Professional Learning Communities: Keeping the Focus on Instructional Practice

ERIC Educational Resources Information Center

Spencer, Elizabeth J.

2016-01-01

The inclusion of professional learning community (PLC) groups is now a common initiative in many districts across the country. While this step supports the professional development of teachers, an effective PLC program must go beyond just bringing colleagues together during a common time. The author recommends organizational structures for schools…

Multiprog Virtual Laboratory Applied to PLC Programming Learning

ERIC Educational Resources Information Center

Shyr, Wen-Jye

2010-01-01

This study develops a Multiprog virtual laboratory for a mechatronics education designed to teach how to programme a programmable logic controller (PLC). The study was carried out with 34 students in the Department of Industry Education and Technology at National Changhua University of Education in Taiwan. In total, 17 students were assigned to…

WeaselBoard :

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

Mulder, John C.; Schwartz, Moses Daniel; Berg, Michael J.

2013-10-01

Critical infrastructures, such as electrical power plants and oil refineries, rely on programmable logic controllers (PLCs) to control essential processes. State of the art security cannot detect attacks on PLCs at the hardware or firmware level. This renders critical infrastructure control systems vulnerable to costly and dangerous attacks. WeaselBoard is a PLC backplane analysis system that connects directly to the PLC backplane to capture backplane communications between modules. WeaselBoard forwards inter-module traffic to an external analysis system that detects changes to process control settings, sensor values, module configuration information, firmware updates, and process control program (logic) updates. WeaselBoard provides zero-daymore » exploit detection for PLCs by detecting changes in the PLC and the process. This approach to PLC monitoring is protected under U.S. Patent Application 13/947,887.« less

Changes in Teachers' Beliefs and Classroom Practices Concerning Inquiry-Based Instruction Following a Year-Long RET-PLC Program

ERIC Educational Resources Information Center

Miranda, Rommel J.; Damico, Julie B.

2015-01-01

This mixed-methods study examines how engaging science teachers in a summer Research Experiences for Teachers (RET) followed by an academic-year Professional Learning Community (PLC) focused on translating teacher research experiences to inquiry-based classroom lessons might facilitate changes in their beliefs and classroom practices regarding…

Research of vibration controlling based on programmable logic controller for electrostatic precipitator

NASA Astrophysics Data System (ADS)

Zhang, Zisheng; Li, Yanhu; Li, Jiaojiao; Liu, Zhiqiang; Li, Qing

2013-03-01

In order to improve the reliability, stability and automation of electrostatic precipitator, circuits of vibration motor for ESP and vibration control ladder diagram program are investigated using Schneider PLC with high performance and programming software of Twidosoft. Operational results show that after adopting PLC, vibration motor can run automatically; compared with traditional control system of vibration based on single-chip microcomputer, it has higher reliability, better stability and higher dust removal rate, when dust emission concentrations <= 50 mg m-3, providing a new method for vibration controlling of ESP.

Training peers to deliver a church-based diabetes prevention program.

PubMed

Tang, Tricia S; Nwankwo, Robin; Whiten, Yolanda; Oney, Christina

2012-01-01

The purpose of this study was to examine the feasibility and acceptability of training peers to function as lifestyle coaches and to deliver a church-based lifestyle modification program. We recruited 6 African-American adults to participate in an 8-hour peer lifestyle coach (PLC) training program followed by a subsequent 2-hour booster session. The PLC training program addressed several key areas, including: (1) developing empowerment-based facilitation, active listening, and behavior change skills; (2) learning self-management strategies (eg, reading food labels, counting calories); (3) practicing session delivery; and (4) interpreting clinical lab results. Training evaluation was conducted retrospectively (immediately following the delivery of the diabetes prevention intervention rather than after the 8-hour training session) and measured program satisfaction and efficacy from the perspective of participants. Peer lifestyle coaches' confidence levels for performing core skills (eg, asking open-ended questions, 5-step behavioral goal-setting process) and advanced skills (eg, addressing resistance, discussing sensitive topics) were uniformly high. Similarly, PLCs were very satisfied with the length of training, balance between content and skills development, and preparation for leading group- and individual-based support activities. Findings suggest that it is feasible to customize a PLC training program that is acceptable to participants and that equips participants with the knowledge and skills to facilitate a church-based diabetes prevention intervention.

Professional Learning Communities: Concepts in Action in a Principal Preparation Program, an Elementary School Team, a Leadership Team, and a Business Partnership

ERIC Educational Resources Information Center

Servais, Kristine; Derrington, Mary Lynne; Sanders, Kellie

2009-01-01

The Professional Learning Community (PLC) model has moved to the forefront in the field of education as one of the most effective frameworks to improve student achievement and overall school success. The research conducted for this paper provides evidence for systemic and action based improvement using the PLC model in four diverse venues:…

Algorithms and theory for the design and programming of industrial control systems materialized with PLC's

NASA Astrophysics Data System (ADS)

Montoya Villena, Rafael

According to its title, the general objective of the Thesis consists in developing a clear, simple and systematic methodology for programming type PLC devices. With this aim in mind, we will use the following elements: Codification of all variables types. This section is very important since it allows us working with little information. The necessary rules are given to codify all type of phrases produced in industrial processes. An algorithm that describes process evolution and that has been called process D.F. This is one of the most important contributions, since it will allow us, together with information codification, representing the process evolution in a graphic way and with any design theory used. Theory selection. Evidently, the use of some kind of design method is necessary to obtain logic equations. For this particular case, we will use binodal theory, an ideal theory for wired technologies, since it can obtain highly reduced schemas for relatively simple automatisms, which means a minimum number of components used. User program outline algorithm (D.F.P.). This is another necessary contribution and perhaps the most important one, since logic equations resulting from binodal theory are compatible with process evolution if wired technology is used, whether it is electric, electronic, pneumatic, etc. On the other hand, PLC devices performance characteristics force the program instructions order to validate or not the automatism, as we have proven in different articles and lectures at congresses both national and international. Therefore, we will codify any information concerning the automating process, graphically represent its temporal evolution and, applying binodal theory and D.F.P (previously adapted), succeed in making logic equations compatible with the process to be automated and the device in which they will be implemented (PLC in our case)

Verification of operation of the actuator control system using the integration the B&R Automation Studio software with a virtual model of the actuator system

NASA Astrophysics Data System (ADS)

Herbuś, K.; Ociepka, P.

2017-08-01

In the work is analysed a sequential control system of a machine for separating and grouping work pieces for processing. Whereas, the area of the considered problem is related with verification of operation of an actuator system of an electro-pneumatic control system equipped with a PLC controller. Wherein to verification is subjected the way of operation of actuators in view of logic relationships assumed in the control system. The actuators of the considered control system were three drives of linear motion (pneumatic cylinders). And the logical structure of the system of operation of the control system is based on the signals flow graph. The tested logical structure of operation of the electro-pneumatic control system was implemented in the Automation Studio software of B&R company. This software is used to create programs for the PLC controllers. Next, in the FluidSIM software was created the model of the actuator system of the control system of a machine. To verify the created program for the PLC controller, simulating the operation of the created model, it was utilized the approach of integration these two programs using the tool for data exchange in the form of the OPC server.

The Legionella pneumophila Dot/Icm-secreted Effector PlcC/CegC1 Together with PlcA and PlcB Promotes Virulence and Belongs to a Novel Zinc Metallophospholipase C Family Present in Bacteria and Fungi*

PubMed Central

Aurass, Philipp; Schlegel, Maren; Metwally, Omar; Harding, Clare R.; Schroeder, Gunnar N.; Frankel, Gad; Flieger, Antje

2013-01-01

Legionella pneumophila is a water-borne bacterium that causes pneumonia in humans. PlcA and PlcB are two previously defined L. pneumophila proteins with homology to the phosphatidylcholine-specific phospholipase C (PC-PLC) of Pseudomonas fluorescens. Additionally, we found that Lpg0012 shows similarity to PLCs and has been shown to be a Dot/Icm-injected effector, CegC1, which is designated here as PlcC. It remained unclear, however, whether these L. pneumophila proteins exhibit PLC activity. PlcC expressed in Escherichia coli hydrolyzed a broad phospholipid spectrum, including PC, phosphatidylglycerol (PG), and phosphatidylinositol. The addition of Zn2+ ions activated, whereas EDTA inhibited, PlcC-derived PLC activity. Protein homology search revealed that the three Legionella enzymes and P. fluorescens PC-PLC share conserved domains also present in uncharacterized fungal proteins. Fifteen conserved amino acids were essential for enzyme activity as identified via PlcC mutagenesis. Analysis of defined L. pneumophila knock-out mutants indicated Lsp-dependent export of PG-hydrolyzing PLC activity. PlcA and PlcB exhibited PG-specific activity and contain a predicted Sec signal sequence. In line with the reported requirement of host cell contact for Dot/Icm-dependent effector translocation, PlcC showed cell-associated PC-specific PLC activity after bacterial growth in broth. A PLC triple mutant, but not single or double mutants, exhibited reduced host killing in a Galleria mellonella infection model, highlighting the importance of the three PLCs in pathogenesis. In summary, we describe here a novel Zn2+-dependent PLC family present in Legionella, Pseudomonas, and fungi with broad substrate preference and function in virulence. PMID:23457299

The Legionella pneumophila Dot/Icm-secreted effector PlcC/CegC1 together with PlcA and PlcB promotes virulence and belongs to a novel zinc metallophospholipase C family present in bacteria and fungi.

PubMed

Aurass, Philipp; Schlegel, Maren; Metwally, Omar; Harding, Clare R; Schroeder, Gunnar N; Frankel, Gad; Flieger, Antje

2013-04-19

Legionella pneumophila is a water-borne bacterium that causes pneumonia in humans. PlcA and PlcB are two previously defined L. pneumophila proteins with homology to the phosphatidylcholine-specific phospholipase C (PC-PLC) of Pseudomonas fluorescens. Additionally, we found that Lpg0012 shows similarity to PLCs and has been shown to be a Dot/Icm-injected effector, CegC1, which is designated here as PlcC. It remained unclear, however, whether these L. pneumophila proteins exhibit PLC activity. PlcC expressed in Escherichia coli hydrolyzed a broad phospholipid spectrum, including PC, phosphatidylglycerol (PG), and phosphatidylinositol. The addition of Zn(2+) ions activated, whereas EDTA inhibited, PlcC-derived PLC activity. Protein homology search revealed that the three Legionella enzymes and P. fluorescens PC-PLC share conserved domains also present in uncharacterized fungal proteins. Fifteen conserved amino acids were essential for enzyme activity as identified via PlcC mutagenesis. Analysis of defined L. pneumophila knock-out mutants indicated Lsp-dependent export of PG-hydrolyzing PLC activity. PlcA and PlcB exhibited PG-specific activity and contain a predicted Sec signal sequence. In line with the reported requirement of host cell contact for Dot/Icm-dependent effector translocation, PlcC showed cell-associated PC-specific PLC activity after bacterial growth in broth. A PLC triple mutant, but not single or double mutants, exhibited reduced host killing in a Galleria mellonella infection model, highlighting the importance of the three PLCs in pathogenesis. In summary, we describe here a novel Zn(2+)-dependent PLC family present in Legionella, Pseudomonas, and fungi with broad substrate preference and function in virulence.

Prognostic significance of pleural lavage cytology after thoracotomy and before closure of the chest in lung cancer.

PubMed

Taniguchi, Yuji; Nakamura, Hiroshige; Miwa, Ken; Adachi, Yoshin; Fujioka, Shinji; Haruki, Tomohiro; Horie, Yasushi

2009-07-01

Some reports have described pleural lavage cytology (PLC) to be a prognostic factor for non-small cell lung cancer (NSCLC) patients. However, there have only been a few reports describing the findings both immediately after thoracotomy (PLC after thoracotomy) and before the closure of the chest (PLC before closure). From April 2002 to April 2008, both PLC after thoracotomy and PLC before closure were performed in 296 consecutive patients who underwent resections for NSCLC. PLC after thoracotomy was positive in 14 patients. The survival rate in the PLC after thoracotomy positive cases was significantly poorer than in PLC after thoracotomy negative cases (P=0.047). In contrast, there were 26 PLC before closure positive cases. The survival rate in the PLC before closure positive cases was significantly poorer than in the PLC before closure negative cases (P<0.0001). Multivariate analyses revealed that PLC after thoracotomy is not an independent prognostic factor in our study. However, PLC before closure was an independent prognostic factor based on multivariate analyses. We conclude that PLC before closure was found to be a better prognostic factor than PLC after thoracotomy for NSCLC patients.

Change Management in Dental Education: A Professional Learning Community.

PubMed

Palatta, Anthony M

2018-06-01

Professional learning communities (PLCs) are defined as "a group of people sharing and critically interrogating their practice in an ongoing, reflective, collaborative, inclusive, learning-oriented, growth-promoting way." PLCs have been found to be an effective change management strategy in business and education when confronted by rapid change. The American Dental Education Association's Commission on Change and Innovation in Dental Education new national program-ADEA CCI 2.0-includes the development of a PLC. By employing an "engage and learn" model PLC centered on continuous quality improvement and systems thinking, dental faculty can identify internal and external barriers to change that could lead to innovative solutions to complex issues. This article argues that a PLC is a viable change management strategy to counteract the effect of multiple external forces impacting dental education and thus to develop future-ready faculty.

PLC based automatic control of pasteurize mix in ice cream production

NASA Astrophysics Data System (ADS)

Yao, Xudong; Liang, Kai

2013-03-01

This paper describes the automatic control device of pasteurized mix in the ice cream production process.We design a scheme of control system using FBD program language and develop the programmer in the STEP 7-Micro/WIN software, check for any bugs before downloading into PLC .These developed devices will able to provide flexibility and accuracy to control the step of pasteurized mix. The operator just Input the duration and temperature of pasteurized mix through control panel. All the steps will finish automatically without any intervention in a preprogrammed sequence stored in programmable logic controller (PLC). With the help of this equipment we not only can control the quality of ice cream for various conditions, but also can simplify the production process. This control system is inexpensive and can be widely used in ice cream production industry.

Programming Programmable Logic Controller. High-Technology Training Module.

ERIC Educational Resources Information Center

Lipsky, Kevin

This training module on programming programmable logic controllers (PLC) is part of the memory structure and programming unit used in a packaging systems equipment control course. In the course, students assemble, install, maintain, and repair industrial machinery used in industry. The module contains description, objectives, content outline,…

Design of belt conveyor electric control device based on CC-link bus

NASA Astrophysics Data System (ADS)

Chen, Goufen; Zhan, Minhua; Li, Jiehua

2016-01-01

In view of problem of the existing coal mine belt conveyor is no field bus communication function, two levels belt conveyor electric control system design is proposed based on field bus. Two-stage belt conveyor electric control system consists of operation platform, PLC control unit, various sensors, alarm device and the water spraying device. The error protection is realized by PLC programming, made use of CC-Link bus technology, the data share and the cooperative control came true between host station and slave station. The real-time monitor was achieved by the touch screen program. Practical application shows that the system can ensure the coalmine production, and improve the automatic level of the coalmine transport equipment.

Global regulator Anr represses PlcH phospholipase activity in Pseudomonas aeruginosa when oxygen is limiting.

PubMed

Jackson, Angelyca A; Daniels, Emily F; Hammond, John H; Willger, Sven D; Hogan, Deborah A

2014-10-01

Haemolytic phospholipase C (PlcH) is a potent virulence and colonization factor that is expressed at high levels by Pseudomonas aeruginosa within the mammalian host. The phosphorylcholine liberated from phosphatidylcholine and sphingomyelin by PlcH is further catabolized into molecules that both support growth and further induce plcH expression. We have shown previously that the catabolism of PlcH-released choline leads to increased activity of Anr, a global transcriptional regulator that promotes biofilm formation and virulence. Here, we demonstrated the presence of a negative feedback loop in which Anr repressed plcH transcription and we proposed that this regulation allowed for PlcH levels to be maintained in a way that promotes productive host-pathogen interactions. Evidence for Anr-mediated regulation of PlcH came from data showing that growth at low oxygen (1%) repressed PlcH abundance and plcH transcription in the WT, and that plcH transcription was enhanced in an Δanr mutant. The plcH promoter featured an Anr consensus sequence that was conserved across all P. aeruginosa genomes and mutation of conserved nucleotides within the Anr consensus sequence increased plcH expression under hypoxic conditions. The Anr-regulated transcription factor Dnr was not required for this effect. The loss of Anr was not sufficient to completely derepress plcH transcription as GbdR, a positive regulator of plcH, was required for expression. Overexpression of Anr was sufficient to repress plcH transcription even at 21 % oxygen. Anr repressed plcH expression and phospholipase C activity in a cell culture model for P. aeruginosa-epithelial cell interactions. The Authors.

Design and control of multifunctional sorting and training platform based on PLC control

NASA Astrophysics Data System (ADS)

Wan, Hongqiang; Ge, Shuai; Han, Peiying; Li, Fancong; Zhang, Simiao

2018-05-01

Electromechanical integration, as a multi-disciplinary subject, has been paid much attention by universities and is widely used in the automation production of enterprises. Aiming at the problem of the lack of control among enterprises and the lack of training among colleges and universities, this paper presents a design of multifunctional sorting training platform based on PLC control. Firstly, the structure of the platform is determined and three-dimensional modeling is done. Then design the platform's aerodynamic control and electrical control. Finally, realize the platform sorting function through PLC programming and configuration software development. The training platform can be used to design the practical training experiment, which has a strong advance and pertinence in the electromechanical integration teaching. At the same time, the platform makes full use of modular thinking to make the sorting modules more flexible. Compared with the traditional training platform, its teaching effect is more significant.

Data acquisition and control system with a programmable logic controller (PLC) for a pulsed chemical oxygen-iodine laser

NASA Astrophysics Data System (ADS)

Yu, Haijun; Li, Guofu; Duo, Liping; Jin, Yuqi; Wang, Jian; Sang, Fengting; Kang, Yuanfu; Li, Liucheng; Wang, Yuanhu; Tang, Shukai; Yu, Hongliang

2015-02-01

A user-friendly data acquisition and control system (DACS) for a pulsed chemical oxygen -iodine laser (PCOIL) has been developed. It is implemented by an industrial control computer，a PLC, and a distributed input/output (I/O) module, as well as the valve and transmitter. The system is capable of handling 200 analogue/digital channels for performing various operations such as on-line acquisition, display, safety measures and control of various valves. These operations are controlled either by control switches configured on a PC while not running or by a pre-determined sequence or timings during the run. The system is capable of real-time acquisition and on-line estimation of important diagnostic parameters for optimization of a PCOIL. The DACS system has been programmed using software programmable logic controller (PLC). Using this DACS, more than 200 runs were given performed successfully.

Activated PLC-γ1 is Catalytically Induced at LAT but Activated PLC-γ1 is Localized at both LAT- and TCR-Containing Complexes

PubMed Central

Cruz-Orcutt, Noemi; Vacaflores, Aldo; Connolly, Sean F.; Bunnell, Stephen C.; Houtman, Jon C.D.

2014-01-01

Phospholipase C-γ1 (PLC-γ1) is a key regulator of T cell receptor (TCR)-induced signaling. Activation of the TCR enhances PLC-γ1 enzymatic function, resulting in calcium influx and the activation of PKC family members and RasGRP. The current model is that phosphorylation of LAT tyrosine 132 facilitates the recruitment of PLC-γ1, leading to its activation and function at the LAT complex. In this study, we examined the phosphorylation kinetics of LAT and PLC-γ1 and the cellular localization of activated PLC-γ1. We observed that commencement of the phosphorylation of LAT tyrosine 132 and PLC-γ1 tyrosine 783 occurred simultaneously, supporting the current model. However, once begun, PLC-γ1 activation occurred more rapidly than LAT tyrosine 132. The association of LAT and PLC-γ1 was more transient than the interaction of LAT and Grb2 and a pool of activated PLC-γ1 translocated away from LAT to cellular structures containing the TCR. These studies demonstrate that LAT and PLC-γ1 form transient interactions that catalyze the activation of PLC-γ1, but that activated PLC-γ1 resides in both LAT and TCR clusters. Together, this work highlights that our current model is incomplete and the activation and function of PLC-γ1 in T cells is highly complex. PMID:24412752

Silencing of the tomato phosphatidylinositol-phospholipase C2 (SlPLC2) reduces plant susceptibility to Botrytis cinerea.

PubMed

Gonorazky, Gabriela; Guzzo, María Carla; Abd-El-Haliem, Ahmed M; Joosten, Matthieu H A J; Laxalt, Ana María

2016-12-01

The tomato [Solanum lycopersicum (Sl)] phosphatidylinositol-phospholipase C (PI-PLC) gene family is composed of six members, named SlPLC1 to SlPLC6, differentially regulated on pathogen attack. We have previously shown that the fungal elicitor xylanase induces a raise of SlPLC2 and SlPLC5 transcripts and that SlPLC2, but not SlPLC5, is required for xylanase-induced expression of defense-related genes. In this work we studied the role of SlPLC2 in the interaction between tomato and the necrotrophic fungus Botrytis cinerea. Inoculation of tomato leaves with B. cinerea increases SlPLC2 transcript levels. We knocked-down the expression of SlPLC2 by virus-induced gene silencing and plant defense responses were analyzed upon B. cinerea inoculation. SlPLC2 silenced plants developed smaller necrotic lesions concomitantly with less proliferation of the fungus. Silencing of SlPLC2 resulted as well in a reduced production of reactive oxygen species. Upon B. cinerea inoculation, transcript levels of the salicylic acid (SA)-defense pathway marker gene SlPR1a were diminished in SlPLC2 silenced plants compared to non-silenced infected plants, while transcripts of the jasmonic acid (JA)-defense gene markers Proteinase Inhibitor I and II (SlPI-I and SlPI-II) were increased. This implies that SlPLC2 participates in plant susceptibility to B. cinerea. © 2016 BSPP and John Wiley & Sons Ltd.

Expression of phosphoinositide-specific phospholipase C isoforms in native endothelial cells.

PubMed

Béziau, Delphine M; Toussaint, Fanny; Blanchette, Alexandre; Dayeh, Nour R; Charbel, Chimène; Tardif, Jean-Claude; Dupuis, Jocelyn; Ledoux, Jonathan

2015-01-01

Phospholipase C (PLC) comprises a superfamily of enzymes that play a key role in a wide array of intracellular signalling pathways, including protein kinase C and intracellular calcium. Thirteen different mammalian PLC isoforms have been identified and classified into 6 families (PLC-β, γ, δ, ε, ζ and η) based on their biochemical properties. Although the expression of PLC isoforms is tissue-specific, concomitant expression of different PLC has been reported, suggesting that PLC family is involved in multiple cellular functions. Despite their critical role, the PLC isoforms expressed in native endothelial cells (ECs) remains undetermined. A conventional PCR approach was initially used to elucidate the mRNA expression pattern of PLC isoforms in 3 distinct murine vascular beds: mesenteric (MA), pulmonary (PA) and middle cerebral arteries (MCA). mRNA encoding for most PLC isoforms was detected in MA, MCA and PA with the exception of η2 and β2 (only expressed in PA), δ4 (only expressed in MCA), η1 (expressed in all but MA) and ζ (not detected in any vascular beds tested). The endothelial-specific PLC expression was then sought in freshly isolated ECs. Interestingly, the PLC expression profile appears to differ across the investigated arterial beds. While mRNA for 8 of the 13 PLC isoforms was detected in ECs from MA, two additional PLC isoforms were detected in ECs from PA and MCA. Co-expression of multiple PLC isoforms in ECs suggests an elaborate network of signalling pathways: PLC isoforms may contribute to the complexity or diversity of signalling by their selective localization in cellular microdomains. However in situ immunofluorescence revealed a homogeneous distribution for all PLC isoforms probed (β3, γ2 and δ1) in intact endothelium. Although PLC isoforms play a crucial role in endothelial signal transduction, subcellular localization alone does not appear to be sufficient to determine the role of PLC in the signalling microdomains found in the native endothelium.

Prediction of posterior ligamentous complex injury in thoracolumbar fractures using non-MRI imaging techniques.

PubMed

Rajasekaran, Shanmuganathan; Maheswaran, Anupama; Aiyer, Siddharth N; Kanna, Rishi; Dumpa, Srikanth Reddy; Shetty, Ajoy Prasad

2016-06-01

We aimed to formulate a radiological index based on plain radiographs and computer tomography (CT) to reliably detect posterior ligamentous complex (PLC) injury without need for MRI. Sixty out of 148 consecutive thoracolumbar fractures with doubtful PLC were assessed with MRI, CT and radiographs. PLC injury was assessed with the following radiological parameters: superior-inferior end plate angle (SIEA), vertebral body height (BH), local kyphosis (LK), inter-spinous distance (ISD) and inter-pedicular distance (IPD) and correlated with MRI findings of PLC injury. Statistical analysis was performed to identify the predictive values for the parameters to identify PLC damage. MRI identified PLC injury in 25/60 cases. The ISD and LK were found to be significant predictors of PLC injury. On radiographs the mean LK with PLC damage was 25.86° compared to 21.02° with an intact PLC (p = 0.006). The ISD difference was 6.70 mm in cases with PLC damage compared to 2.86 mm with an intact PLC (p = 0.011). In CT images, the mean LK with PLC damage was 22.96° compared to 18.44° with an intact PLC ( p = 0.019). The ISD difference was 3.10 mm with PLC damage compared to 1.62 mm without PLC damage (p = 0.005). On plain radiographs the presence of LK greater than 20 °(CI 64-95) and ISD difference greater than 2 mm (CI 70-97) can predict PLC injury. These guidelines may be utilised in the emergency room especially when the associated cost, availability and time delay in performing MRI are a concern.

PDZ Domain-containing 1 (PDZK1) Protein Regulates Phospholipase C-β3 (PLC-β3)-specific Activation of Somatostatin by Forming a Ternary Complex with PLC-β3 and Somatostatin Receptors*

PubMed Central

Kim, Jung Kuk; Kwon, Ohman; Kim, Jinho; Kim, Eung-Kyun; Park, Hye Kyung; Lee, Ji Eun; Kim, Kyung Lock; Choi, Jung Woong; Lim, Seyoung; Seok, Heon; Lee-Kwon, Whaseon; Choi, Jang Hyun; Kang, Byoung Heon; Kim, Sanguk; Ryu, Sung Ho; Suh, Pann-Ghill

2012-01-01

Phospholipase C-β (PLC-β) is a key molecule in G protein-coupled receptor (GPCR)-mediated signaling. Many studies have shown that the four PLC-β subtypes have different physiological functions despite their similar structures. Because the PLC-β subtypes possess different PDZ-binding motifs, they have the potential to interact with different PDZ proteins. In this study, we identified PDZ domain-containing 1 (PDZK1) as a PDZ protein that specifically interacts with PLC-β3. To elucidate the functional roles of PDZK1, we next screened for potential interacting proteins of PDZK1 and identified the somatostatin receptors (SSTRs) as another protein that interacts with PDZK1. Through these interactions, PDZK1 assembles as a ternary complex with PLC-β3 and SSTRs. Interestingly, the expression of PDZK1 and PLC-β3, but not PLC-β1, markedly potentiated SST-induced PLC activation. However, disruption of the ternary complex inhibited SST-induced PLC activation, which suggests that PDZK1-mediated complex formation is required for the specific activation of PLC-β3 by SST. Consistent with this observation, the knockdown of PDZK1 or PLC-β3, but not that of PLC-β1, significantly inhibited SST-induced intracellular Ca2+ mobilization, which further attenuated subsequent ERK1/2 phosphorylation. Taken together, our results strongly suggest that the formation of a complex between SSTRs, PDZK1, and PLC-β3 is essential for the specific activation of PLC-β3 and the subsequent physiologic responses by SST. PMID:22528496

76 FR 44079 - M (2003) PLC (f/k/a Marconi PLC), Mayfair Mining & Minerals, Inc., MM2 Group, Inc., Nayna...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-22

... SECURITIES AND EXCHANGE COMMISSION [File No. 500-1] M (2003) PLC (f/k/a Marconi PLC), Mayfair Mining & Minerals, Inc.,MM2 Group, Inc., Nayna Networks, Inc., NCT Group, Inc., and Neptune Industries... securities of M (2003) PLC (f/k/a Marconi PLC) because it has not filed any periodic reports since the period...

Pleomorphic lobular carcinoma of the breast: a comparison of cytopathological features with other lobular carcinoma variants.

PubMed

Ohashi, R; Matsubara, M; Watarai, Y; Yanagihara, K; Yamashita, K; Tsuchiya, S-I; Takei, H; Naito, Z

2017-04-01

Pleomorphic lobular carcinoma (PLC) is a subtype of breast cancer with unique morphological features, but it remains controversial whether PLC should be considered an independent disease entity. The aim of this study was to illustrate cytopathological characteristics of PLC in comparison with other lobular carcinoma variants. We investigated clinicopathological features of PLC (n = 11) compared with those of other variants of invasive lobular carcinoma (ILC, non-PLC) (n = 32). Histological variants of the non-PLC group consisted of classic (n = 25), solid (n = 2), alveolar (n = 1) and a tubulolobular type (n = 4). A review of cytological reports and fine needle aspiration (FNA) smear samples was performed for the PLC (n = 9) and non-PLC (n = 27) groups. Patients with PLC were older, and had a higher nuclear grade and a higher incidence of axillary lymph node metastasis and triple negative phenotype than non-PLC patients (P = 0.007, P < 0.001, P = 0.02 and P < 0.001, respectively). Cytological findings in PLC included medium- to large-sized nuclei, prominent nucleoli, a moderate-to-severe degree of pleomorphism, apocrine change and background necrosis, none of which were evident in the smears of the non-PLC group (P < 0.001, P = 0.002, P < 0.001, P < 0.001, and P = 0.03, respectively). Despite these differences, patients with PLC and non-PLC showed similar clinical outcomes in our follow-up period. Based on our results, a cytological diagnosis of PLC should be proposed if there are moderate- to large-sized nuclei, prominent nucleoli, a moderate-to severe degree of nuclear pleomorphism, apocrine change and necrosis in the background in FNA biopsy samples. © 2016 John Wiley & Sons Ltd.

Generating Safety-Critical PLC Code From a High-Level Application Software Specification

NASA Technical Reports Server (NTRS)

2008-01-01

The benefits of automatic-application code generation are widely accepted within the software engineering community. These benefits include raised abstraction level of application programming, shorter product development time, lower maintenance costs, and increased code quality and consistency. Surprisingly, code generation concepts have not yet found wide acceptance and use in the field of programmable logic controller (PLC) software development. Software engineers at Kennedy Space Center recognized the need for PLC code generation while developing the new ground checkout and launch processing system, called the Launch Control System (LCS). Engineers developed a process and a prototype software tool that automatically translates a high-level representation or specification of application software into ladder logic that executes on a PLC. All the computer hardware in the LCS is planned to be commercial off the shelf (COTS), including industrial controllers or PLCs that are connected to the sensors and end items out in the field. Most of the software in LCS is also planned to be COTS, with only small adapter software modules that must be developed in order to interface between the various COTS software products. A domain-specific language (DSL) is a programming language designed to perform tasks and to solve problems in a particular domain, such as ground processing of launch vehicles. The LCS engineers created a DSL for developing test sequences of ground checkout and launch operations of future launch vehicle and spacecraft elements, and they are developing a tabular specification format that uses the DSL keywords and functions familiar to the ground and flight system users. The tabular specification format, or tabular spec, allows most ground and flight system users to document how the application software is intended to function and requires little or no software programming knowledge or experience. A small sample from a prototype tabular spec application is shown.

Prognostic impact of pleural lavage cytology in patients with primary lung cancer.

PubMed

Tomizawa, Kenji; Nishino, Masaya; Sesumi, Yuichi; Kobayashi, Yoshihisa; Sato, Katsuaki; Chiba, Masato; Shimoji, Masaki; Suda, Kenichi; Shimizu, Shigeki; Sato, Takao; Takemoto, Toshiki; Mitsudomi, Tetsuya

2016-12-01

Positive pleural lavage cytology (PLC) has been reported to have a negative prognostic impact in patients with surgically resected non-small cell lung cancer (NSCLC). However, positive PLC does not upgrade the stage according to the 7th edition of TNM classification for lung cancer. The objectives of this study were to evaluate the prognostic impact of positive PLC in patients with NSCLC and to clarify its contribution to TNM classification. Seven hundred fifty-four patients who underwent surgical resection of NSCLC from January 2007 through December 2013 were retrospectively studied. PLC was performed using 50ml of saline immediately after thoracotomy. Thirty-eight of the 754 patients were positive for PLC (5.1%). The overall survival (OS) of patients with positive PLC was significantly shorter than that of those with negative PLC (P=0.007, log-rank test). In multivariate analyses of OS, positive PLC was a significant independent prognostic factor (hazard ratio=2.21, 95% confidence interval: 1.21-4.04, P=0.009). The OS of patients with positive PLC was significantly shorter than that of those with negative PLC and pT1 (P<0.0001) or negative PLC and pT2 (P<0.0001) and almost overlapped with that of those with negative PLC and pT3 disease (P=0.601). Positive PLC is an independent prognostic factor in patients with resected NSCLC. Based on our analyses, we propose that patients with positive PLC be staged as pT3. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Iron-Regulated Phospholipase C Activity Contributes to the Cytolytic Activity and Virulence of Acinetobacter baumannii

PubMed Central

Fiester, Steven E.; Schmidt, Robert E.; Beckett, Amber C.; Ticak, Tomislav; Carrier, Mary V.; Ghosh, Rajarshi; Ohneck, Emily J.; Metz, Maeva L.; Sellin Jeffries, Marlo K.; Actis, Luis A.

2016-01-01

Acinetobacter baumannii is an opportunistic Gram-negative pathogen that causes a wide range of infections including pneumonia, septicemia, necrotizing fasciitis and severe wound and urinary tract infections. Analysis of A. baumannii representative strains grown in Chelex 100-treated medium for hemolytic activity demonstrated that this pathogen is increasingly hemolytic to sheep, human and horse erythrocytes, which interestingly contain increasing amounts of phosphatidylcholine in their membranes. Bioinformatic, genetic and functional analyses of 19 A. baumannii isolates showed that the genomes of each strain contained two phosphatidylcholine-specific phospholipase C (PC-PLC) genes, which were named plc1 and plc2. Accordingly, all of these strains were significantly hemolytic to horse erythrocytes and their culture supernatants tested positive for PC-PLC activity. Further analyses showed that the transcriptional expression of plc1 and plc2 and the production of phospholipase and thus hemolytic activity increased when bacteria were cultured under iron-chelation as compared to iron-rich conditions. Testing of the A. baumannii ATCC 19606T plc1::aph-FRT and plc2::aph isogenic insertion derivatives showed that these mutants had a significantly reduced PC-PLC activity as compared to the parental strain, while testing of plc1::ermAM/plc2::aph demonstrated that this double PC-PLC isogenic mutant expressed significantly reduced cytolytic and hemolytic activity. Interestingly, only plc1 was shown to contribute significantly to A. baumannii virulence using the Galleria mellonella infection model. Taken together, our data demonstrate that both PLC1 and PLC2, which have diverged from a common ancestor, play a concerted role in hemolytic and cytolytic activities; although PLC1 seems to play a more critical role in the virulence of A. baumannii when tested in an invertebrate model. These activities would provide access to intracellular iron stores this pathogen could use during growth in the infected host. PMID:27875572

Mechanism of enhanced oral absorption of morin by phospholipid complex based self-nanoemulsifying drug delivery system.

PubMed

Zhang, Jinjie; Li, Jianbo; Ju, Yuan; Fu, Yao; Gong, Tao; Zhang, Zhirong

2015-02-02

Phospholipid complex (PLC) based self-nanoemulsifying drug delivery system (PLC-SNEDDS) has been developed for efficient delivery of drugs with poor solubility and low permeability. In the present study, a BCS class IV drug and a P-glycoprotein (P-gp) substrate, morin, was selected as the model drug to elucidate the oral absorption mechanism of PLC-SNEDDS. PLC-SNEDDS was superior to PLC in protecting morin from degradation by intestinal enzymes in vitro. In situ perfusion study showed increased intestinal permeability by PLC was duodenum-specific. In contrast, PLC-SNEDDS increased morin permeability in all intestinal segments and induced a change in the main absorption site of morin from colon to ileum. Moreover, ileum conducted the lymphatic transport of PLC-SNEDDS, which was proven by microscopic intestinal visualization of Nile red labeled PLC-SNEDDS and lymph fluids in vivo. Low cytotoxicity and increased Caco-2 cell uptake suggested a safe and efficient delivery of PLC-SNEDDS. The increased membrane fluidity and disrupted actin filaments were closely associated with the increased cell uptake of PLC-SNEDDS. PLC-SNEDDS could be internalized into enterocytes as an intact form in a cholesterol-dependent manner via clathrin-mediated endocytosis and macropinocytosis. The enhanced oral absorption of morin was attributed to the P-gp inhibition by Cremophor RH and the intact internalization of M-PLC-SNEDDS into Caco-2 cells bypassing P-gp recognition. Our findings thus provide new insights into the development of novel nanoemulsions for poorly absorbed drugs.

Intrinsic Pleckstrin Homology (PH) Domain Motion in Phospholipase C-β Exposes a Gβγ Protein Binding Site.

PubMed

Kadamur, Ganesh; Ross, Elliott M

2016-05-20

Mammalian phospholipase C-β (PLC-β) isoforms are stimulated by heterotrimeric G protein subunits and members of the Rho GTPase family of small G proteins. Although recent structural studies showed how Gαq and Rac1 bind PLC-β, there is a lack of consensus regarding the Gβγ binding site in PLC-β. Using FRET between cerulean fluorescent protein-labeled Gβγ and the Alexa Fluor 594-labeled PLC-β pleckstrin homology (PH) domain, we demonstrate that the PH domain is the minimal Gβγ binding region in PLC-β3. We show that the isolated PH domain can compete with full-length PLC-β3 for binding Gβγ but not Gαq, Using sequence conservation, structural analyses, and mutagenesis, we identify a hydrophobic face of the PLC-β PH domain as the Gβγ binding interface. This PH domain surface is not solvent-exposed in crystal structures of PLC-β, necessitating conformational rearrangement to allow Gβγ binding. Blocking PH domain motion in PLC-β by cross-linking it to the EF hand domain inhibits stimulation by Gβγ without altering basal activity or Gαq response. The fraction of PLC-β cross-linked is proportional to the fractional loss of Gβγ response. Cross-linked PLC-β does not bind Gβγ in a FRET-based Gβγ-PLC-β binding assay. We propose that unliganded PLC-β exists in equilibrium between a closed conformation observed in crystal structures and an open conformation where the PH domain moves away from the EF hands. Therefore, intrinsic movement of the PH domain in PLC-β modulates Gβγ access to its binding site. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Intrinsic Pleckstrin Homology (PH) Domain Motion in Phospholipase C-β Exposes a Gβγ Protein Binding Site*

PubMed Central

Kadamur, Ganesh

2016-01-01

Mammalian phospholipase C-β (PLC-β) isoforms are stimulated by heterotrimeric G protein subunits and members of the Rho GTPase family of small G proteins. Although recent structural studies showed how Gαq and Rac1 bind PLC-β, there is a lack of consensus regarding the Gβγ binding site in PLC-β. Using FRET between cerulean fluorescent protein-labeled Gβγ and the Alexa Fluor 594-labeled PLC-β pleckstrin homology (PH) domain, we demonstrate that the PH domain is the minimal Gβγ binding region in PLC-β3. We show that the isolated PH domain can compete with full-length PLC-β3 for binding Gβγ but not Gαq, Using sequence conservation, structural analyses, and mutagenesis, we identify a hydrophobic face of the PLC-β PH domain as the Gβγ binding interface. This PH domain surface is not solvent-exposed in crystal structures of PLC-β, necessitating conformational rearrangement to allow Gβγ binding. Blocking PH domain motion in PLC-β by cross-linking it to the EF hand domain inhibits stimulation by Gβγ without altering basal activity or Gαq response. The fraction of PLC-β cross-linked is proportional to the fractional loss of Gβγ response. Cross-linked PLC-β does not bind Gβγ in a FRET-based Gβγ-PLC-β binding assay. We propose that unliganded PLC-β exists in equilibrium between a closed conformation observed in crystal structures and an open conformation where the PH domain moves away from the EF hands. Therefore, intrinsic movement of the PH domain in PLC-β modulates Gβγ access to its binding site. PMID:27002154

Phospholipase C-gamma 1 binding to intracellular receptors for activated protein kinase C.

PubMed

Disatnik, M H; Hernandez-Sotomayor, S M; Jones, G; Carpenter, G; Mochly-Rosen, D

1994-01-18

Phospholipase C-gamma 1 (PLC-gamma 1; EC 3.1.4.11) hydrolyzes phosphatidylinositol 4,5-bisphosphate to generate diacylglycerol and inositol 1,4,5-trisphosphate and is activated in response to growth factor stimulation and tyrosine phosphorylation. Concomitantly, the enzyme translocates from the cytosol to the particulate cell fraction. A similar process of activation-induced translocation from the cytosol to the cell particulate fraction has also been described for protein kinase C (PKC). We have previously shown that activated PKC binds to specific receptor proteins, receptors for activated C kinase, or RACKs, of approximately 30 kDa. Here, we show that PLC-gamma 1 bound to these RACKs and inhibited subsequent PKC binding to RACKs. However, unlike PKC, the binding of PLC-gamma 1 to RACKs did not require phospholipids and calcium. After epidermal growth factor treatment of intact A-431 cells, the binding of PLC-gamma 1 to RACKs increased as compared with PLC-gamma 1 from control cells. This increase in PLC-gamma 1 binding to RACKs was due to the phosphorylation of PLC-gamma 1. Additional data indicated that PLC-gamma 1 binds to RACKs in solution; epidermal growth factor receptor-dependent PLC-gamma 1 phosphorylation and activation decreased in the presence of RACKs. It is possible that, in vivo, PLC-gamma 1 associates with RACKs or with other PLC-gamma 1-specific anchoring proteins in the particulate cell fraction. Since a PKC C2 homologous region is present in PLC-gamma 1, the C2 region may mediate the activation-induced translocation of the enzyme to the cell particulate fraction and the anchoring protein-PLC-gamma 1 complex may be the active translocated form of PLC-gamma 1.

Realization of PLC to the Variable Frequency Speed Regulation System of Mine Local Ventilator based on RS-485 Communication

NASA Astrophysics Data System (ADS)

Ma, Kai; Li, Jian; Yun, Yichong

2018-03-01

The article first introduces the merits of serial communication in the PLC to the variable frequency speed regulation system of mine local ventilator, and then sets up a hardware application development platform of PLC and inverter based on RS-485 communication technology, next presents communication initialization of the PLC and Inverter. Finally according to the control requirements, PLC send run operation & monitoring instruction to Inverter, realizes the serial communication control between the PLC and Inverter.

20(S)-Protopanaxadiol Phospholipid Complex: Process Optimization, Characterization, In Vitro Dissolution and Molecular Docking Studies.

PubMed

Pu, Yiqiong; Zhang, Xitong; Zhang, Qi; Wang, Bing; Chen, Yuxi; Zang, Chuanqi; Wang, Yuqin; Dong, Tina Ting-Xia; Zhang, Tong

2016-10-19

20( S )-Protopanaxadiol (PPD), a bioactive compound extracted from ginseng, possesses cardioprotective, neuroprotective, anti-inflammatory, antiestrogenic, anticancer and anxiolytic effects. However, the clinical application of PPD is limited by its weak aqueous solubility. In this study, we optimized an efficient method of preparing its phospholipid complex (PPD-PLC) using a central composite design and response surface analysis. The prepared PPD-PLC was characterized by differential scanning calorimetric, powder X-ray diffraction, Fourier-transformed infrared spectroscopy and nuclear magnetic resonance analyses associated with molecular docking calculation. The equilibrium solubility of PPD-PLC in water and n -octanol increased 6.53- and 1.53-times, respectively. Afterwards, using PPD-PLC as the intermediate, the PPD-PLC-loaded dry suspension (PPD-PLC-SU) was prepared with our previous method. In vitro evaluations were conducted on PPD-PLC and PPD-PLC-SU, including dissolution behaviors and stability properties under different conditions. Results of in vitro dissolution behavior revealed the improved dissolution extents and rates of PPD-PLC and PPD-PLC-SU ( p < 0.05). Results of the formulation stability investigation also exposed the better stability of PPD-PLC-SU compared with free PPD. Therefore, phospholipid complex technology is a useful formulation strategy for BCS II drugs, as it could effectively improve their hydrophilicity and lipophilicity.

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

Zvi H. Meiksin

A temporary installation of Transtek's in-mine communications system in the Lake Lynn mine was used in the mine rescue training programs offered by NIOSH in April and May 2002. We developed and implemented a software program that permits point-to-point data transmission through our in-mine system. We also developed a wireless data transceiver for use in a PLC (programmed logic controller) to remotely control long-wall mining equipment.

Calmodulin is a phospholipase C-beta interacting protein.

PubMed

McCullar, Jennifer S; Larsen, Shana A; Millimaki, Ryan A; Filtz, Theresa M

2003-09-05

Phospholipase C-beta 3 (PLC beta 3) is an important effector enzyme in G protein-coupled signaling pathways. Activation of PLC beta 3 by G alpha and G beta gamma subunits has been fairly well characterized, but little is known about other protein interactions that may also regulate PLC beta 3 function. A yeast two-hybrid screen of a mouse brain cDNA library with the amino terminus of PLC beta 3 has yielded potential PLC beta 3 interacting proteins including calmodulin (CaM). Physical interaction between CaM and PLC beta 3 is supported by a positive secondary screen in yeast and the identification of a CaM binding site in the amino terminus of PLC beta 3. Co-precipitation of in vitro translated and transcribed amino- and carboxyl-terminal PLC beta 3 revealed CaM binding at a putative amino-terminal binding site. Direct physical interaction of PLC beta 3 and PLC beta 1 isoforms with CaM is supported by pull-down of both isoenzymes with CaM-Sepharose beads from 1321N1 cell lysates. CaM inhibitors reduced M1-muscarinic receptor stimulation of inositol phospholipid hydrolysis in 1321N1 astrocytoma cells consistent with a physiologic role for CaM in modulation of PLC beta activity. There was no effect of CaM kinase II inhibitors, KN-93 and KN-62, on M1-muscarinic receptor stimulation of inositol phosphate hydrolysis, consistent with a direct interaction between PLC beta isoforms and CaM.

Recent research progress with phospholipase C from Bacillus cereus.

PubMed

Lyu, Yan; Ye, Lidan; Xu, Jun; Yang, Xiaohong; Chen, Weiwei; Yu, Hongwei

2016-01-01

Phospholipase C (PLC) catalyzes the hydrolysis of phospholipids to produce phosphate monoesters and diacylglycerol. It has many applications in the enzymatic degumming of plant oils. PLC Bc , a bacterial PLC from Bacillus cereus, is an optimal choice for this activity in terms of its wide substrate spectrum, high activity, and approved safety. Unfortunately, its large-scale production and reliable high-throughput screening of PLC Bc remain challenging. Herein, we summarize the research progress regarding PLC Bc with emphasis on the screening methods, expression systems, catalytic mechanisms and inhibitor of PLC Bc . This review hopefully will inspire new achievements in related areas, to promote the sustainable development of PLC Bc and its application.

Assessing child and adolescent pragmatic language competencies: toward evidence-based assessments.

PubMed

Russell, Robert L; Grizzle, Kenneth L

2008-06-01

Using language appropriately and effectively in social contexts requires pragmatic language competencies (PLCs). Increasingly, deficits in PLCs are linked to child and adolescent disorders, including autism spectrum, externalizing, and internalizing disorders. As the role of PLCs expands in diagnosis and treatment of developmental psychopathology, psychologists and educators will need to appraise and select clinical and research PLC instruments for use in assessments and/or studies. To assist in this appraisal, 24 PLC instruments, containing 1,082 items, are assessed by addressing four questions: (1) Can PLC domains targeted by assessment items be reliably identified?, (2) What are the core PLC domains that emerge across the 24 instruments?, (3) Do PLC questionnaires and tests assess similar PLC domains?, and (4) Do the instruments achieve content, structural, diagnostic, and ecological validity? Results indicate that test and questionnaire items can be reliably categorized into PLC domains, that PLC domains featured in questionnaires and tests significantly differ, and that PLC instruments need empirical confirmation of their dimensional structure, content validity across all developmental age bands, and ecological validity. Progress in building a better evidence base for PLC assessments should be a priority in future research.

Binding of phosphoinositide-specific phospholipase C-zeta (PLC-zeta) to phospholipid membranes: potential role of an unstructured cluster of basic residues.

PubMed

Nomikos, Michail; Mulgrew-Nesbitt, Anna; Pallavi, Payal; Mihalyne, Gyongyi; Zaitseva, Irina; Swann, Karl; Lai, F Anthony; Murray, Diana; McLaughlin, Stuart

2007-06-01

Phospholipase C-zeta (PLC-zeta) is a sperm-specific enzyme that initiates the Ca2+ oscillations in mammalian eggs that activate embryo development. It shares considerable sequence homology with PLC-delta1, but lacks the PH domain that anchors PLC-delta1 to phosphatidylinositol 4,5-bisphosphate, PIP2. Thus it is unclear how PLC-zeta interacts with membranes. The linker region between the X and Y catalytic domains of PLC-zeta, however, contains a cluster of basic residues not present in PLC-delta1. Application of electrostatic theory to a homology model of PLC-zeta suggests this basic cluster could interact with acidic lipids. We measured the binding of catalytically competent mouse PLC-zeta to phospholipid vesicles: for 2:1 phosphatidylcholine/phosphatidylserine (PC/PS) vesicles, the molar partition coefficient, K, is too weak to be of physiological significance. Incorporating 1% PIP2 into the 2:1 PC/PS vesicles increases K about 10-fold, to 5x10(3) M-1, a biologically relevant value. Expressed fragments corresponding to the PLC-zeta X-Y linker region also bind with higher affinity to polyvalent than monovalent phosphoinositides on nitrocellulose filters. A peptide corresponding to the basic cluster (charge=+7) within the linker region, PLC-zeta-(374-385), binds to PC/PS vesicles with higher affinity than PLC-zeta, but its binding is less sensitive to incorporating PIP2. The acidic residues flanking this basic cluster in PLC-zeta may account for both these phenomena. FRET experiments suggest the basic cluster could not only anchor the protein to the membrane, but also enhance the local concentration of PIP2 adjacent to the catalytic domain.

Pulmonary lymphangitic carcinomatosis (PLC): spectrum of FDG-PET findings.

PubMed

Acikgoz, Gunsel; Kim, Sung M; Houseni, Mohamed; Cermik, Tevfik F; Intenzo, Charles M; Alavi, Abass

2006-11-01

The lungs are among the most common sites for metastases from a multitude of cancers. The majority of pulmonary metastases appear nodular on radiologic images. Interstitial spread of tumor through pulmonary lymphatics, also known as pulmonary lymphangitic carcinomatosis (PLC), is not uncommon and constitutes approximately 7% of pulmonary metastases. PLC is most often seen with adenocarcinoma of a variety of histologies such as thyroid carcinoma, and melanoma. It is usually noted in late stages of malignancy and therefore is indicative of a poor prognosis. Diagnosis of PLC is usually based on a combination of clinical and radiologic findings. However, the diagnosis is difficult when patients have limited clinical findings or have a history of or the possibility of other interstitial lung diseases. High-resolution computed tomography (HRCT) has been the modality of choice in the radiologic diagnosis of PLC. Imaging features of PLC on HRCT include thickening of interlobular septa, fissures, and bronchovascular bundles. Distribution of PLC may be focal or diffuse, unilateral or bilateral, and symmetric or asymmetric. Although FDG-PET has been extensively used in primary or secondary lung malignancies, its role and appearance in PLC have not been well determined in the literature. In this communication, we describe a spectrum of FDG-PET and CT findings in 5 cases with PLC. Similar to CT, the distribution of PLC can be extensive or limited on the FDG-PET. Diffuse, lobar, or segmental FDG uptake in the lungs is seen in extensive PLC. In limited PLC, a linear or a hazy area of FDG uptake extending from the tumor can be seen. Recognition of various patterns related to PLC on FDG-PET may allow accurate diagnosis of disease and could potentially influence the management of these patients.

Characterization of phospholipase C gamma enzymes with gain-of-function mutations.

PubMed

Everett, Katy L; Bunney, Tom D; Yoon, Youngdae; Rodrigues-Lima, Fernando; Harris, Richard; Driscoll, Paul C; Abe, Koichiro; Fuchs, Helmut; de Angelis, Martin Hrabé; Yu, Philipp; Cho, Wohnwa; Katan, Matilda

2009-08-21

Phospholipase C gamma isozymes (PLC gamma 1 and PLC gamma 2) have a crucial role in the regulation of a variety of cellular functions. Both enzymes have also been implicated in signaling events underlying aberrant cellular responses. Using N-ethyl-N-nitrosourea (ENU) mutagenesis, we have recently identified single point mutations in murine PLC gamma 2 that lead to spontaneous inflammation and autoimmunity. Here we describe further, mechanistic characterization of two gain-of-function mutations, D993G and Y495C, designated as ALI5 and ALI14. The residue Asp-993, mutated in ALI5, is a conserved residue in the catalytic domain of PLC enzymes. Analysis of PLC gamma 1 and PLC gamma 2 with point mutations of this residue showed that removal of the negative charge enhanced PLC activity in response to EGF stimulation or activation by Rac. Measurements of PLC activity in vitro and analysis of membrane binding have suggested that ALI5-type mutations facilitate membrane interactions without compromising substrate binding and hydrolysis. The residue mutated in ALI14 (Tyr-495) is within the spPH domain. Replacement of this residue had no effect on folding of the domain and enhanced Rac activation of PLC gamma 2 without increasing Rac binding. Importantly, the activation of the ALI14-PLC gamma 2 and corresponding PLC gamma 1 variants was enhanced in response to EGF stimulation and bypassed the requirement for phosphorylation of critical tyrosine residues. ALI5- and ALI14-type mutations affected basal activity only slightly; however, their combination resulted in a constitutively active PLC. Based on these data, we suggest that each mutation could compromise auto-inhibition in the inactive PLC, facilitating the activation process; in addition, ALI5-type mutations could enhance membrane interaction in the activated state.

Phospholipase C-ε signaling mediates endothelial cell inflammation and barrier disruption in acute lung injury

PubMed Central

Bijli, Kaiser M.; Fazal, Fabeha; Slavin, Spencer A.; Leonard, Antony; Grose, Valerie; Alexander, William B.; Smrcka, Alan V.

2016-01-01

Phospholipase C-ε (PLC-ε) is a unique PLC isoform that can be regulated by multiple signaling inputs from both Ras family GTPases and heterotrimeric G proteins and has primary sites of expression in the heart and lung. Whereas the role of PLC-ε in cardiac function and pathology has been documented, its relevance in acute lung injury (ALI) is unclear. We used PLC-ε−/− mice to address the role of PLC-ε in regulating lung vascular inflammation and injury in an aerosolized bacterial LPS inhalation mouse model of ALI. PLC-ε−/− mice showed a marked decrease in LPS-induced proinflammatory mediators (ICAM-1, VCAM-1, TNF-α, IL-1β, IL-6, macrophage inflammatory protein 2, keratinocyte-derived cytokine, monocyte chemoattractant protein 1, and granulocyte-macrophage colony-stimulating factor), lung neutrophil infiltration and microvascular leakage, and loss of VE-cadherin compared with PLC-ε+/+ mice. These data identify PLC-ε as a critical determinant of proinflammatory and leaky phenotype of the lung. To test the possibility that PLC-ε activity in endothelial cells (EC) could contribute to ALI, we determined its role in EC inflammation and barrier disruption. RNAi knockdown of PLC-ε inhibited NF-κB activity in response to diverse proinflammatory stimuli, thrombin, LPS, TNF-α, and the nonreceptor agonist phorbol 13-myristate 12-acetate (phorbol esters) in EC. Depletion of PLC-ε also inhibited thrombin-induced expression of NF-κB target gene, VCAM-1. Importantly, PLC-ε knockdown also protected against thrombin-induced EC barrier disruption by inhibiting the loss of VE-cadherin at adherens junctions and formation of actin stress fibers. These data identify PLC-ε as a novel regulator of EC inflammation and permeability and show a hitherto unknown role of PLC-ε in the pathogenesis of ALI. PMID:27371732

Phospholipase C-ε signaling mediates endothelial cell inflammation and barrier disruption in acute lung injury.

PubMed

Bijli, Kaiser M; Fazal, Fabeha; Slavin, Spencer A; Leonard, Antony; Grose, Valerie; Alexander, William B; Smrcka, Alan V; Rahman, Arshad

2016-08-01

Phospholipase C-ε (PLC-ε) is a unique PLC isoform that can be regulated by multiple signaling inputs from both Ras family GTPases and heterotrimeric G proteins and has primary sites of expression in the heart and lung. Whereas the role of PLC-ε in cardiac function and pathology has been documented, its relevance in acute lung injury (ALI) is unclear. We used PLC-ε(-/-) mice to address the role of PLC-ε in regulating lung vascular inflammation and injury in an aerosolized bacterial LPS inhalation mouse model of ALI. PLC-ε(-/-) mice showed a marked decrease in LPS-induced proinflammatory mediators (ICAM-1, VCAM-1, TNF-α, IL-1β, IL-6, macrophage inflammatory protein 2, keratinocyte-derived cytokine, monocyte chemoattractant protein 1, and granulocyte-macrophage colony-stimulating factor), lung neutrophil infiltration and microvascular leakage, and loss of VE-cadherin compared with PLC-ε(+/+) mice. These data identify PLC-ε as a critical determinant of proinflammatory and leaky phenotype of the lung. To test the possibility that PLC-ε activity in endothelial cells (EC) could contribute to ALI, we determined its role in EC inflammation and barrier disruption. RNAi knockdown of PLC-ε inhibited NF-κB activity in response to diverse proinflammatory stimuli, thrombin, LPS, TNF-α, and the nonreceptor agonist phorbol 13-myristate 12-acetate (phorbol esters) in EC. Depletion of PLC-ε also inhibited thrombin-induced expression of NF-κB target gene, VCAM-1. Importantly, PLC-ε knockdown also protected against thrombin-induced EC barrier disruption by inhibiting the loss of VE-cadherin at adherens junctions and formation of actin stress fibers. These data identify PLC-ε as a novel regulator of EC inflammation and permeability and show a hitherto unknown role of PLC-ε in the pathogenesis of ALI. Copyright © 2016 the American Physiological Society.

Validation of the CNS emotional lability scale for pseudobulbar affect (pathological laughing and crying) in multiple sclerosis patients.

PubMed

Smith, Richard A; Berg, James E; Pope, Laura E; Callahan, Janice D; Wynn, Daniel; Thisted, Ronald A

2004-12-01

Pseudobulbar affect (PBA) or pathological laughing and crying (PLC) is a disorder of affect that occurs in about 10% of multiple sclerosis (MS) patients. The objective of this study was to validate the CNS Emotional Lability Scale (CNS-LS) in MS patients and to correlate the results with the frequency and intensity of episodes of PLC. Physicians at seven private practice referral centers in the United States made a diagnosis concerning PLC based on patient interviews. Clinical coordinators separately administered the CNS-LS, a self-report measure of PLC with seven questions, to MS patients, including patients known to exhibit PLC, patients thought to be free of PLC, and newly diagnosed patients where PLC status was unknown, and the physician was blinded as to the results. A receiver operating characteristic (ROC) curve analysis was performed to define a cut-off best correlating with the physician's diagnosis. Of 90 MS patients selected to complete the survey, 50 were physician diagnosed with PLC; 40 were without PLC, and 15 of these 90 patients were newly diagnosed with MS (<6 months). Scores of 17 or higher corresponded to a sensitivity of 0.94 and a specificity of 0.83 (LR+ = 5.5, LR- = 0.07); 89% of patients were correctly diagnosed. The area under the ROC curve was 0.95. Symptoms were greater in patients diagnosed as PLC than in non-PLC patients as evidenced by mean number of episodes/week, number of days/week with episodes, duration of an episode and total time in an episode. Similar results were observed if patients were classified as PLC or non-PLC according to CNS-LS score > or = 17, suggesting that the CNS-LS is a valid measure for the assessment of PLC in MS patients and could be a useful instrument for clinical and research purposes.

10 CFR Appendix Q to Subpart B of... - Uniform Test Method for Measuring the Energy Consumption of Fluorescent Lamp Ballasts

Code of Federal Regulations, 2010 CFR

2010-01-01

... fluorescent lamp is designed to operate. 1.14PLC control signal means a power line carrier (PLC) signal that....3Power Line Carrier (PLC) Control Signal. Measure the PLC control signal power (watts), using a wattmeter... have a frequency response that is at least 10 times higher than the PLC being measured in order to...

10 CFR Appendix Q to Subpart B of... - Uniform Test Method for Measuring the Energy Consumption of Fluorescent Lamp Ballasts

Code of Federal Regulations, 2011 CFR

2011-01-01

... fluorescent lamp is designed to operate. 1.14PLC control signal means a power line carrier (PLC) signal that....3Power Line Carrier (PLC) Control Signal. Measure the PLC control signal power (watts), using a wattmeter... have a frequency response that is at least 10 times higher than the PLC being measured in order to...

Silica-based PLC with heterogeneously-integrated PDs for one-chip DP-QPSK receiver.

PubMed

Kurata, Yu; Nasu, Yusuke; Tamura, Munehisa; Kasahara, Ryoichi; Aozasa, Shinichi; Mizuno, Takayuki; Yokoyama, Haruki; Tsunashima, Satoshi; Muramoto, Yoshifumi

2012-12-10

To realize a DP-QPSK receiver PLC, we heterogeneously integrated eight high-speed PDs on a silica-based PLC platform with a PBS, 90-degree optical hybrids and a VOA. The use of a 2.5%-Δ waveguide reduced the receiver PLC size to 11 mm x 11 mm. We successfully demonstrated 32 Gbaud DP-QPSK signal demodulation with the receiver PLC.

Variance in total levels of phospholipase C zeta (PLC-ζ) in human sperm may limit the applicability of quantitative immunofluorescent analysis as a diagnostic indicator of oocyte activation capability.

PubMed

Kashir, Junaid; Jones, Celine; Mounce, Ginny; Ramadan, Walaa M; Lemmon, Bernadette; Heindryckx, Bjorn; de Sutter, Petra; Parrington, John; Turner, Karen; Child, Tim; McVeigh, Enda; Coward, Kevin

2013-01-01

To examine whether similar levels of phospholipase C zeta (PLC-ζ) protein are present in sperm from men whose ejaculates resulted in normal oocyte activation, and to examine whether a predominant pattern of PLC-ζ localization is linked to normal oocyte activation ability. Laboratory study. University laboratory. Control subjects (men with proven oocyte activation capacity; n = 16) and men whose sperm resulted in recurrent intracytoplasmic sperm injection failure (oocyte activation deficient [OAD]; n = 5). Quantitative immunofluorescent analysis of PLC-ζ protein in human sperm. Total levels of PLC-ζ fluorescence, proportions of sperm exhibiting PLC-ζ immunoreactivity, and proportions of PLC-ζ localization patterns in sperm from control and OAD men. Sperm from control subjects presented a significantly higher proportion of sperm exhibiting PLC-ζ immunofluorescence compared with infertile men diagnosed with OAD (82.6% and 27.4%, respectively). Total levels of PLC-ζ in sperm from individual control and OAD patients exhibited significant variance, with sperm from 10 out of 16 (62.5%) exhibiting levels similar to OAD samples. Predominant PLC-ζ localization patterns varied between control and OAD samples with no predictable or consistent pattern. The results indicate that sperm from control men exhibited significant variance in total levels of PLC-ζ protein, as well as significant variance in the predominant localization pattern. Such variance may hinder the diagnostic application of quantitative PLC-ζ immunofluorescent analysis. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Knockdown of phospholipase C-β1 in the medial prefrontal cortex of male mice impairs working memory among multiple schizophrenia endophenotypes

PubMed Central

Kim, Seong-Wook; Seo, Misun; Kim, Duk-Soo; Kang, Moonkyung; Kim, Yeon-Soo; Koh, Hae-Young; Shin, Hee-Sup

2015-01-01

Background Decreased expression of phospholipase C-β1 (PLC-β1) has been observed in the brains of patients with schizophrenia, but, to our knowledge, no studies have shown a possible association between this altered PLC-β1 expression and the pathogenesis of schizophrenia. Although PLC-β1-null (PLC-β1−/−) mice exhibit multiple endophenotypes of schizophrenia, it remains unclear how regional decreases in PLC-β1 expression in the brain contribute to specific behavioural defects. Methods We selectively knocked down PLC-β1 in the medial prefrontal cortex (mPFC) using a small hairpin RNA strategy in mice. Results Silencing PLC-β1 in the mPFC resulted in working memory deficits, as assayed using the delayed non-match-to-sample T-maze task. Notably, however, other schizophrenia- related behaviours observed in PLC-β1−/− mice, including phenotypes related to locomotor activity, sociability and sensorimotor gating, were normal in PLC-β1 knockdown mice. Limitations Phenotypes of PLC-β1 knockdown mice, such as locomotion, anxiety and sensorimotor gating, have already been published in our previous studies. Further, the neural mechanisms underlying the working memory deficit in mice may be different from those in human schizophrenia. Conclusion These results indicate that PLC-β1 signalling in the mPFC is required for working memory. Importantly, these results support the notion that the decrease in PLC-β1 expression in the brains of patients with schizophrenia is a pathogenically relevant molecular marker of the disorder. PMID:25268789

Contributions of PIP(2)-specific-phospholipase C and free salicylic acid to heat acclimation-induced thermotolerance in pea leaves.

PubMed

Liu, Hong-Tao; Huang, Wei-Dong; Pan, Qiu-Hong; Weng, Fang-Hua; Zhan, Ji-Cheng; Liu, Yan; Wan, Si-Bao; Liu, Yan-Yan

2006-03-01

The relationship between the accumulation in endogenous free salicylic acid (SA) induced by heat acclimation (37 degrees C) and the activity of PIP(2)-phospholipase C (PIP(2)-PLC; EC 3.1.4.3) in the plasma membrane fraction was investigated in pea (Pisum sativum L.) leaves. We focused our attention on the hypothesis that positive SA signals induced by heat acclimation may be relayed by PIP(2)-PLC. Heat acclimation induced an abrupt elevation of free SA preceding the activation of PLC toward PIP(2). Immunoblotting indicated a molecular mass with 66.5kDa PLC plays key role in the development of thermotolerance in pea leaves. In addition, some characterizations of PLC toward PIP(2) isolated from pea leaves with two-phase purification containing calcium concentration, pH and a protein concentration were also studied. Neomycin sulfate, a well-known PIP(2)-PLC inhibitor, was employed to access the involvement of PIP(2)-PLC in the acquisition of heat acclimation induced-thermotolerance. We were able to identify a PIP(2)-PLC, which was similar to a conventional PIP(2)-PLC in higher plants, from pea leaves suggesting that PIP(2)-PLC was involved in the signal pathway that leads to the acquisition of heat acclimation induced-thermotolerance. On the basis of these results, we conclude that the involvement of free SA may function as the upstream event in the stimulation of PIP(2)-PLC in response to heat acclimation treatment.

PC-PLC/sphingomyelin synthase activity plays a central role in the development of myogenic tone in murine resistance arteries

PubMed Central

Zacharia, Joseph; Fairfax, Seth; Wier, Withrow Gil

2015-01-01

Myogenic tone is an intrinsic property of the vasculature that contributes to blood pressure control and tissue perfusion. Earlier investigations assigned a key role in myogenic tone to phospholipase C (PLC) and its products, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Here, we used the PLC inhibitor, U-73122, and two other, specific inhibitors of PLC subtypes (PI-PLC and PC-PLC) to delineate the role of PLC in myogenic tone of pressurized murine mesenteric arteries. U-73122 inhibited depolarization-induced contractions (high external K+ concentration), thus confirming reports of nonspecific actions of U-73122 and its limited utility for studies of myogenic tone. Edelfosine, a specific inhibitor of PI-PLC, did not affect depolarization-induced contractions but modulated myogenic tone. Because PI-PLC produces IP3, we investigated the effect of blocking IP3 receptor-mediated Ca2+ release on myogenic tone. Incubation of arteries with xestospongin C did not affect tone, consistent with the virtual absence of Ca2+ waves in arteries with myogenic tone. D-609, an inhibitor of PC-PLC and sphingomyelin synthase, strongly inhibited myogenic tone and had no effect on depolarization-induced contraction. D-609 appeared to act by lowering cytoplasmic Ca2+ concentration to levels below those that activate contraction. Importantly, incubation of pressurized arteries with a membrane-permeable analog of DAG induced vasoconstriction. The results therefore mandate a reexamination of the signaling pathways activated by the Bayliss mechanism. Our results suggest that PI-PLC and IP3 are not required in maintaining myogenic tone, but DAG, produced by PC-PLC and/or SM synthase, is likely through multiple mechanisms to increase Ca2+ entry and promote vasoconstriction. PMID:25888510

Regulation and physiological functions of mammalian phospholipase C.

PubMed

Nakamura, Yoshikazu; Fukami, Kiyoko

2017-04-01

Phospholipase C (PLC) is a key enzyme in phosphoinositide metabolism. PLC hydrolyses phosphatidylinositol 4,5-bis-phosphate to generate two second messengers, inositol 1,4,5-trisphosphate and diacylglycerol, that generate diverse cellular responses. PLC is activated by various signalling molecules, including Ca2+, heterometric G proteins, small G proteins, and receptor/non-receptor tyrosine kinases. In addition to their enzymatic activity, some PLC subtypes also function as a guanine nucleotide exchange factor, GTPase-activating protein, and adaptor protein, independent of their lipase activity. There are 13 PLC isozymes in mammals, and they are categorized into six classes based on structure. Generation and analysis of genetically modified mice has revealed the unexpectedly diverse physiological functions of PLC isozymes. Although all PLC isozymes catalyze the same reaction, each PLC isozyme has unique physiological functions. This review focuses on the regulation and physiological functions of PLCs. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Effects of Phospholipase C on Fusarium graminearum Growth and Development.

