The Satellite Test Unit (STU), part of the Passive Aerodynamically Stabilized Magnetically Damped

NASA Technical Reports Server (NTRS)

1996-01-01

STS-77 ESC VIEW --- The Satellite Test Unit (STU), part of the Passive Aerodynamically Stabilized Magnetically Damped Satellite (PAMS) is seen moments after its ejection from the cargo bay of the Space Shuttle Endeavour. The scene was photographed with an Electronic Still Camera (ESC) onboard Endeavour's crew cabin during the deployment. The six-member crew will continue operations (tracking, rendezvousing and station-keeping) with PAMS-STU periodically throughout the remainder of the mission. GMT: 03:29:31.

The Satellite Test Unit (STU), part of the Passive Aerodynamically Stabilized Magnetically Damped

NASA Technical Reports Server (NTRS)

1996-01-01

STS-77 ESC VIEW --- The Satellite Test Unit (STU), part of the Passive Aerodynamically Stabilized Magnetically Damped Satellite (PAMS) is seen moments after its ejection from the cargo bay of the Space Shuttle Endeavour. The scene was photographed with an Electronic Still Camera (ESC) onboard Endeavour's crew cabin during the deployment. The six-member crew will continue operations (tracking, rendezvousing and station-keeping) with PAMS-STU periodically throughout the remainder of the mission. GMT: 03:29:43.

The Satellite Test Unit (STU), part of the Passive Aerodynamically Stabilized Magnetically Damped

NASA Technical Reports Server (NTRS)

1996-01-01

STS-77 ESC VIEW --- The Satellite Test Unit (STU), part of the Passive Aerodynamically Stabilized Magnetically Damped Satellite (PAMS) is seen moments after its ejection from the cargo bay of the Space Shuttle Endeavour. The scene was photographed with an Electronic Still Camera (ESC) onboard Endeavour's crew cabin during the deployment. The six-member crew will continue operations (tracking, rendezvousing and station-keeping) with PAMS-STU periodically throughout the remainder of the mission. GMT: 03:29:29.

STS-92 group photo on Launch Pad 39A

NASA Technical Reports Server (NTRS)

2000-01-01

During Terminal Countdown Demonstration Test (TCDT) activities at Launch Pad 39A, the STS-92 crew poses for a group photo. In the background is Space Shuttle Discovery. Standing, left to right, on the crawlerway ramp are Mission Specialists Koichi Wakata of Japan, Michael Lopez-Alegria, Jeff Wisoff, Bill McArthur and Leroy Chiao; Pilot Pam Melroy; and Commander Brian Duffy. The TCDT provides emergency egress training, simulated countdown exercises and opportunities to inspect the mission payloads in the orbiter's payload bay. STS-92 is scheduled to launch Oct. 5 at 9:30 p.m. EDT on the fifth flight to the International Space Station. It will carry two elements of the Space Station, the Integrated Truss Structure Z1 and the third Pressurized Mating Adapter. The mission is also the 100th flight in the Shuttle program.

STS-92 group photo on Launch Pad 39A

NASA Technical Reports Server (NTRS)

2000-01-01

During Terminal Countdown Demonstration Test (TCDT) activities at Launch Pad 39A, the STS-92 crew poses for a group photo. Standing, left to right, on the crawlerway ramp are Mission Specialists Koichi Wakata of Japan, Michael Lopez-Alegria, Jeff Wisoff, Bill McArthur and Leroy Chiao; Pilot Pam Melroy; and Commander Brian Duffy. The TCDT provides emergency egress training, simulated countdown exercises and opportunities to inspect the mission payloads in the orbiter's payload bay. In the background is Space Shuttle Discovery. STS-92 is scheduled to launch Oct. 5 at 9:30 p.m. EDT on the fifth flight to the International Space Station. It will carry two elements of the Space Station, the Integrated Truss Structure Z1 and the third Pressurized Mating Adapter. The mission is also the 100th flight in the Shuttle program.

STS-92 Mission Specialist Chiao is ready to drive the M-113

NASA Technical Reports Server (NTRS)

2000-01-01

STS-92 Mission Specialist Leroy Chiao gets into the driver's side for his turn to drive the M-113, part of emergency egress training during Terminal Countdown Demonstration Test (TCDT) activities. Behind him are Pilot Pam Melroy (left) and Mission Specialist Michael Lopez-Alegria. The tracked vehicle could be used by the crew in the event of an emergency at the pad during which the crew must make a quick exit from the area. The TCDT also provides simulated countdown exercises and opportunities to inspect the mission payloads in the orbiter's payload bay. STS-92 is scheduled to launch Oct. 5 at 9:30 p.m. EDT on the fifth flight to the International Space Station. It will carry two elements of the Space Station, the Integrated Truss Structure Z1 and the third Pressurized Mating Adapter. The mission is also the 100th flight in the Shuttle program.

The Impact of an Incentive on the Use of an Online Self-Directed Wellness and Self-Management Program

PubMed Central

Greene, Jessica

2014-01-01

Background Those who pay for health care are increasingly looking for strategies to influence individuals to take a more active role in managing their health. Incenting health plan members and/or employees to participate in wellness programs is a widely used approach. Objective In this study, we examine financial incentives to health plan members to participate in an online self-management/wellness program—US $20 for completing the patient activation measure (PAM) and an additional US $40 for completing 8 learning modules. We examined whether the characteristics of plan members differed by the degree to which they responded to the incentives. Further, we examined whether participation in the wellness program was associated with improvements in PAM scores and changes in health care utilization. Methods This retrospective study compared demographic characteristics and change in PAM scores and health utilization for 144,625 health plan members in 2011. Four groups were compared: (1) those who were offered the incentives but chose not to participate (n=128,634), (2) those who received the initial incentive (PAM only) but did not complete 8 topics (n=7099), (3) those who received both incentives (completing 8 topics but no more) (n=2693), and (4) those who received both incentives and continued using the online program beyond what was required by the incentives (n=6249). Results The vast majority of health plan members did not participate in the program (88.91%, 128,634/144,675). Of those who participated, only 7099 of 16,041 (44.25%) completed the PAM for the first incentive, 2693 (16.79%) completed 8 topics for the second incentive, and 6249 (38.96%) received both incentives and continued using the program beyond the incentive requirements. Nonparticipants were more likely to be men and to have lower health risk scores on average than the other three groups of participants (P<.001). In multivariate regression models, those who used the online program (8 topics or beyond) increased their PAM score by approximately 1 point more than those who only took the PAM and did not use the wellness program (P<.03). In addition, emergency department visits were lower for all groups who responded to any level of the incentive as compared to those who did not (P<.01). No differences were found in other types of utilization. Conclusions The incentive was not sufficient to spark most health plan members to use the wellness program. However, the fact that many program participants went beyond the incentive in their use of the online wellness program suggests that the users of the online program found value in using it, and it was their own internal motivation that stimulated this additional use. Providing an incentive for program participation may be an effective pathway for working with less activated patients, particularly if the program is tailored to the needs of the less activated. PMID:25280348

Assessing Patient Activation among High-Need, High-Cost Patients in Urban Safety Net Care Settings.

