singularities (`repulsons') in extended supergravity theories are investigated. The short-distance antigravity properties of the repulsons are tested at the classical and the quantum level by a scalar test-particle. Using a partial wave expansion it is shown that the particle is totally reflected at the origin. A high-frequency incoming particle undergoes a phase shift of icons/Journals/Common/pi" ALT="pi" ALIGN="TOP"/>/2. However, the phase shift for a low-frequency particle depends upon the physical data of the repulson. The curvature singularity at a finite distance rh turns out to be transparent for the scalar test-particle and the coordinate singularity at the origin serves as the repulsive barrier to bounce back the particles.

Discovering Hidden Controlling Parameters using Data Analytics and Dimensional Analysis

NASA Astrophysics Data System (ADS)

Del Rosario, Zachary; Lee, Minyong; Iaccarino, Gianluca

2017-11-01

Dimensional Analysis is a powerful tool, one which takes a priori information and produces important simplifications. However, if this a priori information - the list of relevant parameters - is missing a relevant quantity, then the conclusions from Dimensional Analysis will be incorrect. In this work, we present novel conclusions in Dimensional Analysis, which provide a means to detect this failure mode of missing or hidden parameters. These results are based on a restated form of the Buckingham Pi theorem that reveals a ridge function structure underlying all dimensionless physical laws. We leverage this structure by constructing a hypothesis test based on sufficient dimension reduction, allowing for an experimental data-driven detection of hidden parameters. Both theory and examples will be presented, using classical turbulent pipe flow as the working example. Keywords: experimental techniques, dimensional analysis, lurking variables, hidden parameters, buckingham pi, data analysis. First author supported by the NSF GRFP under Grant Number DGE-114747.

PLC-mediated PI(4,5)P2 hydrolysis regulates activation and inactivation of TRPC6/7 channels

PubMed Central

Itsuki, Kyohei; Imai, Yuko; Hase, Hideharu; Okamura, Yasushi; Inoue, Ryuji

2014-01-01

Transient receptor potential classical (or canonical) (TRPC)3, TRPC6, and TRPC7 are a subfamily of TRPC channels activated by diacylglycerol (DAG) produced through the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) by phospholipase C (PLC). PI(4,5)P2 depletion by a heterologously expressed phosphatase inhibits TRPC3, TRPC6, and TRPC7 activity independently of DAG; however, the physiological role of PI(4,5)P2 reduction on channel activity remains unclear. We used Förster resonance energy transfer (FRET) to measure PI(4,5)P2 or DAG dynamics concurrently with TRPC6 or TRPC7 currents after agonist stimulation of receptors that couple to Gq and thereby activate PLC. Measurements made at different levels of receptor activation revealed a correlation between the kinetics of PI(4,5)P2 reduction and those of receptor-operated TRPC6 and TRPC7 current activation and inactivation. In contrast, DAG production correlated with channel activation but not inactivation; moreover, the time course of channel inactivation was unchanged in protein kinase C–insensitive mutants. These results suggest that inactivation of receptor-operated TRPC currents is primarily mediated by the dissociation of PI(4,5)P2. We determined the functional dissociation constant of PI(4,5)P2 to TRPC channels using FRET of the PLCδ Pleckstrin homology domain (PHd), which binds PI(4,5)P2, and used this constant to fit our experimental data to a model in which channel gating is controlled by PI(4,5)P2 and DAG. This model predicted similar FRET dynamics of the PHd to measured FRET in either human embryonic kidney cells or smooth muscle cells, whereas a model lacking PI(4,5)P2 regulation failed to reproduce the experimental data, confirming the inhibitory role of PI(4,5)P2 depletion on TRPC currents. Our model also explains various PLC-dependent characteristics of channel activity, including limitation of maximum open probability, shortening of the peak time, and the bell-shaped response of total current. In conclusion, our studies demonstrate a fundamental role for PI(4,5)P2 in regulating TRPC6 and TRPC7 activity triggered by PLC-coupled receptor stimulation. PMID:24470487

Effects of in utero pestivirus infection on bovine fetal bone geometry, biomechanical properties and composition.

PubMed

Webb, Brett T; McGilvray, Kirk C; Smirnova, Natalia P; Hansen, Thomas R; Norrdin, Robert W

2013-11-01

Transplacental viral infection of the fetus can result in abnormal trabecular and cortical bone modeling in long bones through impaired bone resorption and formation. Although such infections are frequently associated with neonatal fractures in humans and animals, their effect on the biomechanical properties of the developing skeleton remain poorly understood. The goal of this study was to determine the effects of transplacental bovine viral diarrhea virus (BVDV) infection on the biomechanical properties of fetal femora. Pregnant heifers were inoculated intranasally with non-cytopathic BVDV or media alone on day 75 of gestation to produce persistently infected (PI) and control fetuses, respectively, which were then removed on days 192 and 245 of gestation. Histomorphometry, compositional analysis and 'four-point bending until failure' were performed on fetal femora. Altered cortical geometry largely accounted for differences in calculated elastic modulus (PI vs. control, and day 192 vs. day 245) and ultimate stress (day 192 vs. day 245). Fetal infection with BVDV did not significantly impair inherent biomechanical properties of bone but rather resulted in decreased periosteal apposition rates, manifested as smaller femoral mid-diaphyseal diameters. There were no differences between PI and control fetuses in cortical thickness ratio, ash density or calcium/phosphorous content; however, cortical thickness ratio decreased with fetal age. Thus even when cortical thickness ratios are similar, differences in mid-diaphyseal diameter affect the error associated with the calculation of stress and strain by classical beam theory equations. Copyright © 2013. Published by Elsevier Ltd.

Phosphatidylinositol 4,5-bisphosphate optical uncaging potentiates exocytosis

PubMed Central

Wierda, Keimpe DB; Pinheiro, Paulo S; Nadler, André; McCarthy, Anthony W; Ziomkiewicz, Iwona; Kruse, Martin; Reither, Gregor; Rettig, Jens; Lehmann, Martin; Haucke, Volker; Hille, Bertil

2017-01-01

Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] is essential for exocytosis. Classical ways of manipulating PI(4,5)P2 levels are slower than its metabolism, making it difficult to distinguish effects of PI(4,5)P2 from those of its metabolites. We developed a membrane-permeant, photoactivatable PI(4,5)P2, which is loaded into cells in an inactive form and activated by light, allowing sub-second increases in PI(4,5)P2 levels. By combining this compound with electrophysiological measurements in mouse adrenal chromaffin cells, we show that PI(4,5)P2 uncaging potentiates exocytosis and identify synaptotagmin-1 (the Ca2+ sensor for exocytosis) and Munc13-2 (a vesicle priming protein) as the relevant effector proteins. PI(4,5)P2 activation of exocytosis did not depend on the PI(4,5)P2-binding CAPS-proteins, suggesting that PI(4,5)P2 uncaging may bypass CAPS-function. Finally, PI(4,5)P2 uncaging triggered the rapid fusion of a subset of readily-releasable vesicles, revealing a rapid role of PI(4,5)P2 in fusion triggering. Thus, optical uncaging of signaling lipids can uncover their rapid effects on cellular processes and identify lipid effectors. PMID:29068313

Molecular biology of bladder cancer.

PubMed

Martin-Doyle, William; Kwiatkowski, David J

2015-04-01

Classic as well as more recent large-scale genomic analyses have uncovered multiple genes and pathways important for bladder cancer development. Genes involved in cell-cycle control, chromatin regulation, and receptor tyrosine and PI3 kinase-mammalian target of rapamycin signaling pathways are commonly mutated in muscle-invasive bladder cancer. Expression-based analyses have identified distinct types of bladder cancer that are similar to subsets of breast cancer, and have prognostic and therapeutic significance. These observations are leading to novel therapeutic approaches in bladder cancer, providing optimism for therapeutic progress. Copyright © 2015 Elsevier Inc. All rights reserved.

Real-time control of combined surface water quantity and quality: polder flushing.

PubMed

Xu, M; van Overloop, P J; van de Giesen, N C; Stelling, G S

2010-01-01

In open water systems, keeping both water depths and water quality at specified values is critical for maintaining a 'healthy' water system. Many systems still require manual operation, at least for water quality management. When applying real-time control, both quantity and quality standards need to be met. In this paper, an artificial polder flushing case is studied. Model Predictive Control (MPC) is developed to control the system. In addition to MPC, a 'forward estimation' procedure is used to acquire water quality predictions for the simplified model used in MPC optimization. In order to illustrate the advantages of MPC, classical control [Proportional-Integral control (PI)] has been developed for comparison in the test case. The results show that both algorithms are able to control the polder flushing process, but MPC is more efficient in functionality and control flexibility.

The receptor tyrosine kinase MerTK activates phospholipase C γ2 during recognition of apoptotic thymocytes by murine macrophages

PubMed Central

Todt, Jill C.; Hu, Bin; Curtis, Jeffrey L.

2008-01-01

Apoptotic leukocytes must be cleared efficiently by macrophages (Mø). Apoptotic cell phagocytosis by Mø requires the receptor tyrosine kinase (RTK) MerTK (also known as c-Mer and Tyro12), the phosphatidylserine receptor (PS-R), and the classical protein kinase C (PKC) isoform βII, which translocates to Mø membrane and cytoskeletal fractions in a PS-R-dependent fashion. How these molecules cooperate to induce phagocytosis is unknown. Because the phosphatidylinositol-specific phospholipase (PI-PLC) PLC γ2 is downstream of RTKs in some cell types and can activate classical PKCs, we hypothesized that MerTK signals via PLC γ2. To test this hypothesis, we examined the interaction of MerTK and PLC γ2 in resident murine PMø and in the murine Mø cell line J774A.1 (J774) following exposure to apoptotic thymocytes. We found that, as with PMø, J774 phagocytosis of apoptotic thymocytes was inhibited by antibody against MerTK. Western blotting and immunoprecipitation showed that exposure to apoptotic cells produced three time-dependent changes in PMø and J774: (1) tyrosine phosphorylation of MerTK; (2) association of PLC γ2 with MerTK; and (3) tyrosine phosphorylation of PLC γ2. Phosphorylation of PLC γ2 and its association with MerTK was also induced by cross-linking MerTK using antibody. A PI-PLC appears to be required for phagocytosis of apoptotic cells because the PI-PLC inhibitor Et-18-OCH3 and the PLC inhibitor U73122, but not the inactive control U73343, blocked phagocytosis without impairing adhesion. On apoptotic cell adhesion to Mø, MerTK signals at least in part via PLC γ2. PMID:14704368

Discrete roles and bifurcation of PTEN signaling and mTORC1-mediated anabolic metabolism underlie IL-7–driven B lymphopoiesis

PubMed Central

Zeng, Hu; Yu, Mei; Tan, Haiyan; Li, Yuxin; Su, Wei; Shi, Hao; Dhungana, Yogesh; Guy, Cliff; Neale, Geoffrey; Cloer, Caryn; Peng, Junmin; Wang, Demin; Chi, Hongbo

2018-01-01

Interleukin-7 (IL-7) drives early B lymphopoiesis, but the underlying molecular circuits remain poorly understood, especially how Stat5 (signal transducer and activator of transcription 5)–dependent and Stat5-independent pathways contribute to this process. Combining transcriptome and proteome analyses and mouse genetic models, we show that IL-7 promotes anabolic metabolism and biosynthetic programs in pro-B cells. IL-7–mediated activation of mTORC1 (mechanistic target of rapamycin complex 1) supported cell proliferation and metabolism in a Stat5-independent, Myc-dependent manner but was largely dispensable for cell survival or Rag1 and Rag2 gene expression. mTORC1 was also required for Myc-driven lymphomagenesis. PI3K (phosphatidylinositol 3-kinase) and mTORC1 had discrete effects on Stat5 signaling and independently controlled B cell development. PI3K was actively suppressed by PTEN (phosphatase and tensin homolog) in pro-B cells to ensure proper IL-7R expression, Stat5 activation, heavy chain rearrangement, and cell survival, suggesting the unexpected bifurcation of the classical PI3K-mTOR signaling. Together, our integrative analyses establish IL-7R–mTORC1–Myc and PTEN-mediated PI3K suppression as discrete signaling axes driving B cell development, with differential effects on IL-7R–Stat5 signaling. PMID:29399633

A Simulink Library of cryogenic components to automatically generate control schemes for large Cryorefrigerators

NASA Astrophysics Data System (ADS)

Bonne, François; Alamir, Mazen; Hoa, Christine; Bonnay, Patrick; Bon-Mardion, Michel; Monteiro, Lionel

2015-12-01

In this article, we present a new Simulink library of cryogenics components (such as valve, phase separator, mixer, heat exchanger...) to assemble to generate model-based control schemes. Every component is described by its algebraic or differential equation and can be assembled with others to build the dynamical model of a complete refrigerator or the model of a subpart of it. The obtained model can be used to automatically design advanced model based control scheme. It also can be used to design a model based PI controller. Advanced control schemes aim to replace classical user experience designed approaches usually based on many independent PI controllers. This is particularly useful in the case where cryoplants are submitted to large pulsed thermal loads, expected to take place in future fusion reactors such as those expected in the cryogenic cooling systems of the International Thermonuclear Experimental Reactor (ITER) or the Japan Torus-60 Super Advanced Fusion Experiment (JT- 60SA). The paper gives the example of the generation of the dynamical model of the 400W@1.8K refrigerator and shows how to build a Constrained Model Predictive Control for it. Based on the scheme, experimental results will be given. This work is being supported by the French national research agency (ANR) through the ANR-13-SEED-0005 CRYOGREEN program.

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

PubMed

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

2017-08-01

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

Predicting memory performance under conditions of proactive interference: immediate and delayed judgments of learning.

PubMed

Wahlheim, Christopher N

2011-07-01

Four experiments examined the monitoring accuracy of immediate and delayed judgments of learning (JOLs) under conditions of proactive interference (PI). PI was produced using paired-associate learning tasks that conformed to variations of classic A-B, A-D paradigms. Results revealed that the relative monitoring accuracy of interference items was better for delayed than for immediate JOLs. However, delayed JOLs were overconfident for interference items, but not for items devoid of interference. Intrusions retrieved prior to delayed JOLs produced inflated predictions of performance. These results show that delayed JOLs enhance monitoring accuracy in PI situations, except when intrusions are mistaken for target responses.

Velocity control of servo systems using an integral retarded algorithm.

PubMed

Ramírez, Adrián; Garrido, Rubén; Mondié, Sabine

2015-09-01

This paper presents a design technique for the delay-based controller called Integral Retarded (IR), and its applications to velocity control of servo systems. Using spectral analysis, the technique yields a tuning strategy for the IR by assigning a triple real dominant root for the closed-loop system. This result ultimately guarantees a desired exponential decay rate σ(d) while achieving the IR tuning as explicit function of σ(d) and system parameters. The intentional introduction of delay allows using noisy velocity measurements without additional filtering. The structure of the controller is also able to avoid velocity measurements by using instead position information. The IR is compared to a classical PI, both tested in a laboratory prototype. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

Quantum dynamics in phase space: Moyal trajectories 2

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

Braunss, G.

Continuing a previous paper [G. Braunss, J. Phys. A: Math. Theor. 43, 025302 (2010)] where we had calculated Planck-Constant-Over-Two-Pi {sup 2}-approximations of quantum phase space viz. Moyal trajectories of examples with one and two degrees of freedom, we present in this paper the calculation of Planck-Constant-Over-Two-Pi {sup 2}-approximations for four examples: a two-dimensional Toda chain, the radially symmetric Schwarzschild field, and two examples with three degrees of freedom, the latter being the nonrelativistic spherically Coulomb potential and the relativistic cylinder symmetrical Coulomb potential with a magnetic field H. We show in particular that an Planck-Constant-Over-Two-Pi {sup 2}-approximation of the nonrelativisticmore » Coulomb field has no singularity at the origin (r= 0) whereas the classical trajectories are singular at r= 0. In the third example, we show in particular that for an arbitrary function {gamma}(H, z) the expression {beta}{identical_to}p{sub z}+{gamma}(H, z) is classically ( Planck-Constant-Over-Two-Pi = 0) a constant of motion, whereas for Planck-Constant-Over-Two-Pi {ne} 0 this holds only if {gamma}(H, z) is an arbitrary polynomial of second order in z. This statement is shown to extend correspondingly to a cylinder symmetrical Schwarzschild field with a magnetic field. We exhibit in detail a number of properties of the radially symmetric Schwarzschild field. We exhibit finally the problems of the nonintegrable Henon-Heiles Hamiltonian and give a short review of the regular Hilbert space representation of Moyal operators.« less

GSTP1 Polymorphisms and their Association with Glutathione Transferase and Peroxidase Activities in Patients with Motor Neuron Disease.

PubMed

Gajewska, Beata; Kaźmierczak, Beata; Kuźma-Kozakiewicz, Magdalena; Jamrozik, Zygmunt; Barańczyk-Kuźma, Anna

2015-01-01

Glutathione S-transferase pi (GSTP1) is a crucial enzyme in detoxification of electrophilic compounds and organic peroxides. Together with Se-dependent glutathione peroxidase (Se-GSHPx) it protects cells against oxidative stress which may be a primary factor implicated in motor neuron disease (MND) pathogenesis. We investigated GSTP1 polymorphisms and their relationship with GST and Se-GSTPx activities in a cohort of Polish patients with MND. Results were correlated with clinical phenotypes. The frequency of genetic variants for GSTP1 exon 5 (I105V) and exon 6 (A114V) was studied in 104 patients and 100 healthy controls using real-time polymerase chain reaction. GST transferase activity was determined in serum with 1-chloro-2,4-dinitrobenzene, its peroxidase activity with cumene hydroperoxide, and Se-GSHPx activity with hydrogen peroxide. There were no differences in the prevalence of GSTP1 polymorphism I105V and A114V between MND and controls, however the occurrence of CT variant in codon 114 was associated with a higher risk for MND. GSTP1 polymorphisms were less frequent in classic ALS than in progressive bulbar palsy. In classic ALS C* (heterozygous I /V and A /V) all studied activities were significantly lower than in classic ALS A* (homozygous I /I and A/A). GST peroxidase activity and Se-GSHPx activity were lower in classic ALS C* than in control C*, but in classic ALS A* Se-GSHPx activity was significantly higher than in control A*. It can be concluded that the presence of GSTP1 A114V but not I105V variant increases the risk of MND, and combined GSTP1 polymorphisms in codon 105 and 114 may result in lower protection of MND patients against the toxicity of electrophilic compounds, organic and inorganic hydroperoxides.

In vitro phosphorylation of insulin receptor substrate 1 by protein kinase C-zeta: functional analysis and identification of novel phosphorylation sites.

PubMed

Sommerfeld, Mark R; Metzger, Sabine; Stosik, Magdalene; Tennagels, Norbert; Eckel, Jürgen

2004-05-18

Protein kinase C-zeta (PKC-zeta) participates both in downstream insulin signaling and in the negative feedback control of insulin action. Here we used an in vitro approach to identify PKC-zeta phosphorylation sites within insulin receptor substrate 1 (IRS-1) and to characterize the functional implications. A recombinant IRS-1 fragment (rIRS-1(449)(-)(664)) containing major tyrosine motifs for interaction with phosphatidylinositol (PI) 3-kinase strongly associated to the p85alpha subunit of PI 3-kinase after Tyr phosphorylation by the insulin receptor. Phosphorylation of rIRS-1(449)(-)(664) by PKC-zeta induced a prominent inhibition of this process with a mixture of classical PKC isoforms being less effective. Both PKC-zeta and the classical isoforms phosphorylated rIRS-1(449)(-)(664) on Ser(612). However, modification of this residue did not reduce the affinity of p85alpha binding to pTyr-containing peptides (amino acids 605-615 of rat IRS-1), as determined by surface plasmon resonance. rIRS-1(449)(-)(664) was then phosphorylated by PKC-zeta using [(32)P]ATP and subjected to tryptic phosphopeptide mapping based on two-dimensional HPLC coupled to mass spectrometry. Ser(498) and Ser(570) were identified as novel phosphoserine sites targeted by PKC-zeta. Both sites were additionally confirmed by phosphopeptide mapping of the corresponding Ser --> Ala mutants of rIRS-1(449)(-)(664). Ser(570) was specifically targeted by PKC-zeta, as shown by immunoblotting with a phosphospecific antiserum against Ser(570) of IRS-1. Binding of p85alpha to the S570A mutant was less susceptible to inhibition by PKC-zeta, when compared to the S612A mutant. In conclusion, our in vitro data demonstrate a strong inhibitory action of PKC-zeta at the level of IRS-1/PI 3-kinase interaction involving multiple serine phosphorylation sites. Whereas Ser(612) appears not to participate in the negative control of insulin signaling, Ser(570) may at least partly contribute to this process.

Low order H∞ optimal control for ACFA blended wing body aircraft

NASA Astrophysics Data System (ADS)

Haniš, T.; Kucera, V.; Hromčík, M.

2013-12-01

Advanced nonconvex nonsmooth optimization techniques for fixed-order H∞ robust control are proposed in this paper for design of flight control systems (FCS) with prescribed structure. Compared to classical techniques - tuning of and successive closures of particular single-input single-output (SISO) loops like dampers, attitude stabilizers, etc. - all loops are designed simultaneously by means of quite intuitive weighting filters selection. In contrast to standard optimization techniques, though (H2, H∞ optimization), the resulting controller respects the prescribed structure in terms of engaged channels and orders (e. g., proportional (P), proportional-integral (PI), and proportional-integralderivative (PID) controllers). In addition, robustness with regard to multimodel uncertainty is also addressed which is of most importance for aerospace applications as well. Such a way, robust controllers for various Mach numbers, altitudes, or mass cases can be obtained directly, based only on particular mathematical models for respective combinations of the §ight parameters.

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

PubMed

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

2010-04-01

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

Magnesium prevents phosphate-induced calcification in human aortic vascular smooth muscle cells.

PubMed

Louvet, Loïc; Büchel, Janine; Steppan, Sonja; Passlick-Deetjen, Jutta; Massy, Ziad A

2013-04-01

Vascular calcification (VC) is prevalent in patients suffering from chronic kidney disease. Factors promoting calcification include abnormalities in mineral metabolism, particularly high phosphate levels. Inorganic phosphate (Pi) is a classical inducer of in vitro VC. Recently, an inverse relationship between serum magnesium concentrations and VC has been reported. The present study aimed to investigate the effects of magnesium on Pi-induced VC at the cellular level using primary HAVSMC. Alive and fixed HAVSMC were assessed during 14 days in the presence of Pi with increasing concentrations of magnesium (Mg(2+)) chloride. Mineralization was measured using quantification of calcium, von Kossa and alizarin red stainings. Cell viability and secretion of classical VC markers were also assessed using adequate tests. Involvement of transient receptor potential melastatin (TRPM) 7 was assessed using 2-aminoethoxy-diphenylborate (2-APB) inhibitor. Co-incubation with Mg(2+) significantly decreased Pi-induced VC in live HAVSMC, no effect was found in fixed cells. At potent concentrations in Pi-induced HAVSMC, Mg(2+) significantly improved cell viability and restored to basal level increased secretions of osteocalcin and matrix gla protein, whereas a decrease in osteopontin secretion was partially restored. The block of TRPM7 with 2-APB at 10(-4) M led to the inefficiency of Mg(2+) to prevent VC. Increasing Mg(2+) concentrations significantly reduced VC, improved cell viability and modulated secretion of VC markers during cell-mediated matrix mineralization clearly pointing to a cellular role for Mg(2+) and 2-APB further involved TRPM7 and a potential Mg(2+) entry to exert its effects. Further investigations are needed to shed light on additional cellular mechanism(s) by which Mg(2+) is able to prevent VC.

Solution to automatic generation control problem using firefly algorithm optimized I(λ)D(µ) controller.

PubMed

Debbarma, Sanjoy; Saikia, Lalit Chandra; Sinha, Nidul

2014-03-01

Present work focused on automatic generation control (AGC) of a three unequal area thermal systems considering reheat turbines and appropriate generation rate constraints (GRC). A fractional order (FO) controller named as I(λ)D(µ) controller based on crone approximation is proposed for the first time as an appropriate technique to solve the multi-area AGC problem in power systems. A recently developed metaheuristic algorithm known as firefly algorithm (FA) is used for the simultaneous optimization of the gains and other parameters such as order of integrator (λ) and differentiator (μ) of I(λ)D(µ) controller and governor speed regulation parameters (R). The dynamic responses corresponding to optimized I(λ)D(µ) controller gains, λ, μ, and R are compared with that of classical integer order (IO) controllers such as I, PI and PID controllers. Simulation results show that the proposed I(λ)D(µ) controller provides more improved dynamic responses and outperforms the IO based classical controllers. Further, sensitivity analysis confirms the robustness of the so optimized I(λ)D(µ) controller to wide changes in system loading conditions and size and position of SLP. Proposed controller is also found to have performed well as compared to IO based controllers when SLP takes place simultaneously in any two areas or all the areas. Robustness of the proposed I(λ)D(µ) controller is also tested against system parameter variations. © 2013 ISA. Published by Elsevier Ltd. All rights reserved.

Phosphate transport in pig proximal small intestines during postnatal development: lack of modulation by calcitriol.

PubMed

Schröder, B; Hattenhauer, O; Breves, G

1998-04-01

The role of calcitriol in the intestinal absorption of inorganic phosphate (Pi) during postnatal development was studied in newborn [<1 week postpartum (pp)], suckling (3-4 weeks pp), and weaned (>6 weeks pp) control piglets (con) and piglets suffering from inherited calcitriol deficiency (def). In addition, a number of def piglets were treated with vitamin D3 (def-D3). Regardless of age, plasma calcitriol concentrations in def piglets were unphysiologically low (16-21 pg/ml) and differed significantly from those in respective con animals (60-69 pg/ml) and vitamin D3-treated def piglets (50-56 pg/ml). However, newborn and suckling def piglets had normal Ca (approximately 3.0 mmol/liter) and Pi (approximately 2.8 mmol/liter) plasma levels. Def piglets became hypocalcemic (1.9 mmol/liter) and hypophosphatemic (1.9 mmol/liter) between 4-6 weeks pp. Treatment with vitamin D3 significantly increased plasma Ca (3.2 mmol/liter) and Pi (2.7 mmol/liter) levels in weaned def animals. Regardless of calcitriol status, net Pi flux rates (active Pi absorption, as determined with the in vitro Ussing-chamber technique) from the upper small intestines was maximal at birth [170-224 nmol/(cm2 x h)] and decreased by approximately 80% during the first week of life before remaining constant [30-50 nmol/(cm2 x h)] during the following development. In weaned def piglets, net Pi flux rates were significantly lower by about 80% compared with those in con animals. Treatment of def piglets with vitamin D3 had no effect in newborn and suckling animals but reconstituted net Pi flux rates to normal values at weaning age. Age-dependent and calcitriol-mediated changes in net Pi flux rates were paralleled by respective maximum velocity values of Na+-dependent Pi uptake across the brush border membrane of the enterocytes (newborn piglets, 1.9-2.2 nmol/(mg protein 10 sec); suckling piglets, 0.4-0.6 nmol/(mg protein x 10 sec); weaned piglets, 0.7, 0.3, and 0.7 nmol/(mg protein x 10 sec) in con, def, and def-D3 animals, respectively). These findings suggest that the apical Pi uptake represents the major rate-limiting step of the overall transepithelial Pi transport. At weaning, Na+/Pi transport across the intestinal brush-border membrane is clearly stimulated by calcitriol, but no significant effects of age or calcitriol on the Km values (0.5-0.7 mmol/liter) were observed. In conclusion, our findings reveal calcitriol-independent mechanisms for active intestinal Pi absorption during the neonatal and suckling periods. The onset of the classical calcitriol-dependent mechanism for active intestinal Pi absorption does not occur until weaning.