PubMed

Zhu, Qili; Zhou, Benguo; Gao, Zhengliang; Liang, Yuancun

2015-12-01

Phospholipase C (PLC) plays important roles in regulating various biological processes in eukaryotes. Currently, little is known about the function of PLC in filamentous fungi, especially the plant pathogenic fungi. Fusarium graminearum is the causal agent of Fusarium head blight in many cereal crops. BLAST search revealed that Fusarium genome contains six FgPLC genes. Using quantitative RT-PCR, different FgPLC gene expressions in mycelia were analyzed. To investigate the role of FgPLC in F. graminearum biology, a pharmacological study using a known inhibitor of PLC (U73122) was conducted. Results showed that inhibition of FgPLC resulted in significant alterations of mycelial growth, conidiation, conidial germination, perithecium formation, and expressions of Tri5 and Tri6 genes. As expected, the treatment of F. graminearum with U73343, an inactive analog of U73122, showed no effect on F. graminearum biology. Our results suggested strongly that FgPLC plays important roles in F. graminearum growth and development.

Plant phospholipase C family: Regulation and functional role in lipid signaling.

PubMed

Singh, Amarjeet; Bhatnagar, Nikita; Pandey, Amita; Pandey, Girdhar K

2015-08-01

Phospholipase C (PLC), a major membrane phospholipid hydrolyzing enzyme generates signaling messengers such as diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) in animals, and their phosphorylated forms such as phosphatidic acid (PA) and inositol hexakisphosphate (IP6) are thought to regulate various cellular processes in plants. Based on substrate specificity, plant PLC family is sub-divided into phosphatidylinositol-PLC (PI-PLC) and phosphatidylcholine-PLC (PC-PLC) groups. The activity of plant PLCs is regulated by various factors and the major ones include, Ca(2+) concentration, phospholipid substrate, post-translational modifications and interacting proteins. Most of the PLC members have been localized at the plasma membrane, suited for their function of membrane lipid hydrolysis. Several PLC members have been implicated in various cellular processes and signaling networks, triggered in response to a number of environmental cues and developmental events in different plant species, which makes them potential candidates for genetically engineering the crop plants for stress tolerance and enhancing the crop productivity. In this review article, we are focusing mainly on the plant PLC signaling and regulation, potential cellular and physiological role in different abiotic and biotic stresses, nutrient deficiency, growth and development. Copyright © 2015 Elsevier Ltd. All rights reserved.

78 FR 34550 - Airworthiness Directives; Rolls-Royce plc Turbojet Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-10

... Airworthiness Directives; Rolls-Royce plc Turbojet Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for all Rolls-Royce plc..., contact Defence Aerospace Communications at Rolls-Royce plc, P.O. Box 3, Gypsy Patch Lane, Filton, Bristol...

76 FR 29814 - Statutory Debarment and Reinstatement of BAE Systems plc

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2011-05-23

... Department of State [Public Notice: 7465] Statutory Debarment and Reinstatement of BAE Systems plc Bureau of Political-Military Affairs; Statutory Debarment and Reinstatement of BAE Systems plc and Policy...'') (22 CFR Parts 120-130), imposed a statutory debarment on BAE Systems plc (``BAES'') as a result of its...

Reproductive factors, menopausal hormone therapies and primary liver cancer risk: a systematic review and dose-response meta-analysis of observational studies.

PubMed

Zhong, Guo-Chao; Liu, Yan; Chen, Nan; Hao, Fa-Bao; Wang, Kang; Cheng, Jia-Hao; Gong, Jian-Ping; Ding, Xiong

2016-12-01

A striking gender disparity in the incidence and outcome of primary liver cancer (PLC) has been well recognized. Mounting evidence from basic research suggests that hormonal factors may be involved in the gender disparity of PLC. Whether hormonal exposures in human subjects are associated with PLC risk is largely unknown. Whether reproductive factors and use of menopausal hormone therapies (MHTs) in women are associated with PLC risk remains controversial. We conducted this study to clarify this issue. PubMed and EMBASE were searched to July, 2016 for studies published in English or Chinese. Observational studies (cohort, nested case-control and case-control) that provided risk estimates of reproductive factors, MHTs and PLC risk were eligible. The quality of included studies was determined based on the Newcastle-Ottawa quality assessment scale. Summary risk ratios (RRs) were calculated using a random-effects model. Dose-response analysis was conducted where possible. Fifteen peer-reviewed studies, involving 1795 PLC cases and 2 256 686 women, were included. Overall meta-analyses on parity and PLC risk did not find any significant associations; however, when restricting to studies with PLC cases ≥100, increasing parity was found to be significantly associated with a decreased risk of PLC [RR for the highest versus lowest parity 0.67, 95% CI 0.52, 0.88; RR for parous versus nulliparous 0.71, 95% CI 0.53, 0.94; RR per one live birth increase 0.93, 95% CI 0.88, 0.99]. A J-shaped relationship between parity and PLC risk was identified (P non-linearity  < 0.01). Compared with never users, the pooled RRs of PLC were 0.60 (95% CI 0.37, 0.96) for ever users of MHT, 0.73 (95% CI 0.46, 1.17) for ever users of estrogen-only therapy (ET) and 0.67 (95% CI 0.45, 1.02) for ever users of estrogen-progestin therapy (EPT). The pooled RR of PLC for the oldest versus youngest category of menarcheal age was 0.50 (95% CI 0.32, 0.79). Oophorectomy was significantly associated with an increased risk of PLC (RR 2.23, 95% CI 1.46, 3.41). No significant association of age at first birth, and spontaneous or induced abortion with PLC risk was found. No meta-analysis was performed for the association of age at menopause, breastfeeding, hysterectomy, menopausal status and stillbirth with PLC risk owing to huge methodological heterogeneity and/or very limited studies. Parity is associated with PLC risk in a J-shaped dose-response pattern. Late age at menarche and ever use of MHT are associated with a reduced risk of PLC, whereas there is no association of ever use of ET and EPT, age at first birth, or spontaneous and induced abortion with PLC risk. Compared to women with no history of oophorectomy, those with a history of oophorectomy are at an increased risk of PLC. Our findings provide some epidemiological support for a role of hormonal exposures in the development of PLC in women. However, these findings should be interpreted with much caution because of the limited number of studies and potential biases, and need to be validated by studies with good design and large sample size. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

77 FR 13483 - Airworthiness Directives; Rolls-Royce plc (RR) Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-07

... Directives; Rolls-Royce plc (RR) Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... service information identified in this AD, contact Rolls-Royce plc, Corporate Communications, P.O. Box 31...), or, have Rolls-Royce plc revise Alert Service Bulletin (ASB) No. RB.211-72-AF964 to remove the...

78 FR 10172 - Lisa Anne Cornell and G. Ware Cornell, Jr. v. Princess Cruise Lines, Ltd. (Corp), Carnival PLC...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-13

.... Princess Cruise Lines, Ltd. (Corp), Carnival PLC, and Carnival Corporation; Notice of Filing of Complaint...,'' against Princess Cruise Lines, Ltd (Corp), Carnival plc, and Carnival Corporation hereinafter... from ports in the United States;'' Respondent Carnival plc ``is a corporation established under the...

76 FR 65136 - Airworthiness Directives; Rolls-Royce plc (RR) Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-20

... Airworthiness Directives; Rolls-Royce plc (RR) Turbofan Engines AGENCY: Federal Aviation Administration (FAA... information identified in this AD, contact Rolls-Royce plc, Corporate Communications, P.O. Box 31, Derby...-166679 (76 FR 24793, May 3, 2011), and adding the following new AD: Rolls-Royce plc: Docket No. FAA-2010...

75 FR 46864 - Airworthiness Directives; Short Brothers PLC Model SD3 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-04

...-0225; Directorate Identifier 2009-NM-203-AD] RIN 2120-AA64 Airworthiness Directives; Short Brothers PLC... this proposed AD, contact Short Brothers PLC, Airworthiness, P.O. Box 241, Airport Road, Belfast, BT3... Brothers PLC: Docket No. FAA-2010-0225; Directorate Identifier 2009-NM-203-AD. Comments Due Date (a) We...

77 FR 6668 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-09

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... all Rolls-Royce plc RB211-Trent 500 series turbofan engines. This AD requires a one-time inspection of... RB211- Trent 560A2-61 turbofan engines that have not complied with Rolls- Royce plc Service Bulletin No...

78 FR 11976 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-21

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... (AD) for all Rolls-Royce plc (RR) RB211-524 series turbofan engines. That AD currently requires...-16724 (76 FR 40217, July 8, 2011), for all RR plc RB211-524 series turbofan engines. That AD required...

Conjugated polyelectrolyte based real-time fluorescence assay for phospholipase C.

PubMed

Liu, Yan; Ogawa, Katsu; Schanze, Kirk S

2008-01-01

A fluorescence turnoff assay for phospholipase C (PLC) from Clostridium perfringens is developed based on the reversible interaction between the natural substrate, phosphatidylcholine, and a fluorescent, water-soluble conjugated polyelectrolyte (CPE). The fluorescence intensity of the CPE in water is increased substantially by the addition of the phospholipid due to the formation of a CPE-lipid complex. Incubation of the CPE-lipid complex with the enzyme PLC causes the fluorescence intensity to decrease (turnoff sensor); the response arises due to PLC-catalyzed hydrolysis of the phosphatidylcholine, which effectively disrupts the CPE-lipid complex. The PLC assay operates with phospholipid substrate concentrations in the micromolar range, and the analytical detection limit for PLC is <1 nM. The optimized assay provides a convenient, rapid, and real-time sensor for PLC activity. The real-time fluorescence intensity from the CPE can be converted to substrate concentration by using an ex situ calibration curve, allowing PLC-catalyzed reaction rates and kinetic parameters to be determined. PLC activation by Ca2+ and inhibition by EDTA and fluoride ion are demonstrated using the optimized sensor.

Multiple roles of phosphoinositide-specific phospholipase C isozymes.

PubMed

Suh, Pann-Ghill; Park, Jae-Il; Manzoli, Lucia; Cocco, Lucio; Peak, Joanna C; Katan, Matilda; Fukami, Kiyoko; Kataoka, Tohru; Yun, Sanguk; Ryu, Sung Ho

2008-06-30

Phosphoinositide-specific phospholipase C is an effector molecule in the signal transduction process. It generates two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. Currently, thirteen mammal PLC isozymes have been identified, and they are divided into six groups: PLC-beta, -gamma, -delta, -epsilon, -zeta and -eta. Sequence analysis studies demonstrated that each isozyme has more than one alternative splicing variant. PLC isozymes contain the X and Y domains that are responsible for catalytic activity. Several other domains including the PH domain, the C2 domain and EF hand motifs are involved in various biological functions of PLC isozymes as signaling proteins. The distribution of PLC isozymes is tissue and organ specific. Recent studies on isolated cells and knockout mice depleted of PLC isozymes have revealed their distinct phenotypes. Given the specificity in distribution and cellular localization, it is clear that each PLC isozyme bears a unique function in the modulation of physiological responses. In this review, we discuss the structural organization, enzymatic properties and molecular diversity of PLC splicing variants and study functional and physiological roles of each isozyme.

Kinetic Analysis of Phospholipase C from Catharanthus roseus Transformed Roots Using Different Assays1

PubMed Central

Hernández-Sotomayor, S.M. Teresa; De Los Santos-Briones, César; Muñoz-Sánchez, J. Armando; Loyola-Vargas, Victor M.

1999-01-01

The properties of phospholipase C (PLC) partially purified from Catharanthus roseus transformed roots were analyzed using substrate lipids dispersed in phospholipid vesicles, phospholipid-detergent mixed micelles, and phospholipid monolayers spread at an air-water interface. Using [33P]phosphatidylinositol 4,5-bisphosphate (PIP2) of high specific radioactivity, PLC activity was monitored directly by measuring the loss of radioactivity from monolayers as a result of the release of inositol phosphate and its subsequent dissolution on quenching in the subphase. PLC activity was markedly affected by the surface pressure of the monolayer, with reduced activity at extremes of initial pressure. The optimum surface pressure for PIP2 hydrolysis was 20 mN/m. Depletion of PLC from solution by incubation with sucrose-loaded PIP2 vesicles followed by ultracentrifugation demonstrated stable attachment of PLC to the vesicles. A mixed micellar system was established to assay PLC activity using deoxycholate. Kinetic analyses were performed to determine whether PLC activity was dependent on both bulk PIP2 and PIP2 surface concentrations in the micelles. The interfacial Michaelis constant was calculated to be 0.0518 mol fraction, and the equilibrium dissociation constant of PLC for the lipid was 45.5 μm. These findings will add to our understanding of the mechanisms of regulation of plant PLC. PMID:10444091

The association of pathological laughing and crying and cognitive impairment in multiple sclerosis.

PubMed

Hanna, Joshua; Feinstein, Anthony; Morrow, Sarah A

2016-02-15

Pathological laughing and crying (PLC) is common in multiple sclerosis (MS), defined as emotional expression that is exaggerated/incongruent with underlying mood. In other neurological disorders, PLC is associated with cognitive impairment (CI). Few studies have examined this relationship in MS. To determine the association between PLC and CI in an MS population. Retrospective chart review study of 153 MS subjects assessed in an outpatient clinic for CI. Data was collected on the minimal assessment of cognitive function in MS (MACFIMS), the Center for neurological study-lability scale (CNS-LS), a screening measure for PLC symptoms and the hospital anxiety and depression scale (HADS). Analyses of covariance compared performance on the MACFIMS between PLC (CNS-LS score ≥ 17, HADS-D ≤ 7) and non-PLC groups. MS subjects positive for PLC on the CNS-LS but without depression had lower scores on the controlled oral word association test, a measure of verbal fluency, and the California verbal learning test - 2 immediate recall score, a verbal memory measure. This study demonstrates a connection between CI, specifically verbal fluency and verbal learning, and PLC in MS subjects. Further studies are warranted to explore the causative relationship between CI and PLC. Copyright © 2015. Published by Elsevier B.V.

Insulin-like growth factor-binding protein 7 alters the sensitivity to interferon-based anticancer therapy in hepatocellular carcinoma cells.

PubMed

Tomimaru, Y; Eguchi, H; Wada, H; Noda, T; Murakami, M; Kobayashi, S; Marubashi, S; Takeda, Y; Tanemura, M; Umeshita, K; Doki, Y; Mori, M; Nagano, H

2010-05-11

A striking efficiency of interferon (IFN)-based anticancer therapy for advanced hepatocellular carcinoma (HCC) has been reported. Because its clinical efficiency greatly depends on each patient's local response, prediction of local response is crucial. Continuous exposure of IFN-alpha to parental PLC/PRF/5 cells (PLC-P) and a limiting dilution method resulted in the establishment of IFN-resistant cell clones (PLC-Rs). Microarray analyses of PLC-P and PLC-Rs identified insulin-like growth factor-binding protein 7 (IGFBP7) as one of the most significantly downregulated genes in PLC-Rs. Changes in anticancer effects of IFN-alpha were examined in HCC cells after genetic manipulation of IGFBP7 expression. The correlation between immunohistochemically determined IGFBP7 expression and the response to IFN-alpha/5-fluorouracil (5-FU) therapy was investigated in surgically resected HCC specimens. PLC-R cells showed a remarkable downregulation of IGFBP7 and resistance to IFN-alpha, compared with PLC-P. Parental PLC/PRF/5 cells transfected with short hairpin RNA against IGFBP7 showed a significant resistance to IFN-alpha relative to control cells (IC(50) fold increase=14.38 times). Insulin-like growth factor-binding protein 7 transfection into PLC-R restored sensitivity to IFN-alpha. In resected specimens, IGFBP7 expression significantly correlated with the response to IFN-alpha/5-FU therapy. IGFBP7 could be a useful predictor of the response to IFN-based therapy in advanced HCC.

Development of a liquid chromatography-mass spectrometry based enzyme activity assay for phosphatidylcholine-specific phospholipase C.

PubMed

Murakami, Chiaki; Mizuno, Satoru; Kado, Sayaka; Sakane, Fumio

2017-06-01

Phosphatidylcholine (PC)-specific phospholipase C (PC-PLC) hydrolyzes PC to generate the second messenger 1,2-diacylglycerol (DG) and phosphocholine. PC-PLC plays pivotal roles in inflammation, carcinogenesis, tumor progression, atherogenesis, and subarachnoid hemorrhage. Although the activity of PC-PLC in mammalian tissues was discovered approximately 40 years ago, neither the protein nor its gene has been identified. In the present study, we developed a non-radioactive enzyme activity assay for PC-PLC based on mass spectrometric detection of DG following HPLC separation. This new liquid chromatography-mass spectrometry (LC-MS) assay directly determines a specific reaction product, 1-palmitoyl-2-oleoyl-DG, that is generated from 1-palmitoyl-2-oleoyl-PC by purified Bacillus cereus PC-PLC. The LC-MS assay offers several advantages including a lower background (0.02% versus 91%), higher signal background ratio (4242 versus 1.06)/signal noise ratio (7494 versus 4.4), higher sensitivity (≥32-fold), and lower limit of quantitation (0.04 pmol versus 0.69 pmol of PC-PLC), than a conventional fluorometric assay, which indirectly detects phosphocholine produced in the reaction. In addition to Bacillus cereus PC-PLC, the LC-MS assay was applicable to the measurement of mammalian PC-PLC prepared from the mouse brain. The radioisotope-free, highly sensitive and precise LC-MS assay for PC-PLC would be useful for the purification and identification of PC-PLC protein. Copyright © 2017 Elsevier Inc. All rights reserved.

The binding of activated Gαq to phospholipase C-β exhibits anomalous affinity.

PubMed

Navaratnarajah, Punya; Gershenson, Anne; Ross, Elliott M

2017-10-06

Upon activation by the G q family of Gα subunits, Gβγ subunits, and some Rho family GTPases, phospholipase C-β (PLC-β) isoforms hydrolyze phosphatidylinositol 4,5-bisphosphate to the second messengers inositol 1,4,5-trisphosphate and diacylglycerol. PLC-β isoforms also function as GTPase-activating proteins, potentiating G q deactivation. To elucidate the mechanism of this mutual regulation, we measured the thermodynamics and kinetics of PLC-β3 binding to Gα q FRET and fluorescence correlation spectroscopy, two physically distinct methods, both yielded K d values of about 200 nm for PLC-β3-Gα q binding. This K d is 50-100 times greater than the EC 50 for Gα q -mediated PLC-β3 activation and for the Gα q GTPase-activating protein activity of PLC-β. The measured K d was not altered either by the presence of phospholipid vesicles, phosphatidylinositol 4,5-bisphosphate and Ca 2+ , or by the identity of the fluorescent labels. FRET-based kinetic measurements were also consistent with a K d of 200 nm We determined that PLC-β3 hysteresis, whereby PLC-β3 remains active for some time following either Gα q -PLC-β3 dissociation or PLC-β3-potentiated Gα q deactivation, is not sufficient to explain the observed discrepancy between EC 50 and K d These results indicate that the mechanism by which Gα q and PLC-β3 mutually regulate each other is far more complex than a simple, two-state allosteric model and instead is probably kinetically determined. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Phosphatidylinositol-Specific Phospholipase C Contributes to Survival of Staphylococcus aureus USA300 in Human Blood and Neutrophils

PubMed Central

White, Mark J.; Boyd, Jeffrey M.

2014-01-01

Staphylococcus aureus is an important human pathogen that employs a large repertoire of secreted virulence factors to promote disease pathogenesis. Many strains of S. aureus possess a plc gene that encodes a phosphatidylinositol (PI)-specific phospholipase C (PI-PLC) capable of hydrolyzing PI and cleaving glycosyl-PI (GPI)-linked proteins from cell surfaces. Despite being secreted by virulent staphylococci, the contribution of PI-PLC to the capacity of S. aureus to cause disease remains undefined. Our goal in these studies was to understand PI-PLC in the context of S. aureus biology. Among a collection of genetically diverse clinical isolates of S. aureus, community-associated methicillin-resistant S. aureus (CA-MRSA) USA300 secreted the most PI-PLC. Screening a collection of two-component system (TCS) mutants of S. aureus, we identified both the agr quorum-sensing system and the SrrAB TCS to be positive regulators of plc gene expression. Real-time PCR and PI-PLC enzyme assays of the TCS mutants, coupled with SrrA promoter binding studies, demonstrated that SrrAB was the predominant transcriptional activator of plc. Furthermore, plc regulation was linked to oxidative stress both in vitro and in vivo in a SrrAB-dependent manner. A Δplc mutant in a CA-MRSA USA300 background exhibited a survival defect in human whole blood and in isolated neutrophils. However, the same mutant strain displayed no survival defect in murine models of infection or murine whole blood. Overall, these data identify potential links between bacterial responses to the host innate immune system and to oxidative stress and suggest how PI-PLC could contribute to the pathogenesis of S. aureus infections. PMID:24452683

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

Participation of PLA2 and PLC in DhL-induced activation of Rhinella arenarum oocytes.

PubMed

Zapata-Martínez, J; Medina, M F; Gramajo-Bühler, M C; Sánchez-Toranzo, G

2016-08-01

Rhinella arenarum oocytes can be artificially activated, a process known as parthenogenesis, by a sesquiterpenic lactone of the guaianolide group, dehydroleucodine (DhL). Transient increases in the concentration of cytosolic Ca2+ are essential to trigger egg activation events. In this sense, the 1-4-5 inositol triphosphate receptors (IP3R) seem to be involved in the Ca2+ transient release induced by DhL in this species. We analyzed the involvement of phosphoinositide metabolism, especially the participation of phospholipase A2 (PLA2) and phospholipase C (PLC) in DhL-induced activation. Different doses of quinacrine, aristolochic acid (ATA) (PLA2 inhibitors) or neomycin, an antibiotic that binds to PIP2, thus preventing its hydrolysis, were used in mature Rhinella arenarum oocytes. In order to assay the participation of PI-PLC and PC- PLC we used U73122, a competitive inhibitor of PI-PLC dependent events and D609, an inhibitor of PC-PLC. We found that PLA2 inhibits quinacrine more effectively than ATA. This difference could be explained by the fact that quinacrine is not a specific inhibitor for PLA2 while ATA is specific for this enzyme. With respect to the participation of PLC, a higher decrease in oocyte activation was detected when cells were exposed to neomycin. Inhibition of PC-PLC with D609 and IP-PLC with U73122 indicated that the last PLC has a significant participation in the effect of DhL-induced activation. Results would indicate that DhL induces activation of in vitro matured oocytes of Rhinella arenarum by activation of IP-PLC, which in turn may induce IP3 formation which produces Ca2+ release.

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

PubMed Central

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

2011-01-01

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

Peptide microarray profiling identifies phospholipase C gamma 1 (PLC-γ1) as a potential target for t(8;21) AML

PubMed Central

Mahmud, Hasan; Scherpen, Frank J.G.; de Boer, Tiny Meeuwsen; Lourens, Harm-Jan; Schoenherr, Caroline; Eder, Matthias; Scherr, Michaela; Guryev, Victor; De Bont, Eveline S.

2017-01-01

The t(8;21) (q22;q22) chromosomal translocation is one of the most frequent genetic alterations in acute myeloid leukemia (AML) which has a need for improved therapeutic strategies. We found PLC-γ1 as one of the highest phosphorylated peptides in t(8;21) AML samples compared to NBM or CN-AML in our previous peptide microarray. PLC-γ1 is known to play a role in cancer progression, however, the impact of PLC-γ1 in AML is currently unknown. Therefore, we aimed to study the functional role of PLC-γ1 by investigating the cellular growth, survival and its underlying mechanism in t(8;21) AML. In this study, PLC-γ1 expression was significantly higher in t(8;21) AML compared to other karyotypes. The PLC-γ1 protein expression was suppressed in AML1-ETO knock down cells indicating that it might induce kasumi-1 cell death. ShRNA-mediated PLC-γ1 knockdown in kasumi-1 cells significantly blocked cell growth, induced apoptosis and cell cycle arrest which was explained by the increased activation of apoptotic related and cell cycle regulatory protein expressions. Gene expression array analysis showed the up-regulation of apoptotic and DNA damage response genes together with the downregulation of cell growth, proliferation and differentiation genes in the PLC-γ1 suppressed kasumi-1 cells, consistent with the observed phenotypic effects. Importantly, PLC-γ1 suppressed kasumi-1 cells showed higher chemosensitivity to the chemotherapeutic drug treatments and lower cell proliferation upon hypoxic stress. Taken together, these in vitro finding strongly support an important role for PLC-γ1 in the survival of t(8;21) AML mimicking kasumi-1 cells and identify PLC-γ1 as a potential therapeutic target for t(8;21) AML treatment. PMID:28978037

Phosphatidylcholine hydrolysis and c-myc expression are in collaborating mitogenic pathways activated by colony-stimulating factor 1.

PubMed

Xu, X X; Tessner, T G; Rock, C O; Jackowski, S

1993-03-01

Stimulation of diglyceride production via phospholipase C (PLC) hydrolysis of phosphatidylcholine was an early event in the mitogenic action of colony-stimulating factor 1 (CSF-1) in the murine macrophage cell line BAC1.2F5 and was followed by a second phase of diglyceride production that persisted throughout the G1 phase of the cell cycle. Addition of phosphatidylcholine-specific PLC (PC-PLC) from Bacillus cereus to the medium of quiescent cells raised the intracellular diglyceride concentration and stimulated [3H]thymidine incorporation, although PC-PLC did not support continuous proliferation. PC-PLC treatment did not induce tyrosine phosphorylation or turnover of the CSF-1 receptor. The major protein kinase C (PKC) isotype in BAC1.2F5 cells was PKC-delta. Diglyceride production from PC-PLC did not target PKC-delta, since unlike phorbol esters, PC-PLC treatment neither decreased the electrophoretic mobility of PKC-delta nor increased the amount of GTP bound to Ras, and PC-PLC was mitogenically active in BAC1.2F5 cells in which PKC-delta was downregulated by prolonged treatment with phorbol ester. PC-PLC mimicked CSF-1 action by elevating c-fos and junB mRNAs to 40% of the level induced by CSF-1; however, PC-PLC induced c-myc mRNA to only 5% of the level in CSF-1-stimulated cells. PC-PLC addition to CSF-1-dependent BAC1.2F5 clones that constitutively express c-myc increased [3H]thymidine incorporation to 86% of the level evoked by CSF-1 and supported slow growth in the absence of CSF-1. Therefore, PC-PLC is a component of a signal transduction pathway leading to transcription of c-fos and junB that collaborates with c-myc and is independent of PKC-delta and Ras activation.

Interaction of phospholipase C with liposome: A conformation transition of the enzyme is critical and specific to liposome composition for burst hydrolysis and fusion in concert

NASA Astrophysics Data System (ADS)

Patra, Samir Kumar; Sengupta, Dipta; Deb, Moonmoon; Kar, Swayamsiddha; Kausar, Chahat

2017-02-01

Phospholipase C (PLC)1 is known to help the pathogen B. cereus entry to the host cell and human PLC is over expressed in multiple cancers. Knowledge of dynamic activity of the enzyme PLC while in action on membrane lipids is essential and helpful to drug design and delivery. In view of this, interactions of PLC with liposome of various lipid compositions have been visualized by testing enzyme activity and microenvironments around the intrinsic fluorophores of the enzyme. Overall change of the protein's conformation has been monitored by fluorescence spectroscopy and circular dichroism (CD). Liposome aggregation and fusion were predicted by increase in turbidity and vesicle size. PLC in solution has high fluorescence and exhibit appreciable shift in its emission maxima, upon gradual change in excitation wavelength towards the red edge of the absorption band. REES fluorescence studies indicated that certain Trp fluorophores of inactive PLC are in motionally restricted compact/rigid environments in solution conformation. PLC fluorescence decreased in association with liposome and Trps loosed rigidity where liposome aggregation and fusion occurred. We argue that the structural flexibility is the cause of decrease of fluorescence, mostly to gain optimum conformation for maximum activity of the enzyme PLC. Further studies deciphered that the enzyme PLC undergoes change of conformation when mixed to LUVs prepared with specific lipids. CD data at the far-UV and near-UV regions of PLC in solution are in excellent agreement with the previous reports. CD analyses of PLC with LUVs, showed significant reduction of α-helices, increase of β-sheets; and confirmed dramatic change of orientations of Trps. In case of liposome composed of lipid raft like composition, the enzyme binds very fast, hydrolyze PC with higher rate, exhibit highest structural flexibility and promote vesicle fusion. These data strongly suggest marked differences in conformation transition induced PLC activation and liposome fusion on the lipid composition.

A Complex Extracellular Sphingomyelinase of Pseudomonas aeruginosa Inhibits Angiogenesis by Selective Cytotoxicity to Endothelial Cells

PubMed Central

Vasil, Michael L.; Stonehouse, Martin J.; Vasil, Adriana I.; Wadsworth, Sandra J.; Goldfine, Howard; Bolcome, Robert E.; Chan, Joanne

2009-01-01

The hemolytic phospholipase C (PlcHR) expressed by Pseudomonas aeruginosa is the original member of a Phosphoesterase Superfamily, which includes phosphorylcholine-specific phospholipases C (PC-PLC) produced by frank and opportunistic pathogens. PlcHR, but not all its family members, is also a potent sphingomyelinase (SMase). Data presented herein indicate that picomolar (pM) concentrations of PlcHR are selectively lethal to endothelial cells (EC). An RGD motif of PlcHR contributes to this selectivity. Peptides containing an RGD motif (i.e., GRGDS), but not control peptides (i.e., GDGRS), block the effects of PlcHR on calcium signaling and cytotoxicity to EC. Moreover, RGD variants of PlcHR (e.g., RGE, KGD) are significantly reduced in their binding and toxicity, but retain the enzymatic activity of the wild type PlcHR. PlcHR also inhibits several EC-dependent in vitro assays (i.e., EC migration, EC invasion, and EC tubule formation), which represent key processes involved in angiogenesis (i.e., formation of new blood vessels from existing vasculature). Finally, the impact of PlcHR in an in vivo model of angiogenesis in transgenic zebrafish, and ones treated with an antisense morpholino to knock down a key blood cell regulator, were evaluated because in vitro assays cannot fully represent the complex processes of angiogenesis. As little as 2 ng/embryo of PlcHR was lethal to ∼50% of EGFP-labeled EC at 6 h after injection of embryos at 48 hpf (hours post-fertilization). An active site mutant of PlcHR (Thr178Ala) exhibited 120-fold reduced inhibitory activity in the EC invasion assay, and 20 ng/embryo elicited no detectable inhibitory activity in the zebrafish model. Taken together, these observations are pertinent to the distinctive vasculitis and poor wound healing associated with P. aeruginosa sepsis and suggest that the potent antiangiogenic properties of PlcHR are worthy of further investigation for the treatment of diseases where angiogenesis contributes pathological conditions (e.g., vascularization of tumors, diabetic retinopathy). PMID:19424430

Phosphatidic acid regulates signal output by G protein coupled receptors through direct interaction with phospholipase C-beta(1).

PubMed

Litosch, Irene; Pujari, Rajeshree; Lee, Shawn J

2009-09-01

Phosphatidic acid (PA), generated downstream of monomeric Rho GTPases via phospholipase D (PLD) and additionally by diacylglycerol kinases (DGK), both stimulates phospholipase C-beta(1) (PLC-beta(1)) and potentiates stimulation of PLC-beta(1) activity by Galpha(q) in vitro. PA is a potential candidate for integrating signaling by monomeric and heterotrimeric G proteins to regulate signal output by G protein coupled receptors (GPCR), and we have sought to understand the mechanisms involved. We previously identified the region spanning residues 944-957, lying within the PLC-beta(1) C-terminus alphaA helix and flexible loop of the Galpha(q) binding domain, as required for stimulation of lipase activity by PA in vitro. Regulation by PA does not require residues essential for stimulation by Galpha(q) or GTPase activating activity. The present studies evaluated shorter alanine/glycine replacement mutants and finally point mutations to identify Tyr(952) and Ile(955) as key determinants for regulation by PA, assessed by both in vitro enzymatic and cell-based co-transfection assays. Replacement of Tyr(952) and Ile(955), PLC-beta(1) (Y952G/I955G), results in an 85% loss in stimulation by PA relative to WT-PLC-beta(1) in vitro. COS 7 cells co-transfected with PLC-beta(1) (Y952G/I955G) demonstrate a 10-fold increase in the EC(50) for stimulation and a 60% decrease in maximum stimulation by carbachol via Galpha(q) linked m1 muscarinic receptors, relative to cells co-transfected with WT-PLC-beta(1) but otherwise similar conditions. Residues required for regulation by PA are not essential for stimulation by G protein subunits. WT-PLC-beta(1) and PLC-beta(1) (Y952G/I955G) activity is increased comparably by co-transfection with Galpha(q) and neither is markedly affected by co-transfection with Gbeta(1)gamma(2). Inhibiting PLD-generated PA production by 1-butanol has little effect on maximum stimulation, but shifts the EC(50) for agonist stimulation of WT-PLC-beta(1) by 10-fold, producing a phenotype similar to PLC-beta(1) (Y952G/I955G) with respect to agonist potency. 1-Butanol is without effect on carbachol stimulated PLC activity in cells co-transfected with either PLC-beta(1)(Y952G/I955G) or on endogenous PLC activity, indicating that regulation by PA requires direct interaction with the PLC-beta(1) PA-binding region. These data show that endogenous PA regulates signal output by Galpha(q)-linked GPCRs in transfected cells directly through PLC-beta(1). Galpha(q) and PA may co-ordinate to regulate signaling. Regulation by PA may constitute part of a mechanism that routes receptor signaling to specific PLC isoforms.

76 FR 30529 - Airworthiness Directives; Rolls-Royce plc (RR) RB211-535 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-26

... Airworthiness Directives; Rolls-Royce plc (RR) RB211-535 Series Turbofan Engines AGENCY: Federal Aviation... To Change Related Information Paragraph One commenter, Rolls-Royce plc asked us to use a different... Airlines, and Rolls-Royce plc asked us to change the definition of a shop visit to the definition in the...

31 CFR 594.513 - Transactions with entities under the control of the Palestinian President and certain other...

Code of Federal Regulations, 2011 CFR

2011-07-01

... the Palestinian Legislative Council (PLC) who were not elected to the PLC on the party slate of Hamas... authorized to reject transactions with members of the Palestinian Legislative Council (PLC) who were elected to the PLC on the party slate of Hamas or any other Foreign Terrorist Organization (FTO), Specially...

31 CFR 595.511 - Transactions with entities under the control of the Palestinian President and certain other...

Code of Federal Regulations, 2011 CFR

2011-07-01

... the Palestinian Legislative Council (PLC) who were not elected to the PLC on the party slate of Hamas... authorized to reject transactions with members of the Palestinian Legislative Council (PLC) who were elected to the PLC on the party slate of Hamas or any other Foreign Terrorist Organization (FTO), Specially...

31 CFR 594.513 - Transactions with entities under the control of the Palestinian President and certain other...

Code of Federal Regulations, 2010 CFR

2010-07-01

... the Palestinian Legislative Council (PLC) who were not elected to the PLC on the party slate of Hamas... authorized to reject transactions with members of the Palestinian Legislative Council (PLC) who were elected to the PLC on the party slate of Hamas or any other Foreign Terrorist Organization (FTO), Specially...

76 FR 1985 - Airworthiness Directives; Short Brothers PLC Model SD3 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-12

... Airworthiness Directives; Short Brothers PLC Model SD3 Airplanes AGENCY: Federal Aviation Administration (FAA..., June 16, 2006) and adding the following new AD: 2010-24-06 Short Brothers PLC: Amendment 39-16525..., Amendment 39-14644. Applicability (c) This AD applies to all Short Brothers PLC Model SD3-60 SHERPA, SD3...

31 CFR 597.509 - Transactions with entities under the control of the Palestinian President and certain other...

Code of Federal Regulations, 2011 CFR

2011-07-01

... Council; (3) Members of the Palestinian Legislative Council (PLC) who were not elected to the PLC on the... institutions are authorized to reject transactions with members of the Palestinian Legislative Council (PLC) who were elected to the PLC on the party slate of Hamas or any other Foreign Terrorist Organization...

77 FR 21588 - Hart and Cooley, Inc., A Subsidiary of Tomkins, PLC Including On-Site Leased Workers from...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-10

... Subsidiary of Tomkins, PLC Including On- Site Leased Workers from Reliable, Masiello Employment Services..., applicable to workers of Hart and Cooley, Inc., a subsidiary of Tomkins, PLC, including on-site leased... issued as follows: ``All workers from Hart and Cooley, Inc., a subsidiary of Tomkins, PLC, including on...

31 CFR 597.509 - Transactions with entities under the control of the Palestinian President and certain other...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Council; (3) Members of the Palestinian Legislative Council (PLC) who were not elected to the PLC on the... institutions are authorized to reject transactions with members of the Palestinian Legislative Council (PLC) who were elected to the PLC on the party slate of Hamas or any other Foreign Terrorist Organization...

77 FR 10355 - Airworthiness Directives; Rolls-Royce plc (RR) RB211-Trent 800 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

... Airworthiness Directives; Rolls-Royce plc (RR) RB211-Trent 800 Series Turbofan Engines AGENCY: Federal Aviation... effective March 28, 2012. ADDRESSES: For service information identified in this AD, contact Rolls-Royce plc... Rolls-Royce plc: Amendment 39-16956; Docket No. FAA-2010- 0755; Directorate Identifier 2010-NE-12-AD. (a...

31 CFR 595.511 - Transactions with entities under the control of the Palestinian President and certain other...

Code of Federal Regulations, 2010 CFR

2010-07-01

... the Palestinian Legislative Council (PLC) who were not elected to the PLC on the party slate of Hamas... authorized to reject transactions with members of the Palestinian Legislative Council (PLC) who were elected to the PLC on the party slate of Hamas or any other Foreign Terrorist Organization (FTO), Specially...

75 FR 28655 - Rexam Closure Systems, Inc. a Subsidiary of Rexam PLC Including On-Site Leased Workers From...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-21

..., Inc. a Subsidiary of Rexam PLC Including On-Site Leased Workers From Addeco Employment Services..., applicable to the workers of Rexam Closure Systems, Inc., a subsidiary of Rexam PLC, Hamlet, North Carolina... Rexam Closure Systems, Inc., a subsidiary of Rexam PLC purchased Owens Illinois Manufacturing. Some...

75 FR 12154 - Airworthiness Directives; Short Brothers PLC Model SD3 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-15

...-0225; Directorate Identifier 2009-NM-203-AD] RIN 2120-AA64 Airworthiness Directives; Short Brothers PLC... Brothers PLC, Airworthiness, P.O. Box 241, Airport Road, Belfast, BT3 9DZ Northern Ireland; telephone +44(0... 34801, June 16, 2006) and adding the following new AD: Short Brothers PLC: Docket No. FAA-2010-0225...

The Integration of DCS I/O to an Existing PLC

NASA Technical Reports Server (NTRS)

Sadhukhan, Debashis; Mihevic, John

2013-01-01

At the NASA Glenn Research Center (GRC), Existing Programmable Logic Controller (PLC) I/O was replaced with Distributed Control System (DCS) I/O, while keeping the existing PLC sequence Logic. The reason for integration of the PLC logic and DCS I/O, along with the evaluation of the resulting system is the subject of this paper. The pros and cons of the old system and new upgrade are described, including operator workstation screen update times. Detail of the physical layout and the communication between the PLC, the DCS I/O and the operator workstations are illustrated. The complex characteristics of a central process control system and the plan to remove the PLC processors in future upgrades is also discussed.

Electromechanical Componentry. High-Technology Training Module.

ERIC Educational Resources Information Center

Lindemann, Don

This training module on electromechanical components contains 10 units for a two-year vocational program packaging system equipment control course at Wisconsin Indianhead Technical College. This module describes the functions of electromechanical devices essential for understanding input/output devices for Programmable Logic Control (PLC)…

Investigating the neuroanatomical substrate of pathological laughing and crying in amyotrophic lateral sclerosis with multimodal neuroimaging techniques.

PubMed

Christidi, Foteini; Karavasilis, Efstratios; Ferentinos, Panagiotis; Xirou, Sophia; Velonakis, Georgios; Rentzos, Michalis; Zouvelou, Vasiliki; Zalonis, Ioannis; Efstathopoulos, Efstathios; Kelekis, Nikolaos; Evdokimidis, Ioannis

2018-02-01

Pathological laughing and crying (PLC) is common in several neurological and psychiatric diseases and is associated with a distributed network involving the frontal cortex, the brainstem and cortico-pontine-cerebellar circuits. By applying multimodal neuroimaging approach, we examined the neuroanatomical substrate of PLC in a sample of patients with amyotrophic lateral sclerosis (ALS). We studied 56 non-demented ALS patients and 25 healthy controls (HC). PLC was measured in ALS using the Center of Neurologic Study Lability Scale (CNS-LS; cutoff score: 13). All participants underwent 3D-T1-weighted and 30-directional diffusion-weighted imaging at 3T. Voxel-based morphometry and tract-based spatial-statistics analysis was used to examine gray matter (GM) and white matter (WM) differences between ALS patients with and without PLC (ALS-PLC and ALS-nonPLC, respectively). Comparisons were restricted to regions with detected differences between ALS and HC, controlling for age, gender, total intracranial volume and depressive symptoms. In regions with significant differences between ALS and HC, ALS-PLC patients showed decreased GM volume in left orbitofrontal cortex, frontal operculum, and putamen and bilateral frontal poles, compared to ALS-nonPLC. They also had decreased fractional anisotropy in left cingulum bundle and posterior corona radiata. WM abnormalities were additionally detected in WM associative and ponto-cerebellar tracts (using a more liberal threshold). PLC in ALS is driven by both GM and WM abnormalities which highlight the role of circuits rather than isolated centers in the emergence of this condition. ALS is suggested as a useful natural experimental model to study PLC.

The control of inositol lipid hydrolysis.

PubMed

Katan, M

1996-01-01

Hydrolysis of PIP2 by specific PLC enzymes is involved in the regulation of different cellular processes by many extracellular signals. The need stringently to control this reaction is reflected by the fact that there are many PLC isozymes and multiple mechanisms linking these isozymes to various receptors. For two of the three PLC families found in mammalian cells (PLC beta and gamma), the components of the main regulatory pathways have been identified. PLC beta isozymes are regulated through G protein coupled receptors. Their activity is stimulated by interaction with alpha subunit from the Gq family and interaction with G protein beta gamma subunits. PLC gamma isozymes are regulated through receptor and non-receptor tyrosine kinases. The combination of SH2 dependent complex formation with phosphorylated tyrosine kinases and the subsequent phosphorylation of PLC gamma leads to stimulation of its activity. Although components that stimulate PLC beta and gamma isozymes have been identified, the molecular mechanism of stimulation remains largely unknown. Each signalling component operating within this general framework represents a family of related proteins. It is not clear what all the functional differences between members of the same family may be and to what extent they could determine specificity of individual signalling pathways. Similarly, it is not known to what extent alterations in PLC function/expression contribute to human pathologies. In the context of oncology, there is evidence for upregulation of PLC gamma in parallel with increased expression of the EGF receptor (Artega et al. 1991). However, it is not clear yet whether this is causally involved or a bystander effect.

Three branches of phospholipase C signaling pathway promote hepatocyte growth in rat liver regeneration.

PubMed

Xu, G G; Geng, Z; Zhou, X C; He, Y G; He, T T; Mei, J X; Yang, Y J; Liu, Y Q; Xu, C S

2015-05-29

In general, the phospholipase C (PLC) signaling pathway is involved in many physiological activities, including cell growth. However, little is known regarding how the PLC signaling pathway participates in regulating hepatocyte (HC) growth during liver regeneration (LR). To further explore the influence of the PLC signaling pathway on HCs at the cellular level, HCs of high purity and vitality were isolated using Percoll density-gradient centrifugation after partial hepatectomy. The genes of the PLC signaling pathway and target genes of transcription factors in the pathway were obtained by searching the pathways and transcription factor databases, and changes in gene expression of isolated HCs were examined using the Rat Genome 230 2.0 Microarray. The results suggested that various genes involved in the pathway (including 151 known genes and 39 homologous genes) and cell growth (including 262 known genes and 37 homologous genes) were associated with LR. Subsequently, the synergetic effect of these genes in LR was analyzed using a mathematical model (Et) according to their expression profiles. The results showed that the Et values of G protein-coupled receptor/PLC, integrin/PLC, and growth factor receptor/PLC branches of the PLC pathway were all significantly strengthened during the progression and termination phases of LR. The synergetic effect of target genes, in parallel with target gene-related cell growth, was also enhanced during whole rat LR, suggesting the potential positive effect of PLC on HC growth. The present data indicate that the PLC signaling pathway may promote HC growth through 3 mechanisms during rat LR after partial hepatectomy.

Tailoring the mechanical and biodegradable properties of binary blends of biomedical thermoplastic elastomer.

PubMed

Ang, Hui Ying; Chan, Jingni; Toong, Daniel; Venkatraman, Subbu S; Chia, Sing Joo; Huang, Ying Ying

2018-03-01

Blending polymers with complementary properties capitalizes on the inherent advantages of both components, making it possible to tailor the behaviour of the resultant material. A polymer blend consisting of an elastomer and thermoplastic can help to improve the mechanical integrity of the system without compromising on its processibility. A series of blends of biodegradable Poly(L-lactide-co-ɛ-caprolactone) (PLC) and Poly-(l,l-lactide-co-glycolic acid) (PLLGA), and PLC with Poly-(d,l-lactide-co-glycolic acid) (PDLLGA) were evaluated as a potential material for a biodegradable vesicourethral connector device. Based on the Tg of the blends, PLC/PLLGA formed an immiscible mixture while PLC/PDLLGA resulted in a compatible blend. The results showed that with the blending of PLC, the failure mode of PLLGA and PDLLGA changed from brittle to ductile fracture, with an significant decreas in tensile modulus and strength. SEM images demonstrated the different blend morphologies of different compositions during degradation. Gel Permeation Chromatography (GPC) and mechanical characterization revealed the degradation behaviour of the blends in this order (fastest to slowest): PDLLGA and PLC/PDLLGA blends > PLLGA and PLC/PLLGA blends > PLC. The PLC/PLLGA (70:30) blend was recommended as a suitable for the vesicourethral connector device application, highlighting the tailoring of blends to achieve a desired mechanical performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

75 FR 801 - Airworthiness Directives; Rolls-Royce plc RB211-Trent 500, 700, and 800 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-06

...-0674; Directorate Identifier 2009-NE-25-AD] RIN 2120-AA64 Airworthiness Directives; Rolls-Royce plc... airworthiness directive (AD) for Rolls-Royce plc RB211-Trent 800 series turbofan engines. That AD currently... through Friday, except Federal holidays. Fax: (202) 493-2251. Contact Rolls-Royce plc, P.O. Box 31, DERBY...

75 FR 61361 - Airworthiness Directives; Rolls-Royce plc (RR) RB211-535 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-05

...-0994; Directorate Identifier 2009-NE-39-AD] RIN 2120-AA64 Airworthiness Directives; Rolls-Royce plc (RR...-Royce plc., P.O. Box 31, Derby, DE24 8BJ, United Kingdom; Telephone: 011 44 1332 242424, Fax: 011 44... docket. Relevant Service Information Rolls-Royce plc has issued Alert Service Bulletin (ASB) RB.211-72...

75 FR 264 - Airworthiness Directives; Rolls-Royce plc RB211-Trent 800 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-05

...-1004; Directorate Identifier 2009-NE-36-AD] RIN 2120-AA64 Airworthiness Directives; Rolls-Royce plc.... Contact Rolls-Royce plc, P.O. Box 31, Derby, England; telephone: 011-44-1332-249428; fax: 011-44-1332... condition may exist on Rolls-Royce plc RB211 Trent 800 series turbofan engines. The MCAI states: During 2004...

75 FR 17630 - Airworthiness Directives; Rolls-Royce plc RB211 Trent 700 and Trent 800 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-07

...-0364; Directorate Identifier 2009-NE-27-AD] RIN 2120-AA64 Airworthiness Directives; Rolls-Royce plc... Service Information Rolls-Royce plc has issued Alert Service Bulletin RB.211-72-AG086, dated December 4... adding the following new AD: Rolls-Royce plc: Docket No. FAA-2010-0364; Directorate Identifier 2009-NE-27...

78 FR 39062 - Group Lotus plc; Modification of a Temporary Exemption From an Advanced Air Bag Requirement of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-28

...-0086] Group Lotus plc; Modification of a Temporary Exemption From an Advanced Air Bag Requirement of... temporary exemption granted to Group Lotus plc (Lotus) on March 8, 2013. The agency granted Lotus an... Lotus Plc (Lotus) a temporary exemption from the higher maximum speed (56 km/h (35 mph)) belted test...

76 FR 52288 - Airworthiness Directives; Rolls-Royce plc (RR) Trent 800 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-22

...-0836; Directorate Identifier 2010-NE-38-AD] RIN 2120-AA64 Airworthiness Directives; Rolls-Royce plc (RR... plc, P.O. Box 31, Derby, DE24 8BJ, United Kingdom: telephone 44 (0) 1332 242424; fax 44 (0) 1332.... Relevant Service Information Rolls-Royce plc has issued Alert Service Bulletin RB.211-73-AD685, Revision 5...

75 FR 61114 - Airworthiness Directives; Rolls-Royce plc RB211-Trent 800 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-04

... Airworthiness Directives; Rolls-Royce plc RB211-Trent 800 Series Turbofan Engines AGENCY: Federal Aviation.... Fax: (202) 493-2251. Contact Rolls-Royce plc, P.O. Box 31, Derby, England, DE248BJ; telephone: 011-44... proposed AD, for Rolls- Royce plc RB211-Trent 800 series turbofan engines. That proposed AD would have...

75 FR 34172 - Rexam Closure Systems, Inc., a Subsidiary of Rexam PLC, Including On-Site Leased Workers From...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

..., Inc., a Subsidiary of Rexam PLC, Including On-Site Leased Workers From Addeco Employment Services and... PLC, Hamlet, North Carolina. The notice was published in the Federal Register on April 23, 2010 (75 FR... at the Hamlet, North Carolina location of Rexam Closure Systems, Inc., a subsidiary of Rexam PLC. The...

76 FR 72650 - Airworthiness Directives; Rolls-Royce plc (RR) RB211 Trent 800 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-25

...-0959; Directorate Identifier 2011-NE-25-AD] RIN 2120-AA64 Airworthiness Directives; Rolls-Royce plc (RR... holidays. Fax: (202) 493-2251. Contact Rolls-Royce plc, P.O. Box 31, Derby, DE24 8BJ, United Kingdom; phone... airplane. Relevant Service Information Rolls-Royce plc has issued Alert Service Bulletin RB.211-72-AG456...

75 FR 15321 - Airworthiness Directives; Rolls-Royce plc RB211-Trent 800 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-29

... Directives; Rolls-Royce plc RB211-Trent 800 Series Turbofan Engines AGENCY: Federal Aviation Administration... Rolls-Royce plc: Amendment 39-16239. Docket No. FAA-2009- 1004; Directorate Identifier 2009-NE-36-AD.... Applicability (c) This AD applies to Rolls-Royce plc models RB211-Trent 875- 17, Trent 877-17, Trent 884-17...

A non-catalytic histidine residue influences the function of the metalloprotease of Listeria monocytogenes.

PubMed

Forster, Brian M; Bitar, Alan Pavinski; Marquis, Hélène

2014-01-01

Mpl, a thermolysin-like metalloprotease, and PC-PLC, a phospholipase C, are synthesized as proenzymes by the intracellular bacterial pathogen Listeria monocytogenes. During intracellular growth, L. monocytogenes is temporarily confined in a membrane-bound vacuole whose acidification leads to Mpl autolysis and Mpl-mediated cleavage of the PC-PLC N-terminal propeptide. Mpl maturation also leads to the secretion of both Mpl and PC-PLC across the bacterial cell wall. Previously, we identified negatively charged and uncharged amino acid residues within the N terminus of the PC-PLC propeptide that influence the ability of Mpl to mediate the maturation of PC-PLC, suggesting that these residues promote the interaction of the PC-PLC propeptide with Mpl. In the present study, we identified a non-catalytic histidine residue (H226) that influences Mpl secretion across the cell wall and its ability to process PC-PLC. Our results suggest that a positive charge at position 226 is required for Mpl functions other than autolysis. Based on the charge requirement at this position, we hypothesize that this residue contributes to the interaction of Mpl with the PC-PLC propeptide.

Phosphoinositide-specific phospholipase C in oat roots: association with the actin cytoskeleton.

PubMed

Huang, Chiung-Hua; Crain, Richard C

2009-10-01

Phosphoinositide-specific phospholipase C (PI-PLC) activities are involved in mediating plant cell responses to environmental stimuli. Two variants of PI-PLC have been partially purified from the roots of oat seedlings; one cytosolic and one particulate. Although the cytosolic enzyme was significantly purified, the activity still co-migrated with a number of other proteins on heparin HPLC and also on size-exclusion chromatography. The partially purified PI-PLC was tested by Western blotting, and we found that actin and actin-binding proteins, profilin and tropomyosin, co-purified with cytosolic phospholipase C. After a non-ionic detergent (Triton X-100) treatment, PI-PLC activities still remained with the actin cytoskeleton. The effects of phalloidin and F-buffer confirmed this association; these conditions, which favor actin polymerization, decreased the release of PI-PLC from the cytoskeleton. The treatments of latrunculin and G-buffer, the conditions that favor actin depolymerization, increased the release of PI-PLC from the cytoskeleton. These results suggest that oat PI-PLC associates with the actin cytoskeleton.

Minifactory: a precision assembly system adaptable to the product life cycle

NASA Astrophysics Data System (ADS)

Muir, Patrick F.; Rizzi, Alfred A.; Gowdy, Jay W.

1997-12-01

Automated product assembly systems are traditionally designed with the intent that they will be operated with few significant changes for as long as the product is being manufactured. This approach to factory design and programming has may undesirable qualities which have motivated the development of more 'flexible' systems. In an effort to improve agility, different types of flexibility have been integrated into factory designs. Specifically, automated assembly systems have been endowed with the ability to assemble differing products by means of computer-controlled robots, and to accommodate variations in parts locations and dimensions by means of sensing. The product life cycle (PLC) is a standard four-stage model of the performance of a product from the time that it is first introduced in the marketplace until the time that it is discontinued. Manufacturers can improve their return on investment by adapting the production process to the PLC. We are developing two concepts to enable manufacturers to more readily achieve this goal: the agile assembly architecture (AAA), an abstract framework for distributed modular automation; and minifactory, our physical instantation of this architecture for the assembly of precision electro-mechanical devices. By examining the requirements which each PLC stage places upon the production system, we identify characteristics of factory design and programming which are appropriate for that stage. As the product transitions from one stage to the next, the factory design and programing should also transition from one embodiment to the next in order to achieve the best return on investment. Modularity of the factory components, highly flexible product transport mechanisms, and a high level of distributed intelligence are key characteristics of minifactory that enable this adaptation.

Power Line Communication (PLC) in Space - Current Status and Outlook

NASA Astrophysics Data System (ADS)

Wolf, J.

2012-05-01

The Power Line Communication (PLC) technology as known from various terrestrial applications, e.g. in building automation, in the automotive sector and on aircraft, appears to be a promising technology for the use on spacecraft. Starting from a critical overview on existing terrestrial PLC applications with their pros and cons, the paper gives a motivation for the introduction of the PLC technology on spacecraft, discusses the potential areas where it can be applied and is highlighting the potential problem areas. A short overview of on-going ESA PLC activities is provided and an outlook is given.

Trend on High-speed Power Line Communication Technology

NASA Astrophysics Data System (ADS)

Ogawa, Osamu

High-speed power line communication (PLC) is useful technology to easily build the communication networks, because construction of new infrastructure is not necessary. In Europe and America, PLC has been used for broadband networks since the beginning of 21th century. In Japan, high-speed PLC was deregulated only indoor usage in 2006. Afterward it has been widely used for home area network, LAN in hotels and school buildings and so on. And recently, PLC is greatly concerned as communication technology for smart grid network. In this paper, the author surveys the high-speed PLC technology and its current status.

Posterolateral Corner Injuries of the Knee at the National Football League Combine: An Imaging and Outcomes Analysis.

PubMed

Chahla, Jorge; Kennedy, Nicholas I; Cinque, Mark E; Sanchez, George; Logan, Catherine; Vopat, Bryan G; Beaulieu-Jones, Brendin; Price, Mark; Whalen, Jim; LaPrade, Robert F; Provencher, Matthew T

2018-03-01

(1) To determine the epidemiology, examination findings, imaging findings, and associated injuries of posterolateral corner (PLC) injuries in players participating in the National Football League (NFL) Combine and (2) to evaluate the impact of PLC injuries on performance compared with matched controls. All PLC injuries identified at the NFL Combine between 2009 and 2015 were reviewed. The inclusion criteria were any player who had clinical findings or a previous surgical procedure consistent with a PLC injury and who participated in medical and performance testing at the NFL Combine. PLC injuries were identified by evaluating the side-to-side difference in lateral-compartment laxity with varus stress and reviewing magnetic resonance imaging studies. NFL performance outcomes (draft position and number of games played or started within the first 2 years) were compared with matched controls. Of the 2,285 players assessed at the NFL Combine, 16 (0.7%) were identified with a history of a grade II or III PLC tear and surgical management whereas 7 additional players (0.3%) had a PLC injury diagnosed on clinical examination, for 23 total PLC injuries (1%). On examination, 13 of 22 knees (59%) were shown to be stable; however, most of those managed surgically had significantly improved stability (13 of 15 stable) versus none of those managed nonsurgically (0 of 7 stable). Surgically managed PLC-injured athletes started significantly fewer games than controls (5.3 vs 10.5, P = .03); the mean draft position for players with surgically treated PLC injuries was 139.7 versus controls' mean draft position of 111.3. Of the 16 athletes treated operatively, 2 reported a PLC injury recurrence; both were managed nonoperatively. A small percentage of players at the NFL Combine had evidence of a previous PLC injury (1%), with 0.4% having residual varus asymmetry on clinical examination. A worse overall mean draft position for isolated PLC-injured athletes versus controls was found: 132.8 versus 111.3 (P = .02). It is recommended that the use of varus stress radiographs be considered for NFL Combine athletes to objectively determine their grade of injury. LEVEL OF EVIDENCE: Level IV, retrospective case series. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

75 FR 27964 - Airworthiness Directives; Rolls-Royce plc (RR) RB211-22B and RB211-524 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-19

...-1157; Directorate Identifier 2009-NE-26-AD] RIN 2120-AA64 Airworthiness Directives; Rolls-Royce plc (RR... p.m., Monday through Friday, except Federal holidays. Fax: (202) 493-2251. Contact Rolls-Royce plc... Information Rolls-Royce plc has issued Alert Service Bulletin RB.211-72-AF336, dated October 24, 2007. The...

75 FR 61363 - Airworthiness Directives; Rolls-Royce plc RB211-524 Series, -535 Series, RB211 Trent 700 Series...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-05

...-0993; Directorate Identifier 2010-NE-08-AD] RIN 2120-AA64 Airworthiness Directives; Rolls-Royce plc... Federal holidays. Fax: (202) 493-2251. Contact Rolls-Royce plc, P.O. Box 31, Derby, DE24 8BJ, United... examining the MCAI in the AD docket. Relevant Service Information Rolls-Royce plc has issued Alert Service...

76 FR 12277 - Airworthiness Directives; Rolls-Royce plc RB211-Trent 768, 772, and 772B Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-07

... Airworthiness Directives; Rolls-Royce plc RB211-Trent 768, 772, and 772B Turbofan Engines AGENCY: Federal...). Those ADs both require the same initial and repetitive visual inspections of Rolls-Royce plc RB211-Trent... FR 24911, May 6, 1998): 98-09-27R1 Rolls-Royce plc: Amendment 39-16620. Docket No. FAA-2010- 0960...

75 FR 69611 - Airworthiness Directives; Rolls-Royce plc RB211-Trent 768, 772, and 772B Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-15

...-0960; Directorate Identifier 98-ANE-09-AD] RIN 2120-AA64 Airworthiness Directives; Rolls-Royce plc... repetitive visual inspections of Rolls-Royce plc RB211-Trent 768 and 772 series turbofan engine thrust... directive (AD) 98-09-27, Amendment 39-10508 (63 FR 24911, May 6, 1998): Rolls-Royce plc: Docket No. FAA-2010...

75 FR 58290 - Airworthiness Directives; Rolls-Royce plc RB211 Trent 700 and Trent 800 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

... Airworthiness Directives; Rolls-Royce plc RB211 Trent 700 and Trent 800 Series Turbofan Engines AGENCY: Federal...-20-11 Rolls-Royce plc: Amendment 39-16446. Docket No. FAA- 2010-0364; Directorate Identifier 2009-NE.... Affected ADs (b) None. Applicability (c) This AD applies to Rolls-Royce plc model (RR) RB211 Trent 768-60...

Phospholipase C-beta4 is essential for the progression of the normal sleep sequence and ultradian body temperature rhythms in mice.

PubMed

Ikeda, Masayuki; Hirono, Moritoshi; Sugiyama, Takashi; Moriya, Takahiro; Ikeda-Sagara, Masami; Eguchi, Naomi; Urade, Yoshihiro; Yoshioka, Tohru

2009-11-09

THE SLEEP SEQUENCE: i) non-REM sleep, ii) REM sleep, and iii) wakefulness, is stable and widely preserved in mammals, but the underlying mechanisms are unknown. It has been shown that this sequence is disrupted by sudden REM sleep onset during active wakefulness (i.e., narcolepsy) in orexin-deficient mutant animals. Phospholipase C (PLC) mediates the signaling of numerous metabotropic receptors, including orexin receptors. Among the several PLC subtypes, the beta4 subtype is uniquely localized in the geniculate nucleus of thalamus which is hypothesized to have a critical role in the transition and maintenance of sleep stages. In fact, we have reported irregular theta wave frequency during REM sleep in PLC-beta4-deficient mutant (PLC-beta4-/-) mice. Daily behavioral phenotypes and metabotropic receptors involved have not been analyzed in detail in PLC-beta4-/- mice, however. Therefore, we analyzed 24-h sleep electroencephalogram in PLC-beta4-/- mice. PLC-beta4-/- mice exhibited normal non-REM sleep both during the day and nighttime. PLC-beta4-/- mice, however, exhibited increased REM sleep during the night, their active period. Also, their sleep was fragmented with unusual wake-to-REM sleep transitions, both during the day and nighttime. In addition, PLC-beta4-/- mice reduced ultradian body temperature rhythms and elevated body temperatures during the daytime, but had normal homeothermal response to acute shifts in ambient temperatures (22 degrees C-4 degrees C). Within the most likely brain areas to produce these behavioral phenotypes, we found that, not orexin, but group-1 metabotropic glutamate receptor (mGluR)-mediated Ca(2+) mobilization was significantly reduced in the dorsal lateral geniculate nucleus (LGNd) of PLC-beta4-/- mice. Voltage clamp recordings revealed that group-1 mGluR-mediated currents in LGNd relay neurons (inward in wild-type mice) were outward in PLC-beta4-/- mice. These lines of evidence indicate that impaired LGNd relay, possibly mediated via group-1 mGluR, may underlie irregular sleep sequences and ultradian body temperature rhythms in PLC-beta4-/- mice.

PLC-γ directly binds activated c-Src, which is necessary for carbachol-mediated inhibition of NHE3 activity in Caco-2/BBe cells

PubMed Central

Lee, Luke J.; Kovbasnjuk, Olga; Li, Xuhang; Donowitz, Mark

2013-01-01

Elevated levels of intracellular Ca2+ ([Ca2+]i) inhibit Na+/H+ exchanger 3 (NHE3) activity in the intact intestine. We previously demonstrated that PLC-γ directly binds NHE3, an interaction that is necessary for [Ca2+]i inhibition of NHE3 activity, and that PLC-γ Src homology 2 (SH2) domains may scaffold Ca2+ signaling proteins necessary for regulation of NHE3 activity. [Ca2+]i regulation of NHE3 activity is also c-Src dependent; however, the mechanism by which c-Src is involved is undetermined. We hypothesized that the SH2 domains of PLC-γ might link c-Src to NHE3-containing complexes to mediate [Ca2+]i inhibition of NHE3 activity. In Caco-2/BBe cells, carbachol (CCh) decreased NHE3 activity by ∼40%, an effect abolished with the c-Src inhibitor PP2. CCh treatment increased the amount of active c-Src as early as 1 min through increased Y416 phosphorylation. Coimmunoprecipitation demonstrated that c-Src associated with PLC-γ, but not NHE3, under basal conditions, an interaction that increased rapidly after CCh treatment and occurred before the dissociation of PLC-γ and NHE3 that occurred 10 min after CCh treatment. Finally, direct binding to c-Src only occurred through the PLC-γ SH2 domains, an interaction that was prevented by blocking the PLC-γ SH2 domain. This study demonstrated that c-Src 1) activity is necessary for [Ca2+]i inhibition of NHE3 activity, 2) activation occurs rapidly (∼1 min) after CCh treatment, 3) directly binds PLC-γ SH2 domains and associates dynamically with PLC-γ under elevated [Ca2+]i conditions, and 4) does not directly bind NHE3. Under elevated [Ca2+]i conditions, PLC-γ scaffolds c-Src into NHE3-containing multiprotein complexes before dissociation of PLC-γ from NHE3 and subsequent endocytosis of NHE3. PMID:23703528

Prospective analysis of magnetic resonance imaging accuracy in diagnosing traumatic injuries of the posterior ligamentous complex of the thoracolumbar spine.

PubMed

Pizones, Javier; Sánchez-Mariscal, Felisa; Zúñiga, Lorenzo; Álvarez, Patricia; Izquierdo, Enrique

2013-04-20

Prospective cohort study. To study magnetic resonance imaging (MRI) accuracy in diagnosing posterior ligamentous complex (PLC) damage, when applying the new dichotomic instability criteria in a prospective cohort of patients with vertebral fracture. Recent studies dispute MRI accuracy to diagnose PLC injuries. They analyze the complex based on 3 categories (intact/indeterminate/rupture), including the indeterminate in the ruptured group (measurement bias) in the accuracy analysis. Moreover, fractures with conservative treatment (selection bias) are not included. Both facts reduce the specificity. A recent study has proposed new criteria where posterior instability is determined with supraspinous ligament (SSL) rupture. Prospective study of patients with acute thoracolumbar fracture, using radiography and MRI (FS-T2-w/short-tau inversion-recovery sequences). 1. The integrity (ruptured/unruptured) of each isolated component of the PLC (facet capsules, interspinous ligament, SSL, and ligamentum flavum) was assessed via MRI and surgical findings. 2. PLC integrity as a whole was assessed, adopting the new dichotomic stability criteria from previous studies. In the MR images, PLC is considered ruptured when the SSL is found discontinued, and intact when not (this excludes the "indeterminate" category). In surgically treated fractures, PLC stability as a whole was assessed dynamically (ruptured/unruptured). In conservative fractures, PLC stability was assessed according to change in vertebral kyphosis measured with the local kyphotic angle at 2-year follow-up (ruptured if difference is > 5°/unruptured if difference is < 5°).3. Comparative analysis among findings provided MRI accuracy in diagnosing PLC damage. Fifty-eight vertebral fractures were studied (38 surgical, 20 conservative), of which 50% were in males; average age, 40.4 years. MRI sensitivity for injury diagnosis of each isolated PLC component varied between 92.3% (interspinous ligament) and 100% (ligamentum flavum). Specificity varied between 52% (facet capsules) and 100% (SSL). PLC integrity sensitivity and specificity as a whole were 91% and 100%, respectively. Adopting the new stability criteria, MRI accuracy in PLC injury diagnosis increases. Specificity is increased (true positives) both in isolated component analysis and PLC as a whole.

PLC-γ directly binds activated c-Src, which is necessary for carbachol-mediated inhibition of NHE3 activity in Caco-2/BBe cells.

PubMed

Zachos, Nicholas C; Lee, Luke J; Kovbasnjuk, Olga; Li, Xuhang; Donowitz, Mark

2013-08-01

Elevated levels of intracellular Ca(2+) ([Ca(2+)]i) inhibit Na(+)/H(+) exchanger 3 (NHE3) activity in the intact intestine. We previously demonstrated that PLC-γ directly binds NHE3, an interaction that is necessary for [Ca(2+)]i inhibition of NHE3 activity, and that PLC-γ Src homology 2 (SH2) domains may scaffold Ca(2+) signaling proteins necessary for regulation of NHE3 activity. [Ca(2+)]i regulation of NHE3 activity is also c-Src dependent; however, the mechanism by which c-Src is involved is undetermined. We hypothesized that the SH2 domains of PLC-γ might link c-Src to NHE3-containing complexes to mediate [Ca(2+)]i inhibition of NHE3 activity. In Caco-2/BBe cells, carbachol (CCh) decreased NHE3 activity by ∼40%, an effect abolished with the c-Src inhibitor PP2. CCh treatment increased the amount of active c-Src as early as 1 min through increased Y(416) phosphorylation. Coimmunoprecipitation demonstrated that c-Src associated with PLC-γ, but not NHE3, under basal conditions, an interaction that increased rapidly after CCh treatment and occurred before the dissociation of PLC-γ and NHE3 that occurred 10 min after CCh treatment. Finally, direct binding to c-Src only occurred through the PLC-γ SH2 domains, an interaction that was prevented by blocking the PLC-γ SH2 domain. This study demonstrated that c-Src 1) activity is necessary for [Ca(2+)]i inhibition of NHE3 activity, 2) activation occurs rapidly (∼1 min) after CCh treatment, 3) directly binds PLC-γ SH2 domains and associates dynamically with PLC-γ under elevated [Ca(2+)]i conditions, and 4) does not directly bind NHE3. Under elevated [Ca(2+)]i conditions, PLC-γ scaffolds c-Src into NHE3-containing multiprotein complexes before dissociation of PLC-γ from NHE3 and subsequent endocytosis of NHE3.