PubMed

Napoles, Tessa M; Burke, Nancy J; Shim, Janet K; Davis, Elizabeth; Moskowitz, David; Yen, Irene H

2017-12-01

We sought to examine the literature using the Patient Activation Measure (PAM) or the Patient Enablement Instrument (PEI) with high-need, high-cost (HNHC) patients receiving care in urban safety net settings. Urban safety net care management programs serve low-income, racially/ethnically diverse patients living with multiple chronic conditions. Although many care management programs track patient progress with the PAM or the PEI, it is not clear whether the PAM or the PEI is an effective and appropriate tool for HNHC patients receiving care in urban safety net settings in the United States. We searched PubMed, EMBASE, Web of Science, and PsycINFO for articles published between 2004 and 2015 that used the PAM and between 1998 and 2015 that used the PEI. The search was limited to English-language articles conducted in the United States and published in peer-reviewed journals. To assess the utility of the PAM and the PEI in urban safety net care settings, we defined a HNHC patient sample as racially/ethnically diverse, low socioeconomic status (SES), and multimorbid. One hundred fourteen articles used the PAM. All articles using the PEI were conducted outside the U.S. and therefore were excluded. Nine PAM studies (8%) included participants similar to those receiving care in urban safety net settings, three of which were longitudinal. Two of the three longitudinal studies reported positive changes following interventions. Our results indicate that research on patient activation is not commonly conducted on racially and ethnically diverse, low SES, and multimorbid patients; therefore, there are few opportunities to assess the appropriateness of the PAM in such populations. Investigators expressed concerns with the potential unreliability and inappropriate nature of the PAM on multimorbid, older, and low-literacy patients. Thus, the PAM may not be able to accurately assess patient progress among HNHC patients receiving care in urban safety net settings. Assessing progress in the urban safety net care setting requires measures that account for the social and structural challenges and competing demands of HNHC patients.

Military Review: Desert Shield/Desert Storm

DTIC Science & Technology

1991-04-01

aid station Equipment and Doctrine (BAS) provides initial medical care. This is a Physical size and personnel presence, both pa- small "tailgate...Staff Collge , Fort Jona ha Cape. 1962), 315. Leavenworti, Kansas, 16 May 1986. 6 Carver. 122 Lieutenant Colonel Thomas V. MorLey is G3 (operatios and pam

STS-120 crew on Discovery middeck

NASA Image and Video Library

2007-10-31

S120-E-007889 (1 Nov. 2007) --- Astronauts Pam Melroy (left), STS-120 commander; George Zamka (bottom right), pilot; and European Space Agency's (ESA) Paolo Nespoli, mission specialist, sleep in their sleeping bags, which are secured on the middeck of the Space Shuttle Discovery while docked with the International Space Station.

Fully Automated Data Collection Using PAM and the Development of PAM/SPACE Reversible Cassettes

NASA Astrophysics Data System (ADS)

Hiraki, Masahiko; Watanabe, Shokei; Chavas, Leonard M. G.; Yamada, Yusuke; Matsugaki, Naohiro; Igarashi, Noriyuki; Wakatsuki, Soichi; Fujihashi, Masahiro; Miki, Kunio; Baba, Seiki; Ueno, Go; Yamamoto, Masaki; Suzuki, Mamoru; Nakagawa, Atsushi; Watanabe, Nobuhisa; Tanaka, Isao

2010-06-01

To remotely control and automatically collect data in high-throughput X-ray data collection experiments, the Structural Biology Research Center at the Photon Factory (PF) developed and installed sample exchange robots PAM (PF Automated Mounting system) at PF macromolecular crystallography beamlines; BL-5A, BL-17A, AR-NW12A and AR-NE3A. We developed and installed software that manages the flow of the automated X-ray experiments; sample exchanges, loop-centering and X-ray diffraction data collection. The fully automated data collection function has been available since February 2009. To identify sample cassettes, PAM employs a two-dimensional bar code reader. New beamlines, BL-1A at the Photon Factory and BL32XU at SPring-8, are currently under construction as part of Targeted Proteins Research Program (TPRP) by the Ministry of Education, Culture, Sports, Science and Technology of Japan. However, different robots, PAM and SPACE (SPring-8 Precise Automatic Cryo-sample Exchanger), will be installed at BL-1A and BL32XU, respectively. For the convenience of the users of both facilities, pins and cassettes for PAM and SPACE are developed as part of the TPRP.

The Link: Connecting Juvenile Justice and Child Welfare. Volume 3, Number 2, Spring 2004

ERIC Educational Resources Information Center

Blassingame, Kelley M., Ed.

2004-01-01

This issue of "The Link" includes the following articles: (1) "Oregon Crafts Guidelines for Effective Girls Programming - By Pam Patton and Marcia Morgan" (Pam Patton and Marcia Morgan); (2) "Linking Child Placement and Juvenile Delinquency: Research Examines the Role of Placement in Increased Delinquency Rates"; and (3) "Unlocking the Future:…

2007 Precision Strike Annual Programs Review

DTIC Science & Technology

2007-04-25

Adapting our methods • Remaining a flexible combined-arms force • Enabling a generation of combat- experienced decision-makers by distributing...Sustain Propulsion Network RadioMEMS IMU Flexible Engagement Options Requirements Capabilities Precision Attack Missile (PAM) 67” (with Canister...Aimpoint 6 PAM Seeker Modes PAM’s Multiple Targeting Modes Increase Flexibility , Improve Lethality PAM’s Multiple Targeting Modes Increase Flexibility

RECEPTOR MODEL COMPARISONS AND WIND DIRECTION ANALYSES OF VOLATILE ORGANIC COMPOUNDS AND SUBMICROMETER PARTICLES IN AN ARID, BINATIONAL, URBAN AIRSHED

EPA Science Inventory

The relationship between continuous measurements of volatile organic compounds sources and particle number was evaluated at a Photochemical Assessment Monitoring Station Network (PAMS) site located near the U.S.-Mexico Border in central El Paso, TX. Sources of volatile organic...