Congestion control and routing over satellite networks

NASA Astrophysics Data System (ADS)

Cao, Jinhua

Satellite networks and transmissions find their application in fields of computer communications, telephone communications, television broadcasting, transportation, space situational awareness systems and so on. This thesis mainly focuses on two networking issues affecting satellite networking: network congestion control and network routing optimization. Congestion, which leads to long queueing delays, packet losses or both, is a networking problem that has drawn the attention of many researchers. The goal of congestion control mechanisms is to ensure high bandwidth utilization while avoiding network congestion by regulating the rate at which traffic sources inject packets into a network. In this thesis, we propose a stable congestion controller using data-driven, safe switching control theory to improve the dynamic performance of satellite Transmission Control Protocol/Active Queue Management (TCP/AQM) networks. First, the stable region of the Proportional-Integral (PI) parameters for a nominal model is explored. Then, a PI controller, whose parameters are adaptively tuned by switching among members of a given candidate set, using observed plant data, is presented and compared with some classical AQM policy examples, such as Random Early Detection (RED) and fixed PI control. A new cost detectable switching law with an interval cost function switching algorithm, which improves the performance and also saves the computational cost, is developed and compared with a law commonly used in the switching control literature. Finite-gain stability of the system is proved. A fuzzy logic PI controller is incorporated as a special candidate to achieve good performance at all nominal points with the available set of candidate controllers. Simulations are presented to validate the theory. An effocient routing algorithm plays a key role in optimizing network resources. In this thesis, we briefly analyze Low Earth Orbit (LEO) satellite networks, review the Cross Entropy (CE) method and then develop a novel on-demand routing system named Cross Entropy Accelerated Ant Routing System (CEAARS) for regular constellation LEO satellite networks. By implementing simulations on an Iridium-like satellite network, we compare the proposed CEAARS algorithm with the two approaches to adaptive routing protocols on the Internet: distance-vector (DV) and link-state (LS), as well as with the original Cross Entropy Ant Routing System (CEARS). DV algorithms are based on distributed Bellman Ford algorithm, and LS algorithms are implementation of Dijkstras single source shortest path. The results show that CEAARS not only remarkably improves the convergence speed of achieving optimal or suboptimal paths, but also reduces the number of overhead ants (management packets).

The effect of Liuwei Dihuang decoction on PI3K/Akt signaling pathway in liver of type 2 diabetes mellitus (T2DM) rats with insulin resistance.

PubMed

Dai, Bing; Wu, Qinxuan; Zeng, Chengxi; Zhang, Jiani; Cao, Luting; Xiao, Zizeng; Yang, Menglin

2016-11-04

Liuwei Dihaung decoction (LWDHT) is a well-known classic traditional Chinese medicine formula, consists of six herbs including Rehmannia glutinosa Libosch.(family: Scrophulariaceae), Cornus officinalis Sieb.(family: Cornaceae), Dioscorea opposite Thunb.(family: Dioscoreaceae), Alisma orientale(G. Samuelsson) Juz (family: Alismataceae), Poria cocos (Schw.) Wolf (family: Polyporaceae) and Paeonia suffruticosa Andrews (family: Paeoniaceae). It has been used in the treatment of many types of diseases with signs of deficiency of Yin in the kidneys in China clinically. This study is aimed at investigating the effect of Liuwei dihuang decoction on PI3K/Akt signaling pathway in liver of T2DM rats with insulin resistance. T2DM model was induced in male Sprague-Dawley (SD) rats by high sugar and high fat diets combined with small dose of streptozocin (STZ) injection. The successful T2DM rats were randomly allocated three group--vehicle group, positive control group and Liuwei Dihuang decoction group. After 12-weeks treatment with distilled water, rosiglitazone and LWDHT by intragastric administration respectively, the rats were put to death in batches. The variance of fasting blood glucose (FBG) and fasting insulin (FINS) in serum were determined, the pathological changes of each rats' liver were observed by hematoxylin-eosin (HE) staining, the expression of insulin receptor substrate 2(IRS2), phosphatidylinositol 3-kinase (PI3K) and protein kinas B (Akt) involving the canonical PI3K/Akt signaling pathway were detected by Real-time fluorescent quantitative PCR (RT-PCR), and the expression level of IRS2, PI3K, Akt protein and phosphorylated IRS2, PI3K, Akt protein were evaluated by Western Blot. All the data were analyzed by SPSS 17.0. Four weeks of treatment with LWDHT could significantly decrease the level of FBG and FINS in serum, improve the cellular morphology of liver, kidney, pancreas tissue, and the expression of IRS2, PI3K, Akt mRNA and phosphorylated IRS2, PI3K, Akt protein involved in the canonical PI3K/Akt signaling pathway of T2DM rats in liver were significantly up-regulated, while the total IRS2, PI3K, and Akt protein had no obvious changes. The results suggest that Liuwei Dihuang decoction could intervene insulin resistance of T2DM, in part, through regulation of canonical PI3K/Akt signaling pathway of T2DM rats in liver. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Primary transmission of chronic wasting disease versus scrapie prions from small ruminants to transgenic mice expressing ovine or cervid prion protein.

PubMed

Madsen-Bouterse, Sally A; Schneider, David A; Zhuang, Dongyue; Dassanayake, Rohana P; Balachandran, Aru; Mitchell, Gordon B; O'Rourke, Katherine I

2016-09-01

Development of mice expressing either ovine (Tg338) or cervid (TgElk) prion protein (PrP) have aided in characterization of scrapie and chronic wasting disease (CWD), respectively. Experimental inoculation of sheep with CWD prions has demonstrated the potential for interspecies transmission but, infection with CWD versus classical scrapie prions may be difficult to differentiate using validated diagnostic platforms. In this study, mouse bioassay in Tg338 and TgElk was utilized to evaluate transmission of CWD versus scrapie prions from small ruminants. Mice (≥5 per homogenate) were inoculated with brain homogenates from clinically affected sheep or goats with naturally acquired classical scrapie, white-tailed deer with naturally acquired CWD (WTD-CWD) or sheep with experimentally acquired CWD derived from elk (sheep-passaged-CWD). Survival time (time to clinical disease) and attack rates (brain accumulation of protease resistant PrP, PrPres) were determined. Inoculation with classical scrapie prions resulted in clinical disease and 100 % attack rates in Tg338, but no clinical disease at endpoint (>300 days post-inoculation, p.i.) and low attack rates (6.8 %) in TgElk. Inoculation with WTD-CWD prions yielded no clinical disease or brain PrPres accumulation in Tg338 at endpoint (>500 days p.i.), but rapid onset of clinical disease (~121 days p.i.) and 100 % attack rate in TgElk. Sheep-passaged-CWD resulted in transmission to both mouse lines with 100 % attack rates at endpoint in Tg338 and an attack rate of ~73 % in TgElk with some culled due to clinical disease. These primary transmission observations demonstrate the potential of bioassay in Tg338 and TgElk to help differentiate possible infection with CWD versus classical scrapie prions in sheep and goats.

Evaluation of the light scattering and the turbidity microtiter plate-based methods for the detection of the excipient-mediated drug precipitation inhibition.

PubMed

Petruševska, Marija; Urleb, Uroš; Peternel, Luka

2013-11-01

The excipient-mediated precipitation inhibition is classically determined by the quantification of the dissolved compound in the solution. In this study, two alternative approaches were evaluated, one is the light scattering (nephelometer) and other is the turbidity (plate reader) microtiter plate-based methods which are based on the quantification of the compound precipitate. Following the optimization of the nephelometer settings (beam focus, laser gain) and the experimental conditions, the screening of 23 excipients on the precipitation inhibition of poorly soluble fenofibrate and dipyridamole was performed. The light scattering method resulted in excellent correlation (r>0.91) between the calculated precipitation inhibitor parameters (PIPs) and the precipitation inhibition index (PI(classical)) obtained by the classical approach for fenofibrate and dipyridamole. Among the evaluated PIPs AUC100 (nephelometer) resulted in only four false positives and lack of false negatives. In the case of the turbidity-based method a good correlation of the PI(classical) was obtained for the PIP maximal optical density (OD(max), r=0.91), however, only for fenofibrate. In the case of the OD(max) (plate reader) five false positives and two false negatives were identified. In conclusion, the light scattering-based method outperformed the turbidity-based one and could be reliably used for identification of novel precipitation inhibitors. Copyright © 2013 Elsevier B.V. All rights reserved.

Implementation and comparative study of control strategies for an isolated DFIG based WECS

NASA Astrophysics Data System (ADS)

Bouchiba, Nouha; Barkia, Asma; Sallem, Souhir; Chrifi-Alaoui, Larbi; Drid, Saïd; Kammoun, M. B. A.

2017-10-01

Nowadays, a global interest for renewable energy sources has been growing intensely. In particular, a wind energy has become the most popular. In case of autonomous systems, wind energy conversion system (WECS) based on a double fed induction generator (DFIG) is widely used. In this paper, in order to control the stand-alone system outputs under wind speed and load variations, three kinds of nonlinear control strategies have been proposed, applied and compared, such as: Classical PI controller, Back-Stepping and Sliding Mode controllers. A series of experiments have been conducted to evaluate and to compare the developed controllers' dynamic performances under load demand and speed variations. The design and the implementation of different control strategies to a 1.5kW doubly fed induction machine is carried out using a dSpace DS1104 card based on MATLAB/Simulink environment. Experimental results are presented to show the validity of the implemented controllers and demonstrate the effectiveness of each controller compared with others.

[Clinical significance and mechanism of upregulation of PI3Kp110α in non-small cell lung carcinoma].

PubMed

Xiong, Y; Qu, L L; Li, D; Wang, Y; Li, T

2017-10-23

Objective: To investigate the clinical significance and mechanism of upregulation of phosphoinositide 3-kinase p110α(PI3Kp110α)in non-small cell lung carcinoma (NSCLC). Methods: Expressions of PI3Kp110α and other components in PI3K signaling pathway (including phospho-Akt (p-Akt, Ser 473), MET, ROS1, HER-2, ALK, total EGFR and mutant EGFR) and p53 (the transcription factor of PIK3CA) mutation in NSCLC were detected by immunohistochemistry. The relationships between PI3Kp110α expression and clinicopathological characteristics, expressions of other proteins in PI3K pathway and p53 mutation were analyzed. Results: In 170 NSCLC patients, 72 cases (42.4%) showed lower expression and 98 cases (57.6%) showed higher expression of PI3Kp110α. Upregulation of PI3Kp110α was not significantly associated with gender, age, T stage and pathologic grade ( P >0.05). While upregulation of PI3Kp110α was significantly associated with smoking status of patients, pathologic classification, N stage, TNM stage and Ki-67 index ( P <0.05). Expression of PI3Kp110α was positively correlated with expressions of MET ( P <0.05) and mutant EGFR ( P =0.018), while not significantly related with expressions of p-Akt(Ser473), HER-2, ALK, ROS1, total EGFR or p53 mutation ( P >0.05). Conclusions: Upregulation of PI3Kp110α is closely related with tumorigenesis of non-smoking lung adenocarcinoma. MET overexpression and EGFR mutation may be crucial to upregulate expression of PI3Kp110α in NSCLC. Overexpression of PI3Kp110α may inhibit tumor cell proliferation in NSCLC through a different pathway other than classical PI3K pathway. Upregulation of PI3Kp110α may predict favorable prognosis of NSCLC patients.

Cognitive and Neural Sciences Division. 1988 Programs

DTIC Science & Technology

1988-08-01

the P.I. uses a delayed reinforcement autoshaping procedure which incorporates features of both classical and operant conditioning paradigms...Progress: The PT has completed initial dose-response study of effects of TMT on autoshaping and has submitted a paper that separates "non-specific

An interactive activation and competition model of person knowledge, suggested by proactive interference by traits spontaneously inferred from behaviours.

PubMed

Wang, Yuanbo E; Higgins, Nancy C; Uleman, James S; Michaux, Aaron; Vipond, Douglas

2016-03-01

People unconsciously and unintentionally make inferences about others' personality traits based on their behaviours. In this study, a classic memory phenomenon--proactive interference (PI)--is for the first time used to detect spontaneous trait inferences. PI should occur when lists of behaviour descriptions, all implying the same trait, are to be remembered. Switching to a new trait should produce 'release' from proactive interference (or RPI). Results from two experiments supported these predictions. PI and RPI effects are consistent with an interactive activation and competition model of person perception (e.g., McNeill & Burton, 2002, J. Exp. Psychol., 55A, 1141), which predicts categorical organization of social behaviours based on personality traits. Advantages of this model are discussed. © 2015 The British Psychological Society.

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.

Time-scaling based sliding mode control for Neuromuscular Electrical Stimulation under uncertain relative degrees.

PubMed

Oliveira, Tiago Roux; Costa, Luiz Rennó; Catunda, João Marcos Yamasaki; Pino, Alexandre Visintainer; Barbosa, William; Souza, Márcio Nogueira de

2017-06-01

This paper addresses the application of the sliding mode approach to control the arm movements by artificial recruitment of muscles using Neuromuscular Electrical Stimulation (NMES). Such a technique allows the activation of motor nerves using surface electrodes. The goal of the proposed control system is to move the upper limbs of subjects through electrical stimulation to achieve a desired elbow angular displacement. Since the human neuro-motor system has individual characteristics, being time-varying, nonlinear and subject to uncertainties, the use of advanced robust control schemes may represent a better solution than classical Proportional-Integral (PI) controllers and model-based approaches, being simpler than more sophisticated strategies using fuzzy logic or neural networks usually applied in this control problem. The objective is the introduction of a new time-scaling base sliding mode control (SMC) strategy for NMES and its experimental evaluation. The main qualitative advantages of the proposed controller via time-scaling procedure are its independence of the knowledge of the plant relative degree and the design/tuning simplicity. The developed sliding mode strategy allows for chattering alleviation due to the impact of the integrator in smoothing the control signal. In addition, no differentiator is applied to construct the sliding surface. The stability analysis of the closed-loop system is also carried out by using singular perturbation methods. Experimental results are conducted with healthy volunteers as well as stroke patients. Quantitative results show a reduction of 45% in terms of root mean square (RMS) error (from 5.9° to [Formula: see text] ) in comparison with PI control scheme, which is similar to that obtained in the literature. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Recreating History with Archimedes and Pi

ERIC Educational Resources Information Center

Santucci, Lora C.

2011-01-01

Using modern technology to examine classical mathematics problems at the high school level can reduce difficult computations and encourage generalizations. When teachers combine historical context with access to technology, they challenge advanced students to think deeply, spark interest in students whose primary interest is not mathematics, and…

Pi2 detection using Empirical Mode Decomposition (EMD)

NASA Astrophysics Data System (ADS)

Mieth, Johannes Z. D.; Frühauff, Dennis; Glassmeier, Karl-Heinz

2017-04-01

Empirical Mode Decomposition has been used as an alternative method to wavelet transformation to identify onset times of Pi2 pulsations in data sets of the Scandinavian Magnetometer Array (SMA). Pi2 pulsations are magnetohydrodynamic waves occurring during magnetospheric substorms. Almost always Pi2 are observed at substorm onset in mid to low latitudes on Earth's nightside. They are fed by magnetic energy release caused by dipolarization processes. Their periods lie between 40 to 150 seconds. Usually, Pi2 are detected using wavelet transformation. Here, Empirical Mode Decomposition (EMD) is presented as an alternative approach to the traditional procedure. EMD is a young signal decomposition method designed for nonlinear and non-stationary time series. It provides an adaptive, data driven, and complete decomposition of time series into slow and fast oscillations. An optimized version using Monte-Carlo-type noise assistance is used here. By displaying the results in a time-frequency space a characteristic frequency modulation is observed. This frequency modulation can be correlated with the onset of Pi2 pulsations. A basic algorithm to find the onset is presented. Finally, the results are compared to classical wavelet-based analysis. The use of different SMA stations furthermore allows the spatial analysis of Pi2 onset times. EMD mostly finds application in the fields of engineering and medicine. This work demonstrates the applicability of this method to geomagnetic time series.

Current advance methods for the identification of blast resistance genes in rice.

PubMed

Tanweer, Fatah A; Rafii, Mohd Y; Sijam, Kamaruzaman; Rahim, Harun A; Ahmed, Fahim; Latif, Mohammad A

2015-05-01

Rice blast caused by Magnaporthe oryzae is one of the most devastating diseases of rice around the world and crop losses due to blast are considerably high. Many blast resistant rice varieties have been developed by classical plant breeding and adopted by farmers in various rice-growing countries. However, the variability in the pathogenicity of the blast fungus according to environment made blast disease a major concern for farmers, which remains a threat to the rice industry. With the utilization of molecular techniques, plant breeders have improved rice production systems and minimized yield losses. In this article, we have summarized the current advanced molecular techniques used for controlling blast disease. With the advent of new technologies like marker-assisted selection, molecular mapping, map-based cloning, marker-assisted backcrossing and allele mining, breeders have identified more than 100 Pi loci and 350 QTL in rice genome responsible for blast disease. These Pi genes and QTLs can be introgressed into a blast-susceptible cultivar through marker-assisted backcross breeding. These molecular techniques provide timesaving, environment friendly and labour-cost-saving ways to control blast disease. The knowledge of host-plant interactions in the frame of blast disease will lead to develop resistant varieties in the future. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Transport Pathways—Proton Motive Force Interrelationship in Durum Wheat Mitochondria

PubMed Central

Trono, Daniela; Laus, Maura N.; Soccio, Mario; Pastore, Donato

2014-01-01

In durum wheat mitochondria (DWM) the ATP-inhibited plant mitochondrial potassium channel (PmitoKATP) and the plant uncoupling protein (PUCP) are able to strongly reduce the proton motive force (pmf) to control mitochondrial production of reactive oxygen species; under these conditions, mitochondrial carriers lack the driving force for transport and should be inactive. However, unexpectedly, DWM uncoupling by PmitoKATP neither impairs the exchange of ADP for ATP nor blocks the inward transport of Pi and succinate. This uptake may occur via the plant inner membrane anion channel (PIMAC), which is physiologically inhibited by membrane potential, but unlocks its activity in de-energized mitochondria. Probably, cooperation between PIMAC and carriers may accomplish metabolite movement across the inner membrane under both energized and de-energized conditions. PIMAC may also cooperate with PmitoKATP to transport ammonium salts in DWM. Interestingly, this finding may trouble classical interpretation of in vitro mitochondrial swelling; instead of free passage of ammonia through the inner membrane and proton symport with Pi, that trigger metabolite movements via carriers, transport of ammonium via PmitoKATP and that of the counteranion via PIMAC may occur. Here, we review properties, modulation and function of the above reported DWM channels and carriers to shed new light on the control that they exert on pmf and vice-versa. PMID:24821541

X-ray emission from an Ap star /Phi Herculis/ and a late B star /Pi Ceti/

NASA Technical Reports Server (NTRS)

Cash, W.; Snow, T. P., Jr.; Charles, P.

1979-01-01

Using the HEAO 1 soft X-ray sky survey, a search was conducted for X-ray emission from 18 stars in the spectral range B5-A7. The detection of 0.25 keV X-ray sources consistent with the positions of Pi Ceti, a normal B7 V star, and Phi Herculis, a classic Ap star was reported. The detection of these stars argues for large mass motions in the upper layers of stars in this spectral range, and argues against radiative diffusion as the source of abundance anomalies in Ap stars.

X-38 Application of Dynamic Inversion Flight Control

NASA Technical Reports Server (NTRS)

Wacker, Roger; Munday, Steve; Merkle, Scott

2001-01-01

This paper summarizes the application of a nonlinear dynamic inversion (DI) flight control system (FCS) to an autonomous flight test vehicle in NASA's X-38 Project, a predecessor to the International Space Station (ISS) Crew Return Vehicle (CRV). Honeywell's Multi-Application Control-H (MACH) is a parameterized FCS design architecture including both model-based DI rate-compensation and classical P+I command-tracking. MACH was adopted by X-38 in order to shorten the design cycle time for different vehicle shapes and flight envelopes and evolving aerodynamic databases. Specific design issues and analysis results are presented for the application of MACH to the 3rd free flight (FF3) of X-38 Vehicle 132 (V132). This B-52 drop test, occurring on March 30, 2000, represents the first flight test of MACH and one of the first few known applications of DI in the primary FCS of an autonomous flight test vehicle.

Regulatory parameters of the lung immune response during the early phase of experimental trichinellosis.

PubMed

Falduto, Guido H; Vila, Cecilia C; Saracino, María P; Gentilini, María V; Venturiello, Stella M

2016-11-15

Parasitic infection caused by Trichinella spiralis provokes an early stimulation of the mucosal immune system which causes an allergic inflammatory response in the lungs. The present work was intended to characterize the kinetics of emergence of regulatory parameters in Wistar rat lungs during this early inflammatory response, between days 0 and 13p.i. The presence of regulatory cells such as regulatory T cells (Tregs) and alternatively activated macrophages (AAM) was analyzed in lung cell suspensions. Moreover, a regulatory cytokine (TGF-β) was studied in lung tissue extracts. Considering that newborn larvae (NBL) travel along the pulmonary microvasculature, the ability of this parasite stage to modulate the activation of lung macrophages was evaluated. For this purpose, lung macrophages from non-infected or infected rats (day 6p.i.) were cultured with live or dead NBL. Arginase activity (characteristic of AAM) and nitric oxide (NO produced by iNOS, characteristic of classical activated macrophages) were measured after 48h. Our results revealed a significant increase in the percentage of Tregs on days 6 and 13p.i., arginase activity on day 13p.i. and TGF-β levels on days 6 and 13p.i. Lung macrophages from non-infected rats cultured with live NBL showed a significant increase in arginase activity and NO levels. Live and dead NBL induced a significant increase in arginase activity in lung macrophages from infected rats. Only live NBL significantly increased NO levels in these macrophages. The present work demonstrates for the first time, the emergence of regulatory parameters in the early lung immune response during T. spiralis infection. The immumodulatory properties exerted by NBL during its passage through this organ could be the cause of such regulation. Moreover, we have shown the ability of NBL to activate macrophages from the lung parenchyma by the classical and alternative pathways. Copyright © 2016 Elsevier B.V. All rights reserved.

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...

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.

An RNA-Seq Transcriptome Analysis of Orthophosphate-Deficient White Lupin Reveals Novel Insights into Phosphorus Acclimation in Plants1[W][OA

PubMed Central

O’Rourke, Jamie A.; Yang, S. Samuel; Miller, Susan S.; Bucciarelli, Bruna; Liu, Junqi; Rydeen, Ariel; Bozsoki, Zoltan; Uhde-Stone, Claudia; Tu, Zheng Jin; Allan, Deborah; Gronwald, John W.; Vance, Carroll P.

2013-01-01

Phosphorus, in its orthophosphate form (Pi), is one of the most limiting macronutrients in soils for plant growth and development. However, the whole-genome molecular mechanisms contributing to plant acclimation to Pi deficiency remain largely unknown. White lupin (Lupinus albus) has evolved unique adaptations for growth in Pi-deficient soils, including the development of cluster roots to increase root surface area. In this study, we utilized RNA-Seq technology to assess global gene expression in white lupin cluster roots, normal roots, and leaves in response to Pi supply. We de novo assembled 277,224,180 Illumina reads from 12 complementary DNA libraries to build what is to our knowledge the first white lupin gene index (LAGI 1.0). This index contains 125,821 unique sequences with an average length of 1,155 bp. Of these sequences, 50,734 were transcriptionally active (reads per kilobase per million reads ≥ 3), representing approximately 7.8% of the white lupin genome, using the predicted genome size of Lupinus angustifolius as a reference. We identified a total of 2,128 sequences differentially expressed in response to Pi deficiency with a 2-fold or greater change and P ≤ 0.05. Twelve sequences were consistently differentially expressed due to Pi deficiency stress in three species, Arabidopsis (Arabidopsis thaliana), potato (Solanum tuberosum), and white lupin, making them ideal candidates to monitor the Pi status of plants. Additionally, classic physiological experiments were coupled with RNA-Seq data to examine the role of cytokinin and gibberellic acid in Pi deficiency-induced cluster root development. This global gene expression analysis provides new insights into the biochemical and molecular mechanisms involved in the acclimation to Pi deficiency. PMID:23197803

Response statistics of rotating shaft with non-linear elastic restoring forces by path integration

NASA Astrophysics Data System (ADS)

Gaidai, Oleg; Naess, Arvid; Dimentberg, Michael

2017-07-01

Extreme statistics of random vibrations is studied for a Jeffcott rotor under uniaxial white noise excitation. Restoring force is modelled as elastic non-linear; comparison is done with linearized restoring force to see the force non-linearity effect on the response statistics. While for the linear model analytical solutions and stability conditions are available, it is not generally the case for non-linear system except for some special cases. The statistics of non-linear case is studied by applying path integration (PI) method, which is based on the Markov property of the coupled dynamic system. The Jeffcott rotor response statistics can be obtained by solving the Fokker-Planck (FP) equation of the 4D dynamic system. An efficient implementation of PI algorithm is applied, namely fast Fourier transform (FFT) is used to simulate dynamic system additive noise. The latter allows significantly reduce computational time, compared to the classical PI. Excitation is modelled as Gaussian white noise, however any kind distributed white noise can be implemented with the same PI technique. Also multidirectional Markov noise can be modelled with PI in the same way as unidirectional. PI is accelerated by using Monte Carlo (MC) estimated joint probability density function (PDF) as initial input. Symmetry of dynamic system was utilized to afford higher mesh resolution. Both internal (rotating) and external damping are included in mechanical model of the rotor. The main advantage of using PI rather than MC is that PI offers high accuracy in the probability distribution tail. The latter is of critical importance for e.g. extreme value statistics, system reliability, and first passage probability.

Accelerated path-integral simulations using ring-polymer interpolation

NASA Astrophysics Data System (ADS)

Buxton, Samuel J.; Habershon, Scott

2017-12-01

Imaginary-time path-integral (PI) molecular simulations can be used to calculate exact quantum statistical mechanical properties for complex systems containing many interacting atoms and molecules. The limiting computational factor in a PI simulation is typically the evaluation of the potential energy surface (PES) and forces at each ring-polymer "bead"; for an n-bead ring-polymer, a PI simulation is typically n times greater than the corresponding classical simulation. To address the increased computational effort of PI simulations, several approaches have been developed recently, most notably based on the idea of ring-polymer contraction which exploits either the separation of the PES into short-range and long-range contributions or the availability of a computationally inexpensive PES which can be incorporated to effectively smooth the ring-polymer PES; neither approach is satisfactory in applications to systems modeled by PESs given by on-the-fly ab initio calculations. In this article, we describe a new method, ring-polymer interpolation (RPI), which can be used to accelerate PI simulations without any prior assumptions about the PES. In simulations of liquid water modeled by an empirical PES (or force field) under ambient conditions, where quantum effects are known to play a subtle role in influencing experimental observables such as radial distribution functions, we find that RPI can accurately reproduce the results of fully-converged PI simulations, albeit with far fewer PES evaluations. This approach therefore opens the possibility of large-scale PI simulations using ab initio PESs evaluated on-the-fly without the drawbacks of current methods.

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 Laws for a Dual-Spin Stabilized Platform

NASA Technical Reports Server (NTRS)

Lim, K. B.; Moerder, D. D.

2008-01-01

This paper describes two attitude control laws suitable for atmospheric flight vehicles with a steady angular momentum bias in the vehicle yaw axis. This bias is assumed to be provided by an internal flywheel, and is introduced to enhance roll and pitch stiffness. The first control law is based on Lyapunov stability theory, and stability proofs are given. The second control law, which assumes that the angular momentum bias is large, is based on a classical PID control. It is shown that the large yaw-axis bias requires that the PI feedback component on the roll and pitch angle errors be cross-fed. Both control laws are applied to a vehicle simulation in the presence of disturbances for several values of yaw-axis angular momentum bias. It is seen that both control laws provide a significant improvement in attitude performance when the bias is sufficiently large, but the nonlinear control law is also able to provide improved performance for a small value of bias. This is important because the smaller bias corresponds to a smaller requirement for mass to be dedicated to the flywheel.

LINC-NIRVANA piston control elements

NASA Astrophysics Data System (ADS)

Brix, Mario; Pott, Jörg-Uwe; Bertram, Thomas; Rost, Steffen; Borelli, Jose Luis; Herbst, Thomas M.; Kuerster, Martin; Rohloff, Ralf-Rainer

2010-07-01

We review the status of hardware developments related to the Linc-Nirvana optical path difference (OPD) control. The status of our telescope vibration measurements is given. We present the design concept of a feed-forward loop to damp the impact of telescope mirror vibrations on the OPD seen by Linc-Nirvana. At the focus of the article is a description of the actuator of the OPD control loop. The weight and vibration optimized construction of this actuator (aka piston mirror) and its mount has a complex dynamical behavior, which prevents classical PI feedback control from delivering fast and precise motion of the mirror surface. Therefore, an H-; optimized control strategy will be applied, custom designed for the piston mirror. The effort of realizing a custom controller on a DSP to drive the piezo is balanced by the outlook of achieving more than 5x faster servo bandwidths. The laboratory set-up to identify the system, and verify the closed loop control performance is presented. Our goal is to achieve 30 Hz closed-loop control bandwidth at a precision of 30 nm.

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.

Gravitational vacuum condensate stars.

PubMed

Mazur, Pawel O; Mottola, Emil

2004-06-29

A new final state of gravitational collapse is proposed. By extending the concept of Bose-Einstein condensation to gravitational systems, a cold, dark, compact object with an interior de Sitter condensate p(v) = -rho(v) and an exterior Schwarzschild geometry of arbitrary total mass M is constructed. These regions are separated by a shell with a small but finite proper thickness l of fluid with equation of state p = +rho, replacing both the Schwarzschild and de Sitter classical horizons. The new solution has no singularities, no event horizons, and a global time. Its entropy is maximized under small fluctuations and is given by the standard hydrodynamic entropy of the thin shell, which is of the order k(B)lMc/Planck's over 2 pi, instead of the Bekenstein-Hawking entropy formula, S(BH) = 4 pi k(B)GM(2)/Planck's over 2 pi c. Hence, unlike black holes, the new solution is thermodynamically stable and has no information paradox.

pi-Turns: types, systematics and the context of their occurrence in protein structures.