SDF-1 signaling via the CXCR4-TCR heterodimer requires PLC-β3 and PLC-γ1 for distinct cellular responses 1

PubMed Central

Kremer, Kimberly N.; Clift, Ian C.; Miamen, Alexander G.; Bamidele, Adebowale O.; Qian, Nan-Xin; Humphreys, Troy D.; Hedin, Karen E.

2011-01-01

The CXCR4 chemokine receptor is a G protein-coupled receptor (GPCR) that signals in T lymphocytes by forming a heterodimer with the T cell antigen receptor (TCR). CXCR4 and TCR functions are consequently highly cross-regulated, affecting T cell immune activation, cytokine secretion, and T cell migration. The CXCR4-TCR heterodimer stimulates T cell migration and activation of the ERK MAP kinase and downstream AP-1-dependent cytokine transcription in response to SDF-1, the sole chemokine ligand of CXCR4. These responses require Gi-type G proteins as well as TCR ITAM domains and the ZAP-70 tyrosine kinase, thus indicating that the CXCR4-TCR heterodimer signals to integrate GPCR-associated and TCR-associated signaling molecules in response to SDF-1. Yet, the phospholipase C (PLC) isozymes responsible for coupling the CXCR4-TCR heterodimer to distinct downstream cellular responses are incompletely characterized. Here, we demonstrate that PLC activity is required for SDF-1 to induce ERK activation, migration, and CXCR4 endocytosis in human T cells. SDF-1 signaling via the CXCR4-TCR heterodimer uses PLC-β3 to activate the Ras-ERK pathway and increase intracellular Ca2+ concentrations, while PLC-γ1 is dispensable for these outcomes. In contrast, PLC-γ1, but not PLC-β3, is required for SDF-1-mediated migration, via a mechanism independent of LAT. These results increase understanding of the signaling mechanisms employed by the CXCR4-TCR heterodimer, characterize new roles for PLC-β3 and PLC-γ1 in T cells, and suggest that multiple PLCs may also be activated downstream of other chemokine receptors in order to distinctly regulate migration versus other signaling functions. PMID:21705626

Propionyl-L-Carnitine is Efficacious in Ulcerative Colitis Through its Action on the Immune Function and Microvasculature.

PubMed

Scioli, Maria Giovanna; Stasi, Maria Antonietta; Passeri, Daniela; Doldo, Elena; Costanza, Gaetana; Camerini, Roberto; Fociani, Paolo; Arcuri, Gaetano; Lombardo, Katia; Pace, Silvia; Borsini, Franco; Orlandi, Augusto

2014-03-20

Microvascular endothelial dysfunction characterizes ulcerative colitis (UC), the most widespread form of inflammatory bowel disease. Intestinal mucosal microvessels in UC display aberrant expression of cell adhesion molecules (CAMs) and increased inflammatory cell recruitment. Propionyl-L-carnitine (PLC), an ester of L-carnitine required for the mitochondrial transport of fatty acids, ameliorates propionyl-CoA bioavailability and reduces oxidative stress in ischemic tissues. The present study aimed to document the efficacy of anti-oxidative stress properties of PLC in counteracting intestinal microvascular endothelial dysfunction and inflammation. To evaluate the efficacy in vivo, we analyzed the effects in intestinal biopsies of patients with mild-to-moderate UC receiving oral PLC co-treatment and in rat TNBS-induced colitis; in addition, we investigated antioxidant PLC action in TNF-α-stimulated human intestinal microvascular endothelial cells (HIMECs) in vitro. Four-week PLC co-treatment reduced intestinal mucosal polymorph infiltration and CD4(+) lymphocytes, ICAM-1(+) and iNOS(+) microvessels compared with placebo-treated patients with UC. Oral and intrarectal administration of PLC but not L-carnitine or propionate reduced intestinal damage and microvascular dysfunction in rat TNBS-induced acute and reactivated colitis. In cultured TNF-α-stimulated HIMECs, PLC restored β-oxidation and counteracted NADPH oxidase 4-generated oxidative stress-induced CAM expression and leukocyte adhesion. Inhibition of β-oxidation by L-aminocarnitine increased reactive oxygen species production and PLC beneficial effects on endothelial dysfunction and leukocyte adhesion. Finally, PLC reduced iNOS activity and nitric oxide accumulation in rat TNBS-induced colitis and in HIMEC cultures. Our results show that the beneficial antioxidant effect of PLC targeting intestinal microvasculature restores endothelial β-oxidation and function, and reduces mucosal inflammation in UC patients.

Propionyl-L-Carnitine is Efficacious in Ulcerative Colitis Through its Action on the Immune Function and Microvasculature

PubMed Central

Scioli, Maria Giovanna; Stasi, Maria Antonietta; Passeri, Daniela; Doldo, Elena; Costanza, Gaetana; Camerini, Roberto; Fociani, Paolo; Arcuri, Gaetano; Lombardo, Katia; Pace, Silvia; Borsini, Franco; Orlandi, Augusto

2014-01-01

Objectives: Microvascular endothelial dysfunction characterizes ulcerative colitis (UC), the most widespread form of inflammatory bowel disease. Intestinal mucosal microvessels in UC display aberrant expression of cell adhesion molecules (CAMs) and increased inflammatory cell recruitment. Propionyl-L-carnitine (PLC), an ester of L-carnitine required for the mitochondrial transport of fatty acids, ameliorates propionyl-CoA bioavailability and reduces oxidative stress in ischemic tissues. The present study aimed to document the efficacy of anti-oxidative stress properties of PLC in counteracting intestinal microvascular endothelial dysfunction and inflammation. Methods: To evaluate the efficacy in vivo, we analyzed the effects in intestinal biopsies of patients with mild-to-moderate UC receiving oral PLC co-treatment and in rat TNBS-induced colitis; in addition, we investigated antioxidant PLC action in TNF-α-stimulated human intestinal microvascular endothelial cells (HIMECs) in vitro. Results: Four-week PLC co-treatment reduced intestinal mucosal polymorph infiltration and CD4+ lymphocytes, ICAM-1+ and iNOS+ microvessels compared with placebo-treated patients with UC. Oral and intrarectal administration of PLC but not L-carnitine or propionate reduced intestinal damage and microvascular dysfunction in rat TNBS-induced acute and reactivated colitis. In cultured TNF-α-stimulated HIMECs, PLC restored β-oxidation and counteracted NADPH oxidase 4-generated oxidative stress-induced CAM expression and leukocyte adhesion. Inhibition of β-oxidation by L-aminocarnitine increased reactive oxygen species production and PLC beneficial effects on endothelial dysfunction and leukocyte adhesion. Finally, PLC reduced iNOS activity and nitric oxide accumulation in rat TNBS-induced colitis and in HIMEC cultures. Conclusions: Our results show that the beneficial antioxidant effect of PLC targeting intestinal microvasculature restores endothelial β-oxidation and function, and reduces mucosal inflammation in UC patients. PMID:24646507

Coronary vasospasm induced in transgenic mouse with increased phospholipase C-δ1 activity.

PubMed

Shibutani, Shuji; Osanai, Tomohiro; Ashitate, Toshihiro; Sagara, Shigeki; Izumiyama, Kei; Yamamoto, Yuko; Hanada, Kenji; Echizen, Takashi; Tomita, Hirofumi; Fujita, Takeshi; Miwa, Takeshi; Matsubara, Hiroaki; Homma, Yoshimi; Okumura, Ken

2012-02-28

We reported that phospholipase C (PLC)-δ1 activity was enhanced 3-fold in patients with coronary spastic angina. We detected variant PLC-δ1 with replacement of arginine 257 by histidine (R257H) showing increased enzymatic activity. We tested the hypothesis that increased PLC-δ1 activity causes enhanced coronary vasomotility. We generated transgenic (TG) mice with human R257H variant PLC-δ1 in vascular smooth muscle cells. PLC enzymatic activity in the coronary artery was increased by 2.57 and 1.89 times, respectively, in homozygous and heterozygous TG compared with wild-type (WT) mice. ST elevation after ergometrine occurred in 17 of 18 homozygous TG, 6 of 20 heterozygous TG, and 3 of 22 WT mice (P<0.01, homozygous TG versus WT; P<0.05, homozygous TG versus heterozygous TG; P=NS, heterozygous TG versus WT). ST elevation was associated with bradyarrhythmias in homozygous TG mice. Focal coronary artery narrowing was documented with the microvascular filling technique in 3 of 5 homozygous TG mice after ergometrine but not in any of 7 WT mice (P<0.05). In the isolated Langendorff hearts, coronary perfusion pressure was increased after ergometrine in homozygous TG mice (P<0.01) but not in heterozygous TG or WT mice. Coronary perfusion pressure increase after prostaglandin F2α was similar among homozygous TG, heterozygous TG, and WT mice. Cultured rat aortic smooth muscle cells transfected with variant PLC-δ1 showed a higher PLC activity than those with WT PLC-δ1 (P<0.05) and furthermore showed greater intracellular Ca2+ response to acetylcholine in variant than in WT PLC-δ1 (P<0.05). Increased PLC-δ1 activity enhances coronary vasomotility such as that seen in patients with coronary spastic angina.

PLC-Mediated Signaling Pathway in Pollen Tubes Regulates the Gametophytic Self-incompatibility of Pyrus Species

PubMed Central

Qu, Haiyong; Guan, Yaqin; Wang, Yongzhang; Zhang, Shaolin

2017-01-01

Among the Rosaceae species, the gametophytic self-incompatibility (GSI) is controlled by a single multi-allelic S locus, which is composed of the pistil-S and pollen-S genes. The pistil-S gene encodes a polymorphic ribonuclease (S-RNase), which is essential for identifying self-pollen. However, the S-RNase system has not been fully characterized. In this study, the self-S-RNase inhibited the Ca2+-permeable channel activity at pollen tube apices and the selectively decreased phospholipase C (PLC) activity in the plasma membrane of Pyrus pyrifolia pollen tubes. Self-S-RNase decreased the Ca2+ influx through a PLC-mediated signaling pathway. Phosphatidylinositol-specific PLC has a 26-amino acid insertion in pollen tubes of the ‘Jinzhuili’ cultivar, which is a spontaneous self-compatible mutant of the ‘Yali’ cultivar. ‘Yali’ plants exhibit a typical S-RNase-based GSI. Upon self-pollination, PLC gene expression is significantly higher in ‘Jinzhuili’ pollen tubes than that in ‘Yali’ pollen tubes. Moreover, the PLC in pollen tubes can only interact with one of the two types of S-RNase from the style. In the Pyrus x bretschneideri Rehd, the PLC directly interacted with the S7-RNase in the pollen tube, but not with the S34-RNase. Collectively, our results reveal that the effects of S-RNase on PLC activity are required for S-specific pollen rejection, and that PLC-IP3 participates in the self-incompatibility reaction of Pyrus species. PMID:28729872

PLC-Mediated Signaling Pathway in Pollen Tubes Regulates the Gametophytic Self-incompatibility of Pyrus Species.

PubMed

Qu, Haiyong; Guan, Yaqin; Wang, Yongzhang; Zhang, Shaolin

2017-01-01

Among the Rosaceae species, the gametophytic self-incompatibility (GSI) is controlled by a single multi-allelic S locus, which is composed of the pistil-S and pollen-S genes. The pistil-S gene encodes a polymorphic ribonuclease (S-RNase), which is essential for identifying self-pollen. However, the S-RNase system has not been fully characterized. In this study, the self-S-RNase inhibited the Ca 2+ -permeable channel activity at pollen tube apices and the selectively decreased phospholipase C ( PLC ) activity in the plasma membrane of Pyrus pyrifolia pollen tubes. Self-S-RNase decreased the Ca 2+ influx through a PLC -mediated signaling pathway. Phosphatidylinositol-specific PLC has a 26-amino acid insertion in pollen tubes of the 'Jinzhuili' cultivar, which is a spontaneous self-compatible mutant of the 'Yali' cultivar. 'Yali' plants exhibit a typical S-RNase-based GSI. Upon self-pollination, PLC gene expression is significantly higher in 'Jinzhuili' pollen tubes than that in 'Yali' pollen tubes. Moreover, the PLC in pollen tubes can only interact with one of the two types of S-RNase from the style. In the Pyrus x bretschneideri Rehd, the PLC directly interacted with the S 7 -RNase in the pollen tube, but not with the S 34 -RNase. Collectively, our results reveal that the effects of S-RNase on PLC activity are required for S-specific pollen rejection, and that PLC -IP 3 participates in the self-incompatibility reaction of Pyrus species.

A PLC-γ1 Feedback Pathway Regulates Lck Substrate Phosphorylation at the T-Cell Receptor and SLP-76 Complex.

PubMed

Belmont, Judson; Gu, Tao; Mudd, Ashley; Salomon, Arthur R

2017-08-04

Phospholipase C gamma 1 (PLC-γ1) occupies a critically important position in the T-cell signaling pathway. While its functions as a regulator of both Ca 2+ signaling and PKC-family kinases are well characterized, PLC-γ1's role in the regulation of early T-cell receptor signaling events is incompletely understood. Activation of the T-cell receptor leads to the formation of a signalosome complex between SLP-76, LAT, PLC-γ1, Itk, and Vav1. Recent studies have revealed the existence of both positive and negative feedback pathways from SLP-76 to the apical kinase in the pathway, Lck. To determine if PLC-γ1 contributes to the regulation of these feedback networks, we performed a quantitative phosphoproteomic analysis of PLC-γ1-deficient T cells. These data revealed a previously unappreciated role for PLC-γ1 in the positive regulation of Zap-70 and T-cell receptor tyrosine phosphorylation. Conversely, PLC-γ1 negatively regulated the phosphorylation of SLP-76-associated proteins, including previously established Lck substrate phosphorylation sites within this complex. While the positive and negative regulatory phosphorylation sites on Lck were largely unchanged, Tyr 192 phosphorylation was elevated in Jgamma1. The data supports a model wherein Lck's targeting, but not its kinase activity, is altered by PLC-γ1, possibly through Lck Tyr 192 phosphorylation and increased association of the kinase with protein scaffolds SLP-76 and TSAd.

Phospholipase C produced by Clostridium botulinum types C and D: comparison of gene, enzymatic, and biological activities with those of Clostridium perfringens alpha-toxin.

PubMed

Fatmawati, Ni Nengah Dwi; Sakaguchi, Yoshihiko; Suzuki, Tomonori; Oda, Masataka; Shimizu, Kenta; Yamamoto, Yumiko; Sakurai, Jun; Matsushita, Osamu; Oguma, Keiji

2013-01-01

Clostridium botulinum type C and D strains recently have been found to produce PLC on egg yolk agar plates. To characterize the gene, enzymatic and biological activities of C. botulinum PLCs (Cb-PLCs), the cb-plc genes from 8 strains were sequenced, and 1 representative gene was cloned and expressed as a recombinant protein. The enzymatic and hemolytic activities of the recombinant Cb-PLC were measured and compared with those of the Clostridium perfringens alpha-toxin. Each of the eight cb-plc genes encoded a 399 amino acid residue protein preceded by a 27 residue signal peptide. The protein consists of 2 domains, the N- and C-domains, and the overall amino acid sequence identity between Cb-PLC and alpha-toxin was greater than 50%, suggesting that Cb-PLC is homologous to the alpha-toxin. The key residues in the N-domain were conserved, whereas those in the C-domain which are important in membrane interaction were different than in the alpha-toxin. As expected, Cb-PLC could hydrolyze egg yolk phospholipid, p-nitrophenylphosphorylcholine, and sphingomyelin, and also exhibited hemolytic activity;however, its activities were about 4- to over 200-fold lower than those of alpha-toxin. Although Cb-PLC showed weak enzymatic and biological activities, it is speculated that Cb-PLC might play a role in the pathogenicity of botulism or for bacterial survival.

75 FR 50877 - Airworthiness Directives; Rolls-Royce plc RB211-524C2 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-18

... Airworthiness Directives; Rolls-Royce plc RB211-524C2 Series Turbofan Engines AGENCY: Federal Aviation.... The FAA amends Sec. 39.13 by adding the following new AD: 2010-17-13 Rolls-Royce plc (Formerly Rolls...) None. Applicability (c) This AD applies to Rolls-Royce plc (RR) model RB211-524C2-19 and RB211-524C2-B...

75 FR 33738 - Airworthiness Directives; Rolls-Royce plc (RR) RB211-524 Series and RB211 Trent 500, 700, and 800...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-15

...-0562; Directorate Identifier 2009-NE-29-AD] RIN 2120-AA64 Airworthiness Directives; Rolls-Royce plc (RR...-2251. Contact Rolls-Royce plc, P.O. Box 31, Derby, DE24 8BJ, United Kingdom; phone: 011 44 1332 242424... by examining the MCAI in the AD docket. Relevant Service Information Rolls-Royce plc has issued Alert...

76 FR 20229 - Airworthiness Directives; Rolls-Royce plc (RR) RB211-Trent 768-60 and Trent 772-60 Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-12

... Airworthiness Directives; Rolls-Royce plc (RR) RB211-Trent 768-60 and Trent 772-60 Turbofan Engines AGENCY... holidays. For service information identified in this AD, contact Rolls-Royce plc, P.O. Box 31, Derby, DE24..., September 16, 1998), and adding the following new AD: 2011-08-10 Rolls-Royce plc: Amendment 39-16660; Docket...

76 FR 65941 - Airworthiness Directives; Rolls-Royce plc RB211-524 Series, RB211-Trent 700 Series, and RB211...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-25

... Airworthiness Directives; Rolls-Royce plc RB211-524 Series, RB211-Trent 700 Series, and RB211-Trent 800 Series...-Royce plc (RR), asked us to consider changing the information for getting the service information to... plc, PO Box 31, Derby, DE24 8BJ, United Kingdom, phone: 011-44-1331-242424, fax: 011-44-1332- 249936...

The Phospholipase C Isozymes and Their Regulation

PubMed Central

Gresset, Aurelie; Sondek, John

2013-01-01

The physiological effects of many extracellular neurotransmitters, hormones, growth factors, and other stimuli are mediated by receptor-promoted activation of phospholipase C (PLC) and consequential activation of inositol lipid signaling pathways. These signaling responses include the classically described conversion of phosphatidylinositol(4,5)P2 to the Ca2+-mobilizing second messenger inositol(1,4,5)P3 and the protein kinase C-activating second messenger diacylglycerol as well as alterations in membrane association or activity of many proteins that harbor phosphoinositide binding domains. The 13 mammalian PLCs elaborate a minimal catalytic core typified by PLC-δ to confer multiple modes of regulation of lipase activity. PLC-β isozymes are activated by Gαq- and Gβγ-subunits of heterotrimeric G proteins, and activation of PLC-γ isozymes occurs through phosphorylation promoted by receptor and non-receptor tyrosine kinases. PLC-ε and certain members of the PLC-β and PLC-γ subclasses of isozymes are activated by direct binding of small G proteins of the Ras, Rho, and Rac subfamilies of GTPases. Recent high resolution three dimensional structures together with biochemical studies have illustrated that the X/Y linker region of the catalytic core mediates autoinhibition of most if not all PLC isozymes. Activation occurs as a consequence of removal of this autoinhibition. PMID:22403074

Pathological Laughter and Crying and Psychiatric Comorbidity After Traumatic Brain Injury.

PubMed

Roy, Durga; McCann, Una; Han, Dingfen; Rao, Vani

2015-01-01

There are limited data regarding the incidence of pathological laughter and crying (PLC) after traumatic brain injury (TBI). This study aimed to identify the occurrence of PLC in the first year after TBI and to determine whether there is a relationship between PLC and other clinical features or demographics. Subjects who sustained a first-time TBI were recruited from acute trauma units and were assessed at 3, 6, and 12 months after TBI. Rates of PLC at 3, 6, and 12 months after TBI were 21.4%, 17.5%, and 15.5%, respectively. Patients with PLC had higher percentages of psychiatric diagnoses, including personality changes, depressive disorders, and mood disorders secondary to a general medical condition, as well as higher rates of posttraumatic stress disorder. Univariate logistic and linear regression analyses indicated a significant association between PLC and scores on the Clinical Anxiety Scale 3 months after TBI and on the Hamilton Depression Rating Scale 12 months after TBI. Individuals who have PLC during the first year after TBI are more likely to have any psychiatric diagnosis as well as higher rates of mood and anxiety symptoms. In addition, PLC in the early TBI period may serve as a predictor of depression and anxiety symptoms at 12 months after TBI.

Revealing Transient Interactions between Phosphatidylinositol-specific Phospholipase C and Phosphatidylcholine--Rich Lipid Vesicles

NASA Astrophysics Data System (ADS)

Yang, Boqian; He, Tao; Grauffel, Cédric; Reuter, Nathalie; Roberts, Mary; Gershenson, Anne

2013-03-01

Phosphatidylinositol-specific phospholipase C (PI-PLC) enzymes transiently interact with target membranes. Previous fluorescence correlation spectroscopy (FCS) experiments showed that Bacillus thuringiensis PI-PLC specifically binds to phosphatidylcholine (PC)-rich membranes and preferentially interacts with unilamellar vesicles that show larger curvature. Mutagenesis studies combined with FCS measurements of binding affinity highlighted the importance of interfacial PI-PLC tyrosines in the PC specificity. All-atom molecular dynamics simulations of PI-PLC performed in the presence of a PC membrane indicate these tyrosines are involved in specific cation-pi interactions with choline headgroups. To further understand those transient interactions between PI-PLC and PC-rich vesicles, we monitor single fluorescently labeled PI-PLC proteins as they cycle on and off surface-tethered small unilamellar vesicles using total internal reflection fluorescent microscopy. The residence times on vesicles along with vesicle size information, based on vesicle fluorescence intensity, reveal the time scales of PI-PLC membrane interactions as well as the curvature dependence. The PC specificity and the vesicle curvature dependence of this PI-PLC/membrane interaction provide insight into how the interface modulates protein-membrane interactions. This work was supported by the National Institute of General Medical Science of the National Institutes of Health (R01GM060418).

Optical interconnection for a polymeric PLC device using simple positional alignment.

PubMed

Ryu, Jin Hwa; Kim, Po Jin; Cho, Cheon Soo; Lee, El-Hang; Kim, Chang-Seok; Jeong, Myung Yung

2011-04-25

This study proposes a simple cost-effective method of optical interconnection between a planar lightwave circuit (PLC) device chip and an optical fiber. It was conducted to minimize and overcome the coupling loss caused by lateral offset which is due to the process tolerance and the dimensional limitation existing between PLC device chips and fiber array blocks with groove structures. A PLC device chip and a fiber array block were simultaneously fabricated in a series of polymer replication processes using the original master. The dimensions (i.e., width and thickness) of the under-clad of the PLC device chip were identical to those of the fiber array block. The PLC device chip and optical fiber were aligned by simple positional control for the vertical direction of the PLC device chip under a particular condition. The insertion loss of the proposed 1 x 2 multimode optical splitter device interconnection was 4.0 dB at 850 nm and the coupling loss was below 0.1 dB compared with single-fiber based active alignment.

Pleural lavage cytology as an independent prognostic factor in non-small-cell lung cancer patients with stage I disease and adenocarcinoma.

PubMed

Hokka, Daisuke; Uchino, Kazuya; Tane, Kenta; Ogawa, Hiroyuki; Tane, Sinya; Tanaka, Yugo; Tauchi, Shunsuke; Nishio, Wataru; Yoshimura, Masahiro; Maniwa, Yoshimasa

2015-01-01

We previously reported that cancer cells may be detected through pleural lavage cytology (PLC). In this study, we sought to re-examine the prognostic significance of the PLC status based on an extended dataset with an additional follow-up period. Pleural lavage following thoracotomy was cytologically examined in 1,317 consecutive patients who were diagnosed with NSCLC between 1987 and 2004 at the Thoracic Surgery Units of Kobe University Graduate School of Medicine and Hyogo Cancer Center. Among the investigated patients, 46 exhibited positive cytological findings. The prognosis of these patients was significantly worse compared to that of patients without positive PLC. Of the 844 pathological stage I patients, 18 had a positive PLC status and their prognosis was significantly worse compared to that of patients with stage I disease without positive PLC. In conclusion, positive PLC findings were associated with a poor prognosis and this finding was significant for patients with stage I disease. These results suggest the need for PLC status evaluation during staging and treatment planning in patients with NSCLC.

Clostridium perfringens Phospholipase C Induced ROS Production and Cytotoxicity Require PKC, MEK1 and NFκB Activation

PubMed Central

Monturiol-Gross, Laura; Flores-Díaz, Marietta; Pineda-Padilla, Maria Jose; Castro-Castro, Ana Cristina; Alape-Giron, Alberto

2014-01-01

Clostridium perfringens phospholipase C (CpPLC), also called α-toxin, is the most toxic extracellular enzyme produced by this bacteria and is essential for virulence in gas gangrene. At lytic concentrations, CpPLC causes membrane disruption, whereas at sublytic concentrations this toxin causes oxidative stress and activates the MEK/ERK pathway, which contributes to its cytotoxic and myotoxic effects. In the present work, the role of PKC, ERK 1/2 and NFκB signalling pathways in ROS generation induced by CpPLC and their contribution to CpPLC-induced cytotoxicity was evaluated. The results demonstrate that CpPLC induces ROS production through PKC, MEK/ERK and NFκB pathways, the latter being activated by the MEK/ERK signalling cascade. Inhibition of either of these signalling pathways prevents CpPLC's cytotoxic effect. In addition, it was demonstrated that NFκB inhibition leads to a significant reduction in the myotoxicity induced by intramuscular injection of CpPLC in mice. Understanding the role of these signalling pathways could lead towards developing rational therapeutic strategies aimed to reduce cell death during a clostridialmyonecrosis. PMID:24466113

The Glycosylphosphatidylinositol-PLC in Trypanosoma brucei Forms a Linear Array on the Exterior of the Flagellar Membrane Before and After Activation

PubMed Central

Hanrahan, Orla; Webb, Helena; O'Byrne, Robert; Brabazon, Elaine; Treumann, Achim; Sunter, Jack D.; Carrington, Mark; Voorheis, H. Paul

2009-01-01

Bloodstream forms of Trypanosoma brucei contain a glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC) that cleaves the GPI-anchor of the variable surface glycoprotein (VSG). Its location in trypanosomes has been controversial. Here, using confocal microscopy and surface labelling techniques, we show that the GPI-PLC is located exclusively in a linear array on the outside of the flagellar membrane, close to the flagellar attachment zone, but does not co-localize with the flagellar attachment zone protein, FAZ1. Consequently, the GPI-PLC and the VSG occupy the same plasma membrane leaflet, which resolves the topological problem associated with the cleavage reaction if the VSG and the GPI-PLC were on opposite sides of the membrane. The exterior location requires the enzyme to be tightly regulated to prevent VSG release under basal conditions. During stimulated VSG release in intact cells, the GPI-PLC did not change location, suggesting that the release mechanism involves lateral diffusion of the VSG in the plane of the membrane to the fixed position of the GPI-PLC. PMID:19503825

76 FR 24793 - Airworthiness Directives; Rolls-Royce plc (RR) RB211-524 Series and RB211 Trent 500, 700, and 800...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-03

... Airworthiness Directives; Rolls-Royce plc (RR) RB211-524 Series and RB211 Trent 500, 700, and 800 Series... adding the following new AD: 2011-09-07 Rolls-Royce plc (RR): Amendment 39-16669. Docket No. FAA- 2010... identified in this AD, contact Rolls-Royce plc, P.O. Box 31, Derby, DE24 8BJ, United Kingdom; phone: 011 44...

75 FR 51654 - Airworthiness Directives; Rolls-Royce plc (RR) RB211-22B and RB211-524 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-23

... Airworthiness Directives; Rolls-Royce plc (RR) RB211-22B and RB211-524 Series Turbofan Engines AGENCY: Federal... Rolls-Royce plc: Amendment 39-16402. Docket No. FAA-2009- 1157; Directorate Identifier 2009-NE-26-AD...) None. Applicability (c) This AD applies to Rolls-Royce plc RB211-22B series and RB211-524B4-D-02, RB211...

Automation of Underground Cable Laying Equipment Using PLC and Hmi

NASA Astrophysics Data System (ADS)

Mal Kothari, Kesar; Samba, Vishweshwar; Tania, Kinza; Udayakumar, R., Dr; Karthikeyan, Ram, Dr

2018-04-01

Underground cable laying is an alternative for overhead cable laying of telecommunication and power transmission lines. It is becoming very popular in recent times because of some of its advantages over overhead cable laying. This type of cable laying is mostly practiced in developed countries because it is more expensive than overhead cable laying. Underground cable laying is more suitable when land is not available, and it also increases the aesthetics. This paper implements the automation on a manually operated cable pulling winch machine using programmable logic controller (PLC). Winch machines are useful in underground cable laying. The main aim of the project is to replace all the mechanical functions with electrical controls which are operated through a touch screen (HMI). The idea is that the machine should shift between parallel and series circuit automatically based on the pressure sensed instead of manually operating the solenoid valve. Traditional means of throttling the engine using lever and wire is replaced with a linear actuator. Sensors such as proximity, pressure and load sensor are used to provide the input to the system. The HMI used will display the speed, length and tension of the rope being winded. Ladder logic is used to program the PLC.

Development of Algorithms for Control of Humidity in Plant Growth Chambers

NASA Technical Reports Server (NTRS)

Costello, Thomas A.

2003-01-01

Algorithms were developed to control humidity in plant growth chambers used for research on bioregenerative life support at Kennedy Space Center. The algorithms used the computed water vapor pressure (based on measured air temperature and relative humidity) as the process variable, with time-proportioned outputs to operate the humidifier and de-humidifier. Algorithms were based upon proportional-integral-differential (PID) and Fuzzy Logic schemes and were implemented using I/O Control software (OPTO-22) to define and download the control logic to an autonomous programmable logic controller (PLC, ultimate ethernet brain and assorted input-output modules, OPTO-22), which performed the monitoring and control logic processing, as well the physical control of the devices that effected the targeted environment in the chamber. During limited testing, the PLC's successfully implemented the intended control schemes and attained a control resolution for humidity of less than 1%. The algorithms have potential to be used not only with autonomous PLC's but could also be implemented within network-based supervisory control programs. This report documents unique control features that were implemented within the OPTO-22 framework and makes recommendations regarding future uses of the hardware and software for biological research by NASA.

Antitumour effects of PLC-gamma1-(SH2)2-TAT fusion proteins on EGFR/c-erbB-2-positive breast cancer cells.

PubMed

Katterle, Y; Brandt, B H; Dowdy, S F; Niggemann, B; Zänker, K S; Dittmar, T

2004-01-12

Due to its pivotal role in the growth factor-mediated tumour cell migration, the adaptor protein phospholipase C-gamma1 (PLC-gamma1) is an appropriate target to block ultimately the spreading of EGFR/c-erbB-2-positive tumour cells, thereby minimising metastasis formation. Here, we present an approach to block PLC-gamma1 activity by using protein-based PLC-gamma1 inhibitors consisting of PLC-gamma1 SH2 domains, which were fused to the TAT-transduction domain to ensure a high protein transduction efficiency. Two proteins were generated containing one PLC-gamma1-SH2-domain (PS1-TAT) or two PLC-gamma1-SH2 domains (PS2-TAT). PS2-TAT treatment of the EGFR/c-erbB-2-positive cell line MDA-HER2 resulted in a reduction of the EGF-mediated PLC-gamma1 tyrosine phosphorylation of about 30%, concomitant with a complete abrogation of the EGF-driven calcium influx. In addition to this, long-term PS2-TAT treatment both reduces the EGF-mediated migration of about 75% combined with a markedly decreased time locomotion of single MDA-HER2 cells as well as decreases the proliferation of MDA-HER2 cells by about 50%. Due to its antitumoral capacity on EGFR/c-erbB-2-positive breast cancer cells, we conclude from our results that the protein-based PLC-gamma1 inhibitor PS2-TAT may be a means for novel adjuvant antitumour strategies to minimise metastasis formation because of the blockade of cell migration and proliferation.

Phospholipase C mediated Suppression of Dark Noise Enables Single Photon Detection in Drosophila Photoreceptors

PubMed Central

Katz, Ben; Minke, Baruch

2012-01-01

Drosophila photoreceptor cells use the ubiquitous G-protein-mediated phospholipase C (PLC) cascade to achieve ultimate single photon sensitivity. This is manifested in the single photon responses (quantum bumps). In photoreceptor cells, dark activation of Gqα molecules occurs spontaneously and produces unitary dark events (dark bumps). A high rate of spontaneous Gqα activation and dark bump production potentially hampers single photon detection. We found that in wild type flies the in vivo rate of spontaneous Gqα activation is very high. Nevertheless, this high rate is not manifested in a substantially high rate of dark bumps. Therefore, it is unclear how phototransduction suppresses dark bump production, arising from spontaneous Gqα activation, while still maintaining high-fidelity representation of single photons. In this study we show that reduced PLC catalytic activity selectively suppressed production of dark bumps but not light-induced bumps. Manipulations of PLC activity using PLC mutant flies and Ca2+ modulations revealed that a critical level of PLC activity is required to induce bump production. The required minimal level of PLC activity, selectively suppressed random production of single Gqα-activated dark bumps despite a high rate of spontaneous Gqα activation. This minimal PLC activity level is reliably obtained by photon induced synchronized activation of several neighboring Gqα molecules activating several PLC molecules, but not by random activation of single Gqα molecules. We thus demonstrate how a G-protein-mediated transduction system, with PLC as its target, selectively suppresses its intrinsic noise while preserving reliable signaling. PMID:22357856

Requirement of the Listeria monocytogenes broad-range phospholipase PC-PLC during infection of human epithelial cells.

PubMed

Gründling, Angelika; Gonzalez, Mark D; Higgins, Darren E

2003-11-01

In this study, we investigated the requirement of the Listeria monocytogenes broad-range phospholipase C (PC-PLC) during infection of human epithelial cells. L. monocytogenes is a facultative intracellular bacterial pathogen of humans and a variety of animal species. After entering a host cell, L. monocytogenes is initially surrounded by a membrane-bound vacuole. Bacteria promote their escape from this vacuole, grow within the host cell cytosol, and spread from cell to cell via actin-based motility. Most infection studies with L. monocytogenes have been performed with mouse cells or an in vivo mouse model of infection. In all mouse-derived cells tested, the pore-forming cytolysin listeriolysin O (LLO) is absolutely required for lysis of primary vacuoles formed during host cell entry. However, L. monocytogenes can escape from primary vacuoles in the absence of LLO during infection of human epithelial cell lines Henle 407, HEp-2, and HeLa. Previous studies have shown that the broad-range phospholipase C, PC-PLC, promotes lysis of Henle 407 cell primary vacuoles in the absence of LLO. Here, we have shown that PC-PLC is also required for lysis of HEp-2 and HeLa cell primary vacuoles in the absence of LLO expression. Furthermore, our results indicated that the amount of PC-PLC activity is critical for the efficiency of vacuolar lysis. In an LLO-negative derivative of L. monocytogenes strain 10403S, expression of PC-PLC has to increase before or upon entry into human epithelial cells, compared to expression in broth culture, to allow bacterial escape from primary vacuoles. Using a system for inducible PC-PLC expression in L. monocytogenes, we provide evidence that phospholipase activity can be increased by elevated expression of PC-PLC or Mpl, the enzyme required for proteolytic activation of PC-PLC. Lastly, by using the inducible PC-PLC expression system, we demonstrate that, in the absence of LLO, PC-PLC activity is not only required for lysis of primary vacuoles in human epithelial cells but is also necessary for efficient cell-to-cell spread. We speculate that the additional requirement for PC-PLC activity is for lysis of secondary double-membrane vacuoles formed during cell-to-cell spread.

Phospholipase C-β4 Is Essential for the Progression of the Normal Sleep Sequence and Ultradian Body Temperature Rhythms in Mice

PubMed Central

Ikeda, Masayuki; Hirono, Moritoshi; Sugiyama, Takashi; Moriya, Takahiro; Ikeda-Sagara, Masami; Eguchi, Naomi; Urade, Yoshihiro; Yoshioka, Tohru

2009-01-01

Background The sleep sequence: i) non-REM sleep, ii) REM sleep, and iii) wakefulness, is stable and widely preserved in mammals, but the underlying mechanisms are unknown. It has been shown that this sequence is disrupted by sudden REM sleep onset during active wakefulness (i.e., narcolepsy) in orexin-deficient mutant animals. Phospholipase C (PLC) mediates the signaling of numerous metabotropic receptors, including orexin receptors. Among the several PLC subtypes, the β4 subtype is uniquely localized in the geniculate nucleus of thalamus which is hypothesized to have a critical role in the transition and maintenance of sleep stages. In fact, we have reported irregular theta wave frequency during REM sleep in PLC-β4-deficient mutant (PLC-β4−/−) mice. Daily behavioral phenotypes and metabotropic receptors involved have not been analyzed in detail in PLC-β4−/− mice, however. Methodology/Principal Findings Therefore, we analyzed 24-h sleep electroencephalogram in PLC-β4−/− mice. PLC-β4−/− mice exhibited normal non-REM sleep both during the day and nighttime. PLC-β4−/− mice, however, exhibited increased REM sleep during the night, their active period. Also, their sleep was fragmented with unusual wake-to-REM sleep transitions, both during the day and nighttime. In addition, PLC-β4−/− mice reduced ultradian body temperature rhythms and elevated body temperatures during the daytime, but had normal homeothermal response to acute shifts in ambient temperatures (22°C–4°C). Within the most likely brain areas to produce these behavioral phenotypes, we found that, not orexin, but group-1 metabotropic glutamate receptor (mGluR)-mediated Ca2+ mobilization was significantly reduced in the dorsal lateral geniculate nucleus (LGNd) of PLC-β4−/− mice. Voltage clamp recordings revealed that group-1 mGluR-mediated currents in LGNd relay neurons (inward in wild-type mice) were outward in PLC-β4−/− mice. Conclusions/Significance These lines of evidence indicate that impaired LGNd relay, possibly mediated via group-1 mGluR, may underlie irregular sleep sequences and ultradian body temperature rhythms in PLC-β4−/− mice. PMID:19898623

Research of communication quality assessment algorithm according to the standard G3-PLC

NASA Astrophysics Data System (ADS)

Chebotayev, Pavel; Klimenko, Aleksey; Myakochin, Yuri; Polyakov, Igor; Shelupanov, Alexander; Urazayev, Damir; Zykov, Dmitriy

2017-11-01

The present paper deals with the quality assessment of PLC channel which is a part of fault-tolerant self-organizing heterogeneous communication system. The PLC implementation allows to reduce exploitation costs when constructing new info-communication networks. PLC is used for transmitting information between various devices in alternating current mains. There exist different approaches to transfer information over power lines. Their differences resulted from the requirements of typical apps which use PLC as a data transmission channel. In the process of research described in this paper, the simulation of a signal in AC mains with regard to different kinds of noise caused by power line loads was performed.

Fluorescent Phosphatidylinositol 4,5-Bisphosphate Derivatives with Modified 6-Hydroxy Group as Novel Substrates for Phospholipase C

PubMed Central

Wang, Xiaoyang; Barrett, Matthew; Sondek, John; Harden, T. Kendall; Zhang, Qisheng

2013-01-01

The capacity to monitor spatiotemporal activity of phospholipase C (PLC) isozymes with a PLC-selective sensor would dramatically enhance understanding of the physiological function and disease relevance of these signaling proteins. Previous structural and biochemical studies defined critical roles for several of the functional groups of the endogenous substrate of PLC isozymes, phosphatidylinositol 4,5-bisphosphate (PIP2), indicating that these sites cannot be readily modified without compromising interactions with the lipase active site. However, the role of the 6-hydroxy group of PIP2 for interaction and hydrolysis by PLC has not been explored, possibly due to challenges in synthesizing 6-hydroxy derivatives. Here, we describe an efficient route for the synthesis of novel, fluorescent PIP2 derivatives modified at the 6-hydroxy group. Two of these derivatives were used in assays of PLC activity in which the fluorescent PIP2 substrates were separated from their diacylglycerol products and reaction rates quantified by fluorescence. Both PIP2 analogues effectively function as substrates of PLC-δ1, and the KM and Vmax values obtained with one of these are similar to those observed with native PIP2 substrate. These results indicate that the 6-hydroxy group can be modified to develop functional substrates for PLC isozymes, thereby serving as the foundation for further development of PLC-selective sensors. PMID:22703043

Distinct Phospholipase C-β Isozymes Mediate Lysophosphatidic Acid Receptor 1 Effects on Intestinal Epithelial Homeostasis and Wound Closure

PubMed Central

Lee, Sei-Jung; Leoni, Giovanna; Neumann, Philipp-Alexander; Chun, Jerold; Nusrat, Asma

2013-01-01

Maintenance of the epithelial barrier in the intestinal tract is necessary to protect the host from the hostile luminal environment. Phospholipase C-β (PLC-β) has been implicated to control myriad signaling cascades. However, the biological effects of selective PLC-β isozymes are poorly understood. We describe novel findings that lysophosphatidic acid (LPA) regulates PLC-β1 and PLC-β2 via two distinct pathways to enhance intestinal epithelial cell (IEC) proliferation and migration that facilitate wound closure and recovery of the intestinal epithelial barrier. LPA acting on the LPA1 receptor promotes IEC migration by facilitating the interaction of Gαq with PLC-β2. LPA-induced cell proliferation is PLC-β1 dependent and involves translocation of Gαq to the nucleus, where it interacts with PLC-β1 to induce cell cycle progression. An in vivo study using LPA1-deficient mice (Lpar1−/−) shows a decreased number of proliferating IECs and migration along the crypt-luminal axis. Additionally, LPA enhances migration and proliferation of IECs in an LPA1-dependent manner, and Lpar1−/− mice display defective mucosal wound repair that requires cell proliferation and migration. These findings delineate novel LPA1-dependent lipid signaling that facilitates mucosal wound repair via spatial targeting of distinct PLC-βs within the cell. PMID:23478264

Virtual PLC's @ Their Best: A Daily Diatribe

ERIC Educational Resources Information Center

Jaeger, Paige

2010-01-01

Years ago, working in isolation meant that to develop professionally, librarians had to read journals and wait for the two times per year there were librarian conferences locally, statewide, or nationally that would help them improve their program. Now colleagues, suggestions, and Professional Learning Communities (PLCs) are merely a click away.…

Fear conditioning is associated with altered integration of PLC and ERK signaling in the hippocampus.

PubMed

Buckley, Colin T; Caldwell, Kevin K

2004-12-01

The extracellular signal-regulated protein kinases (ERKs) are proline-directed, serine/threonine kinases that regulate a variety of cellular functions, including proliferation, differentiation, and plasticity. In the present report, we provide evidence that ERK2 and phosphatidylinositol-specific phospholipase C (PLC)-beta and -gamma isozymes interact in the rat hippocampal formation. We found that anti-PLC-beta1a, -beta2, -beta4, -gamma1 and -gamma2, but not -beta3, immune complexes isolated from rat hippocampal formation postnuclear fractions contain anti-ERK2 immunoreactivity. Further, we show that PLC catalytic activity is associated with anti-ERK2 immunoprecipitates isolated from the hippocampal formation, and that the amount of enzyme activity is significantly increased following fear-conditioned learning. The observed interactions may be mediated by consensus sequences conforming to an ERK2 docking site, termed a D-domain, that we identified in PLC-beta1a, -beta2, -beta4 -gamma1 and -gamma2. Based on these results, we propose that PLC-beta and PLC-gamma isozymes form signaling complexes with ERK2 in rat brain, and these complexes play critical roles in learning and memory, as well as a variety of other neuronal functions.

Membrane-induced Allosteric Control of Phospholipase C-β Isozymes*

PubMed Central

Charpentier, Thomas H.; Waldo, Gary L.; Barrett, Matthew O.; Huang, Weigang; Zhang, Qisheng; Harden, T. Kendall; Sondek, John

2014-01-01

All peripheral membrane proteins must negotiate unique constraints intrinsic to the biological interface of lipid bilayers and the cytosol. Phospholipase C-β (PLC-β) isozymes hydrolyze the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to propagate diverse intracellular responses that underlie the physiological action of many hormones, neurotransmitters, and growth factors. PLC-β isozymes are autoinhibited, and several proteins, including Gαq, Gβγ, and Rac1, directly engage distinct regions of these phospholipases to release autoinhibition. To understand this process, we used a novel, soluble analog of PIP2 that increases in fluorescence upon cleavage to monitor phospholipase activity in real time in the absence of membranes or detergents. High concentrations of Gαq or Gβ1γ2 did not activate purified PLC-β3 under these conditions despite their robust capacity to activate PLC-β3 at membranes. In addition, mutants of PLC-β3 with crippled autoinhibition dramatically accelerated the hydrolysis of PIP2 in membranes without an equivalent acceleration in the hydrolysis of the soluble analog. Our results illustrate that membranes are integral for the activation of PLC-β isozymes by diverse modulators, and we propose a model describing membrane-mediated allosterism within PLC-β isozymes. PMID:25193662

Phosphorylation of Nephrin Triggers Ca2+ Signaling by Recruitment and Activation of Phospholipase C-{gamma}1.

PubMed

Harita, Yutaka; Kurihara, Hidetake; Kosako, Hidetaka; Tezuka, Tohru; Sekine, Takashi; Igarashi, Takashi; Ohsawa, Ikuroh; Ohta, Shigeo; Hattori, Seisuke

2009-03-27

A specialized intercellular junction between podocytes, known as the slit diaphragm (SD), forms the essential structural frame-work for glomerular filtration in the kidney. In addition, mounting evidence demonstrates that the SD also plays a crucial role as a signaling platform in physiological and pathological states. Nephrin, the major component of the SD, is tyrosine-phosphorylated by a Src family tyrosine kinase, Fyn, in developing or injured podocytes, recruiting Nck to Nephrin via its Src homology 2 domain to regulate dynamic actin remodeling. Dysregulated Ca(2+) homeostasis has also been implicated in podocyte damage, but the mechanism of how podocytes respond to injury is largely unknown. Here we have identified phospholipase C-gamma1 (PLC-gamma1) as a novel phospho-Nephrin-binding protein. When HEK293T cells expressing a chimeric protein consisting of CD8 and Nephrin cytoplasmic domain (CD) were treated with anti-CD8 and anti-mouse antibodies, clustering of Nephrin and phosphorylation of Nephrin-CD were induced. Upon this clustering, PLC-gamma1 was bound to phosphorylated Nephrin Tyr-1204, which induced translocation of PLC-gamma1 from cytoplasm to the CD8/Nephrin cluster on the plasma membrane. The recruitment of PLC-gamma1 to Nephrin activated PLC-gamma1, as detected by phosphorylation of PLC-gamma1 Tyr-783 and increase in inositol 1,4,5-trisphosphate level. We also found that Nephrin Tyr-1204 phosphorylation triggers the Ca(2+) response in a PLC-gamma1-dependent fashion. Furthermore, PLC-gamma1 is significantly phosphorylated in injured podocytes in vivo. Given the profound effect of PLC-gamma in diverse cellular functions, regulation of the Ca(2+) signaling by Nephrin may be important in modulating the glomerular filtration barrier function.

PLC-γ1 Signaling Plays a Subtype-Specific Role in Postbinding Cell Entry of Influenza A Virus

PubMed Central

Zhu, Liqian; Ly, Hinh

2014-01-01

Host signaling pathways and cellular proteins play important roles in the influenza viral life cycle and can serve as antiviral targets. In this study, we report the engagement of host phosphoinositide-specific phospholipase γ1 (PLC-γ1) in mediating cell entry of influenza virus H1N1 but not H3N2 subtype. Both PLC-γ1-specific inhibitor and short hairpin RNA (shRNA) strongly suppress the replication of H1N1 but not H3N2 viruses in cell culture, suggesting that PLC-γ1 plays an important subtype-specific role in the influenza viral life cycle. Further analyses demonstrate that PLC-γ1 activation is required for viral postbinding cell entry. In addition, H1N1, but not H3N2, infection leads to the phosphorylation of PLC-γ1 at Ser 1248 immediately after infection and independent of viral replication. We have further shown that H1N1-induced PLC-γ1 activation is downstream of epidermal growth factor receptor (EGFR) signaling. Interestingly, both H1N1 and H3N2 infections activate EGFR, but only H1N1 infection leads to PLC-γ1 activation. Taking our findings together, we have identified for the first time the subtype-specific interplay of host PLC-γ1 signaling and H1N1 virus that is critical for viral uptake early in the infection. Our study provides novel insights into how virus interacts with the cellular signaling network by demonstrating that viral determinants can regulate how the host signaling pathways function in virally infected cells. PMID:24155396

Preeclampsia serum-induced collagen I expression and intracellular calcium levels in arterial smooth muscle cells are mediated by the PLC-γ1 pathway

PubMed Central

Jiang, Rongzhen; Teng, Yincheng; Huang, Yajuan; Gu, Jinghong; Ma, Li; Li, Ming; Zhou, Yuedi

2014-01-01

In women with preeclampsia (PE), endothelial cell (EC) dysfunction can lead to altered secretion of paracrine factors that induce peripheral vasoconstriction and proteinuria. This study examined the hypothesis that PE sera may directly or indirectly, through human umbilical vein ECs (HUVECs), stimulate phospholipase C-γ1-1,4,5-trisphosphate (PLC-γ1-IP3) signaling, thereby increasing protein kinase C-α (PKC-α) activity, collagen I expression and intracellular Ca2+ concentrations ([Ca2+]i) in human umbilical artery smooth muscle cells (HUASMCs). HUASMCs and HUVECs were cocultured with normal or PE sera before PLC-γ1 silencing. Increased PLC-γ1 and IP3 receptor (IP3R) phosphorylation was observed in cocultured HUASMCs stimulated with PE sera (P<0.05). In addition, PE serum significantly increased HUASMC viability and reduced their apoptosis (P<0.05); these effects were abrogated with PLC-γ1 silencing. Compared with normal sera, PE sera increased [Ca2+]i in cocultured HUASMCs (P<0.05), which was inhibited by PLC-γ1 and IP3R silencing. Finally, PE sera-induced PKC-α activity and collagen I expression was inhibited by PLC-γ1 small interfering RNA (siRNA) (P<0.05). These results suggest that vasoactive substances in the PE serum may induce deposition in the extracellular matrix through the activation of PLC-γ1, which may in turn result in thickening and hardening of the placental vascular wall, placental blood supply shortage, fetal hypoxia–ischemia and intrauterine growth retardation or intrauterine fetal death. PE sera increased [Ca2+]i and induced PKC-α activation and collagen I expression in cocultured HUASMCs via the PLC-γ1 pathway. PMID:25257609

WNK1 Promotes PIP2 Synthesis to Coordinate Growth Factor and GPCR-Gq Signaling

PubMed Central

An, Sung-Wan; Cha, Seung-Kuy; Yoon, Joonho; Chang, Seungwoo; Ross, Elliott M.; Huang, Chou-Long

2011-01-01

Summary Background PLC-β signaling is generally thought to be mediated by allosteric activation by G proteins and Ca2+. While availability of the PIP2 substrate is limiting in some cases, its production has not been shown to be independently regulated as a signaling mechanism. WNK1 protein kinase is known to regulate ion homeostasis and cause hypertension when expression is increased by gene mutations. However, its signaling functions remain largely elusive. Results Using diacylglycerol-stimulated TRPC6 and inositol trisphosphate-mediated Ca2+ transients as cellular biosensors, we show that WNK1 stimulates PLC-β signaling in cells by promoting the synthesis of PIP2 via stimulation of phosphatidylinositol 4-kinase IIIα. WNK1 kinase activity is not required. Stimulation of PLC-β by WNK1 and by Gαq are synergistic; WNK1 activity is essential for regulation of PLC-β signaling by Gq-coupled receptors and basal input from Gq is necessary for WNK1 signaling via PLC-β. WNK1 further amplifies PLC-β signaling when it is phosphorylated by Akt kinase in response to insulin-like growth factor. Conclusions WNK1 is a novel regulator of PLC-β that acts by controlling substrate availability. WNK1 thereby coordinates signaling between G protein and Akt kinase pathways. Because PIP2 is itself a signaling molecule, regulation of PIP2 synthesis by WNK1 also allows the cell to initiate PLC signaling while independently controlling the effects of PIP2 on other targets. These findings describe a new signaling pathway for Akt-activating growth factors, a mechanism for G protein-growth factor crosstalk and a means to independently control PLC signaling and PIP2 availability. PMID:22119528

Reduced expression of E-cadherin and p120-catenin and elevated expression of PLC-γ1 and PIKE are associated with aggressiveness of oral squamous cell carcinoma

PubMed Central

Jiang, Yi; Liao, Liyan; Shrestha, Chandrama; Ji, Shangli; Chen, Ying; Peng, Jian; Wang, Larry; Liao, Eryuan; Xie, Zhongjian

2015-01-01

Oral squamous cell carcinoma (OSCC) is one of the most lethal malignant tumors. The cadherin/catenin cell-cell adhesion complex plays a major role in cancer development and progression. p120-catenin (p120) is a cytoplasmic molecule closely associated with E-cadherin which activates phospholipase C-γ1 (PLC-γ1). Our previous studies indicate that activation of PLC-γ1 plays a critical role in epidermal growth factor (EGF)-induced migration and proliferation of squamous cell carcinoma (SCC) cells and phosphatidylinositol 3-kinase enhancer (PIKE) is highly expressed in SCC cells and mediates EGFR-dependent SCC cell proliferation. Our current study was to determine whether the expression of E-cadherin, p120, PLC-γ1, and PIKE, is associated with OSCC. To address this issue, we assessed levels and localization of E-cadherin, p120, PLC-γ1, and PIKE in specimen of 92 patients with OSCC by immunohistochemistry. The results showed that the expression of E-cadherin, and p120 negatively correlated with the tumor differentiation and the expression of PLC-γ1 and PIKE positively correlated with the tumor differentiation. The expression of PLC-γ1 and PIKE in OSCC stage T3 + T4 or in OSCC with lymph node metastasis was significantly higher than that in OSCC stage T1 + T2 or in OSCC without lymph node metastasis. The expression of p120 positively correlated with levels of E-cadherin but negatively correlated with levels of PLC-γ1 and PIKE in OSCC. These data indicate that increased expression of PLC-γ1 and PIKE and decreased expression of E-cadherin and p120 are associated with the aggressiveness of OSCC. PMID:26464646

Dual role of SLP-76 in mediating T cell receptor-induced activation of phospholipase C-gamma1.

PubMed

Beach, Dvora; Gonen, Ronnie; Bogin, Yaron; Reischl, Ilona G; Yablonski, Deborah

2007-02-02

Phospholipase C-gamma1 (PLC-gamma1) activation depends on a heterotrimeric complex of adaptor proteins composed of LAT, Gads, and SLP-76. Upon T cell receptor stimulation, a portion of PLC-gamma1 is recruited to a detergent-resistant membrane fraction known as the glycosphingolipid-enriched membrane microdomains (GEMs), or lipid rafts, to which LAT is constitutively localized. In addition to LAT, PLC-gamma1 GEM recruitment depended on SLP-76, and, in particular, required the Gads-binding domain of SLP-76. The N-terminal tyrosine phosphorylation sites and P-I region of SLP-76 were not required for PLC-gamma1 GEM recruitment, but were required for PLC-gamma1 phosphorylation at Tyr(783). Thus, GEM recruitment can be insufficient for full activation of PLC-gamma1 in the absence of a second SLP-76-mediated event. Indeed, a GEM-targeted derivative of PLC-gamma1 depended on SLP-76 for T cell receptor-induced phosphorylation at Tyr783 and subsequent NFAT activation. On a biochemical level, SLP-76 inducibly associated with both Vav and catalytically active ITK, which efficiently phosphorylated a PLC-gamma1 fragment at Tyr783 in vitro. Both associations were disrupted upon mutation of the N-terminal tyrosine phosphorylation sites of SLP-76. The P-I region deletion disrupted Vav association and reduced SLP-76-associated kinase activity. A smaller deletion within the P-I region, which does not impair PLC-gamma1 activation, did not impair the association with Vav, but reduced SLP-76-associated kinase activity. These results provide new insight into the multiple roles of SLP-76 and the functional importance of its interactions with other signaling proteins.

Propionyl-L-carnitine improves endothelial function, microcirculation and pain management in critical limb ischemia.

PubMed

De Marchi, S; Zecchetto, S; Rigoni, A; Prior, M; Fondrieschi, L; Scuro, A; Rulfo, F; Arosio, E

2012-10-01

Chronic critical limb ischemia (CLI) is a severe condition of hypo-perfusion of lower limbs, which is associated with inflammation and a pro-coagulative state. It is a disease at high risk of amputation and cardiovascular death. Propionyl-L-carnitine (PLC) is efficacious in improving pain free walking distance in peripheral arterial disease with claudication; it also exerts favorable effects on the arterial wall and on endothelial function. The purpose of this study was to evaluate the effects of PLC on microcirculation, endothelial function and pain relief in patients affected by CLI not suitable for surgical intervention. We enrolled 48 patients with CLI. Patients were randomized into two groups: the first group was treated with PLC, the second was treated with saline solution. All of them underwent the following tests: laser Doppler flowmetry at the forefoot at rest and after ischemia, trans cutaneous oxygen partial pressure and carbon dioxide partial pressure at the forefoot at rest and after ischemia, endothelium dependent dilation of the brachial artery. All tests were repeated after treatments. Pain was assessed by visual analog pain scale. Endothelium dependent dilation increased after PLC (9.5 ± 3.2 vs 4.9 ± 1.4 %; p < 0.05). Post-ischemic peak flow with laser-Doppler flow increased after PLC. TcPO2 increased, while TcPCO2 decreased after PLC; CO2 production decreased after PLC. VAS showed a significant reduction in pain perception after active treatment. In CLI patients, PLC can improve microcirculation (post ischemic hyperemia, TcPO2 and TcPCO2 production). PLC also enhances endothelium dependent dilation and reduces analgesic consumption and pain perception.

Phospholipase C-β in immune cells.

PubMed

Kawakami, Toshiaki; Xiao, Wenbin

2013-09-01

Great progress has recently been made in structural and functional research of phospholipase C (PLC)-β. We now understand how PLC-β isoforms (β1-β4) are activated by GTP-bound Gαq downstream of G protein-coupled receptors. Numerous studies indicate that PLC-βs participate in the differentiation and activation of immune cells that control both the innate and adaptive immune systems. The PLC-β3 isoform also interplays with tyrosine kinase-based signaling pathways, to inhibit Stat5 activation by recruiting the protein-tyrosine phosphatase SHP-1, with which PLC-β3 and Stat5 form a multi-molecular signaling platform, named SPS complex. The SPS complex has important regulatory roles in tumorigenesis and immune cell activation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Phospholipase C-β in Immune Cells

PubMed Central

Kawakami, Toshiaki; Xiao, Wenbin

2013-01-01

Great progress has recently been made in structural and functional research of phospholipase C (PLC)-β. We now understand how PLC-β isoforms (β1-β4) are activated by GTP-bound Gαq downstream of G protein-coupled receptors. Numerous studies indicate that PLC-βs participate in the differentiation and activation of immune cells that control both the innate and adaptive immune systems. The PLC-β3 isoform also interplays with tyrosine kinase-based signaling pathways, to inhibit Stat5 activation by recruiting the protein-tyrosine phosphatase SHP-1, with which PLC-β3 and Stat5 form a multi-molecular signaling platform, named SPS complex. The SPS complex has important regulatory roles in tumorigenesis and immune cell activation. PMID:23981313

PLC-based mode multi/demultiplexers for mode division multiplexing

NASA Astrophysics Data System (ADS)

Saitoh, Kunimasa; Hanzawa, Nobutomo; Sakamoto, Taiji; Fujisawa, Takeshi; Yamashita, Yoko; Matsui, Takashi; Tsujikawa, Kyozo; Nakajima, Kazuhide

2017-02-01

Recently developed PLC-based mode multi/demultiplexers (MUX/DEMUXs) for mode division multiplexing (MDM) transmission are reviewed. We firstly show the operation principle and basic characteristics of PLC-based MUX/DEMUXs with an asymmetric directional coupler (ADC). We then demonstrate the 3-mode (2LP-mode) multiplexing of the LP01, LP11a, and LP11b modes by using fabricated PLC-based mode MUX/DEMUX on one chip. In order to excite LP11b mode in the same plane, a PLC-based LP11 mode rotator is introduced. Finally, we show the PLC-based 6-mode (4LP-mode) MUX/DEMUX with a uniform height by using ADCs, LP11 mode rotators, and tapered waveguides. It is shown that the LP21a mode can be excited from the LP11b mode by using ADC, and the two nearly degenerated LP21b and LP02 modes can be (de)multiplexed separately by using tapered mode converter from E13 (E31) mode to LP21b (LP02) mode.

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

Palomar, J.; Wyman, R.

This document provides recommendations to guide reviewers in the application of Programmable Logic Controllers (PLCS) to the control, monitoring and protection of nuclear reactors. The first topics addressed are system-level design issues, specifically including safety. The document then discusses concerns about the PLC manufacturing organization and the protection system engineering organization. Supplementing this document are two appendices. Appendix A summarizes PLC characteristics. Specifically addressed are those characteristics that make the PLC more suitable for emergency shutdown systems than other electrical/electronic-based systems, as well as characteristics that improve reliability of a system. Also covered are PLC characteristics that may create anmore » unsafe operating environment. Appendix B provides an overview of the use of programmable logic controllers in emergency shutdown systems. The intent is to familiarize the reader with the design, development, test, and maintenance phases of applying a PLC to an ESD system. Each phase is described in detail and information pertinent to the application of a PLC is pointed out.« less

Short Stat5-Interacting Peptide Derived from Phospholipase C-β3 Inhibits Hematopoietic Cell Proliferation and Myeloid Differentiation

PubMed Central

Yasudo, Hiroki; Ando, Tomoaki; Xiao, Wenbin; Kawakami, Yuko; Kawakami, Toshiaki

2011-01-01

Constitutive activation of the transcription factor Stat5 in hematopoietic stem/progenitor cells leads to various hematopoietic malignancies including myeloproliferative neoplasm (MPN). Our recent study found that phospholipase C (PLC)-β3 is a novel tumor suppressor involved in MPN, lymphoma and other tumors. Stat5 activity is negatively regulated by the SH2 domain-containing protein phosphatase SHP-1 in a PLC-β3-dependent manner. PLC-β3 can form the multimolecular SPS complex together with SHP-1 and Stat5. The close physical proximity of SHP-1 and Stat5 brought about by interacting with the C-terminal segment of PLC-β3 (PLC-β3-CT) accelerates SHP-1-mediated dephosphorylation of Stat5. Here we identify the minimal sequences within PLC-β3-CT required for its tumor suppressor function. Two of the three Stat5-binding noncontiguous regions, one of which also binds SHP-1, substantially inhibited in vitro proliferation of Ba/F3 cells. Surprisingly, an 11-residue Stat5-binding peptide (residues 988-998) suppressed Stat5 activity in Ba/F3 cells and in vivo proliferation and myeloid differentiation of hematopoietic stem/progenitor cells. Therefore, this study further defines PLC-β3-CT as the Stat5- and SHP-1-binding domain by identifying minimal functional sequences of PLC-β3 for its tumor suppressor function and implies their potential utility in the control of hematopoietic malignancies. PMID:21949826

Dynamics of major histocompatibility complex class I association with the human peptide-loading complex.

PubMed

Panter, Michaela S; Jain, Ankur; Leonhardt, Ralf M; Ha, Taekjip; Cresswell, Peter

2012-09-07

Although the human peptide-loading complex (PLC) is required for optimal major histocompatibility complex class I (MHC I) antigen presentation, its composition is still incompletely understood. The ratio of the transporter associated with antigen processing (TAP) and MHC I to tapasin, which is responsible for MHC I recruitment and peptide binding optimization, is particularly critical for modeling of the PLC. Here, we characterized the stoichiometry of the human PLC using both biophysical and biochemical approaches. By means of single-molecule pulldown (SiMPull), we determined a TAP/tapasin ratio of 1:2, consistent with previous studies of insect-cell microsomes, rat-human chimeric cells, and HeLa cells expressing truncated TAP subunits. We also report that the tapasin/MHC I ratio varies, with the PLC population comprising both 2:1 and 2:2 complexes, based on mutational and co-precipitation studies. The MHC I-saturated PLC may be particularly prevalent among peptide-selective alleles, such as HLA-C4. Additionally, MHC I association with the PLC increases when its peptide supply is reduced by inhibiting the proteasome or by blocking TAP-mediated peptide transport using viral inhibitors. Taken together, our results indicate that the composition of the human PLC varies under normal conditions and dynamically adapts to alterations in peptide supply that may arise during viral infection. These findings improve our understanding of the quality control of MHC I peptide loading and may aid the structural and functional modeling of the human PLC.

Higher dietary intakes of choline and betaine are associated with a lower risk of primary liver cancer: a case-control study.

PubMed

Zhou, Rui-Fen; Chen, Xiao-Lin; Zhou, Zhong-Guo; Zhang, Yao-Jun; Lan, Qiu-Ye; Liao, Gong-Cheng; Chen, Yu-Ming; Zhu, Hui-Lian

2017-04-06

The dietary intake of methyl donors is favorably associated with many diseases, but the findings regarding primary liver cancer (PLC) risk are limited. This study investigated the association between the intake of choline, betaine and methionine and PLC risk in adults. This 1:1 matched case-control study enrolled 644 hospital-based PLC patients and 644 community-based controls who were matched by sex and age, in Guangzhou, China. An interviewer-administered questionnaire and a food-frequency questionnaire were used to collect general information and dietary intake information. Conditional logistic regression showed a significantly inverse association between total choline and betaine intakes and PLC risk. The multivariable-adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) for PLC for the top (vs. bottom) tertile were 0.34 (0.24-0.49; P -trend  < 0.001) for total choline and 0.67 (0.48-0.93; P -trend  = 0.011) for betaine. No significant association was observed between the intake of methionine and PLC risk (P > 0.05). For individual choline compounds, higher consumptions of free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine and sphingomyelin were associated with a lower PLC risk (all P-trend < 0.05). The studied associations were not significantly modified by the folate intake (P-interactions: 0.488-0.890). Our findings suggest that higher choline and betaine intakes may be associated with a lower risk of PLC.

Bacterial phospholipases C as vaccine candidate antigens against cystic fibrosis respiratory pathogens: the Mycobacterium abscessus model.

PubMed

Le Moigne, Vincent; Rottman, Martin; Goulard, Céline; Barteau, Benoît; Poncin, Isabelle; Soismier, Nathalie; Canaan, Stéphane; Pitard, Bruno; Gaillard, Jean-Louis; Herrmann, Jean-Louis

2015-04-27

Vaccine strategies represent one of the fighting answers against multiresistant bacteria in a number of clinical settings like cystic fibrosis (CF). Mycobacterium abscessus, an emerging CF pathogen, raises difficult therapeutic problems due to its intrinsic antibiotic multiresistance. By reverse vaccinology, we identified M. abscessus phospholipase C (MA-PLC) as a potential vaccine target. We deciphered here the protective response generated by vaccination with plasmid DNA encoding the MA-PLC formulated with a tetra functional block copolymer 704, in CF (ΔF508) mice. Protection was tested against aerosolized smooth and rough (hypervirulent) variants of M. abscessus. MA-PLC DNA vaccination (days 0, 21, 42) elicited a strong antibody response. A significant protective effect was obtained against aerosolized M. abscessus (S variant) in ΔF508 mice, but not in wild-type FVB littermates; similar results were observed when: (i) challenging mice with the "hypervirulent" R variant, and; (ii) immunizing mice with purified MA-PLC protein. High IgG titers against MA-PLC protein were measured in CF patients with M. abscessus infection; interestingly, significant titers were also detected in CF patients positive for Pseudomonas aeruginosa versus P. aeruginosa-negative controls. MA-PLC DNA- and PLC protein-vaccinated mice cleared more rapidly M. abscessus than β-galactosidase DNA- or PBS- vaccinated mice in the context of CF. PLCs could constitute interesting vaccine targets against common PLC-producing CF pathogens like P. aeruginosa. Copyright © 2015 Elsevier Ltd. All rights reserved.

Petunia Phospholipase C1 Is Involved in Pollen Tube Growth[W

PubMed Central

Dowd, Peter E.; Coursol, Sylvie; Skirpan, Andrea L.; Kao, Teh-hui; Gilroy, Simon

2006-01-01

Although pollen tube growth is essential for plant fertilization and reproductive success, the regulators of the actin-related growth machinery and the cytosolic Ca2+ gradient thought to determine how these cells elongate remain poorly defined. Phospholipases, their substrates, and their phospholipid turnover products have been proposed as such regulators; however, the relevant phospholipase(s) have not been characterized. Therefore, we cloned cDNA for a pollen-expressed phosphatidylinositol 4,5-bisphosphate (PtdInsP2)–cleaving phospholipase C (PLC) from Petunia inflata, named Pet PLC1. Expressing a catalytically inactive form of Pet PLC1 in pollen tubes caused expansion of the apical Ca2+ gradient, disruption of the organization of the actin cytoskeleton, and delocalization of growth at the tube tip. These phenotypes were suppressed by depolymerizing actin with low concentrations of latrunculin B, suggesting that a critical site of action of Pet PLC1 is in regulating actin structure at the growing tip. A green fluorescent protein (GFP) fusion to Pet PLC1 caused enrichment in regions of the apical plasma membrane not undergoing rapid expansion, whereas a GFP fusion to the PtdInsP2 binding domain of mammalian PLC δ1 caused enrichment in apical regions depleted in PLC. Thus, Pet PLC1 appears to be involved in the machinery that restricts growth to the very apex of the elongating pollen tube, likely through its regulatory action on PtdInsP2 distribution within the cell. PMID:16648366

Propionyl-L-carnitine limits chronic ventricular dilation after myocardial infarction in rats.