Autonomous NanoTechnology Swarm (ANTS) Prospecting Asteroid Mission (PAM), Asteroid Proximity Operations

NASA Technical Reports Server (NTRS)

Marr, Greg; Cooley, Steve; Roithmayr, Carlos; Kay-Bunnell, Linda; Williams, Trevor

2004-01-01

The Autonomous NanoTechnology Swarm (ANTS) is a generic mission architecture based on spatially distributed spacecraft, autonomous and redundant components, and hierarchical organization. The ANTS Prospecting Asteroid Mission (PAM) is an ANTS application which will nominally use a swarm of 1000 spacecraft. There would be 10 types of "specialists" with common spacecraft buses. There would be 10 subswarms of approximately 100 spacecraft each or approximately 10 of each specialist in each swarm. The ANTS PAM primary objective is the exploration of the asteroid belt in search of resources and material with astrobiologically relevant origins and signatures. The ANTS PAM spacecraft will nominally be released from a station in an Earth-Moon L1 libration point orbit, and they will use Solar sails for propulsion. The sail structure would be highly flexible, capable of changing morphology to change cross-section for capture of sunlight or to form effective "tip vanes" for attitude control. ANTS PAM sails would be capable of full to partial deployment, to change effective sail area and center of pressure, and thus allow attitude control. Results of analysis of a transfer trajectory from Earth to a sample target asteroid will be presented. ANTS PAM will require continuous coverage of different asteroid locations as close as one to two asteroid "diameters" from the surface of the asteroid for periods of science data collection during asteroid proximity operations. Hovering spacecraft could meet the science data collection objectives. The results of hovering analysis will be presented. There are locations for which hovering is not possible, for example on the illuminated side of the asteroid. For cases where hovering is not possible, the results of utilizing asteroid formations to orbit the asteroid and achieve the desired asteroid viewing will be presented for sample asteroids. The ability of ANTS PAM to reduce the area of the solar sail during asteroid proximity operations is critical to the maintenance of orbiting formations for a period of time. Results of analysis of potential "traffic" problems during asteroid proximity operations will be presented.

Dynamic contraction behaviour of pneumatic artificial muscle

NASA Astrophysics Data System (ADS)

Doumit, Marc D.; Pardoel, Scott

2017-07-01

The development of a dynamic model for the Pneumatic Artificial Muscle (PAM) is an imperative undertaking for understanding and analyzing the behaviour of the PAM as a function of time. This paper proposes a Newtonian based dynamic PAM model that includes the modeling of the muscle geometry, force, inertia, fluid dynamic, static and dynamic friction, heat transfer and valve flow while ignoring the effect of bladder elasticity. This modeling contribution allows the designer to predict, analyze and optimize PAM performance prior to its development. Thus advancing successful implementations of PAM based powered exoskeletons and medical systems. To date, most muscle dynamic properties are determined experimentally, furthermore, no analytical models that can accurately predict the muscle's dynamic behaviour are found in the literature. Most developed analytical models adequately predict the muscle force in static cases but neglect the behaviour of the system in the transient response. This could be attributed to the highly challenging task of deriving such a dynamic model given the number of system elements that need to be identified and the system's highly non-linear properties. The proposed dynamic model in this paper is successfully simulated through MATLAB programing and validated the pressure, contraction distance and muscle temperature with experimental testing that is conducted with in-house built prototype PAM's.

Mechanism of duplex DNA destabilization by RNA-guided Cas9 nuclease during target interrogation

PubMed Central

Mekler, Vladimir; Minakhin, Leonid; Severinov, Konstantin

2017-01-01

The prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (Cas9) endonuclease cleaves double-stranded DNA sequences specified by guide RNA molecules and flanked by a protospacer adjacent motif (PAM) and is widely used for genome editing in various organisms. The RNA-programmed Cas9 locates the target site by scanning genomic DNA. We sought to elucidate the mechanism of initial DNA interrogation steps that precede the pairing of target DNA with guide RNA. Using fluorometric and biochemical assays, we studied Cas9/guide RNA complexes with model DNA substrates that mimicked early intermediates on the pathway to the final Cas9/guide RNA–DNA complex. The results show that Cas9/guide RNA binding to PAM favors separation of a few PAM-proximal protospacer base pairs allowing initial target interrogation by guide RNA. The duplex destabilization is mediated, in part, by Cas9/guide RNA affinity for unpaired segments of nontarget strand DNA close to PAM. Furthermore, our data indicate that the entry of double-stranded DNA beyond a short threshold distance from PAM into the Cas9/single-guide RNA (sgRNA) interior is hindered. We suggest that the interactions unfavorable for duplex DNA binding promote DNA bending in the PAM-proximal region during early steps of Cas9/guide RNA–DNA complex formation, thus additionally destabilizing the protospacer duplex. The mechanism that emerges from our analysis explains how the Cas9/sgRNA complex is able to locate the correct target sequence efficiently while interrogating numerous nontarget sequences associated with correct PAMs. PMID:28484024

Mechanism of duplex DNA destabilization by RNA-guided Cas9 nuclease during target interrogation.

PubMed

Mekler, Vladimir; Minakhin, Leonid; Severinov, Konstantin

2017-05-23

The prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (Cas9) endonuclease cleaves double-stranded DNA sequences specified by guide RNA molecules and flanked by a protospacer adjacent motif (PAM) and is widely used for genome editing in various organisms. The RNA-programmed Cas9 locates the target site by scanning genomic DNA. We sought to elucidate the mechanism of initial DNA interrogation steps that precede the pairing of target DNA with guide RNA. Using fluorometric and biochemical assays, we studied Cas9/guide RNA complexes with model DNA substrates that mimicked early intermediates on the pathway to the final Cas9/guide RNA-DNA complex. The results show that Cas9/guide RNA binding to PAM favors separation of a few PAM-proximal protospacer base pairs allowing initial target interrogation by guide RNA. The duplex destabilization is mediated, in part, by Cas9/guide RNA affinity for unpaired segments of nontarget strand DNA close to PAM. Furthermore, our data indicate that the entry of double-stranded DNA beyond a short threshold distance from PAM into the Cas9/single-guide RNA (sgRNA) interior is hindered. We suggest that the interactions unfavorable for duplex DNA binding promote DNA bending in the PAM-proximal region during early steps of Cas9/guide RNA-DNA complex formation, thus additionally destabilizing the protospacer duplex. The mechanism that emerges from our analysis explains how the Cas9/sgRNA complex is able to locate the correct target sequence efficiently while interrogating numerous nontarget sequences associated with correct PAMs.