PubMed

Dasgupta, Bhaskar; Chakrabarti, Pinak

2008-09-22

For a proper understanding of protein structure and folding it is important to know if a polypeptide segment adopts a conformation inherent in the sequence or it depends on the context of its flanking secondary structures. Turns of various lengths have been studied and characterized starting from three-residue gamma-turn to six-residue pi-turn. The Schellman motif occurring at the C-terminal end of alpha-helices is a classical example of hydrogen bonded pi-turn involving residues at (i) and (i+5) positions. Hydrogen bonded and non-hydrogen bonded beta- and alpha-turns have been identified previously; likewise, a systematic characterization of pi-turns would provide valuable insight into turn structures. An analysis of protein structures indicates that at least 20% of pi-turns occur independent of the Schellman motif. The two categories of pi-turns, designated as pi-HB and SCH, have been further classified on the basis of backbone conformation and both have AAAa as the major class. They differ in the residue usage at position (i+1), the former having a large preference for Pro that is absent in the latter. As in the case of shorter length beta- and alpha-turns, pi-turns have also been identified not only on the basis of the existence of hydrogen bond, but also using the distance between terminal C alpha-atoms, and this resulted in a comparable number of non-hydrogen-bonded pi-turns (pi-NHB). The presence of shorter beta- and alpha-turns within all categories of pi-turns, the subtle variations in backbone torsion angles along the turn residues, the location of the turns in the context of tertiary structures have been studied. pi-turns have been characterized, first using hydrogen bond and the distance between C alpha atoms of the terminal residues, and then using backbone torsion angles. While the Schellman motif has a structural role in helix termination, many of the pi-HB turns, being located on surface cavities, have functional role and there is also sequence conservation.

Pleth variability index and respiratory system compliance to direct PEEP settings in mechanically ventilated patients, an exploratory study.

PubMed

Zhou, Jing; Han, Yi

2016-01-01

To analyze the ability of pleth variability index (PVI) and respiratory system compliance (RSC) on evaluating the hemodynamic and respiratory effects of positive end expiratory pressure (PEEP), then to direct PEEP settings in mechanically ventilated critical patients. We studied 22 mechanically ventilated critical patients in the intensive care unit. Patients were monitored with classical monitor and a pulse co-oximeter, with pulse sensors attached to patients' index fingers. Hemodynamic data [heart rate (HR), perfusion index (PI), PVI, central venous pressure (CVP), mean arterial pressure (MAP), peripheral blood oxygen saturation (SPO2), peripheral blood oxygen content (SPOC) and peripheral blood hemoglobin (SPHB)] as well as the respiratory data [respiratory rate (RR), tidal volume (VT), RSC and controlled airway pressure] were recorded for 15 min each at 3 different levels of PEEP (0, 5 and 10 cmH2O). Different levels of PEEP (0, 5 and 10 cmH2O) had no obvious effect on RR, HR, MAP, SPO2 and SPOC. However, 10 cmH2O PEEP induced significant hemodynamic disturbances, including decreases of PI, and increases of both PVI and CVP. Meanwhile, 5 cmH2O PEEP induced no significant changes on hemodynamics such as CVP, PI and PVI, but improved the RSC. RSC and PVI may be useful in detecting the hemodynamic and respiratory effects of PEEP, thus may help clinicians individualize PEEP settings in mechanically ventilated patients.

Phosphatidyl-Inositol-3 Kinase Inhibitors Regulate Peptidoglycan-Induced Myeloid Leukocyte Recruitment, Inflammation, and Neurotoxicity in Mouse Brain.

PubMed

Arroyo, Daniela S; Gaviglio, Emilia A; Peralta Ramos, Javier M; Bussi, Claudio; Avalos, Maria P; Cancela, Liliana M; Iribarren, Pablo

2018-01-01

Acute brain injury leads to the recruitment and activation of immune cells including resident microglia and infiltrating peripheral myeloid cells (MC), which contribute to the inflammatory response involved in neuronal damage. We previously reported that TLR2 stimulation by peptidoglycan (PGN) from Staphylococcus aureus, in vitro and in vivo , induced microglial cell activation followed by autophagy induction. In this report, we evaluated if phosphatidyl-inositol-3 kinase (PI3K) pharmacological inhibitors LY294200 and 3-methyladenine (3-MA) can modulate the innate immune response to PGN in the central nervous system. We found that injection of PGN into the mouse brain parenchyma (caudate putamen) triggered an inflammatory reaction, which involved activation of microglial cells, recruitment of infiltrating MC to injection site, production of pro-inflammatory mediators, and neuronal injury. In addition, we observed the accumulation of LC3B + CD45 + cells and colocalization of LC3B and lysosomal-associated membrane protein 1 in brain cells. Besides, we found that pharmacological inhibitors of PI3K, including the classical autophagy inhibitor 3-MA, reduced the recruitment of MC, microglial cell activation, and neurotoxicity induced by brain PGN injection. Collectively, our results suggest that PI3K pathways and autophagic response may participate in the PGN-induced microglial activation and MC recruitment to the brain. Thus, inhibition of these pathways could be therapeutically targeted to control acute brain inflammatory conditions.

Phosphatidyl-Inositol-3 Kinase Inhibitors Regulate Peptidoglycan-Induced Myeloid Leukocyte Recruitment, Inflammation, and Neurotoxicity in Mouse Brain

PubMed Central

Arroyo, Daniela S.; Gaviglio, Emilia A.; Peralta Ramos, Javier M.; Bussi, Claudio; Avalos, Maria P.; Cancela, Liliana M.; Iribarren, Pablo

2018-01-01

Acute brain injury leads to the recruitment and activation of immune cells including resident microglia and infiltrating peripheral myeloid cells (MC), which contribute to the inflammatory response involved in neuronal damage. We previously reported that TLR2 stimulation by peptidoglycan (PGN) from Staphylococcus aureus, in vitro and in vivo, induced microglial cell activation followed by autophagy induction. In this report, we evaluated if phosphatidyl-inositol-3 kinase (PI3K) pharmacological inhibitors LY294200 and 3-methyladenine (3-MA) can modulate the innate immune response to PGN in the central nervous system. We found that injection of PGN into the mouse brain parenchyma (caudate putamen) triggered an inflammatory reaction, which involved activation of microglial cells, recruitment of infiltrating MC to injection site, production of pro-inflammatory mediators, and neuronal injury. In addition, we observed the accumulation of LC3B+ CD45+ cells and colocalization of LC3B and lysosomal-associated membrane protein 1 in brain cells. Besides, we found that pharmacological inhibitors of PI3K, including the classical autophagy inhibitor 3-MA, reduced the recruitment of MC, microglial cell activation, and neurotoxicity induced by brain PGN injection. Collectively, our results suggest that PI3K pathways and autophagic response may participate in the PGN-induced microglial activation and MC recruitment to the brain. Thus, inhibition of these pathways could be therapeutically targeted to control acute brain inflammatory conditions. PMID:29719536

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.

A Simulation Study of Rater Agreement Measures with 2x2 Contingency Tables

ERIC Educational Resources Information Center

Ato, Manuel; Lopez, Juan Jose; Benavente, Ana

2011-01-01

A comparison between six rater agreement measures obtained using three different approaches was achieved by means of a simulation study. Rater coefficients suggested by Bennet's [sigma] (1954), Scott's [pi] (1955), Cohen's [kappa] (1960) and Gwet's [gamma] (2008) were selected to represent the classical, descriptive approach, [alpha] agreement…

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.

Reexamining the P-Element Invasion of Drosophila melanogaster Through the Lens of piRNA Silencing

PubMed Central

Kelleher, Erin S.

2016-01-01

Transposable elements (TEs) are both important drivers of genome evolution and genetic parasites with potentially dramatic consequences for host fitness. The recent explosion of research on regulatory RNAs reveals that small RNA-mediated silencing is a conserved genetic mechanism through which hosts repress TE activity. The invasion of the Drosophila melanogaster genome by P elements, which happened on a historical timescale, represents an incomparable opportunity to understand how small RNA-mediated silencing of TEs evolves. Repression of P-element transposition emerged almost concurrently with its invasion. Recent studies suggest that this repression is implemented in part, and perhaps predominantly, by the Piwi-interacting RNA (piRNA) pathway, a small RNA-mediated silencing pathway that regulates TE activity in many metazoan germlines. In this review, I consider the P-element invasion from both a molecular and evolutionary genetic perspective, reconciling classic studies of P-element regulation with the new mechanistic framework provided by the piRNA pathway. I further explore the utility of the P-element invasion as an exemplar of the evolution of piRNA-mediated silencing. In light of the highly-conserved role for piRNAs in regulating TEs, discoveries from this system have taxonomically broad implications for the evolution of repression. PMID:27516614

Formal Modeling of Multi-Agent Systems using the Pi-Calculus and Epistemic Logic

NASA Technical Reports Server (NTRS)

Rorie, Toinette; Esterline, Albert

1998-01-01

Multi-agent systems have become important recently in computer science, especially in artificial intelligence (AI). We allow a broad sense of agent, but require at least that an agent has some measure of autonomy and interacts with other agents via some kind of agent communication language. We are concerned in this paper with formal modeling of multi-agent systems, with emphasis on communication. We propose for this purpose to use the pi-calculus, an extension of the process algebra CCS. Although the literature on the pi-calculus refers to agents, the term is used there in the sense of a process in general. It is our contention, however, that viewing agents in the AI sense as agents in the pi-calculus sense affords significant formal insight. One formalism that has been applied to agents in the AI sense is epistemic logic, the logic of knowledge. The success of epistemic logic in computer science in general has come in large part from its ability to handle concepts of knowledge that apply to groups. We maintain that the pi-calculus affords a natural yet rigorous means by which groups that are significant to epistemic logic may be identified, encapsulated, structured into hierarchies, and restructured in a principled way. This paper is organized as follows: Section 2 introduces the pi-calculus; Section 3 takes a scenario from the classical paper on agent-oriented programming [Sh93] and translates it into a very simple subset of the n-calculus; Section 4 then shows how more sophisticated features of the pi-calculus may bc brought into play; Section 5 discusses how the pi-calculus may be used to define groups for epistemic logic; and Section 6 is the conclusion.

An RNA-Seq transcriptome analysis of orthophosphate-deficient white lupin reveals novel insights into phosphorus acclimation in plants.

PubMed

O'Rourke, Jamie A; Yang, S Samuel; Miller, Susan S; Bucciarelli, Bruna; Liu, Junqi; Rydeen, Ariel; Bozsoki, Zoltan; Uhde-Stone, Claudia; Tu, Zheng Jin; Allan, Deborah; Gronwald, John W; Vance, Carroll P

2013-02-01

Phosphorus, in its orthophosphate form (P(i)), is one of the most limiting macronutrients in soils for plant growth and development. However, the whole-genome molecular mechanisms contributing to plant acclimation to P(i) deficiency remain largely unknown. White lupin (Lupinus albus) has evolved unique adaptations for growth in P(i)-deficient soils, including the development of cluster roots to increase root surface area. In this study, we utilized RNA-Seq technology to assess global gene expression in white lupin cluster roots, normal roots, and leaves in response to P(i) supply. We de novo assembled 277,224,180 Illumina reads from 12 complementary DNA libraries to build what is to our knowledge the first white lupin gene index (LAGI 1.0). This index contains 125,821 unique sequences with an average length of 1,155 bp. Of these sequences, 50,734 were transcriptionally active (reads per kilobase per million reads ≥ 3), representing approximately 7.8% of the white lupin genome, using the predicted genome size of Lupinus angustifolius as a reference. We identified a total of 2,128 sequences differentially expressed in response to P(i) deficiency with a 2-fold or greater change and P ≤ 0.05. Twelve sequences were consistently differentially expressed due to P(i) deficiency stress in three species, Arabidopsis (Arabidopsis thaliana), potato (Solanum tuberosum), and white lupin, making them ideal candidates to monitor the P(i) status of plants. Additionally, classic physiological experiments were coupled with RNA-Seq data to examine the role of cytokinin and gibberellic acid in P(i) deficiency-induced cluster root development. This global gene expression analysis provides new insights into the biochemical and molecular mechanisms involved in the acclimation to P(i) deficiency.

Evaluation of the risk of classical swine fever (CSF) spread from backyard pigs to other domestic pigs by using the spatial stochastic disease spread model Be-FAST: the example of Bulgaria.

PubMed

Martínez-López, Beatriz; Ivorra, Benjamin; Ramos, Angel Manuel; Fernández-Carrión, Eduardo; Alexandrov, Tsviatko; Sánchez-Vizcaíno, José Manuel

2013-07-26

The study presented here is one of the very first aimed at exploring the potential spread of classical swine fever (CSF) from backyard pigs to other domestic pigs. Specifically, we used a spatial stochastic spread model, called Be-FAST, to evaluate the potential spread of CSF virus (CSFV) in Bulgaria, which holds a large number of backyards (96% of the total number of pig farms) and is one of the very few countries for which backyard pigs and farm counts are available. The model revealed that, despite backyard pigs being very likely to become infected, infections from backyard pigs to other domestic pigs were rare. In general, the magnitude and duration of the CSF simulated epidemics were small, with a median [95% PI] number of infected farms per epidemic of 1 [1,4] and a median [95% PI] duration of the epidemic of 44 [17,101] days. CSFV transmission occurs primarily (81.16%) due to indirect contacts (i.e. vehicles, people and local spread) whereas detection of infected premises was mainly (69%) associated with the observation of clinical signs on farm rather than with implementation of tracing or zoning. Methods and results of this study may support the implementation of risk-based strategies more cost-effectively to prevent, control and, ultimately, eradicate CSF from Bulgaria. The model may also be easily adapted to other countries in which the backyard system is predominant. It can also be used to simulate other similar diseases such as African swine fever. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins.

PubMed

Turkington, Hannah L; Juozapaitis, Mindaugas; Tsolakos, Nikos; Corrales-Aguilar, Eugenia; Schwemmle, Martin; Hale, Benjamin G

2018-03-01

Recently, two influenza A virus (FLUAV) genomes were identified in Central and South American bats. These sequences exhibit notable divergence from classical FLUAV counterparts, and functionally, bat FLUAV glycoproteins lack canonical receptor binding and destroying activity. Nevertheless, other features that distinguish these viruses from classical FLUAVs have yet to be explored. Here, we studied the viral nonstructural protein NS1, a virulence factor that modulates host signaling to promote efficient propagation. Like all FLUAV NS1 proteins, bat FLUAV NS1s bind double-stranded RNA and act as interferon antagonists. Unexpectedly, we found that bat FLUAV NS1s are unique in being unable to bind host p85β, a regulatory subunit of the cellular metabolism-regulating enzyme, phosphoinositide 3-kinase (PI3K). Furthermore, neither bat FLUAV NS1 alone nor infection with a chimeric bat FLUAV efficiently activates Akt, a PI3K effector. Structure-guided mutagenesis revealed that the bat FLUAV NS1-p85β interaction can be reengineered (in a strain-specific manner) by changing two to four NS1 residues (96L, 99M, 100I, and 145T), thereby creating a hydrophobic patch. Notably, ameliorated p85β-binding is insufficient for bat FLUAV NS1 to activate PI3K, and a chimeric bat FLUAV expressing NS1 with engineered hydrophobic patch mutations exhibits cell-type-dependent, but species-independent, propagation phenotypes. We hypothesize that bat FLUAV hijacking of PI3K in the natural bat host has been selected against, perhaps because genes in this metabolic pathway were differentially shaped by evolution to suit the unique energy use strategies of this flying mammal. These data expand our understanding of the enigmatic functional divergence between bat FLUAVs and classical mammalian and avian FLUAVs. IMPORTANCE The potential for novel influenza A viruses to establish infections in humans from animals is a source of continuous concern due to possible severe outbreaks or pandemics. The recent discovery of influenza A-like viruses in bats has raised questions over whether these entities could be a threat to humans. Understanding unique properties of the newly described bat influenza A-like viruses, such as their mechanisms to infect cells or how they manipulate host functions, is critical to assess their likelihood of causing disease. Here, we characterized the bat influenza A-like virus NS1 protein, a key virulence factor, and found unexpected functional divergence of this protein from counterparts in other influenza A viruses. Our study dissects the molecular changes required by bat influenza A-like virus NS1 to adopt classical influenza A virus properties and suggests consequences of bat influenza A-like virus infection, potential future evolutionary trajectories, and intriguing virus-host biology in bat species. Copyright © 2018 Turkington et al.

Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins

PubMed Central

Turkington, Hannah L.; Juozapaitis, Mindaugas; Tsolakos, Nikos; Corrales-Aguilar, Eugenia; Schwemmle, Martin

2017-01-01

ABSTRACT Recently, two influenza A virus (FLUAV) genomes were identified in Central and South American bats. These sequences exhibit notable divergence from classical FLUAV counterparts, and functionally, bat FLUAV glycoproteins lack canonical receptor binding and destroying activity. Nevertheless, other features that distinguish these viruses from classical FLUAVs have yet to be explored. Here, we studied the viral nonstructural protein NS1, a virulence factor that modulates host signaling to promote efficient propagation. Like all FLUAV NS1 proteins, bat FLUAV NS1s bind double-stranded RNA and act as interferon antagonists. Unexpectedly, we found that bat FLUAV NS1s are unique in being unable to bind host p85β, a regulatory subunit of the cellular metabolism-regulating enzyme, phosphoinositide 3-kinase (PI3K). Furthermore, neither bat FLUAV NS1 alone nor infection with a chimeric bat FLUAV efficiently activates Akt, a PI3K effector. Structure-guided mutagenesis revealed that the bat FLUAV NS1-p85β interaction can be reengineered (in a strain-specific manner) by changing two to four NS1 residues (96L, 99M, 100I, and 145T), thereby creating a hydrophobic patch. Notably, ameliorated p85β-binding is insufficient for bat FLUAV NS1 to activate PI3K, and a chimeric bat FLUAV expressing NS1 with engineered hydrophobic patch mutations exhibits cell-type-dependent, but species-independent, propagation phenotypes. We hypothesize that bat FLUAV hijacking of PI3K in the natural bat host has been selected against, perhaps because genes in this metabolic pathway were differentially shaped by evolution to suit the unique energy use strategies of this flying mammal. These data expand our understanding of the enigmatic functional divergence between bat FLUAVs and classical mammalian and avian FLUAVs. IMPORTANCE The potential for novel influenza A viruses to establish infections in humans from animals is a source of continuous concern due to possible severe outbreaks or pandemics. The recent discovery of influenza A-like viruses in bats has raised questions over whether these entities could be a threat to humans. Understanding unique properties of the newly described bat influenza A-like viruses, such as their mechanisms to infect cells or how they manipulate host functions, is critical to assess their likelihood of causing disease. Here, we characterized the bat influenza A-like virus NS1 protein, a key virulence factor, and found unexpected functional divergence of this protein from counterparts in other influenza A viruses. Our study dissects the molecular changes required by bat influenza A-like virus NS1 to adopt classical influenza A virus properties and suggests consequences of bat influenza A-like virus infection, potential future evolutionary trajectories, and intriguing virus-host biology in bat species. PMID:29237829

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...

Lycium barbarum Polysaccharides Protect against Trimethyltin Chloride-Induced Apoptosis via Sonic Hedgehog and PI3K/Akt Signaling Pathways in Mouse Neuro-2a Cells.

PubMed

Zhao, Wanyun; Pan, Xiaoqi; Li, Tao; Zhang, Changchun; Shi, Nian

2016-01-01

Trimethyltin chloride (TMT) is a classic neurotoxicant that can cause severe neurodegenerative diseases. Some signaling pathways involving cell death play pivotal roles in the central nervous system. In this study, the role of Sonic Hedgehog (Shh) and PI3K/Akt pathways in TMT-induced apoptosis and protective effect of Lycium barbarum polysaccharides (LBP) on mouse neuro-2a (N2a) cells were investigated. Results showed that TMT treatment significantly enhanced apoptosis, upregulated proapoptotic Bax, downregulated antiapoptotic Bcl-2 expression, and increased caspase-3 activity in a dose-dependent manner in N2a cells. TMT induced oxidative stress in cells, performing reactive oxygen species (ROS) and malondialdehyde (MDA) excessive generation, and superoxide dismutase (SOD) activity reduction. TMT significantly decreased phosphorylated glycogen synthase kinase-3β (GSK-3β) and inhibited Shh and PI3K/Akt pathways. However, the addition of LBP upregulated GSK-3β phosphorylation, activated Shh and PI3K/Akt pathways, and eventually reduced apoptosis and oxidative stress caused by TMT. The interaction between Shh and PI3K/Akt pathways was clarified by specific PI3K inhibitor LY294002 or Shh inhibitor GDC-0449. Moreover, LY294002 and GDC-0449 pretreatment both induced phosphorylated GSK-3β downregulation and significantly promoted apoptosis induced by TMT. These results suggest that LBP could reduce TMT-induced N2a cells apoptosis by regulating GSK-3β phosphorylation, Shh, and PI3K/Akt signaling pathways.

Lycium barbarum Polysaccharides Protect against Trimethyltin Chloride-Induced Apoptosis via Sonic Hedgehog and PI3K/Akt Signaling Pathways in Mouse Neuro-2a Cells

PubMed Central

Zhao, Wanyun; Pan, Xiaoqi; Li, Tao; Zhang, Changchun; Shi, Nian

2016-01-01

Trimethyltin chloride (TMT) is a classic neurotoxicant that can cause severe neurodegenerative diseases. Some signaling pathways involving cell death play pivotal roles in the central nervous system. In this study, the role of Sonic Hedgehog (Shh) and PI3K/Akt pathways in TMT-induced apoptosis and protective effect of Lycium barbarum polysaccharides (LBP) on mouse neuro-2a (N2a) cells were investigated. Results showed that TMT treatment significantly enhanced apoptosis, upregulated proapoptotic Bax, downregulated antiapoptotic Bcl-2 expression, and increased caspase-3 activity in a dose-dependent manner in N2a cells. TMT induced oxidative stress in cells, performing reactive oxygen species (ROS) and malondialdehyde (MDA) excessive generation, and superoxide dismutase (SOD) activity reduction. TMT significantly decreased phosphorylated glycogen synthase kinase-3β (GSK-3β) and inhibited Shh and PI3K/Akt pathways. However, the addition of LBP upregulated GSK-3β phosphorylation, activated Shh and PI3K/Akt pathways, and eventually reduced apoptosis and oxidative stress caused by TMT. The interaction between Shh and PI3K/Akt pathways was clarified by specific PI3K inhibitor LY294002 or Shh inhibitor GDC-0449. Moreover, LY294002 and GDC-0449 pretreatment both induced phosphorylated GSK-3β downregulation and significantly promoted apoptosis induced by TMT. These results suggest that LBP could reduce TMT-induced N2a cells apoptosis by regulating GSK-3β phosphorylation, Shh, and PI3K/Akt signaling pathways. PMID:27143997

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.

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

Osovski, Shmuel; Moiseyev, Nimrod

The recent pioneering experiments of the [Nature 412, 52 (2001)] and [Science, 293, 274 (2001)] groups have demonstrated the dynamical tunneling of cold atoms interacting with standing electromagnetic waves. It has been shown [Phys. Rev. Lett. 89, 253201 (2002)], that the tunneling oscillations observed in these experiments correspondingly stems from two- and three-Floquet quantum state mechanism and can be controlled by varying the experimental parameters. The question where are the fingerprints of the classical chaotic dynamics in a quantum dynamical process which is controlled by 2 or 3 quantum states remains open. Our calculations show that although the effective ({Dirac_h}/2{pi})more » associated with the two experiments is large, and the quantum system is far from its semiclassical limit, the quantum Floquet-Bloch quasienergy states still can be classified as regular and chaotic states. In both experiments the quantum and the classical phase-space entropies are quite similar, although the classical phase space is a mixed regular-chaotic space. It is also shown that as the wave packet which is initially localized at one of the two inner regular islands oscillates between them through the chaotic sea, it accumulates a random phase which causes the decay of the amplitude of the oscillating mean momentum, , as measured in both experiments. The extremely high sensitivity of the rate of decay of the oscillations of to the very small changes in the population of different Floquet-Bloch states, is another type of fingerprint of chaos in quantum dynamics that presumably was measured in the NIST and AUSTIN experiments for the first time.« less

A closed-loop photon beam control study for the Advanced Light Source

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

Portmann, G.; Bengtsson, J.

1993-05-01

The third generation Advanced Light Source (ALS) will produce extremely bright photon beams using undulators and wigglers. In order to position the photon beams accurate to the micron level, a closed-loop feedback system is being developed. Using photon position monitors and dipole corrector magnets, a closed-loop system can automatically compensate for modeling uncertainties and exogenous disturbances. The following paper will present a dynamics model for the perturbations of the closed orbit of the electron beam in the ALS storage ring including the vacuum chamber magnetic field penetration effects. Using this reference model, two closed-loop feedback algorithms will be compared --more » a classical PI controller and a two degree-of-freedom approach. The two degree-of-freedom method provides superior disturbance rejection while maintaining the desired performance goals. Both methods will address the need to gain schedule the controller due to the time varying dynamics introduced by changing field strengths when scanning the insertion devices.« less

X-38 Experimental Controls Laws

NASA Technical Reports Server (NTRS)

Munday, Steve; Estes, Jay; Bordano, Aldo J.

2000-01-01

X-38 Experimental Control Laws X-38 is a NASA JSC/DFRC experimental flight test program developing a series of prototypes for an International Space Station (ISS) Crew Return Vehicle, often called an ISS "lifeboat." X- 38 Vehicle 132 Free Flight 3, currently scheduled for the end of this month, will be the first flight test of a modem FCS architecture called Multi-Application Control-Honeywell (MACH), originally developed by the Honeywell Technology Center. MACH wraps classical P&I outer attitude loops around a modem dynamic inversion attitude rate loop. The dynamic inversion process requires that the flight computer have an onboard aircraft model of expected vehicle dynamics based upon the aerodynamic database. Dynamic inversion is computationally intensive, so some timing modifications were made to implement MACH on the slower flight computers of the subsonic test vehicles. In addition to linear stability margin analyses and high fidelity 6-DOF simulation, hardware-in-the-loop testing is used to verify the implementation of MACH and its robustness to aerodynamic and environmental uncertainties and disturbances.

Toward simulating complex systems with quantum effects

NASA Astrophysics Data System (ADS)

Kenion-Hanrath, Rachel Lynn

Quantum effects like tunneling, coherence, and zero point energy often play a significant role in phenomena on the scales of atoms and molecules. However, the exact quantum treatment of a system scales exponentially with dimensionality, making it impractical for characterizing reaction rates and mechanisms in complex systems. An ongoing effort in the field of theoretical chemistry and physics is extending scalable, classical trajectory-based simulation methods capable of capturing quantum effects to describe dynamic processes in many-body systems; in the work presented here we explore two such techniques. First, we detail an explicit electron, path integral (PI)-based simulation protocol for predicting the rate of electron transfer in condensed-phase transition metal complex systems. Using a PI representation of the transferring electron and a classical representation of the transition metal complex and solvent atoms, we compute the outer sphere free energy barrier and dynamical recrossing factor of the electron transfer rate while accounting for quantum tunneling and zero point energy effects. We are able to achieve this employing only a single set of force field parameters to describe the system rather than parameterizing along the reaction coordinate. Following our success in describing a simple model system, we discuss our next steps in extending our protocol to technologically relevant materials systems. The latter half focuses on the Mixed Quantum-Classical Initial Value Representation (MQC-IVR) of real-time correlation functions, a semiclassical method which has demonstrated its ability to "tune'' between quantum- and classical-limit correlation functions while maintaining dynamic consistency. Specifically, this is achieved through a parameter that determines the quantumness of individual degrees of freedom. Here, we derive a semiclassical correction term for the MQC-IVR to systematically characterize the error introduced by different choices of simulation parameters, and demonstrate the ability of this approach to optimize MQC-IVR simulations.

Viète's Formula and an Error Bound without Taylor's Theorem

ERIC Educational Resources Information Center

Boucher, Chris

2018-01-01

This note presents a derivation of Viète's classic product approximation of pi that relies on only the Pythagorean Theorem. We also give a simple error bound for the approximation that, while not optimal, still reveals the exponential convergence of the approximation and whose derivation does not require Taylor's Theorem.