PubMed

Micheletti, R; Di Paola, E D; Schiavone, A; English, E; Benatti, P; Capasso, J M; Anversa, P; Bianchi, G

1993-04-01

To determine whether propionyl-L-carnitine (PLC) administration ameliorates ventricular remodeling after myocardial infarction, we performed coronary occlusion in rats and examined the long-term effects of the drug 19-24 wk after surgery. In view of the well-established role of angiotensin-converting enzyme (ACE) inhibitors in the reduction of ventricular dilation after infarction, the therapeutic impact of oral PLC (60 mg/kg) was compared with that of enalapril (1 mg/kg). Infarct size measured planimetrically was found to be comparable in untreated, PLC-treated, and enalapril-treated rats, averaging 40-46% of the left ventricular free wall. Heart weight was increased 14, 16, and 11% with no treatment, with PLC, and with enalapril, respectively. The relationship between left ventricular filling pressure and chamber volume demonstrated that PLC and enalapril significantly prevented the expansion in cavitary size after infarction. These protective influences were observed throughout the range of filling pressures measured, from 0 to 30 mmHg. At a uniform reference point of filling pressure of 4 mmHg, untreated infarcted hearts showed an expansion in ventricular volume of 2.17-fold (P < 0.0001). Corresponding increases in this parameter after PLC and enalapril were 36 and 43%, respectively, both not statistically significant. Moreover, PLC was capable of reducing the alterations in myocardial compliance associated with myocardial infarction. In conclusion, PLC reduces the magnitude of decompensated eccentric hypertrophy produced by myocardial infarction in a manner similar to that found with ACE inhibition.

77 FR 13485 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-07

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... series turbofan engines. This AD requires inspecting the front combustion liner head section for cracking.... (c) Applicability This AD applies to Rolls-Royce plc (RR) RB211-Trent 800 turbofan engines, all...

The study of fix composite panel and steel plates on testing stand

NASA Astrophysics Data System (ADS)

Wróbel, A.; Płaczek, M.; Wachna, M.

2016-08-01

In this paper the practical possibilities of strength verification analysis of composite materials used in the manufacture of selected components of railway wagons are presented. Real laboratory stand for measurements in a scale controlled by PLC controller were made. The study of different types of connections of composite materials with sheet metal is presented. In one of the chapter of this paper principles construction of testing stand with pneumatic cylinder were presented. Mainly checking of displacements and stresses generated on the sheet as a result of pneumatic actuators load for composite boards was carried out. The use of the controller with operating panel allows to easy programming testing cycle. The user can define the force generated by the actuator by change of air pressure in cylinder. Additionally the location of acting cylinders and their jump can be changed by operator. The examination of the volume displacements was done by displacement sensor, and the tensile strain gauge. All parameters are written in CatmanEasy - data acquisition software. This article presents the study of stresses and displacements in the composite plates joined with sheet metal, in summary of this article, the authors compare the obtained results with the computer simulation results in the article: "Simulation of stresses in an innovative combination of composite with sheet".

78 FR 65313 - Actavis, Inc. a corporation, and Warner Chilott PLC; Analysis of Agreement Containing Consent...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... FEDERAL TRADE COMMISSION [File No. 131 0152] Actavis, Inc. a corporation, and Warner Chilott PLC; Analysis of Agreement Containing Consent Orders To Aid Public Comment AGENCY: Federal Trade Commission... (``Consent Agreement'') from Actavis, Inc. (``Actavis'') and Warner Chilcott plc (``Warner Chilcott'') that...

76 FR 80430 - Rio Tinto plc and Rio Tinto Limited; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-23

... SECURITIES AND EXCHANGE COMMISSION [Investment Company Act Release No. 29889; 812-13777] Rio Tinto plc and Rio Tinto Limited; Notice of Application December 19, 2011. AGENCY: Securities and Exchange... Company Act of 1940 (the ``Act''). SUMMARY: Summary of Application: Rio Tinto plc (``RTP'') and Rio Tinto...

76 FR 25353 - Hikma Pharmaceuticals PLC; Analysis of Agreement Containing Consent Orders To Aid Public Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

... FEDERAL TRADE COMMISSION [File No. 111 0051] Hikma Pharmaceuticals PLC; Analysis of Agreement Containing Consent Orders To Aid Public Comment AGENCY: Federal Trade Commission. ACTION: Proposed consent... Pharmaceuticals PLC (``Hikma'') that is designed to remedy the anticompetitive effects of Hikma's acquisition of...

77 FR 56760 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-14

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... all Rolls-Royce plc (RR) RB211-Trent 800 series turbofan engines. This AD requires removing from...-17, 892-17, 892B-17, and 895-17 turbofan engines that have an intermediate pressure (IP) turbine disc...

77 FR 73268 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-10

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... certain Rolls-Royce plc (RR) RB211-Trent 900 series turbofan engines. This AD requires inspection of the... turbofan engines, all serial numbers. (d) Reason This AD was prompted by a Trent 900 engine experiencing a...

78 FR 23316 - The Royal Bank of Scotland plc, et al.; Notice of Application and Temporary Order

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-18

... SECURITIES AND EXCHANGE COMMISSION [Release No. IC-30462; 812-14148] The Royal Bank of Scotland... Bank of Scotland plc (``RBS plc''), Citizens Investment Advisors (``Citizens IA''), a separately... Management, Exemptive Applications Office). SUPPLEMENTARY INFORMATION: The following is a temporary order and...

Demonstration of Supervisory Control and Data Acquisition (SCADA) Virtualization Capability in the US Army Research Laboratory (ARL)/Sustaining Base Network Assurance Branch (SBNAB) US Army Cyber Analytics Laboratory (ACAL) SCADA Hardware Testbed

DTIC Science & Technology

2015-05-01

application ,1 while the simulated PLC software is the open source ModbusPal Java application . When queried using the Modbus TCP protocol, ModbusPal reports...and programmable logic controller ( PLC ) components. The HMI and PLC components were instantiated with software and installed in multiple virtual...creating and capturing HMI– PLC network traffic over a 24-h period in the virtualized network and inspect the packets for errors.  Test the

Mineral fiber-mediated activation of phosphoinositide-specific phospholipase c in human bronchoalveolar carcinoma-derived alveolar epithelial A549 cells.

PubMed

Loreto, Carla; Carnazza, Maria Luisa; Cardile, Venera; Libra, Massimo; Lombardo, Laura; Malaponte, Grazia; Martinez, Giuseppina; Musumeci, Giuseppe; Papa, Veronica; Cocco, Lucio

2009-02-01

Given the role of phosphoinositide-specific phospholipase C (PLC) isozymes in the control of cell growth and differentiation we were prompted to analyze the expression of some of these PLC in human bronchoalveolar carcinoma-derived alveolar epithelial A549 cells. The effects of several fluoro-edenite fibers were compared with those of tremolite, a member of the calcic amphibole group of asbestos that originates from Calabria (Italy), and crocidolite, that, due to its high toxicity, is one of the most studied asbestos amphiboles. Our data show an increased expression of both PLC beta1 and PLC gamma1 in A549 cells treated with asbestos-like fibers, hinting at a role of PLC signalling in those cancerous cells.

Regulation of Transient Receptor Potential channels by the phospholipase C pathway

PubMed Central

Rohacs, Tibor

2013-01-01

Transient Receptor Potential (TRP) channels were discovered while analyzing visual mutants in drosophila. The protein encoded by the transient receptor potential (trp) gene is a Ca2+ permeable cation channel activated downstream of the phospholipase C (PLC) pathway. While searching for homologues in other organisms, a surprisingly large number of mammalian TRP channels were cloned. The regulation of TRP channels is quite diverse, but many of them are either activated downstream of the PLC pathway, or modulated by it. This review will summarize the current knowledge on regulation of TRP channels by the PLC pathway, with special focus on TRPC-s, which can be considered as effectors of the PLC pathway, and the heat and capsaicin sensitive TRPV1, which is modulated by the PLC pathway in a complex manner. PMID:23916247

Stability and local toxicity evaluation of a liposomal prilocaine formulation.

PubMed

Cereda, Cintia M Saia; Tófoli, Giovana R; de Brito Junior, Rui B; de Jesus, Marcelo B; Fraceto, Leonardo F; Groppo, Francisco C; de Araujo, Daniele R; de Paula, Eneida

2008-01-01

This study reports a physicochemical stability evaluation of a previously reported liposomal prilocaine (PLC(LUV)) formulation (Cereda et al. J. Pharm. Pharmaceut. Sci. 7:235, 2004) before and after steam sterilization as well as its local toxicity evaluation. Prilocaine (PLC) was encapsulated into extruded unilamellar liposomes (LUVs) composed by egg phosphatidylcholine:cholesterol:alfa-tocopherol (4:3:0.07, mole %). Laser light-scattering analysis (p > 0.05) and thiobarbituric acid reaction (p > 0.05) were used to evaluate the liposomes physical (size) and chemical (oxidation) stability, respectively. The prilocaine chemical stability was followed by (1)H-nuclear magnetic resonance. These tests detected no differences on the physicochemical stability of PLC or PLC(LUV), sterilized or not, up to 30 days after preparation (p > 0.05). Finally, the paw edema test and histological analysis of rat oral mucosa were used to assess the possible inflammatory effects of PLC(LUV). PLC(LUV) did not evoke rat paw edema (p > 0.05), and no significant differences were found in histological analysis, when compared to the control groups (p > 0.05). The present work shows that PLC(LUV) is stable for a 30-day period and did not induce significant inflammatory effects both in the paw edema test and in histological analysis, giving supporting evidence for its safety and possible clinical use in dentistry.

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

Wolf, B.A.; Florholmen, J.; Turk, J.

Stimulation of intact islets with D-glucose, the major insulin secretagogue, or with carbachol, a muscarinic agonist, results in the accumulation of inositoltrisphosphate (IP/sub 3/) suggesting that activation of phospholipase C (PLC) has a major role in stimulus-secretion coupling. Carbachol activation of PLC is an example of receptor-mediated activation in islets, whereas, the mechanism of glucose activation of PLC is controversial since a glucose receptor has not been identified. They have measured PLC activity in digitonin-permeabilized islets. Islets were labeled with /sup 3/H-inositol, permeabilized and IP/sub 3/ accumulation measured by HPLC. Carbachol, in the presence of ATP, GTP and 1 ..mu..Mmore » free Ca/sup 2 +/ released two-fold more Ins 1,3,4-P/sub 3/ than control in a time-dependent manner. Glucose, under the same conditions also significantly released more Ins 1,3,4-P/sub 3/ than control. This effect was not due to metabolism of glucose nor to an effect on the IP/sub 3/-phosphomonoesterase. Preliminary Ca/sup 2 +/-dependency studies indicate that PLC is not activated by Ca/sup 2 +/ in the submicromolar range. In conclusion, these studies show that Ca/sup 2 +/ does not activate PLC, and furthermore, that D-glucose may be recognized directly by PLC.« less

The Study of the Impact of Professional Learning Communities and Student Achievement

ERIC Educational Resources Information Center

Phillips, Jori K.

2014-01-01

The purpose of this study was to determine if a difference existed between student learning, using the Missouri Assessment Program (MAP), and Professional Learning Community (PLC) implementation within fifth-grade populations in the state of Missouri. The following research questions were utilized to drive the research: What is the difference in…

76 FR 22148 - Petitions for Modification of Application of Existing Mandatory Safety Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-20

..., grounded phase, under-voltage, and ground monitoring protection; (b) the trailing cable short-circuit... activated; (c) the solenoid valves will be connected to the CO monitoring system through PLC programming... surface location, either the CO monitoring room or the security station. Either, two miners on each shift...

A Program Evaluation of a Professional Learning Community

ERIC Educational Resources Information Center

Lloyd, Tracy

2012-01-01

The No Child Left Behind (NCLB) legislation of 2001 increased the stakes for all schools to increase student achievement by mandating all students meet or exceed state standards by 2014. A small rural school responded 5 years ago to their failure to make adequate yearly progress (AYP) by implementing professional learning communities (PLC) as a…

Phospholipase C-{delta}{sub 1} regulates interleukin-1{beta} and tumor necrosis factor-{alpha} mRNA expression

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

Chung, Eric; Jakinovich, Paul; Bae, Aekyung

Phospholipase C-{delta}{sub 1} (PLC{delta}{sub 1}) is a widely expressed highly active PLC isoform, modulated by Ca{sup 2+} that appears to operate downstream from receptor signaling and has been linked to regulation of cytokine production. Here we investigated whether PLC{delta}{sub 1} modulated expression of the pro-inflammatory cytokines interleukin-1{beta} (IL-1{beta}), tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-6 (IL-6) in rat C6 glioma cells. Expression of PLC{delta}{sub 1} was specifically suppressed by small interfering RNA (siRNA) and the effects on cytokine mRNA expression, stimulated by the Toll-like receptor (TLR) agonist, lipopolysaccharide (LPS), were examined. Real-time polymerase chain reaction (RT-PCR) results showed that PLC{delta}{sub 1}more » knockdown enhanced expression IL-1{beta} and tumor necrosis factor-{alpha} (TNF-{alpha}) mRNA by at least 100 fold after 4 h of LPS stimulation compared to control siRNA treatment. PLC{delta}{sub 1} knock down caused persistently high Nf{kappa}b levels at 4 h of LPS stimulation compared to control siRNA-treated cells. PLC{delta}{sub 1} knockdown was also associated with elevated nuclear levels of c-Jun after 30 min of LPS stimulation, but did not affect LPS-stimulated p38 or p42/44 MAPK phosphorylation, normally associated with TLR activation of cytokine gene expression; rather, enhanced protein kinase C (PKC) phosphorylation of cellular proteins was observed in the absence of LPS stimulation. An inhibitor of PKC, bisindolylmaleimide II (BIM), reversed phosphorylation, prevented elevation of nuclear c-Jun levels, and inhibited LPS-induced increases of IL-1{beta} and TNF-{alpha} mRNA's induced by PLC{delta}{sub 1} knockdown. Our results show that loss of PLC{delta}{sub 1} enhances PKC/c-Jun signaling and up-modulates pro-inflammatory cytokine gene transcription in concert with the TLR-stimulated p38MAPK/Nf{kappa}b pathway. Our findings are consistent with the idea that PLC{delta}{sub 1} is a suppressor of PKC activity.« less

Plantaricyclin A, a Novel Circular Bacteriocin Produced by Lactobacillus plantarum NI326: Purification, Characterization, and Heterologous Production.

PubMed

Borrero, Juan; Kelly, Eoin; O'Connor, Paula M; Kelleher, Philip; Scully, Colm; Cotter, Paul D; Mahony, Jennifer; van Sinderen, Douwe

2018-01-01

Bacteriocins from lactic acid bacteria (LAB) are of increasing interest in recent years due to their potential as natural preservatives against food and beverage spoilage microorganisms. In a screening study for LAB, we isolated from olives a strain, Lactobacillus plantarum NI326, with activity against the beverage-spoilage bacterium Alicyclobacillus acidoterrestris Genome sequencing of NI326 enabled the identification of a gene cluster (designated plc ) encoding a putative circular bacteriocin and proteins involved in its modification, transport, and immunity. This novel bacteriocin, named plantaricyclin A (PlcA), was grouped into the circular bacteriocin subgroup II due to its high degree of similarity with other gassericin A-like bacteriocins. Purification of PlcA from the supernatant of Lb. plantarum NI326 resulted in an active peptide with a molecular mass of 5,570 Da, corresponding to that predicted from the (processed) PlcA amino acid sequence. The plc gene cluster was cloned and expressed in Lactococcus lactis NZ9000, resulting in the production of an active 5,570-Da bacteriocin in the supernatant. PlcA is believed to be produced as a 91-amino-acid precursor with a 33-amino-acid leader peptide, which is predicted to be removed, followed by joining of the N and C termini via a covalent linkage to form the mature 58-amino-acid circular bacteriocin PlcA. We report the characterization of a circular bacteriocin produced by Lb. plantarum The inhibition displayed against A. acidoterrestris highlights its potential use as a preservative in food and beverages. IMPORTANCE In this work, we describe the purification and characterization of an antimicrobial peptide, termed plantaricyclin A (PlcA), produced by a Lactobacillus plantarum strain isolated from olives. This peptide has a circular structure, and all genes involved in its production, circularization, and secretion were identified. PlcA shows antimicrobial activity against different strains, including Alicyclobacillus acidoterrestris , a common spoilage bacterium, which causes substantial economic losses in the beverage industry every year. In this study, we describe a circular antimicrobial peptide, PlcA, for a Lactobacillus plantarum strain. Copyright © 2017 American Society for Microbiology.

Plantaricyclin A, a Novel Circular Bacteriocin Produced by Lactobacillus plantarum NI326: Purification, Characterization, and Heterologous Production

PubMed Central

Borrero, Juan; Kelly, Eoin; O'Connor, Paula M.; Kelleher, Philip; Scully, Colm; Cotter, Paul D.; Mahony, Jennifer

2017-01-01

ABSTRACT Bacteriocins from lactic acid bacteria (LAB) are of increasing interest in recent years due to their potential as natural preservatives against food and beverage spoilage microorganisms. In a screening study for LAB, we isolated from olives a strain, Lactobacillus plantarum NI326, with activity against the beverage-spoilage bacterium Alicyclobacillus acidoterrestris. Genome sequencing of NI326 enabled the identification of a gene cluster (designated plc) encoding a putative circular bacteriocin and proteins involved in its modification, transport, and immunity. This novel bacteriocin, named plantaricyclin A (PlcA), was grouped into the circular bacteriocin subgroup II due to its high degree of similarity with other gassericin A-like bacteriocins. Purification of PlcA from the supernatant of Lb. plantarum NI326 resulted in an active peptide with a molecular mass of 5,570 Da, corresponding to that predicted from the (processed) PlcA amino acid sequence. The plc gene cluster was cloned and expressed in Lactococcus lactis NZ9000, resulting in the production of an active 5,570-Da bacteriocin in the supernatant. PlcA is believed to be produced as a 91-amino-acid precursor with a 33-amino-acid leader peptide, which is predicted to be removed, followed by joining of the N and C termini via a covalent linkage to form the mature 58-amino-acid circular bacteriocin PlcA. We report the characterization of a circular bacteriocin produced by Lb. plantarum. The inhibition displayed against A. acidoterrestris highlights its potential use as a preservative in food and beverages. IMPORTANCE In this work, we describe the purification and characterization of an antimicrobial peptide, termed plantaricyclin A (PlcA), produced by a Lactobacillus plantarum strain isolated from olives. This peptide has a circular structure, and all genes involved in its production, circularization, and secretion were identified. PlcA shows antimicrobial activity against different strains, including Alicyclobacillus acidoterrestris, a common spoilage bacterium, which causes substantial economic losses in the beverage industry every year. In this study, we describe a circular antimicrobial peptide, PlcA, for a Lactobacillus plantarum strain. PMID:29030449

Regulation of Drosophila transient receptor potential-like (TrpL) channels by phospholipase C-dependent mechanisms.

PubMed

Estacion, M; Sinkins, W G; Schilling, W P

2001-01-01

Patch clamp and fura-2 fluorescence were employed to characterize receptor-mediated activation of recombinant Drosophila TrpL channels expressed in Sf9 insect cells. TrpL was activated by receptor stimulation and by exogenous application of diacylglycerol (DAG) or poly-unsaturated fatty acids (PUFAs). Activation of TrpL was blocked more than 70% by U73122, suggesting that the effect of these agents was dependent upon phospholipase C (PLC). In fura-2 assays, extracellular application of bacterial phosphatidylinositol (PI)-PLC or phosphatidylcholine (PC)-PLC caused a transient increase in TrpL channel activity, the magnitude of which was significantly less than that observed following receptor stimulation. TrpL channels were also activated in excised inside-out patches by cytoplasmic application of mammalian PLC-b2, bacterial PI-PLC and PC-PLC, but not by phospholipase D (PLD). The phospholipases had little or no effect when examined in either whole-cell or cell-attached configurations.TrpL activity was inhibited by addition of phosphatidylinositol-4,5-bisphosphate (PIP2) to excised inside-out membrane patches exhibiting spontaneous channel activity or to patches pre-activated by treatment with PLC. The effect was reversible, specific for PIP2, and was not observed with phosphatidylethanolamine (PE), PI, PC or phosphatidylserine (PS). However, antibodies against PIP2 consistently failed to activate TrpL in inside-out patches. It is concluded that both the hydrolysis of PIP2 and the generation of DAG are required to rapidly activate TrpL following receptor stimulation, or that some other PLC-dependent mechanism plays a crucial role in the activation process.

Angiotensin II stimulates calcineurin activity in proximal tubule epithelia through AT-1 receptor-mediated tyrosine phosphorylation of the PLC-gamma1 isoform.

PubMed

Lea, Janice P; Jin, Shao G; Roberts, Brian R; Shuler, Michael S; Marrero, Mario B; Tumlin, James A

2002-07-01

Angiotensin II (AngII) contributes to the maintenance of extracellular fluid volume by regulating sodium transport in the nephron. In nonepithelial cells, activation of phospholipase C (PLC) by AT-1 receptors stimulates the generation of 1,4,5-trisphosphate (IP(3)) and the release of intracellular calcium. Calcineurin, a serine-threonine phosphatase, is activated by calcium and calmodulin, and both PLC and calcineurin have been linked to sodium transport in the proximal tubule. An examination of whether AngII activates calcineurin in a model of proximal tubule epithelia (LLC-PK1 cells) was performed; AngII increased calcineurin activity within 30 s. An examination of whether AngII activates PLC in proximal tubule epithelia was also performed after first showing that all three families of PLC isoforms are present in LLC-PK1 cells. Application of AngII increased IP(3) generation by 60% within 15 s, which coincided with AngII-induced tyrosine phosphorylation of the PLC-gamma1 isoform also observed at 15 s. AngII-induced tyrosine phosphorylation was blocked by the AT-1 receptor antagonist, Losartan. Subsequently, an inhibitor of tyrosine phosphorylation blocked the AngII-induced activation of calcineurin, as did coincubation with an inhibitor of PLC activity and with an antagonist of the AT-1 receptor. It is therefore concluded that AngII stimulates calcineurin phosphatase activity in proximal tubule epithelial cells through a mechanism involving AT-1 receptor-mediated tyrosine phosphorylation of the PLC isoform.

Real time control “es-dawet” mixer using dasboard based on PLC and WSN

NASA Astrophysics Data System (ADS)

Siagian, Pandapotan; Hutauruk, Sindak; Kisno

2017-09-01

The aim of this study is to monitor and acquire the remote parameters like Speed control a DC Motor, IR Sensor, Temperature of pasteurize mix of ice cream, and send these real values over wireless network. A proposed system is dashboard monitoring system for PLC based system wirelessly using ZigBee protocol. To implement this a ZigBee model is connected to a programmed digital signal controller which would transmit the data to Zigbee coordinator which is connected to a PC through RS232 serial communication. Person can need only to send the reply about the process that is to be carried out and PLC will check the status of the web base sent by person and take the action according to it where wired communication is either more expensive or impossible due to physical conditions. A low cost system for measured the parameters of motor such as IR Sensor, Speed control a DC Motor by PWM and temperature with Zigbee protocol connectivity. A database is built to execute monitoring and to save the motor parameters received by radio frequency (RF) data acquisition system. Experimental results show that the proposed system is less costly, provides higher accuracy as well as safe and gives visual environment.

Development of High School Professional Learning Community Leaders: Effectiveness of One District's Approach

ERIC Educational Resources Information Center

Middendorf, Beth N.

2013-01-01

Research indicated leadership played a key role in successfully implementing professional learning communities (PLCs). There has been little research on pragmatic approaches to developing PLC leaders. The purpose of this study was to examine the effectiveness of the Gene School District's two-part PLC leader development: PLC Institute and ongoing…

13 CFR 107.1530 - How a Licensee computes SBA's Profit Participation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... steps in paragraphs (e) through (g) of this section. (e) Compute the “PLC ratio”—(1) General rule. The “PLC ratio” is the highest ratio of outstanding Participating Securities to Leverageable Capital that... reduced PLC ratio as follows: (i) Divide the highest dollar amount of Participating Securities you have...

13 CFR 107.1530 - How a Licensee computes SBA's Profit Participation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... steps in paragraphs (e) through (g) of this section. (e) Compute the “PLC ratio”—(1) General rule. The “PLC ratio” is the highest ratio of outstanding Participating Securities to Leverageable Capital that... reduced PLC ratio as follows: (i) Divide the highest dollar amount of Participating Securities you have...

Peer Learning Community Guide. CEELO FastFact

ERIC Educational Resources Information Center

Schilder, Diane; Brown, Kirsty Clarke; Gillaspy, Kathi

2014-01-01

States and technical assistance centers have asked the Center on Enhancing Early Learning Outcomes (CEELO) for guidance on establishing and maintaining a peer learning community (PLC). This document is designed to delineate the steps to establish and sustain a Peer Learning Community (PLC). It begins with a definition of a PLC and then presents…

The Futility of PLC Lite

ERIC Educational Resources Information Center

DuFour, Rick; Reeves, Douglas

2016-01-01

Although many schools around the world have claimed to embrace the Professional Learning Community process, it would be more accurate to describe the current state of affairs in many schools as PLC Lite. Educators rename their traditional faculty or department meetings as PLC meetings, engage in book studies that result in no action, or devote…

A Case Study Examination of Best Practices of Professional Learning Communities

ERIC Educational Resources Information Center

Akopoff, Tanya M.

2010-01-01

A current trend in education is that small teacher groups, called professional learning communities (PLC), are being advocated as a tool to help teachers reach struggling students. Educators planning to use PLC as an intervention strategy can benefit from research-based information about PLC best practices. This multiple case study addressed the…

Professional Learning Communities: Teachers Working Collaboratively for Continuous Improvement

ERIC Educational Resources Information Center

Griffith, Louise Ann

2009-01-01

Current research indicates that a professional learning community (PLC) is an effective means for helping teachers to bridge the gap between research and practice. A PLC is a team of educators systematically working together to improve teaching practice and student learning. This study evaluated the PLC formed by teachers at a public elementary…

78 FR 17297 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-21

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... (AD) for all Rolls-Royce plc (RR) RB211 Trent 500 series turbofan engines. That AD currently requires... 9, 2012), for all RR RB211 Trent 500 series turbofan engines. That AD requires a one-time inspection...

78 FR 6749 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-31

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... (AD) for all Rolls-Royce plc (RR) models RB211 Trent 768-60, 772-60, and 772B-60 turbofan engines... 772B-60 turbofan engines. (d) Reason This AD was prompted by low-pressure (LP) compressor blade partial...

77 FR 32007 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-31

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... all Rolls-Royce plc (RR) RB211-Trent 800 series turbofan engines. This AD requires removal from...-17, 877- 17, 884-17, 884B-17, 892-17, 892B-17, and 895-17 turbofan engines. (d) Reason This AD was...

The Relationship between Professional Learning Community Implementation and Academic Achievement and Graduation Rates in Georgia High Schools

ERIC Educational Resources Information Center

Hardinger, Regina Gail

2013-01-01

Many educational administrators in Georgia continue to struggle with low student academic achievement and low high school graduation rates. DuFour's professional learning community (PLC) theory suggests a positive relationship between levels of PLC implementation and academic achievement and between levels of PLC implementation and graduation…

Promoting a Culture of Collaboration and Reflection through a Professional Learning Community

ERIC Educational Resources Information Center

Murdaugh, Erica Charlanda Russell

2017-01-01

The purpose of this qualitative Action Research Study was to describe eight elementary English Language Arts (ELA) teachers' perceptions of a Professional Learning Community (PLC). The teacher-participants' opinions about the PLC were used to improve the existing PLC to promote a more reflective and collaborative environment where ELA teachers…

Efficient Implementation of a Symbol Timing Estimator for Broadband PLC.

PubMed

Nombela, Francisco; García, Enrique; Mateos, Raúl; Hernández, Álvaro

2015-08-21

Broadband Power Line Communications (PLC) have taken advantage of the research advances in multi-carrier modulations to mitigate frequency selective fading, and their adoption opens up a myriad of applications in the field of sensory and automation systems, multimedia connectivity or smart spaces. Nonetheless, the use of these multi-carrier modulations, such as Wavelet-OFDM, requires a highly accurate symbol timing estimation for reliably recovering of transmitted data. Furthermore, the PLC channel presents some particularities that prevent the direct use of previous synchronization algorithms proposed in wireless communication systems. Therefore more research effort should be involved in the design and implementation of novel and robust synchronization algorithms for PLC, thus enabling real-time synchronization. This paper proposes a symbol timing estimator for broadband PLC based on cross-correlation with multilevel complementary sequences or Zadoff-Chu sequences and its efficient implementation in a FPGA; the obtained results show a 90% of success rate in symbol timing estimation for a certain PLC channel model and a reduced resource consumption for its implementation in a Xilinx Kyntex FPGA.

Separation of integrin-dependent adhesion from morphological changes based on differential PLC specificities.

PubMed

Wooten, D K; Teague, T K; McIntyre, B W

1999-01-01

In normal lymphocytes an inside-out signal up-regulating integrin adhesion is followed by a ligand-mediated outside-in cell spreading signal. Protein kinase C (PKC) inhibition blocks lymphocyte adherence to and spreading on fibronectin. In contrast, putative PLC inhibitors yield distinct differences with respect to adhesion and morphology. The phosphatidylinositol-specific phospholipase C (PLC) inhibitor neomycin blocked spreading of CD3/CD28-activated T cells on fibronectin by disrupting adhesion. Furthermore, when an additional inside-out signal for fibronectin adhesion is unnecessary such as with HPB-ALL T leukemic or phorbol-myristate-acetate-treated normal T cells, neomycin treatment does not alter adhesion or morphology. However, the phosphatidylcholine-specific PLC inhibitor D609 abrogates cell spreading without affecting adhesion to fibronectin in these cells as well as the CD3/CD28-activated T cells. These results strongly suggest that inside-out signaling for the integrin alpha4beta1 in lymphocytes proceeds through phosphatidylinositol-specific PLC and PKC, whereas the outside-in signal utilizes phosphatidylcholine-specific PLC and PKC.

Tamoxifen-loaded nanoparticles based on a novel mixture of biodegradable polyesters: characterization and in vitro evaluation as sustained release systems.

PubMed

Pérez, Elena; Benito, Marta; Teijón, César; Olmo, Rosa; Teijón, José M; Blanco, M Dolores

2012-01-01

Nanoparticles (NP) from mixtures of two poly(D,L-lactide-co-caprolactone) (PLC) copolymers, PLC 40/60 and PLC 86/14, with poly(D,L-lactide) (PDLLA) and PCL were prepared: PLC 40/60-PCL (25:75), PLC 86/14-PCL (75:25) and PLC 86/14-PLA (75:25). Tamoxifen was loaded with encapsulation efficiency between 65% and 75% (29.9-36.3 µg TMX/ mg NP). All selected systems showed spherical shape and nano-scale size. TMX-loaded NPs were in the range of 293-352 nm. TMX release from NP took place with different profiles depending on polymeric composition of the particles. After 60 days, 59.81% and 82.65% of the loaded drug was released. The cytotoxicity of unloaded NP in MCF7 and HeLa cells was very low. Cell uptake of NP took place in both cell types by unspecific internalization in a time dependent process. The administration of 6 and 10 µm TMX by TMX-loaded NP was effective on both cellular types, mainly in MCF7 cells.

Oncolytic Adenovirus Complexes Coated with Lipids and Calcium Phosphate for Cancer Gene Therapy.

PubMed

Chen, Jianhua; Gao, Pei; Yuan, Sujing; Li, Rongxin; Ni, Aimin; Chu, Liang; Ding, Li; Sun, Ying; Liu, Xin-Yuan; Duan, Yourong

2016-12-27

Oncolytic adenovirus (Onco Ad ) is a promising therapeutic agent for treating cancer. However, the therapeutic potential of Onco Ad is hindered by hepatic sequestration and the host immune response in vivo. Here, we constructed a PEG/Lipids/calcium phosphate (CaP)-Onco Ad (PLC-Onco Ad ) delivery system for ZD55-IL-24, an oncolytic adenovirus that carries the IL-24 gene. The negatively charged PLC-ZD55-IL-24 were disperse and resisted serum-induced aggregation. Compared to naked ZD55-IL-24, the systemic administration of PLC-ZD55-IL-24 in BALB/c mice resulted in reduced liver sequestration and systemic toxicity and evaded the innate immune response. In addition, masking the surface of Onco Ad protected it from neutralization by pre-existing neutralizing antibody. PLC-Onco Ad achieved efficient targeted delivery in Huh-7-bearing nude mice, and intravenous administration of a high dose of PLC-ZD55-IL-24 increased therapeutic efficacy without inducing toxicity. The developed PLC-Onco Ad delivery system represents a promising improvement for oncolytic adenovirus-based cancer gene therapy in vivo.

Akt interaction with PLC(gamma) regulates the G(2)/M transition triggered by FGF receptors from MDA-MB-231 breast cancer cells.

PubMed

Browaeys-Poly, Edith; Perdereau, Dominique; Lescuyer, Arlette; Burnol, Anne-Françoise; Cailliau, Katia

2009-12-01

Estrogen-independent breast cancer cell growth is under the control of fibroblast growth factors receptors (FGFRs), but the role of phospholipase C gamma (PLC(gamma)) and Akt, the downstream effectors activated by FGFRs, in cell proliferation is still unresolved. FGFRs from highly invasive MDA-MB-231 cells were expressed in Xenopus oocyte, a powerful model system to assess the G(2)/M checkpoint regulation. Under FGF1 stimulation, an analysis of the progression in the M-phase of the cell cycle and of the Akt signaling cascades were performed using the phosphatidylinositol-3-kinase inhibitor, LY294002, and a mimetic peptide of the SH3 domain of PLC(gamma). Activated Akt binds and phosphorylates PLC(gamma) before Akt targets the tumor suppressor Chfr. Disruption of the Akt-PLC(gamma) interaction directs Akt binding to Chfr and accelerates the alleviation of the G(2)/M checkpoint. The PLC(gamma)-Akt interaction, triggered by FGF receptors from estrogen-independent breast cancer cells MDA-MB-231, regulates progression in the M-phase of the cell cycle.

Improvement on the freeze-thaw stability of corn starch gel by the polysaccharide from leaves of Corchorus olitorius L.

PubMed

Yamazaki, Eiji; Sago, Toru; Kasubuchi, Yoshiaki; Imamura, Kazuhito; Matsuoka, Toshio; Kurita, Osamu; Nambu, Hironobu; Matsumura, Yasuki

2013-04-15

Effect of the polysaccharide from leaves of Corchorus olitorius L. (PLC) on the freeze-thaw (FT) stability of corn starch gel was studied. PLC was incorporated into the starch gel at 0.7% and total solid was adjusted to 6.0%. The syneresis was measured by the centrifugal-filtration method and, as a result, addition of PLC reduced effectively the syneresis of the starch gel even after 5 FT cycles, which was less than one third that of the normal starch gel. The rheological changes of the starch/PLC gel during the FT treatments were evaluated while the gel remained on the rheometer plate. The starch/PLC gel had less significant changes in the rheological parameters during the FT cycles than starch/guar gum or xanthan gum gel systems. SEM images showed that PLC stabilized the gel matrix surrounding pores, which would contribute to both a lower syneresis production and a higher stability in the rheological behavior at FT. Copyright © 2013 Elsevier Ltd. All rights reserved.

[The value of serum alpha-L-fucosidase activity in the diagnosis of primary liver cancer].

PubMed

Wei, X; Wang, S; Rui, J

2000-03-01

To analyse the value of serum alpha-L-fucosidase (AFU) in the diagnosis of primary liver cancer (PLC). Serum AFU was studied in 141 patients with PLC, 17 patients with secondary liver cancer, 16 patients with cirrhosis, and 30 controls. Rank correlation analysis was used to assess the relation between value of AFU activity and TNM staging. The results were compared to those of serum AFP determination. AFU was increased in 108 of 141 (76.6%) patients. The positive rate was statistically different from that in patients with secondary liver cancer, cirrhosis, and that in normal individual. The AFU level was correlated with TNM stage. In 25 PLC patients with AFU > 500 nmol.L-1.S-1, the average survival time was only 71 days. In 36 PLC patients who had received effective treatment, the serum AFU decreased to a significantly lower level than that examined before treatment. The positive rate of AFP in PLC patients was 64.5%. It rose to 86.2% if both parameters were used. AFU is a useful marker of PLC for diagnosis and posttreatment monitoring.

Automatisms in EMIR instrument to improve operation, safety and maintenance

NASA Astrophysics Data System (ADS)

Fernández Izquierdo, Patricia; Núñez Cagigal, Miguel; Barreto Rodríguez, Roberto; Martínez Rey, Noelia; Santana Tschudi, Samuel; Barreto Cabrera, Maria; Patrón Recio, Jesús; Garzón López, Francisco

2014-08-01

EMIR is the NIR imager and multiobject spectrograph being built as a common user instrument for the 10-m class GTC. Big cryogenic instruments demand a reliable design and a specific hardware and software to increase its safety and productivity. EMIR vacuum, cooling and heating systems are monitored and partially controlled by a Programmable Logic Controller (PLC) in industrial format with a touch screen. The PLC aids the instrument operator in the maintenance tasks recovering autonomously vacuum if required or proposing preventive maintenance actions. The PLC and its associated hardware improve EMIR safety having immediate reactions against eventual failure modes in the instrument or in external supplies, including hardware failures during the heating procedure or failure in the PLC itself. EMIR PLC provides detailed information periodically about status and alarms of vacuum and cooling components or external supplies.

Important role of PLC-γ1 in hypoxic increase in intracellular calcium in pulmonary arterial smooth muscle cells

PubMed Central

Yadav, Vishal R.; Song, Tengyao; Joseph, Leroy; Mei, Lin; Zheng, Yun-Min

2013-01-01

An increase in intracellular calcium concentration ([Ca2+]i) in pulmonary arterial smooth muscle cells (PASMCs) induces hypoxic cellular responses in the lungs; however, the underlying molecular mechanisms remain incompletely understood. We report, for the first time, that acute hypoxia significantly enhances phospholipase C (PLC) activity in mouse resistance pulmonary arteries (PAs), but not in mesenteric arteries. Western blot analysis and immunofluorescence staining reveal the expression of PLC-γ1 protein in PAs and PASMCs, respectively. The activity of PLC-γ1 is also augmented in PASMCs following hypoxia. Lentiviral shRNA-mediated gene knockdown of mitochondrial complex III Rieske iron-sulfur protein (RISP) to inhibit reactive oxygen species (ROS) production prevents hypoxia from increasing PLC-γ1 activity in PASMCs. Myxothiazol, a mitochondrial complex III inhibitor, reduces the hypoxic response as well. The PLC inhibitor U73122, but not its inactive analog U73433, attenuates the hypoxic vasoconstriction in PAs and hypoxic increase in [Ca2+]i in PASMCs. PLC-γ1 knockdown suppresses its protein expression and the hypoxic increase in [Ca2+]i. Hypoxia remarkably increases inositol 1,4,5-trisphosphate (IP3) production, which is blocked by U73122. The IP3 receptor (IP3R) antagonist 2-aminoethoxydiphenyl borate (2-APB) or xestospongin-C inhibits the hypoxic increase in [Ca2+]i. PLC-γ1 knockdown or U73122 reduces H2O2-induced increase in [Ca2+]i in PASMCs and contraction in PAs. 2-APB and xestospongin-C produce similar inhibitory effects. In conclusion, our findings provide novel evidence that hypoxia activates PLC-γ1 by increasing RISP-dependent mitochondrial ROS production in the complex III, which causes IP3 production, IP3R opening, and Ca2+ release, playing an important role in hypoxic Ca2+ and contractile responses in PASMCs. PMID:23204067

Injury of the posterior ligamentous complex of the thoracolumbar spine: a prospective evaluation of the diagnostic accuracy of magnetic resonance imaging.

PubMed

Vaccaro, Alexander R; Rihn, Jeffrey A; Saravanja, Davor; Anderson, David G; Hilibrand, Alan S; Albert, Todd J; Fehlings, Michael G; Morrison, William; Flanders, Adam E; France, John C; Arnold, Paul; Anderson, Paul A; Friel, Brian; Malfair, David; Street, John; Kwon, Brian; Paquette, Scott; Boyd, Michael; Dvorak, Marcel F S; Fisher, Charles

2009-11-01

Prospective diagnostic imaging study. To determine the accuracy of magnetic resonance imaging (MRI) in diagnosing injury of the posterior ligamentous complex (PLC) in patients with thoracolumbar trauma. Treatment decisions in thoracolumbar injury patients are currently based on the status of the PLC. It is, therefore, important to understand the accuracy of MRI in diagnosing varying degrees of PLC injury. Prior studies report that MRI is up to 100% sensitive for diagnosing PCL injury. Patients with an acute injury from T1 to L3 who required posterior surgery were prospectively studied. A musculoskeletal radiologist, based on the preoperative MRI findings, characterized each of the 6 components of the PLC as intact, incompletely disrupted, or disrupted. During the surgical procedure, the surgeon identified each component of the PLC as intact, incompletely disrupted, or disrupted. The radiologist's interpretation and surgical findings were compared. Forty-two patients with 62 levels of injury were studied. There were 33 males (78.6%) and 9 females (21.4%), and the average age was 35.7 years. According to the kappa score, there was a moderate level of agreement between the radiologist's interpretation and the intraoperative findings for all PLC components except the thoracolumbar fascia, for which there was slight agreement. The sensitivity for the various PLC components ranged from 79% (left facet capsule) to 90% (interspinous ligament). The specificity ranged from 53% (thoracolumbar fascia) to 65% (ligamentum flavum). There was less agreement between the radiologist and surgeon for the patients with less severe neurologic compromise, i.e., those patients with an AIS grade of either D or E. The sensitivity and specificity of MRI for diagnosing injury of the PLC are lower than previously reported in the literature. The integrity of the PLC as determined by MRI should not be used in isolation to determine treatment.

The influence of intraoperative pleural perfusion with matrine-cisplatin or cisplatin on stromal cell-derived factor-1 in non-small cell lung cancer patients with subclinical pleural metastasis.

PubMed

Yang, Cheng-Liang; Liu, Shun-Shou; Ma, Ye-Gang; Liu, Yong-Yu; Xue, Yi-Xue; Huang, Bo

2012-06-01

The early diagnosis and treatment of non-small cell lung cancer (NSCLC) in patients with subclinical pleural metastasis is currently a challenge. In an effort to establish a method for the diagnosis and treatment of these patients, we conducted a single-blind study during which intraoperative pleural lavage cytology (PLC) was performed in 164 patients with NSCLC without obvious pleural effusion. Stromal cell-derived factor-1 (SDF-1) serum concentrations were analyzed using enzyme-linked immunoassay on day 1 prior to tumor resection and on day 7 postoperatively. Western blot analysis was used for the detection of CXCR4 protein expression in resected tumors. Intraoperative pleural perfusion chemotherapy, with either cisplatin or cisplatin plus matrine, was given to patients with positive PLC. A group of 30 patients with NSCLC that did not undergo intraoperative PLC were used as a control group. Of the 164 study patients, 41 (25%) patients had positive PLC. Serum SDF-1 concentrations were higher in PLC-positive patients compared with patients negative for PLC and control patients. Serum SDF-1 concentrations were also lower at postoperative day 7 in patients treated with cisplatin plus matrine compared with control patients and those perfused with cisplatin alone. A lower incidence of chemotherapy-related adverse events was observed in patients treated with cisplatin plus matrine versus those treated with cisplatin alone during the first postoperative month. Patients with positive PLC showed a higher CXCR4 protein expression than patients with negative PLC. Based on the results of this study, PLC combined with serum SDF-1 concentration measurements may be considered as an effective index to determine the risk of subclinical pleural metastasis in patients with lung cancer. In addition, cisplatin plus matrine was confirmed as an initial approach for pleural perfusion and was superior to cisplatin alone.

Interrater reliability of identifying indicators of posterior ligamentous complex disruption when plain films are indeterminate in thoracolumbar injuries.

PubMed

Schweitzer, Karl M; Vaccaro, Alexander R; Harrop, James S; Hurlbert, John; Carrino, John A; Rechtine, Glenn R; Schwartz, David G; Alanay, Ahmet; Sharma, Dinesh K; Anderson, D Greg; Lee, Joon Y; Arnold, Paul M

2007-09-01

The Spine Trauma Study Group (STSG) has proposed a novel thoracolumbar injury classification system and score (TLICS) in an attempt to define traumatic spinal injuries and direct appropriate management schemes objectively. The TLICS assigns specific point values based on three variables to generate a final severity score that guides potential treatment options. Within this algorithm, significant emphasis has been placed on posterior ligamentous complex (PLC) integrity. The purpose of this study was to determine the interrater reliability of indicators surgeons use when assessing PLC disruption on imaging studies, including computed tomography (CT) and magnetic resonance imaging (MRI). Orthopedic surgeons and neurosurgeons retrospectively reviewed a series of thoracolumbar injury case studies. Thirteen case studies, including images, were distributed to STSG members for individual, independent evaluation of the following three criteria: (1) diastasis of the facet joints on CT; (2) posterior edema-like signal in the region of PLC components on sagittal T2-weighted fat saturation (FAT SAT) MRI; and (3) disrupted PLC components on sagittal T1-weighted MRI. Interrater agreement on the presence or absence of each of the three criteria in each of the 13 cases was assessed. Absolute interrater percent agreement on diastasis of the facet joints on CT and posterior edema-like signal in the region of PLC components on sagittal T2-weighted FAT SAT MRI was similar (agreement 70.5%). Interrater agreement on disrupted PLC components on sagittal T1-weighted MRI was 48.9%. Facet joint diastasis on CT was the most reliable indicator of PLC disruption as assessed by both Cohen's kappa (kappa = 0.395) and intraclass correlation coefficient (ICC 0.430). The interrater reliability of assessing diastasis of the facet joints on CT had fair to moderate agreement. The reliability of assessing the posterior edema-like signal in the region of PLC components was lower but also fair, whereas the reliability of identifying disrupted PLC components was poor.

Using Software Zelio Soft in Educational Process to Simulation Control Programs for Intelligent Relays

NASA Astrophysics Data System (ADS)

Michalik, Peter; Mital, Dusan; Zajac, Jozef; Brezikova, Katarina; Duplak, Jan; Hatala, Michal; Radchenko, Svetlana

2016-10-01

Article deals with point to using intelligent relay and PLC systems in practice, to their architecture and principles of programming and simulations for education process on all types of school from secondary to universities. Aim of the article is proposal of simple examples of applications, where is demonstrated methodology of programming on real simple practice examples and shown using of chosen instructions. In practical part is described process of creating schemas and describing of function blocks, where are described methodologies of creating program and simulations of output reactions on changeable inputs for intelligent relays.

The effect of a dynamic PCL brace on patellofemoral compartment pressures in PCL-and PCL/PLC-deficient knees.

PubMed

Welch, Tyler; Keller, Thomas; Maldonado, Ruben; Metzger, Melodie; Mohr, Karen; Kvitne, Ronald

2017-12-01

The natural history of posterior cruciate ligament (PCL) deficiency includes the development of arthrosis in the patellofemoral joint (PFJ). The purpose of this biomechanical study was to evaluate the hypothesis that dynamic bracing reduces PFJ pressures in PCL- and combined PCL/posterolateral corner (PLC)-deficient knees. Controlled Laboratory Study. Eight fresh frozen cadaveric knees with intact cruciate and collateral ligaments were included. PFJ pressures and force were measured using a pressure mapping system via a lateral arthrotomy at knee flexion angles of 30°, 60°, 90°, and 120° in intact, PCL-deficient, and PCL/PLC-deficient knees under a combined quadriceps/hamstrings load of 400 N/200 N. Testing was then repeated in PCL- and PCL/PLC-deficient knees after application of a dynamic PCL brace. Application of a dynamic PCL brace led to a reduction in peak PFJ pressures in PCL-deficient knees. In addition, the brace led to a significant reduction in peak pressures in PCL/PLC-deficient knees at 60°, 90°, and 120° of flexion. Application of the dynamic brace also led to a reduction in total PFJ force across all flexion angles for both PCL- and PCL/PLC-deficient knees. Dynamic bracing reduces PFJ pressures in PCL- and combined PCL/PLC-deficient knees, particularly at high degrees of knee flexion.

A rapid-acting, long-acting insulin formulation based on a phospholipid complex loaded PHBHHx nanoparticles.

PubMed

Peng, Qiang; Zhang, Zhi-Rong; Gong, Tao; Chen, Guo-Qiang; Sun, Xun

2012-02-01

The application of poly(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) for sustained and controlled delivery of hydrophilic insulin was made possible by preparing insulin phospholipid complex loaded biodegradable PHBHHx nanoparticles (INS-PLC-NPs). The INS-PLC-NPs produced by a solvent evaporation method showed a spherical shape with a mean particle size, zeta potential and entrapment efficiency of 186.2 nm, -38.4 mv and 89.73%, respectively. In vitro studies demonstrated that only 20% of insulin was released within 31 days with a burst release of 5.42% in the first 8 h. The hypoglycaemic effect in STZ induced diabetic rats lasted for more than 3 days after the subcutaneous injection of INS-PLC-NPs, which significantly prolonged the therapeutic effect compared with the administration of insulin solution. The pharmacological bioavailability (PA) of INS-PLC-NPs relative to insulin solution was over 350%, indicating that the bioavailability of insulin was significantly enhanced by INS-PLC-NPs. Therefore, the INS-PLC-NPs system is promising to serve as a long lasting insulin release formulation, by which the patient compliance can be enhanced significantly. This study also showed that phospholipid complex loaded biodegradable nanoparticles (PLC-NPs) have a great potential to be used as a sustained delivery system for hydrophilic proteins to be encapsulated in hydrophobic polymers. Copyright © 2011 Elsevier Ltd. All rights reserved.

Clinicopathological characteristics and survival outcomes in pleomorphic lobular breast carcinoma of the breast: a SEER population-based study.

PubMed

Yang, Li-Peng; Sun, He-Fen; Zhao, Yang; Chen, Meng-Ting; Zhang, Nong; Jin, Wei

2017-12-01

The purpose of this study was to explore the clinicopathological features and survival outcome of pleomorphic lobular carcinoma (PLC) of breast, we identified 131 PLC patients and 460,109 invasive ductal carcinoma (IDC) patients in the Surveillance, Epidemiology, and End Result (SEER) database. PLCs presented with increased lymph node involvement, older age, higher AJCC stage and grade, and lower median survival months (PLC 84 ± 51.03 vs. IDC 105.2 ± 64.39 P < 0.01). Compared to IDC patients, PLC patients were more inclined to be treated with mastectomy. In univariate analysis, PLC patients showed a worse disease-specific survival (DSS) than that of IDC patients (hazard ratio = 0.691, 95% confidence interval 0.534-0.893, P < 0.01). In multivariate analysis, we took into account other prognostic factors and found that the histology types were no longer an independent prognostic factor (P = 0.120). DSS have no difference between matched IDC and PLC groups (P = 0.615). This result may be due to PLCs presenting higher tumor stage, higher tumor grade, and higher rate of LN metastasis than IDCs. Our conclusion is that PLC and IDC have many different characteristics, but there is not enough difference on the DSS. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Insulin receptor-mediated signaling via phospholipase C-γ regulates growth and differentiation in Drosophila.

PubMed

Murillo-Maldonado, Juan M; Zeineddine, Fouad Bou; Stock, Rachel; Thackeray, Justin; Riesgo-Escovar, Juan R

2011-01-01

Coordination between growth and patterning/differentiation is critical if appropriate final organ structure and size is to be achieved. Understanding how these two processes are regulated is therefore a fundamental and as yet incompletely answered question. Here we show through genetic analysis that the phospholipase C-γ (PLC-γ) encoded by small wing (sl) acts as such a link between growth and patterning/differentiation by modulating some MAPK outputs once activated by the insulin pathway; particularly, sl promotes growth and suppresses ectopic differentiation in the developing eye and wing, allowing cells to attain a normal size and differentiate properly. sl mutants have previously been shown to have a combination of both growth and patterning/differentiation phenotypes: small wings, ectopic wing veins, and extra R7 photoreceptor cells. We show here that PLC-γ activated by the insulin pathway participates broadly and positively during cell growth modulating EGF pathway activity, whereas in cell differentiation PLC-γ activated by the insulin receptor negatively regulates the EGF pathway. These roles require different SH2 domains of PLC-γ, and act via classic PLC-γ signaling and EGF ligand processing. By means of PLC-γ, the insulin receptor therefore modulates differentiation as well as growth. Overall, our results provide evidence that PLC-γ acts during development at a time when growth ends and differentiation begins, and is important for proper coordination of these two processes.

77 FR 37740 - Stagecoach Group plc and Coach USA, Inc., et al.-Acquisition of Control of Assets-American Coach...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-22

... DEPARMENT OF TRANSPORATION Surface Transportation Board [Docket No. MCF 21045 \\1\\] Stagecoach Group plc and Coach USA, Inc., et al.--Acquisition of Control of Assets--American Coach Lines of Atlanta... Application. SUMMARY: On May 25, 2012, Stagecoach Group plc (Stagecoach), a noncarrier, and a number of its...

13 CFR 107.1530 - How a Licensee computes SBA's Profit Participation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... PLC ratio. (f) Compute the Profit Participation Rate (before indexing). Compute the Profit Participation Rate (before indexing) using the table in this paragraph (f). Then go to paragraph (g) of this... Profit Participation Rate is: 1 or less 9%×PLC Ratio. More than 1 9%+[3%×(PLC ratio-1)]. (g) Indexing the...

13 CFR 107.1530 - How a Licensee computes SBA's Profit Participation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... PLC ratio. (f) Compute the Profit Participation Rate (before indexing). Compute the Profit Participation Rate (before indexing) using the table in this paragraph (f). Then go to paragraph (g) of this... Profit Participation Rate is: 1 or less 9%×PLC Ratio. More than 1 9%+[3%×(PLC ratio-1)]. (g) Indexing the...

13 CFR 107.1530 - How a Licensee computes SBA's Profit Participation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... PLC ratio. (f) Compute the Profit Participation Rate (before indexing). Compute the Profit Participation Rate (before indexing) using the table in this paragraph (f). Then go to paragraph (g) of this... Profit Participation Rate is: 1 or less 9%×PLC Ratio. More than 1 9%+[3%×(PLC ratio-1)]. (g) Indexing the...

Troubleshooting of an Electromechanical System (Westinghouse PLC Controlling a Pneumatic Robot). High-Technology Training Module.

ERIC Educational Resources Information Center

Tucker, James D.

This training module on the troubleshooting of an electromechanical system, The Westinghouse Programmable Logic Controller (PLC) controlling a pneumatic robot, is used for a troubleshooting unit in an electromechanical systems/robotics and automation systems course. In this unit, students locate and repair a defect in a PLC-operated machine. The…

Dopamine suppresses neuronal activity of Helisoma B5 neurons via a D2-like receptor, activating PLC and K channels.

PubMed

Zhong, L R; Artinian, L; Rehder, V

2013-01-03

Dopamine (DA) plays fundamental roles as a neurotransmitter and neuromodulator in the central nervous system. How DA modulates the electrical excitability of individual neurons to elicit various behaviors is of great interest in many systems. The buccal ganglion of the freshwater pond snail Helisoma trivolvis contains the neuronal circuitry for feeding and DA is known to modulate the feeding motor program in Helisoma. The buccal neuron B5 participates in the control of gut contractile activity and is surrounded by dopaminergic processes, which are expected to release DA. In order to study whether DA modulates the electrical activity of individual B5 neurons, we performed experiments on physically isolated B5 neurons in culture and on B5 neurons within the buccal ganglion in situ. We report that DA application elicited a strong hyperpolarization in both conditions and turned the electrical activity from a spontaneously firing state to an electrically silent state. Using the cell culture system, we demonstrated that the strong hyperpolarization was inhibited by the D2 receptor antagonist sulpiride and the phospholipase C (PLC) inhibitor U73122, indicating that DA affected the membrane potential of B5 neurons through the activation of a D2-like receptor and PLC. Further studies revealed that the DA-induced hyperpolarization was inhibited by the K channel blockers 4-aminopyridine and tetraethylammonium, suggesting that K channels might serve as the ultimate target of DA signaling. Through its modulatory effect on the electrical activity of B5 neurons, the release of DA in vivo may contribute to a neuronal output that results in a variable feeding motor program. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Comprehensive Genomic Analysis and Expression Profiling of Phospholipase C Gene Family during Abiotic Stresses and Development in Rice

PubMed Central

Singh, Amarjeet; Kanwar, Poonam; Pandey, Amita; Tyagi, Akhilesh K.; Sopory, Sudhir K.; Kapoor, Sanjay; Pandey, Girdhar K.

2013-01-01

Background Phospholipase C (PLC) is one of the major lipid hydrolysing enzymes, implicated in lipid mediated signaling. PLCs have been found to play a significant role in abiotic stress triggered signaling and developmental processes in various plant species. Genome wide identification and expression analysis have been carried out for this gene family in Arabidopsis, yet not much has been accomplished in crop plant rice. Methodology/Principal Findings An exhaustive in-silico exploration of rice genome using various online databases and tools resulted in the identification of nine PLC encoding genes. Based on sequence, motif and phylogenetic analysis rice PLC gene family could be divided into phosphatidylinositol-specific PLCs (PI-PLCs) and phosphatidylcholine- PLCs (PC-PLC or NPC) classes with four and five members, respectively. A comparative analysis revealed that PLCs are conserved in Arabidopsis (dicots) and rice (monocot) at gene structure and protein level but they might have evolved through a separate evolutionary path. Transcript profiling using gene chip microarray and quantitative RT-PCR showed that most of the PLC members expressed significantly and differentially under abiotic stresses (salt, cold and drought) and during various developmental stages with condition/stage specific and overlapping expression. This finding suggested an important role of different rice PLC members in abiotic stress triggered signaling and plant development, which was also supported by the presence of relevant cis-regulatory elements in their promoters. Sub-cellular localization of few selected PLC members in Nicotiana benthamiana and onion epidermal cells has provided a clue about their site of action and functional behaviour. Conclusion/Significance The genome wide identification, structural and expression analysis and knowledge of sub-cellular localization of PLC gene family envisage the functional characterization of these genes in crop plants in near future. PMID:23638098

SS-mPEG chemical modification of recombinant phospholipase C for enhanced thermal stability and catalytic efficiency.

PubMed

Fang, Xian; Wang, Xueting; Li, Guiling; Zeng, Jun; Li, Jian; Liu, Jingwen

2018-05-01

PEGylation is one of the most promising and extensively studied strategies for improving the properties of proteins as well as enzymic physical and thermal stability. Phospholipase C, hydrolyzing the phospholipids offers tremendous applications in diverse fields. However, the poor thermal stability and higher cost of production have restricted its industrial application. This study focused on improving the stabilization of recombinant PLC by chemical modification with methoxypolyethylene glycol-Succinimidyl Succinate (SS-mPEG, MW 5000). PLC gene from isolate Bacillus cereus HSL3 was fused with SUMO, a novel small ubiquitin-related modifier expression vector and over expressed in Escherichia coli. The soluble fraction of SUMO-PLC reached 80% of the total recombinant protein. The enzyme exhibited maximum catalytic activity at 80 °C and was relatively thermostable at 40-70 °C. It showed extensive substrate specificity pattern and marked activity toward phosphatidylcholine, which made it a typical non-specific PLC for industrial purpose. SS-mPEG-PLC complex exhibited an enhanced thermal stability at 70-80 °C and the catalytic efficiency (K cat /K m ) had increased by 3.03 folds compared with free PLC. CD spectrum of SS-mPEG-PLC indicated a possible enzyme aggregation after chemical modification, which contributed to the higher thermostability of SS-mPEG-PLC. The increase of antiparallel β sheets in secondary structure also made it more stable than parallel β sheets. The presence of SS-mPEG chains on the enzyme molecule surface somewhat changed the binding rate of the substrates, leading to a significant improvement in catalytic efficiency. This study provided an insight into the addition of SS-mPEG for enhancing the industrial applications of phospholipase C at higher temperature. Copyright © 2018 Elsevier B.V. All rights reserved.

Signal-dependent Hydrolysis of Phosphatidylinositol 4,5-Bisphosphate without Activation of Phospholipase C

PubMed Central

Lev, Shaya; Katz, Ben; Tzarfaty, Vered; Minke, Baruch

2012-01-01

In Drosophila, a phospholipase C (PLC)-mediated signaling cascade, couples photo-excitation of rhodopsin to the opening of the transient receptor potential (TRP) and TRP-like (TRPL) channels. A lipid product of PLC, diacylglycerol (DAG), and its metabolites, polyunsaturated fatty acids (PUFAs) may function as second messengers of channel activation. However, how can one separate between the increase in putative second messengers, change in pH, and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) depletion when exploring the TRPL gating mechanism? To answer this question we co-expressed the TRPL channels together with the muscarinic (M1) receptor, enabling the openings of TRPL channels via G-protein activation of PLC. To dissect PLC activation of TRPL into its molecular components, we used a powerful method that reduced plasma membrane-associated PI(4,5)P2 in HEK cells within seconds without activating PLC. Upon the addition of a dimerizing drug, PI(4,5)P2 was selectively hydrolyzed in the cell membrane without producing DAG, inositol trisphosphate, or calcium signals. We show that PI(4,5)P2 is not an inhibitor of TRPL channel activation. PI(4,5)P2 hydrolysis combined with either acidification or application of DAG analogs failed to activate the channels, whereas PUFA did activate the channels. Moreover, a reduction in PI(4,5)P2 levels or inhibition of DAG lipase during PLC activity suppressed the PLC-activated TRPL current. This suggests that PI(4,5)P2 is a crucial substrate for PLC-mediated activation of the channels, whereas PUFA may function as the channel activator. Together, this study defines a narrow range of possible mechanisms for TRPL gating. PMID:22065576

Increases in intracellular calcium via activation of potentially multiple phospholipase C isozymes in mouse olfactory neurons

PubMed Central

Szebenyi, Steven A.; Ogura, Tatsuya; Sathyanesan, Aaron; AlMatrouk, Abdullah K.; Chang, Justin; Lin, Weihong

2014-01-01

Phospholipase C (PLC) and internal Ca2+ stores are involved in a variety of cellular functions. However, our understanding of PLC in mammalian olfactory sensory neurons (OSNs) is generally limited to its controversial role in odor transduction. Here we employed single-cell Ca2+ imaging and molecular approaches to investigate PLC-mediated Ca2+ responses and its isozyme gene transcript expression. We found that the pan-PLC activator m-3M3FBS (25 μM) induces intracellular Ca2+ increases in vast majority of isolated mouse OSNs tested. Both the response amplitude and percent responding cells depend on m-3M3FBS concentrations. In contrast, the inactive analog o-3M3FBS fails to induce Ca2+ responses. The m-3M3FBS-induced Ca2+ increase is blocked by the PLC inhibitor U73122, while its inactive analog U73433 has no effect. Removal of extracellular Ca2+ does not change significantly the m-3M3FBS-induced Ca2+ response amplitude. Additionally, in the absence of external Ca2+, we found that a subset of OSNs respond to an odorant mixture with small Ca2+ increases, which are significantly suppressed by U73122. Furthermore, using reverse transcription polymerase chain reaction and real-time quantitative polymerase chain reaction, we found that multiple PLC isozyme gene transcripts are expressed in olfactory turbinate tissue in various levels. Using RNA in situ hybridization analysis, we further show expression of β4, γ1, γ2 gene transcripts in OSNs. Taken together, our results establish that PLC isozymes are potent enzymes for mobilizing intracellular Ca2+ in mouse OSNs and provide molecular insight for PLC isozymes-mediated complex cell signaling and regulation in the peripheral olfactory epithelium. PMID:25374507

Characteristic proteins in the plasma of postoperative colorectal and liver cancer patients with Yin deficiency of liver-kidney syndrome

PubMed Central

Ji, Qing; Wang, Wenhai; Luo, Yunquan; Cai, Feifei; Lu, Yiyu; Deng, Wanli; Li, Qi; Su, Shibing

2017-01-01

Systems biology and bioinformatics provide the feasibility for the basic research associated with “same traditional Chinese medicine (TCM) syndrome in different diseases”. In this study, the plasma proteins in postoperative colorectal (PCC) and postoperative liver cancer (PLC) patients with YDLKS (Yin deficiency of liver-kidney syndrome) were screened out using iTRAQ combined with LC-MS/MS technology. The results demonstrated that, KNG1, AMBP, SERPING1, etc, were all differentially expressed in both PCC and PLC patients with YDLKS, and associated closely with complement and coagulation cascades pathway. C7 and C2 were another two representative factors involving in former pathway. Further validation showed that, the C7 levels were increased significantly in PLC (P < 0.05) and PCC (P < 0.05) with YDLKS group compared to those of NS (no obvious TCM syndromes) group. The AMBP levels were down-regulated significantly in PLC with YDLKS group compared to those of PCC with YDLKS group (P < 0.05). The significant differences of SERPING1 levels (and C2 levels) were shown between YDLKS and NS in PCC (P < 0.01). There were also significant differences of C2 levels between PCC and PLC patients with YDLKS (P < 0.05). Moreover, significant differences of C2 levels were also found between PLC and PCC patients with YDLKS (P < 0.01). ROC curves indicated that, C7 and SERPING1 independently had a potential diagnostic value in distinguishing YDLKS from NS in PLC and PCC, providing the evidences for the material basis of “same TCM syndrome in different diseases” in PCC and PLC patients with YDLKS. PMID:29262557

Effects of propionyl-L-carnitine on ischemia-reperfusion injury in hamster cheek pouch microcirculation.

PubMed

Lapi, Dominga; Sabatino, Lina; Altobelli, Giovanna Giuseppina; Mondola, Paolo; Cimini, Vincenzo; Colantuoni, Antonio

2010-01-01

Propionyl-l-carnitine (pLc) exerts protective effects in different experimental models of ischemia-reperfusion (I/R). The aim of the present study was to assess the effects of intravenously and topically applied pLc on microvascular permeability increase induced by I/R in the hamster cheek pouch preparation. The hamster cheek pouch microcirculation was visualized by fluorescence microscopy. Microvascular permeability, leukocyte adhesion to venular walls, perfused capillary length, and capillary red blood cell velocity (V(RBC)) were evaluated by computer-assisted methods. E-selectin expression was assessed by in vitro analysis. Lipid peroxidation and reactive oxygen species (ROS) formation were determined by thiobarbituric acid-reactive substances (TBARS) and 2'-7'-dichlorofluorescein (DCF), respectively. In control animals, I/R caused a significant increase in permeability and in the leukocyte adhesion in venules. Capillary perfusion and V(RBC) decreased. TBARS levels and DCF fluorescence significantly increased compared with baseline. Intravenously infused pLc dose-dependently prevented leakage and leukocyte adhesion, preserved capillary perfusion, and induced vasodilation at the end of reperfusion, while ROS concentration decreased. Inhibition of nitric oxide synthase prior to pLc caused vasoconstriction and partially blunted the pLc-induced protective effects; inhibition of the endothelium-derived hyperpolarizing factor (EDHF) abolished pLc effects. Topical application of pLc on cheek pouch membrane produced the same effects as observed with intravenous administration. pLc decreased the E-selectin expression. pLc prevents microvascular changes induced by I/R injury. The reduction of permeability increase could be mainly due to EDHF release induce vasodilatation together with NO. The reduction of E-selectin expression prevents leukocyte adhesion and permeability increase.

Signal-dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate without activation of phospholipase C: implications on gating of Drosophila TRPL (transient receptor potential-like) channel.

PubMed

Lev, Shaya; Katz, Ben; Tzarfaty, Vered; Minke, Baruch

2012-01-06

In Drosophila, a phospholipase C (PLC)-mediated signaling cascade, couples photo-excitation of rhodopsin to the opening of the transient receptor potential (TRP) and TRP-like (TRPL) channels. A lipid product of PLC, diacylglycerol (DAG), and its metabolites, polyunsaturated fatty acids (PUFAs) may function as second messengers of channel activation. However, how can one separate between the increase in putative second messengers, change in pH, and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) depletion when exploring the TRPL gating mechanism? To answer this question we co-expressed the TRPL channels together with the muscarinic (M1) receptor, enabling the openings of TRPL channels via G-protein activation of PLC. To dissect PLC activation of TRPL into its molecular components, we used a powerful method that reduced plasma membrane-associated PI(4,5)P(2) in HEK cells within seconds without activating PLC. Upon the addition of a dimerizing drug, PI(4,5)P(2) was selectively hydrolyzed in the cell membrane without producing DAG, inositol trisphosphate, or calcium signals. We show that PI(4,5)P(2) is not an inhibitor of TRPL channel activation. PI(4,5)P(2) hydrolysis combined with either acidification or application of DAG analogs failed to activate the channels, whereas PUFA did activate the channels. Moreover, a reduction in PI(4,5)P(2) levels or inhibition of DAG lipase during PLC activity suppressed the PLC-activated TRPL current. This suggests that PI(4,5)P(2) is a crucial substrate for PLC-mediated activation of the channels, whereas PUFA may function as the channel activator. Together, this study defines a narrow range of possible mechanisms for TRPL gating.