User Instructions for the Policy Analysis Modeling System (PAMS)

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

McNeil, Michael A.; Letschert, Virginie E.; Van Buskirk, Robert D.

PAMS uses country-specific and product-specific data to calculate estimates of impacts of a Minimum Efficiency Performance Standard (MEPS) program. The analysis tool is self-contained in a Microsoft Excel spreadsheet, and requires no links to external data, or special code additions to run. The analysis can be customized to a particular program without additional user input, through the use of the pull-down menus located on the Summary page. In addition, the spreadsheet contains many areas into which user-generated input data can be entered for increased accuracy of projection. The following is a step-by-step guide for using and customizing the tool.

Harnessing biosynthesis and quantitative NMR for late stage functionalization of lead molecules: Application to the M1 positive allosteric modulator (PAM) program.

PubMed

Brodney, Michael A; Sharma, Raman; Lazzaro, John T; Walker, Gregory S; Scott Obach, R

2018-06-15

A facile method for late stage diversification of lead molecules for the M1 PAM program using biosynthesis is described. Liver microsomes from several species are screened to identify a high turnover system. Subsequent incubations using less than 1 mg of substrate generate nanomole quantities of drug metabolites that are purified, characterized by microcryoprobe NMR spectroscopy, and quantified to known concentrations to enable rapid biology testing. The late-stage diversification of lead compounds provides rapid SAR feedback to the medicinal chemistry design cycle. Copyright © 2018 Elsevier Ltd. All rights reserved.

STS-120 and Expedition 16 Commanders in Node 1/Unity module

NASA Image and Video Library

2007-11-04

S120-E-008350 (4 Nov. 2007) --- Astronauts Pam Melroy (foreground), STS-120 commander; and Peggy Whitson, Expedition 16 commander, add the STS-120 crew patch in the Unity node to the growing collection of those representing shuttle crews who have worked on the International Space Station. A location in the Unity node serves as one of the traditional posting sites for the patches.

STS-92 Pilot Pam Melroy suits up for launch

NASA Technical Reports Server (NTRS)

2000-01-01

In the Operations and Checkout Building, STS-92 Pilot Pamela Ann Melroy smiles during suit check before heading out to the Astrovan for the ride to Launch Pad 39A. During the 11-day mission to the International Space Station, four extravehicular activities (EVAs), or spacewalks, are planned for construction. The payload includes the Integrated Truss Structure Z-1 and the third Pressurized Mating Adapter. The Z-1 truss is the first of 10 that will become the backbone of the Space Station, eventually stretching the length of a football field. PMA-3 will provide a Shuttle docking port for solar array installation on the sixth Station flight and Lab installation on the seventh Station flight. Launch is scheduled for 7:17 p.m. EDT. Landing is expected Oct. 22 at 2:10 p.m. EDT.

Terrorism as a Perceived Threat to US Armed Forces Serving OCONUS and the Army’s Program of Addressing That Threat.

DTIC Science & Technology

1986-03-27

many terrorist groups with plastique and other explosives to build bombs. 6 Using these explosives they have produced vehicle bombs which are totally...US Army War College Study, 19 April 1982. 3. TRADOC Pam 525-37, Military Operations, US Army Operational Concept For Terrorism Counteraction, 19...Army (U). Counterintelligence Special Report. (Overall Report (S)), 1981. 30. US Army. TRADOC Pam 525-37. "Military Operations." US Army Concept For

SpaceX CRS-10 Post Launch News Conference

NASA Image and Video Library

2017-02-19

In the Press Site auditorium of NASA's Kennedy Space Center in Florida, NASA and industry leaders speak to media at a post-launch news conference following the liftoff of SpaceX CRS-10, a commercial resupply services mission to the International Space Station. From left are: William Spetch, deputy manager of the International Space Station Transportation Office; Jessica Jensen, Dragon mission manager for SpaceX; and Pam Underwood, manager of the Operations Integration Division of the Federal Aviation Administration Office of Commercial Space Transportation. SpaceX CRS-10 lifted off atop a Falcon 9 rocket from Kennedy's Launch Complex 39A at 9:39 a.m. EST.

SpaceX CRS-10 Post Launch News Conference

NASA Image and Video Library

2017-02-19

In the Press Site auditorium of NASA's Kennedy Space Center in Florida, NASA and industry leaders speak to media at a post-launch news conference following the liftoff of SpaceX CRS-10, a commercial resupply services mission to the International Space Station. From left are: George Diller, NASA Communications; William Spetch, deputy manager of the International Space Station Transportation Office; Jessica Jensen, Dragon mission manager for SpaceX; and Pam Underwood, manager of the Operations Integration Division of the Federal Aviation Administration Office of Commercial Space Transportation. SpaceX CRS-10 lifted off atop a Falcon 9 rocket from Kennedy's Launch Complex 39A at 9:39 a.m. EST.

SpaceX CRS-10 Post Launch Press Conference

NASA Image and Video Library

2017-02-19

In the Press Site auditorium of NASA's Kennedy Space Center in Florida, NASA and industry leaders speak to media at a post-launch news conference following the liftoff of SpaceX CRS-10, a commercial resupply services mission to the International Space Station. From left are: George Diller, NASA Communications; William Spetch, deputy manager of the International Space Station Transportation Office; Jessica Jensen, Dragon mission manager for SpaceX; and Pam Underwood, manager of the Operations Integration Division of the Federal Aviation Administration Office of Commercial Space Transportation. SpaceX CRS-10 lifted off atop a Falcon 9 rocket from Kennedy's Launch Complex 39A at 9:39 a.m. EST.