Case studies on design, simulation and visualization of control and measurement applications using REX control system

NASA Astrophysics Data System (ADS)

Ozana, Stepan; Pies, Martin; Docekal, Tomas

2016-06-01

REX Control System is a professional advanced tool for design and implementation of complex control systems that belongs to softPLC category. It covers the entire process starting from simulation of functionality of the application before deployment, through implementation on real-time target, towards analysis, diagnostics and visualization. Basically it consists of two parts: the development tools and the runtime system. It is also compatible with Simulink environment, and the way of implementation of control algorithm is very similar. The control scheme is finally compiled (using RexDraw utility) and uploaded into a chosen real-time target (using RexView utility). There is a wide variety of hardware platforms and real-time operating systems supported by REX Control System such as for example Windows Embedded, Linux, Linux/Xenomai deployed on SBC, IPC, PAC, Raspberry Pi and others with many I/O interfaces. It is modern system designed both for measurement and control applications, offering a lot of additional functions concerning data archiving, visualization based on HTML5, and communication standards. The paper will sum up possibilities of its use in educational process, focused on control of case studies of physical models with classical and advanced control algorithms.

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

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.

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.

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

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.

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

Pi (Spleen)-deficiency syndrome in tumor microenvironment is the pivotal pathogenesis of colorectal cancer immune escape.

PubMed

Sun, Xue-Gang; Lin, Xiao-Chang; Diao, Jian-Xin; Yu, Zhi-Ling; Li, Kun

2016-10-01

Cancer immunoediting consists of three sequential phases: elimination, equilibrium, and escape. For colorectal adenoma-carcinoma sequence, the adenoma dysplastic progression may represent an equilibrium phase and the cancer stage as escape phase. Immune system eliminates transformed enterocytes by destroying them at first, sculpts them at the same time and selects the variants subsequently that are no longer recognized and insensitive to immune effectors, and finally induces immunosuppressive state within the tumor microenvironment that facilitates immune escape and tumor outgrowth. Immunosuppression and inflammation are the two crucial features of Pi (Spleen)-deficiency. Classic quotations, immune evidence and clinical observations suggest that Spleen (but not other organs) deficiency is the key pathogenesis of colorectal cancer (CRC) microenvironment. Weakness of old age, immunosuppressive cytokines from chronic inflammation, tumor-derived immunosuppressive factors and surrendered immune cells-regulatory T cells, myeloid-derived suppressor cells and tumor associated macrophages (TAMs) constitutes CRC microenvironment of Pi-deficiency. Furthermore, excess in superficiality, such as phlegm stagnation, blood stasis and toxin accumulation are induced by chronic inflammation on the basis of asthenia in origin, an immunosuppressive state. Great masters of Chinese medicine emphasize that strengthen Pi is the chief therapeutic principle for CRC which receives good therapeutic effects. So, Pi-deficiency based syndrome is the pivotal pathogenesis of tumor microenvironment. The immunosuppressive microenvironment facilitates immune escape which play an important role in the transition from adenoma to adenocarcinoma. There are some signs that strengthen Pi based treatment has potential capacity to ameliorate tumor environment. It might be a novel starting point to explore the mechanism of strengthen Pi based therapy in the prevention and treatment of CRC through regulation of tumor environment and immunoediting.

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.

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

Classical r matrix of the su(2 vertical bar 2) super Yang-Mills spin chain

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

Torrielli, Alessandro

2007-05-15

In this note we straightforwardly derive and make use of the quantum R matrix for the su(2 vertical bar 2) super Yang-Mills spin chain in the manifest su(1 vertical bar 2)-invariant formulation, which solves the standard quantum Yang-Baxter equation, in order to obtain the correspondent (undressed) classical r matrix from the first order expansion in the 'deformation' parameter 2{pi}/{radical}({lambda}) and check that this last solves the standard classical Yang-Baxter equation. We analyze its bialgebra structure, its dependence on the spectral parameters, and its pole structure. We notice that it still preserves an su(1 vertical bar 2) subalgebra, thereby admitting anmore » expression in terms of a combination of projectors, which spans only a subspace of su(1 vertical bar 2)xsu(1 vertical bar 2). We study the residue at its simple pole at the origin and comment on the applicability of the classical Belavin-Drinfeld type of analysis.« less

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.

Fuzzy-PI-based centralised control of semi-isolated FP-SEPIC/ZETA BDC in a PV/battery hybrid system

NASA Astrophysics Data System (ADS)

Mahendran, Venmathi; Ramabadran, Ramaprabha

2016-11-01

Multiport converters with centralised controller have been most commonly used in stand-alone photovoltaic (PV)/battery hybrid system to supply the load smoothly without any disturbances. This study presents the performance analysis of four-port SEPIC/ZETA bidirectional converter (FP-SEPIC/ZETA BDC) using various types of centralised control schemes like Fuzzy tuned proportional integral controller (Fuzzy-PI), fuzzy logic controller (FLC) and conventional proportional integral (PI) controller. The proposed FP-SEPIC/ZETA BDC with various control strategy is derived for simultaneous power management of a PV source using distributed maximum power point tracking (DMPPT) algorithm, a rechargeable battery, and a load by means of centralised controller. The steady state and the dynamic response of the FP-SEPIC/ZETA BDC are analysed using three different types of controllers under line and load regulation. The Fuzzy-PI-based control scheme improves the dynamic response of the system when compared with the FLC and the conventional PI controller. The power balance between the ports is achieved by pseudorandom carrier modulation scheme. The response of the FP-SEPIC/ZETA BDC is also validated experimentally using hardware prototype model of 500 W system. The effectiveness of the control strategy is validated using simulation and experimental results.

Balance point characterization of interstitial fluid volume regulation.

PubMed

Dongaonkar, R M; Laine, G A; Stewart, R H; Quick, C M

2009-07-01

The individual processes involved in interstitial fluid volume and protein regulation (microvascular filtration, lymphatic return, and interstitial storage) are relatively simple, yet their interaction is exceedingly complex. There is a notable lack of a first-order, algebraic formula that relates interstitial fluid pressure and protein to critical parameters commonly used to characterize the movement of interstitial fluid and protein. Therefore, the purpose of the present study is to develop a simple, transparent, and general algebraic approach that predicts interstitial fluid pressure (P(i)) and protein concentrations (C(i)) that takes into consideration all three processes. Eight standard equations characterizing fluid and protein flux were solved simultaneously to yield algebraic equations for P(i) and C(i) as functions of parameters characterizing microvascular, interstitial, and lymphatic function. Equilibrium values of P(i) and C(i) arise as balance points from the graphical intersection of transmicrovascular and lymph flows (analogous to Guyton's classical cardiac output-venous return curves). This approach goes beyond describing interstitial fluid balance in terms of conservation of mass by introducing the concept of inflow and outflow resistances. Algebraic solutions demonstrate that P(i) and C(i) result from a ratio of the microvascular filtration coefficient (1/inflow resistance) and effective lymphatic resistance (outflow resistance), and P(i) is unaffected by interstitial compliance. These simple algebraic solutions predict P(i) and C(i) that are consistent with reported measurements. The present work therefore presents a simple, transparent, and general balance point characterization of interstitial fluid balance resulting from the interaction of microvascular, interstitial, and lymphatic function.

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.

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.

Ceratocystis cacaofunesta genome analysis reveals a large expansion of extracellular phosphatidylinositol-specific phospholipase-C genes (PI-PLC).

PubMed

Molano, Eddy Patricia Lopez; Cabrera, Odalys García; Jose, Juliana; do Nascimento, Leandro Costa; Carazzolle, Marcelo Falsarella; Teixeira, Paulo José Pereira Lima; Alvarez, Javier Correa; Tiburcio, Ricardo Augusto; Tokimatu Filho, Paulo Massanari; de Lima, Gustavo Machado Alvares; Guido, Rafael Victório Carvalho; Corrêa, Thamy Lívia Ribeiro; Leme, Adriana Franco Paes; Mieczkowski, Piotr; Pereira, Gonçalo Amarante Guimarães

2018-01-17

The Ceratocystis genus harbors a large number of phytopathogenic fungi that cause xylem parenchyma degradation and vascular destruction on a broad range of economically important plants. Ceratocystis cacaofunesta is a necrotrophic fungus responsible for lethal wilt disease in cacao. The aim of this work is to analyze the genome of C. cacaofunesta through a comparative approach with genomes of other Sordariomycetes in order to better understand the molecular basis of pathogenicity in the Ceratocystis genus. We present an analysis of the C. cacaofunesta genome focusing on secreted proteins that might constitute pathogenicity factors. Comparative genome analyses among five Ceratocystidaceae species and 23 other Sordariomycetes fungi showed a strong reduction in gene content of the Ceratocystis genus. However, some gene families displayed a remarkable expansion, in particular, the Phosphatidylinositol specific phospholipases-C (PI-PLC) family. Also, evolutionary rate calculations suggest that the evolution process of this family was guided by positive selection. Interestingly, among the 82 PI-PLCs genes identified in the C. cacaofunesta genome, 70 genes encoding extracellular PI-PLCs are grouped in eight small scaffolds surrounded by transposon fragments and scars that could be involved in the rapid evolution of the PI-PLC family. Experimental secretome using LC-MS/MS validated 24% (86 proteins) of the total predicted secretome (342 proteins), including four PI-PLCs and other important pathogenicity factors. Analysis of the Ceratocystis cacaofunesta genome provides evidence that PI-PLCs may play a role in pathogenicity. Subsequent functional studies will be aimed at evaluating this hypothesis. The observed genetic arsenals, together with the analysis of the PI-PLC family shown in this work, reveal significant differences in the Ceratocystis genome compared to the classical vascular fungi, Verticillium and Fusarium. Altogether, our analyses provide new insights into the evolution and the molecular basis of plant pathogenicity.

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.

In Vitro Determination of Prebiotic Properties of Oligosaccharides Derived from an Orange Juice Manufacturing By-Product Stream

PubMed Central

Manderson, K.; Pinart, M.; Tuohy, K. M.; Grace, W. E.; Hotchkiss, A. T.; Widmer, W.; Yadhav, M. P.; Gibson, G. R.; Rastall, R. A.

2005-01-01

Fermentation properties of oligosaccharides derived from orange peel pectin were assessed in mixed fecal bacterial culture. The orange peel oligosaccharide fraction contained glucose in addition to rhamnogalacturonan and xylogalacturonan pectic oligosaccharides. Twenty-four-hour, temperature- and pH-controlled, stirred anaerobic fecal batch cultures were used to determine the effects that oligosaccharides derived from orange products had on the composition of the fecal microbiota. The effects were measured through fluorescent in situ hybridization to determine changes in bacterial populations, fermentation end products were analyzed by high-performance liquid chromatography to assess short-chain fatty acid concentrations, and subsequently, a prebiotic index (PI) was determined. Pectic oligosaccharides (POS) were able to increase the bifidobacterial and Eubacterium rectale numbers, albeit resulting in a lower prebiotic index than that from fructo-oligosaccharide metabolism. Orange albedo maintained the growth of most bacterial populations and gave a PI similar to that of soluble starch. Fermentation of POS resulted in an increase in the Eubacterium rectale numbers and concomitantly increased butyrate production. In conclusion, this study has shown that POS can have a beneficial effect on the fecal microflora; however, a classical prebiotic effect was not found. An increase in the Eubacterium rectale population was found, and butyrate levels increased, which is of potential benefit to the host. PMID:16332825

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

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

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.

Fast Implicit Methods For Elliptic Moving Interface Problems

DTIC Science & Technology

2015-12-11

analyzed, and tested for the Fourier transform of piecewise polynomials given on d-dimensional simplices in D-dimensional Euclidean space. These transforms...evaluation, and one to three orders of magnitude slower than the classical uniform Fast Fourier Transform. Second, bilinear quadratures ---which...a fast algorithm was derived, analyzed, and tested for the Fourier transform of pi ecewise polynomials given on d-dimensional simplices in D

Long-term changes in forest composition and diversity following early logging (1919-1923) and the decline of American chestnut (Castanea dentata)

Treesearch

Katherine J. Elliott; Wayne T. Swank

2008-01-01

Chestnut blight fungus (Endothia parasitica [Murr.] P.I. And. & H.W. And. is a classic example of an invasive species, which severely damaged populations of its host, Castanea dentata, and had widespread and long-term impacts on eastern North American forests. Concurrently, forests were further disturbed by lumbering, which was common across the...

Design and Implementation of a Discrete-Time Proportional Integral (PI) Controller for the Temperature Control of a Heating Pad.

PubMed

Khan, Pathan Fayaz; Sengottuvel, S; Patel, Rajesh; Gireesan, K; Baskaran, R; Mani, Awadhesh

2018-05-01

Contact heat evoked potentials (CHEPs) are recorded from the brain by giving thermal stimulations through heating pads kept on the surface of the skin. CHEP signals have crucial diagnostic implications in human pain activation studies. This work proposes a novel design of a digital proportional integral (PI) controller based on Arduino microcontroller with a view to explore the suitability of an electric heating pad for use as a thermode in a custom-made, cost-effective CHEP stimulator. The purpose of PI controller is to set, regulate, and deliver desired temperatures on the surface of the heating pad in a user-defined pattern. The transfer function of the heating system has been deduced using the parametric system identification method, and the design parameters of the controller have been identified using the root locus technique. The efficiency of the proposed PI controller in circumventing the well-known integrator windup problem (error in the integral term builds excessively, leading to large transients in the controller output) in tracking the reference input and the controller effort (CE) in rejecting output disturbances to maintain the set temperature of the heating pad have been found to be superior compared with the conventional PI controller and two of the existing anti-windup models.

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.

Group B Streptococcus serotypes III and V induce apoptosis and necrosis of human epithelial A549 cells.

PubMed

Da Costa, Andréia Ferreira Eduardo; Pereira, Camila Serva; Santos, Gabriela Da Silva; Carvalho, Técia Maria Ulisses; Hirata, Raphael; De Mattos-Guaraldi, Ana Luiza; Rosa, Ana Cláudia De Paula; Nagao, Prescilla Emy

2011-05-01

Although group B Streptococcus (GBS) has been classically described as an exclusively extracellular pathogen, growing evidence suggests that it may be internalized by epithelial cells. However, the fates of intracellular GBS and of infected respiratory epithelial cells remain unclear. Little is known about the bacterial components involved in these processes. The present study investigated the bacterial internalization by A549 cells and the apoptosis/necrosis of the infected human epithelial cells. The morphological changes in A549 cells observed from 2 h post-infection with GBS included vacuolization and the formation of apoptotic bodies. Flow cytometry revealed that 81.2% of apoptotic A549 cells were infected with GBS serotype III 90356-liquor. Moreover, a double-staining assay using propidium iodide (PI)/Annexin V (AV) gave information about the numbers of viable (PI-/AV-) (18.27%) vs. early apoptotic (PI-/AV+) (73.83%) and late apoptotic cells (PI+/AV+) (7.37%) during infection of A549 cells with GBS III 90356-liquor. In addition, 37% necrotic cells were observed in A549 cells infected with GBS serotype V 90186-blood. In conclusion, GBS serotypes III and V induce apoptosis of epithelial cells in the early stages of GBS infection, resulting in tissue destruction, bacterial spreading and, in consequence, invasive disease or systemic infection.

Case studies on design, simulation and visualization of control and measurement applications using REX control system

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

Ozana, Stepan, E-mail: stepan.ozana@vsb.cz; Pies, Martin, E-mail: martin.pies@vsb.cz; Docekal, Tomas, E-mail: docekalt@email.cz

REX Control System is a professional advanced tool for design and implementation of complex control systems that belongs to softPLC category. It covers the entire process starting from simulation of functionality of the application before deployment, through implementation on real-time target, towards analysis, diagnostics and visualization. Basically it consists of two parts: the development tools and the runtime system. It is also compatible with Simulink environment, and the way of implementation of control algorithm is very similar. The control scheme is finally compiled (using RexDraw utility) and uploaded into a chosen real-time target (using RexView utility). There is a widemore » variety of hardware platforms and real-time operating systems supported by REX Control System such as for example Windows Embedded, Linux, Linux/Xenomai deployed on SBC, IPC, PAC, Raspberry Pi and others with many I/O interfaces. It is modern system designed both for measurement and control applications, offering a lot of additional functions concerning data archiving, visualization based on HTML5, and communication standards. The paper will sum up possibilities of its use in educational process, focused on control of case studies of physical models with classical and advanced control algorithms.« less

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...

Augmented Adaptive Control of a Wind Turbine in the Presence of Structural Modes

NASA Technical Reports Server (NTRS)

Frost, Susan A.; Balas, Mark J.; Wright, Alan D.

2010-01-01

Wind turbines operate in highly turbulent environments resulting in aerodynamic loads that can easily excite turbine structural modes, potentially causing component fatigue and failure. Two key technology drivers for turbine manufacturers are increasing turbine up time and reducing maintenance costs. Since the trend in wind turbine design is towards larger, more flexible turbines with lower frequency structural modes, manufacturers will want to develop methods to operate in the presence of these modes. Accurate models of the dynamic characteristics of new wind turbines are often not available due to the complexity and expense of the modeling task, making wind turbines ideally suited to adaptive control. In this paper, we develop theory for adaptive control with rejection of disturbances in the presence of modes that inhibit the controller. We use this method to design an adaptive collective pitch controller for a high-fidelity simulation of a utility-scale, variable-speed wind turbine operating in Region 3. The objective of the adaptive pitch controller is to regulate generator speed, accommodate wind gusts, and reduce the interference of certain structural modes in feedback. The control objective is accomplished by collectively pitching the turbine blades. The adaptive pitch controller for Region 3 is compared in simulations with a baseline classical Proportional Integrator (PI) collective pitch controller.

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

Improved Control Strategy for Subsynchronous Resonance Mitigation with Fractional-order PI Controller

NASA Astrophysics Data System (ADS)

Raju, D. Koteswara; Umre, Bhimrao S.; Junghare, A. S.; Chitti Babu, B.

2016-12-01

This paper explores a robust Fractional-order PI (FOPI) controller to diminish Subsynchronous Resonance (SSR) using Static Synchronous series compensator (SSSC). The diminution of SSR is accomplished by increasing the network damping with the injection of voltage of subsynchronous component into the line at those frequencies which are proximate to the torsional mode frequency of the turbine-generator shaft. The voltage of subsynchronous frequency component is extracted from the transmission line and further the similar quantity of series voltage is injected by SSSC into the line to make the current of subsynchronous frequency component to zero which is the major source of oscillations in the turbine-generator shaft. The insertion and fine tuning of Fractional-order PI controller in the control scheme of SSSC the subsynchronous oscillations are reduced to 4 % as compared to conventional PI controller. The studied system is modelled and simulated using MATLAB-Simulink and the results are analysed to show the precision and robustness of the proposed control strategy.

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.

MEASUREMENT OF TIME INTERVALS FOR TIME CORRELATED RADIOACTIVE DECAY

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

Lindeman, H.; Mornel, E.; Galil, U.

1960-11-01

The distribution of time intervals between successive counts was measured for radioactive decay in the thorium series. The measurements showed that the classical Marsden-Barratt law does not apply to this case of timecorrelated decay. They appeared, however, to be in agreement with the theory of Lindeman-Rosen, taking into account the fact that the counter receives only the radiation emitted in a solid angle near to 2 pi . (auth)

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.

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

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.

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

Corneal Biofilms: From Planktonic to Microcolony Formation in an Experimental Keratitis Infection with Pseudomonas Aeruginosa.

PubMed

Saraswathi, Padmanabhan; Beuerman, Roger W

2015-10-01

Microbial biofilms commonly comprise part of the infectious scenario, complicating the therapeutic approach. The purpose of this study was to determine in a mouse model of corneal infection if mature biofilms formed and to visualize the stages of biofilm formation. A bacterial keratitis model was established using Pseudomonas aeruginosa ATCC 9027 (1 × 10(8) CFU/ml) to infect the cornea of C57BL/6 black mouse. Eyes were examined post-infection (PI) on days 1, 2, 3, 5, and 7, and imaged by slit lamp microscopy, and light, confocal, and electron microscopy to identify the stages of biofilm formation and the time of appearance. On PI day 1, Gram staining showed rod-shaped bacteria adherent on the corneal surface. On PI days 2 and 3, bacteria were seen within webs of extracellular polymeric substance (EPS) and glycocalyx secretion, imaged by confocal microscopy. Scanning electron microscopy demonstrated microcolonies of active infectious cells bound with thick fibrous material. Transmission electron microscopy substantiated the formation of classical biofilm architecture with P. aeruginosa densely packed within the extracellular polymeric substances on PI days 5 and 7. Direct visual evidence showed that biofilms routinely developed on the biotic surface of the mouse cornea. The mouse model can be used to develop new approaches to deal therapeutically with biofilms in corneal infections. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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.

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

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.

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

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.

An intelligent control scheme for precise tip-motion control in atomic force microscopy.

PubMed

Wang, Yanyan; Hu, Xiaodong; Xu, Linyan

2016-01-01

The paper proposes a new intelligent control method to precisely control the tip motion of the atomic force microscopy (AFM). The tip moves up and down at a high rate along the z direction during scanning, requiring the utilization of a rapid feedback controller. The standard proportional-integral (PI) feedback controller is commonly used in commercial AFMs to enable topography measurements. The controller's response performance is determined by the set of the proportional (P) parameter and the integral (I) parameter. However, the two parameters cannot be automatically altered simultaneously according to the scanning speed and the surface topography during continuors scanning, leading to an inaccurate measurement. Thus a new intelligent controller combining the fuzzy controller and the PI controller is put forward in the paper. The new controller automatically selects the most appropriate PI parameters to achieve a fast response rate on basis of the tracking errors. In the experimental setup, the new controller is realized with a digital signal process (DSP) system, implemented in a conventional AFM system. Experiments are carried out by comparing the new method with the standard PI controller. The results demonstrate that the new method is more robust and effective for the precise tip motion control, corresponding to the achievement of a highly qualified image by shortening the response time of the controller. © Wiley Periodicals, Inc.

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.

Suppression of Androgen Receptor Transactivation by Akt Kinase

DTIC Science & Technology

2005-01-01

with the potential to be particularly effective. A therapy Endocrine Societcs 84th Annual Meeting, San Francisco, June 19-22,2002, that suppresses the...PI3K/Akt pathway combined with classic p. 526 (abstr.), Endocrine Society Press, Bethesda, MD ablation therapy could reach the maximal effect in 10...10):2409-2423 Printed in U.S.A. Copyright © 2004 by The Endocrine Society do!: 10.1210/me.2004-0117 Regulation of Androgen Receptor Signaling by PTEN

ROSAT survey of emission from Be stars

NASA Technical Reports Server (NTRS)

Grady, Carol

1993-01-01

ROSAT pointed observations of bright, classical Be stars have demonstrated that detection of soft x-rays at a level expected for normal B stars of comparable T(sub eff) and luminosity is anti-correlated with the presence of episodes of enhanced mass ejection and formation of a dense, moderately ionized equatorial circumstellar disk. At epochs of lower than average disk column density, x-ray flaring has been detected in 2 Be stars, lambda Eri and pi Aqr.

Electronic Structure and Lattice Dynamics of Dimensionally Constrained and Disordered Solids.

DTIC Science & Technology

1985-02-28

zcopdsga ihaPI model 1124.A look-in amplifier. Th. data were digitized and punched on paper tape and a PDP 11/20 computer averaged the data and generated a...of S- presentation. Section 2 of this paper will review the classical formalism which is used to describe the intraband contribution. Section 3 will...the expo- for low absorption laser components. In recent years , nential dependence of K(w). Duthler’ estimated the extensive theoretical and

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

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.

High pressure common rail injection system modeling and control.

PubMed

Wang, H P; Zheng, D; Tian, Y

2016-07-01

In this paper modeling and common-rail pressure control of high pressure common rail injection system (HPCRIS) is presented. The proposed mathematical model of high pressure common rail injection system which contains three sub-systems: high pressure pump sub-model, common rail sub-model and injector sub-model is a relative complicated nonlinear system. The mathematical model is validated by the software Matlab and a virtual detailed simulation environment. For the considered HPCRIS, an effective model free controller which is called Extended State Observer - based intelligent Proportional Integral (ESO-based iPI) controller is designed. And this proposed method is composed mainly of the referred ESO observer, and a time delay estimation based iPI controller. Finally, to demonstrate the performances of the proposed controller, the proposed ESO-based iPI controller is compared with a conventional PID controller and ADRC. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Modified Adaptive Control for Region 3 Operation in the Presence of Wind Turbine Structural Modes

NASA Technical Reports Server (NTRS)

Frost, Susan Alane; Balas, Mark J.; Wright, Alan D.

2010-01-01

Many challenges exist for the operation of wind turbines in an efficient manner that is reliable and avoids component fatigue and failure. Turbines operate in highly turbulent environments resulting in aerodynamic loads that can easily excite turbine structural modes, possibly causing component fatigue and failure. Wind turbine manufacturers are highly motivated to reduce component fatigue and failure that can lead to loss of revenue due to turbine down time and maintenance costs. The trend in wind turbine design is toward larger, more flexible turbines that are ideally suited to adaptive control methods due to the complexity and expense required to create accurate models of their dynamic characteristics. In this paper, we design an adaptive collective pitch controller for a high-fidelity simulation of a utility-scale, variable-speed horizontal axis wind turbine operating in Region 3. The objective of the adaptive pitch controller is to regulate generator speed, accommodate wind gusts, and reduce the excitation of structural modes in the wind turbine. The control objective is accomplished by collectively pitching the turbine blades. The adaptive collective pitch controller for Region 3 was compared in simulations with a baseline classical Proportional Integrator (PI) collective pitch controller. The adaptive controller will demonstrate the ability to regulate generator speed in Region 3, while accommodating gusts, and reducing the excitation of certain structural modes in the wind turbine.

TASI/PiTP/ISS Lectures on Moduli and Microphysics

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

Silverstein, E

2004-05-10

I review basic forces on moduli that lead to their stabilization, for example in the supercritical and KKLT models of de Sitter space in string theory, as well as an AdS{sub 4} x S{sup 3} x S{sup 3} model I include which is not published elsewhere. These forces come from the classical dilaton tadpole in generic dimensionality, internal curvature, fluxes, and branes and orientifolds as well as non-perturbative effects. The resulting (A)dS solutions of string theory make detailed predictions for microphysical entropy, whose leading behavior we exhibit on the Coulomb branch of the system. Finally, I briefly review recent developmentsmore » concerning the role of velocity-dependent effects in the dynamics of moduli. These lecture notes are based on material presented at various stages in the 1999 TASI, 2002 PiTP, 2003 TASI, and 2003 ISS schools.« less

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.

Silibinin inhibits migration and invasion of the rhabdoid tumor G401 cell line via inactivation of the PI3K/Akt signaling pathway.

PubMed

Li, Yumei; Zhang, Chunmei; Cai, Danfeng; Chen, Congde; Mu, Dongmei

2017-12-01

Rhabdoid tumors, which tend to occur prior to the age of 2 years, are one of the most aggressive malignancies and have a poor prognosis due to the frequency of metastasis. Silibinin, a natural extract, has been approved as a potential tumor suppressor in various studies, however, whether or not it also exerts its antitumor capacity in rhabdoid tumors, particularly with regards to tumor migration and invasion, is unclear. The rhabdoid tumor G401 cell line was used in the present in vitro study. An MTT assay was used to assess the cytotoxicity of silibinin on G401 cells, cell migration was studied using a wound healing assay and a Transwell migration assay, and cell invasion was determined using a Transwell invasion assay. The underlying mechanism in silibinin inhibited cell migration and invasion was investigated by western blot analysis and further confirmed using a specific inhibitor. Experimental results demonstrated that high doses of silibinin suppressed cell viability, and that low doses of silibinin inhibited cell migration and invasion without affecting cell proliferation. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway was involved in the silibinin-induced inhibition of metastasis. Silibinin inactivated the PI3K/Akt pathway, and inhibited cell migration and invasion, an effect that was further enhanced when LY294002, a classic PI3K inhibitor, was used concurrently. In general, silibinin inhibits migration and invasion of the rhabdoid tumor G401 cell line via inactivation of the PI3K/Akt signaling pathway and may be a potential chemotherapeutic drug to combat rhabdoid tumors in the future.

Controllable 0–π Josephson junctions containing a ferromagnetic spin valve

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

Gingrich, E. C.; Niedzielski, Bethany M.; Glick, Joseph A.