Comprehensive genomic analysis and expression profiling of phospholipase C gene family during abiotic stresses and development in rice.

PubMed

Singh, Amarjeet; Kanwar, Poonam; Pandey, Amita; Tyagi, Akhilesh K; Sopory, Sudhir K; Kapoor, Sanjay; Pandey, Girdhar K

2013-01-01

Phospholipase C (PLC) is one of the major lipid hydrolysing enzymes, implicated in lipid mediated signaling. PLCs have been found to play a significant role in abiotic stress triggered signaling and developmental processes in various plant species. Genome wide identification and expression analysis have been carried out for this gene family in Arabidopsis, yet not much has been accomplished in crop plant rice. An exhaustive in-silico exploration of rice genome using various online databases and tools resulted in the identification of nine PLC encoding genes. Based on sequence, motif and phylogenetic analysis rice PLC gene family could be divided into phosphatidylinositol-specific PLCs (PI-PLCs) and phosphatidylcholine- PLCs (PC-PLC or NPC) classes with four and five members, respectively. A comparative analysis revealed that PLCs are conserved in Arabidopsis (dicots) and rice (monocot) at gene structure and protein level but they might have evolved through a separate evolutionary path. Transcript profiling using gene chip microarray and quantitative RT-PCR showed that most of the PLC members expressed significantly and differentially under abiotic stresses (salt, cold and drought) and during various developmental stages with condition/stage specific and overlapping expression. This finding suggested an important role of different rice PLC members in abiotic stress triggered signaling and plant development, which was also supported by the presence of relevant cis-regulatory elements in their promoters. Sub-cellular localization of few selected PLC members in Nicotiana benthamiana and onion epidermal cells has provided a clue about their site of action and functional behaviour. The genome wide identification, structural and expression analysis and knowledge of sub-cellular localization of PLC gene family envisage the functional characterization of these genes in crop plants in near future.

Characteristic proteins in the plasma of postoperative colorectal and liver cancer patients with Yin deficiency of liver-kidney syndrome.

PubMed

Ji, Qing; Wang, Wenhai; Luo, Yunquan; Cai, Feifei; Lu, Yiyu; Deng, Wanli; Li, Qi; Su, Shibing

2017-11-28

Systems biology and bioinformatics provide the feasibility for the basic research associated with "same traditional Chinese medicine (TCM) syndrome in different diseases". In this study, the plasma proteins in postoperative colorectal (PCC) and postoperative liver cancer (PLC) patients with YDLKS (Yin deficiency of liver-kidney syndrome) were screened out using iTRAQ combined with LC-MS/MS technology. The results demonstrated that, KNG1, AMBP, SERPING1, etc, were all differentially expressed in both PCC and PLC patients with YDLKS, and associated closely with complement and coagulation cascades pathway. C7 and C2 were another two representative factors involving in former pathway. Further validation showed that, the C7 levels were increased significantly in PLC ( P < 0.05) and PCC ( P < 0.05) with YDLKS group compared to those of NS (no obvious TCM syndromes) group. The AMBP levels were down-regulated significantly in PLC with YDLKS group compared to those of PCC with YDLKS group ( P < 0.05). The significant differences of SERPING1 levels (and C2 levels) were shown between YDLKS and NS in PCC ( P < 0.01). There were also significant differences of C2 levels between PCC and PLC patients with YDLKS ( P < 0.05). Moreover, significant differences of C2 levels were also found between PLC and PCC patients with YDLKS ( P < 0.01). ROC curves indicated that, C7 and SERPING1 independently had a potential diagnostic value in distinguishing YDLKS from NS in PLC and PCC, providing the evidences for the material basis of "same TCM syndrome in different diseases" in PCC and PLC patients with YDLKS.

Effects of Propionyl-L-Carnitine on Ischemia–Reperfusion Injury in Hamster Cheek Pouch Microcirculation

PubMed Central

Lapi, Dominga; Sabatino, Lina; Altobelli, Giovanna Giuseppina; Mondola, Paolo; Cimini, Vincenzo; Colantuoni, Antonio

2010-01-01

Background and purpose Propionyl-l-carnitine (pLc) exerts protective effects in different experimental models of ischemia–reperfusion (I/R). The aim of the present study was to assess the effects of intravenously and topically applied pLc on microvascular permeability increase induced by I/R in the hamster cheek pouch preparation. Methods The hamster cheek pouch microcirculation was visualized by fluorescence microscopy. Microvascular permeability, leukocyte adhesion to venular walls, perfused capillary length, and capillary red blood cell velocity (VRBC) were evaluated by computer-assisted methods. E-selectin expression was assessed by in vitro analysis. Lipid peroxidation and reactive oxygen species (ROS) formation were determined by thiobarbituric acid-reactive substances (TBARS) and 2′-7′-dichlorofluorescein (DCF), respectively. Results In control animals, I/R caused a significant increase in permeability and in the leukocyte adhesion in venules. Capillary perfusion and VRBC decreased. TBARS levels and DCF fluorescence significantly increased compared with baseline. Intravenously infused pLc dose-dependently prevented leakage and leukocyte adhesion, preserved capillary perfusion, and induced vasodilation at the end of reperfusion, while ROS concentration decreased. Inhibition of nitric oxide synthase prior to pLc caused vasoconstriction and partially blunted the pLc-induced protective effects; inhibition of the endothelium-derived hyperpolarizing factor (EDHF) abolished pLc effects. Topical application of pLc on cheek pouch membrane produced the same effects as observed with intravenous administration. pLc decreased the E-selectin expression. Conclusions pLc prevents microvascular changes induced by I/R injury. The reduction of permeability increase could be mainly due to EDHF release induce vasodilatation together with NO. The reduction of E-selectin expression prevents leukocyte adhesion and permeability increase. PMID:21423374

Improving immunization of programmable logic controllers using weighted median filters.

PubMed

Paredes, José L; Díaz, Dhionel

2005-04-01

This paper addresses the problem of improving immunization of programmable logic controllers (PLC's) to electromagnetic interference with impulsive characteristics. A filtering structure, based on weighted median filters, that does not require additional hardware and can be implemented in legacy PLC's is proposed. The filtering operation is implemented in the binary domain and removes the impulsive noise presented in the discrete input adding thus robustness to PLC's. By modifying the sampling clock structure, two variants of the filter are obtained. Both structures exploit the cyclic nature of the PLC to form an N-sample observation window of the discrete input, hence a status change on it is determined by the filter output taking into account all the N samples avoiding thus that a single impulse affects the PLC functionality. A comparative study, based on a statistical analysis, of the different filters' performances is presented.

Boron nitride nanotube reinforced polylactide-polycaprolactone copolymer composite: mechanical properties and cytocompatibility with osteoblasts and macrophages in vitro.

PubMed

Lahiri, Debrupa; Rouzaud, Francois; Richard, Tanisha; Keshri, Anup K; Bakshi, Srinivasa R; Kos, Lidia; Agarwal, Arvind

2010-09-01

Biodegradable polylactide-polycaprolactone copolymer (PLC) has been reinforced with 0, 2 and 5wt.% boron nitride nanotubes (BNNTs) for orthopedic scaffold application. Elastic modulus of the PLC-5wt.% BNNT composite, evaluated through nanoindentation technique, shows a 1370% increase. The same amount of BNNT addition to PLC enhances the tensile strength by 109%, without any adverse effect on the ductility up to 240% elongation. Interactions of the osteoblasts and macrophages with bare BNNTs prove them to be non-cytotoxic. PLC-BNNT composites displayed increased osteoblast cell viability as compared to the PLC matrix. The addition of BNNTs also resulted in an increase in the expression levels of the Runx2 gene, the main regulator of osteoblast differentiation. These results indicate that BNNT is a potential reinforcement for composites for orthopedic applications. 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

PLAT: An Automated Fault and Behavioural Anomaly Detection Tool for PLC Controlled Manufacturing Systems.

PubMed

Ghosh, Arup; Qin, Shiming; Lee, Jooyeoun; Wang, Gi-Nam

2016-01-01

Operational faults and behavioural anomalies associated with PLC control processes take place often in a manufacturing system. Real time identification of these operational faults and behavioural anomalies is necessary in the manufacturing industry. In this paper, we present an automated tool, called PLC Log-Data Analysis Tool (PLAT) that can detect them by using log-data records of the PLC signals. PLAT automatically creates a nominal model of the PLC control process and employs a novel hash table based indexing and searching scheme to satisfy those purposes. Our experiments show that PLAT is significantly fast, provides real time identification of operational faults and behavioural anomalies, and can execute within a small memory footprint. In addition, PLAT can easily handle a large manufacturing system with a reasonable computing configuration and can be installed in parallel to the data logging system to identify operational faults and behavioural anomalies effectively.

PLAT: An Automated Fault and Behavioural Anomaly Detection Tool for PLC Controlled Manufacturing Systems

PubMed Central

Ghosh, Arup; Qin, Shiming; Lee, Jooyeoun

2016-01-01

Operational faults and behavioural anomalies associated with PLC control processes take place often in a manufacturing system. Real time identification of these operational faults and behavioural anomalies is necessary in the manufacturing industry. In this paper, we present an automated tool, called PLC Log-Data Analysis Tool (PLAT) that can detect them by using log-data records of the PLC signals. PLAT automatically creates a nominal model of the PLC control process and employs a novel hash table based indexing and searching scheme to satisfy those purposes. Our experiments show that PLAT is significantly fast, provides real time identification of operational faults and behavioural anomalies, and can execute within a small memory footprint. In addition, PLAT can easily handle a large manufacturing system with a reasonable computing configuration and can be installed in parallel to the data logging system to identify operational faults and behavioural anomalies effectively. PMID:27974882

The Portevin–Le Chatelier effect: a review of experimental findings

PubMed Central

Yilmaz, Ahmet

2011-01-01

The Portevin–Le Chatelier (PLC) effect manifests itself as an unstable plastic flow during tensile tests of some dilute alloys under certain regimes of strain rate and temperature. The plastic strain becomes localized in the form of bands which move along a specimen gauge in various ways as the PLC effect occurs. Because the localization of strain causes degradation of the inherent structural properties and surface quality of materials, understanding the effect is crucial for the effective use of alloys. The characteristic behaviors of localized strain bands and techniques commonly used to study the PLC effect are summarized in this review. A brief overview of experimental findings, the effect of material properties and test parameters on the PLC effect, and some discussion on the mechanisms of the effect are included. Tests for predicting the early failure of structural materials due to embrittlement induced by the PLC effect are also discussed. PMID:27877450

Two-Dimensional Planar Lightwave Circuit Integrated Spatial Filter Array and Method of Use Thereof

NASA Technical Reports Server (NTRS)

Dimov, Fedor (Inventor); Ai, Jun (Inventor)

2015-01-01

A large coherent two-dimensional (2D) spatial filter array (SFA), 30 by 30 or larger, is produced by coupling a 2D planar lightwave circuit (PLC) array with a pair of lenslet arrays at the input and output side. The 2D PLC array is produced by stacking a plurality of chips, each chip with a plural number of straight PLC waveguides. A pupil array is coated onto the focal plane of the lenslet array. The PLC waveguides are produced by deposition of a plural number of silica layers on the silicon wafer, followed by photolithography and reactive ion etching (RIE) processes. A plural number of mode filters are included in the silica-on-silicon waveguide such that the PLC waveguide is transparent to the fundamental mode but higher order modes are attenuated by 40 dB or more.

Regulation of PLCβ2 by the electrostatic and mechanical properties of lipid bilayers

PubMed Central

Arduin, Alessia; Gaffney, Piers R. J.; Ces, Oscar

2015-01-01

Phosphoinositide-specific phospholipase C (PLC) is an important family of enzymes constituting a junction between phosphoinositide lipid signaling and the trans-membrane signal transduction processes that are crucial to many living cells. However, the regulatory mechanism of PLC is not yet understood in detail. To address this issue, activity studies were carried out using lipid vesicles in a model system that was specifically designed to study protein-protein and lipid-protein interactions in concert. Evidence was found for a direct interaction between PLC and the GTPases that mediate phospholipase activation. Furthermore, for the first time, the relationships between PLC activity and substrate presentation in lipid vesicles of various sizes, as well as lipid composition and membrane mechanical properties, were analyzed. PLC activity was found to depend upon the electrostatic potential and the stored curvature elastic stress of the lipid membranes. PMID:26243281

76 FR 14797 - Airworthiness Directives; Rolls-Royce plc (RR) RB211-Trent 900 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-18

.... Relevant Service Information Rolls-Royce plc has issued Trent 900 Series Propulsion Systems Alert Service... incorporating software 10.6 can be found in Rolls-Royce plc Trent 900 Series Propulsion Systems Alert Service... Propulsion Systems Alert SB No. RB.211-73-AG639, dated December 3, 2010, for related information. (i) Contact...

77 FR 75831 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-26

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... certain serial numbers (S/Ns) of Rolls-Royce plc (RR) RB211-Trent 768-60, 772- 60, and 772B-60 turbofan... use any of the RB211-Trent 768-60, 772-60, and 772B-60 turbofan engines listed by S/N in this AD...

75 FR 15326 - Airworthiness Directives; Rolls-Royce plc RB211-Trent 500, 700, and 800 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-29

... Airworthiness Directives; Rolls-Royce plc RB211-Trent 500, 700, and 800 Series Turbofan Engines AGENCY: Federal... the final stages of approach. The investigation of the incident has established that, under certain...), with a proposed AD. The proposed AD applies to Rolls-Royce plc RB211-Trent 500, 700, and 800 series...

Multiple receptors coupled to phospholipase C gate long-term depression in visual cortex.

PubMed

Choi, Se-Young; Chang, Jeff; Jiang, Bin; Seol, Geun-Hee; Min, Sun-Seek; Han, Jung-Soo; Shin, Hee-Sup; Gallagher, Michela; Kirkwood, Alfredo

2005-12-07

Long-term depression (LTD) in sensory cortices depends on the activation of NMDA receptors. Here, we report that in visual cortical slices, the induction of LTD (but not long-term potentiation) also requires the activation of receptors coupled to the phospholipase C (PLC) pathway. Using immunolesions in combination with agonists and antagonists, we selectively manipulated the activation of alpha1 adrenergic, M1 muscarinic, and mGluR5 glutamatergic receptors. Inactivation of these PLC-coupled receptors prevents the induction of LTD, but only when the three receptors were inactivated together. LTD is fully restored by activating any one of them or by supplying intracellular D-myo-inositol-1,4,5-triphosphate (IP3). LTD was also impaired by intracellular application of PLC or IP3 receptor blockers, and it was absent in mice lacking PLCbeta1, the predominant PLC isoform in the forebrain. We propose that visual cortical LTD requires a minimum of PLC activity that can be supplied independently by at least three neurotransmitter systems. This essential requirement places PLC-linked receptors in a unique position to control the induction of LTD and provides a mechanism for gating visual cortical plasticity via extra-retinal inputs in the intact organism.

Phosphoinositide-3-Kinase Is the Primary Mediator of Phosphoinositide-Dependent Inhibition in Mammalian Olfactory Receptor Neurons

PubMed Central

Ukhanov, Kirill; Corey, Elizabeth; Ache, Barry W.

2016-01-01

Odorants inhibit as well as excite primary olfactory receptor neurons (ORNs) in many animal species. Growing evidence suggests that inhibition of mammalian ORNs is mediated by phosphoinositide (PI) signaling through activation of phosphoinositide 3-kinase (PI3K), and that canonical adenylyl cyclase III signaling and PI3K signaling interact to provide the basis for ligand-induced selective signaling. As PI3K is known to act in concert with phospholipase C (PLC) in some cellular systems, the question arises as to whether they work together to mediate inhibitory transduction in mammalian ORNs. The present study is designed to test this hypothesis. While we establish that multiple PLC isoforms are expressed in the transduction zone of rat ORNs, that odorants can activate PLC in ORNs in situ, and that pharmacological blockade of PLC enhances the excitatory response to an odorant mixture in some ORNs in conjunction with PI3K blockade, we find that by itself PLC does not account for an inhibitory response. We conclude that PLC does not make a measurable independent contribution to odor-evoked inhibition, and that PI3K is the primary mediator of PI-dependent inhibition in mammalian ORNs. PMID:27147969

Absorptive capacity, technological innovation, and product life cycle: a system dynamics model.

PubMed

Zou, Bo; Guo, Feng; Guo, Jinyu

2016-01-01

While past research has recognized the importance of the dynamic nature of absorptive capacity, there is limited knowledge on how to generate a fair and comprehensive analytical framework. Based on interviews with 24 Chinese firms, this study develops a system-dynamics model that incorporates an important feedback loop among absorptive capacity, technological innovation, and product life cycle (PLC). The simulation results reveal that (1) PLC affects the dynamic process of absorptive capacity; (2) the absorptive capacity of a firm peaks in the growth stage of PLC, and (3) the market demand at different PLC stages is the main driving force in firms' technological innovations. This study also explores a sensitivity simulation using the variables of (1) time spent in founding an external knowledge network, (2) research and development period, and (3) knowledge diversity. The sensitivity simulation results show that the changes of these three variables have a greater impact on absorptive capacity and technological innovation during growth and maturity stages than in the introduction and declining stages of PLC. We provide suggestions on how firms can adjust management policies to improve their absorptive capacity and technological innovation performance during different PLC stages.

Revisiting the role of phospholipases C in virulence and the lifecycle of Mycobacterium tuberculosis

PubMed Central

Le Chevalier, Fabien; Cascioferro, Alessandro; Frigui, Wafa; Pawlik, Alexandre; Boritsch, Eva C.; Bottai, Daria; Majlessi, Laleh; Herrmann, Jean Louis; Brosch, Roland

2015-01-01

Mycobacterium tuberculosis, the agent of human tuberculosis has developed different virulence mechanisms and virulence-associated tools during its evolution to survive and multiply inside the host. Based on previous reports and by analogy with other bacteria, phospholipases C (PLC) of M. tuberculosis were thought to be among these tools. To get deeper insights into the function of PLCs, we investigated their putative involvement in the intracellular lifestyle of M. tuberculosis, with emphasis on phagosomal rupture and virulence, thereby re-visiting a research theme of longstanding interest. Through the construction and use of an M. tuberculosis H37Rv PLC-null mutant (ΔPLC) and control strains, we found that PLCs of M. tuberculosis were not required for induction of phagosomal rupture and only showed marginal, if any, impact on virulence of M. tuberculosis in the cellular and mouse infection models used in this study. In contrast, we found that PLC-encoding genes were strongly upregulated under phosphate starvation and that PLC-proficient M. tuberculosis strains survived better than ΔPLC mutants under conditions where phosphatidylcholine served as sole phosphate source, opening new perspectives for studies on the role of PLCs in the lifecycle of M. tuberculosis. PMID:26603639

Programmable logic controller implementation of an auto-tuned predictive control based on minimal plant information.

PubMed

Valencia-Palomo, G; Rossiter, J A

2011-01-01

This paper makes two key contributions. First, it tackles the issue of the availability of constrained predictive control for low-level control loops. Hence, it describes how the constrained control algorithm is embedded in an industrial programmable logic controller (PLC) using the IEC 61131-3 programming standard. Second, there is a definition and implementation of a novel auto-tuned predictive controller; the key novelty is that the modelling is based on relatively crude but pragmatic plant information. Laboratory experiment tests were carried out in two bench-scale laboratory systems to prove the effectiveness of the combined algorithm and hardware solution. For completeness, the results are compared with a commercial proportional-integral-derivative (PID) controller (also embedded in the PLC) using the most up to date auto-tuning rules. Copyright © 2010 ISA. Published by Elsevier Ltd. All rights reserved.

Clinical and Radiological Discrimination of Solitary Pulmonary Lesions in Colorectal Cancer Patients.

PubMed

Ohtaki, Yoichi; Shimizu, Kimihiro; Nagashima, Toshiteru; Nakazawa, Seshiru; Obayashi, Kai; Azuma, Yoko; Iijima, Misaki; Kosaka, Takayuki; Yajima, Toshiki; Ogawa, Hiroomi; Tsutsumi, Soichi; Arai, Motohiro; Mogi, Akira; Kuwano, Hiroyuki

2018-04-01

The lung is one of the most common organs of metastasis from colorectal cancer (CRC), and we have encountered lung cancer patients with a history of CRC. There have been few studies regarding methods used to discriminate between primary lung cancer (PLC) and pulmonary metastasis from CRC (PM-CRC) based only on preoperative findings. We retrospectively investigated predictive factors discriminating between these lesions in patients with a history of CRC. Between 2006 and 2015, 117 patients with a history of CRC (44 patients with 47 PLC and 73 patients with 102 PM-CRC) underwent subsequent or concurrent resection of pulmonary lesions. We compared the clinical and radiological characteristics of 100 patients with solitary lesions (43 PLC and 57 PM-CRC). Using univariate and multivariate analyses, we examined predictive factors for discrimination of these two lesions. All tumors with findings of ground-glass opacity (GGO) were PLC (n = 19). In a multivariate analysis of 81 radiologically solid tumors, two factors were found to be significant independent predictors of PLC: a history of stage I CRC and presence of pleural indentation. All tumors in 26 patients with either GGO or both a stage I CRC history and pleural indentation were PLC, while most tumors in patients without all three factors were PM-CRC (43/44; 97.7%). The presence or absence of GGO, pathological CRC stage, and pleural indentation could be useful factors to distinguish between PLC and PM-CRC.

The effects of venlafaxine and cognitive behavioral therapy alone and combined in the treatment of co-morbid alcohol use-anxiety disorders.

PubMed

Ciraulo, Domenic A; Barlow, David H; Gulliver, Suzy Bird; Farchione, Todd; Morissette, Sandra B; Kamholz, Barbara W; Eisenmenger, Katherine; Brown, Bonnie; Devine, Eric; Brown, Timothy A; Knapp, Clifford M

2013-11-01

The effects of the antidepressant venlafaxine (VEN-225 mg daily) and transdiagnostic cognitive behavioral treatment (CBT) alone and in combination on alcohol intake in subjects with co-morbid alcohol use disorders (AUDs) and anxiety disorders were compared. Drinking outcomes and anxiety were assessed for 81 subjects treated for 11 weeks with one of 4 conditions: 1) VEN-CBT, 2) VEN-Progressive Muscle Relaxation therapy (PMR), 3) Placebo (PLC)-CBT and 4) a comparison group of PLC-PMR. For subjects who reported taking at least one dose of study medication, the Time×Group interaction was significant for percent days of heavy drinking and drinks consumed per day. For the measure of percent days heavy drinking, the paired comparison of PLC-CBT versus PLC-PMR group indicated that the PLC-CBT group had greater drinking reductions, whereas other groups were not superior to the comparison group. In Week 11, the proportion of subjects in the PLC-CBT group that had a 50% reduction from baseline in percent days heavy drinking was significantly greater than those in the comparison group. Of the 3 "active treatment" groups only the PLC-CBT group had significantly decreased heavy drinking when contrasted to the comparison group. This finding suggests that the transdiagnostic CBT approach of Barlow and colleagues may have value in the management of heavy drinking in individuals with co-morbid alcoholism and anxiety. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Characteristics and synergistic effects of co-combustion of carbonaceous wastes with coal.

PubMed

Onenc, Sermin; Retschitzegger, Stefan; Evic, Nikola; Kienzl, Norbert; Yanik, Jale

2018-01-01

This study presents combustion behavior and emission results obtained for different fuels: poultry litter (PL) and its char (PLC), scrap tires (ST) and its char (STC) and blends of char/lignite (PLC/LIG and STC/LIG). The combustion parameters and emissions were investigated via a non-isothermal thermogravimetric method and experiments in a lab-scale reactor. Fuel indexes were used for the prediction of high temperature corrosion risks and slagging potentials of the fuels used. The addition of chars to lignite caused a lowering of the combustion reactivity (anti-synergistic effect). There was a linear correlation between the NO x emissions and the N content of the fuel. The form of S and the concentrations of alkali metals in the fuel had a strong effect on the extent of SO 2 emissions. The use of PL and PLC in blends reduced SO 2 emissions and sulphur compounds in the fly ash. The 2S/Cl ratio in the fuel showed that only PLC and STC/PLC would show a risk of corrosion during combustion. The ratio of basic to acidic oxides in fuel indicated that ST, STC and STC/LIG have low slagging potential. The molar (Si+P+K)/(Ca+Mg) ratio, which was used for PL, PLC and PLC containing blends, showed that the ash melting temperatures of these fuels would be higher than 1000 °C. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modulation of intracellular Ca(2+) via alpha(1B)-adrenoreceptor signaling molecules, G alpha(h) (transglutaminase II) and phospholipase C-delta 1.

PubMed

Kang, Sung Koo; Kim, Dae Kyong; Damron, Derek S; Baek, Kwang Jin; Im, Mie-Jae

2002-04-26

We characterized the alpha(1B)-adrenoreceptor (alpha(1B)-AR)-mediated intracellular Ca(2+) signaling involving G alpha(h) (transglutaminase II, TGII) and phospholipase C (PLC)-delta 1 using DDT1-MF2 cell. Expression of wild-type TGII and a TGII mutant lacking transglutaminase activity resulted in significant increases in a rapid peak and a sustained level of intracellular Ca(2+) concentration ([Ca(2+)](i)) in response to activation of the alpha(1B)-AR. Expression of a TGII mutant lacking the interaction with the receptor or PLC-delta 1 substantially reduced both the peak and sustained levels of [Ca(2+)](i). Expression of TGII mutants lacking the interaction with PLC-delta 1 resulted in a reduced capacitative Ca(2+) entry. Reduced expression of PLC-delta 1 displayed a transient elevation of [Ca(2+)](i) and a reduction in capacitative Ca(2+) entry. Expression of the C2-domain of PLC-delta 1, which contains the TGII interaction site, resulted in reduction of the alpha(1B)-AR-evoked peak increase in [Ca(2+)](i), while the sustained elevation in [Ca(2+)](i) and capacitative Ca(2+) entry remained unchanged. These findings demonstrate that stimulation of PLC-delta 1 via coupling of the alpha(1B)-AR with TGII evokes both Ca(2+) release and capacitative Ca(2+) entry and that capacitative Ca(2+) entry is mediated by the interaction of TGII with PLC-delta 1.

10 CFR 431.324 - Uniform test method for the measurement of energy efficiency and standby mode energy consumption...

Code of Federal Regulations, 2011 CFR

2011-01-01

... ballast in accordance with the circuit shown in Figure 2. ER09MR10.006 (iii) Power Line Carrier (PLC) Control Signal. Measure the PLC control signal power (watts), using a wattmeter capable of indicating true... wattmeter must have a frequency response that is at least 10 times higher than the PLC being measured to...

78 FR 55664 - Revisions to the Export Administration Regulations (EAR): Unverified List (UVL)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-11

... subject to the EAR), where an end- use check, such as a pre-license check (PLC) or a post-shipment... persons because an end-use check, such as a PLC or a PSV, cannot be completed satisfactorily for reasons... conduct an end-use check, such as a PLC or a PSV, at all because, among other potential reasons, BIS was...

Professional Learning Communities (PLCs) as a Means for School-Based Science Curriculum Change

NASA Astrophysics Data System (ADS)

Browne, Christi L.

The challenge of school-based science curriculum change and educational reform is often presented to science teachers and departments who are not necessarily prepared for the complexity of considerations that change movements require. The development of a Professional Learning Community (PLC) focused on a science department's curriculum change efforts, may provide the necessary tools to foster sustainable school-based curriculum science changes. This research presents a case study of an evolving science department PLC consisting of 10 middle school science teachers from the same middle school and their efforts of school-based science curriculum change. A transformative mixed model case study with qualitative data and deepened by quantitative analysis, was chosen to guide the investigation. Collected data worked to document the essential developmental steps, the occurrence and frequency of the five essential dimensions of successful PLCs, and the influences the science department PLC had on the middle school science department's progression through school-based science curriculum change, and the barriers, struggles and inhibiting actions of the science department PLC. Findings indicated that a science department PLC was unique in that it allowed for a focal science departmental lens of science curriculum change to be applied to the structure and function of the PLC and therefore the process, proceedings, and results were directly aligned to and driven by the science department. The science PLC, while logically difficult to set-up and maintain, became a professional science forum where the middle school science teachers were exposed to new science teaching and learning knowledge, explored new science standards, discussed effects on student science learning, designed and critically analyzed science curriculum change application. Conclusions resulted in the science department PLC as an identified tool providing the ability for science departmental actions to lead to outcomes of science curriculum change improvements with the consideration but not the dictation of the larger school community and state agendas. Thus, the study's results work to fuse previously separated research on general PLCs and curriculum change efforts into a cohesive understanding of the unexplored potential of a science PLC and school-based science curriculum change.

Targeting annexin A7 by a small molecule suppressed the activity of phosphatidylcholine-specific phospholipase C in vascular endothelial cells and inhibited atherosclerosis in apolipoprotein E⁻/⁻mice.

PubMed

Li, H; Huang, S; Wang, S; Zhao, J; Su, L; Zhao, B; Zhang, Y; Zhang, S; Miao, J

2013-09-19

Phosphatidylcholine-specific phospholipase C (PC-PLC) is a key factor in apoptosis and autophagy of vascular endothelial cells (VECs), and involved in atherosclerosis in apolipoprotein E⁻/⁻ (apoE⁻/⁻) mice. But the endogenous regulators of PC-PLC are not known. We recently found a small chemical molecule (6-amino-2, 3-dihydro-3-hydroxymethyl-1, 4-benzoxazine, ABO) that could inhibit oxidized low-density lipoprotein (oxLDL)-induced apoptosis and promote autophagy in VECs, and further identified ABO as an inhibitor of annexin A7 (ANXA7) GTPase. Based on these findings, we hypothesize that ANXA7 is an endogenous regulator of PC-PLC, and targeting ANXA7 by ABO may inhibit atherosclerosis in apoE⁻/⁻ mice. In this study, we tested our hypothesis. The results showed that ABO suppressed oxLDL-induced increase of PC-PLC level and activity and promoted the co-localization of ANXA7 and PC-PLC in VECs. The experiments of ANXA7 knockdown and overexpression demonstrated that the action of ABO was ANXA7-dependent in cultured VECs. To investigate the relation of ANXA7 with PC-PLC in atherosclerosis, apoE⁻/⁻ mice fed with a western diet were treated with 50 or 100 mg/kg/day ABO. The results showed that ABO decreased PC-PLC levels in the mouse aortic endothelium and PC-PLC activity in serum, and enhanced the protein levels of ANXA7 in the mouse aortic endothelium. Furthermore, both dosages of ABO significantly enhanced autophagy and reduced apoptosis in the mouse aortic endothelium. As a result, ABO significantly reduced atherosclerotic plaque area and effectively preserved a stable plaques phenotype, including reduced lipid deposition and pro-inflammatory macrophages, increased anti-inflammatory macrophages, collagen content and smooth muscle cells, and less cell death in the plaques. In conclusion, ANXA7 was an endogenous regulator of PC-PLC, and targeting ANXA7 by ABO inhibited atherosclerosis in apoE⁻/⁻ mice.

Qidong hepatitis B virus infection cohort: a 25-year prospective study in high risk area of primary liver cancer.

PubMed

Chen, Taoyang; Qian, Gengsun; Fan, Chunsun; Sun, Yan; Wang, Jinbing; Lu, Peixin; Xue, Xuefeng; Wu, Yan; Zhang, Qinan; Jin, Yan; Wu, Yiqian; Gan, Yu; Lu, Jianquan; Kensler, Thomas W; Groopman, John D; Tu, Hong

2018-01-01

Qidong hepatitis B virus (HBV) infection cohort (QBC) is a prospective community-based study designed to investigate causative factors of primary liver cancer (PLC) in Qidong, China, where both PLC and HBV infection are highly endemic. Residents aged 20-65 years, living in seven townships of Qidong, were surveyed using hepatitis B surface antigen (HBsAg) serum test and invited to participate in QBC from June 1991 to December 1991. A total of 852 and 786 participants were enrolled in HBsAg-positive and HBsAg-negative sub-cohorts in May 1992, respectively. All participants were actively followed up in person, received HBsAg, alanine aminotransferase (ALT), alpha-fetoprotein (AFP) tests and upper abdominal ultrasonic examination, and donated blood and urine samples once or twice a year. The total response rate was 99.6%, and the number of incident PLC was 201 till the end of February 2017. The ratio of incidence rates was 12.32 (95% confidence interval[CI]=7.16-21.21, P < 0.0001) in HBsAg-positive arm compared with HBsAg-negative arm. The relative risk of PLC was 13.25 (95% CI=6.67-26.33, P < 0.0001) and 28.05 (95% CI=13.87-56.73, P < 0.0001) in the HBsAg+/HBeAg- group and the HBsAg+/HBeAg+ group, respectively, as compared to the HBsAg-/HBeAg- group. A series of novel PLC-related mutations including A2159G, A2189C and G2203W at the C gene, A799G, A987G and T1055A at the P gene of HBV genome were identified by using samples from the cohort. The mutation in hepatitis B virus (HBV) basal core promoter region of HBV genome has an accumulative effect on the occurrence of PLC. In addition, the tripartite relationship of aflatoxin exposure, P53 mutation and PLC was also investigated. Dynamic prediction model for PLC risk by using its long-term follow-up information and serial blood samples for QBC was developed. This model is expected to improve the efficiency of PLC screening in HBV infection individuals.

Satisfactory knee function after single-stage posterolateral corner reconstruction in the multi-ligament injured/dislocated knee using the anatomic single-graft technique.

PubMed

Sanders, Thomas L; Johnson, Nick R; Pareek, Ayoosh; Krych, Aaron J; Marx, Robert G; Stuart, Michael J; Levy, Bruce A

2018-04-01

Increasing importance has been placed on the posterolateral corner (PLC) in maintaining varus and rotational stability of the knee. The goal of this study was to evaluate knee function and clinical stability following a single-graft PLC reconstruction technique and identify factors associated with poor knee function. This study identified patients with a multi-ligament knee injury between 2006 and 2013. Patients who received a single-graft fibular collateral ligament and PLC reconstruction with a single-stage surgery during the study period and had a minimum follow-up of 2 years after surgery were included. Functional outcomes were assessed using Lysholm and IKDC scores. Varus and rotational knee laxity and range of motion were assessed using physical examination. The final study cohort included 61 patients who underwent PLC reconstruction using a single-graft technique. The mean IKDC score was 74.1 (± 22.3) and the mean Lysholm score was 80.3 (± 21.8) at mean follow-up of 3.8 years (range 2-9 years). Mean range of motion at final follow-up measured from 0° to 126° [range flexion: 95-145, range extension: 0-5]. Fifty-eight patients (95%) had grade 0 varus laxity in full knee extension, and 54 patients (88.5%) had grade 0 varus laxity at 30° of knee flexion. Female gender was associated with a lower postoperative IKDC score (p = 0.04). Surgical treatment of the PLC using a single-graft technique can result in satisfactory knee function and stable physical examination findings at minimum 2 years after surgery. Female gender was predictive of poor knee function after PLC reconstruction. Surgical treatment of PLC injuries should be individualized based on the timing of surgery, specific injured knee structures, and physical examination findings. This study helps validate the use of a single-graft technique for PLC reconstruction and can be used to help counsel patients about expected knee function after surgical treatment of PLC injuries. Level of evidence IV.

Prognostic value of intraoperative pleural lavage cytology for non-small cell lung cancer: the influence of positive pleural lavage cytology results on T classification.

PubMed

Kameyama, Kotaro; Okumura, Norihito; Miyaoka, Etsuo; Asamura, Hisao; Yoshino, Ichiro; Tada, Hirohito; Fujii, Yoshitaka; Nakanishi, Yoichi; Eguchi, Kenji; Mori, Masaki; Kobayashi, Hideo; Sawabata, Noriyoshi; Okumura, Meinoshin; Yokoi, Kohei

2014-12-01

Although positive pleural lavage cytology (PLC) has been demonstrated to be closely associated with a poor prognosis for patients with lung cancer, it has not been incorporated into the TNM staging system of the Union for International Cancer Control. The aim of our study was to retrospectively examine the clinical significance of PLC status and illustrate the recommendations of the International Pleural Lavage Cytology Collaborators (IPLCC) in a large national database. The Japanese Joint Committee of Lung Cancer Registry database included 11,073 patients with non-small cell lung cancer who underwent resections in 2004. We extracted the clinicopathologic data for 4171 patients (37.3%) who underwent PLC. These patients were staged according to the seventh edition of the Union for International Cancer Control TNM classification and by recommendations of the IPLCC, in which T was singly upgraded up to a maximum of T4 for those who were PLC-positive. Prognoses based on these 2 systems were compared. A total of 217 patients (5.2%) were PLC-positive, which was significantly associated with a higher incidence of adenocarcinoma and advanced disease. The 5-year survival for patients with positive and negative PLC results were 44.5% and 72.8%, respectively, and this difference in survival was statistically significant (P < .001). Multivariate analysis showed that positive PLC status was an independent factor for a poor prognosis (hazard ratio, 1.57; P < .001). Significant differences in survival were also found between patients with positive and negative PLC results in the same T categories and stages, including T2a, T3, stage IB, and stage IIIA. The IPLCC recommendations adjusted the prognostic differences in all T categories and stages. The significant difference in survival disappeared between the 2 groups in all T categories and stages. Our results indicate that a T category upgrade is prognostically adequate for patients who are PLC-positive. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Transvaginal cholecystectomy versus single-incision laparoscopic cholecystectomy versus four-port laparoscopic cholecystectomy: a prospective cohort study.

PubMed

Solomon, Daniel; Shariff, Amir H; Silasi, Dan-Arin; Duffy, Andrew J; Bell, Robert L; Roberts, Kurt E

2012-10-01

This report describes the first prospective cohort study comparing transvaginal cholecystectomies (TVC) with single incision laparoscopic cholecystectomies (SILC) and four-port laparoscopic cholecystectomies (4PLC). Between May 2009 and August 2010, 14 patients underwent a TVC. These patients were compared with patients who underwent SILC (22 patients) or 4PLC (11 patients) in a concurrent, randomized, controlled trial. Demographic data, operative time, numerical pain scales, complications, and return to work were recorded. Mean age (TVC: 33.5 ± 3.0 year; SILC: 38.4 ± 3.3 year; 4PLC: 35.5 ± 4.1 year; p = 0.58) and mean BMI (TVC: 28.8 ± 1.5 kg/m(2); SILC: 31.8 ± 1 kg/m(2); 4PLC: 31.4 ± 2.2 kg/m(2); p = 0.35) were not statistically significant. However, mean operative time (TVC: 67 ± 3.9 min; SILC: 48.9 ± 2.6 min; 4PLC: 42.3 ± 3.9 min; p < 0.001) was significantly longer for TVC. Numerical pain scales showed significantly lower pain scores on POD 1 and 3 for TVC compared with SILC and 4PLC (TVC: 4.1 ± 0.5 and 2.9 ± 0.7; SILC: 6.1 ± 0.5 and 5.3 ± 0.5; 4PLC: 5.7 ± 0.4 and 4.7 ± 0.3; p = 0.02) with equilibration of pain scores by days 14 and 30. Return to work (TVC: 6.4 ± 1.5 days; SILC: 13.1 ± 1.3 days; 4PLC: 14.1 ± 1.4 days; p < 0.001) also was significantly faster for patients in the TVC group. One conversion in the TVC group to a 4PLC was necessary due to adhesions within the pelvis. One dislodged IUD was seen and immediately replaced in the TVC group. One hernia was observed in the SILC group. Transvaginal cholecystectomy is a safe and well-tolerated procedure with statistically significantly less pain at 1 and 3 days after surgery, with a faster return to work but longer operative times compared with single incision and four-port laparoscopic cholecystectomy.

Design and Research of the Sewage Treatment Control System

NASA Astrophysics Data System (ADS)

Chu, J.; Hu, W. W.

Due to the rapid development of China's economy, the water pollution has become a problem that we have to face. In particular, how to deal with industrial wastewater has become a top priority. In wastewater treatment, the control system based on PLC has met the design requirement in real-time, reliability, precision and so on. The integration of sequence control and process control in PLC, has the characteristics of high reliability, simple network, convenient and flexible use. PLC is a powerful tool for small and medium-sized industrial automation. Therefore, the sewage treatment control system take PLC as the core of control system, can nicely solve the problem of industrial wastewater in a certain extent.

78 FR 65304 - Orders Granting Authority To Import and Export Natural Gas, and To Import and Export Liquefied...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... And Electric Company........ 13-95-NG Barclays Bank PLC 13-99-NG AGENCY: Office of Fossil Energy, Department of Energy. ACTION: Notice of orders. SUMMARY: The Office of Fossil Energy (FE) of the Department... attached appendix and may be found on the FE Web site at http://www.fossil.energy.gov/programs...

Freeze-thaw-induced embolism in Pinus contorta: centrifuge experiments validate the 'thaw-expansion hypothesis' but conflict with ultrasonic emission data.

PubMed

Mayr, Stefan; Sperry, John S

2010-03-01

*The 'thaw-expansion hypothesis' postulates that xylem embolism is caused by the formation of gas bubbles on freezing and their expansion on thawing. We evaluated the hypothesis using centrifuge experiments and ultrasonic emission monitoring in Pinus contorta. *Stem samples were exposed to freeze-thaw cycles at varying xylem pressure (P) in a centrifuge before the percentage loss of hydraulic conductivity (PLC) was measured. Ultrasonic acoustic emissions were registered on samples exposed to freeze-thaw cycles in a temperature chamber. *Freeze-thaw exposure of samples spun at -3 MPa induced a PLC of 32% (one frost cycle) and 50% (two cycles). An increase in P to -0.5 MPa during freezing had no PLC effect, whereas increased P during thaw lowered PLC to 7%. Ultrasonic acoustic emissions were observed during freezing and thawing at -3 MPa, but not in air-dried or water-saturated samples. A decrease in minimum temperature caused additional ultrasonic acoustic emissions, but had no effect on PLC. *The centrifuge experiments indicate that the 'thaw-expansion hypothesis' correctly describes the embolization process. Possible explanations for the increase in PLC on repeated frost cycles and for the ultrasonic acoustic emissions observed during freezing and with decreasing ice temperature are discussed.

Pharmacologic inhibition of phospholipase C in the brain attenuates early memory formation in the honeybee (Apis mellifera L.)

PubMed Central

Iino, Shiori; Kubo, Takeo

2018-01-01

ABSTRACT Although the molecular mechanisms involved in learning and memory in insects have been studied intensively, the intracellular signaling mechanisms involved in early memory formation are not fully understood. We previously demonstrated that phospholipase C epsilon (PLCe), whose product is involved in calcium signaling, is almost selectively expressed in the mushroom bodies, a brain structure important for learning and memory in the honeybee. Here, we pharmacologically examined the role of phospholipase C (PLC) in learning and memory in the honeybee. First, we identified four genes for PLC subtypes in the honeybee genome database. Quantitative reverse transcription-polymerase chain reaction revealed that, among these four genes, three, including PLCe, were expressed higher in the brain than in sensory organs in worker honeybees, suggesting their main roles in the brain. Edelfosine and neomycin, pan-PLC inhibitors, significantly decreased PLC activities in homogenates of the brain tissues. These drugs injected into the head of foragers significantly attenuated memory acquisition in comparison with the control groups, whereas memory retention was not affected. These findings suggest that PLC in the brain is involved in early memory formation in the honeybee. To our knowledge, this is the first report of a role for PLC in learning and memory in an insect. PMID:29330349

Evidence for the cytotoxic effects of Mycobacterium tuberculosis phospholipase C towards macrophages.

PubMed

Bakala N'goma, J C; Schué, M; Carrière, F; Geerlof, A; Canaan, S

2010-12-01

Phospholipase Cs (PLCs) contribute importantly to the virulence and pathogenicity of several bacteria. It has been reported in previous studies that mutations in the four predicted plc genes of Mycobacterium tuberculosis inhibit the growth of these bacteria during the late phase of infection in mice. These enzymes have not yet been fully characterised, mainly because they are not easy to produce in large quantities. With a view to elucidating the role of all Mycobacterium tuberculosis phospholipase Cs (PLC-A, PLC-B, PLC-C and PLC-D), a large amount of active, soluble recombinant PLCs, were expressed and purified using Mycobacterium smegmatis as expression system. These enzymes showed different pH activity profiles. PLC-C was found to be the most active of the four recombinant PLCs under acidic conditions. All the enzymes tested induced cytotoxic effects on mouse macrophage RAW 264.7 cell lines, via direct or indirect enzymatic hydrolysis of cell membrane phospholipids. These results open new prospects for characterising biochemical and structural features of Mycobacterium tuberculosis PLCs, which might lead to the identification of novel anti-tuberculosis drug targets. All mycobacterial phospholipase Cs can now be studied in order to determine their role in the virulence and pathogenicity of bacteria of this kind. 2010 Elsevier B.V. All rights reserved.

The role of isolated posterior cruciate ligament reconstruction in knees with combined posterior cruciate ligament and posterolateral complex injury.

PubMed

Lee, Dong-Yeong; Park, Young-Jin; Kim, Dong-Hee; Kim, Hyun-Jung; Nam, Dae-Cheol; Park, Jin-Sung; Hwang, Sun-Chul

2017-08-14

This is a meta-analysis comparing biomechanical outcomes to determine whether an isolated posterior cruciate ligament (PCL) reconstruction can restore normal knee kinematics in a combined PCL/posterolateral complex (PLC) injury and whether double-bundle (DB) PCL reconstruction is superior in controlling posterior and rotational laxity compared with single-bundle (SB) PCL reconstruction in a PCL/PLC-deficient knee. A number of electronic databases were searched for relevant articles published through August 2016 that compared biomechanical outcomes of PCL reconstruction in patients who underwent reconstruction for combined PCL/PLC deficiencies. Data were searched, extracted, analysed, and assessed for quality according to Cochrane Collaboration guidelines, and biomechanical outcomes were evaluated using various outcome values. The results are presented as relative ratios for binary outcomes and standard mean differences for continuous outcomes with 95% confidence intervals. Five biomechanical studies were included in this meta-analysis. There were significant differences in laxities such as posterior tibial translation (PTT), external rotation, varus rotation, and PTT coupled with external rotation in the isolated PCL reconstruction group compared with the native PCL group. Furthermore, there were no significant differences in laxities such as PTT, external rotation, or varus rotation between the SB and DB PCL reconstruction groups. Isolated PCL reconstruction, whether SB or DB, could not restore normal knee kinematics in the PCL/PLC-deficient knee. In such cases, residual laxity after isolated PCL reconstruction can be controlled successfully with PLC reconstruction. Therefore, simultaneous PCL and PLC reconstruction is recommended for patients with combined PCL/PLC injury.

Static respiratory muscle work during immersion with positive and negative respiratory loading.

PubMed

Taylor, N A; Morrison, J B

1999-10-01

Upright immersion imposes a pressure imbalance across the thorax. This study examined the effects of air-delivery pressure on inspiratory muscle work during upright immersion. Eight subjects performed respiratory pressure-volume relaxation maneuvers while seated in air (control) and during immersion. Hydrostatic, respiratory elastic (lung and chest wall), and resultant static respiratory muscle work components were computed. During immersion, the effects of four air-delivery pressures were evaluated: mouth pressure (uncompensated); the pressure at the lung centroid (PL,c); and at PL,c +/-0.98 kPa. When breathing at pressures less than the PL,c, subjects generally defended an expiratory reserve volume (ERV) greater than the immersed relaxation volume, minus residual volume, resulting in additional inspiratory muscle work. The resultant static inspiratory muscle work, computed over a 1-liter tidal volume above the ERV, increased from 0.23 J. l(-1), when subjects were breathing at PL,c, to 0.83 J. l(-1) at PL,c -0.98 kPa (P < 0.05), and to 1.79 J. l(-1) at mouth pressure (P < 0.05). Under the control state, and during the above experimental conditions, static expiratory work was minimal. When breathing at PL,c +0.98 kPa, subjects adopted an ERV less than the immersed relaxation volume, minus residual volume, resulting in 0.36 J. l(-1) of expiratory muscle work. Thus static inspiratory muscle work varied with respiratory loading, whereas PL,c air supply minimized this work during upright immersion, restoring lung-tissue, chest-wall, and static muscle work to levels obtained in the control state.

Mycobacterium abscessus Phospholipase C Expression Is Induced during Coculture within Amoebae and Enhances M. abscessus Virulence in Mice

PubMed Central

Bakala N'Goma, Jean Claude; Le Moigne, Vincent; Soismier, Nathalie; Laencina, Laura; Le Chevalier, Fabien; Roux, Anne-Laure; Poncin, Isabelle; Serveau-Avesque, Carole; Rottman, Martin; Gaillard, Jean-Louis; Etienne, Gilles; Brosch, Roland; Canaan, Stéphane

2014-01-01

Mycobacterium abscessus is a pathogenic, rapidly growing mycobacterium involved in pulmonary and cutaneo-mucous infections worldwide, to which cystic fibrosis patients are exquisitely susceptible. The analysis of the genome sequence of M. abscessus showed that this bacterium is endowed with the metabolic pathways typically found in environmental microorganisms that come into contact with soil, plants, and aquatic environments, where free-living amoebae are frequently present. M. abscessus also contains several genes that are characteristically found only in pathogenic bacteria. One of them is MAB_0555, encoding a putative phospholipase C (PLC) that is absent from most other rapidly growing mycobacteria, including Mycobacterium chelonae and Mycobacterium smegmatis. Here, we report that purified recombinant M. abscessus PLC is highly cytotoxic to mouse macrophages, presumably due to hydrolysis of membrane phospholipids. We further showed by constructing and using an M. abscessus PLC knockout mutant that loss of PLC activity is deleterious to M. abscessus intracellular survival in amoebae. The importance of PLC is further supported by the fact that M. abscessus PLC was found to be expressed only in amoebae. Aerosol challenge of mice with M. abscessus strains that were precultured in amoebae enhanced M. abscessus lung infectivity relative to M. abscessus grown in broth culture. Our study underlines the importance of PLC for the virulence of M. abscessus. Despite the difficulties of isolating M. abscessus from environmental sources, our findings suggest that M. abscessus has evolved in close contact with environmental protozoa, which supports the argument that amoebae may contribute to the virulence of opportunistic mycobacteria. PMID:25486995

Phospholipase C-β1 and β4 Contribute to Non-Genetic Cell-to-Cell Variability in Histamine-Induced Calcium Signals in HeLa Cells

PubMed Central

Ishida, Sachiko; Matsu-ura, Toru; Fukami, Kiyoko; Michikawa, Takayuki; Mikoshiba, Katsuhiko

2014-01-01

A uniform extracellular stimulus triggers cell-specific patterns of Ca2+ signals, even in genetically identical cell populations. However, the underlying mechanism that generates the cell-to-cell variability remains unknown. We monitored cytosolic inositol 1,4,5-trisphosphate (IP3) concentration changes using a fluorescent IP3 sensor in single HeLa cells showing different patterns of histamine-induced Ca2+ oscillations in terms of the time constant of Ca2+ spike amplitude decay and the Ca2+ oscillation frequency. HeLa cells stimulated with histamine exhibited a considerable variation in the temporal pattern of Ca2+ signals and we found that there were cell-specific IP3 dynamics depending on the patterns of Ca2+ signals. RT-PCR and western blot analyses showed that phospholipase C (PLC)-β1, -β3, -β4, -γ1, -δ3 and -ε were expressed at relatively high levels in HeLa cells. Small interfering RNA-mediated silencing of PLC isozymes revealed that PLC-β1 and PLC-β4 were specifically involved in the histamine-induced IP3 increases in HeLa cells. Modulation of IP3 dynamics by knockdown or overexpression of the isozymes PLC-β1 and PLC-β4 resulted in specific changes in the characteristics of Ca2+ oscillations, such as the time constant of the temporal changes in the Ca2+ spike amplitude and the Ca2+ oscillation frequency, within the range of the cell-to-cell variability found in wild-type cell populations. These findings indicate that the heterogeneity in the process of IP3 production, rather than IP3-induced Ca2+ release, can cause cell-to-cell variability in the patterns of Ca2+ signals and that PLC-β1 and PLC-β4 contribute to generate cell-specific Ca2+ signals evoked by G protein-coupled receptor stimulation. PMID:24475116

Melatonin Promotes Brain-Derived Neurotrophic Factor (BDNF) Expression and Anti-Apoptotic Effects in Neonatal Hemolytic Hyperbilirubinemia via a Phospholipase (PLC)-Mediated Mechanism

PubMed Central

Luo, Yong; Peng, Mei; Wei, Hong

2017-01-01

Background Melatonin therapy shows positive effects on neuroprotective factor brain-derived neurotrophic factor (BDNF) expression and neuronal apoptosis in neonatal hemolytic hyperbilirubinemia. We hypothesized that melatonin promotes BDNF expression and anti-apoptotic effects in neonatal hemolytic hyperbilirubinemia through a phospholipase (PLC)-mediated mechanism. Material/Methods A phenylhydrazine hydrochloride (PHZ)-induced neonatal hemolytic hyperbilirubinemia model was constructed in neonatal rats. Four experimental groups – a control group (n=30), a PHZ group (n=30), a PHZ + melatonin group (n=30), and a PHZ + melatonin+U73122 (a PLC inhibitor) group (n=30) – were constructed. Trunk blood was assayed for serum hemoglobin, hematocrit, total and direct bilirubin, BDNF, S100B, and tau protein levels. Brain tissue levels of neuronal apoptosis, BDNF expression, PLC activity, IP3 content, phospho- and total Ca2+/calmodulin-dependent protein kinase type IV (CaMKIV) expression, and phospho- and total cAMP response element binding protein (CREB) expression were also assayed. Results PHZ-induced hemolytic hyperbilirubinemia was validated by significantly decreased serum hemoglobin and hematocrit as well as significantly increased total and direct serum bilirubin (p<0.05). Neonatal bilirubin-induced neurotoxicity was validated by significantly decreased serum BDNF, brain BDNF, and serum S100B, along with significantly increased serum tau protein (p<0.05). PHZ-induced hemolytic hyperbilirubinemia significantly decreased serum BDNF, brain BDNF, and PLC/IP3/Ca2+ pathway activation while increasing neuronal apoptosis levels (p<0.05), all of which were partially rescued by melatonin therapy (p<0.05). Pre-treatment with the PLC inhibitor U73122 largely abolished the positive effects of melatonin on PLC/IP3/Ca2+ pathway activation, downstream BDNF levels, and neuronal apoptosis (p<0.05). Conclusions Promotion of BDNF expression and anti-apoptotic effects in neonatal hemolytic hyperbilirubinemia by melatonin largely operates via a PLC-mediated mechanism. PMID:29247156

Csseverin inhibits apoptosis through mitochondria-mediated pathways triggered by Ca2 + dyshomeostasis in hepatocarcinoma PLC cells

PubMed Central

Zhou, Lina; Zhao, Lu; Shang, Mei; He, Tongtong; Tang, Zeli; Sun, Hengchang; Ren, Pengli; Lin, Zhipeng; Chen, Tingjin; Yu, Jinyun; Xu, Jin; Yu, Xinbing; Huang, Yan

2017-01-01

Background Numerous experimental and epidemiological studies have demonstrated a link between Clonorchis sinensis (C. sinensis) infestation and cholangiocarcinoma (CCA) as well as hepatocellular carcinoma (HCC). The underlying molecular mechanism involved in the malignancy of CCA and HCC has not yet been addressed. Csseverin, a component of the excretory/secretory products of C. sinensis (CsESPs), was confirmed to cause obvious apoptotic inhibition in the human HCC cell line PLC. However, the antiapoptotic mechanism is unclear. In the present study, we investigated the cellular features of the antiapoptotic mechanism upon transfection of the Csseverin gene. Methods In the present study, we evaluated the effects of Csseverin gene overexpression on the apoptosis of PLC cells using an Annexin PE/7-AAD assay. Western blotting was applied to quantify the activation of caspase-3 and caspase-9, the mitochondrial translocation of Bax and the release of Cyt c upon Csseverin overexpression in PLC cells. Laser scanning confocal microscopy was used to analyze the changes of intracellular calcium. Fluorescence assay and immunofluorescence assays were performed to observe the changes of the mitochondrial permeability transition pore (MPTP). Results The overexpression of Csseverin in PLC cells showed apoptosis resistance after the induction of apoptosis. Additionally, the activation of caspase-3 and caspase-9 was specifically weakened in Csseverin overexpression PLC cells. The overexpression of Csseverin reduced the increase in intracellular free Ca2+, thereby inhibiting MPTP opening in PLC cells. Moreover, Bax mitochondrial translocation and the subsequent release of Cyt c were downregulated in apoptotic Csseverin overexpression PLC cells. Conclusions The present findings suggest that Csseverin, a component of CsESPs, confers protection from human HCC cell apoptosis via the inactivation of membranous Ca2+ channels. Csseverin might be involved in the process of HCC through C. sinensis infestation in affected patients. PMID:29125839

Inhibition of Phosphatidylcholine-Specific Phospholipase C Interferes with Proliferation and Survival of Tumor Initiating Cells in Squamous Cell Carcinoma

PubMed Central

Ferri, Renata; Mercurio, Laura; Canevari, Silvana; Podo, Franca; Miotti, Silvia; Iorio, Egidio

2015-01-01

Purpose The role of phosphatidylcholine-specific phospholipase C (PC-PLC), the enzyme involved in cell differentiation and proliferation, has not yet been explored in tumor initiating cells (TICs). We investigated PC-PLC expression and effects of PC-PLC inhibition in two adherent (AD) squamous carcinoma cell lines (A431 and CaSki), with different proliferative and stemness potential, and in TIC-enriched floating spheres (SPH) originated from them. Results Compared with immortalized non-tumoral keratinocytes (HaCaT) A431-AD cells showed 2.5-fold higher PC-PLC activity, nuclear localization of a 66-kDa PC-PLC isoform, but a similar distribution of the enzyme on plasma membrane and in cytoplasmic compartments. Compared with A431-AD, A431-SPH cells showed about 2.8-fold lower PC-PLC protein and activity levels, but similar nuclear content. Exposure of adherent cells to the PC-PLC inhibitor D609 (48h) induced a 50% reduction of cell proliferation at doses comprised between 33 and 50 μg/ml, without inducing any relevant cytotoxic effect (cell viability 95±5%). In A431-SPH and CaSki-SPH D609 induced both cytostatic and cytotoxic effects at about 20 to 30-fold lower doses (IC50 ranging between 1.2 and 1.6 μg/ml). Furthermore, D609 treatment of A431-AD and CaSki-AD cells affected the sphere-forming efficiency, which dropped in both cells, and induced down-modulation of stem-related markers mRNA levels (Oct4, Nestin, Nanog and ALDH1 in A431; Nestin and ALDH1 in CaSki cells). Conclusions These data suggest that the inhibition of PC-PLC activity may represent a new therapeutic approach to selectively target the most aggressive and tumor promoting sub-population of floating spheres originated from squamous cancer cells possessing different proliferative and stemness potential. PMID:26402860

Enhanced expression of Gqα and PLC-β1 proteins contributes to vascular smooth muscle cell hypertrophy in SHR: role of endogenous angiotensin II and endothelin-1.

PubMed

Atef, Mohammed Emehdi; Anand-Srivastava, Madhu B

2014-07-01

Vascular Gqα signaling has been shown to contribute to cardiac hypertrophy. In addition, angiotensin II (ANG II) was shown to induce vascular smooth muscle cell (VSMC) hypertrophy through Gqα signaling; however, the studies on the role of Gqα and PLC-β1 proteins in VSMC hypertrophy in animal model are lacking. The present study was therefore undertaken to examine the role of Gqα/PLC-β1 proteins and the signaling pathways in VSMC hypertrophy using spontaneously hypertensive rats (SHR). VSMC from 16-wk-old SHR and not from 12-wk-old SHR exhibited enhanced levels of Gqα/PLC-β1 proteins compared with age-matched Wistar-Kyoto (WKY) rats as determined by Western blotting. However, protein synthesis as determined by [(3)H]leucine incorporation was significantly enhanced in VSMC from both 12- and 16-wk-old SHR compared with VSMC from age-matched WKY rats. Furthermore, the knockdown of Gqα/PLC-β1 in VSMC from 16-wk-old SHR by antisense and small interfering RNA resulted in attenuation of protein synthesis. In addition, the enhanced expression of Gqα/PLC-β1 proteins, enhanced phosphorylation of ERK1/2, and enhanced protein synthesis in VSMC from SHR were attenuated by the ANG II AT1 and endothelin-1 (ET-1) ETA receptor antagonists losartan and BQ123, respectively, but not by the ETB receptor antagonist BQ788. In addition, PD98059 decreased the enhanced expression of Gqα/PLC-β1 and protein synthesis in VSMC from SHR. These results suggest that the enhanced levels of endogenous ANG II and ET-1 through the activation of AT1 and ETA receptors, respectively, and MAP kinase signaling, enhanced the expression of Gqα/PLC-β1 proteins in VSMC from 16-wk-old SHR and result in VSMC hypertrophy. Copyright © 2014 the American Physiological Society.

Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction

PubMed Central

Scioli, Maria Giovanna; Lo Giudice, Pietro; Bielli, Alessandra; Tarallo, Valeria; De Rosa, Alfonso; De Falco, Sandro; Orlandi, Augusto

2015-01-01

Background Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO) production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC) is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery. Methods and Results We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS) reduction, inducible nitric oxide synthase (iNOS) and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and reduction of NADPH-oxidase 4 (Nox4) expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM) expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction. Conclusion PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction. Antioxidant therapy and pharmacological targeting of endothelial dysfunction may represent a promising tool for the treatment of delayed wound healing or chronic ulcers. PMID:26473356

PLC-based mode multi/demultiplexer for MDM transmission

NASA Astrophysics Data System (ADS)

Hanzawa, N.; Saitoh, K.; Sakamoto, T.; Matsui, T.; Tsujikawa, K.; Koshiba, M.; Yamamoto, F.

2013-12-01

We propose a PLC-based multi/demultiplexer (MUX/DEMUX) with a mode conversion function for mode division multiplexing (MDM) transmission applications. The PLC-based mode MUX/DEMUX can realize a low insertion loss and a wide working wavelength bandwidth. We designed and demonstrated a two-mode (LP01 and LP11 modes) and a three-mode (LP01, LP11, and LP21 modes) MUX/DEMUX for use in the C-band.

PLC Hardware Discrimination using RF-DNA fingerprinting

DTIC Science & Technology

2014-06-19

PLC HARDWARE DISCRIMINATION USING RF-DNA FINGERPRINTING THESIS Bradley C. Wright, Civilian, USAF AFIT-ENG-T-14-J-12 DEPARTMENT OF THE AIR FORCE AIR...protection in the United States. AFIT-ENG-T-14-J-12 PLC HARDWARE DISCRIMINATION USING RF-DNA FINGERPRINTING THESIS Presented to the Faculty Department...DISCRIMINATION USING RF-DNA FINGERPRINTING Bradley C. Wright, B.S.E.E. Civilian, USAF Approved: /signed/ Maj Samuel J. Stone, PhD (Chairman) /signed/ Michael A

Study on TCM Syndrome Differentiation of Primary Liver Cancer Based on the Analysis of Latent Structural Model.

PubMed

Gu, Zhan; Qi, Xiuzhong; Zhai, Xiaofeng; Lang, Qingbo; Lu, Jianying; Ma, Changping; Liu, Long; Yue, Xiaoqiang

2015-01-01

Primary liver cancer (PLC) is one of the most common malignant tumors because of its high incidence and high mortality. Traditional Chinese medicine (TCM) plays an active role in the treatment of PLC. As the most important part in the TCM system, syndrome differentiation based on the clinical manifestations from traditional four diagnostic methods has met great challenges and questions with the lack of statistical validation support. In this study, we provided evidences for TCM syndrome differentiation of PLC using the method of analysis of latent structural model from clinic data, thus providing basis for establishing TCM syndrome criteria. And also we obtain the common syndromes of PLC as well as their typical clinical manifestations, respectively.

Automated turn pike using PLC and SCADA

NASA Astrophysics Data System (ADS)

Silpa Sreedhar, P.; Aiswarya, P.; Kathirvelan, J.

2017-11-01

We propose a smart turnpike based on Programmable Logic Controller (PLC) and Supervisory Control and Data Acquisition Systems (SCADA) in this paper. In this work, the basic idea is to measure the weight of the vehicles and classify them according to its weight to the respective lanes. It is difficult for the turnpike people to monitor the whole process all the time. So, this PLC based diversion system can be implemented in turnpikes to reduce the difficulties. This method will work based on weight sensors (piezo-resistive) whose output will be fed to a PLC, which will control the vehicle diversion. Using SCADA software, the whole process can be monitored from a remote area. The algorithm developed in this successfully installed in real time system.

Fiber-Coupled Planar Light-Wave Circuit for Seed Laser Control in High Spectral Resolution Lidar Systems

NASA Technical Reports Server (NTRS)

Cook, Anthony; McNeil, Shirley; Switzer, Gregg; Battle, Philip

2010-01-01

Precise laser remote sensing of aerosol extinction and backscatter in the atmosphere requires a high-power, pulsed, frequency doubled Nd:YAG laser that is wavelength- stabilized to a narrow absorption line such as found in iodine vapor. One method for precise wavelength control is to injection seed the Nd:YAG laser with a low-power CW laser that is stabilized by frequency converting a fraction of the beam to 532 nm, and to actively frequency-lock it to an iodine vapor absorption line. While the feasibility of this approach has been demonstrated using bulk optics in NASA Langley s Airborne High Spectral Resolution Lidar (HSRL) program, an ideal, lower cost solution is to develop an all-waveguide, frequency-locked seed laser in a compact, robust package that will withstand the temperature, shock, and vibration levels associated with airborne and space-based remote sensing platforms. A key technology leading to this miniaturization is the integration of an efficient waveguide frequency doubling element, and a low-voltage phase modulation element into a single, monolithic, planar light-wave circuit (PLC). The PLC concept advances NASA's future lidar systems due to its compact, efficient and reliable design, thus enabling use on small aircraft and satellites. The immediate application for this technology is targeted for NASA Langley's HSRL system for aerosol and cloud characterization. This Phase I effort proposes the development of a potassium titanyl phosphate (KTP) waveguide phase modulator for future integration into a PLC. For this innovation, the proposed device is the integration of a waveguide-based frequency doubler and phase modulator in a single, fiber pigtail device that will be capable of efficient second harmonic generation of 1,064-nm light and subsequent phase modulation of the 532 nm light at 250 MHz, providing a properly spectrally formatted beam for HSRL s seed laser locking system. Fabrication of the integrated PLC chip for NASA Langley, planned for the Phase II effort, will require full integration and optimization of the waveguide components (SHG waveguide, splitters, and phase modulator) onto a single, monolithic device. The PLC will greatly reduce the size and weight, improve electrical- to-optical efficiency, and significantly reduce the cost of NASA Langley s current stabilized HSRL seed laser system built around a commercial off-the-shelf seed laser that is free-space coupled to a bulk doubler and bulk phase modulator.

Breeding objectives for Targhee sheep.

PubMed

Borg, R C; Notter, D R; Kuehn, L A; Kott, R W

2007-11-01

Breeding objectives were developed for Targhee sheep under rangeland production conditions. Traits considered were those for which EPD were available from the US National Sheep Improvement Program and included direct and maternal effects on 120-d weaning weight (WW and MM, respectively); yearling weight (YW); yearling fleece weight, fiber diameter, and staple length; and percent lamb crop (PLC), measured as the number of lambs born per 100 ewes lambing. A bioeconomic model was used to predict the effects of a change of 1 additive SD in EPD for each trait, holding all other traits constant at their mean, on animal performance, feed requirements, feed costs, and economic returns. Resulting economic weightings were then used to derive selection indexes. Indexes were derived separately for 3 prolificacy levels (1.41, 1.55, and 1.70 lambs/ewe lambing), 2 triplet survival levels (50 and 67%), 2 lamb pricing policies (with or without discounting of prices for heavy feeder lambs), and 3 forage cost scenarios (renting pasture, purchasing hay, or reducing flock size to accommodate increased nutrient requirements for production). Increasing PLC generally had the largest impact on profitability, although an increase in WW was equally important, with low feed costs and no discounting of prices for heavy feeder lambs. Increases in PLC were recommended at all 3 prolificacy levels, but with low triplet survival the value of increasing PLC eventually declined as the mean litter size increased to approximately 2.15 lambs/ewe lambing and above. Increasing YW (independent of WW) increased ewe maintenance costs and reduced profitability. Predicted changes in breeding values for WW and YW under index selection varied with lamb pricing policy and feed costs. With low feed costs or no discounts for heavy lambs, YW increased at a modest rate in association with increasing WW, but with high feed costs or discounting of heavy lambs, genetic trends in WW were reduced by approximately 50% to constrain increases in YW. Changes in EPD for MM or fleece traits generally had smaller effects on profitability than changes in PLC, WW, and YW. Two indexes designed to address current rangeland production conditions (low forage costs and discounting of heavy feeder lambs) or more intensive and integrated production with retained ownership and value-based marketing of lambs (higher forage costs and no discounting of heavy lambs) were anticipated to meet the needs of most Targhee producers.