STS-92 crew get training on driving the M-113 armored vehicle

NASA Technical Reports Server (NTRS)

2000-01-01

As part of emergency egress training during Terminal Countdown Demonstration Test (TCDT) activities, members of the STS-92 crew get instructions about the M-113 they are seated in at Launch Pad 39A. Seen on the left are Pilot Pam Melroy and Mission Specialists Leroy Chaio and Koichi Wakata of Japan In the middle, giving the instructions, is Capt. George Hoggard, trainer with the KSC Fire Department. At right are Commander Brian Duffy (leaning back) and Mission Specialist Michael Lopez-Alegria. The other crew members (not seen) are Mission Specialists Jeff Wisoff and Bill McArthur. The tracked vehicle could be used by the crew in the event of an emergency at the pad during which the crew must make a quick exit from the area. The TCDT also provides simulated countdown exercises and opportunities to inspect the mission payloads in the orbiter's payload bay. STS-92 is scheduled to launch Oct. 5 at 9:30 p.m. EDT on the fifth flight to the International Space Station. It will carry two elements of the Space Station, the Integrated Truss Structure Z1 and the third Pressurized Mating Adapter. The mission is also the 100th flight in the Shuttle program.

KSC-07pd0641

NASA Image and Video Library

2007-03-15

KENNEDY SPACE CENTER, FLA. -- In the Space Station Processing Facility, Mission STS-120 Pilot George Zamka (left) and Commander Pam Melroy stand in front of the Node 2 module with it's new name, Harmony, unveiled. The name, Harmony, was chosen from an academic competition involving thousands of students in kindergarten through high school. The Node 2 Challenge required students to learn about the International Space Station, build a scale model of the module, and write an essay explaining their proposed name. This will be the first U.S. piece of the space station named by someone other than a NASA official. Node 2 is a pressurized module that will act as a connecting port and passageway to additional international science labs and supply spacecraft. It also will be a work platform for the station's robotic arm. The module is scheduled to fly on mission STS-120 aboard Space Shuttle Atlantis targeted for later this year. Photo credit: NASA/Jim Grossmann

KSC-07pd0640

NASA Image and Video Library

2007-03-15

KENNEDY SPACE CENTER, FLA. -- In the Space Station Processing Facility, Mission STS-120 Commander Pam Melroy speaks to members of the press and guests during a ceremony to unveil the new name of NASA's Node 2 module, Harmony. The name, Harmony, was chosen from an academic competition involving thousands of students in kindergarten through high school. The Node 2 Challenge required students to learn about the International Space Station, build a scale model of the module, and write an essay explaining their proposed name. This will be the first U.S. piece of the space station named by someone other than a NASA official. Node 2 is a pressurized module that will act as a connecting port and passageway to additional international science labs and supply spacecraft. It also will be a work platform for the station's robotic arm. The module is scheduled to fly on mission STS-120 aboard Space Shuttle Atlantis targeted for later this year. Photo credit: NASA/Jim Grossmann

Controlling tailwater sediment and phosphorus concentrations with polyacrylamide in the Imperial Valley, California.

PubMed

Goodson, Christopher C; Schwartz, Gregory; Amrhein, Christopher

2006-01-01

External loading of phosphorus (P) from agricultural surface discharge (tailwater) is the main cause of excessive algae growth and the eutrophication of the Salton Sea, California. Continuous polyacrylamide (PAM) applications to agricultural irrigation water inflows were evaluated as a means of reducing sediment and P in tailwater. Zero (control) and 1 mg L(-1) PAM (PAM1) treatments were compared at 17 Imperial Valley field sites. Five and 10 mg L(-1) PAM treatments (PAM5, PAM10) were conducted at one site. The particulate phosphorus (Pp) fraction was determined as the difference between total phosphorus (Pt) and the soluble phosphorus (Ps) fraction. We observed 73, 82, and 98% turbidity reduction with PAM1, PAM5, and PAM10 treatments. Although eight field sites had control tailwater sediment concentrations above the New River total maximum daily loads (TMDL), all but one were made compliant during their paired PAM1 treatments. While PAM1 and PAM10 reduced tail water Pp by 31 and 78%, none of the treatments tested reduced Ps. This may have been caused by high irrigation water Na concentrations which would reduce Ca adsorption and Ca-phosphate bridging on the PAM. The PAM1 treatments resulted in <0.5 mg L(-1) drain water polyacrylamide concentrations 1.6 km downstream of PAM addition, while PAM5 and PAM10 treatments produced > 2 mg L(-1) drain water polyacrylamide concentrations. We concluded that, although PAM practically eliminates Imperial Valley tailwater sediment loads, it does not effectively reduce tailwater Ps, the P fraction most responsible for the eutrophication of the Salton Sea.

KSC-07pd0637

NASA Image and Video Library

2007-03-15

KENNEDY SPACE CENTER, FLA. -- In the Space Station Processing Facility, Mission STS-120 Pilot George Zamka (left) and Commander Pam Melroy begin to unveil the Node 2 module's new name, Harmony, as Russ Romanella, director of International Space Station and Spacecraft Processing presides over the ceremony. The name, Harmony, was chosen from an academic competition involving thousands of students in kindergarten through high school. The Node 2 Challenge required students to learn about the International Space Station, build a scale model of the module, and write an essay explaining their proposed name. This will be the first U.S. piece of the space station named by someone other than a NASA official. Node 2 is a pressurized module that will act as a connecting port and passageway to additional international science labs and supply spacecraft. It also will be a work platform for the station's robotic arm. The module is scheduled to fly on mission STS-120 aboard Space Shuttle Atlantis targeted for later this year. Photo credit: NASA/Jim Grossmann

PRIMARY ACQUIRED MELANOSIS OF THE CONJUNCTIVA: EXPERIENCE WITH 311 EYES

PubMed Central

Shields, Jerry A.; Shields, Carol L.; Mashayekhi, Arman; Marr, Brian P.; Benavides, Raquel; Thangappan, Archana; Phan, Laura; Eagle, Ralph C.