Superconductivity and ferromagnetism are antagonistic forms of order, and rarely coexist. Many interesting new phenomena occur, however, in hybrid superconducting/ferromagnetic systems. For example, a Josephson junction containing a ferromagnetic material can exhibit an intrinsic phase shift of π in its ground state for certain thicknesses of the material. Such ‘π-junctions’ were first realized experimentally in 2001, and have been proposed as circuit elements for both high-speed classical superconducting computing and for quantum computing. Here we demonstrate experimentally that the phase state of a Josephson junction containing two ferromagnetic layers can be toggled between 0 and pi by changing the relativemore » orientation of the two magnetizations. These controllable 0–π junctions have immediate applications in cryogenic memory, where they serve as a necessary component to an ultralow power superconducting computer. Such a fully superconducting computer is estimated to be orders of magnitude more energy-efficient than current semiconductor-based supercomputers. Here, phase-controllable junctions also open up new possibilities for superconducting circuit elements such as superconducting ‘programmable logic’, where they could function in superconducting analogues to field-programmable gate arrays.« less

Quad-rotor flight path energy optimization

NASA Astrophysics Data System (ADS)

Kemper, Edward

Quad-Rotor unmanned areal vehicles (UAVs) have been a popular area of research and development in the last decade, especially with the advent of affordable microcontrollers like the MSP 430 and the Raspberry Pi. Path-Energy Optimization is an area that is well developed for linear systems. In this thesis, this idea of path-energy optimization is extended to the nonlinear model of the Quad-rotor UAV. The classical optimization technique is adapted to the nonlinear model that is derived for the problem at hand, coming up with a set of partial differential equations and boundary value conditions to solve these equations. Then, different techniques to implement energy optimization algorithms are tested using simulations in Python. First, a purely nonlinear approach is used. This method is shown to be computationally intensive, with no practical solution available in a reasonable amount of time. Second, heuristic techniques to minimize the energy of the flight path are tested, using Ziegler-Nichols' proportional integral derivative (PID) controller tuning technique. Finally, a brute force look-up table based PID controller is used. Simulation results of the heuristic method show that both reliable control of the system and path-energy optimization are achieved in a reasonable amount of time.

Controllable 0–π Josephson junctions containing a ferromagnetic spin valve

DOE PAGES

Gingrich, E. C.; Niedzielski, Bethany M.; Glick, Joseph A.; ...

2016-03-14

Superconductivity and ferromagnetism are antagonistic forms of order, and rarely coexist. Many interesting new phenomena occur, however, in hybrid superconducting/ferromagnetic systems. For example, a Josephson junction containing a ferromagnetic material can exhibit an intrinsic phase shift of π in its ground state for certain thicknesses of the material. Such ‘π-junctions’ were first realized experimentally in 2001, and have been proposed as circuit elements for both high-speed classical superconducting computing and for quantum computing. Here we demonstrate experimentally that the phase state of a Josephson junction containing two ferromagnetic layers can be toggled between 0 and pi by changing the relativemore » orientation of the two magnetizations. These controllable 0–π junctions have immediate applications in cryogenic memory, where they serve as a necessary component to an ultralow power superconducting computer. Such a fully superconducting computer is estimated to be orders of magnitude more energy-efficient than current semiconductor-based supercomputers. Here, phase-controllable junctions also open up new possibilities for superconducting circuit elements such as superconducting ‘programmable logic’, where they could function in superconducting analogues to field-programmable gate arrays.« less

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

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.

Differences in Aβ brain networks in Alzheimer's disease and healthy controls.

PubMed

Duan, Huoqiang; Jiang, Jiehui; Xu, Jun; Zhou, Hucheng; Huang, Zhemin; Yu, Zhihua; Yan, Zhuangzhi

2017-01-15

The prevailing β-amyloid (Aβ)-cascade hypothesis is the most classical Alzheimer's disease (AD) pathogenesis. In this hypothesis, excessive Aβ plaque deposition in human brain is considered to be the cause of AD. Carbon 11-labeled Pittsburgh compound B Positron emission tomography (11C-PiB PET) is the latest technology to detect Aβ plaques in vivo. Thus, it is possible to investigate the difference of Aβ brain networks between AD patients and Health Controls (HC) by analyzing 11C-PiB PET images. In this study, a graph-theoretical method was employed to investigate the topological properties of Aβ networks in 18 Chinese AD patients and 16 HC subjects from Huashan Hospital, Shanghai. The results showed that both groups demonstrated small-world property, and this property was more obvious in AD group. Additionally, the clustering coefficients and path lengths were significantly lower in AD group. The global efficiency was larger in AD than in HC. A direct comparison between with and without regression found that sex, age and weight had no significant effect on the Aβ network. Moreover, three altered regions in AD group were identified, including left cuneus (CUN.L), right caudate nucleus (CAU.R) and left superior frontal gyrus (SFGdor. L). A voxel-wise correlation analysis showed that in AD patients, the regions of strengthened connection with CUN.L were mainly located in frontal cortex and parietal cortex, the regions of strengthen connection with CAU.R were mainly located in temporal cortex. Finally, a machine learning based analysis demonstrated that the three regions could be better biomarkers than the whole brain for AD classification. Copyright © 2016 Elsevier B.V. All rights reserved.

Herbal prescription Chang'an II repairs intestinal mucosal barrier in rats with post-inflammation irritable bowel syndrome

PubMed Central

Wang, Feng-yun; Su, Min; Zheng, Yong-qiu; Wang, Xiao-ge; Kang, Nan; Chen, Ting; Zhu, En-lin; Bian, Zhao-xiang; Tang, Xu-dong

2015-01-01

Aim: The herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model. Methods: A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g·kg−1·d−1, ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4+ and CD8+ cells were counted and IL-1β and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier. Results: PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4+/CD8+ cell ratio in lamina propria and submucosa, and increased IL-1β and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4+/CD8+ cell ratio and expression of IL-1β and IL-4. Conclusion: Chang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects. PMID:25960135

Herbal prescription Chang'an II repairs intestinal mucosal barrier in rats with post-inflammation irritable bowel syndrome.

PubMed

Wang, Feng-yun; Su, Min; Zheng, Yong-qiu; Wang, Xiao-ge; Kang, Nan; Chen, Ting; Zhu, En-lin; Bian, Zhao-xiang; Tang, Xu-dong

2015-06-01

The herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model. A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g · kg(-1) · d(-1), ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4(+) and CD8(+) cells were counted and IL-1β and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier. PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4(+)/CD8(+) cell ratio in lamina propria and submucosa, and increased IL-1β and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4(+)/CD8(+) cell ratio and expression of IL-1β and IL-4. Chang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects.

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.

Metabolic, Genomic, and Biochemical Analyses of Glandular Trichomes from the Wild Tomato Species Lycopersicon hirsutum Identify a Key Enzyme in the Biosynthesis of MethylketonesW⃞

PubMed Central

Fridman, Eyal; Wang, Jihong; Iijima, Yoko; Froehlich, John E.; Gang, David R.; Ohlrogge, John; Pichersky, Eran

2005-01-01

Medium-length methylketones (C7-C15) are highly effective in protecting plants from numerous pests. We used a biochemical genomics approach to elucidate the pathway leading to synthesis of methylketones in the glandular trichomes of the wild tomato Lycopersicon hirsutum f glabratum (accession PI126449). A comparison of gland EST databases from accession PI126449 and a second L. hirsutum accession, LA1777, whose glands do not contain methylketones, showed that the expression of genes for fatty acid biosynthesis is elevated in PI126449 glands, suggesting de novo biosynthesis of methylketones. A cDNA abundant in the PI126449 gland EST database but rare in the LA1777 database was similar in sequence to plant esterases. This cDNA, designated Methylketone Synthase 1 (MKS1), was expressed in Escherichia coli and the purified protein used to catalyze in vitro reactions in which C12, C14, and C16 β-ketoacyl–acyl-carrier-proteins (intermediates in fatty acid biosynthesis) were hydrolyzed and decarboxylated to give C11, C13, and C15 methylketones, respectively. Although MKS1 does not contain a classical transit peptide, in vitro import assays showed that it was targeted to the stroma of plastids, where fatty acid biosynthesis occurs. Levels of MKS1 transcript, protein, and enzymatic activity were correlated with levels of methylketones and gland density in a variety of tomato accessions and in different plant organs. PMID:15772286

An adaptive recurrent neural-network controller using a stabilization matrix and predictive inputs to solve a tracking problem under disturbances.

PubMed

Fairbank, Michael; Li, Shuhui; Fu, Xingang; Alonso, Eduardo; Wunsch, Donald

2014-01-01

We present a recurrent neural-network (RNN) controller designed to solve the tracking problem for control systems. We demonstrate that a major difficulty in training any RNN is the problem of exploding gradients, and we propose a solution to this in the case of tracking problems, by introducing a stabilization matrix and by using carefully constrained context units. This solution allows us to achieve consistently lower training errors, and hence allows us to more easily introduce adaptive capabilities. The resulting RNN is one that has been trained off-line to be rapidly adaptive to changing plant conditions and changing tracking targets. The case study we use is a renewable-energy generator application; that of producing an efficient controller for a three-phase grid-connected converter. The controller we produce can cope with the random variation of system parameters and fluctuating grid voltages. It produces tracking control with almost instantaneous response to changing reference states, and virtually zero oscillation. This compares very favorably to the classical proportional integrator (PI) controllers, which we show produce a much slower response and settling time. In addition, the RNN we propose exhibits better learning stability and convergence properties, and can exhibit faster adaptation, than has been achieved with adaptive critic designs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Investigating β-adrenergic-induced cardiac hypertrophy through computational approach: classical and non-classical pathways.

PubMed

Khalilimeybodi, Ali; Daneshmehr, Alireza; Sharif-Kashani, Babak

2018-07-01

The chronic stimulation of β-adrenergic receptors plays a crucial role in cardiac hypertrophy and its progression to heart failure. In β-adrenergic signaling, in addition to the well-established classical pathway, Gs/AC/cAMP/PKA, activation of non-classical pathways such as Gi/PI3K/Akt/GSK3β and Gi/Ras/Raf/MEK/ERK contribute in cardiac hypertrophy. The signaling network of β-adrenergic-induced hypertrophy is very complex and not fully understood. So, we use a computational approach to investigate the dynamic response and contribution of β-adrenergic mediators in cardiac hypertrophy. The proposed computational model provides insights into the effects of β-adrenergic classical and non-classical pathways on the activity of hypertrophic transcription factors CREB and GATA4. The results illustrate that the model captures the dynamics of the main signaling mediators and reproduces the experimental observations well. The results also show that despite the low portion of β2 receptors out of total cardiac β-adrenergic receptors, their contribution in the activation of hypertrophic mediators and regulation of β-adrenergic-induced hypertrophy is noticeable and variations in β1/β2 receptors ratio greatly affect the ISO-induced hypertrophic response. The model results illustrate that GSK3β deactivation after β-adrenergic receptor stimulation has a major influence on CREB and GATA4 activation and consequent cardiac hypertrophy. Also, it is found through sensitivity analysis that PKB (Akt) activation has both pro-hypertrophic and anti-hypertrophic effects in β-adrenergic signaling.

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

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.

Does the Loss of Stromal Caveolin-1 Remodel the Tumor Microenvironment by Activating Src-Mediated PEAK1 and PI3K Pathways

DTIC Science & Technology

2016-09-01

Inhibition of MAP kinase pathway prevents plasma protrusions Next we used a selective inhibitor of MAP kinases , PD98059, to address whether we can...from human patients harbor AKT1 and that AKT1 kinase activity is sustained in these particles, nominating them as active signaling platforms...with the extracellular matrix (ECM) and extracellular molecules (2). Though many classic extracellular signaling molecules (e.g., hormones, peptide

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.

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 Sliding Mode Control of PMSM Based on Rapid Nonlinear Tracking Differentiator and Disturbance Observer

PubMed Central

Zhou, Zhanmin; Zhang, Bao; Mao, Dapeng

2018-01-01

Torque ripples caused by cogging torque, flux harmonics, and current measurement error seriously restrict the application of a permanent magnet synchronous motor (PMSM), which has been paid more and more attention for the use in inertial stabilized platforms. Sliding mode control (SMC), in parallel with the classical proportional integral (PI) controller, has a high advantage to suppress the torque ripples as its invariance to disturbances. However, since the high switching gain tends to cause chattering and it requires derivative of signals which is not readily obtainable without an acceleration signal sensor. Therefore, this paper proposes a robust SMC scheme based on a rapid nonlinear tracking differentiator (NTD) and a disturbance observer (DOB) to further improve the performance of the SMC. The NTD is employed to providing the derivative of the signal, and the DOB is utilized to estimate the system lumped disturbances, including parameter variations and external disturbances. On the one hand, DOB can compensate the robust SMC speed controller, it can reduce the chattering of SMC on the other hand. Experiments were carried out on an ARM and DSP-based platform. The obtained experimental results demonstrate that the robust SMC scheme has an improved performance with inertia stability and it exhibits a satisfactory anti-disturbance performance compared to the traditional methods. PMID:29596387

Robust Sliding Mode Control of PMSM Based on a Rapid Nonlinear Tracking Differentiator and Disturbance Observer.

PubMed

Zhou, Zhanmin; Zhang, Bao; Mao, Dapeng

2018-03-29

Torque ripples caused by cogging torque, flux harmonics, and current measurement error seriously restrict the application of a permanent magnet synchronous motor (PMSM), which has been paid more and more attention for the use in inertial stabilized platforms. Sliding mode control (SMC), in parallel with the classical proportional integral (PI) controller, has a high advantage to suppress the torque ripples as its invariance to disturbances. However, since the high switching gain tends to cause chattering and it requires derivative of signals which is not readily obtainable without an acceleration signal sensor. Therefore, this paper proposes a robust SMC scheme based on a rapid nonlinear tracking differentiator (NTD) and a disturbance observer (DOB) to further improve the performance of the SMC. The NTD is employed to providing the derivative of the signal, and the DOB is utilized to estimate the system lumped disturbances, including parameter variations and external disturbances. On the one hand, DOB can compensate the robust SMC speed controller, it can reduce the chattering of SMC on the other hand. Experiments were carried out on an ARM and DSP-based platform. The obtained experimental results demonstrate that the robust SMC scheme has an improved performance with inertia stability and it exhibits a satisfactory anti-disturbance performance compared to the traditional methods.

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.

Intelligent control for PMSM based on online PSO considering parameters change

NASA Astrophysics Data System (ADS)

Song, Zhengqiang; Yang, Huiling

2018-03-01

A novel online particle swarm optimization method is proposed to design speed and current controllers of vector controlled interior permanent magnet synchronous motor drives considering stator resistance variation. In the proposed drive system, the space vector modulation technique is employed to generate the switching signals for a two-level voltage-source inverter. The nonlinearity of the inverter is also taken into account due to the dead-time, threshold and voltage drop of the switching devices in order to simulate the system in the practical condition. Speed and PI current controller gains are optimized with PSO online, and the fitness function is changed according to the system dynamic and steady states. The proposed optimization algorithm is compared with conventional PI control method in the condition of step speed change and stator resistance variation, showing that the proposed online optimization method has better robustness and dynamic characteristics compared with conventional PI controller design.

Accounting for the differences in the structures and relative energies of the highly homoatomic np pi-np pi (n > or = 3)-bonded S2I4 2+, the Se-I pi-bonded Se2I4 2+, and their higher-energy isomers by AIM, MO, NBO, and VB methodologies.

PubMed

Brownridge, Scott; Crawford, Margaret-Jane; Du, Hongbin; Harcourt, Richard D; Knapp, Carsten; Laitinen, Risto S; Passmore, Jack; Rautiainen, J Mikko; Suontamo, Reijo J; Valkonen, Jussi

2007-02-05

The bonding in the highly homoatomic np pi-np pi (n > or = 3)-bonded S2I42+ (three sigma + two pi bonds), the Se-I pi-bonded Se2I42+ (four sigma + one pi bonds), and their higher-energy isomers have been studied using modern DFT and ab initio calculations and theoretical analysis methods: atoms in molecules (AIM), molecular orbital (MO), natural bond orbital (NBO), and valence bond (VB) analyses, giving their relative energies, theoretical bond orders, and atomic charges. The aim of this work was to seek theory-based answers to four main questions: (1) Are the previously proposed simple pi*-pi* bonding models valid for S2I42+ and Se2I42+? (2) What accounts for the difference in the structures of S2I42+ and Se2I42+? (3) Why are the classically bonded isolobal P2I4 and As2I4 structures not adopted? (4) Is the high experimentally observed S-S bond order supported by theoretical bond orders, and how does it relate to high bond orders between other heavier main group elements? The AIM analysis confirmed the high bond orders and established that the weak bonds observed in S2I42+ and Se2I42+ are real and the bonding in these cations is covalent in nature. The full MO analysis confirmed that S2I42+ contains three sigma and two pi bonds, that the positive charge is essentially equally distributed over all atoms, that the bonding between S2 and two I2+ units in S2I42+ is best described by two mutually perpendicular 4c2e pi*-pi* bonds, and that in Se2I42+, two SeI2+ moieties are joined by a 6c2e pi*-pi* bond, both in agreement with previously suggested models. The VB treatment provided a complementary approach to MO analysis and provided insight how the formation of the weak bonds affects the other bonds. The NBO analysis and the calculated AIM charges showed that the minimization of the electrostatic repulsion between EI2+ units (E = S, Se) and the delocalization of the positive charge are the main factors that explain why the nonclassical structures are favored for S2I42+ and Se2I42+. The difference in the structures of S2I42+ and Se2I42+ is related to the high strength of the S-S pi bond compared to the weak S-I sigma bond and the additional stabilization from increased delocalization of positive charge in the structure of S2I42+ compared to the structure of Se2I42+. The investigation of the E2X42+ series (E = S, Se, Te; X = Cl, Br, I) revealed that only S2I42+ adopts the highly np pi-np pi (n > or = 3)-bonded structure, while all other dications favor the pi-bonded Se2I42+ structure. Theoretical bond order calculations for S2I42+ confirm the previously presented experimentally based bond orders for S-S (2.1-2.3) and I-I (1.3-1.5) bonds. The S-S bond is determined to have the highest reported S-S bond order in an isolated compound and has a bond order that is either similar to or slightly less than the Si-Si bond order in the proposed triply bonded [(Me3Si)2CH]2(iPr)SiSi triple bond SiSi(iPr)[CH(SiMe3)2]2 depending on the definition of bond orders used.

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.

Contributions of nuclear magnetic resonance to renal biochemistry

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

Ross, B.; Freeman, D.; Chan, L.

/sup 31/P NMR as a descriptive technique is of interest to nephrologists. Particular contributions of /sup 31/P NMR to our understanding of renal function may be enumerated.: Free metabolite levels are different from those classically accepted; in particular, ADP and Pi are low with implications for the control of renal metabolism and Pi transport, and, via the phosphorylation potential, for Na+ transport. Renal pH is heterogeneous; between cortex, outer medulla, and papilla, and between cell and lumen, a large pH gradient exists. Also, quantitation between cytosol and mitochondrion of the pH gradient is now feasible. In acute renal failure ofmore » either ischemic or nonischemic origin, both ATP depletion and acidification of the renal cell result in damage, with increasing evidence for the importance of the latter. Measurements of renal metabolic rate in vivo suggest the existence of a prodromal phase of acute renal failure, which could lead to its detection at an earlier and possibly reversible stage. Human renal cancers show a unique /sup 31/P NMR spectrum and a very acidic environment. Cancer chemotherapy may alter this and detection of such changes with NMR offers a method of therapeutic monitoring with significance beyond nephrology. Renal cortex and medulla have a different T1 relaxation time, possibly due to differences in lipid composition. It seems that NMR spectroscopy has much to offer to the future understanding of the relationship between renal biochemistry and function. 56 references.« less

Apelin-13 exerts antidepressant-like and recognition memory improving activities in stressed rats.

PubMed

Li, E; Deng, Haifeng; Wang, Bo; Fu, Wan; You, Yong; Tian, Shaowen

2016-03-01

Apelin is the endogenous ligand for the G-protein-coupled receptor (APJ). The localization of APJ in limbic structures suggests a potential role for apelin in emotional processes. However, the role of apelin in the regulation of stress-induced responses such as depression and memory impairment is largely unknown. In the present study, we evaluated the role of apelin-13 in the regulation of stress-induced depression and memory impairment in rats. We report that repeated intracerebroventricular injections of apelin-13 reversed behavioral despair (immobility) in the forced swim (FS) test, a model widely used for the selection of new antidepressant agents. Apelin-13 also reversed behavioral deficits (escape failure) in the learned helplessness test. The magnitude of the antiimmobility and anti-escape failure effects of apelin-13 was comparable to that of imipramine, a classic antidepressant used as a positive control. Rats exposed to FS stress showed memory performance impairment in the novel object recognition test, and this impairment was improved by apelin-13 treatment. Apelin-13 did not affect recognition memory performance in non-stressed rats. Furthermore, the pretreatment of LY294002 (PI3K inhibitors) or PD98059 (ERK1/2 inhibitor) blocked apelin-13-mediated activities in FS-stressed rats. These findings suggest that apelin-13 exerts antidepressant-like and recognition memory improving activities through activating PI3K and ERK1/2 signaling pathways in stressed rats. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

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 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.

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.

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.

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.

Deriving Flood-Mediated Connectivity between River Channels and Floodplains: Data-Driven Approaches

NASA Astrophysics Data System (ADS)

Zhao, Tongtiegang; Shao, Quanxi; Zhang, Yongyong

2017-03-01

The flood-mediated connectivity between river channels and floodplains plays a fundamental role in flood hazard mapping and exerts profound ecological effects. The classic nearest neighbor search (NNS) fails to derive this connectivity because of spatial heterogeneity and continuity. We develop two novel data-driven connectivity-deriving approaches, namely, progressive nearest neighbor search (PNNS) and progressive iterative nearest neighbor search (PiNNS). These approaches are illustrated through a case study in Northern Australia. First, PNNS and PiNNS are employed to identify flood pathways on floodplains through forward tracking. That is, progressive search is performed to associate newly inundated cells in each time step to previously inundated cells. In particular, iterations in PiNNS ensure that the connectivity is continuous - the connection between any two cells along the pathway is built through intermediate inundated cells. Second, inundated floodplain cells are collectively connected to river channel cells through backward tracing. Certain river channel sections are identified to connect to a large number of inundated floodplain cells. That is, the floodwater from these sections causes widespread floodplain inundation. Our proposed approaches take advantage of spatial-temporal data. They can be applied to achieve connectivity from hydro-dynamic and remote sensing data and assist in river basin planning and management.

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

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.

Feasibility and effects of home-based smartphone-delivered automated feedback training for gait in people with Parkinson's disease: A pilot randomized controlled trial.

PubMed

Ginis, Pieter; Nieuwboer, Alice; Dorfman, Moran; Ferrari, Alberto; Gazit, Eran; Canning, Colleen G; Rocchi, Laura; Chiari, Lorenzo; Hausdorff, Jeffrey M; Mirelman, Anat

2016-01-01

Inertial measurement units combined with a smartphone application (CuPiD-system) were developed to provide people with Parkinson's disease (PD) real-time feedback on gait performance. This study investigated the CuPiD-system's feasibility and effectiveness compared with conventional gait training when applied in the home environment. Forty persons with PD undertook gait training for 30 min, three times per week for six weeks. Participants were randomly assigned to i) CuPiD, in which a smartphone application offered positive and corrective feedback on gait, or ii) an active control, in which personalized gait advice was provided. Gait, balance, endurance and quality of life were assessed before and after training and at four weeks follow-up using standardized tests. Both groups improved significantly on the primary outcomes (single and dual task gait speed) at post-test and follow-up. The CuPiD group improved significantly more on balance (MiniBESTest) at post-test (from 24.8 to 26.1, SD ∼ 5) and maintained quality of life (SF-36 physical health) at follow-up whereas the control group deteriorated (from 50.4 to 48.3, SD ∼ 16). No other statistically significant differences were found between the two groups. The CuPiD system was well-tolerated and participants found the tool user-friendly. CuPiD was feasible, well-accepted and seemed to be an effective approach to promote gait training, as participants improved equally to controls. This benefit may be ascribed to the real-time feedback, stimulating corrective actions and promoting self-efficacy to achieve optimal performance. Further optimization of the system and adequately-powered studies are warranted to corroborate these findings and determine cost-effectiveness.

Combination of prostate imaging reporting and data system (PI-RADS) score and prostate-specific antigen (PSA) density predicts biopsy outcome in prostate biopsy naïve patients.

PubMed

Washino, Satoshi; Okochi, Tomohisa; Saito, Kimitoshi; Konishi, Tsuzumi; Hirai, Masaru; Kobayashi, Yutaka; Miyagawa, Tomoaki

2017-02-01

To assess the value of the Prostate Imaging Reporting and Data System (PI-RADS) scoring system, for prostate multi-parametric magnetic resonance imaging (mpMRI) to detect prostate cancer, and classical parameters, such as prostate-specific antigen (PSA) level, prostate volume and PSA density, for predicting biopsy outcome in biopsy naïve patients who have suspected prostate cancer. Patients who underwent mpMRI at our hospital, and who had their first prostate biopsy between July 2010 and April 2014, were analysed retrospectively. The prostate biopsies were taken transperineally under transrectal ultrasonography guidance. In all, 14 cores were biopsied as a systematic biopsy in all patients. Two cognitive fusion-targeted biopsy cores were added for each lesion in patients who had suspicious or equivocal lesions on mpMRI. The PI-RADS scoring system version 2.0 (PI-RADS v2) was used to describe the MRI findings. Univariate and multivariate analyses were performed to determine significant predictors of prostate cancer and clinically significant prostate cancer. In all, 288 patients were analysed. The median patient age, PSA level, prostate volume and PSA density were 69 years, 7.5 ng/mL, 28.7 mL, and 0.26 ng/mL/mL, respectively. The biopsy results were benign, clinically insignificant, and clinically significant prostate cancer in 129 (45%), 18 (6%) and 141 (49%) patients, respectively. The multivariate analysis revealed that PI-RADS v2 score and PSA density were independent predictors for prostate cancer and clinically significant prostate cancer. When PI-RADS v2 score and PSA density were combined, a PI-RADS v2 score of ≥4 and PSA density ≥0.15 ng/mL/mL, or PI-RADS v2 score of 3 and PSA density of ≥0.30 ng/mL/mL, was associated with the highest clinically significant prostate cancer detection rates (76-97%) on the first biopsy. Of the patients in this group with negative biopsy results, 22% were subsequently diagnosed as prostate cancer. In contrast, a PI-RADS v2 score of ≤3 and PSA density of <0.15 ng/mL/mL yielded no clinically significant prostate cancer and no additional detection of prostate cancer on further biopsies. A combination of PI-RADS v2 score and PSA density can help in the decision-making process before prostate biopsy and in the follow-up strategy in biopsy naïve patients. Patients with a PI-RADS v2 score of ≤3 and PSA density of <0.15 ng/mL/mL may avoid unnecessary biopsies. © 2016 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.

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.

Entrainment and Control of Bacterial Populations: An in Silico Study over a Spatially Extended Agent Based Model.

PubMed

Mina, Petros; Tsaneva-Atanasova, Krasimira; Bernardo, Mario di

2016-07-15

We extend a spatially explicit agent based model (ABM) developed previously to investigate entrainment and control of the emergent behavior of a population of synchronized oscillating cells in a microfluidic chamber. Unlike most of the work in models of control of cellular systems which focus on temporal changes, we model individual cells with spatial dependencies which may contribute to certain behavioral responses. We use the model to investigate the response of both open loop and closed loop strategies, such as proportional control (P-control), proportional-integral control (PI-control) and proportional-integral-derivative control (PID-control), to heterogeinities and growth in the cell population, variations of the control parameters and spatial effects such as diffusion in the spatially explicit setting of a microfluidic chamber setup. We show that, as expected from the theory of phase locking in dynamical systems, open loop control can only entrain the cell population in a subset of forcing periods, with a wide variety of dynamical behaviors obtained outside these regions of entrainment. Closed-loop control is shown instead to guarantee entrainment in a much wider region of control parameter space although presenting limitations when the population size increases over a certain threshold. In silico tracking experiments are also performed to validate the ability of classical control approaches to achieve other reference behaviors such as a desired constant output or a linearly varying one. All simulations are carried out in BSim, an advanced agent-based simulator of microbial population which is here extended ad hoc to include the effects of control strategies acting onto the population.

The Akt-inhibitor Erufosine induces apoptotic cell death in prostate cancer cells and increases the short term effects of ionizing radiation.