Pharmacokinetics of propionyl-l-carnitine in humans: evidence for saturable tubular reabsorption

PubMed Central

Pace, S; Longo, A; Toon, S; Rolan, P; Evans, A M

2000-01-01

Aims Propionyl-l-carnitine (PLC) is an endogenous compound which, along with l-carnitine (LC) and acetyl-l-carnitine (ALC), forms a component of the endogenous carnitine pool in humans and most, if not all, animal species. PLC is currently under investigation for the treatment of peripheral artery disease, and the present study was conducted to assess the pharmacokinetics of intravenous propionyl-l-carnitine hydrochloride. Methods This was a placebo-controlled, double-blind, parallel group, dose-escalating study in which 24 healthy males were divided into four groups of six. Four subjects from each group received propionyl-l-carnitine hydrochloride and two received placebo. The doses (1 g, 2 g, 4 g and 8 g) were administered as a constant rate infusion over 2 h and blood and urine were collected for 24 h from the start of the infusion. PLC, ALC and LC in plasma and urine were quantified by h.p.l.c. Results All 24 subjects successfully completed the study and the infusions were well tolerated. In addition to the expected increase in PLC levels, the plasma concentrations and urinary excretion of LC and ALC also increased above baseline values following intravenous propionyl-l-carnitine hydrochloride administration. At a dose of 1 g, PLC was found to have a mean (± s.d.) half-life of 1.09 ± 0.15 h, a clearance of 11.6 ± 0.24 l h−1 and a volume of distribution of 18.3 ± 2.4 l. None of these parameters changed with dose. In placebo-treated subjects, endogenous PLC, LC and ALC underwent extensive renal tubular reabsorption, as indicated by renal excretory clearance to GFR ratios of less than 0.1. The renal-excretory clearance of PLC, which was 0.33 ± 0.38 l h−1 under baseline condition, increased (P < 0.001) from 1.98 ± 0.59 l h−1 at a dose of 1 g to 5.55 ± 1.50 l h−1 at a dose of 8 g (95% confidence interval for the difference was 2.18,4.97). As a consequence, the percent of the dose excreted unchanged in urine increased (P < 0.001) from 18.1 ± 5.5% (1 g) to 50.3 ± 13.3% (8 g). The renal-excretory clearance of LC and ALC also increased substantially after PLC administration and there was evidence for renal metabolism of PLC to LC and ALC. Conclusions Intravenous administration of propionyl-l-carnitine hydrochloride caused significant increases in the renal excretory clearances of PLC, LC and ALC, due to saturation of the renal tubular reabsorption process–as a consequence there was a substantial increase with dose in the fraction excreted unchanged in urine. Despite the marked increase in the renal clearance of PLC, total clearance remained unchanged, suggesting a compensatory reduction in the clearance of the compound by non excretory routes. PMID:11069438

A Systematic Review of the Outcomes of Posterolateral Corner Knee Injuries, Part 2: Surgical Treatment of Chronic Injuries.

PubMed

Moulton, Samuel G; Geeslin, Andrew G; LaPrade, Robert F

2016-06-01

There are a variety of reported surgical techniques outcomes of chronic grade III posterolateral corner (PLC) knee injuries. It is unknown if outcomes differ among the various surgical treatments. To systematically review the literature and report subjective and objective outcomes for surgical treatment strategies for chronic grade III PLC injuries to determine the optimal surgical technique. Systematic review; Level of evidence, 4. A systematic review of the literature including Cochrane, PubMed, Medline, and Embase was performed. The following search terms were used: posterolateral corner knee, posterolateral knee, posterolateral instability, multiligament knee, and knee dislocation. Inclusion criteria were outcome studies of surgical treatment for chronic PLC knee injuries with a minimum 2-year follow-up, subjective outcomes, objective outcomes including varus stability, and subgroup data on PLC injuries. Two investigators independently reviewed all abstracts. Accepted definitions of varus stability on examination or stress radiographs, and the need for revision surgery, were used to categorically define success and failure. Fifteen studies with a total of 456 patients were included in this study. The 15 studies included 5 with level 3 evidence and 10 with level 4 evidence. The mean age of the patients in each study ranged from 25.2 to 40 years, the reported mean time to surgery ranged from 5.5 to 52.8 months, and the mean follow-up duration ranged from 2 to 16.3 years. Mean postoperative Lysholm scores ranged from 65.5 to 91.8; mean postoperative International Knee Documentation Committee (IKDC) scores ranged from 62.6 to 86.0. Based on objective stability, there was an overall success rate of 90% and a 10% failure rate of PLC reconstruction. A variety of surgical techniques were reported. Chronic PLC injuries were reconstructed in all studies, and while techniques varied, the surgical management of chronic PLC injuries had a 90% success rate and a 10% failure rate according to the individual investigators' examination or stress radiographic assessment of objective outcomes. More than half of the 456 patients had a combined posterior cruciate ligament-PLC injury. Surgical techniques included variations of fibular slings, capsular shifts, and anatomic-based techniques (fibular tunnel and tibial tunnel). Further research is needed to determine the optimal surgical technique for treating chronic grade III PLC injuries. © 2015 The Author(s).

Domain organization of p130, PLC-related catalytically inactive protein, and structural basis for the lack of enzyme activity.

PubMed

Kanematsu, T; Yoshimura, K; Hidaka, K; Takeuchi, H; Katan, M; Hirata, M

2000-05-01

The 130-kDa protein (p130) was isolated as a novel inositol 1,4, 5-trisphosphate [Ins(1,4,5)P3]-binding protein similar to phospholipase C-delta1 (PLC-delta1), but lacking catalytic activity [Kanematsu, T., Takeya, H., Watanabe, Y., Ozaki, S., Yoshida, M., Koga, T., Iwanaga, S. & Hirata, M. (1992) J. Biol. Chem. 267, 6518-6525; Kanematsu, T., Misumi, Y., Watanabe, Y., Ozaki, S., Koga, T., Iwanaga, S., Ikehara, Y. & Hirata, M. (1996) Biochem. J. 313, 319-325]. To test experimentally the domain organization of p130 and structural basis for lack of PLC activity, we subjected p130 to limited proteolysis and also constructed a number of chimeras with PLC-delta1. Trypsin treatment of p130 produced four major polypeptides with molecular masses of 86 kDa, 55 kDa, 33 kDa and 25 kDa. Two polypeptides of 86 kDa and 55 kDa started at Lys93 and were calculated to end at Arg851 and Arg568, respectively. Using the same approach, it has been found that the polypeptides of 33 kDa and 25 kDa are likely to correspond to regions between Val569 and Arg851 and Lys869 and Leu1096, respectively. All the proteolytic sites were in interconnecting regions between the predicted domains, therefore supporting domain organization based on sequence similarity to PLC-delta1 and demonstrating that all domains of p130, including the unique region at the C-terminus, are stable, tightly folded structures. p130 truncated at either or both the N-terminus (94 amino acids) and C-terminus (851-1096 amino acids) expressed in COS-1 cells showed no catalytic activity, indicating that p130 has intrinsically no PLC activity. A number of chimeric molecules between p130 and PLC-delta1 were constructed and assayed for PLC activity. It was shown that structural differences in interdomain interactions exist between the two proteins, as only some domains of p130 could replace the corresponding structures in PLC-delta1 to form a functional enzyme. These results suggest that p130 and the related proteins could represent a new protein family that may play some distinct role in cells due to the capability of binding Ins(1,4,5)P3 but the lack of catalytic activity.

Frequency and characteristics of melanomas missed at a pigmented lesion clinic: a registry-based study.

PubMed

Carli, Paolo; Nardini, Paolo; Crocetti, Emanuele; De Giorgi, Vincenzo; Giannotti, Benvenuto

2004-10-01

To ensure the removal of all melanomas at an early phase, a number of benign lesions are currently excised for diagnostic evaluation. Nevertheless, little is known about the frequency of melanomas missed (neither recognized nor excised for diagnostic verification) by early detection practices. This study aimed to investigate the diagnostic performance of a specialized pigmented lesion clinic (PLC) through linkage with a local cancer registry. In 1997, 1741 individuals resident in the area of Florence and Prato, Italy, the catchment area of the Tuscany Cancer Registry (RTT), were consecutively examined at a specialized PLC that has been running since 1992 at the Department of Dermatology of Florence. The outcomes of dermatological consultations retrieved from PLC case notes were compared with all the diagnoses of both in situ and invasive melanoma recorded by the RTT until 31 December 1999. The performance of the PLC in detecting cutaneous melanoma was evaluated in terms of sensitivity, specificity and predictive values, with the RTT data as the gold standard. In the population examined at the PLC, 15 newly incident melanomas, all histologically demonstrated, were recorded by the RTT. In 13 of the 15 cases, excision of the lesion had been recommended by PLC staff, while two melanomas, one in situ and one level II 0.60 mm thick invasive, were missed and were subsequently excised 586 and 824 days, respectively, after the first PLC examination. The clinical and dermoscopic features of the invasive lesion were in agreement with a 'featureless' melanoma, and lacked the well-established parameters of malignancy. A total of 67 benign pigmented skin lesions were excised for diagnostic evaluation. Thus the PLC showed a sensitivity in detecting cutaneous melanoma of 86.7% (95% confidence interval [CI] 85.1-88.3%), a specificity of 95.4% (95% CI 94.3-96.3%), a positive predictive value of 13.7% (95% CI 12.1-15.3%) and a negative predictive value of 99.9% (95% CI 99.7-100.0%). The ratio of melanomas to benign skin lesions excised was 1:5.1. In conclusion, specialized examination of pigmented skin lesions at the PLC offered good level of diagnostic performance, with an acceptable cost in terms of benign lesions removed and overall a low risk of missing melanomas.

Professional learning communities (PLCs) for early childhood science education

NASA Astrophysics Data System (ADS)

Eum, Jungwon

This study explored the content, processes, and dynamics of Professional Learning Community (PLC) sessions. This study also investigated changes in preschool teachers' attitudes and beliefs toward science teaching after they participated in two different forms of PLCs including workshop and face-to-face PLC as well as workshop and online PLC. Multiple sources of data were collected for this study including participant artifacts and facilitator field notes during the PLC sessions. The participants in this study were eight teachers from NAEYC-accredited child care centers serving 3- to 5-year-old children in an urban Midwest city. All teachers participated in a workshop entitled, "Ramps and Pathways." Following the workshop, the first group engaged in face-to-face PLC sessions and the other group engaged in online PLC sessions. Qualitative data were collected through audio recordings, online archives, and open-ended surveys. The teachers' dialogue during the face-to-face PLC sessions was audiotaped, transcribed, and analyzed for emerging themes. Online archives during the online PLC sessions were collected and analyzed for emerging themes. Four main themes and 13 subthemes emanated from the face-to-face sessions, and 3 main themes and 7 subthemes emanated from the online sessions. During the face-to-face sessions, the teachers worked collaboratively by sharing their practices, supporting each other, and planning a lesson together. They also engaged in inquiry and reflection about their science teaching and child learning in a positive climate. During the online sessions, the teachers shared their thoughts and documentation and revisited their science teaching and child learning. Five themes and 15 subthemes emanated from the open-ended survey responses of face-to-face group teachers, and 3 themes and 7 subthemes emanated from the open-ended survey responses of online group teachers. Quantitative data collected in this study showed changes in teachers' attitudes and beliefs toward science teaching. Face-to-face group teachers' comfort with planning and doing different science activities increased significantly after the workshop and after the combination of workshop and face-to-face PLC. This study contributes to the research about various forms of professional development and their process and outcome in early childhood science education and informs early childhood professional communities of creative ways to improve science teaching and learning.

Epac2-dependent mobilization of intracellular Ca2+ by glucagon-like peptide-1 receptor agonist exendin-4 is disrupted in β-cells of phospholipase C-ɛ knockout mice

PubMed Central

Dzhura, Igor; Chepurny, Oleg G; Kelley, Grant G; Leech, Colin A; Roe, Michael W; Dzhura, Elvira; Afshari, Parisa; Malik, Sundeep; Rindler, Michael J; Xu, Xin; Lu, Youming; Smrcka, Alan V; Holz, George G

2010-01-01

Calcium can be mobilized in pancreatic β-cells via a mechanism of Ca2+-induced Ca2+ release (CICR), and cAMP-elevating agents such as exendin-4 facilitate CICR in β-cells by activating both protein kinase A and Epac2. Here we provide the first report that a novel phosphoinositide-specific phospholipase C-ɛ (PLC-ɛ) is expressed in the islets of Langerhans, and that the knockout (KO) of PLC-ɛ gene expression in mice disrupts the action of exendin-4 to facilitate CICR in the β-cells of these mice. Thus, in the present study, in which wild-type (WT) C57BL/6 mouse β-cells were loaded with the photolabile Ca2+ chelator NP-EGTA, the UV flash photolysis-catalysed uncaging of Ca2+ generated CICR in only 9% of the β-cells tested, whereas CICR was generated in 82% of the β-cells pretreated with exendin-4. This action of exendin-4 to facilitate CICR was reproduced by cAMP analogues that activate protein kinase A (6-Bnz-cAMP-AM) or Epac2 (8-pCPT-2′-O-Me-cAMP-AM) selectively. However, in β-cells of PLC-ɛ KO mice, and also Epac2 KO mice, these test substances exhibited differential efficacies in the CICR assay such that exendin-4 was partly effective, 6-Bnz-cAMP-AM was fully effective, and 8-pCPT-2′-O-Me-cAMP-AM was without significant effect. Importantly, transduction of PLC-ɛ KO β-cells with recombinant PLC-ɛ rescued the action of 8-pCPT-2′-O-Me-cAMP-AM to facilitate CICR, whereas a K2150E PLC-ɛ with a mutated Ras association (RA) domain, or a H1640L PLC-ɛ that is catalytically dead, were both ineffective. Since 8-pCPT-2′-O-Me-cAMP-AM failed to facilitate CICR in WT β-cells transduced with a GTPase activating protein (RapGAP) that downregulates Rap activity, the available evidence indicates that a signal transduction ‘module’ comprised of Epac2, Rap and PLC-ɛ exists in β-cells, and that the activities of Epac2 and PLC-ɛ are key determinants of CICR in this cell type. PMID:21041529

Effects of carbohydrate ingestion during exercise on substrate oxidation in physically active women with different body compositions.

PubMed

Mitchell, Nicole M; Potteiger, Jeffery A; Bernardoni, Brittney; Claytor, Randal P

2013-03-01

We examined the effects of consuming a 6% carbohydrate (CHO) beverage during exercise on substrate oxidation in active, young Caucasian women with higher body fat (HF) (>25%) and lower body fat (LF) (<25%). The HF group (n = 9) had 32.4% ± 5.6% fat and the LF group (n = 8) had 20.0% ± 3.0% fat. Subjects completed 2 sessions of 45 min of treadmill exercise at 55% of maximal oxygen consumption. Immediately prior to and at 15-min intervals during exercise, subjects consumed 25% of a total volume of a CHO beverage (1 g CHO·kg(-1)) or a placebo (PLC). During exercise and for 2 h after exercise, expired gases were analyzed to determine oxidation rates for CHO (CHO-OX) and fat (FAT-OX). During exercise, significant differences (p < 0.05) in CHO-OX (mg·kg fat-free mass(-1)·min(-1)) were found between groups for the CHO trial (LF, 35.4 ± 4.7 vs. HF, 29.8 ± 3.6) and the PLC trial (LF, 33.7 ± 6.4 vs. HF, 26.3 ± 4.3). CHO-OX was significantly higher during the first hour of recovery in both the LF group (CHO, 9.3 ± 2.1 vs. PLC, 5.3 ± 2.4) and the HF group (CHO, 8.7 ± 2.0 vs. PLC, 4.2 ± 1.0), but during the second hour of recovery, only the HF group had a higher CHO-OX (CHO, 5.3 ± 1.8 vs. PLC, 3.9 ± 1.1). FAT-OX was significantly lower during the first hour of recovery in both the LF group (CHO, 0.6 ± 0.4 vs. PLC, 1.0 ± 0.4) and the HF group (CHO, 0.4 ± 0.4 vs. PLC, 1.4 ± 0.4), as well as during the second hour of recovery in both the LF group (CHO, 0.8 ± 0.4 vs. PLC, 1.3 ± 0.5) and the HF group (CHO, 0.9 ± 0.6 vs. PLC, 1.6 ± 0). CHO ingestion promotes CHO-OX and suppresses FAT-OX during and following exercise in physically active women with low and high levels of body fat.

Contribution of phospholipase C-beta3 phosphorylation to the rapid attenuation of opioid-activated phosphoinositide response.

PubMed

Strassheim, D; Law, P Y; Loh, H H

1998-06-01

Activation of the delta-opioid receptor in NG108-15 neuroblastoma X glioma hybrid cells results in a transient increase at the intracellular level of inositol-1,4,5-triphosphate [Ins(1,4,5)P3]. This time course in the transient increase in the Ins(1,4,5)P3 level is distinctly different from that observed in the homologous opioid receptor desensitization as measured by the inhibition of adenylyl cyclase activity. One probable mechanism for this rapid loss in Ins(1,4,5)P3 response is the feedback regulation of the phospholipase C activity. Regulation by protein phosphorylation was suggested by the observations that the opioid-mediated response was potentiated by calphostin C, an inhibitor of protein kinase C (PKC), and was abolished by either phorbol-12-myristate-13-acetate, a PKC activator, or calyculin A, a protein phosphatase1/2A inhibitor. The direct phosphorylation of phospholipase C was demonstrated by immunoprecipitation of PLC-beta3 from metabolically labeled NG108-15 cells challenged with the delta-selective agonist [D-Pen2, D-Pen5]enkephalin (DPDPE). A time- and DPDPE concentration-dependent and naloxone-reversible increase in the PLC-beta3 phosphorylation can be demonstrated. This PLC-beta3 phosphorylation was mainly due to PKC activation because pretreatment of NG108-15 cells with calphostin C could block the DPDPE effect. Activation of the PLC-beta3 by DPDPE was one of the prerequisites for agonist-mediated PLC-beta3 phosphorylation because the aminosteroid phospholipase C inhibitor U73122 could block the DPDPE effect. In addition to DPDPE, lysophosphatidic acid (LPA) stimulated the PLC-beta3 phosphorylation, but bradykinin did not. Furthermore, the LPA- and DPDPE-mediated PLC-beta3 phosphorylation was additive and was much less than that observed with phorbol-12-myristate-13-acetate. The effect of DPDPE was specific to PLC-beta3; the betagamma-insensitive phospholipase C-beta1 was not phosphorylated in the presence of either DPDPE or LPA. These results indicate that although PKC phosphorylation of PLC-beta3 is not obligatory for the opioid receptor desensitization, it seems to play a significant facilatory role in the mechanisms allowing desensitization of opioid-activated phospholipase C response before that of adenylyl cyclase inhibition.

Comparison of 2 surgical techniques for reconstructing posterolateral corner of the knee: a cadaveric study evaluated by navigation system.

PubMed

Ho, Eric Po-Yan; Lam, Mak-Ham; Chung, Mandy Man-Ling; Fong, Daniel Tik-Pui; Law, Billy Kan-Yip; Yung, Patrick Shu-Hang; Chan, Wood-Yee; Chan, Kai-Ming

2011-01-01

This study aimed to evaluate the immediate effect on knee kinematics by 2 different techniques of posterolateral corner (PLC) reconstruction. Five intact formalin-preserved cadaveric knees were used in this study. A navigation system was used to measure knee kinematics (posterior translation, varus angulation, and external rotation) after application of a constant force and torque to the tibia. Four different conditions of the knee were evaluated during the biomechanical test: intact knee and PLC-sectioned knee and PLC-reconstructed knee by the double-femoral tunnel technique and single-femoral tunnel technique. Sectioning of the PLC structures resulted in significant increases in external rotation at 30° of flexion from 11.2° (SD, 2.6) to 24.6° (SD, 6.2), posterior translation at 30° of flexion from 3.4 mm (SD, 1.5) to 7.4 mm (SD, 3.8), and varus angulation at 0° of flexion from 2.3° (SD, 2.1) to 7.9° (SD, 5.1). Both reconstruction techniques significantly restored the varus stability. The external rotation and posterior translation at 30° of flexion after reconstruction with the double-femoral tunnel technique were 10.2° (SD, 1.3) and 3.4° (SD, 2.7), respectively, which were significantly better than those of the single-femoral tunnel technique. Both techniques of reconstruction showed improved stability compared with PLC-sectioned knees. The double-femoral tunnel technique in PLC reconstruction showed better rotational stability and resistance to posterior translation than the single-femoral tunnel technique without compromising varus stability. PLC reconstruction by a double-femoral tunnel technique achieves better rotational control and resistance to posterior translation. Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

PLC-beta2 monitors the drug-induced release of differentiation blockade in tumoral myeloid precursors.

PubMed

Brugnoli, Federica; Bovolenta, Matteo; Benedusi, Mascia; Miscia, Sebastianó; Capitani, Silvano; Bertagnolo, Valeria

2006-05-01

The differentiation therapy in treatment of acute promyelocytic leukemia (APL), based on the administration of all-trans retinoic acid (ATRA), is currently flanked with the use of As2O3, a safe and effective agent for patients showing a resistance to ATRA treatment. A synergy between ATRA and As3O3 was also reported in inducing granulocytic differentiation of APL-derived cells. We have demonstrated that phospholipase C-beta2 (PLC-beta2), highly expressed in neutrophils and nearly absent in tumoral promyelocytes, largely increases during ATRA treatment of APL-derived cells and strongly correlates with the responsiveness of APL patients to ATRA-based differentiating therapies. Here we report that, in APL-derived cells, low doses of As3O3 induce a slight increase of PLC-beta2 together with a moderate maturation, and cooperate with ATRA to provoke a significant increase of PLC-beta2 expression. Remarkably, the amounts of PLC-beta2 draw a parallel with the differentiation levels reached by both ATRA-responsive and -resistant cells treated with ATRA/As2O3 combinations. PLC-beta2 is not necessary for the progression of tumoral promyelocytes along the granulocytic lineage and is unable to overcome the differentiation block or to potentiate the agonist-induced maturation. On the other hand, since its expression closely correlates with the differentiation level reached by APL-derived cells induced to maturate by drugs presently employed in APL therapies, PLC-beta2 represents indeed a specific marker to test the ability of differentiation agents to induce the release of the maturation blockade of tumoral myeloid precursors.

Neurologic outcome after thoracolumbar partial lateral corpectomy for intervertebral disc disease in 72 dogs.

PubMed

Salger, Florian; Ziegler, Luisa; Böttcher, Irene Christine; Oechtering, Gerhard; Böttcher, Peter; Flegel, Thomas

2014-07-01

To determine neurologic outcome and factors influencing outcome after thoracolumbar partial lateral corpectomy (PLC) in dogs with intervertebral disc disease (IVDD) causing ventral spinal cord compression. Retrospective case series. Dogs with IVDD (n = 72; 87 PLC). Dogs with IVDD between T9 and L5 were included if treated by at least 1 PLC. Exclusion criteria were: previous spinal surgery, combination of PLC with another surgical procedure. Neurologic outcome was assessed by: (1) modified Frankel score (MFS) based on neurologic examinations at 4 time points (before surgery, immediately after PLC, at discharge and 4 weeks after PLC); and (2) owner questionnaire. The association of the following factors with neurologic outcome was analyzed: age, body weight, duration of current neurologic dysfunction (acute, chronic), IVDD localization, breed (chondrodystrophic, nonchondrodystrophic), number of PLCs, degree of presurgical spinal cord compression and postsurgical decompression, slot depth, presurgical MFS. Presurgical spinal cord compression was determined by CT myelography (71 dogs) or MRI (1 dog), whereas postsurgical decompression and slot depth were determined on CT myelography (69 dogs). MFS was improved in 18.7%, 31.7%, and 64.2% of dogs at the 3 postsurgical assessments, whereas it was unchanged in 62.6%, 52.8%, and 32.0% at corresponding time points. Based on owner questionnaire, 91.4% of dogs were ambulatory 6 months postsurgically with 74.5% having a normal gait. Most improvement in neurologic function developed within 6 months after surgery. Presurgical MFS was the only variable significantly associated with several neurologic outcome measurements (P < .01). PLC is an option for decompression in ventrally compressing thoracolumbar IVDD. Prognosis is associated with presurgical neurologic condition. © Copyright 2014 by The American College of Veterinary Surgeons.

The association between fasting blood glucose and the risk of primary liver cancer in Chinese males: a population-based prospective study.

PubMed

Feng, Xiaoshuang; Wang, Gang; Li, Ni; Lyu, Zhangyan; Chen, Shuohua; Wei, Luopei; Chen, Yuheng; Xie, Shuanghua; Yang, Wenjing; Yin, Jian; Cui, Hong; Chen, Hongda; Ren, Jiansong; Shi, Jufang; Wu, Shouling; Dai, Min; He, Jie

2017-10-24

To investigate the association between fasting blood glucose (FBG) levels and the risk of incident primary liver cancer (PLC) in Chinese males, a large prospective cohort was performed in the current study. A total of 109 169 males participating in the routine checkups every two years were recruited in the Kailuan male cohort study since May 2006. Cox proportional hazards regression models and restricted cubic spline (RCS) were used to evaluate the association between levels of baseline FBG and the risk of incident PLC. Compared to the males with normal FBG (3.9⩽FBG<6.1 mmol l -1 ), the males with impaired fasting glucose (IFG: 6.1⩽FBG<7.0 mmol l -1 ) and diabetes mellitus (DM: FBG ⩾7.0 mmol l -1 ) had a 60% (95% CI: 1.09-2.35) and a 58% (95% CI: 1.07-2.34) higher risk of incident PLC, respectively. Subgroup analysis found that IFG increased the risk of PLC among the non-smoker (HR=1.73, 95% CI: 1.01-2.98) and current alcohol drinker (HR=1.80, 95% CI: 1.03-3.16). While DM increased the risk of PLC especially among the males with normal BMI (<25 kg m -2 ) (HR=1.76, 95% CI: 1.05-2.94) and the HBV negativity (HR=1.89, 95% CI: 1.16-3.09), RCS analysis showed a positive non-linearly association between the FBG levels and the risk of PLC (p-overall=0.041, p-non-linear=0.049). Increased FBG may be an important and potentially modifiable exposure that could have key scientific and clinical importance for preventing PLC development.

Mycobacterium abscessus phospholipase C expression is induced during coculture within amoebae and enhances M. abscessus virulence in mice.

PubMed

Bakala N'Goma, Jean Claude; Le Moigne, Vincent; Soismier, Nathalie; Laencina, Laura; Le Chevalier, Fabien; Roux, Anne-Laure; Poncin, Isabelle; Serveau-Avesque, Carole; Rottman, Martin; Gaillard, Jean-Louis; Etienne, Gilles; Brosch, Roland; Herrmann, Jean-Louis; Canaan, Stéphane; Girard-Misguich, Fabienne

2015-02-01

Mycobacterium abscessus is a pathogenic, rapidly growing mycobacterium involved in pulmonary and cutaneo-mucous infections worldwide, to which cystic fibrosis patients are exquisitely susceptible. The analysis of the genome sequence of M. abscessus showed that this bacterium is endowed with the metabolic pathways typically found in environmental microorganisms that come into contact with soil, plants, and aquatic environments, where free-living amoebae are frequently present. M. abscessus also contains several genes that are characteristically found only in pathogenic bacteria. One of them is MAB_0555, encoding a putative phospholipase C (PLC) that is absent from most other rapidly growing mycobacteria, including Mycobacterium chelonae and Mycobacterium smegmatis. Here, we report that purified recombinant M. abscessus PLC is highly cytotoxic to mouse macrophages, presumably due to hydrolysis of membrane phospholipids. We further showed by constructing and using an M. abscessus PLC knockout mutant that loss of PLC activity is deleterious to M. abscessus intracellular survival in amoebae. The importance of PLC is further supported by the fact that M. abscessus PLC was found to be expressed only in amoebae. Aerosol challenge of mice with M. abscessus strains that were precultured in amoebae enhanced M. abscessus lung infectivity relative to M. abscessus grown in broth culture. Our study underlines the importance of PLC for the virulence of M. abscessus. Despite the difficulties of isolating M. abscessus from environmental sources, our findings suggest that M. abscessus has evolved in close contact with environmental protozoa, which supports the argument that amoebae may contribute to the virulence of opportunistic mycobacteria. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Pathological laughter as prodromal manifestation of transient ischemic attacks--case report and brief review.

PubMed

Dulamea, Adriana O; Matei, Costel; Mindruta, Ioana; Ionescu, Virgil

2015-10-12

Based on a case report, the authors reviewed the data about involuntary emotional expression disorder (IEED). IEED includes the syndromes of pathological laughing and crying (PLC) and emotional lability (EL). PLC is a rare disorder of emotional expression characterized by relatively uncontrollable episodes of laughter and crying or both that do not have an apparent motivating stimulus. Authors report the case of a 59-year-old man who presented with recurrent episodes of PLC of approximately 2 min duration, consisting of accelerated breathing, emission of guttural, snoring sounds, frowning of the eyebrows, followed by laughter accompanied by motor restlessness of all four limbs. PLC episodes preceded left carotid transient ischemic attacks (TIA's) manifested by reversible aphasia and right hemiparesis. Electroencephalography performed during PLC episodes revealed no spike-wave activity. Brain magnetic resonance imaging showed lacunar infarcts in the left lenticulo-capsulo-thalamic area and multiple round lesions in the cortical-subcortical and in the deep white matter of frontal-parietal-occipital lobes bilaterally, with T2 hyperintensity, T1 isointensity and no diffusion changes. The episodes were interpreted as transient ischemic attacks although gelastic seizures could not be excluded. The etiological investigations revealed unstable plaques on the left carotid artery bulb and the aortic arch and a degenerative mitral valve stenosis. The patient was treated first with antiplatelet therapy and antiepileptic drugs but PLC stopped only after anticoagulation was started. During follow-up the patient continued to have left carotid and vertebrobasilar TIA's being on oral anticoagulation. The patient became asymptomatic only after mitral valve replacement was performed. This case illustrates the difficulty distinguishing between gelastic epilepsy and TIA's in cases of PLC episodes and discuss the neuroanatomic bases and pathophysiology of this rare condition.

Does pyogenic liver abscess increase the risk of delayed-onset primary liver cancer?

PubMed Central

Chu, Chia-Sheng; Lin, Che-Chen; Peng, Cheng-Yuan; Chuang, Po-Heng; Su, Wen-Pang; Lai, Shih-Wei; Chen, Hsuan-Ju; Chung, Chi-Jung; Lai, Hsueh-Chou

2017-01-01

Abstract Delayed-onset primary liver cancer (PLC) including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in patients with pyogenic liver abscess (PLA) is not common. The relationship between PLA and delayed-onset PLC is unclear. We investigated the association in a nationwide cohort study. From Taiwan National Health Insurance claims data, a cohort of 17,531 patients with PLA was generated after excluding patients with a history of cancer (n = 2034) and those diagnosed with PLC (n = 572) and other cancers (n = 627) within 1 year of a diagnosis of PLA. An age-, sex-, index year-, and diabetes mellitus (DM)-matched control cohort of 70,124 persons without PLA was selected from the same dataset. Both cohorts were followed up until the end of 2011. The risk of PLC was estimated for both cohorts. The incidence of PLC was nearly 2-fold greater in the PLA group than in the control cohort (29.3 per 10,000 person-years vs. 16.2 per 10,000 person-years). The incidences of HCC and ICC were 1.5- (22.1 per 10,000 person-years vs. 15.0 per 10,000 person-years) and 11-fold greater (6.73 per 10,000 person-years vs. 0.62 per 10,000 person-years), respectively, in the PLA group than in the control cohort. The PLA cohort also had high risks of PLC (adjusted hazard ratio [aHR] = 1.56; 95% confidence interval [CI] = 1.35–1.81), HCC (aHR = 1.34; 95% CI = 1.15–1.57), and ICC (aHR = 6.94; 95% CI = 4.23–11.57). In conclusion, in this nationwide cohort study, PLA increased the risk of delayed-onset PLC. PMID:28834881

NMDA receptor blockade in the prelimbic cortex activates the mesolimbic system and dopamine-dependent opiate reward signaling.

PubMed

Tan, Huibing; Rosen, Laura G; Ng, Garye A; Rushlow, Walter J; Laviolette, Steven R

2014-12-01

N-Methyl-D-aspartate (NMDA) receptors in the medial prefrontal cortex (mPFC) are involved in opiate reward processing and modulate sub-cortical dopamine (DA) activity. NMDA receptor blockade in the prelimbic (PLC) division of the mPFC strongly potentiates the rewarding behavioural properties of normally sub-reward threshold doses of opiates. However, the possible functional interactions between cortical NMDA and sub-cortical DAergic motivational neural pathways underlying these effects are not understood. This study examines how NMDA receptor modulation in the PLC influences opiate reward processing via interactions with sub-cortical DAergic transmission. We further examined whether direct intra-PLC NMDA receptor modulation may activate DA-dependent opiate reward signaling via interactions with the ventral tegmental area (VTA). Using an unbiased place conditioning procedure (CPP) in rats, we performed bilateral intra-PLC microinfusions of the competitive NMDA receptor antagonist, (2R)-amino-5-phosphonovaleric acid (AP-5), prior to behavioural morphine place conditioning and challenged the rewarding effects of morphine with DA receptor blockade. We next examined the effects of intra-PLC NMDA receptor blockade on the spontaneous activity patterns of presumptive VTA DA or GABAergic neurons, using single-unit, extracellular in vivo neuronal recordings. We show that intra-PLC NMDA receptor blockade strongly activates sub-cortical DA neurons within the VTA while inhibiting presumptive non-DA GABAergic neurons. Behaviourally, NMDA receptor blockade activates a DA-dependent opiate reward system, as pharmacological blockade of DA transmission blocked morphine reward only in the presence of intra-PLC NMDA receptor antagonism. These findings demonstrate a cortical NMDA-mediated mechanism controlling mesolimbic DAergic modulation of opiate reward processing.

The presence of a protein activator of sarcolemmal polyphosphoinositide phospholipase C in cardiac cytosol

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

Quist, E.E.; Kriewaldt, S.D.; Powell, P.B.

1989-01-01

To study polyphosphoinositide phospholipase (PL) C, isolated sarcolemmal membranes were preincubated with Mg({sup 32}P)-ATP to label phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-diphosphate (PIP{sub 2}). After washing, PLC activity was determined by measuring the release of {sup 32}P-labeled inositol diphosphate (IP{sub 2}) and/or inositol trisphospate (IP{sub 3}) from membrane PIP and PIP{sub 2} during incubation at 25{degree}C and pH 7.4. Increasing concentrations of Ca{sup 2+} (0-100 {mu}M) increased IP{sub 2} by 100% over the 0 Ca{sup 2+} control levels. Ca{sup 2+} dependent PLC hydrolyzed both PIP and PIP{sub 2} with apparent D{sub A}'s of approximately 0.5 and 70 {mu}M. Addition ofmore » dialyzed cytosol further increased IP{sub 2} release by 250% without affecting the K{sub A}'s for Ca{sup 2+} activation. The cytosolic activator was partially purified by DEAE Sephacel chromatography was heat labile and sensitive to trypsin pretreatment identifying it as a protein. In contrast, 10 mM NaF increased the Ca{sup 2+} affinity for PLC 2-fold. These results show that cardiac sarcolemma possess a membrane bound Ca{sup 2+} dependent PLC activity which is regulated by a cytosolic protein activator and a G protein. The cytosolic activator would potentially amplify the amount of sarcolemmal polyphosphoinositides hydrolyzed by PLC in response to muscarinic receptor activation by acetylcholine. In addition, activation of PLC by NaF or other G protein activators could result from increasing the Ca{sup 2+} affinity of PLC to physiological intracellular Ca{sup 2+} levels.« less

The use of programmable logic controllers (PLC) for rocket engine component testing

NASA Technical Reports Server (NTRS)

Nail, William; Scheuermann, Patrick; Witcher, Kern

1991-01-01

Application of PLCs to the rocket engine component testing at a new Stennis Space Center Component Test Facility is suggested as an alternative to dedicated specialized computers. The PLC systems are characterized by rugged design, intuitive software, fault tolerance, flexibility, multiple end device options, networking capability, and built-in diagnostics. A distributed PLC-based system is projected to be used for testing LH2/LOx turbopumps required for the ALS/NLS rocket engines.

Engineering and Design: Control Stations and Control Systems for Navigation Locks and Dams

DTIC Science & Technology

1997-05-30

of human intelli- hypothetical lock and dam configurations. Finally, b. Terminology. (1) PLC system. The computer- based systems utilize special...electrical industry for industrial use. There- fore, for purposes of this document, a computer- based system is referred to as a PLC system. (2) Relay- based ...be custom made, because most of today’s control systems of any complexity are PLC - based , the standard size of a given motor starter cubicle is not

Olfactory transduction pathways in the Senegalese sole Solea senegalensis.

PubMed

Velez, Z; Hubbard, P C; Barata, E N; Canário, A V M

2013-09-01

This study tested whether differences in sensitivity between the upper and lower olfactory epithelia of Solea senegalensis are associated with different odorant receptors and transduction pathways, using the electro-olfactogram. Receptor mechanisms were assessed by cross-adaptation with amino acids (L-cysteine, L-phenylalanine and 1-methyl-L-tryptophan) and bile acids (taurocholic acid and cholic acid). This suggested that relatively specific receptors exist for 1-methyl-L-tryptophan and L-phenylalanine (food-related odorants) in the lower epithelium, and for taurocholic acid (conspecific-derived odorant) in the upper. Inhibition by U73122 [a phospholipase C (PLC) inhibitor] suggested that olfactory responses to amino acids were mediated mostly, but not entirely, by PLC-mediated transduction (IC50 ; 15-55 nM), whereas bile acid responses were mediated by both PLC and adenylate cyclase-cyclic adenosine monophosphate (AC-cAMP) (using SQ-22536; an AC inhibitor). Simultaneous application of both drugs rarely inhibited responses completely, suggesting possible involvement of non-PLC and non-AC mediated mechanisms. For aromatic amino acids and bile acids, there were differences in the contribution of each transduction pathway (PLC, AC and non-PLC and non-AC) between the two epithelia. These results suggest that differences in sensitivity of the two epithelia are associated with differences in odorant receptors and transduction mechanisms. © 2013 The Fisheries Society of the British Isles.

3D digital image correlation investigation of PLC effect in a new Ni-Co base superalloy

NASA Astrophysics Data System (ADS)

Gao, Y.; Fu, S. H.; Cheng, T.; Huo, X.; Zhang, Q. C.

2013-06-01

Repeated plastic instability accompanying serrated yielding in stress-strain curves and localization of deformation is observed during plastic deformation of many metallic alloys when tensile specimens are deformed under certain experimental conditions of temperature, strain rate, and pre-deformation. This phenomenon is referred to as the Portevin- Le Chatelier (PLC) effect. TMW alloy, a newly developed Ni-Co base superalloy for aircraft engine application, also exhibit PLC effect during tensile test at temperatures ranging from 300 ° to 600 °, which are also the temperature range for engine working. In this paper, a 3D digital image correlation (3D DIC) measurement system was established to observe the localization of deformation (PLC band) in a tensile test performed on TMW alloy specimen at temperature of 400 °. The 3D DIC system, with displacement measurement accuracy up to 0.01 pixels and strain measurement accuracy up to 100 μɛ, has a high performance in displacement field calculation with more than 10000 points every second on a 3.1G Hz CPU computer. The test result shows that, the PLC bands are inclined at an angle of about 60° to the tensile axis. Unlike tensile test performed on aluminums alloy, the widths of PLC bands of TMW alloy specimen, ranging from 4 mm to 4.5 mm, are much greater than the specimen thickness (0.25 mm).

Constitutive Macropinocytosis in Oncogene-transformed Fibroblasts Depends on Sequential Permanent Activation of Phosphoinositide 3-Kinase and Phospholipase C

PubMed Central

Amyere, Mustapha; Payrastre, Bernard; Krause, Ulrike; Smissen, Patrick Van Der; Veithen, Alex; Courtoy, Pierre J.

2000-01-01

Macropinocytosis results from the closure of lamellipodia generated by membrane ruffling, thereby reflecting cortical actin dynamics. Both transformation of Rat-1 fibroblasts by v-Src or K-Ras and stable transfection for expression of dominant-positive, wild-type phosphoinositide 3-kinase (PI3K) regulatory subunit p85α constitutively led to stress fiber disruption, cortical actin recruitment, extensive ruffling, and macropinosome formation, as measured by a selective acceleration of fluid-phase endocytosis. These alterations closely correlated with activation of PI3K and phosphatidylinositol-specific phospholipase C (PI-PLC), as assayed by 3-phosphoinositide synthesis in situ and in vitro and inositol 1,4,5 trisphosphate steady-state levels, respectively; they were abolished by stable transfection of v-Src–transformed cells for dominant-negative truncated p85α expression and by pharmacological inhibitors of PI3K and PI-PLC, indicating a requirement for both enzymes. Whereas PI3K activation resisted PI-PLC inhibition, PI-PLC activation was abolished by a PI3K inhibitor and dominant-negative transfection, thus placing PI-PLC downstream of PI3K. Together, these data suggest that permanent sequential activation of both PI3K and PI-PLC is necessary for the dramatic reorganization of the actin cytoskeleton in oncogene-transformed fibroblasts, resulting in constitutive ruffling and macropinocytosis. PMID:11029048

Robust, low-noise, polarization-maintaining mode-locked Er-fiber laser with a planar lightwave circuit (PLC) device as a multi-functional element.

PubMed

Kim, Chur; Kwon, Dohyeon; Kim, Dohyun; Choi, Sun Young; Cha, Sang Jun; Choi, Ki Sun; Yeom, Dong-Il; Rotermund, Fabian; Kim, Jungwon

2017-04-15

We demonstrate a new planar lightwave circuit (PLC)-based device, integrated with a 980/1550 wavelength division multiplexer, an evanescent-field-interaction-based saturable absorber, and an output tap coupler, which can be employed as a multi-functional element in mode-locked fiber lasers. Using this multi-functional PLC device, we demonstrate a simple, robust, low-noise, and polarization-maintaining mode-locked Er-fiber laser. The measured full-width at half-maximum bandwidth is 6 nm centered at 1555 nm, corresponding to 217 fs transform-limited pulse duration. The measured RIN and timing jitter are 0.22% [10 Hz-10 MHz] and 6.6 fs [10 kHz-1 MHz], respectively. Our results show that the non-gain section of mode-locked fiber lasers can be easily implemented as a single PLC chip that can be manufactured by a wafer-scale fabrication process. The use of PLC processes in mode-locked lasers has the potential for higher manufacturability of low-cost and robust fiber and waveguide lasers.

Mechanical properties of drug loaded diblock copolymer bilayers: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Grillo, Damián A.; Albano, Juan M. R.; Mocskos, Esteban E.; Facelli, Julio C.; Pickholz, Mónica; Ferraro, Marta B.

2018-06-01

In this work, we present results of coarse-grained simulations to study the encapsulation of prilocaine (PLC), both neutral and protonated, on copolymer bilayers through molecular dynamics simulations. Using a previously validated membrane model, we have simulated loaded bilayers at different drug concentrations and at low (protonated PLC) and high (neutral PLC) pH levels. We have characterized key structural parameters of the loaded bilayers in order to understand the effects of encapsulation of PLC on the bilayer structure and mechanical properties. Neutral PLC was encapsulated in the hydrophobic region leading to a thickness increase, while the protonated species partitioned between the water phase and the poly(ethylene oxide)-poly(butadiene) (PBD) interface, relaxing the PBD region and leading to a decrease in the thickness. The tangential pressures of the studied systems were calculated, and their components were decomposed in order to gain insights on their compensation. In all cases, it is observed that the loading of the membrane does not significantly decrease the stability of the bilayer, indicating that the system could be used for drug delivery.

Mechanical properties of drug loaded diblock copolymer bilayers: A molecular dynamics study.

PubMed

Grillo, Damián A; Albano, Juan M R; Mocskos, Esteban E; Facelli, Julio C; Pickholz, Mónica; Ferraro, Marta B

2018-06-07

In this work, we present results of coarse-grained simulations to study the encapsulation of prilocaine (PLC), both neutral and protonated, on copolymer bilayers through molecular dynamics simulations. Using a previously validated membrane model, we have simulated loaded bilayers at different drug concentrations and at low (protonated PLC) and high (neutral PLC) pH levels. We have characterized key structural parameters of the loaded bilayers in order to understand the effects of encapsulation of PLC on the bilayer structure and mechanical properties. Neutral PLC was encapsulated in the hydrophobic region leading to a thickness increase, while the protonated species partitioned between the water phase and the poly(ethylene oxide)-poly(butadiene) (PBD) interface, relaxing the PBD region and leading to a decrease in the thickness. The tangential pressures of the studied systems were calculated, and their components were decomposed in order to gain insights on their compensation. In all cases, it is observed that the loading of the membrane does not significantly decrease the stability of the bilayer, indicating that the system could be used for drug delivery.

Pharbilignan C induces apoptosis through a mitochondria-mediated intrinsic pathway in human breast cancer cells.

PubMed

Park, Yong Joo; Choi, Chang-Ik; Chung, Kyu Hyuck; Kim, Ki Hyun

2016-10-01

Pharbitidis Semen, the seed of Morning glory (Pharbitis nil), is a medicinal agent that has traditionally been used as a purgative in Korea. Pharbilignan C (PLC) is a dihydro[b]-benzofuran-type neolignan from Pharbitidis Semen, which reportedly exhibited the most potent cytotoxicity against human tumor cells. To further study the antiproliferative activity of PLC, its molecular mechanisms of action in two breast adenocarcinoma cells, MCF-7 and MDA-MB 231 cells were investigated. PLC inhibited the proliferation of MDA-MB 231 and MCF-7 cells, in order of sensitivity (IC50 of MDA-MB 231 cells: 7.0±2.0μM). PLC induced apoptosis in MDA-MB 231 cells with down regulation of Bcl-2 and up-regulation of Bax expression. It also decreased mitochondrial membrane potential accompanied with increasing initiator caspase, caspase-9 activation and executioner caspase, caspase-3 activation. This study demonstrates that PLC inhibited proliferation of MDA-MB 231 cells by inducing apoptosis via the mitochondria-mediated intrinsic pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cloning, Sequencing, and Role in Virulence of Two Phospholipases (A1 and C) from Mesophilic Aeromonas sp. Serogroup O:34

PubMed Central

Merino, Susana; Aguilar, Alicia; Nogueras, Maria Mercedes; Regue, Miguel; Swift, Simon; Tomás, Juan M.

1999-01-01

Two different representative recombinant clones encoding Aeromonas hydrophila lipases were found upon screening on tributyrin (phospholipase A1) and egg yolk agar (lecithinase-phospholipase C) plates of a cosmid-based genomic library of Aeromonas hydrophila AH-3 (serogroup O34) introduced into Escherichia coli DH5α. Subcloning, nucleotide sequencing, and in vitro-coupled transcription-translation experiments showed that the phospholipase A1 (pla) and C (plc) genes code for an 83-kDa putative lipoprotein and a 65-kDa protein, respectively. Defined insertion mutants of A. hydrophila AH-3 defective in either pla or plc genes were defective in phospholipase A1 and C activities, respectively. Lecithinase (phospholipase C) was shown to be cytotoxic but nonhemolytic or poorly hemolytic. A. hydrophila AH-3 plc mutants showed a more than 10-fold increase in their 50% lethal dose on fish and mice, and complementation of the plc single gene on these mutants abolished this effect, suggesting that Plc protein is a virulence factor in the mesophilic Aeromonas sp. serogroup O:34 infection process. PMID:10417167

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

PubMed

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

2001-10-16

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

Version control system of CAD documents and PLC projects

NASA Astrophysics Data System (ADS)

Khudyakov, P. Yu; Kisel’nikov, A. Yu; Startcev, I. M.; Kovalev, A. A.

2018-05-01

The paper presents the process of developing a version control system for CAD documents and PLC projects. The software was tested and the optimal composition of the modules was selected. The introduction of the system has made it possible to increase the safety and stability of the process control systems, as well as to reduce the number of conflicts for versions of CAD files. The number of incidents at the enterprise related to the use of incorrect versions of PLC projects is reduced to 0.

Families of phosphoinositide-specific phospholipase C: structure and function.

PubMed

Katan, M

1998-12-08

A large number of extracellular signals stimulate hydrolysis of phosphatidylinositol 4,5-bisphosphate by phosphoinositide-specific phospholipase C (PI-PLC). PI-PLC isozymes have been found in a broad spectrum of organisms and although they have common catalytic properties, their regulation involves different signalling pathways. A number of recent studies provided an insight into domain organisation of PI-PLC isozymes and contributed towards better understanding of the structural basis for catalysis, cellular localisation and molecular changes that could underlie the process of their activation.

Evidence for glycosyl-phosphatidylinositol anchoring of Toxoplasma gondii major surface antigens

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

Tomavo, S.; Schwarz, R.T.; Dubremetz, J.F.

1989-10-01

The four major surface antigens of Toxoplasma gondii tachyzoites (P43, P35, P30, and P22) were made water soluble by phosphatidylinositol-specific phospholipase C (PI-PLC). These antigens were biosynthetically labeled with {sup 3}H-fatty acids, ({sup 3}H)ethanolamine, and ({sup 3}H)carbohydrates. Treatment of {sup 3}H-fatty-acid-labeled parasite lysates with PI-PLC removed the radioactive label from these antigens. A cross-reacting determinant was exposed on these antigens after PI-PLC treatment.

Relationships between posterior ligamentous complex injury and radiographic parameters in patients with thoracolumbar burst fractures.

PubMed

Hiyama, Akihiko; Watanabe, Masahiko; Katoh, Hiroyuki; Sato, Masato; Nagai, Toshihiro; Mochida, Joji

2015-02-01

The purpose of this study was to determine whether radiographic findings associated with thoracolumbar burst fractures could also indicate the presence of posterior ligamentous complex (PLC) injuries, which were identified through short-tau inversion-recovery (STIR)-weighted MRI. Sixty-four patients were surgically treated for thoracolumbar burst fractures between April 2007 and February 2014 at our institution. Twenty-four patients were excluded from this study because of the lack of STIR-weighted MRIs, and therefore 40 patients were included in this study. The patients were divided into two groups based upon the integrity of the PLC, which was evaluated using STIR-weighted MRI: a P group with a PLC injury and a C group without such injury. The following radiographic parameters were evaluated: loss of vertebral body height (LOVBH), local kyphosis (LK), vertebral body translation, canal compromise (sagittal transverse ratio, STR), interlaminar distance (ISD), supraspinous distance (SSD) and interspinous distance (ISD). Frankel scale score and total severity score (load sharing and thoracolumbar injury classification systems, respectively) were also evaluated. Preoperative STIR-weighted MRI showed that 25 patients had a PLC injury (P group: 15 men and 10 women), and 15 patients did not have a PLC injury (C group: 8 men and 7 women). More patients in the P group had an LK>20°: 14 patients in the P group and 1 patient in the C group (p<0.01). The % SSD differed between the P and C groups (118.8%±53.4% and 88.0%±24.3%, respectively; p<0.05). Multivariate logistic analysis showed that an LK>20° was a risk factor for PLC injury in patients with thoracolumbar burst fractures (odds ratio, 55.5 [95% confidence interval, 1.30-2360.1]; p<0.05). These results demonstrate that while LOVBH, vertebral body translation, and canal compromise do not correlate significantly with the presence of a PLC injury in patients with thoracolumbar fractures, an LK>20° and increased % SSD are associated with a PLC injury. Copyright © 2014 Elsevier Ltd. All rights reserved.

MathWorks Simulink and C++ integration with the new VLT PLC-based standard development platform for instrument control systems

NASA Astrophysics Data System (ADS)

Kiekebusch, Mario J.; Di Lieto, Nicola; Sandrock, Stefan; Popovic, Dan; Chiozzi, Gianluca

2014-07-01

ESO is in the process of implementing a new development platform, based on PLCs, for upcoming VLT control systems (new instruments and refurbishing of existing systems to manage obsolescence issues). In this context, we have evaluated the integration and reuse of existing C++ libraries and Simulink models into the real-time environment of BECKHOFF Embedded PCs using the capabilities of the latest version of TwinCAT software and MathWorks Embedded Coder. While doing so the aim was to minimize the impact of the new platform by adopting fully tested solutions implemented in C++. This allows us to reuse the in house expertise, as well as extending the normal capabilities of the traditional PLC programming environments. We present the progress of this work and its application in two concrete cases: 1) field rotation compensation for instrument tracking devices like derotators, 2) the ESO standard axis controller (ESTAC), a generic model-based controller implemented in Simulink and used for the control of telescope main axes.

Developing a PLC-friendly state machine model: lessons learned

NASA Astrophysics Data System (ADS)

Pessemier, Wim; Deconinck, Geert; Raskin, Gert; Saey, Philippe; Van Winckel, Hans

2014-07-01

Modern Programmable Logic Controllers (PLCs) have become an attractive platform for controlling real-time aspects of astronomical telescopes and instruments due to their increased versatility, performance and standardization. Likewise, vendor-neutral middleware technologies such as OPC Unified Architecture (OPC UA) have recently demonstrated that they can greatly facilitate the integration of these industrial platforms into the overall control system. Many practical questions arise, however, when building multi-tiered control systems that consist of PLCs for low level control, and conventional software and platforms for higher level control. How should the PLC software be structured, so that it can rely on well-known programming paradigms on the one hand, and be mapped to a well-organized OPC UA interface on the other hand? Which programming languages of the IEC 61131-3 standard closely match the problem domains of the abstraction levels within this structure? How can the recent additions to the standard (such as the support for namespaces and object-oriented extensions) facilitate a model based development approach? To what degree can our applications already take advantage of the more advanced parts of the OPC UA standard, such as the high expressiveness of the semantic modeling language that it defines, or the support for events, aggregation of data, automatic discovery, ... ? What are the timing and concurrency problems to be expected for the higher level tiers of the control system due to the cyclic execution of control and communication tasks by the PLCs? We try to answer these questions by demonstrating a semantic state machine model that can readily be implemented using IEC 61131 and OPC UA. One that does not aim to capture all possible states of a system, but rather one that attempts to organize the course-grained structure and behaviour of a system. In this paper we focus on the intricacies of this seemingly simple task, and on the lessons that we've learned during the development process of such a "PLC-friendly" state machine model.

77 FR 20987 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-09

... Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... the Federal Register. That AD applies to RB211-Trent 800 series turbofan engines. The last comment...

Pyogenic liver abscess as a warning sign for primary liver cancer: a nationwide population-based study.

PubMed

Huang, Wen-Kuan; Lin, Yung-Chang; Chiou, Meng-Jiun; Yang, Tsai-Sheng; Chang, John Wen-Cheng; Yu, Kuang-Hui; Kuo, Chang-Fu; See, Lai-Chu

2013-01-01

There have been no large-scale population-based studies to estimate the subsequent risk of primary liver cancer (PLC) among patients with pyogenic liver abscess (PLA). This study aimed to provide relevant data. The Taiwan Longitudinal Health Insurance Database for the years 2000 and 2005 was used. The PLA group were adult inpatients who were newly diagnosed with PLA from 2000 to 2008. The control group was randomly selected and matched with the PLA group in terms of age, sex, and date in which medical treatment was sought other than for PLA. There were 1,987 patients each in the PLA and control groups. In total, 56 had PLC, 48 (2.4%, 601.5 per 100,000 person-years) from the PLA group, and 8 from the control group. After adjusting for potential covariates, the hazard ratio of PLC for the PLA group was 3.4 times that of the control group (95% confidence interval = 1.6-7.3, p <0.001). The PLC risk for the PLA group was significantly higher within the first year after PLA diagnosis (hazard ratio: 35.4) as compared with the control group and became insignificant (hazard ratio: 2.0, 95% confidence interval = 0.8-4.9) more than one year after PLA diagnosis. Patients with PLA have a higher rate of PLC than matched controls, especially within the first year after the diagnosis of PLA, suggesting PLA is a warning sign for PLC.

Unraveling the Posterolateral Corner of the Knee.

PubMed

Rosas, Humberto G

2016-10-01

Although rare, posterolateral corner (PLC) injuries can result in sustained instability and failed cruciate ligament reconstruction if they are not diagnosed. The anatomy of the PLC was once thought to be perplexing and esoteric-in part because of the varying nomenclature applied to this region in the literature, which added unnecessary complexity. More recently, three major structures have been described as the primary stabilizers of the PLC on the basis of biomechanical study findings: the lateral collateral ligament, popliteus tendon, and popliteofibular ligament. An understanding of the anatomic relationships of these structures with each other and with the surrounding osseous structures is invaluable for improving the diagnostic accuracy of magnetic resonance (MR) imaging in the detection of PLC injuries and allowing a structured and systematic approach when interpreting the imaging findings. The majority of PLC injuries do not occur in isolation and are part of a more complex injury pattern that typically involves other vital supporting structures such as the cruciate ligaments, menisci, and medial ligamentous structures. Therefore, imaging has an ever-increasing role in the recognition of these injuries, as the clinical findings may be difficult to interpret adequately owing to synchronous injuries that dominate the physical examination findings. Furthermore, the diagnosis of acute high-grade PLC injuries is critical because early and aggressive treatment, for which surgical reconstruction is often required, leads to improved long-term outcomes and the prevention of persistent instability that would otherwise result in varus thrust gait, chronic pain, and accelerated cartilage damage. © RSNA, 2016.

Charge Shielding of PIP2 by Cations Regulates Enzyme Activity of Phospholipase C

PubMed Central

Seo, Jong Bae; Jung, Seung-Ryoung; Huang, Weigang; Zhang, Qisheng; Koh, Duk-Su

2015-01-01

Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) of the plasma membrane by phospholipase C (PLC) generates two critical second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. For the enzymatic reaction, PIP2 binds to positively charged amino acids in the pleckstrin homology domain of PLC. Here we tested the hypothesis that positively charged divalent and multivalent cations accumulate around the negatively charged PIP2, a process called electrostatic charge shielding, and therefore inhibit electrostatic PIP2-PLC interaction. This charge shielding of PIP2 was measured quantitatively with an in vitro enzyme assay using WH-15, a PIP2 analog, and various recombinant PLC proteins (β1, γ1, and δ1). Reduction of PLC activity by divalent cations, polyamines, and neomycin was well described by a theoretical model considering accumulation of cations around PIP2 via their electrostatic interaction and chemical binding. Finally, the charge shielding of PIP2 was also observed in live cells. Perfusion of the cations into cells via patch clamp pipette reduced PIP2 hydrolysis by PLC as triggered by M1 muscarinic receptors with a potency order of Mg2+ < spermine4+ < neomycin6+. Accumulation of divalent cations into cells through divalent-permeable TRPM7 channel had the same effect. Altogether our results suggest that Mg2+ and polyamines modulate the activity of PLCs by controlling the amount of free PIP2 available for the enzymes and that highly charged biomolecules can be inactivated by counterions electrostatically. PMID:26658739

Charge Shielding of PIP2 by Cations Regulates Enzyme Activity of Phospholipase C.

PubMed

Seo, Jong Bae; Jung, Seung-Ryoung; Huang, Weigang; Zhang, Qisheng; Koh, Duk-Su

2015-01-01

Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) of the plasma membrane by phospholipase C (PLC) generates two critical second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. For the enzymatic reaction, PIP2 binds to positively charged amino acids in the pleckstrin homology domain of PLC. Here we tested the hypothesis that positively charged divalent and multivalent cations accumulate around the negatively charged PIP2, a process called electrostatic charge shielding, and therefore inhibit electrostatic PIP2-PLC interaction. This charge shielding of PIP2 was measured quantitatively with an in vitro enzyme assay using WH-15, a PIP2 analog, and various recombinant PLC proteins (β1, γ1, and δ1). Reduction of PLC activity by divalent cations, polyamines, and neomycin was well described by a theoretical model considering accumulation of cations around PIP2 via their electrostatic interaction and chemical binding. Finally, the charge shielding of PIP2 was also observed in live cells. Perfusion of the cations into cells via patch clamp pipette reduced PIP2 hydrolysis by PLC as triggered by M1 muscarinic receptors with a potency order of Mg2+ < spermine4+ < neomycin6+. Accumulation of divalent cations into cells through divalent-permeable TRPM7 channel had the same effect. Altogether our results suggest that Mg2+ and polyamines modulate the activity of PLCs by controlling the amount of free PIP2 available for the enzymes and that highly charged biomolecules can be inactivated by counterions electrostatically.

The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder.

PubMed

Greene, R K; Spanos, M; Alderman, C; Walsh, E; Bizzell, J; Mosner, M G; Kinard, J L; Stuber, G D; Chandrasekhar, T; Politte, L C; Sikich, L; Dichter, G S

2018-03-27

Intranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, thus, has received considerable interest as a potential ASD therapeutic agent. Although preclinical research indicates that OT modulates the functional output of the mesocorticolimbic dopamine system that processes rewards, no clinical brain imaging study to date has examined the effects of OT on this system using a reward processing paradigm. To address this, we used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD. In this placebo-controlled double-blind study, 28 children and adolescents with ASD (age: M = 13.43 years, SD = 2.36) completed two fMRI scans, one after intranasal OT administration and one after PLC administration. During both scanning sessions, participants completed social and nonsocial incentive delay tasks. Task-based neural activation and connectivity were examined to assess the impact of OT relative to PLC on mesocorticolimbic brain responses to social and nonsocial reward anticipation and outcomes. Central analyses compared the OT and PLC conditions. During nonsocial reward anticipation, there was greater activation in the right nucleus accumbens (NAcc), left anterior cingulate cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal cortex, and right frontal pole (FP) during the OT condition relative to PLC. Alternatively, during social reward anticipation and outcomes, there were no significant increases in brain activation during the OT condition relative to PLC. A Treatment Group × Reward Condition interaction revealed relatively greater activation in the right NAcc, right caudate nucleus, left ACC, and right OFC during nonsocial relative to social reward anticipation during the OT condition relative to PLC. Additionally, these analyses revealed greater activation during nonsocial reward outcomes during the OT condition relative to PLC in the right OFC and left FP. Finally, functional connectivity analyses generally revealed changes in frontostriatal connections during the OT condition relative to PLC in response to nonsocial, but not social, rewards. The effects of intranasal OT administration on mesocorticolimbic brain systems that process rewards in ASD were observable primarily during the processing of nonsocial incentive salience stimuli. These findings have implications for understanding the effects of OT on neural systems that process rewards, as well as for experimental trials of novel ASD treatments developed to ameliorate social communication impairments in ASD.

Purification and characterization of an extracellular 29-kilodalton phospholipase C from Listeria monocytogenes.

PubMed Central

Geoffroy, C; Raveneau, J; Beretti, J L; Lecroisey, A; Vazquez-Boland, J A; Alouf, J E; Berche, P

1991-01-01

We purified and characterized an extracellular phospholipase produced by Listeria monocytogenes. This enzyme was separated as a homogeneous protein of 29 kDa by chromatography on DEAE-52 cellulose and Bio-Gel P100 columns. It is a zinc-dependent phospholipase C (PLC) that is mainly active at pH 6 to 7 and expresses lecithinase activity and a weaker sphingomyelinase activity. The exoenzyme also hydrolyzed phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin but not phosphatidylinositol. It was distinct from the 36-kDa phosphatidylinositol PLC produced by L. monocytogenes and from the L. ivanovii sphingomyelinase. The pure protein expressed a weak, calcium-independent hemolytic activity and was not toxic in mice. Western immunoblot analysis using a rabbit immune serum raised against the enzyme showed that all virulent strains of L. monocytogenes tested produced in the culture supernatant a 29-kDa PLC. In contrast, no proteins antigenically related to the 29-kDa PLC were detected in supernatants of L. ivanovii, L. seeligeri, L. innocua, or L. welshimeri. The role in virulence of the 29-kDa PLC specifically produced by L. monocytogenes remains to be established. Images PMID:1904842

Regulation of platelet activating factor receptor coupled phosphoinositide-specific phospholipase C activity

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

Morrison, W.J.

1988-01-01

The major objectives of this study were two-fold. The first was to establish whether binding of platelet activating factor (PAF) to its receptor was integral to the stimulation of polyphosphoinositide-specific phospholipase C (PLC) in rabbit platelets. The second was to determine regulatory features of this receptor-coupled mechanism. ({sup 3}H)PAF binding demonstrated two binding sites, a high affinity site with a inhibitory constant (Ki) of 2.65 nM and a low affinity site with a Ki of 0.80 {mu}M. PAF receptor coupled activation of phosphoinositide-specific PLC was studied in platelets which were made refractory, by short term pretreatments, to either PAF ormore » thrombin. Saponin-permeabilized rabbit platelets continue to regulate the mechanism(s) coupling PAF receptors to PLC stimulation. However, TRP{gamma}S and GDP{beta}S, which affect guanine nucleotide regulatory protein functions, were unable to modulate the PLC activity to any appreciable extent as compared to PAF. The possible involvement of protein kinase C (PKC) activation in regulating PAF-stimulated PLC activity was studied in rabbit platelets pretreated with staurosporine followed by pretreatments with PAF or phorbol 12-myristate 13-acetate (PMA).« less

Characterization, mechanical behavior and in vitro evaluation of a melt-drawn scaffold for esophageal tissue engineering.

PubMed

Tan, Yu Jun; Yeong, Wai Yee; Tan, Xipeng; An, Jia; Chian, Kerm Sin; Leong, Kah Fai

2016-04-01

Tubular esophageal scaffolds with fiber diameter ranging from 13.9±1.7μm to 65.7±6.2μm were fabricated from the highly elastic poly(l-lactide-co-ε-caprolactone) (PLC) via a melt-drawing method. The morphology, crystallinity, thermal and mechanical properties of the PLC fibers were investigated. They were highly aligned and have a uniform diameter. PLC is found to be semicrystalline consisting of α- and β- lactide (LA) crystals. The crystallinity increases up to 16.8% with increasing melt-drawing speeds due to strain-induced crystallization. Modulus and strength increases while ductility decreases with an increase in crystallinity of the PLC samples. Moisture will not degrade the overall tensile properties but affect its tangent modulus at the low strain. L929 cells are able to attach and proliferate on the scaffolds very well. The cells seeded on the scaffolds show normal morphology with >90% cell viability after 6 days of culture. These results demonstrate that the PLC fibrous scaffold has good potential for use in esophageal tissue engineering application. Copyright © 2015 Elsevier Ltd. All rights reserved.

The professional learning community as perceived by Israeli school superintendents, principals and teachers

NASA Astrophysics Data System (ADS)

Schechter, Chen

2012-12-01

A professional learning community (PLC) facilitates collaborative learning among colleagues at all levels in their common working environment. PLCs are particularly useful in schools, with teachers and principals meeting regularly to solve problems relating to teaching and learning. Being a means of improving student achievement, PLCs have received growing support from researchers and practitioners alike, yet some professionals are still exploring ways to develop learning networks focusing on teaching and learning issues. The purpose of this study was to examine Israeli teachers', principals', and superintendents' perceptions of inhibiting and fostering factors of the PLC. In this qualitative, topic-oriented study, face-to-face interviews were conducted with 15 teachers from elementary, middle and secondary schools and their respective principals (15) and superintendents (15). Generating themes was inductive, grounded in the perspectives articulated by participants. The principals and the teachers indicated that overload, a lack of resources and top-down commands were PLC-inhibiting factors. The superintendents saw the principal's leadership style as a main PLC-fostering factor. Understanding how these three echelons in the school system perceive the inhibiting and fostering factors of a PLC could indicate whether and how this collaborative learning process can be nurtured and sustained in schools.

Bacillus cereus Induces Permeability of an In Vitro Blood-Retina Barrier▿

PubMed Central

Moyer, A. L.; Ramadan, R. T.; Thurman, J.; Burroughs, A.; Callegan, M. C.

2008-01-01

Most Bacillus cereus toxin production is controlled by the quorum-sensing-dependent, pleiotropic global regulator plcR, which contributes to the organism's virulence in the eye. The purpose of this study was to analyze the effects of B. cereus infection and plcR-regulated toxins on the barrier function of retinal pigment epithelium (RPE) cells, the primary cells of the blood-retina barrier. Human ARPE-19 cells were apically inoculated with wild-type or quorum-sensing-deficient B. cereus, and cytotoxicity was analyzed. plcR-regulated toxins were not required for B. cereus-induced RPE cytotoxicity, but these toxins did increase the rate of cell death, primarily by necrosis. B. cereus infection of polarized RPE cell monolayers resulted in increased barrier permeability, independent of plcR-regulated toxins. Loss of both occludin and ZO-1 expression occurred by 8 h postinfection, but alterations in tight junctions appeared to precede cytotoxicity. Of the several proinflammatory cytokines analyzed, only interleukin-6 was produced in response to B. cereus infection. These results demonstrate the deleterious effects of B. cereus infection on RPE barrier function and suggest that plcR-regulated toxins may not contribute significantly to RPE barrier permeability during infection. PMID:18268029

10 CFR 26.403 - Written policy and procedures.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Written policy and procedures. 26.403 Section 26.403 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS FFD Program for Construction § 26.403 Written policy and procedures. (a) Licensees and other entities who implement an FFD program under this...

10 CFR 26.403 - Written policy and procedures.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Written policy and procedures. 26.403 Section 26.403 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS FFD Program for Construction § 26.403 Written policy and procedures. (a) Licensees and other entities who implement an FFD program under this...

10 CFR 26.403 - Written policy and procedures.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Written policy and procedures. 26.403 Section 26.403 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS FFD Program for Construction § 26.403 Written policy and procedures. (a) Licensees and other entities who implement an FFD program under this...

10 CFR 26.403 - Written policy and procedures.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Written policy and procedures. 26.403 Section 26.403 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS FFD Program for Construction § 26.403 Written policy and procedures. (a) Licensees and other entities who implement an FFD program under this...

10 CFR 26.403 - Written policy and procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Written policy and procedures. 26.403 Section 26.403 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS FFD Program for Construction § 26.403 Written policy and procedures. (a) Licensees and other entities who implement an FFD program under this...