2007-01-01

Purpose To evaluate clinical features and risks for transformation of conjunctival primary acquired melanosis (PAM) into melanoma. Methods Retrospective chart review and Kaplan-Meier estimates of times to PAM enlargement, recurrence, and transformation into melanoma. Main outcome measures: PAM enlargement, recurrence, and transformation into melanoma. Results The mean patient age at diagnosis of PAM was 56 years; 62% were female and 96% Caucasian. The conjunctival quadrant(s) affected by PAM and its extent in clock hours were recorded. Initial management included observation in 62%, biopsy combined with cryotherapy in 34%, and other methods in 4%. Of PAM that was observed, Kaplan-Meier estimates at 10 years revealed PAM enlargement in 35% and transformation into melanoma in 12%. Of those that underwent incisional or excisional biopsy, 10-year estimates of PAM recurrence and transformation into melanoma were 58% and 11%, respectively. Progression to melanoma occurred in 0% of PAM without atypia, 0% of PAM with mild atypia, and 13% of PAM with severe atypia. Multivariable analysis revealed that the most significant factor for both PAM recurrence and progression to melanoma was extent of PAM in clock hours. Conclusion PAM without atypia or with mild atypia shows 0% progression into melanoma, whereas PAM with severe atypia shows progression into melanoma in 13%. The greater the extent of PAM in clock hours, the greater the risk for transformation into melanoma. PMID:18427595

Augmenting the spectral efficiency of enhanced PAM-DMT-based optical wireless communications.

PubMed

Islim, Mohamed Sufyan; Haas, Harald

2016-05-30

The energy efficiency of pulse-amplitude-modulated discrete multitone modulation (PAM-DMT) decreases as the modulation order of M-PAM modulation increases. Enhanced PAM-DMT (ePAM-DMT) was proposed as a solution to the reduced energy efficiency of PAM-DMT. This was achieved by allowing multiple streams of PAM-DMT to be superimposed and successively demodulated at the receiver side. In order to maintain a distortion-free unipolar ePAM-DMT system, the multiple time-domain PAM-DMT streams are required to be aligned. However, aligning the antisymmetry in ePAM-DMT is complex and results in efficiency losses. In this paper, a novel simplified method to apply the superposition modulation on M-PAM modulated discrete multitone (DMT) is introduced. Contrary to ePAM-DMT, the signal generation of the proposed system, termed augmented spectral efficiency discrete multitone (ASE-DMT), occurs in the frequency domain. This results in an improved spectral and energy efficiency. The analytical bit error rate (BER) performance bound of the proposed system is derived and compared with Monte-Carlo simulations. The system performance is shown to offer significant electrical and optical energy savings compared with ePAM-DMT and DC-biased optical orthogonal frequency division multiplexing (DCO-OFDM).

STS-120 Launch

NASA Technical Reports Server (NTRS)

2007-01-01

The Space Shuttle Discovery and its seven-member STS-120 crew headed toward Earth-orbit and a scheduled linkup with the International Space Station (ISS). Liftoff from Kennedy Space Center's launch pad 39A occurred at 11:38:19 a.m. (EDT) on October 23, 2007. Onboard were astronauts Pam Melroy, commander; George Zamka, pilot; Scott Parazynski, Stephanie Wilson, Doug Wheelock, European Space Agency's (ESA) Paolo Nespoli and Daniel Tani, all mission specialists. Discovery linked up with the station for a joint mission of continued construction. The mission delivered the Italian-built U.S. Node 2, named Harmony. During the 14-day mission, the crew installed Harmony, moved and deployed the P6 solar arrays to their permanent position.

STS-120 Launch

NASA Technical Reports Server (NTRS)

2007-01-01

The Space Shuttle Discovery and its seven-member STS-120 crew headed toward Earth-orbit and a scheduled linkup with the International Space Station (ISS). Liftoff from Kennedy Space Center's launch pad 39A occurred at 11:38:19 a.m. (EDT) on October 23, 2007. Onboard were astronauts Pam Melroy, commander; George Zamka, pilot; Scott Parazynski, Stephanie Wilson, Doug Wheelock, European Space Agency's (ESA) Paolo Nespoli, and Daniel Tani, all mission specialists. Discovery linked up with the station for a joint mission of continued construction. The mission delivered the Italian-built U.S. Node 2, named Harmony. During the 14-day mission, the crew installed Harmony, and moved and deployed the P6 solar arrays to their permanent position.

STS-120 Launch

NASA Technical Reports Server (NTRS)

2007-01-01

The Space Shuttle Discovery and its seven-member STS-120 crew headed toward Earth-orbit and a scheduled linkup with the International Space Station (ISS). Liftoff from Kennedy Space Center's launch pad 39A occurred at 11:38:19 a.m. (EDT) on October 23, 2007. Onboard were astronauts Pam Melroy, commander; George Zamka, pilot; Scott Parazynski, Stephanie Wilson, Doug Wheelock, European Space Agency's (ESA) Paolo Nespoli and Daniel Tani, all mission specialists. Discovery linked up with the station for a joint mission of continued construction, The mission delivered the Italian-built U.S. Node 2, named Harmony. During the 14-day mission, the crew installed Harmony, and moved and deployed the P6 solar arrays to their permanent position.

48 CFR 1401.603-2 - Selection.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Acquisition Certification in Contracting (FAC-C) Program Manual. Director, PAM, is the approving authority for all new and reinstated FAC-C certifications. BPCs are authorized to approve renewal FAC-C...

48 CFR 1401.603-2 - Selection.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Acquisition Certification in Contracting (FAC-C) Program Manual. Director, PAM, is the approving authority for all new and reinstated FAC-C certifications. BPCs are authorized to approve renewal FAC-C...

48 CFR 1401.603-2 - Selection.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Acquisition Certification in Contracting (FAC-C) Program Manual. Director, PAM, is the approving authority for all new and reinstated FAC-C certifications. BPCs are authorized to approve renewal FAC-C...

48 CFR 1401.603-2 - Selection.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Acquisition Certification in Contracting (FAC-C) Program Manual. Director, PAM, is the approving authority for all new and reinstated FAC-C certifications. BPCs are authorized to approve renewal FAC-C...

Novel glycolipid TLR2 ligands of the type Pam2Cys-α-Gal: synthesis and biological properties.