PubMed

Rudner, Justine; Ruiner, Carola-Ellen; Handrick, René; Eibl, Hans-Jörg; Belka, Claus; Jendrossek, Verena

2010-11-16

The phosphatidylinositol-3-kinase (PI3K)/Akt pathway is frequently deregulated in prostate cancer and associated with neoplastic transformation, malignant progression, and enhanced resistance to classical chemotherapy and radiotherapy. Thus, it is a promising target for therapeutic intervention. In the present study, the cytotoxic action of the Akt inhibitor Erufosine (ErPC3) was analyzed in prostate cancer cells and compared to the cytotoxicity of the PI3K inhibitor LY294002. Moreover, the efficacy of combined treatment with Akt inhibitors and ionizing radiation in prostate cancer cells was examined. Prostate cancer cell lines PC3, DU145, and LNCaP were treated with ErPC3 (1-100 µM), LY294002 (25-100 µM), irradiated (0-10 Gy), or subjected to combined treatments. Cell viability was determined by the WST-1 assay. Apoptosis induction was analyzed by flow cytometry after staining with propidium iodide in a hypotonic citrate buffer, and by Western blotting using antibodies against caspase-3 and its substrate PARP. Akt activity and regulation of the expression of Bcl-2 family members and key downstream effectors involved in apoptosis regulation were examined by Western blot analysis. The Akt inhibitor ErPC3 exerted anti-neoplastic effects in prostate cancer cells, however with different potency. The anti-neoplastic action of ErPC3 was associated with reduced phosphoserine 473-Akt levels and induction of apoptosis. PC3 and LNCaP prostate cancer cells were also sensitive to treatment with the PI3K inhibitor LY294002. However, the ErPC3-sensitive PC3-cells were less susceptible to LY294002 than the ErPC3-refractory LNCaP cells. Although both cell lines were largely resistant to radiation-induced apoptosis, both cell lines showed higher levels of apoptotic cell death when ErPC3 was combined with radiotherapy. Our data suggest that constitutive Akt activation and survival are controlled by different different molecular mechanisms in the two prostate cancer cell lines - one which is sensitive to the Akt-inhibitor ErPC3 and one which is more sensitive to the PI3K-inhibitor LY294002. Our findings underline the importance for the definition of predictive biomarkers that allow the selection patients that may benefit from the treatment with a specific signal transduction modifier.

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

Hydrogen sulfide promotes autophagy of hepatocellular carcinoma cells through the PI3K/Akt/mTOR signaling pathway.

PubMed

Wang, Shanshan S; Chen, Yuhan H; Chen, Ning; Wang, Lijun J; Chen, Dexi X; Weng, Honglei L; Dooley, Steven; Ding, Huiguo G

2017-03-23

Hydrogen sulfide (H 2 S), in its gaseous form, plays an important role in tumor carcinogenesis. This study investigated the effects of H 2 S on the cell biological functions of hepatocellular carcinoma (HCC). HCC cell lines, HepG2 and HLE, were treated with NaHS, a donor of H 2 S, and rapamycin, a classic autophagy inducer, for different lengths of time. Western blotting, immunofluorescence, transmission electron microscopy (TEM), scratch assay, CCK-8 and flow cytometric analysis were carried out to examine the effects of H 2 S on HCC autophagy, cell behavior and PI3K/Akt/mTOR signaling. Treatment with NaHS upregulated expression of LC3-II and Atg5, two autophagy-related proteins, in HepG2 and HLE cells. TEM revealed increased numbers of intracellular double-membrane vesicles in those cells treated with NaHS. Like rapamycin, NaHS also significantly inhibited expression of p-PI3K, p-Akt and mTOR proteins in HCC cells. Interestingly, the expression of LC3-II was further increased when the cells were treated with NaHS together with rapamycin. In addition, NaHS inhibited HCC cell migration, proliferation and cell division. These findings show that H 2 S can induce HCC cell apoptosis. The biological function of the gasotransmitter H 2 S in HCC cells was enhanced by the addition of rapamycin. Hydrogen sulfide influences multiple biological functions of HCC cells through inhibiting the PI3K/Akt/mTOR signaling pathway.

Na⁺-Dependent High-Affinity Nitrate, Phosphate and Amino Acids Transport in Leaf Cells of the Seagrass Posidonia oceanica (L.) Delile.

PubMed

Rubio, Lourdes; García-Pérez, Delia; García-Sánchez, María Jesús; Fernández, José A

2018-05-24

Posidonia oceanica (L.) Delile is a seagrass, the only group of vascular plants to colonize the marine environment. Seawater is an extreme yet stable environment characterized by high salinity, alkaline pH and low availability of essential nutrients, such as nitrate and phosphate. Classical depletion experiments, membrane potential and cytosolic sodium measurements were used to characterize the high-affinity NO₃ - , Pi and amino acids uptake mechanisms in this species. Net uptake rates of both NO₃ - and Pi were reduced by more than 70% in the absence of Na⁺. Micromolar concentrations of NO₃ - depolarized mesophyll leaf cells plasma membrane. Depolarizations showed saturation kinetics ( Km = 8.7 ± 1 μM NO₃ - ), which were not observed in the absence of Na⁺. NO₃ - induced depolarizations at increasing Na⁺ also showed saturation kinetics ( Km = 7.2 ± 2 mM Na⁺). Cytosolic Na⁺ measured in P. oceanica leaf cells (17 ± 2 mM Na⁺) increased by 0.4 ± 0.2 mM Na⁺ upon the addition of 100 μM NO₃ - . Na⁺-dependence was also observed for high-affinity l-ala and l-cys uptake and high-affinity Pi transport. All together, these results strongly suggest that NO₃ - , amino acids and Pi uptake in P. oceanica leaf cells are mediated by high-affinity Na⁺-dependent transport systems. This mechanism seems to be a key step in the process of adaptation of seagrasses to the marine environment.

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

[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.

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.

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.

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

From classical to quantum mechanics: ``How to translate physical ideas into mathematical language''

NASA Astrophysics Data System (ADS)

Bergeron, H.

2001-09-01

Following previous works by E. Prugovečki [Physica A 91A, 202 (1978) and Stochastic Quantum Mechanics and Quantum Space-time (Reidel, Dordrecht, 1986)] on common features of classical and quantum mechanics, we develop a unified mathematical framework for classical and quantum mechanics (based on L2-spaces over classical phase space), in order to investigate to what extent quantum mechanics can be obtained as a simple modification of classical mechanics (on both logical and analytical levels). To obtain this unified framework, we split quantum theory in two parts: (i) general quantum axiomatics (a system is described by a state in a Hilbert space, observables are self-adjoints operators, and so on) and (ii) quantum mechanics proper that specifies the Hilbert space as L2(Rn); the Heisenberg rule [pi,qj]=-iℏδij with p=-iℏ∇, the free Hamiltonian H=-ℏ2Δ/2m and so on. We show that general quantum axiomatics (up to a supplementary "axiom of classicity") can be used as a nonstandard mathematical ground to formulate physical ideas and equations of ordinary classical statistical mechanics. So, the question of a "true quantization" with "ℏ" must be seen as an independent physical problem not directly related with quantum formalism. At this stage, we show that this nonstandard formulation of classical mechanics exhibits a new kind of operation that has no classical counterpart: this operation is related to the "quantization process," and we show why quantization physically depends on group theory (the Galilei group). This analytical procedure of quantization replaces the "correspondence principle" (or canonical quantization) and allows us to map classical mechanics into quantum mechanics, giving all operators of quantum dynamics and the Schrödinger equation. The great advantage of this point of view is that quantization is based on concrete physical arguments and not derived from some "pure algebraic rule" (we exhibit also some limit of the correspondence principle). Moreover spins for particles are naturally generated, including an approximation of their interaction with magnetic fields. We also recover by this approach the semi-classical formalism developed by E. Prugovečki [Stochastic Quantum Mechanics and Quantum Space-time (Reidel, Dordrecht, 1986)].

Comparison of cross sections from the quasi-classical trajectory method and the j(z)-conserving centrifugal sudden approximation with accurate quantum results for an atom-rigid nonlinear polyatomic collision

NASA Technical Reports Server (NTRS)

Schwenke, David W.

1993-01-01

We report the results of a series of calculations of state-to-state integral cross sections for collisions between O and nonvibrating H2O in the gas phase on a model nonreactive potential energy surface. The dynamical methods used include converged quantum mechanical scattering calculations, the j(z) conserving centrifugal sudden (j(z)-CCS) approximation, and quasi-classical trajectory (QCT) calculations. We consider three total energies 0.001, 0.002, and 0.005 E(h) and the nine initial states with rotational angular momentum less than or equal to 2 (h/2 pi). The j(z)-CCS approximation gives good results, while the QCT method can be quite unreliable for transitions to specific rotational sublevels. However, the QCT cross sections summed over final sublevels and averaged over initial sublevels are in better agreement with the quantum results.

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

[Diagnosis of tropical malaria by express-methods].

PubMed

Popov, A F; Nikiforov, N D; Ivanis, V A; Barkun, S P; Sanin, B I; Fed'kina, L I

2004-01-01

An examination of a thick blood drop and of blood smear for the presence of plasmodia is a classic and indisputable diagnostic test for tropic malaria. However, express-methods, based on the immune-enzyme analysis, have been introduced into the health-care practice primarily in developing and underdeveloped countries. The diagnosis of tropic malaria by using the discussed methods enables, in the non-laboratory settings, a rapid and reliable detection of PI. falciparum in blood. This is important because an untimely diagnosis of tropic malaria increases the risk of the lethal outcome.

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.

Development of a combined feed forward-feedback system for an electron Linac

NASA Astrophysics Data System (ADS)

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

2009-10-01

This paper describes the results of an advanced control algorithm for the stabilization of electron beam energy in a Linac. The approach combines a conventional Proportional-Integral (PI) controller with a neural network (NNET) feed forward algorithm; it utilizes the robustness of PI control and the ability of a feed forward system in order to exert control over a wider range of frequencies. The NNET is trained to recognize jitter occurring in the phase and voltage of one of the klystrons, based on a record of these parameters, and predicts future energy deviations. A systematic approach is developed to determine the optimal NNET parameters that are then applied to the Australian Synchrotron Linac. The system's capability to fully cancel multi-frequency jitter is demonstrated. The NNET system is then augmented with the PI algorithm, and further jitter attenuation is achieved when the NNET is not operating optimally.

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.

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.

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.

Citation classics in periodontology: a controlled study.

PubMed

Nieri, Michele; Saletta, Daniele; Guidi, Luisa; Buti, Jacopo; Franceschi, Debora; Mauro, Saverio; Pini-Prato, Giovanpaolo

2007-04-01

The aims of this study were to identify the most cited articles in Periodontology published from January 1990 to March 2005; and to analyse the differences between citation Classics and less cited articles. The search was carried out in four international periodontal journals: Journal of Periodontology, Journal of Clinical Periodontology, International Journal of Periodontics and Restorative Dentistry and Journal of Periodontal Research. The Classics, that are articles cited at least 100 times, were identified using the Science Citation Index database. From every issue of the journals that contained a Classic, another article was randomly selected and used as a Control. Fifty-five Classics and 55 Controls were identified. Classic articles were longer, used more images, had more authors, and contained more self-references than Controls. Moreover Classics had on the average a bigger sample size, often dealt with etiopathogenesis and prognosis, but were rarely controlled or randomized studies. Classic articles play an instructive role, but are often non-Controlled studies.

Neuro-Fuzzy Computational Technique to Control Load Frequency in Hydro-Thermal Interconnected Power System

NASA Astrophysics Data System (ADS)

Prakash, S.; Sinha, S. K.

2015-09-01

In this research work, two areas hydro-thermal power system connected through tie-lines is considered. The perturbation of frequencies at the areas and resulting tie line power flows arise due to unpredictable load variations that cause mismatch between the generated and demanded powers. Due to rising and falling power demand, the real and reactive power balance is harmed; hence frequency and voltage get deviated from nominal value. This necessitates designing of an accurate and fast controller to maintain the system parameters at nominal value. The main purpose of system generation control is to balance the system generation against the load and losses so that the desired frequency and power interchange between neighboring systems are maintained. The intelligent controllers like fuzzy logic, artificial neural network (ANN) and hybrid fuzzy neural network approaches are used for automatic generation control for the two area interconnected power systems. Area 1 consists of thermal reheat power plant whereas area 2 consists of hydro power plant with electric governor. Performance evaluation is carried out by using intelligent (ANFIS, ANN and fuzzy) control and conventional PI and PID control approaches. To enhance the performance of controller sliding surface i.e. variable structure control is included. The model of interconnected power system has been developed with all five types of said controllers and simulated using MATLAB/SIMULINK package. The performance of the intelligent controllers has been compared with the conventional PI and PID controllers for the interconnected power system. A comparison of ANFIS, ANN, Fuzzy and PI, PID based approaches shows the superiority of proposed ANFIS over ANN, fuzzy and PI, PID. Thus the hybrid fuzzy neural network controller has better dynamic response i.e., quick in operation, reduced error magnitude and minimized frequency transients.

Deinococcus Mn2+-peptide complex: A novel approach to alphavirus vaccine development.

PubMed

Gayen, Manoshi; Gupta, Paridhi; Morazzani, Elaine M; Gaidamakova, Elena K; Knollmann-Ritschel, Barbara; Daly, Michael J; Glass, Pamela J; Maheshwari, Radha K

2017-06-22

Over the last ten years, Chikungunya virus (CHIKV), an Old World alphavirus has caused numerous outbreaks in Asian and European countries and the Americas, making it an emerging pathogen of great global health importance. Venezuelan equine encephalitis virus (VEEV), a New World alphavirus, on the other hand, has been developed as a bioweapon in the past due to its ease of preparation, aerosol dispersion and high lethality in aerosolized form. Currently, there are no FDA approved vaccines against these viruses. In this study, we used a novel approach to develop inactivated vaccines for VEEV and CHIKV by applying gamma-radiation together with a synthetic Mn-decapeptide-phosphate complex (MnDpPi), based on manganous-peptide-orthophosphate antioxidants accumulated in the extremely radiation-resistant bacterium Deinococcus radiodurans. Classical gamma-irradiated vaccine development approaches are limited by immunogenicity-loss due to oxidative damage to the surface proteins at the high doses of radiation required for complete virus-inactivation. However, addition of MnDpPi during irradiation process selectively protects proteins, but not the nucleic acids, from the radiation-induced oxidative damage, as required for safe and efficacious vaccine development. Previously, this approach was used to develop a bacterial vaccine. In the present study, we show that this approach can successfully be applied to protecting mice against viral infections. Irradiation of VEEV and CHIKV in the presence of MnDpPi resulted in substantial epitope preservation even at supra-lethal doses of gamma-rays (50,000Gy). Irradiated viruses were found to be completely inactivated and safe in vivo (neonatal mice). Upon immunization, VEEV inactivated in the presence of MnDpPi resulted in drastically improved protective efficacy. Thus, the MnDpPi-based gamma-inactivation approach described here can readily be applied to developing vaccines against any pathogen of interest in a fast and cost-effective manner. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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.

Electron beam energy and bunch length feed forward control studies using an artificial neural network at the Linac coherent light source

NASA Astrophysics Data System (ADS)

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

2009-11-01

This paper describes the results of an advanced control algorithm for the stabilization of electron beam energy in a Linac. The approach combines a conventional Proportional-Integral (PI) controller with a neural network (NNET) feed forward algorithm; it utilizes the robustness of PI control and the ability of a feed forward system in order to exert control over a wider range of frequencies. The NNET is trained to recognize jitter occurring in the phase and voltage of one of the klystrons, based on a record of these parameters, and predicts future energy deviations. A systematic approach is developed to determine the optimal NNET parameters that are then applied to the Australian Synchrotron Linac. The system's capability to fully cancel multi-frequency jitter is demonstrated. The NNET system is then augmented with the PI algorithm, and further jitter attenuation is achieved when the NNET is not operating optimally.

[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.

Physical control oriented model of large scale refrigerators to synthesize advanced control schemes. Design, validation, and first control results

NASA Astrophysics Data System (ADS)

Bonne, François; Alamir, Mazen; Bonnay, Patrick

2014-01-01

In this paper, a physical method to obtain control-oriented dynamical models of large scale cryogenic refrigerators is proposed, in order to synthesize model-based advanced control schemes. These schemes aim to replace classical user experience designed approaches usually based on many independent PI controllers. This is particularly useful in the case where cryoplants are submitted to large pulsed thermal loads, expected to take place in the cryogenic cooling systems of future fusion reactors such as the International Thermonuclear Experimental Reactor (ITER) or the Japan Torus-60 Super Advanced Fusion Experiment (JT-60SA). Advanced control schemes lead to a better perturbation immunity and rejection, to offer a safer utilization of cryoplants. The paper gives details on how basic components used in the field of large scale helium refrigeration (especially those present on the 400W @1.8K helium test facility at CEA-Grenoble) are modeled and assembled to obtain the complete dynamic description of controllable subsystems of the refrigerator (controllable subsystems are namely the Joule-Thompson Cycle, the Brayton Cycle, the Liquid Nitrogen Precooling Unit and the Warm Compression Station). The complete 400W @1.8K (in the 400W @4.4K configuration) helium test facility model is then validated against experimental data and the optimal control of both the Joule-Thompson valve and the turbine valve is proposed, to stabilize the plant under highly variable thermals loads. This work is partially supported through the European Fusion Development Agreement (EFDA) Goal Oriented Training Program, task agreement WP10-GOT-GIRO.

Physical control oriented model of large scale refrigerators to synthesize advanced control schemes. Design, validation, and first control results

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

Bonne, François; Bonnay, Patrick; Alamir, Mazen

2014-01-29

In this paper, a physical method to obtain control-oriented dynamical models of large scale cryogenic refrigerators is proposed, in order to synthesize model-based advanced control schemes. These schemes aim to replace classical user experience designed approaches usually based on many independent PI controllers. This is particularly useful in the case where cryoplants are submitted to large pulsed thermal loads, expected to take place in the cryogenic cooling systems of future fusion reactors such as the International Thermonuclear Experimental Reactor (ITER) or the Japan Torus-60 Super Advanced Fusion Experiment (JT-60SA). Advanced control schemes lead to a better perturbation immunity and rejection,more » to offer a safer utilization of cryoplants. The paper gives details on how basic components used in the field of large scale helium refrigeration (especially those present on the 400W @1.8K helium test facility at CEA-Grenoble) are modeled and assembled to obtain the complete dynamic description of controllable subsystems of the refrigerator (controllable subsystems are namely the Joule-Thompson Cycle, the Brayton Cycle, the Liquid Nitrogen Precooling Unit and the Warm Compression Station). The complete 400W @1.8K (in the 400W @4.4K configuration) helium test facility model is then validated against experimental data and the optimal control of both the Joule-Thompson valve and the turbine valve is proposed, to stabilize the plant under highly variable thermals loads. This work is partially supported through the European Fusion Development Agreement (EFDA) Goal Oriented Training Program, task agreement WP10-GOT-GIRO.« less

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.

Sequential Activation of Classic PKC and Estrogen Receptor α Is Involved in Estradiol 17ß-D-Glucuronide-Induced Cholestasis

PubMed Central

Barosso, Ismael R.; Zucchetti, Andrés E.; Boaglio, Andrea C.; Larocca, M. Cecilia; Taborda, Diego R.; Luquita, Marcelo G.; Roma, Marcelo G.; Crocenzi, Fernando A.; Sánchez Pozzi, Enrique J.

2012-01-01

Estradiol 17ß-d-glucuronide (E17G) induces acute cholestasis in rat with endocytic internalization of the canalicular transporters bile salt export pump (Abcb11) and multidrug resistance-associated protein 2 (Abcc2). Classical protein kinase C (cPKC) and PI3K pathways play complementary roles in E17G cholestasis. Since non-conjugated estradiol is capable of activating these pathways via estrogen receptor alpha (ERα), we assessed the participation of this receptor in the cholestatic manifestations of estradiol glucuronidated-metabolite E17G in perfused rat liver (PRL) and in isolated rat hepatocyte couplets (IRHC). In both models, E17G activated ERα. In PRL, E17G maximally decreased bile flow, and the excretions of dinitrophenyl-glutathione, and taurocholate (Abcc2 and Abcb11 substrates, respectively) by 60% approximately; preadministration of ICI 182,780 (ICI, ERα inhibitor) almost totally prevented these decreases. In IRHC, E17G decreased the canalicular vacuolar accumulation of cholyl-glycylamido-fluorescein (Abcb11 substrate) with an IC50 of 91±1 µM. ICI increased the IC50 to 184±1 µM, and similarly prevented the decrease in the canalicular vacuolar accumulation of the Abcc2 substrate, glutathione-methylfluorescein. ICI also completely prevented E17G-induced delocalization of Abcb11 and Abcc2 from the canalicular membrane, both in PRL and IRHC. The role of ERα in canalicular transporter internalization induced by E17G was confirmed in ERα-knocked-down hepatocytes cultured in collagen sandwich. In IRHC, the protection of ICI was additive to that produced by PI3K inhibitor wortmannin but not with that produced by cPKC inhibitor Gö6976, suggesting that ERα shared the signaling pathway of cPKC but not that of PI3K. Further analysis of ERα and cPKC activations induced by E17G, demonstrated that ICI did not affect cPKC activation whereas Gö6976 prevented that of ERα, indicating that cPKC activation precedes that of ERα. Conclusion: ERα is involved in the biliary secretory failure induced by E17G and its activation follows that of cPKC. PMID:23209816

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.

S1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells

PubMed Central

Vrzalikova, K; Ibrahim, M; Vockerodt, M; Perry, T; Margielewska, S; Lupino, L; Nagy, E; Soilleux, E; Liebelt, D; Hollows, R; Last, A; Reynolds, G; Abdullah, M; Curley, H; Care, M; Krappmann, D; Tooze, R; Allegood, J; Spiegel, S; Wei, W; Woodman, C B J; Murray, P G

2018-01-01

The Hodgkin/Reed–Sternberg cells of classical Hodgkin lymphoma (HL) are characterised by the aberrant activation of multiple signalling pathways. Here we show that a subset of HL displays altered expression of sphingosine-1-phosphate (S1P) receptors (S1PR)s. S1P activates phosphatidylinositide 3-kinase (PI3-K) in these cells that is mediated by the increased expression of S1PR1 and the decreased expression of S1PR2. We also showed that genes regulated by the PI3-K signalling pathway in HL cell lines significantly overlap with the transcriptional programme of primary HRS cells. Genes upregulated by the PI3-K pathway included the basic leucine zipper transcription factor, ATF-like 3 (BATF3), which is normally associated with the development of dendritic cells. Immunohistochemistry confirmed that BATF3 was expressed in HRS cells of most HL cases. In contrast, in normal lymphoid tissues, BATF3 expression was confined to a small fraction of CD30-positive immunoblasts. Knockdown of BATF3 in HL cell lines revealed that BATF3 contributed to the transcriptional programme of primary HRS cells, including the upregulation of S1PR1. Our data suggest that disruption of this potentially oncogenic feedforward S1P signalling loop could provide novel therapeutic opportunities for patients with HL. PMID:28878352

Glucose-dependent insulinotropic polypeptide directly induces glucose transport in rat skeletal muscle

PubMed Central

Snook, Laelie A.; Nelson, Emery M.; Dyck, David J.; Wright, David C.

2015-01-01

Several gastrointestinal proteins have been identified to have insulinotropic effects, including glucose-dependent insulinotropic polypeptide (GIP); however, the direct effects of incretins on skeletal muscle glucose transport remain largely unknown. Therefore, the purpose of the current study was to examine the role of GIP on skeletal muscle glucose transport and insulin signaling in rats. Relative to a glucose challenge, a mixed glucose+lipid oral challenge increased circulating GIP concentrations, skeletal muscle Akt phosphorylation, and improved glucose clearance by ∼35% (P < 0.05). These responses occurred without alterations in serum insulin concentrations. In an incubated soleus muscle preparation, GIP directly stimulated glucose transport and increased GLUT4 accumulation on the plasma membrane in the absence of insulin. Moreover, the ability of GIP to stimulate glucose transport was mitigated by the addition of the PI 3-kinase (PI3K) inhibitor wortmannin, suggesting that signaling through PI3K is required for these responses. We also provide evidence that the combined stimulatory effects of GIP and insulin on soleus muscle glucose transport are additive. However, the specific GIP receptor antagonist (Pro3)GIP did not attenuate GIP-stimulated glucose transport, suggesting that GIP is not signaling through its classical receptor. Together, the current data provide evidence that GIP regulates skeletal muscle glucose transport; however, the exact signaling mechanism(s) remain unknown. PMID:26041107

Exogenous cathepsin V protein protects human cardiomyocytes HCM from angiotensin Ⅱ-Induced hypertrophy.

PubMed

Huang, Kun; Gao, Lu; Yang, Ming; Wang, Jiliang; Wang, Zheng; Wang, Lin; Wang, Guobin; Li, Huili

2017-08-01

Angiotensin (Ang) Ⅱ-induced cardiac hypertrophy can deteriorate to heart failure, a leading cause of mortality. Endogenous Cathepsin V (CTSV) has been reported to be cardioprotective against hypertrophy. However, little is known about the effect of exogenous CTSV on cardiac hypertrophy. We used the human cardiomyocytes HCM as a cell model to investigate the effects of exogenous CTSV on Ang Ⅱ-induced cardiac cell hypertrophy. Cell surface area and expression of classical markers of hypertrophy were analyzed. We further explored the mechanism of CTSV cardioprotective by assessing the levels and activities of PI3K/Akt/mTOR and MAPK signaling pathway proteins. We found that pre-treating cardiomyocytes with CTSV could significantly inhibit Ang Ⅱ-induced hypertrophy. The mRNA expression of hypertrophy markers ANP, BNP and β-MHC was obviously elevated in Ang Ⅱ-treated cardiac cells. Whereas, exogenous CTSV effectively halted this elevation. Further study revealed that the protective effects of exogenous CTSV might be mediated by repressing the phosphorylation of proteins in the PI3K/Akt/mTOR and MAPK pathways. Based on our results, we concluded that exogenous CTSV inhibited Ang Ⅱ-induced hypertrophy in HCM cells by inhibiting PI3K/Akt/mTOR. This study provides experimental evidence for the application of CTSV protein for the treatment of cardiac hypertrophy. Copyright © 2017 Elsevier Ltd. 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.

Increased Burden of Cerebral Small Vessel Disease in Patients With Type 2 Diabetes and Retinopathy.

PubMed

Sanahuja, Jordi; Alonso, Núria; Diez, Javier; Ortega, Emilio; Rubinat, Esther; Traveset, Alícia; Alcubierre, Núria; Betriu, Àngels; Castelblanco, Esmeralda; Hernández, Marta; Purroy, Francisco; Arcidiacono, Maria Vittoria; Jurjo, Carmen; Fernández, Elvira; Puig-Domingo, Manuel; Groop, Per-Henrik; Mauricio, Dídac

2016-09-01

We sought to examine the presence and severity of brain small vessel disease (SVD) in patients with type 2 diabetes and diabetic retinopathy (DR) compared with those without DR. We evaluated 312 patients with type 2 diabetes without previous cardiovascular disease (men 51%; mean age 57 years; age range 40-75 years); 153 patients (49%) had DR. MRI was performed to evaluate the presence and severity (age-related white matter changes scale) of white matter lesions (WMLs) and lacunes, and transcranial Doppler ultrasound was used to measure the Gosling pulsatility index (PI) of the middle cerebral artery (MCA). The prevalence of lesions of cerebral SVD (WML and/or lacunes) was higher in patients with DR (40.2% vs. 30.1% without DR, P = 0.04). Age (P < 0.01) and systolic blood pressure (P = 0.02) were associated with the presence of SVD. The severity of SVD was associated with age and the presence of DR (P < 0.01 and P = 0.01, respectively). Patients with DR showed a higher MCA PI compared with those without DR (P < 0.01). Age, systolic and diastolic blood pressure, and retinopathy and its severity were associated with an increased MCA PI (P < 0.01 for all variables). A positive correlation was found between MCA PI values and the presence and severity of SVD (P < 0.01 for both variables). Patients with type 2 diabetes who have DR have an increased burden of cerebral SVD compared with those without DR. Our findings suggest that the brain is a target organ for microangiopathy, similar to other classic target organs, like the retina. © 2016 by the American Diabetes Association.

The role of PTEN in regulation of hepatic macrophages activation and function in progression and reversal of liver fibrosis

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

Cheng, Yahui; Tian, Yuanyao; Xia, Jialu

Activation of Kupffer cells (KCs) plays a pivotal role in the pathogenesis of liver fibrosis. The progression and reversal of CCl{sub 4}-induced mouse liver fibrosis showed a mixed induction of hepatic classical (M1) and alternative (M2) macrophage markers. Although the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in modulating myeloid cell activation has recently been identified, its function in macrophage activation during hepatic fibrosis remains to be fully appreciated. In our study, PTEN expression of KCs was remarkably decreased in CCl{sub 4}-induced mice but increased to a near-normal level in reversed mice. Moreover, PTEN was significantlymore » decreased in IL4-induced RAW 264.7 cells in vitro and lower expression of PTEN was observed in M2 macrophages in vivo. In addition, loss- and gain-of-function studies suggested that PTEN regulates M2 macrophages polarization via activation of PI3K/Akt/STAT6 signaling, but had a limited effect on M1 macrophages polarization in vitro. Additionally, Ly294002, a chemical inhibitor of PI3K/Akt, could dramatically down-regulate the hallmarks of M2 macrophages. In conclusion, PTEN mediates macrophages activation by PI3K/Akt/STAT6 signaling pathway, which provides novel compelling evidences on the potential of PTEN in liver injury and opens new cellular target for the pharmacological therapy of liver fibrosis. - Highlights: • CCl{sub 4} treatment triggered a mixed M1/M2 macrophage phenotype in fibrosis. • Lower expression of PTEN in murine M2 macrophages in vivo and vitro. • PTEN modulates M2 macrophages activation via PI3K/Akt/STAT6 signaling. • Provide a new cellular target modulate macrophage mediated hepatic fibrosis.« less

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.