Weintek interfaces for controlling the position of a robotic arm

NASA Astrophysics Data System (ADS)

Barz, C.; Ilia, M.; Ilut, T.; Pop-Vadean, A.; Pop, P. P.; Dragan, F.

2016-08-01

The paper presents the use of Weintek panels to control the position of a robotic arm, operated step by step on the three motor axes. PLC control interface is designed with a Weintek touch screen. The HMI Weintek eMT3070a is the user interface in the process command of the PLC. This HMI controls the local PLC, entering the coordinate on the axes X, Y and Z. The subject allows the development in a virtual environment for e-learning and monitoring the robotic arm actions.

Design and implementation of an Internet based effective controlling and monitoring system with wireless fieldbus communications technologies for process automation--an experimental study.

PubMed

Cetinceviz, Yucel; Bayindir, Ramazan

2012-05-01

The network requirements of control systems in industrial applications increase day by day. The Internet based control system and various fieldbus systems have been designed in order to meet these requirements. This paper describes an Internet based control system with wireless fieldbus communication designed for distributed processes. The system was implemented as an experimental setup in a laboratory. In industrial facilities, the process control layer and the distance connection of the distributed control devices in the lowest levels of the industrial production environment are provided with fieldbus networks. In this paper, the Internet based control system that will be able to meet the system requirements with a new-generation communication structure, which is called wired/wireless hybrid system, has been designed on field level and carried out to cover all sectors of distributed automation, from process control, to distributed input/output (I/O). The system has been accomplished by hardware structure with a programmable logic controller (PLC), a communication processor (CP) module, two industrial wireless modules and a distributed I/O module, Motor Protection Package (MPP) and software structure with WinCC flexible program used for the screen of Scada (Supervisory Control And Data Acquisition), SIMATIC MANAGER package program ("STEP7") used for the hardware and network configuration and also for downloading control program to PLC. Copyright © 2012 ISA. Published by Elsevier Ltd. All rights reserved.

Choline catabolism to glycine betaine contributes to Pseudomonas aeruginosa survival during murine lung infection.

PubMed

Wargo, Matthew J

2013-01-01

Pseudomonas aeruginosa can acquire and metabolize a variety of molecules including choline, an abundant host-derived molecule. In P. aeruginosa, choline is oxidized to glycine betaine which can be used as an osmoprotectant, a sole source of carbon and nitrogen, and as an inducer of the virulence factor, hemolytic phospholipase C (PlcH) via the transcriptional regulator GbdR. The primary objective was to determine the contribution of choline conversion to glycine betaine to P. aeruginosa survival during mouse lung infection. A secondary objective was to gain insight into the relative contributions of the different roles of glycine betaine to P. aeruginosa survival during infection. Using a model of acute murine pneumonia, we determined that deletion of the choline oxidase system (encoded by betBA) decreased P. aeruginosa survival in the mouse lung. Deletion of the glycine betaine demethylase genes (gbcA-B), required for glycine betaine catabolism, did not impact P. aeruginosa survival in the lung. Thus, the defect of the betBA mutant was not due to a requirement for glycine betaine catabolism or dependence on a downstream metabolite. Deletion of betBA decreased the abundance of plcH transcript during infection, which suggested a role for PlcH in the betBA survival defect. To test the contribution of plcH to the betBA mutant phenotype a betBAplcHR double deletion mutant was generated. The betBA and betBAplcHR double mutant had a small but significant survival defect compared to the plcHR single mutant, suggesting that regulation of plcH expression is not the only role for glycine betaine during infection. The conclusion was that choline acquisition and its oxidation to glycine betaine contribute to P. aeruginosa survival in the mouse lung. While defective plcH induction can explain a portion of the betBA mutant phenotype, the exact mechanisms driving the betBA mutant survival defect remain unknown.

Choline Catabolism to Glycine Betaine Contributes to Pseudomonas aeruginosa Survival during Murine Lung Infection

PubMed Central

Wargo, Matthew J.

2013-01-01

Pseudomonas aeruginosa can acquire and metabolize a variety of molecules including choline, an abundant host-derived molecule. In P. aeruginosa, choline is oxidized to glycine betaine which can be used as an osmoprotectant, a sole source of carbon and nitrogen, and as an inducer of the virulence factor, hemolytic phospholipase C (PlcH) via the transcriptional regulator GbdR. The primary objective was to determine the contribution of choline conversion to glycine betaine to P. aeruginosa survival during mouse lung infection. A secondary objective was to gain insight into the relative contributions of the different roles of glycine betaine to P. aeruginosa survival during infection. Using a model of acute murine pneumonia, we determined that deletion of the choline oxidase system (encoded by betBA) decreased P. aeruginosa survival in the mouse lung. Deletion of the glycine betaine demethylase genes (gbcA-B), required for glycine betaine catabolism, did not impact P. aeruginosa survival in the lung. Thus, the defect of the betBA mutant was not due to a requirement for glycine betaine catabolism or dependence on a downstream metabolite. Deletion of betBA decreased the abundance of plcH transcript during infection, which suggested a role for PlcH in the betBA survival defect. To test the contribution of plcH to the betBA mutant phenotype a betBAplcHR double deletion mutant was generated. The betBA and betBAplcHR double mutant had a small but significant survival defect compared to the plcHR single mutant, suggesting that regulation of plcH expression is not the only role for glycine betaine during infection. The conclusion was that choline acquisition and its oxidation to glycine betaine contribute to P. aeruginosa survival in the mouse lung. While defective plcH induction can explain a portion of the betBA mutant phenotype, the exact mechanisms driving the betBA mutant survival defect remain unknown. PMID:23457628

Association of neutrophil-lymphocyte ratio and T lymphocytes with the pathogenesis and progression of HBV-associated primary liver cancer

PubMed Central

Han, Junyan; Wang, Lijia; Li, Mengge; Jiang, Yuyong; Wang, Xianbo; Yang, Zhiyun

2017-01-01

Background The neutrophil–lymphocyte ratio (NLR) is a new prognostic predictor for patients with liver cancer. The association of NLR and T lymphocytes with the pathogenesis and progression of liver cancer is poorly understood. Methods Seventy-three patients with hepatitis B virus (HBV)-associated primary liver cancer (HBV-PLC), 50 patients with HBV-associated liver cirrhosis (HBV-LC) and 37 patients with chronic HBV infection (CHB) were prospectively enrolled from July 1, 2013 to February 28, 2014 in Beijing Ditan Hospital, Capital Medical University (Beijing, China). The NLR, proportions and concentrations of neutrophils and lymphocytes, concentration of subpopulations of lymphocytes, and the expression of CD31 (index for recent thymic output) and HLA-DR (index for activation of T lymphocytes) of T cells in the peripheral blood samples of the patients were assessed and statistically compared between different groups. Results The NLR was significantly increased from patients with CHB, those with HBV-LC to those with HBV-PLC (P<0.05), along with significant increase of neutrophils and decrease of lymphocytes in the same way (P<0.05). The concentrations of T lymphocytes, natural killer cells, B cells, CD4+ T cells and CD8+ T cells were decreased from patients with CHB, those with HBV-LC to those with HBV-PLC, and were significantly reduced in patients with HBV-PLC compared with those in patients with CHB (P<0.05). The CD31 and HLA-DR expression of naive CD4+ and CD8+ T cells was significantly decreased and increased, respectively in patients with HBV-PLC compared with that in patients with CHB. Conclusions Elevated NLR, resulted from the increase of neutrophils and decrease of lymphocytes, is positively associated with the pathogenesis and progression of HBV-PLC. The reduced thymic output and hyperactivation of T lymphocytes may contribute to the decrease of T lymphocytes, which could be also related to the pathogenesis of HBV-PLC. PMID:28231294

Posterolateral Corner Reconstruction using the Anatomical Two-Tailed Graft Technique: Clinical Outcomes in the Multiligament Injured Knee.

PubMed

Woodmass, Jarret M; Sanders, Thomas L; Johnson, Nick R; Wu, Isabella T; Krych, Aaron J; Stuart, Michael J; Levy, Bruce A

2018-02-14

Injury to the posterolateral corner (PLC) of the knee can lead to both varus and rotational instability. Multiple PLC reconstruction techniques have been described, including one-tailed graft (fibula-based constructs) or two-tailed graft (combined fibula- and tibia-based constructs). The purpose of our study was to evaluate the clinical outcomes of anatomical two-tailed graft reconstruction of the PLC in the setting of multiligament knee injuries (MKLIs) with grade III varus instability. Patients were identified through a prospective MLKI database between 2004 and 2013. Patients who received fibular collateral ligament and PLC reconstructions using a two-tailed graft and had a minimum follow-up of 2 years were included. Patients were assessed for clinical laxity grade, range of motion, and functional outcomes using Lysholm and International Knee Documentation Committee (IKDC) scores. Twenty patients (16 male, 4 female) with a mean age of 30.7 (range: 16-52) and a mean follow-up of 52.2 months (range: 24-93 months) were included. Knee dislocation (KD) grades included: 4 KD-1, 10 KD 3-L, 5 KD-4, and 1 KD-5. No patients had isolated PLC injuries. Mean IKDC and Lysholm score were 73.1 ± 25.8 and 78 ± 26, respectively. Mean range of motion was -1.1 to 122.8. In full extension, two patients (10%) had grade 1 laxity to varus stress. In 30 degrees of knee flexion, five (25%) patients had grade 1 laxity, and two (10%) had grade 2 laxity. Anatomical two-tailed PLC reconstruction can reliably restore varus stability when performed on patients with MLKIs and type C posterolateral instability with hyperextension external rotation recurvatum deformity. Satisfactory functional outcome scores were achieved in the majority of patients. This study supports the use of an anatomical two-tailed PLC reconstruction in the multiligament injured knee. The level of evidence is IV, case series. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Validation of life-charts documented with the personal life-chart app - a self-monitoring tool for bipolar disorder.

PubMed

Schärer, Lars O; Krienke, Ute J; Graf, Sandra-Mareike; Meltzer, Katharina; Langosch, Jens M

2015-03-14

Long-term monitoring in bipolar affective disorders constitutes an important therapeutic and preventive method. The present study examines the validity of the Personal Life-Chart App (PLC App), in both German and in English. This App is based on the National Institute of Mental Health's Life-Chart Method, the de facto standard for long-term monitoring in the treatment of bipolar disorders. Methods have largely been replicated from 2 previous Life-Chart studies. The participants documented Life-Charts with the PLC App on a daily basis. Clinicians assessed manic and depressive symptoms in clinical interviews using the Inventory of Depressive Symptomatology, clinician-rated (IDS-C) and the Young Mania Rating Scale (YMRS) on a monthly basis on average. Spearman correlations of the total scores of IDS-C and YMRS were calculated with both the Life-Chart functional impairment rating and mood rating documented with the PLC App. 44 subjects used the PLC App in German and 10 subjects used the PLC App in English. 118 clinical interviews from the German sub-sample and 97 from the English sub-sample were analysed separately. The results in both sub-samples are similar to previous Life-Chart validation studies. Again statistically significant high correlations were found between the Life-Chart function rating assigned through the PLC App and well-established observer-rated methods. Again correlations were weaker for the Life-Chart mood rating than for the Life-Chart function impairment. No relevant correlation was found between the Life-chart mood rating and YMRS in the German sub-sample. This study gives further evidence for the validity of the Life-Chart method as a valid tool for the recognition of both manic and depressive episodes. Documenting Life-Charts with the PLC App (English and German) does not seem to impair the validity of patient ratings.

Transient receptor potential channel M5 and phospholipaseC-beta2 colocalizing in zebrafish taste receptor cells.

PubMed

Yoshida, Yuki; Saitoh, Kana; Aihara, Yoshiko; Okada, Shinji; Misaka, Takumi; Abe, Keiko

2007-10-08

In mammals, transient receptor potential (TRP) channel M5 (TRPM5) is coexpressed with phospholipaseC-beta2 (PLC-beta2) in the taste receptor cells, and both PLC-beta2 and TRPM5 are essential elements in the signal transduction of sweet, bitter and umami stimuli. In this study, we identified the zebrafish homologue of TRPM5 (zfTRPM5) and examined its expression in the gustatory system by in-situ hybridization. Using a transgenic zebrafish line that expressed green fluorescent protein under the control of the PLC-beta2 promoter, we showed that zfTRPM5 is expressed in green fluorescent protein-labeled cells of the taste buds. These results demonstrate that zfTRPM5 and PLC-beta2 colocalize in zebrafish taste receptor cells, suggesting their crucial roles in taste signaling via the fish taste receptors.

NB-PLC channel modelling with cyclostationary noise addition & OFDM implementation for smart grid

NASA Astrophysics Data System (ADS)

Thomas, Togis; Gupta, K. K.

2016-03-01

Power line communication (PLC) technology can be a viable solution for the future ubiquitous networks because it provides a cheaper alternative to other wired technology currently being used for communication. In smart grid Power Line Communication (PLC) is used to support communication with low rate on low voltage (LV) distribution network. In this paper, we propose the channel modelling of narrowband (NB) PLC in the frequency range 5 KHz to 500 KHz by using ABCD parameter with cyclostationary noise addition. Behaviour of the channel was studied by the addition of 11KV/230V transformer, by varying load location and load. Bit error rate (BER) Vs signal to noise ratio SNR) was plotted for the proposed model by employing OFDM. Our simulation results based on the proposed channel model show an acceptable performance in terms of bit error rate versus signal to noise ratio, which enables communication required for smart grid applications.

Experimental analysis of energy absorption behaviour of Al-tube filled with pumice lightweight concrete under axial loading condition

NASA Astrophysics Data System (ADS)

Rajak, D. K.; Deshpande, P. G.; Kumaraswamidhas, L. A.

2017-08-01

This Paper aimed at experimental investigation of compressive behaviour of square tube filled with pumice lightweight concrete (PLC). Square section of 20×20×30 mm is investigated, which is the backbone structure. The compression deformation result shows the better folding mechanism, displacement value, and energy absorption. PLC concrete filled with aluminium thin-wall tubes has been revealed superior energy absorption capacity (EAC) under low strain rate at room temperature. Superior EAC resulted as a result of mutual deformation benefit between aluminium section and PLC is also analysed. PLC was characterised by Fourier Transform Infrared (FTIR) and Field Emission Scanning Electron Microscopy (FESEM), and Energy Dispersive X-ray Spectrometry (EDX) analysis for better understanding of material behaviour. Individual and comparative load bearing graphs is logged for better prospective of analysing. Novel approach aimed at validation of porous lightweight concrete for better lightweight EA filler material.

Crema

DTIC Science & Technology

2015-08-01

Crema FizzBuzz Program .................................................. 8 Figure 4: Hello World program written in C...11 Figure 5: Hello World program written in Crema...KLEE Coverage for " Hello , World" Program ................................................................ 14 Table 2: Qmail State-space Explosion

Dopamine Promotes Motor Cortex Plasticity and Motor Skill Learning via PLC Activation

PubMed Central

Rioult-Pedotti, Mengia-Seraina; Pekanovic, Ana; Atiemo, Clement Osei; Marshall, John; Luft, Andreas Rüdiger

2015-01-01

Dopaminergic neurons in the ventral tegmental area, the major midbrain nucleus projecting to the motor cortex, play a key role in motor skill learning and motor cortex synaptic plasticity. Dopamine D1 and D2 receptor antagonists exert parallel effects in the motor system: they impair motor skill learning and reduce long-term potentiation. Traditionally, D1 and D2 receptor modulate adenylyl cyclase activity and cyclic adenosine monophosphate accumulation in opposite directions via different G-proteins and bidirectionally modulate protein kinase A (PKA), leading to distinct physiological and behavioral effects. Here we show that D1 and D2 receptor activity influences motor skill acquisition and long term synaptic potentiation via phospholipase C (PLC) activation in rat primary motor cortex. Learning a new forelimb reaching task is severely impaired in the presence of PLC, but not PKA-inhibitor. Similarly, long term potentiation in motor cortex, a mechanism involved in motor skill learning, is reduced when PLC is inhibited but remains unaffected by the PKA inhibitor. Skill learning deficits and reduced synaptic plasticity caused by dopamine antagonists are prevented by co-administration of a PLC agonist. These results provide evidence for a role of intracellular PLC signaling in motor skill learning and associated cortical synaptic plasticity, challenging the traditional view of bidirectional modulation of PKA by D1 and D2 receptors. These findings reveal a novel and important action of dopamine in motor cortex that might be a future target for selective therapeutic interventions to support learning and recovery of movement resulting from injury and disease. PMID:25938462

Costimulation of AMPA and metabotropic glutamate receptors underlies phospholipase C activation by glutamate in hippocampus.

PubMed

Kim, Hye-Hyun; Lee, Kyu-Hee; Lee, Doyun; Han, Young-Eun; Lee, Suk-Ho; Sohn, Jong-Woo; Ho, Won-Kyung

2015-04-22

Glutamate, a major neurotransmitter in the brain, activates ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs, respectively). The two types of glutamate receptors interact with each other, as exemplified by the modulation of iGluRs by mGluRs. However, the other way of interaction (i.e., modulation of mGluRs by iGluRs) has not received much attention. In this study, we found that group I mGluR-specific agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) alone is not sufficient to activate phospholipase C (PLC) in rat hippocampus, while glutamate robustly activates PLC. These results suggested that additional mechanisms provided by iGluRs are involved in group I mGluR-mediated PLC activation. A series of experiments demonstrated that glutamate-induced PLC activation is mediated by mGluR5 and is facilitated by local Ca(2+) signals that are induced by AMPA-mediated depolarization and L-type Ca(2+) channel activation. Finally, we found that PLC and L-type Ca(2+) channels are involved in hippocampal mGluR-dependent long-term depression (mGluR-LTD) induced by paired-pulse low-frequency stimulation, but not in DHPG-induced chemical LTD. Together, we propose that AMPA receptors initiate Ca(2+) influx via the L-type Ca(2+) channels that facilitate mGluR5-PLC signaling cascades, which underlie mGluR-LTD in rat hippocampus. Copyright © 2015 the authors 0270-6474/15/356401-12$15.00/0.

Phospholipase C-zeta deficiency as a cause for repetitive oocyte fertilization failure during ovarian stimulation for in vitro fertilization with ICSI: a case report.

PubMed

Chithiwala, Zahabiya H; Lee, Hoi Chang; Hill, David L; Jellerette-Nolan, Teru; Fissore, Rafael; Grow, Daniel; Dumesic, Daniel A

2015-09-01

The purpose of this study is to describe impaired oocyte fertilization from phospholipase C-zeta (PLC-ζ) deficiency in normal-appearing sperm that was successfully treated using calcium (Ca(2+)) ionophore with intracytoplasmic sperm injection (ICSI) of oocytes matured in vitro. An infertile couple undergoing in vitro fertilization (IVF) experienced failed oocyte fertilization following ICSI with normal-appearing sperm. A semen sample collected from the patient was used to assess the expression of sperm PLC- ζ protein by Western blot analysis and immunofluorescence and PLC-ζ bioactivity by an in vitro model of Ca(2+) release. A second IVF cycle was performed using Ca(2+) ionophore with ICSI to enhance Ca(2+)-induced oocyte activation of oocytes matured in vitro. Sperm PLC-ζ protein deficiency was demonstrated by Western blot analysis and immunofluorescence and confirmed by reduced PLC-ζ bioactivity using an in vitro model of Ca(2+) release. Nevertheless, with this sperm and supplementation of Ca(2+) ionophore following ICSI, fertilization of four of six oocytes matured in vitro was obtained. In addition, four embryos underwent cleavage and two of them reached the blastocyst stage. Transfer of these blastocysts into the uterus led to a single pregnancy and live birth. Deficiency of PLC-ζ in normal-appearing human sperm is associated with impaired Ca(2+)-dependent oocyte activation during ICSI. Under this condition, use of Ca(2+) ionophore following ICSI of oocytes matured in vitro improves embryo developmental competence, possibly through the activation of Ca(2+)-dependent mechanisms governing fertilization and preimplantation embryogenesis.

78 FR 6206 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-30

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT..., RB211-Trent 977-84, RB211-Trent 977B-84 and RB211-Trent 980-84 turbofan engines. This AD requires on...

Controlling Laboratory Processes From A Personal Computer

NASA Technical Reports Server (NTRS)

Will, H.; Mackin, M. A.

1991-01-01

Computer program provides natural-language process control from IBM PC or compatible computer. Sets up process-control system that either runs without operator or run by workers who have limited programming skills. Includes three smaller programs. Two of them, written in FORTRAN 77, record data and control research processes. Third program, written in Pascal, generates FORTRAN subroutines used by other two programs to identify user commands with device-driving routines written by user. Also includes set of input data allowing user to define user commands to be executed by computer. Requires personal computer operating under MS-DOS with suitable hardware interfaces to all controlled devices. Also requires FORTRAN 77 compiler and device drivers written by user.

Industrial Control System Process-Oriented Intrusion Detection (iPoid) Algorithm

DTIC Science & Technology

2016-08-01

inspection rules using an intrusion-detection system (IDS) sensor, a simulated Programmable Logic Controller (PLC), and a Modbus client operating...operating system PLC Programmable Logic Controller SCADA supervisory control and data acquisition SIGHUP signal hangup SPAN Switched Port Analyzer

[Study on the quantitative evaluation on the degree of TCM basic syndromes often encountered in patients with primary liver cancer].

PubMed

Li, Dong-tao; Ling, Chang-quan; Zhu, De-zeng

2007-07-01

To establish a quantitative model for evaluating the degree of the TCM basic syndromes often encountered in patients with primary liver cancer (PLC). Medical literatures concerning the clinical investigation and TCM syndrome of PLC were collected and analyzed adopting expert-composed symposium method, and the 100 millimeter scaling was applied in combining with scoring on degree of symptoms to establish a quantitative criterion for symptoms and signs degree classification in patients with PLC. Two models, i.e. the additive model and the additive-multiplicative model, were established by using comprehensive analytic hierarchy process (AHP) as the mathematical tool to estimate the weight of the criterion for evaluating basic syndromes in various layers by specialists. Then the two models were verified in clinical practice and the outcomes were compared with that fuzzy evaluated by specialists. Verification on 459 times/case of PLC showed that the coincidence rate between the outcomes derived from specialists with that from the additive model was 84.53 %, and with that from the additive-multificative model was 62.75 %, the difference between the two showed statistical significance (P<0.01). It could be decided that the additive model is the principle model suitable for quantitative evaluation on the degree of TCM basic syndromes in patients with PLC.

Auto-inhibition and phosphorylation-induced activation of PLC-γ isozymes

PubMed Central

Hajicek, Nicole; Charpentier, Thomas H.; Rush, Jeremy R.; Harden, T. Kendall; Sondek, John

2013-01-01

Multiple extracellular stimuli, such as growth factors and antigens, initiate signaling cascades through tyrosine phosphorylation and activation of phospholipase C (PLC)-γ isozymes. Like most other PLCs, PLC-γ1 is basally auto-inhibited by its X-Y linker, which separates the X-and Y-boxes of the catalytic core. The C-terminal SH2 (cSH2) domain within the X-Y linker is the critical determinant for auto-inhibition of phospholipase activity. Release of auto-inhibition requires an intramolecular interaction between the cSH2 domain and a phosphorylated tyrosine, Tyr783, also located within the X-Y linker. The molecular mechanisms that mediate auto-inhibition and phosphorylation-induced activation have not been defined. Here, we describe structures of the cSH2 domain both alone and bound to a PLC-γ1 peptide encompassing phosphorylated Tyr783. The cSH2 domain remains largely unaltered by peptide engagement. Point mutations in the cSH2 domain located at the interface with the peptide were sufficient to constitutively activate PLC-γ1 suggesting that peptide engagement directly interferes with the capacity of the cSH2 domain to block the lipase active site. This idea is supported by mutations in a complimentary surface of the catalytic core that also enhanced phospholipase activity. PMID:23777354

The Portevin-Le Chatelier Effect in the Ni-Based Superalloy IN100

NASA Astrophysics Data System (ADS)

Fernandez-Zelaia, Patxi; Adair, Benjamin S.; Barker, Vincent M.; Antolovich, Stephen D.

2015-12-01

The Portevin-Le Chatelier (PLC) effect has been studied in the Ni-based superalloy IN100 which is currently used as a disk material in jet engines. A series of tensile tests was carried out at 588 K, 755 K, and 922 K (315 °C, 482 °C, and 649 °C) at plastic strain rates ranging from a low of 6.21 × 10-6 s-1 to a high of 4.92 × 10-2 s-1. The activation energy was determined using the slope of a line on a strain rate/temperature graph which divided the area of the graph into two regions: (1) "PLC behavior observed," and (2) "No PLC behavior observed." A new statistical approach was developed to objectively differentiate between a true PLC effect and experimental uncertainty ( i.e., "noise"). The value of the activation energy was found to be 1.14 eV/atom, which strongly suggests that the rate controlling process was bulk diffusion of C in the lattice. A qualitative model, based on the Orowan equation and slip band dislocation mechanics, was proposed, which unifies the seemingly disparate ideas of the process being controlled by a single atom/dislocation interaction while at the same time exhibiting significant strains during PLC load drops.

The Cish SH2 domain is essential for PLC-γ1 regulation in TCR stimulated CD8+ T cells.

PubMed

Guittard, Geoffrey; Dios-Esponera, Ana; Palmer, Douglas C; Akpan, Itoro; Barr, Valarie A; Manna, Asit; Restifo, Nicholas P; Samelson, Lawrence E

2018-03-28

Cish, participates within a multi-molecular E3 ubiquitin ligase complex, which ubiquitinates target proteins. It has an inhibitory effect on T cell activation mediated by PLC-γ1 regulation, and it functions as a potent checkpoint in CD8 + T cell tumor immunotherapy. To study the structural and functional relationships between Cish and PLC-γ1 during CD8 + T cell activation, we tested mutants of the Cish-SH2 (R107K) and D/BC (L222Q, C226Q) domains. We confirmed that Cish-SH2-specific binding was essential for PLC-γ1 ubiquitination and degradation. This domain was essential for the Cish-mediated inhibition of Ca 2+ release upon TCR stimulation. No effect on inhibition of cytokine release was observed with SH2 or D/BC mutants, although the absence of Cish led to an increased release of IFN-γ and TNF-α. Using imaging we showed that Cish was expressed mostly in the cytoplasm and we did not see any Cish clustering at the plasma membrane upon stimulation. We conclude that the Cish-SH2 domain is essential for PLC-γ1 regulation in TCR-stimulated CD8 + T cells.

A Remote PLC Laboratory (RLab) for Distance Practical Work of Industrial Automation

NASA Astrophysics Data System (ADS)

Haritman, E.; Somantri, Y.; Wahyudin, D.; Mulyana, E.

2018-02-01

A laboratory is an essential equipment for engineering students to do a useful practical work. Therefore, universities should provide an adequate facility for practical work. On the other hand, industrial automation laboratory would offer students beneficial experience by using various educational PLC kits. This paper describes the development of Web-based Programmable Logic Controller (PLC) remote laboratory called RLab. It provides an environment for learners to study PLC application to control the level of the non-interacting tank. The RLab architecture is based on a Moodle and Remote Desktop, which also manages the booking system of the schedule of practical work in the laboratory. The RLab equipped by USB cameras providing a real-time view of PLC environment. To provide a secured system, the RLab combines Moodle and Remote Desktop application for the authentication system and management of remote users. Moodle will send PartnerID and password to connect to TeamViewer. It has been examined that the laboratory requirement, time and flexibility restrictions constitute a significant obstacle facing traditional students desiring to finish the course. A remote access laboratory can be eliminating time and flexibility restrictions. The preliminary study of RLab usability proved that such system is adequate to give the learners a distance practical work environment.

Odorant-stimulated phosphoinositide signaling in mammalian olfactory receptor neurons

PubMed Central

Klasen, K.; Corey, E.A.; Kuck, F.; Wetzel, C.H.; Hatt, H.; Ache, B.W.

2009-01-01

Recent evidence has revived interest in the idea that phosphoinositides (PIs) may play a role in signal transduction in mammalian olfactory receptor neurons (ORNs). To provide direct evidence that odorants indeed activate PI signaling in ORNs, we used adenoviral vectors carrying two different fluorescently tagged probes, the pleckstrin homology (PH) domains of phospholipase Cδ1 (PLCδ1) and the general receptor of phosphoinositides (GRP1), to monitor PI activity in the dendritic knobs of ORNs in vivo. Odorants mobilized PI(4,5)P2/IP3 and PI(3,4,5)P3, the substrates and products of PLC and PI3K. We then measured odorant activation of PLC and PI3K in olfactory ciliary-enriched membranes in vitro using a phospholipid overlay assay and ELISAs. Odorants activated both PLC and PI3K in the olfactory cilia within 2 sec of odorant stimulation. Odorant-dependent activation of PLC and PI3K in the olfactory epithelium could be blocked by enzyme-specific inhibitors. Odorants activated PLC and PI3K with partially overlapping specificity. These results provide direct evidence that odorants indeed activate PI signaling in mammalian ORNs in a manner that is consistent with the idea that PI signaling plays a role in olfactory transduction. PMID:19781634

An IBM 370 assembly language program verifier

NASA Technical Reports Server (NTRS)

Maurer, W. D.

1977-01-01

The paper describes a program written in SNOBOL which verifies the correctness of programs written in assembly language for the IBM 360 and 370 series of computers. The motivation for using assembly language as a source language for a program verifier was the realization that many errors in programs are caused by misunderstanding or ignorance of the characteristics of specific computers. The proof of correctness of a program written in assembly language must take these characteristics into account. The program has been compiled and is currently running at the Center for Academic and Administrative Computing of The George Washington University.

Progressive learning in endoscopy simulation training improves clinical performance: a blinded randomized trial.

PubMed

Grover, Samir C; Scaffidi, Michael A; Khan, Rishad; Garg, Ankit; Al-Mazroui, Ahmed; Alomani, Tareq; Yu, Jeffrey J; Plener, Ian S; Al-Awamy, Mohamed; Yong, Elaine L; Cino, Maria; Ravindran, Nikila C; Zasowski, Mark; Grantcharov, Teodor P; Walsh, Catharine M

2017-11-01

A structured comprehensive curriculum (SCC) that uses simulation-based training (SBT) can improve clinical colonoscopy performance. This curriculum may be enhanced through the application of progressive learning, a training strategy centered on incrementally challenging learners. We aimed to determine whether a progressive learning-based curriculum (PLC) would lead to superior clinical performance compared with an SCC. This was a single-blinded randomized controlled trial conducted at a single academic center. Thirty-seven novice endoscopists were recruited and randomized to either a PLC (n = 18) or to an SCC (n = 19). The PLC comprised 6 hours of SBT, which progressed in complexity and difficulty. The SCC included 6 hours of SBT, with cases of random order of difficulty. Both groups received expert feedback and 4 hours of didactic teaching. Participants were assessed at baseline, immediately after training, and 4 to 6 weeks after training. The primary outcome was participants' performance during their first 2 clinical colonoscopies, as assessed by using the Joint Advisory Group Direct Observation of Procedural Skills assessment tool (JAG DOPS). Secondary outcomes were differences in endoscopic knowledge, technical and communication skills, and global performance in the simulated setting. The PLC group outperformed the SCC group during first and second clinical colonoscopies, measured by JAG DOPS (P < .001). Additionally, the PLC group had superior technical and communication skills and global performance in the simulated setting (P < .05). There were no differences between groups in endoscopic knowledge (P > .05). Our findings demonstrate the superiority of a PLC for endoscopic simulation, compared with an SCC. Challenging trainees progressively is a simple, theory-based approach to simulation whereby the performance of clinical colonoscopies can be improved. (Clinical trial registration number: NCT02000180.). Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Production of monoclonal antibodies to Listeria monocytogenes and their application to determine the virulence of isolates from channel catfish.

PubMed

Erdenlig, S; Ainsworth, A J; Austin, F W

1999-07-01

We produced monoclonal antibodies (MAbs) to the extracellular proteins of Listeria monocytogenes EGD grown in Chelex-treated improved minimal medium. Ten of the positive hybridomas generated were chosen for further characterization. Seven of the MAbs reacted with a protein having a molecular mass of 60 kDa. These MAbs inhibited listeriolysin (LLO)-mediated hemolysis, and two of them were specific for LLO and none of the other thiol-activated toxins tested. In an enzyme-linked immunosorbent assay and Western blot analysis, five of the anti-LLO MAbs reacted with ivanolysin from Listeria ivanovii. Three of the 10 MAbs reacted with a 29-kDa protein on Western blots and neutralized the phosphatidylcholine-specific phospholipase C (PC-PLC) activity of L. monocytogenes. These three anti-PC-PLC MAbs did not react with phospholipases from five different gram-positive bacteria. However, the anti-PC-PLC MAbs recognized a 27-kDa extracellular protein from L. ivanovii and neutralized sphingomyelinase activity in a hemolysis test that demonstrates the antigenic relatedness of listerial phospholipases. These data indicate that listerial thiol-activated toxins possess species-specific epitopes and share group-specific epitopes. This is the first description of MAbs that neutralize listerial PC-PLC, and the data suggest that there is antigenic similarity between L. monocytogenes PC-PLC and L. ivanovii sphingomyelinase. The reactions of the MAbs with catfish isolates of L. monocytogenes suggested that some of the isolates examined lack the LLO and/or PC-PLC required for pathogenicity. The MAbs described here differentiated some catfish isolates from previously described type strain-pathogenic isolates and could be useful for detecting and determining the virulence of L. monocytogenes in food and clinical samples and for detecting L. ivanovii in veterinary clinical samples.

Plant phosphatidylcholine-hydrolyzing phospholipases C NPC3 and NPC4 with roles in root development and brassinolide signaling in Arabidopsis thaliana.

PubMed

Wimalasekera, Rinukshi; Pejchar, Premysl; Holk, André; Martinec, Jan; Scherer, Günther F E

2010-05-01

Phosphatidylcholine-hydrolyzing phospholipase C (PC-PLC) catalyzes the hydrolysis of phosphatidylcholine (PC) to generate phosphocholine and diacylglycerol (DAG). PC-PLC has a long tradition in animal signal transduction to generate DAG as a second messenger besides the classical phosphatidylinositol splitting phospholipase C (PI-PLC). Based on amino acid sequence similarity to bacterial PC-PLC, six putative PC-PLC genes (NPC1 to NPC6) were identified in the Arabidopsis genome. RT-PCR analysis revealed overlapping expression pattern of NPC genes in root, stem, leaf, flower, and silique. In auxin-treated P(NPC3):GUS and P(NPC4):GUS seedlings, strong increase of GUS activity was visible in roots, leaves, and shoots and, to a weaker extent, in brassinolide-treated (BL) seedlings. P(NPC4):GUS seedlings also responded to cytokinin with increased GUS activity in young leaves. Compared to wild-type, T-DNA insertional knockouts npc3 and npc4 showed shorter primary roots and lower lateral root density at low BL concentrations but increased lateral root densities in response to exogenous 0.05-1.0 μM BL. BL-induced expression of TCH4 and LRX2, which are involved in cell expansion, was impaired but not impaired in repression of CPD, a BL biosynthesis gene, in BL-treated npc3 and npc4. These observations suggest NPC3 and NPC4 are important in BL-mediated signaling in root growth. When treated with 0.1 μM BL, DAG accumulation was observed in tobacco BY-2 cell cultures labeled with fluorescent PC as early as 15 min after application. We hypothesize that at least one PC-PLC is a plant signaling enzyme in BL signal transduction and, as shown earlier, in elicitor signal transduction.

Comparative diagnostic efficacy of recombinant LLO and PI-PLC-based ELISAs for detection of listeriosis in animals.

PubMed

Suryawanshi, Rahul D; Malik, Satya Veer Singh; Jayarao, Bhushan; Chaudhari, Sandeep P; Savage, Emily; Vergis, Jess; Kurkure, Nitin V; Barbuddhe, Sukhadeo B; Rawool, Deepak B

2017-06-01

The present study for the first time evaluates the serodiagnostic efficacy of two recombinant antigens namely, listeriolysin O (rLLO) and phosphatidyl-inositol phospholipase C (rPI-PLC). Indirect ELISA with the above recombinant antigens was used on samples collected from bovines (n=106), goats (n=138) and pigs (n=92) having either a history of abortion, emaciation and/or apparently healthy animals. Isolation of Listeria was attempted from the blood samples using USDA-FSIS method. On screening of test sera by rLLO-based ELISA, antibodies against anti-listeriolysin O (ALLO) were observed in goats (22.46%), bovines (15.10%) and pigs (16.31%). As advocated, after adsorption of positive serum samples with streptolysin O (SLO), the seropositivity for ALLO was marginally reduced (p>0.05) in goats (21.73%) and bovines (10.38%), whereas, in pigs the reduction (5.43%) was significant (p<0.05). On the contrary, rPI-PLC-based ELISA revealed higher non-specific seropositivity for antilisterial antibodies in goats (45.65%), bovines (31.13%) and pigs (8.69%). Further, on comparing the seropositivity with isolation rate, of the 16 animals that were culturally-positive for L. monocytogenes, 15 showed ALLO positivity in unadsorbed as well as SLO-adsorbed sera by rLLO-based ELISA, however, rPI-PLC-based ELISA could detect seropositivity in only 5 animals. Moreover, rPI-PLC-based ELISA also showed seropositivity in those animals (7/30) that were culturally positive for other Listeria spp. In conclusion, rLLO can serve as a better antigen than rPI-PLC in ELISA for the serodiagnosis of listeriosis in animals; however, prior adsorption of test sera with SLO is required to avoid false positive results. Copyright © 2017 Elsevier B.V. All rights reserved.

The Metalloprotease Mpl Supports Listeria monocytogenes Dissemination through Resolution of Membrane Protrusions into Vacuoles

PubMed Central

Alvarez, Diego E.

2016-01-01

Listeria monocytogenes is an intracellular pathogen that disseminates within the intestinal epithelium through acquisition of actin-based motility and formation of plasma membrane protrusions that project into adjacent cells. The resolution of membrane protrusions into vacuoles from which the pathogen escapes results in bacterial spread from cell to cell. This dissemination process relies on the mlp-actA-plcB operon, which encodes ActA, a bacterial nucleation-promoting factor that mediates actin-based motility, and PlcB, a phospholipase that mediates vacuole escape. Here we investigated the role of the metalloprotease Mpl in the dissemination process. In agreement with previous findings showing that Mpl is required for PlcB activation, infection of epithelial cells with the ΔplcB or Δmpl strains resulted in the formation of small infection foci. As expected, the ΔplcB strain displayed a strong defect in vacuole escape. However, the Δmpl strain showed an unexpected defect in the resolution of protrusions into vacuoles, in addition to the expected but mild defect in vacuole escape. The Δmpl strain displayed increased levels of ActA on the bacterial surface in protrusions. We mapped an Mpl-dependent processing site in ActA between amino acid residues 207 to 238. Similar to the Δmpl strain, the ΔactA207–238 strain displayed increased levels of ActA on the bacterial surface in protrusions. Although the ΔactA207–238 strain displayed wild-type actin-based motility, it formed small infection foci and failed to resolve protrusions into vacuoles. We propose that, in addition to its role in PlcB processing and vacuole escape, the metalloprotease Mpl is required for ActA processing and protrusion resolution. PMID:27068088

The Metalloprotease Mpl Supports Listeria monocytogenes Dissemination through Resolution of Membrane Protrusions into Vacuoles.

PubMed

Alvarez, Diego E; Agaisse, Hervé

2016-06-01

Listeria monocytogenes is an intracellular pathogen that disseminates within the intestinal epithelium through acquisition of actin-based motility and formation of plasma membrane protrusions that project into adjacent cells. The resolution of membrane protrusions into vacuoles from which the pathogen escapes results in bacterial spread from cell to cell. This dissemination process relies on the mlp-actA-plcB operon, which encodes ActA, a bacterial nucleation-promoting factor that mediates actin-based motility, and PlcB, a phospholipase that mediates vacuole escape. Here we investigated the role of the metalloprotease Mpl in the dissemination process. In agreement with previous findings showing that Mpl is required for PlcB activation, infection of epithelial cells with the ΔplcB or Δmpl strains resulted in the formation of small infection foci. As expected, the ΔplcB strain displayed a strong defect in vacuole escape. However, the Δmpl strain showed an unexpected defect in the resolution of protrusions into vacuoles, in addition to the expected but mild defect in vacuole escape. The Δmpl strain displayed increased levels of ActA on the bacterial surface in protrusions. We mapped an Mpl-dependent processing site in ActA between amino acid residues 207 to 238. Similar to the Δmpl strain, the ΔactA207-238 strain displayed increased levels of ActA on the bacterial surface in protrusions. Although the ΔactA207-238 strain displayed wild-type actin-based motility, it formed small infection foci and failed to resolve protrusions into vacuoles. We propose that, in addition to its role in PlcB processing and vacuole escape, the metalloprotease Mpl is required for ActA processing and protrusion resolution. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The effects of AMPA receptor blockade in the prelimbic cortex on systemic and ventral tegmental area opiate reward sensitivity.

PubMed

De Jaeger, Xavier; Bishop, Stephanie F; Ahmad, Tasha; Lyons, Danika; Ng, Garye Ami; Laviolette, Steven R

2013-02-01

The medial prefrontal cortex (mPFC) is a key neural region involved in opiate-related reward memory processing. AMPA receptor transmission in the mPFC modulates opiate-related reward memory processing, and chronic opiate exposure is associated with alterations in intra-mPFC AMPA receptor function. The objectives of this study were to examine how pharmacological blockade of AMPA receptor transmission in the prelimbic (PLC) division of the mPFC may modulate opiate reward memory acquisition and whether opiate exposure state may modulate the functional role of intra-PLC AMPA receptor transmission during opiate reward learning. Using an unbiased conditioned place preference (CPP) procedure in rats, we performed discrete, bilateral intra-PLC microinfusions of the AMPA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione, prior to behavioral morphine CPP conditioning, using sub-reward threshold conditioning doses of either systemic (0.05 mg/kg; i.p.) or intra-ventral tegmental area (VTA) morphine (250 ng/0.5 μl). We show that, in both opiate-naïve and opiate-dependent states, intra-PLC blockade of AMPA receptor transmission, but not the infralimbic cortex, increases the behavioral reward magnitude of systemic or intra-VTA morphine. This effect is dependent on dopamine (DA)ergic signaling because pre-administration of cis-(Z)-flupenthixol-dihydrochloride (α-flu), a broad-spectrum dopamine receptor antagonist, blocked the morphine-reward potentiating effects of AMPA receptor blockade. These findings suggest a critical role for intra-PLC AMPA receptor transmission in the processing of opiate reward signaling. Furthermore, blockade of AMPA transmission specifically within the PLC is capable of switching opiate reward processing to a DA-dependent reward system, independently of previous opiate exposure history.

Phospholipid complex enriched micelles: A novel drug delivery approach for promoting the antidiabetic effect of repaglinide.

PubMed

Kassem, Ahmed Alaa; Abd El-Alim, Sameh Hosam; Basha, Mona; Salama, Abeer

2017-03-01

To enhance the oral antidiabetic effect of repaglinide (RG), a newly emerging approach, based on the combination of phospholipid complexation and micelle techniques, was employed. Repaglinide-phospholipid complex (RG-PLC) was prepared by the solvent-evaporation method then characterized using Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction (XPRD). The results revealed obvious disappearance of the characteristic peaks of the prepared RG-PLCs confirming the formation of drug-phospholipid complex. RG-PLC enriched micelles (RG-PLC-Ms) were prepared by the solvent-evaporation technique employing poloxamer 188 as surfactant. The prepared RG-PLC-Ms showed high drug encapsulation efficiencies (93.81-99.38%), with nanometric particle diameters (500.61-665.32nm) of monodisperse distribution and high stability (Zeta potential < -29.8mV). The in vitro release of RG from RG-PLC-Ms was pH-dependant according to the release media. A higher release pattern was reported in pH=1.2 compared to a more retarded release in pH=6.8 owing to two different kinetics of drug release. Oral antidiabetic effect of two optimized RG-PLC-M formulations was evaluated in an alloxan-induced diabetic rat model for 7-day treatment protocol. The two investigated formulations depicted normal blood glucose, serum malondialdehyde and insulin levels as well as an improved lipid profile, at the end of daily oral treatment, in contrast to RG marketed tablets implying enhanced antidiabetic effect of the drug. Hence, phospholipid-complex enriched micelles approach holds a promising potential for promoting the antidiabetic effect of RG. Copyright © 2016 Elsevier B.V. All rights reserved.

Activation of Phosphatidylcholine-Specific Phospholipase C in Breast and Ovarian Cancer: Impact on MRS-Detected Choline Metabolic Profile and Perspectives for Targeted Therapy

PubMed Central

Podo, Franca; Paris, Luisa; Cecchetti, Serena; Spadaro, Francesca; Abalsamo, Laura; Ramoni, Carlo; Ricci, Alessandro; Pisanu, Maria Elena; Sardanelli, Francesco; Canese, Rossella; Iorio, Egidio

2016-01-01

Elucidation of molecular mechanisms underlying the aberrant phosphatidylcholine cycle in cancer cells plays in favor of the use of metabolic imaging in oncology and opens the way for designing new targeted therapies. The anomalous choline metabolic profile detected in cancer by magnetic resonance spectroscopy and spectroscopic imaging provides molecular signatures of tumor progression and response to therapy. The increased level of intracellular phosphocholine (PCho) typically detected in cancer cells is mainly attributed to upregulation of choline kinase, responsible for choline phosphorylation in the biosynthetic Kennedy pathway, but can also be partly produced by activation of phosphatidylcholine-specific phospholipase C (PC-PLC). This hydrolytic enzyme, known for implications in bacterial infection and in plant survival to hostile environmental conditions, is reported to be activated in mitogen- and oncogene-induced phosphatidylcholine cycles in mammalian cells, with effects on cell signaling, cell cycle regulation, and cell proliferation. Recent investigations showed that PC-PLC activation could account for 20–50% of the intracellular PCho production in ovarian and breast cancer cells of different subtypes. Enzyme activation was associated with PC-PLC protein overexpression and subcellular redistribution in these cancer cells compared with non-tumoral counterparts. Moreover, PC-PLC coimmunoprecipitated with the human epidermal growth factor receptor-2 (HER2) and EGFR in HER2-overexpressing breast and ovarian cancer cells, while pharmacological PC-PLC inhibition resulted into long-lasting HER2 downregulation, retarded receptor re-expression on plasma membrane and antiproliferative effects. This body of evidence points to PC-PLC as a potential target for newly designed therapies, whose effects can be preclinically and clinically monitored by metabolic imaging methods. PMID:27532027

75 FR 70736 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-18

...: EC10-98-000. Applicants: GDF Suez S.A., International Power PLC. Description: Supplemental Affidavit of...., International Power plc and its Indicated United States Subsidiaries. Filed Date: 10/29/2010. Accession Number... Generation Holdings, LLC. Description: TPF Generation Holdings, LLC submits an application for authorization...

Studies by immune electron microscopy of hepatitis B surface antigen in PLC/PRF/5 cells.

PubMed

Shibayama, T; Watanabe, T; Kojima, H; Yoshikawa, A; Watanabe, S; Kamimura, T; Suzuki, S; Ichida, F

1984-01-01

Electron microscopic studies of the morphology of hepatitis B surface antigen (HBsAg) produced by PLC/PRF/5 cells in vitro were carried out. Aggregates of 20-nm spherical particles in 3-day culture supernatants were observed by immune electron microscopy (IEM). Aggregates of tubular structures were found with IEM in the extracts of the cells. Tubular structures 18 to 22 nm in diameter were seen by electron microscopy (EM) in the cisternae of the endoplasmic reticulum in 2-3% of the cells. The tubular structures in the cytoplasm and extracts of PLC/PRF/5 cells resembled those observed in the hepatocytes of human carriers of hepatitis B virus (HBV). Intracellular localization of HBsAg in PLC/PRF/5 cells by direct peroxidase-conjugated antibody staining was observed on the tubular structures and the cisternal wall, which contained these structures. Rotation technique analysis indicated that the tubular structures were composed of 11 or 12 subunits.

Inhibition of phosphatidylcholine-specific phospholipase C prevents bone marrow stromal cell senescence in vitro.

PubMed

Sun, Chunhui; Wang, Nan; Huang, Jie; Xin, Jie; Peng, Fen; Ren, Yinshi; Zhang, Shangli; Miao, Junying

2009-10-01

Bone marrow stromal cells (BMSCs) can proliferate in vitro and can be transplanted for treating many kinds of diseases. However, BMSCs become senescent with long-term culture, which inhibits their application. To understand the mechanism underlying the senescence, we investigated the activity of phosphatidylcholine-specific phospholipase C (PC-PLC) and levels of integrin beta4, caveolin-1 and ROS with BMSC senescence. The activity of PC-PLC and levels of integrin beta4, caveolin-1 and ROS increased greatly during cell senescence. Selective inhibition of increased PC-PLC activity with D609 significantly decreased the number of senescence-associated beta galactosidase positive cells in BMSCs. Furthermore, D609 restored proliferation of BMSCs and their differentiation into adipocytes. Moreover, D609 suppressed the elevated levels of integrin beta4, caveolin-1 and ROS. The data suggest that PC-PLC is involved in senescence of BMSCs, and its function is associated with integrin beta4, caveolin-1 and ROS. (c) 2009 Wiley-Liss, Inc.

Bidirectional automatic release of reserve for low voltage network made with low capacity PLCs

NASA Astrophysics Data System (ADS)

Popa, I.; Popa, G. N.; Diniş, C. M.; Deaconu, S. I.

2018-01-01

The article presents the design of a bidirectional automatic release of reserve made on two types low capacity programmable logic controllers: PS-3 from Klöckner-Moeller and Zelio from Schneider. It analyses the electronic timing circuits that can be used for making the bidirectional automatic release of reserve: time-on delay circuit and time-off delay circuit (two types). In the paper are present the sequences code for timing performed on the PS-3 PLC, the logical functions for the bidirectional automatic release of reserve, the classical control electrical diagram (with contacts, relays, and time relays), the electronic control diagram (with logical gates and timing circuits), the code (in IL language) made for the PS-3 PLC, and the code (in FBD language) made for Zelio PLC. A comparative analysis will be carried out on the use of the two types of PLC and will be present the advantages of using PLCs.

Insights into MHC class I peptide loading from the structure of the tapasin/ERp57 heterodimer

PubMed Central

Dong, Gang; Wearsch, Pamela A.; Peaper, David R.; Cresswell, Peter; Reinisch, Karin M.

2009-01-01

SUMMARY Tapasin is a glycoprotein critical for loading Major Histocompatibility Complex (MHC) class I molecules with high affinity peptides. It functions within the multimeric peptide-loading complex (PLC) as a disulfide-linked, stable heterodimer with the thiol oxidoreductase ERp57, and this covalent interaction is required to support optimal PLC activity. Here we present the 2.6 Å resolution structure of the tapasin/ERp57 core of the PLC. The structure reveals the basis for the stable dimerization of tapasin and ERp57 and provides the first example of a protein disulfide isomerase family member interacting with a substrate. Mutational analysis identified a conserved surface on tapasin that interacts with MHC class I molecules and is critical for the peptide loading and editing function of the tapasin-ERp57 heterodimer. By combining the tapasin/ERp57 structure with those of other defined PLC components we present a molecular model that illuminates the processes involved in MHC class I peptide loading. PMID:19119025

Design of real-time communication system for image recognition based colony picking instrument

NASA Astrophysics Data System (ADS)

Wang, Qun; Zhang, Rongfu; Yan, Hua; Wu, Huamin

2017-11-01

In order to aachieve autommated observatiion and pickinng of monocloonal colonies, an overall dessign and realizzation of real-time commmunication system based on High-throoughput monooclonal auto-piicking instrumment is propossed. The real-time commmunication system is commposed of PCC-PLC commuunication systtem and Centrral Control CComputer (CCC)-PLC communicatioon system. Bassed on RS232 synchronous serial communnication methood to develop a set of dedicated shoort-range commmunication prootocol betweenn the PC and PPLC. Furthermmore, the systemm uses SQL SSERVER database to rrealize the dataa interaction between PC andd CCC. Moreoover, the commmunication of CCC and PC, adopted Socket Ethernnet communicaation based on TCP/IP protoccol. TCP full-dduplex data cannnel to ensure real-time data eexchange as well as immprove system reliability andd security. We tested the commmunication syystem using sppecially develooped test software, thee test results show that the sysstem can realizze the communnication in an eefficient, safe aand stable way between PLC, PC andd CCC, keep thhe real-time conntrol to PLC annd colony inforrmation collecttion.

PLC-controlled cryostats for the BlackGEM and MeerLICHT detectors

NASA Astrophysics Data System (ADS)

Raskin, Gert; Morren, Johan; Pessemier, Wim; Bloemen, Steven; Klein-Wolt, Marc; Roelfsema, Ronald; Groot, Paul; Aerts, Conny

2016-08-01

BlackGEM is an array of telescopes, currently under development at the Radboud University Nijmegen and at NOVA (Netherlands Research School for Astronomy). It targets the detection of the optical counterparts of gravitational waves. The first three BlackGEM telescopes are planned to be installed in 2018 at the La Silla observatory (Chile). A single prototype telescope, named MeerLICHT, will already be commissioned early 2017 in Sutherland (South Africa) to provide an optical complement for the MeerKAT radio array. The BlackGEM array consists of, initially, a set of three robotic 65-cm wide-field telescopes. Each telescope is equipped with a single STA1600 CCD detector with 10.5k x 10.5k 9-micron pixels that covers a 2.7 square degrees field of view. The cryostats for housing these detectors are developed and built at the KU Leuven University (Belgium). The operational model of BlackGEM requires long periods of reliable hands-off operation. Therefore, we designed the cryostats for long vacuum hold time and we make use of a closed-cycle cooling system, based on Polycold PCC Joule-Thomson coolers. A single programmable logic controller (PLC) controls the cryogenic systems of several BlackGEM telescopes simultaneously, resulting in a highly reliable, cost-efficient and maintenance-friendly system. PLC-based cryostat control offers some distinct advantages, especially for a robotic facility. Apart of temperature monitoring and control, the PLC also monitors the vacuum quality, the power supply and the status of the PCC coolers (compressor power consumption and temperature, pressure in the gas lines, etc.). Furthermore, it provides an alarming system and safe and reproducible procedures for automatic cool down and warm up. The communication between PLC and higher-level software takes place via the OPC-UA protocol, offering a simple to implement, yet very powerful interface. Finally, a touch-panel display on the PLC provides the operator with a user-friendly and robust technical interface. In this contribution, we present the design of the BlackGEM cryostats and of the PLC-based control system.

Quantitation of pilsicainide in microscale samples of human biological fluids using liquid chromatography-tandem mass spectrometry.

PubMed

Shimizu, Mikiko; Hashiguchi, Masayuki; Shiga, Tsuyoshi; Nakamura, Koichi; Tamura, Hiro-omi; Mochizuki, Mayumi

2015-03-15

This paper describes a sensitive, reliable method to determine pilsicainide (PLC) levels in microscale sample volumes of human biological fluids using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI). PLC and quinidine as an internal standard were extracted with diethylether from 0.1mL of alkalinized biological fluids. The extract was injected into an analytical column (l-column 2 ODS, 75mm×2.1mm i.d.). The mobile phase for separation consisted of 5mM ammonium acetate (pH 4.5)/methanol (4:1, v/v) and was delivered at a flow rate of 0.2mL/min. The drift voltage was 100V. The sampling aperture was heated at 120°C and the shield temperature was 260°C. The ion transitions used to monitor analytes were m/z 273→m/z 110 for PLC and m/z 325→m/z 79 for quinidine. The total time for chromatographic separation was less than 8min. The validated concentration ranges of this method for PLC were 5-2000ng/mL in plasma, 5-500ng/mL in ultrafiltered plasma solution, and 25-2000ng/mL in urine. Mean recoveries of PLC in plasma, ultrafiltered plasma solution, and urine were 93.2-99.7%, 91.4-100.6%, and 93.9-104.7%, respectively. Intra- and interday coefficients of variation for PLC were less than 6.0% and 4.3% in plasma, 6.1% and 3.7% in ultrafiltered plasma solution, and 5.4% and 2.5% in urine at the above concentration ranges, respectively. The lower limit of quantification for PLC in plasma, ultrafiltered plasma solution, and urine were 5ng/mL, 5ng/mL, and 25ng/mL, respectively. This method can be applied to pharmacokinetic study and therapeutic drug monitoring in special populations such as neonates, infants, and the elderly by making effective use of residual samples used for general clinical laboratory testing. Copyright © 2015 Elsevier B.V. All rights reserved.

Design and construction of a VHGT-attached WDM-type triplex transceiver module using polymer PLC hybrid integration technology

NASA Astrophysics Data System (ADS)

Jerábek, Vitezslav; Hüttel, Ivan; Prajzler, Václav; Busek, K.; Seliger, P.

2008-11-01

We report about design and construction of the bidirectional transceiver TRx module for subscriber part of the passive optical network PON for a fiber to the home FTTH topology. The TRx module consists of a epoxy novolak resin polymer planar lightwave circuit (PLC) hybrid integration technology with volume holographic grating triplex filter VHGT, surface-illuminated photodetectors and spot-size converted Fabry-Pérot laser diode in SMD package. The hybrid PLC has composed from a two parts-polymer optical waveguide including VHGT filter section and a optoelectronic microwave section. The both parts are placed on the composite substrate.

VLF Radio Field Strength Measurement of power line carrier system in San Diego, California

NASA Technical Reports Server (NTRS)

Mertel, H. K.

1981-01-01

The radio frequency interference (RFI) potential was evaluated for a Powerline Carriet (PLC) installed in San Diego which monitors the performance of an electrical power system. The PLC system generated 30 amperes at 5.79 kHz. The RF radiations were measured to be (typically) 120 dBuV/m at the beginning of the 12 kV powerline and 60 dBuV/m at the end of the powerline. The RF fields varied inversely as the distance squared. Measurements were also performed with a 45 kHz PLC system. The RF fields were of similar amplitude.

Exogenous hydrogen sulfide promotes hepatocellular carcinoma cell growth by activating the STAT3-COX-2 signaling pathway

PubMed Central

Zhen, Yulan; Wu, Qiaomei; Ding, Yiqian; Zhang, Wei; Zhai, Yuansheng; Lin, Xiaoxiong; Weng, Yunxia; Guo, Ruixian; Zhang, Ying; Feng, Jianqiang; Lei, Yiyan; Chen, Jingfu

2018-01-01

The effects of hydrogen sulfide (H2S) on cancer are controversial. Our group previously demonstrated that exogenous H2S promotes the development of cancer via amplifying the activation of the nuclear factor-κB signaling pathway in hepatocellular carcinoma (HCC) cells (PLC/PRF/5). The present study aimed to further investigate the hypothesis that exogenous H2S promotes PLC/PRF/5 cell proliferation and migration, and inhibits apoptosis by activating the signal transducer and activator of transcription 3 (STAT3)-cyclooxygenase-2 (COX-2) signaling pathway. PLC/PRF/5 cells were treated with 500 µmol/l NaHS (a donor of H2S) for 24 h. The expression levels of phosphorylated (p)-STAT3, STAT3, cleaved caspase-3 and COX-2 were measured by western blot assay. Cell viability was detected by Cell Counting kit-8 assay. Apoptotic cells were observed by Hoechst 33258 staining. The expression of STAT3 and COX-2 messenger RNA (mRNA) was detected by semiquantitative reverse transcription-polymerase chain reaction. The production of vascular endothelial growth factor (VEGF) was evaluated by ELISA. The results indicated that treatment of PLC/PRF/5 cells with 500 µmol/l NaHS for 24 h markedly increased the expression levels of p-STAT3 and STAT3 mRNA, leading to COX-2 and COX-2 mRNA overexpression, VEGF induction, decreased cleaved caspase-3 production, increased cell viability and migration, and decreased number of apoptotic cells. However, co-treatment of PLC/PRF/5 cells with 500 µmol/l NaHS and 30 µmol/l AG490 (an inhibitor of STAT3) or 20 µmol/l NS-398 (an inhibitor of COX-2) for 24 h significantly reverted the effects induced by NaHS. Furthermore, co-treatment of PLC/PRF/5 cells with 500 µmol/l NaHS and 30 µmol/l AG490 markedly decreased the NaHS-induced increase in the expression level of COX-2. By contrast, co-treatment of PLC/PRF/5 cells with 500 µmol/l NaHS and 20 µmol/l NS-398 inhibited the NaHS-induced increase in the expression level of p-STAT3. In conclusion, the findings of the present study provide evidence that the STAT3-COX-2 signaling pathway is involved in NaHS-induced cell proliferation, migration, angiogenesis and anti-apoptosis in PLC/PRF/5 cells, and suggest that the positive feedback between STAT3 and COX-2 may serve a crucial role in hepatocellular carcinoma carcinogenesis. PMID:29725404

Motor imaginary-based brain-machine interface design using programmable logic controllers for the disabled.

PubMed

Jeyabalan, Vickneswaran; Samraj, Andrews; Loo, Chu Kiong

2010-10-01

Aiming at the implementation of brain-machine interfaces (BMI) for the aid of disabled people, this paper presents a system design for real-time communication between the BMI and programmable logic controllers (PLCs) to control an electrical actuator that could be used in devices to help the disabled. Motor imaginary signals extracted from the brain’s motor cortex using an electroencephalogram (EEG) were used as a control signal. The EEG signals were pre-processed by means of adaptive recursive band-pass filtrations (ARBF) and classified using simplified fuzzy adaptive resonance theory mapping (ARTMAP) in which the classified signals are then translated into control signals used for machine control via the PLC. A real-time test system was designed using MATLAB for signal processing, KEP-Ware V4 OLE for process control (OPC), a wireless local area network router, an Omron Sysmac CPM1 PLC and a 5 V/0.3A motor. This paper explains the signal processing techniques, the PLC's hardware configuration, OPC configuration and real-time data exchange between MATLAB and PLC using the MATLAB OPC toolbox. The test results indicate that the function of exchanging real-time data can be attained between the BMI and PLC through OPC server and proves that it is an effective and feasible method to be applied to devices such as wheelchairs or electronic equipment.

Novel Networked Remote Laboratory Architecture for Open Connectivity Based on PLC-OPC-LabVIEW-EJS Integration. Application in Remote Fuzzy Control and Sensors Data Acquisition.

PubMed

González, Isaías; Calderón, Antonio José; Mejías, Andrés; Andújar, José Manuel

2016-10-31

In this paper the design and implementation of a network for integrating Programmable Logic Controllers (PLC), the Object-Linking and Embedding for Process Control protocol (OPC) and the open-source Easy Java Simulations (EJS) package is presented. A LabVIEW interface and the Java-Internet-LabVIEW (JIL) server complete the scheme for data exchange. This configuration allows the user to remotely interact with the PLC. Such integration can be considered a novelty in scientific literature for remote control and sensor data acquisition of industrial plants. An experimental application devoted to remote laboratories is developed to demonstrate the feasibility and benefits of the proposed approach. The experiment to be conducted is the parameterization and supervision of a fuzzy controller of a DC servomotor. The graphical user interface has been developed with EJS and the fuzzy control is carried out by our own PLC. In fact, the distinctive features of the proposed novel network application are the integration of the OPC protocol to share information with the PLC and the application under control. The user can perform the tuning of the controller parameters online and observe in real time the effect on the servomotor behavior. The target group is engineering remote users, specifically in control- and automation-related tasks. The proposed architecture system is described and experimental results are presented.

Loss of proliferation and differentiation capacity of aged human periodontal ligament stem cells and rejuvenation by exposure to the young extrinsic environment.

PubMed

Zheng, Wei; Wang, Shi; Ma, Dandan; Tang, Liang; Duan, Yinzhong; Jin, Yan

2009-09-01

The application of periodontal ligament stem cells (PDLSCs) may be effective for periodontal regenerative therapy. As tissue regenerative potential may be negatively regulated by aging, whether aging and its microenvironment modify human PDLSCs remains a question. In this study, we compared the proliferation and differentiation capacity of PDLSCs obtained from young and aged donors. Then, we exposed aged PDLSCs to young periodontal ligament cell-conditioned medium (PLC-CM), and young PDLSCs were exposed to aged PLC-CM. Morphological appearance, colony-forming assay, cell cycle analysis, osteogenic and adipogenic induction media, gene expression of cementoblast phenotype, and in vivo differentiation capacities of PDLSCs were evaluated. PDLSCs obtained from aged donors exhibited decreased proliferation and differentiation capacity when compared with those from young donors. Young PLC-CM enhanced the proliferation and differentiation capacity of PDLSCs from aged donors. Aged PDLSCs induced by young PLC-CM showed enhanced tissue-regenerative capacity to produce cementum/periodontal ligament-like structures, whereas young PDLSCs induced by aged PLC-CM transplants mainly formed connective tissues. To our knowledge, this is the first study to mimic the developmental microenvironment of PDLSCs in vitro, and our data suggest that age influences the proliferation and differentiation potential of human PDLSCs, and that the activity of human PDLSCs can be modulated by the extrinsic microenvironment.

The potential role of postsynaptic phospholipase C activity in synaptic facilitation and behavioral sensitization in Aplysia.

PubMed

Fulton, Daniel; Condro, Michael C; Pearce, Kaycey; Glanzman, David L

2008-07-01

Previous findings indicate that synaptic facilitation, a cellular mechanism underlying sensitization of the siphon withdrawal response (SWR) in Aplysia, depends on a cascade of postsynaptic events, including activation of inositol triphosphate (IP3) receptors and release of Ca2+ from postsynaptic intracellular stores. These findings suggest that phospholipase C (PLC), the enzyme that catalyzes IP3 formation, may play an important role in postsynaptic signaling during facilitation and learning in Aplysia. Using the PLC inhibitor U73122, we found that PLC activity is required for synaptic facilitation following a 10-min treatment with 5-HT, as measured at 20 min after 5-HT washout. Prior work has indicated that facilitation at this time is supported primarily by postsynaptic processes. To determine whether postsynaptic PLC activity is involved in 5-HT-mediated facilitatory actions, we examined the effect of U73122 on enhancement of the response of motor neurons isolated in cell culture to glutamate, the sensory neuron transmitter. A 10-min application of 5-HT induced persistent (>40 min) enhancement of glutamate-evoked potentials (Glu-EPs) recorded from isolated motor neurons, and this enhancement was blocked by U73122. Finally, we showed that injecting U73122 into intact animals before behavioral training impaired intermediate-term sensitization, indicating that PLC activity contributes to this form of nonassociative learning.

HD-03/ES: A Herbal Medicine Inhibits Hepatitis B Surface Antigen Secretion in Transfected Human Hepatocarcinoma PLC/PRF/5 Cells.

PubMed

Varma, Sandeep R; Sundaram, R; Gopumadhavan, S; Vidyashankar, Satyakumar; Patki, Pralhad S

2013-01-01

HD-03/ES is a herbal formulation used for the treatment of hepatitis B. However, the molecular mechanism involved in the antihepatitis B (HBV) activity of this drug has not been studied using in vitro models. The effect of HD-03/ES on hepatitis B surface antigen (HBsAg) secretion and its gene expression was studied in transfected human hepatocarcinoma PLC/PRF/5 cells. The anti-HBV activity was tested based on the inhibition of HBsAg secretion into the culture media, as detected by HBsAg-specific antibody-mediated enzyme assay (ELISA) at concentrations ranging from 125 to 1000  μ g/mL. The effect of HD-03/ES on HBsAg gene expression was analyzed using semiquantitative multiplex RT-PCR by employing specific primers. The results showed that HD-03/ES suppressed HBsAg production with an IC50 of 380  μ g/mL in PLC/PRF/5 cells for a period of 24 h. HD-03/ES downregulated HBsAg gene expression in PLC/PRF/5 cells. In conclusion, HD-03/ES exhibits strong anti-HBV properties by inhibiting the secretion of hepatitis B surface antigen in PLC/PRF/5 cells, and this action is targeted at the transcription level. Thus, HD-03/ES could be beneficial in the treatment of acute and chronic hepatitis B infections.

Novel Networked Remote Laboratory Architecture for Open Connectivity Based on PLC-OPC-LabVIEW-EJS Integration. Application in Remote Fuzzy Control and Sensors Data Acquisition

PubMed Central

González, Isaías; Calderón, Antonio José; Mejías, Andrés; Andújar, José Manuel

2016-01-01

In this paper the design and implementation of a network for integrating Programmable Logic Controllers (PLC), the Object-Linking and Embedding for Process Control protocol (OPC) and the open-source Easy Java Simulations (EJS) package is presented. A LabVIEW interface and the Java-Internet-LabVIEW (JIL) server complete the scheme for data exchange. This configuration allows the user to remotely interact with the PLC. Such integration can be considered a novelty in scientific literature for remote control and sensor data acquisition of industrial plants. An experimental application devoted to remote laboratories is developed to demonstrate the feasibility and benefits of the proposed approach. The experiment to be conducted is the parameterization and supervision of a fuzzy controller of a DC servomotor. The graphical user interface has been developed with EJS and the fuzzy control is carried out by our own PLC. In fact, the distinctive features of the proposed novel network application are the integration of the OPC protocol to share information with the PLC and the application under control. The user can perform the tuning of the controller parameters online and observe in real time the effect on the servomotor behavior. The target group is engineering remote users, specifically in control- and automation-related tasks. The proposed architecture system is described and experimental results are presented. PMID:27809229

Effects of a Single Dose of Parecoxib on Inflammatory Response and Ischemic Tubular Injury Caused by Hemorrhagic Shock in Rats.