PubMed

Thomann, Jean-Sébastien; Monneaux, Fanny; Creusat, Gaëlle; Spanedda, Maria Vittoria; Heurtault, Béatrice; Habermacher, Chloé; Schuber, Francis; Bourel-Bonnet, Line; Frisch, Benoît

2012-05-01

A more complete understanding of the mechanism of action of TLR agonists has fueled the investigation of new synthetic immunoadjuvants. In this context, we designed and synthesized glycolipids of the type Pam(2)Cys-α-Galactose as novel immunoadjuvants. Their synthesis required modifying a hydrophobic tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety, i.e. the minimal structure required for TLR2 agonist activity, by addition of a hydrophilic head, either an α-Galactosylpyranose or an α-Galactosylfuranose to gain respectively Pam(2)CGalp and Pam(2)CGalf. While preparing a carbohydrate building block, an unexpected stereoselectivity was observed during a halide ion-catalytic process on a protected galactofuranose: the alpha anomer was obtained with surprisingly high selectivity (α/β ratio>9) and with good isolated yield (51%). The TLR2 binding properties of Pam(2)CGalp and Pam(2)CGalf were then fully evaluated. Their efficiency in triggering the proliferation of BALB/c mouse splenocytes was also compared to that of Pam(2)CAG and Pam(3)CAG, two well-established ligands of TLRs. Moreover, the maturation state of murine dendritic cells previously incubated with either Pam(2)CGalp or Pam(2)CGalf was monitored by flow cytometry and compared to that induced by lipopolysaccharide. Pam(2)CGalp and Pam(2)CGalf were found to be equivalent TLR2 agonists, and induced splenocyte proliferation and DC maturation. With very similar activity, Pam(2)CGalp and Pam(2)CGalf were also 10-fold to 100-fold better than Pam(2)CAG and Pam(3)CAG at inducing B cell proliferation. This represents the first time a glucidic head has been added to the tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety whilst maintaining the immunomodulating activity. This should greatly enrich the data available on Pam(2)C structure/activity relationships. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

A gene delivery system containing nuclear localization signal: Increased nucleus import and transfection efficiency with the assistance of RanGAP1.

PubMed

Chen, Kang; Guo, Lingling; Zhang, Jiulong; Chen, Qing; Wang, Kuanglei; Li, Chenxi; Li, Weinan; Qiao, Mingxi; Zhao, Xiuli; Hu, Haiyang; Chen, Dawei

2017-01-15

In the present report, a degradable gene delivery system (PAMS/DNA/10NLS) containing nucleus location signal peptide (NLS) was prepared. The agarose gel electrophoresis, particle size and zeta potential of PAMS/DNA/10NLS were similar to those of PAMS/DNA, which proved that NLS did not affect the interaction between PAMS and DNA. PAMS/DNA/10NLS exhibited marked extracellular and intracellular degradation under acidic conditions. The degradation was believed to allow NLS to come into contact with importins easily, which was able to mediate the nucleus import. With the help of NLS, PAMS/DNA/10NLS exhibited a higher transfection capability than PAMS/DNA. Moreover, the transfection of PAMS/DNA/10NLS was less dependent on the breakdown of the nucleus envelope than PAMS/DNA. Considering that GTPase-activating protein 1 (RanGAP1) was able to activate the endogenous GTPase, which was necessary for NLS-mediated nucleus import, RanGAP1 overexpressed cells (RanGAP1 cells) were produced. This result showed that RanGAP1 cells had higher GTPase activities than normal cells. Both the nucleus import and transfection efficiency of PAMS/DNA/10NLS were markedly higher in RanGAP1 cells than that in normal cells. The in vivo transfection results also showed that the transfection efficiency of PAMS/DNA/10NLS was higher in RanGAP1 pre-treated mice than that in normal mice. These findings showed that PAMS/DNA/10NLS is a promising gene delivery system with the assistance of RanGAP1. The present report describes the increased transfection efficiency of a degradable gene delivery system (PAMS/DNA/10NLS) containing nuclear location signal (NLS) with the assistance of GTPase-activating protein 1 (RanGAP1). The physicochemical properties of PAMS/DNA/10NLS were similar to those of PAMS/DNA. PAMS/DNA/10NLS exhibited great extracellular and intracellular degradations, which might allow NLS to contact with importins easily. With the help of NLS, PAMS/DNA/10NLS exhibited a higher transfection capability than PAMS/DNA. The transfection of PAMS/DNA/10NLS had less dependence on the breakdown of nuclear envelope. Both the nuclear import and transfection efficiency of PAMS/DNA/10NLS were higher in RanGAP1 overexpressed cells than that in normal cells. Moreover, the transfection efficiency of PAMS/DNA/10NLS was higher in RanGAP1 pre-treated mice than that in normal mice. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Anti-tumor Effects of Plasma Activated Media and Correlation with Hydrogen Peroxide Concentration

NASA Astrophysics Data System (ADS)

Laroussi, Mounir; Mohades, Soheila; Barekzi, Nazir; Maruthamuthu, Venkat; Razavi, Hamid

2016-09-01

Plasma activated media (PAM) can induce death in cancer cells. In our research, PAM is produced by exposing liquid culture medium to a helium plasma pencil. Reactive oxygen and nitrogen species in the aqueous state are known factors in anti-tumor effects of PAM. The duration of plasma exposure determines the concentrations of reactive species produced in PAM. Stability of the plasma generated reactive species and their lifetime depend on parameters such as the chemical composition of the medium. Here, a complete cell culture medium was employed to make PAM. Later, PAM was used to treat SCaBER cancer cells either as an immediate PAM (right after exposure) or as an aged-PAM (after storage). SCaBER (ATCC®HTB-3™) is an epithelial cell line from a human bladder with the squamous carcinoma disease. A normal epithelial cell line from a kidney tissue of a dog - MDCK (ATCC®CCL-34™) - was used to analyze the selective effect of PAM. Correspondingly, we measured the concentration of hydrogen peroxide- as a stable species with biological impact on cell viability- in both immediate PAM and aged-PAM. In addition, we report on the effect of serum supplemented in PAM on the H2O2 concentration measured by Amplex red assay kit. Finally, we evaluate the effects of PAM on growth and morphological changes in MDCK cells using fluorescence microscopy.

48 CFR 1401.603-3 - Appointment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the bureau/office procedures within the constraints of DOI Integrated Charge Card Program Policy Manual located at http://www.doi.gov/pam/chargecard. Additional guidance is available in the GSA Smart...

48 CFR 1401.603-3 - Appointment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... the bureau/office procedures within the constraints of DOI Integrated Charge Card Program Policy Manual located at http://www.doi.gov/pam/chargecard. Additional guidance is available in the GSA Smart...

Passive Acoustic Mapping with the Angular Spectrum Method

PubMed Central

Crake, Calum; McDannold, Nathan; Clement, Gregory T.