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.

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.

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.

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.

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.

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

Do semiclassical zero temperature black holes exist?

PubMed

Anderson, P R; Hiscock, W A; Taylor, B E

2000-09-18

The semiclassical Einstein equations are solved to first order in epsilon = Planck's over 2pi/M2 for the case of a Reissner-Nordström black hole perturbed by the vacuum stress energy of quantized free fields. Massless and massive fields of spin 0, 1/2, and 1 are considered. We show that in all physically realistic cases, macroscopic zero temperature black hole solutions do not exist. Any static zero temperature semiclassical black hole solutions must then be microscopic and isolated in the space of solutions; they do not join smoothly onto the classical extreme Reissner-Nordström solution as epsilon-->0.

Runge-Lenz vector, accidental SU(2) symmetry, and unusual multiplets for motion on a cone

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

Al-Hashimi, M.H.; Wiese, U.-J.

2008-01-15

We consider a particle moving on a cone and bound to its tip by 1/r or harmonic oscillator potentials. When the deficit angle of the cone divided by 2{pi} is a rational number, all bound classical orbits are closed. Correspondingly, the quantum system has accidental degeneracies in the discrete energy spectrum. An accidental SU(2) symmetry is generated by the rotations around the tip of the cone as well as by a Runge-Lenz vector. Remarkably, some of the corresponding multiplets have fractional 'spin' and unusual degeneracies.

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

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

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.

The canonical quantization of chaotic maps on the torus

NASA Astrophysics Data System (ADS)

Rubin, Ron Shai

In this thesis, a quantization method for classical maps on the torus is presented. The quantum algebra of observables is defined as the quantization of measurable functions on the torus with generators exp (2/pi ix) and exp (2/pi ip). The Hilbert space we use remains the infinite-dimensional L2/ (/IR, dx). The dynamics is given by a unitary quantum propagator such that as /hbar /to 0, the classical dynamics is returned. We construct such a quantization for the Kronecker map, the cat map, the baker's map, the kick map, and the Harper map. For the cat map, we find the same for the propagator on the plane the same integral kernel conjectured in (HB) using semiclassical methods. We also define a quantum 'integral over phase space' as a trace over the quantum algebra. Using this definition, we proceed to define quantum ergodicity and mixing for maps on the torus. We prove that the quantum cat map and Kronecker map are both ergodic, but only the cat map is mixing, true to its classical origins. For Planck's constant satisfying the integrality condition h = 1/N, with N/in doubz+, we construct an explicit isomorphism between L2/ (/IR, dx) and the Hilbert space of sections of an N-dimensional vector bundle over a θ-torus T2 of boundary conditions. The basis functions are distributions in L2/ (/IR, dx), given by an infinite comb of Dirac δ-functions. In Bargmann space these distributions take on the form of Jacobi ϑ-functions. Transformations from position to momentum representation can be implemented via a finite N-dimensional discrete Fourier transform. With the θ-torus, we provide a connection between the finite-dimensional quantum maps given in the physics literature and the canonical quantization presented here and found in the language of pseudo-differential operators elsewhere in mathematics circles. Specifically, at a fixed point of the dynamics on the θ-torus, we return a finite-dimensional matrix propagator. We present this connection explicitly for several examples.

[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.

Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy.

PubMed

Pickard, Mark R; Williams, Gwyn T

2014-06-01

The putative tumour suppressor and apoptosis-promoting gene, growth arrest-specific 5 (GAS5), encodes long ncRNA (lncRNA) and snoRNAs. Its expression is down-regulated in breast cancer, which adversely impacts patient prognosis. In this preclinical study, the consequences of decreased GAS5 expression for breast cancer cell survival following treatment with chemotherapeutic agents are addressed. In addition, functional responses of triple-negative breast cancer cells to GAS5 lncRNA are examined, and mTOR inhibition as a strategy to enhance cellular GAS5 levels is investigated. Breast cancer cell lines were transfected with either siRNA to GAS5 or with a plasmid encoding GAS5 lncRNA and the effects on breast cancer cell survival were determined. Cellular responses to mTOR inhibitors were evaluated by assaying culture growth and GAS5 transcript levels. GAS5 silencing attenuated cell responses to apoptotic stimuli, including classical chemotherapeutic agents; the extent of cell death was directly proportional to cellular GAS5 levels. Imatinib action in contrast, was independent of GAS5. GAS5 lncRNA promoted the apoptosis of triple-negative and oestrogen receptor-positive cells but only dual PI3K/mTOR inhibition was able to enhance GAS5 levels in all cell types. Reduced GAS5 expression attenuates apoptosis induction by classical chemotherapeutic agents in breast cancer cells, providing an explanation for the relationship between GAS5 expression and breast cancer patient prognosis. Clinically, this relationship may be circumvented by the use of GAS5-independent drugs such as imatinib, or by restoration of GAS5 expression. The latter may be achieved by the use of a dual PI3K/mTOR inhibitor, to improve apoptotic responses to conventional chemotherapies.

[Distribution of soil heavy metal and pollution evaluation on the different sampling scales in farmland on Yellow River irrigation area of Ningxia: a case study in Xingqing County of Yinchuan City].

PubMed

Wang, You-Qi; Bai, Yi-Ru; Wang, Jian-Yu

2014-07-01

Determining spatial distributions and analyses contamination condition of soil heavy metals play an important role in evaluation of the quality of agricultural ecological environment and the protection of food safety and human health. Topsoil samples (0-20 cm) from 223 sites in farmland were collected at two scales of sampling grid (1 m x 1 m, 10 m x 10 m) in the Yellow River irrigation area of Ningxia. The objectives of this study were to investigate the spatial variability of total copper (Cu), total zinc (Zn), total chrome (Cr), total cadmium (Cd) and total lead (Pb) on the two sampling scales by the classical and geostatistical analyses. The single pollution index (P(i)) and the Nemerow pollution index (P) were used to evaluate the soil heavy metal pollution. The classical statistical analyses showed that all soil heavy metals demonstrated moderate variability, the coefficient of variation (CV) changed in the following sequence: Cd > Pb > Cr > Zn > Cu. Geostatistical analyses showed that the nugget coefficient of Cd on the 10 m x 10 m scale and Pb on the 1 m x 1 m scale were 100% with pure nugget variograms, which showed weak variability affected by random factors. The nugget coefficient of the other indexes was less than 25%, which showed a strong variability affected by structural factors. The results combined with P(i) and P indicated that most soil heavy metals have slight pollution except total copper, and in general there were the trend of heavy metal accumulation in the study area.

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...

Melatonin, Noncoding RNAs, Messenger RNA Stability and Epigenetics—Evidence, Hints, Gaps and Perspectives

PubMed Central

Hardeland, Rüdiger

2014-01-01

Melatonin is a highly pleiotropic regulator molecule, which influences numerous functions in almost every organ and, thus, up- or down-regulates many genes, frequently in a circadian manner. Our understanding of the mechanisms controlling gene expression is actually now expanding to a previously unforeseen extent. In addition to classic actions of transcription factors, gene expression is induced, suppressed or modulated by a number of RNAs and proteins, such as miRNAs, lncRNAs, piRNAs, antisense transcripts, deadenylases, DNA methyltransferases, histone methylation complexes, histone demethylases, histone acetyltransferases and histone deacetylases. Direct or indirect evidence for involvement of melatonin in this network of players has originated in different fields, including studies on central and peripheral circadian oscillators, shift work, cancer, inflammation, oxidative stress, aging, energy expenditure/obesity, diabetes type 2, neuropsychiatric disorders, and neurogenesis. Some of the novel modulators have also been shown to participate in the control of melatonin biosynthesis and melatonin receptor expression. Future work will need to augment the body of evidence on direct epigenetic actions of melatonin and to systematically investigate its role within the network of oscillating epigenetic factors. Moreover, it will be necessary to discriminate between effects observed under conditions of well-operating and deregulated circadian clocks, and to explore the possibilities of correcting epigenetic malprogramming by melatonin. PMID:25310649

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.

Estrogens Induce Rapid Cytoskeleton Re-Organization in Human Dermal Fibroblasts via the Non-Classical Receptor GPR30

PubMed Central

Carnesecchi, Julie; Malbouyres, Marilyne; de Mets, Richard; Balland, Martial; Beauchef, Gallic; Vié, Katell; Chamot, Christophe; Lionnet, Claire; Ruggiero, Florence; Vanacker, Jean-Marc

2015-01-01

The post-menopausal decrease in estrogen circulating levels results in rapid skin deterioration pointing out to a protective effect exerted by these hormones. The identity of the skin cell type responding to estrogens is unclear as are the cellular and molecular processes they elicit. Here, we reported that lack of estrogens induces rapid re-organization of the human dermal fibroblast cytoskeleton resulting in striking cell shape change. This morphological change was accompanied by a spatial re-organization of focal adhesion and a substantial reduction of their number as evidenced by vinculin and actin co-staining. Cell morphology and cytoskeleton organization was fully restored upon 17β-estradiol (E2) addition. Treatment with specific ER antagonists and cycloheximide respectively showed that the E2 acts independently of the classical Estrogen Receptors and that cell shape change is mediated by non-genomic mechanisms. E2 treatment resulted in a rapid and transient activation of ERK1/2 but not Src or PI3K. We show that human fibroblasts express the non-classical E2 receptor GPR30 and that its agonist G-1 phenocopies the effect of E2. Inhibiting GPR30 through treatment with the G-15 antagonist or specific shRNA impaired E2 effects. Altogether, our data reveal a novel mechanism by which estrogens act on skin fibroblast by regulating cell shape through the non-classical G protein-coupled receptor GPR30 and ERK1/2 activation. PMID:25781607

Estrogens induce rapid cytoskeleton re-organization in human dermal fibroblasts via the non-classical receptor GPR30.

PubMed

Carnesecchi, Julie; Malbouyres, Marilyne; de Mets, Richard; Balland, Martial; Beauchef, Gallic; Vié, Katell; Chamot, Christophe; Lionnet, Claire; Ruggiero, Florence; Vanacker, Jean-Marc

2015-01-01

The post-menopausal decrease in estrogen circulating levels results in rapid skin deterioration pointing out to a protective effect exerted by these hormones. The identity of the skin cell type responding to estrogens is unclear as are the cellular and molecular processes they elicit. Here, we reported that lack of estrogens induces rapid re-organization of the human dermal fibroblast cytoskeleton resulting in striking cell shape change. This morphological change was accompanied by a spatial re-organization of focal adhesion and a substantial reduction of their number as evidenced by vinculin and actin co-staining. Cell morphology and cytoskeleton organization was fully restored upon 17β-estradiol (E2) addition. Treatment with specific ER antagonists and cycloheximide respectively showed that the E2 acts independently of the classical Estrogen Receptors and that cell shape change is mediated by non-genomic mechanisms. E2 treatment resulted in a rapid and transient activation of ERK1/2 but not Src or PI3K. We show that human fibroblasts express the non-classical E2 receptor GPR30 and that its agonist G-1 phenocopies the effect of E2. Inhibiting GPR30 through treatment with the G-15 antagonist or specific shRNA impaired E2 effects. Altogether, our data reveal a novel mechanism by which estrogens act on skin fibroblast by regulating cell shape through the non-classical G protein-coupled receptor GPR30 and ERK1/2 activation.

Comparative pathology in ferrets infected with H1N1 influenza A viruses isolated from different hosts.

PubMed

Smith, Jennifer Humberd; Nagy, Tamas; Driskell, Elizabeth; Brooks, Paula; Tompkins, S Mark; Tripp, Ralph A

2011-08-01

Virus replication and pulmonary disease pathogenesis in ferrets following intranasal infection with a pandemic influenza virus strain (A/California/4/09 [CA09]), a human seasonal influenza H1N1 virus isolate (A/New Caledonia/20/99 [Ncal99]), a classical swine influenza H1N1 virus isolate (A/Swine/Iowa/15/30 [Sw30]), or an avian H1N1 virus isolate (A/Mallard/MN/A108-2355/08 [Mal08]) were compared. Nasal wash virus titers were similar for Ncal99 and Sw30, with peak virus titers of 10(5.1) 50% tissue culture infectious doses (TCID(50))/ml and 10(5.5) TCID(50)/ml occurring at day 3 postinfection (p.i.), respectively. The mean peak titer for CA09 also occurred at day 3 p.i. but was higher (10(7) TCID(50)/ml). In contrast, the peak virus titers (10(3.6) to 10(4.3) TCID(50)/ml) for Mal08 were delayed, occurring between days 5 and 7 p.i. Disease pathogenesis was characterized by microscopic lesions in the nasal turbinates and lungs of all ferrets; however, Sw30 infection was associated with severe bronchointerstitial pneumonia. The results demonstrate that although CA09 is highly transmissible in the human population and replicates well in the ferret model, it causes modest disease compared to other H1N1 viruses, particularly Sw30 infection.

Comparative Pathology in Ferrets Infected with H1N1 Influenza A Viruses Isolated from Different Hosts ▿

PubMed Central

Smith, Jennifer Humberd; Nagy, Tamas; Driskell, Elizabeth; Brooks, Paula; Tompkins, S. Mark; Tripp, Ralph A.

2011-01-01

Virus replication and pulmonary disease pathogenesis in ferrets following intranasal infection with a pandemic influenza virus strain (A/California/4/09 [CA09]), a human seasonal influenza H1N1 virus isolate (A/New Caledonia/20/99 [Ncal99]), a classical swine influenza H1N1 virus isolate (A/Swine/Iowa/15/30 [Sw30]), or an avian H1N1 virus isolate (A/Mallard/MN/A108-2355/08 [Mal08]) were compared. Nasal wash virus titers were similar for Ncal99 and Sw30, with peak virus titers of 105.1 50% tissue culture infectious doses (TCID50)/ml and 105.5 TCID50/ml occurring at day 3 postinfection (p.i.), respectively. The mean peak titer for CA09 also occurred at day 3 p.i. but was higher (107 TCID50/ml). In contrast, the peak virus titers (103.6 to 104.3 TCID50/ml) for Mal08 were delayed, occurring between days 5 and 7 p.i. Disease pathogenesis was characterized by microscopic lesions in the nasal turbinates and lungs of all ferrets; however, Sw30 infection was associated with severe bronchointerstitial pneumonia. The results demonstrate that although CA09 is highly transmissible in the human population and replicates well in the ferret model, it causes modest disease compared to other H1N1 viruses, particularly Sw30 infection. PMID:21593156

Nardosinone protects H9c2 cardiac cells from angiotensin II-induced hypertrophy.

PubMed

Du, Meng; Huang, Kun; Gao, Lu; Yang, Liu; Wang, Wen-Shuo; Wang, Bo; Huang, Kai; Huang, Dan

2013-12-01

Pathological cardiac hypertrophy induced by angiotensin II (AngII) can subsequently give rise to heart failure, a leading cause of mortality. Nardosinone is a pharmacologically active compound extracted from the roots of Nardostachys chinensis, a well-known traditional Chinese medicine. In order to investigate the effects of nardosinone on AngII-induced cardiac cell hypertrophy and the related mechanisms, the myoblast cell line H9c2, derived from embryonic rat heart, was treated with nardosinone (25, 50, 100, and 200 μmol/L) or AngII (1 μmol/L). Then cell surface area and mRNA expression of classical markers of hypertrophy were detected. The related protein levels in PI3K/Akt/mTOR and MEK/ERK signaling pathways were examined by Western blotting. It was found that pretreatment with nardosinone could significantly inhibit the enlargement of cell surface area induced by AngII. The mRNA expression of ANP, BNP and β-MHC was obviously elevated in AngII-treated H9c2 cells, which could be effectively blocked by nardosinone at the concentration of 100 μmol/L. Further study revealed that the protective effects of nardosinone might be mediated by repressing the phosphorylation of related proteins in PI3K/Akt and MEK/ERK signaling pathways. It was suggested that the inhibitory effect of nardosinone on Ang II-induced hypertrophy in H9c2 cells might be mediated by targeting PI3K/Akt and MEK/ERK signaling pathways.

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

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.

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

Fuzzy control of a fluidized bed dryer

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

Taprantzis, A.V.; Siettos, C.I.; Bafas, G.V.

1997-05-01

Fluidized bed dryers are utilized in almost every area of drying applications and therefore improved control strategies are always of great interest. The nonlinear character of the process, exhibited in the mathematical model and the open loop analysis, implies that a fuzzy logic controller is appropriate because, in contrast with conventional control schemes, fuzzy control inherently compensates for process nonlinearities and exhibits more robust behavior. In this study, a fuzzy logic controller is proposed; its design is based on a heuristic approach and its performance is compared against a conventional PI controller for a variety of responses. It is shownmore » that the fuzzy controller exhibits a remarkable dynamic behavior, equivalent if not better than the PI controller, for a wide range of disturbances. In addition, the proposed fuzzy controller seems to be less sensitive to the nonlinearities of the process, achieves energy savings and enables MIMO control.« less

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

Quantum "violation" of Dirichlet boundary condition

NASA Astrophysics Data System (ADS)

Park, I. Y.

2017-02-01

Dirichlet boundary conditions have been widely used in general relativity. They seem at odds with the holographic property of gravity simply because a boundary configuration can be varying and dynamic instead of dying out as required by the conditions. In this work we report what should be a tension between the Dirichlet boundary conditions and quantum gravitational effects, and show that a quantum-corrected black hole solution of the 1PI action no longer obeys, in the naive manner one may expect, the Dirichlet boundary conditions imposed at the classical level. We attribute the 'violation' of the Dirichlet boundary conditions to a certain mechanism of the information storage on the boundary.

Study of CP(N-1) theta-vacua by cluster simulation of SU(N) quantum spin ladders.

PubMed

Beard, B B; Pepe, M; Riederer, S; Wiese, U-J

2005-01-14

D-theory provides an alternative lattice regularization of the 2D CP(N-1) quantum field theory in which continuous classical fields emerge from the dimensional reduction of discrete SU(N) quantum spins. Spin ladders consisting of n transversely coupled spin chains lead to a CP(N-1) model with a vacuum angle theta=npi. In D-theory no sign problem arises and an efficient cluster algorithm is used to investigate theta-vacuum effects. At theta=pi there is a first order phase transition with spontaneous breaking of charge conjugation symmetry for CP(N-1) models with N>2.

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.

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

PubMed

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

2011-12-01

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

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

Raulli, R.; Crews, F.T.

The potency of various alpha adrenergic compounds on stimulation of phosphatidylinositol (PI) hydrolysis was determined using (/sup 3/H)-inositol labelled cerebral cortical slices. Norepinephrine-induced PI hydrolysis was inhibited by the alpha/sub 1/ selective antagonist prazosin (1 ..mu..M) but not the beta receptor antagonist propranolol (1 ..mu..M). Tramazoline, (-)-ephedrine, and (+/-)-phenylpropanolamine were all found to be partial agonists at 1 mM concentrations. Clonidine, naphazoline, trazodone, and the novel antidepressant mianserin at concentrations of 100 ..mu..M to 1 mM produced no significant increase in PI hydrolysis above control levels. The relationship between responses and receptor binding will be discussed.

Application of Static Var Compensator (SVC) With PI Controller for Grid Integration of Wind Farm Using Harmony Search

NASA Astrophysics Data System (ADS)

Keshta, H. E.; Ali, A. A.; Saied, E. M.; Bendary, F. M.

2016-10-01

Large-scale integration of wind turbine generators (WTGs) may have significant impacts on power system operation with respect to system frequency and bus voltages. This paper studies the effect of Static Var Compensator (SVC) connected to wind energy conversion system (WECS) on voltage profile and the power generated from the induction generator (IG) in wind farm. Also paper presents, a dynamic reactive power compensation using Static Var Compensator (SVC) at the a point of interconnection of wind farm while static compensation (Fixed Capacitor Bank) is unable to prevent voltage collapse. Moreover, this paper shows that using advanced optimization techniques based on artificial intelligence (AI) such as Harmony Search Algorithm (HS) and Self-Adaptive Global Harmony Search Algorithm (SGHS) instead of a Conventional Control Method to tune the parameters of PI controller for SVC and pitch angle. Also paper illustrates that the performance of the system with controllers based on AI is improved under different operating conditions. MATLAB/Simulink based simulation is utilized to demonstrate the application of SVC in wind farm integration. It is also carried out to investigate the enhancement in performance of the WECS achieved with a PI Controller tuned by Harmony Search Algorithm as compared to a Conventional Control Method.

Differences in glutathione S-transferase pi expression in transgenic mice with symptoms of neurodegeneration.

PubMed

Kaźmierczak, Beata; Kuźma-Kozakiewicz, Magdalena; Usarek, Ewa; Barańczyk-Kuźma, Anna

2011-01-01

Glutathione S-transferase pi (GST pi) is an enzyme involved in cell protection against toxic electrophiles and products of oxidative stress. GST pi expression was studied in transgenic mice hybrids (B6-C3H) with symptoms of neurodegeneration harboring SOD1G93A (SOD1/+), Dync1h1 (Cra1/+) and double (Cra1/SOD1) mutations, at presymptomatic and symptomatic stages (age 70, 140, 365 days) using RT-PCR and Western blotting. The main changes in GST pi expression were observed in mice with the SODG93A mutation. In SOD1/+ and Cra1/SOD1 transgenics, with the exception of cerebellum, the changes in GST pi-mRNA accompanied those in GST pi protein. In brain cortex of both groups the expression was unchanged at the presymptomatic (age 70 days) but was lower at the symptomatic stage (age 140 days) and at both stages in hippocampus and spinal cord of SOD1/+ but not of Cra1/SOD1 mice compared to age-matched wild-type controls. In cerebellum of the presymptomatic and the symptomatic SOD1/+ mice and presymptomatic Cra1/SOD1 mice, the GST pi-mRNA was drastically elevated but the protein level remained unchanged. In Cra1/+ transgenics there were no changes in GST pi expression in any CNS region both on the mRNA and on the protein level. It can be concluded that the SOD1G93A but not the Dync1h1 mutation significantly decreases detoxification efficiency of GST pi in CNS, however the Dync1h1 mutation reduces the effects caused by the SOD1G93A mutation. Despite similarities in neurological symptoms, the differences in GST pi expression between SOD1/+ and Cra1/+ transgenics indicate a distinct pathogenic entity of these two conditions.

Dynamics of receptor-operated Ca(2+) currents through TRPC channels controlled via the PI(4,5)P2-PLC signaling pathway.

PubMed

Mori, Masayuki X; Itsuki, Kyohei; Hase, Hideharu; Sawamura, Seishiro; Kurokawa, Tatsuki; Mori, Yasuo; Inoue, Ryuji

2015-01-01

Transient receptor potential canonical (TRPC) channels are Ca(2+)-permeable, nonselective cation channels that carry receptor-operated Ca(2+) currents (ROCs) triggered by receptor-induced, phospholipase C (PLC)-catalyzed hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Within the vasculature, TRPC channel ROCs contribute to smooth muscle cell depolarization, vasoconstriction, and vascular remodeling. However, TRPC channel ROCs exhibit a variable response to receptor-stimulation, and the regulatory mechanisms governing TRPC channel activity remain obscure. The variability of ROCs may be explained by their complex regulation by PI(4,5)P2 and its metabolites, which differentially affect TRPC channel activity. To resolve the complex regulation of ROCs, the use of voltage-sensing phosphoinositide phosphatases and model simulation have helped to reveal the time-dependent contribution of PI(4,5)P2 and the possible role of PI(4,5)P2 in the regulation of ROCs. These approaches may provide unprecedented insight into the dynamics of PI(4,5)P2 regulation of TRPC channels and the fundamental mechanisms underlying transmembrane ion flow. Within that context, we summarize the regulation of TRPC channels and their coupling to receptor-mediated signaling, as well as the application of voltage-sensing phosphoinositide phosphatases to this research. We also discuss the controversial bidirectional effects of PI(4,5)P2 using a model simulation that could explain the complicated effects of PI(4,5)P2 on different ROCs.

A PI3-kinase-mediated negative feedback regulates neuronal excitability.

PubMed

Howlett, Eric; Lin, Curtis Chun-Jen; Lavery, William; Stern, Michael

2008-11-01

Use-dependent downregulation of neuronal activity (negative feedback) can act as a homeostatic mechanism to maintain neuronal activity at a particular specified value. Disruption of this negative feedback might lead to neurological pathologies, such as epilepsy, but the precise mechanisms by which this feedback can occur remain incompletely understood. At one glutamatergic synapse, the Drosophila neuromuscular junction, a mutation in the group II metabotropic glutamate receptor gene (DmGluRA) increased motor neuron excitability by disrupting an autocrine, glutamate-mediated negative feedback. We show that DmGluRA mutations increase neuronal excitability by preventing PI3 kinase (PI3K) activation and consequently hyperactivating the transcription factor Foxo. Furthermore, glutamate application increases levels of phospho-Akt, a product of PI3K signaling, within motor nerve terminals in a DmGluRA-dependent manner. Finally, we show that PI3K increases both axon diameter and synapse number via the Tor/S6 kinase pathway, but not Foxo. In humans, PI3K and group II mGluRs are implicated in epilepsy, neurofibromatosis, autism, schizophrenia, and other neurological disorders; however, neither the link between group II mGluRs and PI3K, nor the role of PI3K-dependent regulation of Foxo in the control of neuronal excitability, had been previously reported. Our work suggests that some of the deficits in these neurological disorders might result from disruption of glutamate-mediated homeostasis of neuronal excitability.

Cardiac structure and function in elite Native Hawaiian and Pacific Islander Rugby Football League athletes: an exploratory study.

PubMed

Johnson, Christopher; Forsythe, Lynsey; Somauroo, John; Papadakis, Michael; George, Keith; Oxborough, David

2018-05-01

The aim of this exploratory study was to define the Athletes Heart (AH) phenotype in Native Hawaiian & Pacific Islander (NH&PI) Rugby Football League (RFL) athletes. Specifically, (1) to describe conventional echocardiographic indices of left ventricle (LV) and right ventricle (RV) structure and function in NH&PI RFL players and matched RFL Caucasian controls (CC) and (2) to demonstrate LV and RV mechanics in these populations. Ethnicity is a contributory factor to the phenotypical expression of the AH. There are no data describing the cardiac phenotype in NH&PI athletes. Twenty-one male elite NH&PI RFL athletes were evaluated using conventional echocardiography and myocardial speckle tracking, allowing the assessment of global longitudinal strain (ε) and strain rate (SR); and basal, mid and global radial and circumferential ε and SR. Basal and apical rotation and twist were also assessed. Results were compared with age-matched Caucasian counterparts (CC; n = 21). LV mass [42 ± 9 versus 37 ± 4 g/(m 2.7 )], mean LV wall thickness (MWT: 9.5 ± 0.7 and 8.7 ± 0.4 mm), relative wall thickness (RWT: 0.35 ± 0.04 and 0.31 ± 0.03) and RV wall thickness (5 ± 1 and 4 ± 1 mm, all p < 0.05) were greater in NH&PI compared with CC. LV and RV cavity dimensions and standard indices of LV and RV systolic and diastolic function were similar between groups. NH&PI demonstrated reduced peak LV mid circumferential ε and early diastolic SR, as well as reduced global radial ε. There was reduced basal rotation at 25-35% systole, reduced apical rotation at 25-40% and 60-100% systole and reduced twist at 85-95% systole in NH&PI athletes. There were no differences between the two groups in RV wall mechanics. When compared to Caucasian controls, NH&PI rugby players have a greater LV mass, MWT and RWT with concomitant reductions in circumferential and twist mechanics. This data acts to prompt further research in NH&PI athletes.