PubMed

Takaku, Mariana; da Silva, Andre Carnevali; Iritsu, Nathalie Izumi; Vianna, Pedro Thadeu Galvao; Castiglia, Yara Marcondes Machado

2018-01-01

Parecoxib, a selective COX-2 inhibitor, is used to improve analgesia in postoperative procedures. Here we evaluated whether pretreatment with a single dose of parecoxib affects the function, cell injury, and inflammatory response of the kidney of rats subjected to acute hemorrhage. Inflammatory response was determined according to serum and renal tissue cytokine levels (IL-1 α , IL-1 β , IL-6, IL-10, and TNF- α ). Forty-four adult Wistar rats anesthetized with sevoflurane were randomized into four groups: placebo/no hemorrhage (Plc/NH); parecoxib/no hemorrhage (Pcx/NH); placebo/hemorrhage (Plc/H); and parecoxib/hemorrhage (Pcx/H). Pcx groups received a single dose of intravenous parecoxib while Plc groups received a single dose of placebo (isotonic saline). Animals in hemorrhage groups underwent bleeding of 30% of blood volume. Renal function and renal histology were then evaluated. Plc/H showed the highest serum levels of cytokines, suggesting that pretreatment with parecoxib reduced the inflammatory response in rats subjected to hemorrhage. No difference in tissue cytokine levels between groups was observed. Plc/H showed higher percentage of tubular dilation and degeneration, indicating that parecoxib inhibited tubular injury resulting from renal hypoperfusion. Our findings indicate that pretreatment with a single dose of parecoxib reduced the inflammatory response and tubular renal injury without altering renal function in rats undergoing acute hemorrhage.

The PLC/IP3R/PKC Pathway is Required for Ethanol-enhanced GABA Release

PubMed Central

Kelm, M. Katherine; Weinberg, Richard J.; Criswell, Hugh E.; Breese, George R.

2010-01-01

Summary Research on the actions of ethanol at the GABAergic synapse has traditionally focused on postsynaptic mechanisms, but recent data demonstrate that ethanol also increases both evoked and spontaneous GABA release in many brain regions. Using whole-cell voltage-clamp recordings, we previously showed that ethanol increases spontaneous GABA release at the rat interneuron-Purkinje cell synapse. This presynaptic ethanol effect is dependent on calcium release from internal stores, possibly through activation of inositol 1,4,5-trisphosphate receptors (IP3Rs). After confirming that ethanol targets vesicular GABA release, in the present study we used electron microscopic immunohistochemistry to demonstrate that IP3Rs are located in presynaptic terminals of cerebellar interneurons. Activation of IP3Rs requires binding of IP3, generated through activation of phospholipase C (PLC). We find that the PLC antagonist edelfosine prevents ethanol from increasing spontaneous GABA release. Diacylglycerol generated by PLC and calcium released by activation of the IP3R activate protein kinase C (PKC). Ethanol-enhanced GABA release was blocked by two PKC antagonists, chelerythrine and calphostin C. When a membrane impermeable PKC antagonist, PKC (19-36), was delivered intracellularly to the postsynaptic neuron, ethanol continued to increase spontaneous GABA release. Overall, these results suggest that activation of the PLC/IP3R/PKC pathway is necessary for ethanol to increase spontaneous GABA release from presynaptic terminals onto Purkinje cells. PMID:20206640

Regulation of calreticulin–major histocompatibility complex (MHC) class I interactions by ATP

PubMed Central

Wijeyesakere, Sanjeeva Joseph; Gagnon, Jessica K.; Arora, Karunesh; Brooks, Charles L.; Raghavan, Malini

2015-01-01

The MHC class I peptide loading complex (PLC) facilitates the assembly of MHC class I molecules with peptides, but factors that regulate the stability and dynamics of the assembly complex are largely uncharacterized. Based on initial findings that ATP, in addition to MHC class I-specific peptide, is able to induce MHC class I dissociation from the PLC, we investigated the interaction of ATP with the chaperone calreticulin, an endoplasmic reticulum (ER) luminal, calcium-binding component of the PLC that is known to bind ATP. We combined computational and experimental measurements to identify residues within the globular domain of calreticulin, in proximity to the high-affinity calcium-binding site, that are important for high-affinity ATP binding and for ATPase activity. High-affinity calcium binding by calreticulin is required for optimal nucleotide binding, but both ATP and ADP destabilize enthalpy-driven high-affinity calcium binding to calreticulin. ATP also selectively destabilizes the interaction of calreticulin with cellular substrates, including MHC class I molecules. Calreticulin mutants that affect ATP or high-affinity calcium binding display prolonged associations with monoglucosylated forms of cellular MHC class I, delaying MHC class I dissociation from the PLC and their transit through the secretory pathway. These studies reveal central roles for ATP and calcium binding as regulators of calreticulin–substrate interactions and as key determinants of PLC dynamics. PMID:26420867

Introduction to the Atari Computer. A Program Written in the Pilot Programming Language.

ERIC Educational Resources Information Center

Schlenker, Richard M.

Designed to be an introduction to the Atari microcomputers for beginners, the interactive computer program listed in this document is written in the Pilot programing language. Instructions are given for entering and storing the program in the computer memory for use by students. (MES)

Teacher Metacognition within the Professional Learning Community

ERIC Educational Resources Information Center

Prytula, Michelle P.

2012-01-01

A study of teacher metacognition within the context of the professional learning community (PLC) was conducted to understand how teachers describe their metacognition, what they describe as the catalysts to their metacognition, and how metacognition influences their work. Although the PLC was used as a context for the study, the findings include…

In the Round: Supporting Teachers' Authentic Professional Learning

ERIC Educational Resources Information Center

Strand, Matt

2013-01-01

This is a study of teachers' authentic professional learning at a public school in Poudre School District in northern Colorado. At Polaris Expeditionary Learning School, teachers and administrators have developed a form of school-based instructional rounds referred to herein as PLC rounds (professional learning community rounds). In PLC rounds,…

78 FR 70487 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-26

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... turbofan engines. This AD requires removal of certain high-pressure (HP) and intermediate-pressure (IP..., RB211 Trent 768-60, 772-60, and 772B-60 turbofan engines with turbine disc part numbers (P/Ns) and...

75 FR 27973 - Airworthiness Directives; Rolls-Royce plc RB211-524C2 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-19

... RB211-524C2 Series Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice... Rolls-Royce plc (RR) model RB211-524C2-19 and RB211-524C2-B-19 turbofan engines. These engines are...

78 FR 68360 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-14

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... turbofan engines. The AD number is incorrect in the Regulatory text. This document corrects that error. In... turbofan engines. As published, the AD number 2013-19-17 under Sec. 39.13 [Amended], is incorrect. No other...

78 FR 5126 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-24

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... turbofan engines. This AD requires replacement of the fuel oil heat exchanger (FOHE). This AD was prompted...-84 turbofan engines with a fuel oil heat exchanger (FOHE), part number 47111-1241, installed. (d...

78 FR 61171 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-03

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... (RR) RB211-535E4-B-37 series turbofan engines. This AD requires removal of affected parts using a...-B-37 series turbofan engines. (d) Unsafe Condition This AD was prompted by recalculating the lives...

Investigating the Interactions, Beliefs, and Practices of Teacher-Coach Teams in a STEM After-School Setting

NASA Astrophysics Data System (ADS)

Swanson Hoyle, Kylie Jayne

After-school programs, such as a STEM Career Club, can promote student interest, engagement, and awareness of STEM majors and fields, as well as encourage teachers to become more knowledgeable and competent in STEM areas. In this dissertation study, two schools were selected from a larger NSF-funded project to participate in this study. Teacher- Coaches (T-Coaches) from two rural middle schools in the southeastern United States (U.S.) participated in teacher professional development (TPD) sessions and Professional Learning Community (PLC) meetings to prepare them to lead an after-school STEM Club. The Community of Practice (CoP) framework and Social Cognitive Theory are employed to investigate underlying factors that contribute to teacher interactions and preparations, and differing STEM program outcomes. Data from the Dimensions of Success (DoS) observation tool, the teacher belief interview (TBI), T-Coach participation and attendance at TPD, attendance and audio recordings from PLC meetings, and T-Coach card sorts were analyzed over approximately 6 meetings for 5 months. Findings are presented in two chapters. In Chapter Four, a comparative case study of the interactions of the teachers at two participating middle schools is analyzed. Results indicate that for each case, the club's T-Coaches interacted positively to prepare for club meetings and have a well-functioning CoP within their PLC. The first case (Northern Middle School) interacted in ways that aligned with the CoP framework (enterprise and repertoire), which led them to achieve, on average, desirable ratings on 7 of the 12 DoS dimensions. However, the other case (Southern Middle School), the T-Coaches interacted in ways that demonstrated more equal levels of enterprise, mutuality, and repertoire; this PLC had higher DoS ratings during the STEM Clubs in all dimensions (11/12 met desirable ratings). These findings suggest that high levels of all of the social learning characteristics within PLCs can support more exemplary STEM Club implementation. In Chapter Five, results from the two schools of teachers' beliefs and practices indicate that for STEM program success, the whole of the team is better than the sum of its parts. Since individuals' values on each team aligned with different DoS dimensions, it was more likely that each dimension would be represented during STEM Clubs. Findings suggest that it was necessary for two T-Coaches who valued a certain dimension to ensure a DoS dimension would be met on the DoS rating. However, it was not sufficient that T-Coaches only valued a certain dimension. The dimension was not met if the T-Coaches did not have the training and preparation to meaningfully act on their beliefs. Informed by factors from Bandura's Social Cognitive Theory, these T-Coaches carried out different behaviors at the STEM Clubs depending on their personal beliefs and values, and the environment. Five TPD participation scenarios, ranging from full to no TPD preparation, identified from the findings seemed to predict the quality of the STEM Club, based on DoS scores. The following conclusions can be drawn: 1) Professional learning community meetings aided in the development of T-Coaches' community of practice and preparation for STEM clubs; 2) A CoP with high levels of all of the social learning characteristics (enterprise, mutuality, and repertoire) led to more desirable club outcomes than a team with lower levels in any of these areas; 3) At least two people who have developed the content knowledge and relevant skills and who value club success were needed at club meetings to ensure STEM Club success; 4) Teacher-Coaches became more prepared to lead successful STEM Clubs through engaged attendance at TPD and PLC meetings; 5) Interdisciplinary teacher teams, including non-STEM teachers, can successfully lead STEM clubs if the individuals are able to learn the content/skills.

Generic command interpreter for robot controllers

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

Werner, J.

1991-04-09

Generic command interpreter programs have been written for robot controllers at Sandia National Laboratories (SNL). Each interpreter program resides on a robot controller and interfaces the controller with a supervisory program on another (host) computer. We call these interpreter programs monitors because they wait, monitoring a communication line, for commands from the supervisory program. These monitors are designed to interface with the object-oriented software structure of the supervisory programs. The functions of the monitor programs are written in each robot controller's native language but reflect the object-oriented functions of the supervisory programs. These functions and other specifics of the monitormore » programs written for three different robots at SNL will be discussed. 4 refs., 4 figs.« less

Application programs written by using customizing tools of a computer-aided design system

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

Li, X.; Huang, R.; Juricic, D.

1995-12-31

Customizing tools of Computer-Aided Design Systems have been developed to such a degree as to become equivalent to powerful higher-level programming languages that are especially suitable for graphics applications. Two examples of application programs written by using AutoCAD`s customizing tools are given in some detail to illustrate their power. One tool uses AutoLISP list-processing language to develop an application program that produces four views of a given solid model. The other uses AutoCAD Developmental System, based on program modules written in C, to produce an application program that renders a freehand sketch from a given CAD drawing.

Distinguishing Internet-facing ICS Devices Using PLC Programming Information

DTIC Science & Technology

2014-06-19

the course of this research. I would also like to thank the faculty and students at AFIT who helped me think through some of these problems. Finally, I...21 FTP 143 IMAP 1900 UPnP 6379 Redis 22 SSH 161 SNMP 2323 Telnet 7777 Oracle 23 Telnet 443 HTTPS 3306 MySQL 8000 Qconn 25 SMTP 445 SMB 3389 RDP 8080...250ms over the course of 10,000 samples provided sufficient data to test for statistically significant changes to ladder logic execution times with a

Analysis of data throughput in communication between PLCs and HMI/SCADA systems

NASA Astrophysics Data System (ADS)

Mikolajek, Martin; Koziorek, Jiri

2016-09-01

This paper is focused on Analysis of data throughout in communication between PLCs and HMI/SCADA systems. The first part of paper discusses basic problematic communication between PLC and HMI systems. Next part is about specific types of communications PLC - HMI requests. For those cases paper is talking about response and data throughput1-3 . Subsequent section of this article contains practical parts with various data exchanges between PLC Siemens and HMI. The possibilities of communication that are described in this article are focused on using OPC server for visualization software, custom HMI system and own application created by using .NET with Technology. The last part of this article contains some communication solutions.

PLC-based LP₁₁ mode rotator for mode-division multiplexing transmission.

PubMed

Saitoh, Kunimasa; Uematsu, Takui; Hanzawa, Nobutomo; Ishizaka, Yuhei; Masumoto, Kohei; Sakamoto, Taiji; Matsui, Takashi; Tsujikawa, Kyozo; Yamamoto, Fumihiko

2014-08-11

A PLC-based LP11 mode rotator is proposed. The proposed mode rotator is composed of a waveguide with a trench that provides asymmetry of the waveguide. Numerical simulations show that converting LP11a (LP11b) mode to LP11b (LP11a) mode can be achieved with high conversion efficiency (more than 90%) and little polarization dependence over a wide wavelength range from 1450 nm to 1650 nm. In addition, we fabricate the proposed LP11 mode rotator using silica-based PLC. It is confirmed that the fabricated mode rotator can convert LP11a mode to LP11b mode over a wide wavelength range.

Intelligent Traffic Light Based on PLC Control

NASA Astrophysics Data System (ADS)

Mei, Lin; Zhang, Lijian; Wang, Lingling

2017-11-01

The traditional traffic light system with a fixed control mode and single control function is contradicted with the current traffic section. The traditional one has been unable to meet the functional requirements of the existing flexible traffic control system. This paper research and develop an intelligent traffic light called PLC control system. It uses PLC as control core, using a sensor module for receiving real-time information of vehicles, traffic control mode for information to select the traffic lights. Of which control mode is flexible and changeable, and it also set the countdown reminder to improve the effectiveness of traffic lights, which can realize the goal of intelligent traffic diversion, intelligent traffic diversion.

An Automatic Networking and Routing Algorithm for Mesh Network in PLC System

NASA Astrophysics Data System (ADS)

Liu, Xiaosheng; Liu, Hao; Liu, Jiasheng; Xu, Dianguo

2017-05-01

Power line communication (PLC) is considered to be one of the best communication technologies in smart grid. However, the topology of low voltage distribution network is complex, meanwhile power line channel has characteristics of time varying and attenuation, which lead to the unreliability of power line communication. In this paper, an automatic networking and routing algorithm is introduced which can be adapted to the "blind state" topology. The results of simulation and test show that the scheme is feasible, the routing overhead is small, and the load balance performance is good, which can achieve the establishment and maintenance of network quickly and effectively. The scheme is of great significance to improve the reliability of PLC.

Achieving EMC Emissions Compliance for an Aeronautics Power Line Communications System

NASA Astrophysics Data System (ADS)

Dominiak, S.; Vos, G.; ter Meer, T.; Widmer, H.

2012-05-01

Transmitting data over the power distribution network - Power Line Communications (PLC) -provides an interesting solution to reducing the weight and complexity of wiring networks in commercial aircraft. One of the potential roadblocks for the introduction of this technology is achieving EMC emissions compliance. In this article an overview of the EMC conducted and radiated emissions testing for PLC- enabled aeronautics equipment is presented. Anomalies resulting from chamber resonances leading to discrepancies between the conducted emissions tests and the measured radiated emissions are identified and described. Measurements made according to the current version of the civil aeronautical EMC standard, EUROCAE ED-14F (RTCA DO-160F), show that PLC equipment can achieve full EMC emissions compliance.

From Professional Practice to Practical Leader: Teacher Leadership in Professional Learning Communities

ERIC Educational Resources Information Center

Wilson, Adrianne

2016-01-01

The primary purpose of this research is to illuminate perceptions and lived experiences of secondary teachers through their involvement in a Professional Learning Community (PLC). Teachers' experiences within a PLC were examined for patterns of cultivated leadership. The second purpose of the study was to identify variables that either promote or…

Teachers and Students Together in a Professional Learning Community

ERIC Educational Resources Information Center

Wennergren, Ann-Christine; Blossing, Ulf

2017-01-01

Students represent the majority of the people in a school organisation, but are rarely considered as participants in literature on professional learning communities (PLC). This article explored a PLC with the legitimate participation of students in the classroom. Data was based on interviews with 11 teachers. Community of practice theory provides…

Literacy Training in an Urban High School Professional Learning Community

ERIC Educational Resources Information Center

Ross-Norris, Vicki

2017-01-01

The purpose of this study was to explore the essence of professional learning experiences shared by teachers who participated in a professional learning community (PLC) at a New York City high school in the South Bronx. Guided by Hord's PLC characteristics and Bruner's constructivism theories, this phenomenological study addressed the research…

Global Conceptualization of the Professional Learning Community Process: Transitioning from Country Perspectives to International Commonalities

ERIC Educational Resources Information Center

Huffman, Jane B.; Olivier, Dianne F.; Wang, Ting; Chen, Peiying; Hairon, Salleh; Pang, Nicholas

2016-01-01

The authors seek to find common PLC structures and actions among global educational systems to enhance understanding and practice. Six international researchers formed the Global Professional Learning Community Network (GloPLCNet), conducted literature reviews of each country's involvement with PLC actions, and noted similarities and common…

76 FR 19468 - Notice of Determinations Regarding Eligibility To Apply for Worker Adjustment Assistance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-07

... Hills, CA.... February 14, 2010. Applications, WellPoint Co., BC of CA, Leased Workers Bender, etc. 75.... 75,285 VisLink, Inc., VisLink, North Billerica, MA... February 14, 2010. PLC; Leased Workers from...Link, PLC. 75,300 Key Plastics, LLC, Exterior Hartford City, IN..... February 14, 2010. Division...

Professional Learning Communities: Teachers' Perceptions and Student Achievement

ERIC Educational Resources Information Center

Peters, Erica

2013-01-01

Professional Learning Communities (PLC's) are designed to help schools improve student achievement; all decisions are based on the needs of students. PLC's are an effective way to receive professional development (PD), allow for collaboration with fellow teachers, and offer timely intervention to all students. In a district known for PLC…

Teacher Collaboration and Student Learning in a Professional Learning Community

ERIC Educational Resources Information Center

Vaughan, Mary Elaine

2013-01-01

Researchers have endorsed teacher collaboration within a professional learning community (PLC) that is focused on student learning. Despite these research-based endorsements, several Algebra 1 teachers in a southeastern high school implemented components of a PLC with little or no results in student achievement. The purpose of this study was to…

77 FR 64242 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-19

... plc, P.O. Box 31, Derby, DE24 8BJ, United Kingdom; telephone 011 44 1332 242424; fax 011 44 1332... . For Bombardier service information identified in this proposed AD, contact Short Brothers PLC... investigation into the nature, cause, and extent of the cracking. If final action is later identified, based on...

Developing a Professional Learning Community among Preservice Teachers

ERIC Educational Resources Information Center

Bond, Nathan

2013-01-01

This action research study examined the development of a professional learning community (PLC) among 20 preservice secondary teachers as they met regularly during a semester-long, field-based education course to share artifacts of learning from their professional portfolios. The PLC model described by Hord and Tobia (2012) served as a framework…

20. Photocopy of a drawing (original in the Collection of ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

20. Photocopy of a drawing (original in the Collection of the PL&C, Plan Book A, pp.26-27)--ca. 1833--HAMILTON CANAL, PENSTOCK HURD'S CANAL, AND HAMILTON MANUFACTURING CO.; LAND IN CHELMSFORD BELONGING TO THE PL&C IN AUGUST 1833 - Lowell Canal System, Merrimack & Concord Rivers, Lowell, Middlesex County, MA

78 FR 20509 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-05

... Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed rulemaking...) RB211-535E4-B-37 series turbofan engines. This proposed AD was prompted by recalculating the life of.... (c) Applicability This AD applies to Rolls-Royce plc (RR) RB211-535E4-B-37 series turbofan engines...

77 FR 39157 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-02

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT...-84, and 980-84 turbofan engines. That AD currently requires inspecting the intermediate-pressure (IP... RR model RB211-Trent 970-84, 970B-84, 972-84, 972B-84, 977-84, 977B-84, and 980-84 turbofan engines...

Productive Use of Collaborative Time. Research into Practice

ERIC Educational Resources Information Center

Williamson, Ronald

2012-01-01

Many schools have embraced the idea of professional learning communities (PLC's). While the term is used to describe many types of collaborative activities, PLC's are most successful when they focus intently on improving student learning. In these communities of learners there is a shared commitment to continually learn and act on that learning in…

Experiencing the Product Life Cycle Management Highs and Lows through Dramatic Simulation

ERIC Educational Resources Information Center

Pearce, Glenn; Jackson, John

2009-01-01

Product life cycle (PLC) stages and diagrams are briefly and dispassionately covered in the standard marketing textbook format with little attention to the social-psychological experiences of those actually participating. This qualitative study used process drama as a teaching tool and a research instrument to probe the PLC phenomenon in a…

76 FR 36981 - Airworthiness Directives; Rolls-Royce plc RB211-Trent 500 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... Airworthiness Directives; Rolls-Royce plc RB211--Trent 500 Series Turbofan Engines AGENCY: Federal Aviation... condition on an aviation product. The MCAI describes the unsafe condition as: A Trent 500 engine has been found with thermal distress of the Intermediate Pressure (IP) Turbine Nozzle Guide Vanes. The resultant...

Challenges of Teacher Collaboration within a Professional Learning Community

ERIC Educational Resources Information Center

Seisay, Benson M.

2013-01-01

The professional learning community (PLC) is a powerful tool in education, one that is intended to reform failing schools and improve student achievement. This research gathered data to determine teacher perceptions about challenges of teacher collaboration within a PLC school. The key conceptual framework for this case study originated from work…

Trust and Collaboration in PLC Teams: Teacher Relationships, Principal Support, and Collaborative Benefits

ERIC Educational Resources Information Center

Hallam, Pamela R.; Smith, Henry R.; Hite, Julie M.; Hite, Steven J.; Wilcox, Bradley R.

2015-01-01

Professional learning communities (PLCs) are being recognized as effective in improving teacher collaboration and student achievement. Trust is critical in effectively implementing the PLC model, and the school principal is best positioned to influence school trust levels. Using five facets of trust, this research sought to clarify the impact of…

Experimental Determination of the Permeability in the Lacunar-Canalicular Porosity of Bone

PubMed Central

Gailani, Gaffar; Benalla, Mohammed; Mahamud, Rashal; Cowin, Stephen C.; Cardoso, Luis

2010-01-01

Permeability of the mineralized bone tissue is a critical element in understanding fluid flow occurring in the lacunar-canalicular porosity (PLC) compartment of bone and its role in bone nutrition and mechanotransduction. However, the estimation of bone permeability at the tissue level is affected by the influence of the vascular porosity (PV) in macroscopic samples containing several osteons. In this communication, both analytical and experimental approaches are proposed to estimate the lacunar-canalicular permeability in a single osteon. Data from an experimental stress-relaxation test in a single osteon is used to derive the PLC permeability by curve fitting to theoretical results from a compressible transverse isotropic poroelastic model of a porous annular disk under a ramp loading history (Cowin and Mehrabadi 2007; Gailani and Cowin 2008). The PLC tissue intrinsic permeability in the radial direction of the osteon was found to be dependent on the strain rate used and within the range of O(10−24)−O(10−25). The reported values of PLC permeability are in reasonable agreement with previously reported values derived using FEA and nanoindentation approaches. PMID:19831477

Development of a measurement and control system for a 10 kW@20 K refrigerator based on Siemens PLC S7-300

NASA Astrophysics Data System (ADS)

Li, J.; Liu, L. Q.; Liu, T.; Xu, X. D.; Dong, B.; Lu, W. H.; Pan, W.; Wu, J. H.; Xiong, L. Y.

2017-02-01

A 10 kW@20 K refrigerator has been established by the Technical Institute of Physics and Chemistry, Chinese Academy of Sciences. A measurement and control system based on Siemens PLC S7-300 for this 10 kW@20 K refrigerator is developed. According to the detailed measurement requirements, proper sensors and transmitters are adopted. Siemens S7-300 PLC CPU315-2 PN/DP operates as a master station. Two sets of ET200M DP remote expand I/O, one power meter, two compressors and one vacuum gauge operate as slave stations. Profibus-DP field communication and Modbus communication are used between the master station and the slave stations in this control system. The upper computer HMI (Human Machine Interface) is compiled using Siemens configuration software WinCC V7.0. The upper computer communicates with PLC by means of industrial Ethernet. After commissioning, this refrigerator has been operating with a 10 kW of cooling power at 20 K for more than 72 hours.

Fabrication of a TFF-Attached WDM-Type Triplex Transceiver Module Using Silica PLC Hybrid Integration Technology

NASA Astrophysics Data System (ADS)

Han, Young-Tak; Park, Yoon-Jung; Park, Sang-Ho; Shin, Jang-Uk; Lee, Chul-Wook; Ko, Hyunsung; Baek, Yongsoon; Park, Chul-Hee; Kwon, Yoon-Koo; Hwang, Wol-Yon; Oh, Kwang-Ryong; Sung, Heekyung

2006-12-01

An optical triplex transceiver (TRx) module, which consists of thin-film filter (TFF)-attached wavelength-division multiplexer (WDM) and photodiode (PD) carriers, has been fabricated using a silica planar lightwave circuit (PLC) hybrid integration technology. Two types of TFFs were attached to a diced sidewall of a silica-terraced PLC platform to realize the TFF-attached WDM. The PD carriers with a 45° mirror, on which receiving surface-illuminated PDs were bonded, were assembled with the PLC platform to form receiver (Rx) parts. As the main performances of the packaged TRx module, a very clear transmitter (Tx) eye pattern and minimum Rx sensitivity of -25.7 dBm were obtained under a 1.25-Gb/s Tx Rx operation for digital applications. For an analog Rx application, a module responsivity of about 0.8 A/W was achieved, and a second-order intermodulation distortion value of less than -70 dBc at an optical modulation index of 40% was obtained under a two-tone test of 400 and 450 MHz.

Production of infectious ferret hepatitis E virus in a human hepatocarcinoma cell line PLC/PRF/5.

PubMed

Li, Tian-Cheng; Yoshizaki, Sayaka; Yang, Tingting; Kataoka, Michiyo; Nakamura, Tomofumi; Ami, Yasushi; Yuriko, Suzaki; Takeda, Naokazu; Wakita, Takaji

2016-02-02

A strain of ferret hepatitis E virus (HEV), sF4370, isolated from an imported ferret was used to inoculate a human hepatocarcinoma cell line, PLC/PRF/5. The virus genome and capsid protein were detected in the cell culture supernatant. Immunofluorescence microscopy indicated that the capsid protein was located in the cytoplasm. The virus particles were purified from the culture supernatant by sucrose gradient ultracentrifugation. The capsid protein with molecular mass of ∼72 kDa was detected in fractions with density of 1.150-1.162 g/cm(3), and particles of ferret HEV was associated with cell membrane. The virus recovered from the supernatant was serially passaged with PLC/PRF/5 cells and had the ability to infect ferrets by oral inoculation, indicating that the ferret HEV grown in PLC/PRF/5 was infectious. The establishment of ferret HEV cell culture system might be useful to understand the life cycle, mechanism of infection and replication of ferret HEV. Copyright © 2015 Elsevier B.V. All rights reserved.

Modeling of Hydration, Compressive Strength, and Carbonation of Portland-Limestone Cement (PLC) Concrete.

PubMed

Wang, Xiao-Yong

2017-01-26

Limestone is widely used in the construction industry to produce Portland limestone cement (PLC) concrete. Systematic evaluations of hydration kinetics, compressive strength development, and carbonation resistance are crucial for the rational use of limestone. This study presents a hydration-based model for evaluating the influences of limestone on the strength and carbonation of concrete. First, the hydration model analyzes the dilution effect and the nucleation effect of limestone during the hydration of cement. The degree of cement hydration is calculated by considering concrete mixing proportions, binder properties, and curing conditions. Second, by using the gel-space ratio, the compressive strength of PLC concrete is evaluated. The interactions among water-to-binder ratio, limestone replacement ratio, and strength development are highlighted. Third, the carbonate material contents and porosity are calculated from the hydration model and are used as input parameters for the carbonation model. By considering concrete microstructures and environmental conditions, the carbon dioxide diffusivity and carbonation depth of PLC concrete are evaluated. The proposed model has been determined to be valid for concrete with various water-to-binder ratios, limestone contents, and curing periods.

Assembly of the MHC I peptide-loading complex determined by a conserved ionic lock-switch

PubMed Central

Blees, Andreas; Reichel, Katrin; Trowitzsch, Simon; Fisette, Olivier; Bock, Christoph; Abele, Rupert; Hummer, Gerhard; Schäfer, Lars V.; Tampé, Robert

2015-01-01

Salt bridges in lipid bilayers play a decisive role in the dynamic assembly and downstream signaling of the natural killer and T-cell receptors. Here, we describe the identification of an inter-subunit salt bridge in the membrane within yet another key component of the immune system, the peptide-loading complex (PLC). The PLC regulates cell surface presentation of self-antigens and antigenic peptides via molecules of the major histocompatibility complex class I. We demonstrate that a single salt bridge in the membrane between the transporter associated with antigen processing TAP and the MHC I-specific chaperone tapasin is essential for the assembly of the PLC and for efficient MHC I antigen presentation. Molecular modeling and all-atom molecular dynamics simulations suggest an ionic lock-switch mechanism for the binding of TAP to tapasin, in which an unfavorable uncompensated charge in the ER-membrane is prevented through complex formation. Our findings not only deepen the understanding of the interaction network within the PLC, but also provide evidence for a general interaction principle of dynamic multiprotein membrane complexes in immunity. PMID:26611325

Modeling of Hydration, Compressive Strength, and Carbonation of Portland-Limestone Cement (PLC) Concrete

PubMed Central

Wang, Xiao-Yong

2017-01-01

Limestone is widely used in the construction industry to produce Portland limestone cement (PLC) concrete. Systematic evaluations of hydration kinetics, compressive strength development, and carbonation resistance are crucial for the rational use of limestone. This study presents a hydration-based model for evaluating the influences of limestone on the strength and carbonation of concrete. First, the hydration model analyzes the dilution effect and the nucleation effect of limestone during the hydration of cement. The degree of cement hydration is calculated by considering concrete mixing proportions, binder properties, and curing conditions. Second, by using the gel–space ratio, the compressive strength of PLC concrete is evaluated. The interactions among water-to-binder ratio, limestone replacement ratio, and strength development are highlighted. Third, the carbonate material contents and porosity are calculated from the hydration model and are used as input parameters for the carbonation model. By considering concrete microstructures and environmental conditions, the carbon dioxide diffusivity and carbonation depth of PLC concrete are evaluated. The proposed model has been determined to be valid for concrete with various water-to-binder ratios, limestone contents, and curing periods. PMID:28772472

Competition between Anion Binding and Dimerization Modulates Staphylococcus aureus Phosphatidylinositol-specific Phospholipase C Enzymatic Activity*

PubMed Central

Cheng, Jiongjia; Goldstein, Rebecca; Stec, Boguslaw; Gershenson, Anne; Roberts, Mary F.

2012-01-01

Staphylococcus aureus phosphatidylinositol-specific phospholipase C (PI-PLC) is a secreted virulence factor for this pathogenic bacterium. A novel crystal structure shows that this PI-PLC can form a dimer via helix B, a structural feature present in all secreted, bacterial PI-PLCs that is important for membrane binding. Despite the small size of this interface, it is critical for optimal enzyme activity. Kinetic evidence, increased enzyme specific activity with increasing enzyme concentration, supports a mechanism where the PI-PLC dimerization is enhanced in membranes containing phosphatidylcholine (PC). Mutagenesis of key residues confirm that the zwitterionic phospholipid acts not by specific binding to the protein, but rather by reducing anionic lipid interactions with a cationic pocket on the surface of the S. aureus enzyme that stabilizes monomeric protein. Despite its structural and sequence similarity to PI-PLCs from other Gram-positive pathogenic bacteria, S. aureus PI-PLC appears to have a unique mechanism where enzyme activity is modulated by competition between binding of soluble anions or anionic lipids to the cationic sensor and transient dimerization on the membrane. PMID:23038258

Science Professional Learning Communities: Beyond a singular view of teacher professional development

NASA Astrophysics Data System (ADS)

Jones, M. Gail; Gardner, Grant E.; Robertson, Laura; Robert, Sarah

2013-07-01

Professional Learning Communities (PLCs) are frequently being used as a vehicle to transform science education. This study explored elementary teachers' perceptions about the impact of participating in a science PLC on their own professional development. With the use of The Science Professional Learning Communities Survey and a semi-structured interview protocol, elementary teachers' perceptions of the goals of science PLCs, the constraints and benefits of participation in PLCs, and reported differences in the impact of PLC participation on novice and experienced teachers were examined. Sixty-five elementary teachers who participated in a science PLC were surveyed about their experiences, and a subsample of 16 teachers was interviewed. Results showed that most of the teachers reported their science PLC emphasized sharing ideas with other teachers as well as working to improve students' science standardized test scores. Teachers noted that the PLCs had impacted their science assessment practices as well as their lesson planning. However, a majority of the participants reported a differential impact of PLCs depending on a teacher's level of experience. PLCs were reported as being more beneficial to new teachers than experienced teachers. The interview results demonstrated that there were often competing goals and in some cases a loss of autonomy in planning science lessons. A significant concern was the impact of problematic interpersonal relationships and communication styles on the group functioning. The role of the PLC in addressing issues related to obtaining science resources and enhancing science content knowledge for elementary science teachers is discussed.

Phosphatidylcholine-specific phospholipase C inhibition down- regulates CXCR4 expression and interferes with proliferation, invasion and glycolysis in glioma cells

PubMed Central

Ricci, Alessandro; Pacella, Aurora; Cigliana, Giovanni; Bozzuto, Giuseppina; Podo, Franca; Carpinelli, Giulia

2017-01-01

Background The chemokine receptor CXCR4 plays a crucial role in tumors, including glioblastoma multiforme (GBM), the most aggressive glioma. Phosphatidylcholine-specific phospholipase C (PC-PLC), a catabolic enzyme of PC metabolism, is involved in several aspects of cancer biology and its inhibition down-modulates the expression of growth factor membrane receptors interfering with their signaling pathways. In the present work we investigated the possible interplay between CXCR4 and PC-PLC in GBM cells. Methods Confocal microscopy, immunoprecipitation, western blot analyses, and the evaluation of migration and invasion potential were performed on U87MG cells after PC-PLC inhibition with the xanthate D609. The intracellular metabolome was investigated by magnetic resonance spectroscopy; lactate levels and lactate dehydrogenase (LDH) activity were analyzed by colorimetric assay. Results Our studies demonstrated that CXCR4 and PC-PLC co-localize and are associated on U87MG cell membrane. D609 reduced CXCR4 expression, cell proliferation and invasion, interfering with AKT and EGFR activation and expression. Metabolic analyses showed a decrease in intracellular lactate concentration together with a decrement in LDH activity. Conclusions Our data suggest that inhibition of PC-PLC could represent a new molecular approach in glioma biology not only for its ability in modulating cell metabolism, glioma growth and motility, but also for its inhibitory effect on crucial molecules involved in cancer progression. PMID:28423060

Inhibition of phospholipase C disrupts cytoskeletal organization and gravitropic growth in Arabidopsis roots.

PubMed

Andreeva, Zornitza; Barton, Deborah; Armour, William J; Li, Min Y; Liao, Li-Fen; McKellar, Heather L; Pethybridge, Kylie A; Marc, Jan

2010-10-01

The phospholipase protein superfamily plays an important role in hormonal signalling and cellular responses to environmental stimuli. There is also growing evidence for interactions between phospholipases and the cytoskeleton. In this report we used a pharmacological approach to investigate whether inhibiting a member of the phospholipase superfamily, phospholipase C (PLC), affects microtubules and actin microfilaments as well as root growth and morphology of Arabidopsis thaliana seedlings. Inhibiting PLC activity using the aminosteroid U73122 significantly inhibited root elongation and disrupted root morphology in a concentration-dependent manner, with the response being saturated at 5 μM, whereas the inactive analogue U73343 was ineffective. The primary root appeared to lose growth directionality accompanied by root waving and formation of curls. Immunolabelling of roots exposed to increasingly higher U73122 concentrations revealed that the normal transverse arrays of cortical microtubules in the elongation zone became progressively more disorganized or depolymerized, with the disorganization appearing within 1 h of incubation. Likewise, actin microfilament arrays also were disrupted. Inhibiting PLC using an alternative inhibitor, neomycin, caused similar disruptions to both cytoskeletal organization and root morphology. In seedlings gravistimulated by rotating the culture plates by 90°, both U73122 and neomycin disrupted the normal gravitropic growth of roots and etiolated hypocotyls. The effects of PLC inhibitors are therefore consistent with the notion that, as with phospholipases A and D, PLC likewise interacts with the cytoskeleton, alters growth morphology, and is involved in gravitropism.

Determinants of GPI-PLC Localisation to the Flagellum and Access to GPI-Anchored Substrates in Trypanosomes

PubMed Central

Sunter, Jack; Webb, Helena; Carrington, Mark

2013-01-01

In Trypanosoma brucei, glycosylphosphatidylinositol phospholipase C (GPI-PLC) is a virulence factor that releases variant surface glycoprotein (VSG) from dying cells. In live cells, GPI-PLC is localised to the plasma membrane where it is concentrated on the flagellar membrane, so activity or access must be tightly regulated as very little VSG is shed. Little is known about regulation except that acylation within a short internal motif containing three cysteines is necessary for GPI-PLC to access VSG in dying cells. Here, GPI-PLC mutants have been analysed both for subcellular localisation and for the ability to release VSG from dying cells. Two sequence determinants necessary for concentration on the flagellar membrane were identified. First, all three cysteines are required for full concentration on the flagellar membrane. Mutants with two cysteines localise predominantly to the plasma membrane but lose some of their flagellar concentration, while mutants with one cysteine are mainly localised to membranes between the nucleus and flagellar pocket. Second, a proline residue close to the C-terminus, and distant from the acylated cysteines, is necessary for concentration on the flagellar membrane. The localisation of GPI-PLC to the plasma but not flagellar membrane is necessary for access to the VSG in dying cells. Cellular structures necessary for concentration on the flagellar membrane were identified by depletion of components. Disruption of the flagellar pocket collar caused loss of concentration whereas detachment of the flagellum from the cell body after disruption of the flagellar attachment zone did not. Thus, targeting to the flagellar membrane requires: a titratable level of acylation, a motif including a proline, and a functional flagellar pocket. These results provide an insight into how the segregation of flagellar membrane proteins from those present in the flagellar pocket and cell body membranes is achieved. PMID:23990786

Phosphatidylcholine-specific phospholipase C inhibition reduces HER2-overexpression, cell proliferation and in vivo tumor growth in a highly tumorigenic ovarian cancer model

PubMed Central

Spadaro, Francesca; Abalsamo, Laura; Pisanu, Maria Elena; Ricci, Alessandro; Cecchetti, Serena; Altabella, Luisa; Buoncervello, Maria; Lozneanu, Ludmila; Bagnoli, Marina; Ramoni, Carlo; Canevari, Silvana; Mezzanzanica, Delia

2017-01-01

Antagonizing the oncogenic effects of human epidermal growth factor receptor 2 (HER2) with current anti-HER2 agents has not yet yielded major progress in the treatment of advanced HER2-positive epithelial ovarian cancer (EOC). Using preclinical models to explore alternative molecular mechanisms affecting HER2 overexpression and oncogenicity may lead to new strategies for EOC patient treatment. We previously reported that phosphatidylcholine-specific phospholipase C (PC-PLC) exerts a pivotal role in regulating HER2 overexpression in breast cancer cells. The present study, conducted on two human HER2-overexpressing EOC cell lines - SKOV3 and its in vivo-passaged SKOV3.ip cell variant characterized by enhanced in vivo tumorigenicity - and on SKOV3.ip xenografts implanted in SCID mice, showed: a) about 2-fold higher PC-PLC and HER2 protein expression levels in SKOV3.ip compared to SKOV3 cells; b) physical association of PC-PLC with HER2 in non-raft domains; c) HER2 internalization and ca. 50% reduction of HER2 mRNA and protein expression levels in SKOV3.ip cells exposed to the PC-PLC inhibitor tricyclodecan-9-yl-potassium xanthate (D609); d) differential effects of D609 and trastuzumab on HER2 protein expression and cell proliferation; e) decreased in vivo tumor growth in SKOV3.ip xenografts during in vivo treatment with D609; f) potential use of in vivo magnetic resonance spectroscopy (MRS) and imaging (MRI) parameters as biomarkers of EOC response to PC-PLC inhibition. Overall, these findings support the view that PC-PLC inhibition may represent an effective means to target the tumorigenic effects of HER2 overexpression in EOC and that in vivo MR approaches can efficiently monitor its effects. PMID:28903399

Streamlined structure elucidation of an unknown compound in a pigment formulation.

PubMed

Yüce, Imanuel; Morlock, Gertrud E

2016-10-21

A fast and reliable quality control is important for ink manufacturers to ensure a constant production grade of mixtures and chemical formulations, and unknown components attract their attention. Structure elucidating techniques seem time-consuming in combination with column-based methods, but especially the low solubility of pigment formulations is challenging the analysis. In contrast, layer chromatography is more tolerant with regard to pigment particles. One PLC plate for NMR and FTIR analyses and one HPTLC plate for recording of high resolution mass spectra, MS/MS spectra and for gathering information on polarity and spectral properties were needed to characterize a structure, exemplarily shown for an unknown component in pigment Red 57:1 to be 3-hydroxy-2-naphtoic acid. A preparative layer chromatography (PLC) workflow was developed that used an Automated Multiple Development 2 (AMD 2) system. The 0.5-mm PLC plate could still be operated in the AMD 2 system and allowed a smooth switch from the analytical to the preparative gradient separation. Through automated gradient development and the resulting focusing of bands, the sharpness of the PLC bands was improved. For NMR, the necessary high load of the target compound on the PLC plate was achieved via a selective solvent extraction that discriminated the polar sample matrix and thus increased the application volume of the extract that could maximally be applied without overloading. By doing so, the yield for NMR analysis was improved by a factor of 9. The effectivity gain through a simple, but thoroughly chosen extraction solvent is often overlooked, and for educational purpose, it was clearly illustrated and demonstrated by an extended solvent screening. Thus, PLC using an automated gradient development after a selective extraction was proven to be a new powerful combination for structural elucidation by NMR. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of sodium citrate ingestion during recovery after dehydrating exercise on rehydration and subsequent 40-km cycling time-trial performance in the heat.

PubMed

Suvi, Silva; Mooses, Martin; Timpmann, Saima; Medijainen, Luule; Narõškina, Daria; Unt, Eve; Ööpik, Vahur

2018-06-01

The purpose of this study was to assess the impact of sodium citrate (CIT) ingestion (600 mg·kg -1 ) during recovery from dehydrating cycling exercise (DE) on subsequent 40-km cycling performance in a warm environment (32 °C). Twenty male nonheat-acclimated endurance athletes exercised in the heat until 4% body mass (BM) loss occurred. After 16 h recovery with consumption of water ad libitum and prescribed diet (evening meal 20 kcal·kg -1 , breakfast 12 kcal·kg -1 ) supplemented in a double-blind, randomized, crossover manner with CIT or placebo (PLC), they performed 40-km time-trial (TT) on a cycle ergometer in a warm environment. During recovery greater increases in BM and plasma volume (PV) concomitant with greater water intake and retention occurred in the CIT trial compared with the PLC trial (p < 0.0001). During TT there was greater water intake and smaller BM loss in the CIT trial than in the PLC trial (p < 0.05) with no between-trial differences (p > 0.05) in sweat loss, PV decrement, ratings of perceived exertion, or TT time (CIT 68.10 ± 3.28 min, PLC 68.11 ± 2.87 min). At the end of TT blood lactate concentration was higher (7.58 ± 2.44 mmol·L -1 vs 5.58 ± 1.32 mmol·L -1 ; p = 0.0002) and rectal temperature lower (39.54 ± 0.50 °C vs 39.65 ± 0.52 °C; p = 0.033) in the CIT trial than in the PLC trial. Compared with pre-DE time point, PV had decreased to a lower level in the PLC trial than in the CIT trial (p = 0.0001). In conclusion, CIT enhances rehydration after exercise-induced dehydration but has no impact on subsequent 40-km cycling TT performance in a warm uncompensable environment.

Analysis of interleukin (IL)-1 beta and transforming growth factor (TGF)-beta-induced signal transduction pathways in IL-2 and TGF-beta secretion and proliferation in the thymoma cell line EL4.NOB-1.

PubMed

Siese, A; Jaros, P P; Willig, A

1999-02-01

In the present study we investigated the interleukin (IL)-1beta and transforming growth factor-beta1 (TGF-beta1)-mediated proliferation, and production of IL-2 and TGF-beta, in the murine T-cell line, EL4.NOB-1. This cell line is resistant to TGF-beta concerning growth arrest but not autoinduction or suppression of IL-1-induced IL-2 production. When cocultured with IL-1beta, TGF-beta showed growth-promoting activity that could be antagonized by adding the phosphatidyl choline-dependent phospholipase C (PC-PLC) inhibitor, D609. Using specific enzyme inhibitors of protein kinases (PK) C and A, mitogen-activated protein kinase (MAPK), phospholipase A2 (PLA2), phosphatidylinositol-dependent (PI)-PLC and PC-PLC, we showed that IL-1beta-induced IL-2 synthesis was dependent on all investigated kinases and phospholipases, except PC-PLC. TGF-beta1 was able to inhibit IL-2 synthesis by the activation of PKA and MAPK. The same kinases are involved in TGF-beta autoinduction that is accompanied by a secretion of the active but not the latent growth factor and is antagonized by IL-1beta. Addition of the PI-PLC inhibitor, ET 18OCH3, or the PLA2 inhibitor (quinacrine) alone, resulted in secretion of latent TGF-beta and, in the case of ET 18OCH3, active TGF-beta. These data implicate a role for PI-PLC and PLA2 in the control of latency and secretion. Analysis of specific tyrosine activity and c-Fos expression showed synergistic but no antagonistic effects. These events are therefore not involved in IL- and TGF-beta-regulated IL-2 and TGF-beta production, but might participate in IL-1/TGF-beta-induced growth promotion.

5 CFR 370.105 - Written agreements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Written agreements. 370.105 Section 370... TECHNOLOGY EXCHANGE PROGRAM § 370.105 Written agreements. Before the detail begins, the agency and private sector organization must enter into a written agreement with the individual(s) detailed. The written...

5 CFR 370.105 - Written agreements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Written agreements. 370.105 Section 370... TECHNOLOGY EXCHANGE PROGRAM § 370.105 Written agreements. Before the detail begins, the agency and private sector organization must enter into a written agreement with the individual(s) detailed. The written...

Improving Written Expression of Seventh Grade Mildly Intellectually Disabled Students Utilizing a Basal Reading Program, Journal Writing and Computer Applications.

ERIC Educational Resources Information Center

Wimberly, Sabrenai R.

A practicum was designed to increase mildly intellectually disabled students' written communication skills by demonstrating functional written expression skills in daily assignments and in social communication. A sequenced reading and language program with the integration of journal writing and computer applications was utilized. Seventh- and…

Diversity in Libraries: Academic Residency Programs. Contributions in Librarianship and Information Science.

ERIC Educational Resources Information Center

Cogell, Raquel V., Ed.; Gruwell, Cindy A., Ed.

This book contains 15 essays written by 19 librarians who participated in minority residency programs in academic libraries and 5 essays written by 6 professionals who served as residency program administrators. The following essays are included: (1) "The University of California, Santa Barbara Fellowship--A Program in Transition" (Detrice…

Teacher Professional Learning Communities: Going beyond Contrived Collegiality toward Challenging Debate and Collegial Learning and Professional Growth

ERIC Educational Resources Information Center

Owen, Susanne

2014-01-01

Professional learning community (PLC) is a current "buzz" term in business and educational contexts, seemingly referring to anything from decision making committees to regular meeting groups or collegial learning teams. This paper explores the concept of a PLC within three significantly innovative schools, based on an examination of the…

76 FR 59013 - Airworthiness Directives; Rolls-Royce plc (RR) RB211-Trent 800 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration 14 CFR Part 39 [Docket No. FAA-2010-0821; Directorate Identifier 2010-NE-30-AD; Amendment 39-16657; AD 2011-08-07] RIN 2120-AA64 Airworthiness Directives; Rolls-Royce plc (RR) RB211-Trent 800 Series Turbofan Engines AGENCY: Federal Aviation...

76 FR 51056 - In the Matter of Certain Turbomachinery Blades, Engines, and Components Thereof; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-17

.... SUPPLEMENTARY INFORMATION: The Commission instituted this investigation on December 14, 2010, based on a...- Royce Group plc and Rolls-Royce plc, both of the United Kingdom. 75 FR 77904 (Dec. 14, 2010). The... parties moved to terminate the investigation based on a settlement. On July 22, 2011, the Commission...

78 FR 12255 - Airworthiness Directives; Rolls-Royce (1971) Limited, Bristol Engine Division Turbojet Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-22

...: (202) 493-2251. For service information identified in this AD, contact Rolls-Royce plc, Corporate... received by the closing date and may amend this proposed AD based on those comments. We will post all... this AD, contact Rolls-Royce plc, Corporate Communications, P.O. Box 31, Derby, England, DE248BJ; phone...

Exploring Teachers' Process of Change in Incorporating Problem Solving into the Mathematics Classroom

ERIC Educational Resources Information Center

Rutherford, Vanessa

2012-01-01

This study explores how a problem-solving based professional learning community (PLC) affects the beliefs, knowledge, and instructional practices of two sixth-grade mathematics teachers. An interview and two observations were conducted prior to beginning the year-long PLC in order to gather information about the participants' beliefs,…

The Professional Learning Community as Subversive Activity: Countering the Culture of Conventional Schooling

ERIC Educational Resources Information Center

Nehring, James; Fitzsimons, Gray

2011-01-01

As the professional learning community (PLC) as a desired cultural norm gains popularity within K-12 state schools, greater knowledge of the PLC implementation process is warranted. This study reports findings from semi-structured focus group interviews with teachers in an urban/suburban high school after one year of schoolwide professional…

78 FR 70489 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-26

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT..., and 560A2-61 turbofan engines. This AD requires replacement or repair of the low-pressure (LP...-61, 556B2-61, 560-61, and 560A2-61 turbofan engines. (d) Reason This AD was prompted by reports of...

77 FR 58762 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-24

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT...-Trent 892-17, RB211- Trent 892B-17, and RB211-Trent 895-17 turbofan engines. That AD currently requires...-17, RB211-Trent 892B-17, and RB211-Trent 895-17 turbofan engines. (d) Unsafe Condition This AD was...

78 FR 37703 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-24

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... (RR) model RB211 Trent 768-60, 772-60, and 772B-60 turbofan engines. This AD was prompted by low...) model RB211 Trent 768-60, 772-60, and 772B-60 turbofan engines. (d) Reason This AD was prompted by low...

78 FR 22180 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-15

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT... 972B-84, RB211-Trent 977-84, RB211-Trent 977B-84, and RB211-Trent 980-84 turbofan engines. This AD... 977B-84, and RB211-Trent 980-84 turbofan engines that incorporate RR production Modification 72-G585 or...

Collaborativeness as the Core of Professional Learning Communities beyond Culture and Context: Evidence from Canada, Finland, and Israel

ERIC Educational Resources Information Center

Jäppinen, Aini-Kristiina; Leclerc, Martine; Tubin, Dorit

2016-01-01

Professional learning communities (PLC) have been widely accepted as effective with respect to good atmosphere, adequate leadership practices, and functional working practices. However, the outcomes for school improvement depend on case-specific issues. To identify less culturally and contextually bound issues in 3 PLC settings in Canada, Finland,…

A Longitudinal Assessment of an Initial Cohort in a Psychology Learning Community

ERIC Educational Resources Information Center

Buch, Kim; Spaulding, Sue

2008-01-01

Discipline-based learning communities have become a popular strategy for improving student performance and satisfaction. This article describes the goals and features of a university-based, first-year psychology learning community (PLC) implemented in Fall 2003. We also report the results of a longitudinal assessment of the impact of the PLC on…

76 FR 70452 - Granting of Request for Early Termination of the Waiting Period Under the Premerger Notification...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-14

... plc; Cargill, Incorporated; Kerry Group plc. 10/25/2011 20120050 G J.C. Penney Company, Inc.; Liz Claiborne, Inc.; J.C. Penney Company, Inc. 10/26/2011 20120003 G Vista Equity Partners Fund IV, L.P.; The... Image Development, Inc.; Steiner Leisure Limited. 20120064 G Vention Medical, Inc.; Christine Bieber...

77 FR 39564 - Group Lotus Plc, Receipt of Petition for Temporary Exemption From an Advanced Air Bag Requirement...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-03

... went into effect, low volume manufacturers now have access to advanced air bag technology. Accordingly, NHTSA has concluded that the expense of advanced air bag technology is not now sufficient, in and of...-0086] Group Lotus Plc, Receipt of Petition for Temporary Exemption From an Advanced Air Bag Requirement...

76 FR 37808 - PJM Interconnection, L.L.C.; Notice of Discussion Topics for Staff Technical Conference

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-28

... performance measurement of demand response in PJM's capacity market, the Reliability Pricing Model (RPM). \\1...'s April 7, 2011 filing, which proposes to modify the reference point of capacity demand response... less than the customer's Peak Load Contribution (PLC).\\2\\ \\2\\ PJM describes the PLC as the average of...

A view from the bodies corporate. 5. Integrated dental holdings plc. Interview by F. Stuart-Wilson.

PubMed

Hudaly, David

2003-01-11

My interview with David Hudaly, Chief Executive of IDH plc took place at their unassuming head office in Bolton. I make the mistake of assuming, like many, that IDH's operations are based mainly in the North. David Hudaly puts me right fairly early on in our interview. In fact IDH is not one, but two bodies corporate now with 146 practices across the UK, and incorporating the Whitecross and Petrie Tucker chains (although some of the Whitecross units have recently been sold). The business structure appears at first sight to be more complex than the other corporates I have encountered in this series; IDH floated in February 2002 and is now a plc.

Research on public logistics centers of Zhenzhou city based on GIS

NASA Astrophysics Data System (ADS)

Zeng, Yuhuai; Chen, Shuisen; Tian, Zhihui; Miao, Quansheng

2008-10-01

The regional public logistics center (PLC) is the intermedium that transports goods or commodity from producer to wholesaler, retailer and end consumer through whole supply chains. According to the Central Place Theory, the PLC should be multi-centric and of more kinds of graded degrees. From the road network planning discipline, an unique index---Importance Degree, is presented to measure the capacity of a PLC. The Importance Degree selects three township criteria: total population, gross industry product and budget income as weights to calculate the weighted vectors by principle component analysis method. Finally, through the clustering analysis, we can get the graded degrees of PLCs. It proves that that this research method is very effective for the road network planning of Zhengzhou City.

Modeling MAC layer for powerline communications networks

NASA Astrophysics Data System (ADS)

Hrasnica, Halid; Haidine, Abdelfatteh

2001-02-01

The usage of electrical power distribution networks for voice and data transmission, called Powerline Communications, becomes nowadays more and more attractive, particularly in the telecommunication access area. The most important reasons for that are the deregulation of the telecommunication market and a fact that the access networks are still property of former monopolistic companies. In this work, first we analyze a PLC network and system structure as well as a disturbance scenario in powerline networks. After that, we define a logical structure of the powerline MAC layer and propose the reservation MAC protocols for the usage in the PLC network which provides collision free data transmission. This makes possible better network utilization and realization of QoS guarantees which can make PLC networks competitive to other access technologies.

Survey: Computer Usage in Design Courses.

ERIC Educational Resources Information Center

Henley, Ernest J.

1983-01-01

Presents results of a survey of chemical engineering departments regarding computer usage in senior design courses. Results are categorized according to: computer usage (use of process simulators, student-written programs, faculty-written or "canned" programs; costs (hard and soft money); and available software. Programs offered are…

41 CFR 60-1.40 - Affirmative action programs.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 41 Public Contracts and Property Management 1 2011-07-01 2009-07-01 true Affirmative action... written affirmative action program for each of its establishments, if it has 50 or more employees and: (i... each nonconstruction subcontractor to develop and maintain a written affirmative action program for...

41 CFR 60-1.40 - Affirmative action programs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Affirmative action... written affirmative action program for each of its establishments, if it has 50 or more employees and: (i... each nonconstruction subcontractor to develop and maintain a written affirmative action program for...

WenTong HuoXue Cream Can Inhibit the Reduction of the Pain-Related Molecule PLC-β3 in the Dorsal Root Ganglion of a Rat Model of Diabetic Peripheral Neuropathy

PubMed Central

Feng, Chengcheng; Xu, Lijuan; Guo, Shiyun; Chen, Qian; Shen, Yuguo; Zang, Deng

2018-01-01

WenTong HuoXue Cream (WTHX-Cream) has been shown to effectively alleviate clinical symptoms of diabetic peripheral neuropathy (DPN). This study investigated the gene and protein expression of the pain-related molecule PLC-β3 in the dorsal root ganglion (DRG) of DPN rats. 88 specific pathogen-free male Wistar rats were randomly divided into placebo (10 rats) and DPN model (78 rats) groups, and the 78 model rats were used to establish the DPN model by intraperitoneal injection of streptozotocin and were then fed a high-fat diet for 8 weeks. These rats were randomly divided into the model group, the high-, medium-, and low-dose WTHX-Cream + metformin groups, the metformin group, the capsaicin cream group, and the capsaicin cream + metformin group. After 4 weeks of continuous drug administration, the blood glucose, body weight, behavioral indexes, and sciatic nerve conduction velocity were measured. The pathological structure of the DRG and the sciatic nerve were observed. PLC-β3 mRNA and protein levels in the DRG of rats were measured. Compared with the model group, the high-dose WTHX-Cream group showed increased sciatic nerve conduction velocity, improved sciatic nerve morphological changes, and increased expression of PLC-β3 mRNA and protein in the DRG. This study showed that WTHX-Cream improves hyperalgesia symptoms of DPN by inhibiting the reduction of PLC-β3 mRNA and protein expression in the diabetic DRG of DPN rats. PMID:29599806

The role of microtubules in contractile ring function.

PubMed

Conrad, A H; Paulsen, A Q; Conrad, G W

1992-05-01

During cytokinesis, a cortical contractile ring forms around a cell, constricts to a stable tight neck and terminates in separation of the daughter cells. At first cleavage, Ilyanassa obsoleta embryos form two contractile rings simultaneously. The cleavage furrow (CF), in the animal hemisphere between the spindle poles, constricts to a stable tight neck and separates the daughter cells. The third polar lobe constriction (PLC-3), in the vegetal hemisphere below the spindle, constricts to a transient tight neck, but then relaxes, allowing the polar lobe cytoplasm to merge with one daughter cell. Eggs exposed to taxol, a drug that stabilizes microtubules, before the CF or the PLC-3 develop, fail to form CFs, but form stabilized tight PLCs. Eggs exposed to taxol at the time of PLC-3 formation develop varied numbers of constriction rings in their animal hemispheres and one PLC in their vegetal hemisphere, none of which relax. Eggs exposed to taxol after PLC-3 initiation form stabilized tight CFs and PLCs. At maximum constriction, control embryos display immunolocalization of nonextractable alpha-tubulin in their CFs, but not in their PLCs, and reveal, via electron microscopy, many microtubules extending through their CFs, but not through their PLCs. Embryos which form stabilized tightly constricted CFs and PLCs in the presence of taxol display immunolocalization of nonextractable alpha-tubulin in both constrictions and show many polymerized microtubules extending through both CFs and PLCs. These results suggest that the extension of microtubules through a tight contractile ring may be important for stabilizing that constriction and facilitating subsequent cytokinesis.

The role of microtubules in contractile ring function

NASA Technical Reports Server (NTRS)

Conrad, A. H.; Paulsen, A. Q.; Conrad, G. W.; Spooner, B. S. (Principal Investigator)

1992-01-01

During cytokinesis, a cortical contractile ring forms around a cell, constricts to a stable tight neck and terminates in separation of the daughter cells. At first cleavage, Ilyanassa obsoleta embryos form two contractile rings simultaneously. The cleavage furrow (CF), in the animal hemisphere between the spindle poles, constricts to a stable tight neck and separates the daughter cells. The third polar lobe constriction (PLC-3), in the vegetal hemisphere below the spindle, constricts to a transient tight neck, but then relaxes, allowing the polar lobe cytoplasm to merge with one daughter cell. Eggs exposed to taxol, a drug that stabilizes microtubules, before the CF or the PLC-3 develop, fail to form CFs, but form stabilized tight PLCs. Eggs exposed to taxol at the time of PLC-3 formation develop varied numbers of constriction rings in their animal hemispheres and one PLC in their vegetal hemisphere, none of which relax. Eggs exposed to taxol after PLC-3 initiation form stabilized tight CFs and PLCs. At maximum constriction, control embryos display immunolocalization of nonextractable alpha-tubulin in their CFs, but not in their PLCs, and reveal, via electron microscopy, many microtubules extending through their CFs, but not through their PLCs. Embryos which form stabilized tightly constricted CFs and PLCs in the presence of taxol display immunolocalization of nonextractable alpha-tubulin in both constrictions and show many polymerized microtubules extending through both CFs and PLCs. These results suggest that the extension of microtubules through a tight contractile ring may be important for stabilizing that constriction and facilitating subsequent cytokinesis.

WenTong HuoXue Cream Can Inhibit the Reduction of the Pain-Related Molecule PLC-β3 in the Dorsal Root Ganglion of a Rat Model of Diabetic Peripheral Neuropathy.

PubMed

Feng, Chengcheng; Xu, Lijuan; Guo, Shiyun; Chen, Qian; Shen, Yuguo; Zang, Deng; Ma, Li

2018-01-01

WenTong HuoXue Cream (WTHX-Cream) has been shown to effectively alleviate clinical symptoms of diabetic peripheral neuropathy (DPN). This study investigated the gene and protein expression of the pain-related molecule PLC- β 3 in the dorsal root ganglion (DRG) of DPN rats. 88 specific pathogen-free male Wistar rats were randomly divided into placebo (10 rats) and DPN model (78 rats) groups, and the 78 model rats were used to establish the DPN model by intraperitoneal injection of streptozotocin and were then fed a high-fat diet for 8 weeks. These rats were randomly divided into the model group, the high-, medium-, and low-dose WTHX-Cream + metformin groups, the metformin group, the capsaicin cream group, and the capsaicin cream + metformin group. After 4 weeks of continuous drug administration, the blood glucose, body weight, behavioral indexes, and sciatic nerve conduction velocity were measured. The pathological structure of the DRG and the sciatic nerve were observed. PLC- β 3 mRNA and protein levels in the DRG of rats were measured. Compared with the model group, the high-dose WTHX-Cream group showed increased sciatic nerve conduction velocity, improved sciatic nerve morphological changes, and increased expression of PLC- β 3 mRNA and protein in the DRG. This study showed that WTHX-Cream improves hyperalgesia symptoms of DPN by inhibiting the reduction of PLC- β 3 mRNA and protein expression in the diabetic DRG of DPN rats.

The natural product phyllanthusmin C enhances IFN-γ production by human NK cells through upregulation of TLR-mediated NF-κB signaling.

PubMed

Deng, Youcai; Chu, Jianhong; Ren, Yulin; Fan, Zhijin; Ji, Xiaotian; Mundy-Bosse, Bethany; Yuan, Shunzong; Hughes, Tiffany; Zhang, Jianying; Cheema, Baljash; Camardo, Andrew T; Xia, Yong; Wu, Lai-Chu; Wang, Li-Shu; He, Xiaoming; Kinghorn, A Douglas; Li, Xiaohui; Caligiuri, Michael A; Yu, Jianhua

2014-09-15

Natural products are a major source for cancer drug development. NK cells are a critical component of innate immunity with the capacity to destroy cancer cells, cancer-initiating cells, and clear viral infections. However, few reports describe a natural product that stimulates NK cell IFN-γ production and unravel a mechanism of action. In this study, through screening, we found that a natural product, phyllanthusmin C (PL-C), alone enhanced IFN-γ production by human NK cells. PL-C also synergized with IL-12, even at the low cytokine concentration of 0.1 ng/ml, and stimulated IFN-γ production in both human CD56(bright) and CD56(dim) NK cell subsets. Mechanistically, TLR1 and/or TLR6 mediated PL-C's activation of the NF-κB p65 subunit that in turn bound to the proximal promoter of IFNG and subsequently resulted in increased IFN-γ production in NK cells. However, IL-12 and IL-15Rs and their related STAT signaling pathways were not responsible for the enhanced IFN-γ secretion by PL-C. PL-C induced little or no T cell IFN-γ production or NK cell cytotoxicity. Collectively, we identify a natural product with the capacity to selectively enhance human NK cell IFN-γ production. Given the role of IFN-γ in immune surveillance, additional studies to understand the role of this natural product in prevention of cancer or infection in select populations are warranted. Copyright © 2014 by The American Association of Immunologists, Inc.

The Art and Science of Leadership in Learning Environments: Facilitating a Professional Learning Community across Districts

ERIC Educational Resources Information Center

Hands, Catherine; Guzar, Katlyn; Rodrigue, Anne

2015-01-01

A professional learning community (PLC) is one of the most promising strategies for effecting change in educational practices to improve academic achievement and wellbeing for all students. The PLC facilitator's role in developing and leading blended (online and face-to-face) PLCs with members from Ontario's school districts was examined through a…

Dialogical Habitus Engagement: The Twists and Turns of Teachers' Pedagogical Learning within a Professional Learning Community

ERIC Educational Resources Information Center

Fataar, Aslam; Feldman, Jennifer

2016-01-01

The focus of this article is on the pedagogical learning of five teachers in a professional learning community (PLC). The PLC was conceptualised as a means of generating pedagogical learning and change among the participating teachers in consonance with a socially just educational orientation. The two authors of this article participated in the…

The Role of a Professional Learning Community in Teacher Change: A Perspective from Beliefs and Practices

ERIC Educational Resources Information Center

Tam, Angela Choi Fung

2015-01-01

This longitudinal study aimed to examine the role of a professional learning community (PLC) in changing teachers' beliefs and practices. Teachers of a Chinese department in a Hong Kong secondary school were interviewed and observed. The findings indicate that the features of a PLC-facilitating teacher change are development of a coherent…

Teacher Collaboration in Music Education: The Impact of the DuFour Model on Music Teachers' Attitudes and Their Students' Achievement

ERIC Educational Resources Information Center

Armstrong, Cathryn M.

2010-01-01

The DuFour PLC model is one of several reforms today based on the theory that organizing teachers into learning communities will promote professional collaboration and collegial relationships which will improve teacher skills, motivation, and increase student achievement. A small number of studies have explored the impact of PLC's on teaching…

77 FR 20508 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-05

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT...-Trent 884B-17, RB211-Trent 892-17, RB211- Trent 892B-17, and RB211-Trent 895-17 turbofan engines. That...-17, RB211- Trent 892B-17, and RB211-Trent 895-17 turbofan engines. On September 9, 2011, we also...

78 FR 5 - Airworthiness Directives; Rolls-Royce plc Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-02

... Airworthiness Directives; Rolls-Royce plc Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT...-535E4-C-37 turbofan engines. This AD was prompted by an investigation by RR concluding that certain...- 535E4-B-37; RB211-535E4-B-75; and RB211-535E4-C-37 turbofan engines with intermediate-pressure (IP...

Influence of Professional Learning Community (PLC) on Secondary Science Teachers' Culture of Professional Practice: The Case of Bangladesh

ERIC Educational Resources Information Center

Rahman, S. M. Hafizur

2011-01-01

While the current reform efforts in Bangladesh require a substantive change in how science is taught, an equally substantive change is needed in the culture of professional practice. This study will, therefore, investigate how science teachers' learning in a professional learning community (PLC) influences the ways in which participant teachers…

Uncovering the Secrets behind the Successful Integration of GIS into the Core Curriculum

ERIC Educational Resources Information Center

Beeson, P. A.

2006-01-01

Presbyterian Ladies College (PLC) is a 130-year-old independent girls' school in the eastern suburbs of Melbourne. Teaching students from ages 4 to 18, PLC has a reputation for academic excellence. Geography is a separate subject taught as a part of the core curriculum in the secondary school. The College, which uses principally Macintosh…

The Relationship between Professional Learning Communities, Personal Teacher Efficacy, and Student Achievement at the High School Level

ERIC Educational Resources Information Center

Brooks, Sherri L.

2013-01-01

The purpose of this correlational study was to determine if there was a relationship between professional learning community (PLC), personal teacher efficacy (PTE), and student achievement. The study examined teacher perception of PLC implementation and PET as it related to student achievement at the high school level on the Virginia End-of Course…

Identification of the Elusive Mammalian Enzyme Phosphatidylcholine-Specific Phospholipase C

DTIC Science & Technology

2015-09-01

progression of rheumatoid arthritis (RA). Thus, the main scopes of this proposal are: 1. to identify the PC-PLC gene and protein; and 2. to test PC-PLC...Phosphatidycholine-specific phospholipase C, lipopolisaccharide, oxidized lipoproteins, serum, rheumatoid arthritis , transcriptome sequencing, HUVECs...progression of rheumatoid arthritis (RA). The identification of these factors may ultimately provide alternative “druggable” targets for the treatment