Role of protein kinase A and class II phosphatidylinositol 3-kinase C2β in the downregulation of KCa3.1 channel synthesis and membrane surface expression by lyso-globotriaosylceramide

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

Choi, Ju Yeon; Park, Seonghee, E-mail: sp@ewha.ac.kr

The intermediate conductance calcium-activated potassium channel (KCa3.1) mediates proliferation of many cell types including fibroblasts, and is a molecular target for intervention in various cell proliferative diseases. Our previous study showed that reduction of KCa3.1 channel expression by lyso-globotriaosylceramide (lyso-Gb3) inhibits differentiation into myofibroblasts and collagen synthesis, which might lead to development of ascending thoracic aortic aneurysm secondary to Fabry disease. However, how lyso-Gb3 downregulates KCa3.1 channel expression is unknown. Therefore, we aimed to investigate the underlying mechanisms of lyso-Gb3-mediated KCa3.1 channel downregulation, focusing on the cAMP signaling pathway. We found that lyso-Gb3 increased the intracellular cAMP concentration by upregulationmore » of adenylyl cyclase 6 and inhibited ERK 1/2 phosphorylation through the protein kinase A (PKA) pathway, leading to the inhibition of KCa3.1 channel synthesis, not the exchange protein directly activated by cAMP (Epac) pathway. Moreover, lyso-Gb3 suppressed expression of class II phosphatidylinositol 3-kinase C2β (PI3KC2β) by PKA activation, which reduces the production of phosphatidylinositol 3-phosphate [PI(3)P], and the reduced membrane surface expression of KCa3.1 channel was recovered by increasing the intracellular levels of PI(3)P. Consequently, our findings that lyso-Gb3 inhibited both KCa3.1 channel synthesis and surface expression by increasing intracellular cAMP, and controlled surface expression through changes in PI3KC2β-mediated PI(3)P production, suggest that modulation of PKA and PI3KC2β activity to control of KCa3.1 channel expression can be an alternative important target to attenuate ascending thoracic aortic aneurysms in Fabry disease. - Highlights: • Lyso-Gb3 causes elevation of intracellular cAMP. • Lyso-Gb3 inhibits the ERK 1/2 phosphorylation through PKA, thereby reducing KCa3.1 channel synthesis. • Lyso-Gb3 reduces PI3KC2β-mediated intracellular PI(3)P production. • Lyso-Gb3 reduces both surface and total expression of the KCa3.1 channel. • Increasing intracellular levels of PI(3)P only recovers the reduced surface expression.« less

Maternal serum placental growth factor (PlGF) in small for gestational age pregnancy at 11(+0) to 13(+6) weeks of gestation.

PubMed

Poon, Leona C Y; Zaragoza, Edgar; Akolekar, Ranjit; Anagnostopoulos, Evangelos; Nicolaides, Kypros H

2008-12-01

To investigate the pathogenesis of pregnancies delivering small for gestational age (SGA) neonates by examining biochemical and Doppler indices of placental development during the first trimester of pregnancy. The concentration of placental growth factor (PlGF) at 11(+0)-13(+6) weeks was measured in 296 cases, which delivered SGA neonates, and 609 controls. The newborn was considered to be SGA if the birth weight was less than the fifth percentile after correction for gestation at delivery and sex, maternal racial origin, weight, height and parity. The distributions of uterine artery pulsatility index (PI), PlGF and PAPP-A, expressed in multiples of the median (MoM), in the control and SGA groups were compared. Logistic regression analysis was used to determine if significant contribution is provided by maternal factors, PlGF, PAPP-A and uterine artery PI in predicting SGA. The median PlGF (0.900 MoM) and PAPP-A (0.778 MoM) were lower and uterine artery PI was higher (1.087 MoM) in the SGA group than in the controls (PlGF: 0.991 MoM; PAPP-A: 1.070 MoM; uterine artery PI: 1.030 MoM). In the SGA group there was a significant association between PlGF and PAPP-A (r = 0.368, p < 0.0001) and uterine artery PI (r = 0.191, p = 0.001). Significant contributions for the prediction of SGA were provided by maternal factors, PlGF and PAPP-A and with combined screening the detection rate was 27% at a false-positive rate of 5%. Birth weight is predetermined by placental development during the first trimester of pregnancy. Copyright (c) 2008 John Wiley & Sons, Ltd.

Insulin-like growth factor-1 (IGF-1) promotes primordial follicle growth and reduces DNA fragmentation through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signalling pathway.

PubMed

Bezerra, Maria É S; Barberino, Ricássio S; Menezes, Vanúzia G; Gouveia, Bruna B; Macedo, Taís J S; Santos, Jamile M S; Monte, Alane P O; Barros, Vanessa R P; Matos, Maria H T

2018-05-30

We investigated the effects of insulin-like growth factor 1 (IGF-1) on the morphology and follicular activation of ovine preantral follicles cultured in situ and whether the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway is involved in IGF-1 action in the sheep ovary. Ovine ovarian fragments were fixed for histological and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) analyses (fresh control) or cultured in supplemented alpha-minimum essential medium (α-MEM+; control) or α-MEM+ with IGF-1 (1, 10, 50, 100 or 200ngmL-1) for 7 days. Follicles were classified as normal or atretic, primordial or growing and the oocyte and follicle diameters were measured. DNA fragmentation was evaluated by TUNEL assay. Proliferating cell nuclear antigen (PCNA) immunohistochemistry was performed on the fresh control, α-MEM+ and 100ngmL-1 IGF-1 samples. Inhibition of PI3K activity was performed through pretreatment with the PI3K inhibitor LY294002 and phosphorylated AKT (pAKT) expression was analysed after culture in the absence or presence of LY294002. IGF-1 at 100ngmL-1 increased (P<0.05) follicular activation compared with α-MEM+ and decreased TUNEL-positive cells (P<0.05) compared with other treatments. PCNA-positive cells also increased (P<0.05) in 100ngmL-1 IGF-1. LY294002 significantly inhibited follicular activation stimulated by α-MEM+ and 100ngmL-1 IGF-1 and reduced pAKT expression in follicles. Overall, IGF-1 at 100ngmL-1 promoted primordial follicle activation, cell proliferation and reduced DNA fragmentation after in situ culture through the PI3K/AKT pathway.

Light-dependent activation of phosphoenolpyruvate carboxylase by reversible phosphorylation in cluster roots of white lupin plants: diurnal control in response to photosynthate supply

PubMed Central

Feil, Regina; Lunn, John E.; Plaxton, William C.

2016-01-01

Background and Aims Phosphoenolpyruvate carboxylase (PEPC) is a tightly regulated enzyme that controls carbohydrate partitioning to organic acid anions (malate, citrate) excreted in copious amounts by cluster roots of inorganic phosphate (Pi)-deprived white lupin plants. Excreted malate and citrate solubilize otherwise inaccessible sources of mineralized soil Pi for plant uptake. The aim of this study was to test the hypotheses that (1) PEPC is post-translationally activated by reversible phosphorylation in cluster roots of illuminated white lupin plants, and (2) light-dependent phosphorylation of cluster root PEPC is associated with elevated intracellular levels of sucrose and its signalling metabolite, trehalose-6-phosphate. Methods White lupin plants were cultivated hydroponically at low Pi levels (≤1 µm) and subjected to various light/dark pretreatments. Cluster root PEPC activity and in vivo phosphorylation status were analysed to assess the enzyme’s diurnal, post-translational control in response to light and dark. Levels of various metabolites, including sucrose and trehalose-6-phosphate, were also quantified in cluster root extracts using enzymatic and spectrometric methods. Key Results During the daytime the cluster root PEPC was activated by phosphorylation at its conserved N-terminal seryl residue. Darkness triggered a progressive reduction in PEPC phosphorylation to undetectable levels, and this was correlated with 75–80 % decreases in concentrations of sucrose and trehalose-6- phosphate. Conclusions Reversible, light-dependent regulatory PEPC phosphorylation occurs in cluster roots of Pi-deprived white lupin plants. This likely facilitates the well-documented light- and sucrose-dependent exudation of Pi-solubilizing organic acid anions by the cluster roots. PEPC’s in vivo phosphorylation status appears to be modulated by sucrose translocated from CO2-fixing leaves into the non-photosynthetic cluster roots. PMID:27063365

Controlled self-assembly of conjugated rod-coil block copolymers for applications in organic optoelectronics

NASA Astrophysics Data System (ADS)

Tao, Yuefei

Organic electronics are of great interest in manufacturing light weight, mechanical flexible, and inexpensive large area devices. While significant improvements have been made over the last several years and it is now clear that morphology on the lengthscale of exciton diffusion (10nm) is of crucial importance, a clear relationship between structure and device properties has not emerged. This lack of understanding largely emerges from an inability to control morphology on this lengthscale. This thesis will center around an approach, based on block copolymer self-assembly, to generate equilibrium nanostructures on the 10 nm lengthscale of exciton diffusion and study their effects on device performance. Self-assembly of semiconducting block copolymers is complicated by the non-classical chain shape of conjugated polymers. Unlike classical polymers, the chains do not assume a Gaussian coil shape which is stretched near block copolymer interfaces, instead the chains are elongated and liquid crystalline. Previous work has demonstrated how these new molecular interactions and shapes control the phase diagram of so-called rod-coil block copolymers. Here, we will focus on controlling domain size, orientation, and chemical structure. While domain size can be controlled directly through molecular weight, this requires significant additional synthesis of domain size is to be varied. Here, the domain size is controlled by blending homopolymers into a self-assembling rod-coil block copolymer. When coil-like blocks are incorporated, the domains swell, as expected. When rod-like blocks are incorporated, they interdigitate with the rods of the block copolymers. This results in an increase in interfacial area which forces the coils to rearrange and an overall decrease in domain size with increasing rod content. Control over lamellar orientation is crucial in order to design and control charge transport pathways and exciton recombination or separation interfaces. While numerous techniques have been demonstrated for classical block copolymers, the pi conjugation in the rod blocks allow for additional control mechanisms. Liquid crystals are traditionally aligned in magnetic fields. Here, it is demonstrated that if the rod-like blocks are aligned unidirectionally, the block copolymer interfaces follow to create macroscopic alignment of the nanostructures. Organic Light Emitting Diodes (OLEDs) are generally composed of electron transporting and hole transporting moieties to balance charge recombination. Here, a new multifunctional bipolar rod-coil block copolymer containing the hole transporting and electron transporting materials is synthesized. Self-assembly of this new block copolymer results in 15nm lamellae oriented in grains both parallel and perpendicula to the anode. The self-assembled block copolymer shows superior device performance to controls consisting of a luminescent, analogous homopolymer, and a blend of the two component homopolymers. The effects of the morphologies and chemical structure on photovoltaics is explored with a rod-coil block copolymer, (poly(3-hexylthiophene-b-acrylic perylene)). By varying the kinetics of self-assembly through processing, the block copolymer can be disordered, ordered with only short range registry between the nanodomains, or with long-range order. The short range ordered samples showed the best device performance suggesting that the connectivity that is a biproduct of poor order is beneficial for device performance.

Carbon dioxide diffusion across stomata and mesophyll and photo-biochemical processes as affected by growth CO2 and phosphorus nutrition in cotton.

PubMed

Singh, Shardendu K; Badgujar, Girish; Reddy, Vangimalla R; Fleisher, David H; Bunce, James A

2013-06-15

Nutrients such as phosphorus may exert a major control over plant response to rising atmospheric carbon dioxide concentration (CO2), which is projected to double by the end of the 21st century. Elevated CO2 may overcome the diffusional limitations to photosynthesis posed by stomata and mesophyll and alter the photo-biochemical limitations resulting from phosphorus deficiency. To evaluate these ideas, cotton (Gossypium hirsutum) was grown in controlled environment growth chambers with three levels of phosphate (Pi) supply (0.2, 0.05 and 0.01mM) and two levels of CO2 concentration (ambient 400 and elevated 800μmolmol(-1)) under optimum temperature and irrigation. Phosphate deficiency drastically inhibited photosynthetic characteristics and decreased cotton growth for both CO2 treatments. Under Pi stress, an apparent limitation to the photosynthetic potential was evident by CO2 diffusion through stomata and mesophyll, impairment of photosystem functioning and inhibition of biochemical process including the carboxylation efficiency of ribulose-1,5-bisphosphate carboxylase/oxyganase and the rate of ribulose-1,5-bisphosphate regeneration. The diffusional limitation posed by mesophyll was up to 58% greater than the limitation due to stomatal conductance (gs) under Pi stress. As expected, elevated CO2 reduced these diffusional limitations to photosynthesis across Pi levels; however, it failed to reduce the photo-biochemical limitations to photosynthesis in phosphorus deficient plants. Acclimation/down regulation of photosynthetic capacity was evident under elevated CO2 across Pi treatments. Despite a decrease in phosphorus, nitrogen and chlorophyll concentrations in leaf tissue and reduced stomatal conductance at elevated CO2, the rate of photosynthesis per unit leaf area when measured at the growth CO2 concentration tended to be higher for all except the lowest Pi treatment. Nevertheless, plant biomass increased at elevated CO2 across Pi nutrition with taller plants, increased leaf number and larger leaf area. Copyright © 2013 Elsevier GmbH. All rights reserved.

Reduced Brain GABA in Primary Insomnia: Preliminary Data from 4T Proton Magnetic Resonance Spectroscopy (1H-MRS)

PubMed Central

Winkelman, John W.; Buxton, Orfeu M.; Jensen, J. Eric; Benson, Kathleen L.; O'Connor, Shawn P.; Wang, Wei; Renshaw, Perry F.

2008-01-01

Study Objectives: Both basic and clinical data suggest a potential significant role for GABA in the etiology and maintenance of primary insomnia (PI). Proton magnetic resonance spectroscopy (1H-MRS) can non-invasively determine GABA levels in human brain. Our objective was to assess GABA levels in unmedicated individuals with PI, using 1H-MRS. Design and Setting: Matched-groups, cross-sectional study conducted at two university-based hospitals. Participants: Sixteen non-medicated individuals (8 women) with PI (mean age = 37.3 +/− 8.1) and 16 (7 women) well-screened normal sleepers (mean age = 37.6 +/− 4.5). Methods and Measurements: PI was established with an unstructured clinical interview, a Structured Clinical Interview for DSM-IV (SCID), sleep diary, actigraphy and polysomnography (PSG). 1H-MRS data were collected on a Varian 4 Tesla magnetic resonance imaging/spectroscopy scanner. Global brain GABA levels were averaged from samples in the basal ganglia, thalamus, and temporal, parietal, and occipital white-matter and cortex. Results: Average brain GABA levels were nearly 30% lower in patients with PI (.18 +/− .06) compared to controls (.25 +/− .11). GABA levels were negatively correlated with wake after sleep onset (WASO) on two independent PSGs (r = −0.71, p = 0.0024 and −0.70, p = 0.0048). Conclusions: Our preliminary finding of a global reduction in GABA in non-medicated individuals with PI is the first demonstration of a neurochemical difference in the brains of those with PI compared to normal sleeping controls. 1H-MRS is a valuable tool to assess GABA in vivo, and may provide a means to shed further light on the neurobiology of insomnia. Citation: Winkelman JW; Buxton OM; Jensen JE; Benson KL; O'Connor SP; Wang W; Renshaw PF. Reduced brain GABA in primary insomnia: preliminary data from 4T proton magnetic resonance spectroscopy (1H-MRS). SLEEP 2008;31(11):1499–1506. PMID:19014069

Remodeling of the malaria parasite and host human red cell by vesicle amplification that induces artemisinin resistance

PubMed Central

Coppens, Isabelle; Mbengue, Alassane; Suresh, Niraja; Ghorbal, Mehdi; Slouka, Zdenek; Safeukui, Innocent; Tang, Hsin-Yao; Speicher, David W.; Stahelin, Robert V.; Mohandas, Narla

2018-01-01

Artemisinin resistance threatens worldwide malaria control and elimination. Elevation of phosphatidylinositol-3-phosphate (PI3P) can induce resistance in blood stages of Plasmodium falciparum. The parasite unfolded protein response (UPR) has also been implicated as a proteostatic mechanism that may diminish artemisinin-induced toxic proteopathy. How PI3P acts and its connection to the UPR remain unknown, although both are conferred by mutation in P falciparum Kelch13 (K13), the marker of artemisinin resistance. Here we used cryoimmunoelectron microscopy to show that K13 concentrates at PI3P tubules/vesicles of the parasite’s endoplasmic reticulum (ER) in infected red cells. K13 colocalizes and copurifies with the major virulence adhesin PfEMP1. The PfEMP1-K13 proteome is comprehensively enriched in multiple proteostasis systems of protein export, quality control, and folding in the ER and cytoplasm and UPR. Synthetic elevation of PI3P that induces resistance in absence of K13 mutation also yields signatures of proteostasis and clinical resistance. These findings imply a key role for PI3P-vesicle amplification as a mechanism of resistance of infected red cells. As validation, the major resistance mutation K13C580Y quantitatively increased PI3P tubules/vesicles, exporting them throughout the parasite and the red cell. Chemical inhibitors and fluorescence microscopy showed that alterations in PfEMP1 export to the red cell and cytoadherence of infected cells to a host endothelial receptor are features of multiple K13 mutants. Together these data suggest that amplified PI3P vesicles disseminate widespread proteostatic capacity that may neutralize artemisinins toxic proteopathy and implicate a role for the host red cell in artemisinin resistance. The mechanistic insights generated will have an impact on malaria drug development. PMID:29363540

PIWI Proteins and PIWI-Interacting RNA: Emerging Roles in Cancer.

PubMed

Han, Yi-Neng; Li, Yuan; Xia, Sheng-Qiang; Zhang, Yuan-Yuan; Zheng, Jun-Hua; Li, Wei

2017-01-01

P-Element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a type of noncoding RNAs (ncRNAs) and interact with PIWI proteins. piRNAs were primarily described in the germline, but emerging evidence revealed that piRNAs are expressed in a tissue-specific manner among multiple human somatic tissue types as well and play important roles in transposon silencing, epigenetic regulation, gene and protein regulation, genome rearrangement, spermatogenesis and germ stem-cell maintenance. PIWI proteins were first discovered in Drosophila and they play roles in spermatogenesis, germline stem-cell maintenance, self-renewal, retrotransposons silencing and the male germline mobility control. A growing number of studies have demonstrated that several piRNA and PIWI proteins are aberrantly expressed in various kinds of cancers and may probably serve as a novel biomarker and therapeutic target for cancer treatment. Nevertheless, their specific mechanisms and functions need further investigation. In this review, we discuss about the biogenesis, functions and the emerging role of piRNAs and PIWI proteins in cancer, providing novel insights into the possible applications of piRNAs and PIWI proteins in cancer diagnosis and clinical treatment. © 2017 The Author(s). Published by S. Karger AG, Basel.

Dynamic formation of ER–PM junctions presents a lipid phosphatase to regulate phosphoinositides

PubMed Central

Jensen, Jill B.; Vivas, Oscar; Kruse, Martin; Traynor-Kaplan, Alexis E.; Hille, Bertil

2016-01-01

Endoplasmic reticulum–plasma membrane (ER–PM) contact sites play an integral role in cellular processes such as excitation–contraction coupling and store-operated calcium entry (SOCE). Another ER–PM assembly is one tethered by the extended synaptotagmins (E-Syt). We have discovered that at steady state, E-Syt2 positions the ER and Sac1, an integral ER membrane lipid phosphatase, in discrete ER–PM junctions. Here, Sac1 participates in phosphoinositide homeostasis by limiting PM phosphatidylinositol 4-phosphate (PI(4)P), the precursor of PI(4,5)P2. Activation of G protein–coupled receptors that deplete PM PI(4,5)P2 disrupts E-Syt2–mediated ER–PM junctions, reducing Sac1’s access to the PM and permitting PM PI(4)P and PI(4,5)P2 to recover. Conversely, depletion of ER luminal calcium and subsequent activation of SOCE increases the amount of Sac1 in contact with the PM, depleting PM PI(4)P. Thus, the dynamic presence of Sac1 at ER–PM contact sites allows it to act as a cellular sensor and controller of PM phosphoinositides, thereby influencing many PM processes. PMID:27044890

Carcinogenesis of PIK3CA

PubMed Central

2013-01-01

PIK3CA is the most frequently mutated oncogene in human cancers. PIK3CA is phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha. It controls cell growth, proliferation, motility, survival, differentiation and intracellular trafficking. In most of human cancer alteration occurred frequently in the alpha isoform of phosphatidylinositol 3 kinase. PIK3CA mutations were most frequent in endometrial, ovarian, colorectal, breast, cervical, squamous cell cancer of the head and neck, chondroma, thyroid carcinoma and in cancer family syndrome. Inhibition of PI3K signaling can diminish cell proliferation, and in some circumstances, promote cell death. Consequently, components of this pathway present attractive targets for cancer therapeutics. A number of PI3K pathway inhibitors have been developed and used. PI3K inhibitors (both pan-PI3K and isoform-specific PI3K inhibitors), dual PI3K-mTOR inhibitors that are catalytic site inhibitors of the p110 isoforms and mTOR (the kinase component of both mTORC1 and mTORC2), mTOR catalytic site inhibitors, and AKT inhibitors are the most advanced in the clinic. They are approved for the treatment of several carcinomas. PMID:23768168

Aurora kinase A revives dormant laryngeal squamous cell carcinoma cells via FAK/PI3K/Akt pathway activation

PubMed Central

Yang, Li-yun; He, Chang-yu; Chen, Xue-hua; Su, Li-ping; Liu, Bing-ya; Zhang, Hao

2016-01-01

Revival of dormant tumor cells may be an important tumor metastasis mechanism. We hypothesized that aurora kinase A (AURKA), a cell cycle control kinase, promotes the transition of laryngeal squamous cell carcinoma (LSCC) cells from G0 phase to active division. We therefore investigated whether AURKA could revive dormant tumor cells to promote metastasis. Western blotting revealed that AURKA expression was persistently low in dormant laryngeal cancer Hep2 (D-Hep2) cells and high in non-dormant (T-Hep2) cells. Decreasing AURKA expression in T-Hep2 cells induced dormancy and reduced FAK/PI3K/Akt pathway activity. Increasing AURKA expression in D-Hep2 cells increased FAK/PI3K/Akt pathway activity and enhanced cellular proliferation, migration, invasion and metastasis. In addition, FAK/PI3K/Akt pathway inhibition caused dormancy-like behavior and reduced cellular mobility, migration and invasion. We conclude that AURKA may revive dormant tumor cells via FAK/PI3K/Akt pathway activation, thereby promoting migration and invasion in laryngeal cancer. AURKA/FAK/PI3K/Akt inhibitors may thus represent potential targets for clinical LSCC treatment. PMID:27356739

Salivary Markers and Microbial Flora in Mouth Breathing Late Adolescents

PubMed Central

Caruso, Silvia; Quinzi, Vincenzo; Marchetti, Enrico; Marzo, Giuseppe

2018-01-01

Objective This is a 6-month observational case-control study that aims to estimate plaque index (PI), salivary flow, buffering capacity of saliva, and specific Streptococcus mutans (S. mutans) and Lactobacillus rates in a mouth breathing late adolescents sample, after a professional oral hygiene procedure and home oral hygiene instructions. Subjects and Methods A sample of 20 mouth breathing late adolescents/young adults (average: 19.2 ± 2.5; range: 18–23 years) and a matched control group of nose breathing subjects (average: 18.3 ± 3.2; range 18–23 years) were included in the study. All the participants were subjected to a professional oral hygiene procedure and appropriate home oral hygiene instructions (t0). After three months (t1) and six months (t2), the PI, salivary flow, buffering capacity of saliva, and S. mutans and Lactobacilli rates were recorded. Results The mean buffering capacity of saliva and the salivary flow rate showed no significant difference between the two groups, all over the observational period. For PI, a significantly higher mode (score 1 of PI) was observed in the study group at t1 (score 0 = 35% of subjects; score 1 = 60%; score 2 = 5%) and t2 (score 1 = 65% of subjects, score 2 = 35%), with respect to control group. Furthermore, mouth breathing subjects show a significant 4 times higher risk to develop S. mutans CFU > 105 (CI lower limit: 0.95; CI upper limit: 9.48; chi-square: 4.28; p = 0.03), with respect to the control subjects. Conclusions Mouth breathing late adolescents show a significantly higher risk to develop S. mutans CFU > 105 and an increased level of PI. Interceptive orthodontic treatments in growing subjects, like palatal expansion, are encouraged to improve the nasal air flow. In older subjects, orthodontic treatments should be performed with removable appliances like clear aligners, in order to allow a better oral hygiene level. PMID:29693018

Carbon 11–Labeled Pittsburgh Compound B and Carbon 11–Labeled (R)-PK11195 Positron Emission Tomographic Imaging in Alzheimer Disease

PubMed Central

Wiley, Clayton A.; Lopresti, Brian J.; Venneti, Sriram; Price, Julie; Klunk, William E.; DeKosky, Steven T.; Mathis, Chester A.

2009-01-01

Background Alzheimer disease (AD) is defined neuropathologically by the presence of neurofibrillary tangles and plaques associated with tau and β-amyloid protein deposition. The colocalization of microglia and β-amyloid plaques has been widely reported in pathological examination of AD and suggests that neuroinflammation may play a role in pathogenesis and/or progression. Because postmortem histopathological analyses are limited to single end-stage assessment, the time course and nature of this relationship are not well understood. Objective To image microglial activation and β-amyloid deposition in the brains of subjects with and without AD. Design, Setting, and Participants Using two carbon 11 ([11C])–labeled positron emission tomographic imaging agents, Pittsburgh Compound B (PiB) and (R)-PK11195, we examined the relationship between amyloid deposition and microglial activation in different stages of AD using 5 control subjects, 6 subjects diagnosed with mild cognitive impairment, and 6 patients with mild to moderate AD. Results Consistent with prior reports, subjects with a clinical diagnosis of probable AD showed significantly greater levels of [11C]PiB retention than control subjects, whereas patients with mild cognitive impairment spanned a range from control-like to AD-like levels of [11C]PiB retention. Additionally, 2 asymptomatic control subjects also exhibited evidence of elevated PiB retention in regions associated with the early emergence of plaques in AD and may represent prodromal cases of AD. We observed no differences in brain [11C](R)-PK11195 retention when subjects were grouped by clinical diagnosis or the presence or absence of β-amyloid pathological findings as indicated by analyses of [11C]PiB retention. Conclusions These findings suggest that either microglial activation is limited to later stages of severe AD or [11C](R)-PK11195 is too insensitive to detect the level of microglial activation associated with mild to moderate AD. PMID:19139300

Hyperelastic remodeling in the intrauterine growth restricted (IUGR) carotid artery in the near-term fetus

PubMed Central

Dodson, R. Blair; Rozance, Paul J.; Reina-Romo, Esther; Ferguson, Virginia L.; Hunter, Kendall S.

2013-01-01

A constitutive model for a fiber reinforced hyperelastic material was applied to understand arterial fiber remodeling in a sheep model of Intrauterine Growth Restriction (IUGR). IUGR is associated altered hemodynamics characterized by increased resistance to blood flow in the placenta and elevated fetal arterial pressure and pulsatility. The constitutive model describes the collagen contribution to the mechanics within the arterial wall in both control and IUGR carotid artery through defining the material modulus and the orientation of the microstructure. A sheep model of placental insufficiency induced IUGR (PI-IUGR) was created by exposure of the pregnant ewe to elevated ambient temperatures. Experimental data was collected using pressure–diameter measurements to measure passive compliance in control and PI-IUGR carotid arteries. The constitutive model was optimized to fit the experimental data predicting the material parameters. Specifically, the collagen fiber predicted angle (γ) in the control artery was 49.9° from the circumferential axis while the PI-IUGR was 16.6° with a 23.5% increase in fiber orientation (κ). Quantitative assessment of collagen fiber orientation in secondary harmonic generation images confirmed the shift in orientation between the two groups. Together these suggest vascular remodeling of the ECM fiber orientation plays a major role in arterial stiffening in the PI-IUGR near-term fetal sheep. PMID:23332229

Targeted disruption of Pten in ovarian granulosa cells enhances ovulation and extends the life span of luteal cells.

PubMed

Fan, Heng-Yu; Liu, Zhilin; Cahill, Nicola; Richards, JoAnne S

2008-09-01

FSH activates the phosphatidylinositol-3 kinase (PI3K)/acute transforming retrovirus thymoma protein kinase pathway and thereby enhances granulosa cell differentiation in culture. To identify the physiological role of the PI3K pathway in vivo we disrupted the PI3K suppressor, Pten, in developing ovarian follicles. To selectively disrupt Pten expression in granulosa cells, Ptenfl/fl mice were mated with transgenic mice expressing cAMP response element recombinase driven by Cyp19 promoter (Cyp19-Cre). The resultant Pten mutant mice were fertile, ovulated more oocytes, and produced moderately more pups than control mice. These physiological differences in the Pten mutant mice were associated with hyperactivation of the PI3K/acute transforming retrovirus thymoma protein kinase pathway, decreased susceptibility to apoptosis, and increased proliferation of mutant granulosa cells. Strikingly, corpora lutea of the Pten mutant mice persisted longer than those of control mice. Although the follicular and luteal cell steroidogenesis in Ptenfl/fl;Cyp19-Cre mice was similar to controls, viable nonsteroidogenic luteal cells escaped structural luteolysis. These findings provide the novel evidence that Pten impacts the survival/life span of granulosa/luteal cells and that its loss not only results in the facilitated ovulation but also in the persistence of nonsteroidogenic luteal structures in the adult mouse ovary.