2017-01-01

In the present proof of principle study, we evaluated the homogenous angular spectrum method for passive acoustic mapping (AS-PAM) of microbubble oscillations using simulated and experimental data. In the simulated data we assessed the ability of AS-PAM to form 3D maps of a single and multiple point sources. Then, in the two dimensional limit, we compared the 2D maps from AS-PAM with alternative frequency and time domain passive acoustic mapping (FD- and TD-PAM) approaches. Finally, we assessed the ability of AS-PAM to visualize microbubble activity in vivo with data obtained during 8 different experiments of FUS-induced blood-brain barrier disruption in 3 nonhuman primates, using a clinical MR-guided FUS system. Our in silico results demonstrate AS-PAM can be used to perform 3D passive acoustic mapping. 2D AS-PAM as compared to FD- PAM and TD-PAM is 10 and 200 times faster respectively and has similar sensitivity, resolution, and localization accuracy, even when the noise was 10-fold higher than the signal. In-vivo, the AS-PAM reconstructions of emissions at frequency bands pertinent to the different types of microbubble oscillations were also found to be more sensitive than TD-PAM. AS-PAM of harmonic-only components predicted safe blood-brain barrier disruption, whereas AS-PAM of broadband emissions correctly identified MR-evident tissue damage. The disparity (3.2mm) in the location of the cavitation activity between the three methods was within their resolution limits. These data clearly demonstrate that AS-PAM is a sensitive and fast approach for PAM, thus providing a clinically relevant method to guide therapeutic ultrasound procedures. PMID:28026755

Medical Research and Evaluation Facility (MREF) and studies supporting the medical chemical defense program. Determination of the minimum effective pyridostigmine pretreatment dose in monkeys challenged with 5 x LD50 Soman and treated with atropine/2-PAM. Final report, 22 October 1992-31 August 1993

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

Olson, C.T.; Menton, R.G.; Kiser, R.C.

This task was conducted to determine the minimum dose of pyridostigmine (PYR), and the associated level of erythrocyte acetycholinesterase inhibition (AChE-I), that provides protection from 5 X 48-br GD LD50 of untreated monkeys. Monkeys were injected im with GD and treated with 0.4 mg atropine (ATR) free base and 25.7 mg pralidoxime (2-PAM) per kg BW.

Study of Ground Subsidence in North West Houston using GPS, LiDAR and InSAR techniques

NASA Astrophysics Data System (ADS)

Karacay, A.; Khan, S. D.

2012-12-01

Land subsidence can be caused by natural or human activities, such as carbonate dissolution, extraction of material from mines, soil compaction and fluid withdrawal. This phenomenon affects many cities around the world, such as Nagoya-Japan, Venice-Italy, San Joaquin Valley and Long Beach in California. Recent work by Engelkemeir et al, (2010), suggested that subsidence occurred as high as 5.6 cm/year in northwest Houston. The processes that may contribute to land subsidence in the Houston-Galveston area includes faulting, soil compaction, salt tectonic, water pumping and hydrocarbon extraction. This study aims to assess the possible role of water pumping on subsidence. Northwest Houston has two aquifer systems, the Evangeline and Chicot aquifers that dip in the southeast direction. The effect of water pumping on subsidence from these two aquifers was monitored using InSAR, GPS and LiDAR data. The data from eleven GPS stations were processed using Online Positioning User Service (OPUS) of National Geodetic Survey (NGS). Three of these GPS stations are Continuously Operating Reference Stations (CORS) and eight are Port-A-Measure (PAM) sites. All the GPS data were obtained from Harris-Galveston Subsidence District (HGSD). CORS sites were used as reference stations for processing GPS data from the PAM stations. GPS data show that subsidence rate in northwest Houston decreased to approximately 2 cm/year. In addition, the surface deformation is also estimated using Light Detection and Ranging (LiDAR) technique. For this purpose, raw LiDAR (LAS-Long ASCII Standart) files of 2001 and 2008 were processed. The subsidence rate near the Hockley Fault was calculated by applying zonal statistics method on LiDAR data which shows about 10 cm of subsidence in nine years. This result is supported by processed GPS data from PAM site 48 that show subsidence rate of 1.3 cm/yr. For the InSAR (Interferometric Synthetic Aperture Radar) technique, an image pair of PALSAR (The Phased Array type L-band Synthetic Aperture Radar) for 2008 was processed using Sarscape ENVI. The result demonstrates both uplift (approximately 5 mm near the Tomball salt dome) and subsidence (approximately 5.3 mm on the west part of Tomball region). In order to improve results, other image pairs from PALSAR, ERS1/2 and ENVISAT are being processed to monitor surface changes before and after 2000. Changes of groundwater level in the study area were observed, in order to distinguish the amount of land subsidence caused by groundwater withdrawal. The groundwater historical observation data were taken from The USGS National Water Information System (NWIS). The results of the groundwater level between 1990 and 2011 show approximately 0.5 m per year of water decline in the study area. Results of these complementary techniques will help in assessing the possible role of the water pumping from the subsurface on the subsidence in the area.

KSC-07pd0642

NASA Image and Video Library

2007-03-15

KENNEDY SPACE CENTER, FLA. -- In the Space Station Processing Facility, Mission STS-120 Pilot George Zamka (left, partially hidden) and Commander Pam Melroy (second from right in group), talk with members of the media and guests after a ceremony to unveil NASA's Node 2 module's new name, Harmony. The name, Harmony, was chosen from an academic competition involving thousands of students in kindergarten through high school. The Node 2 Challenge required students to learn about the International Space Station, build a scale model of the module, and write an essay explaining their proposed name. This will be the first U.S. piece of the space station named by someone other than a NASA official. Node 2 is a pressurized module that will act as a connecting port and passageway to additional international science labs and supply spacecraft. It also will be a work platform for the station's robotic arm. The module is scheduled to fly on mission STS-120 aboard Space Shuttle Atlantis targeted for later this year. Photo credit: NASA/Jim Grossmann

Inverse effects of Polyacrylamide (PAM) usage in furrow irrigation on advance time and deep percolation.

PubMed

Meral, Ramazan; Cemek, Bilal; Apan, Mehmet; Merdun, Hasan

2006-10-01

The positive effects of Polyacrylamide (PAM), which is used as a soil conditioner in furrow irrigation, on sediment transport, erosion, and infiltration have been investigated intensively in recent years. However, the effects of PAM have not been considered enough in irrigation system planning and design. As a result of increased infiltration because of PAM, advance time may be inversely affected and deep percolation increases. However, advance time in furrow irrigation is a crucial parameter in order to get high application efficiency. In this study, inverse effects of PAM were discussed, and as an alternative solution, the applicability of surge flow was investigated. PAM application significantly increased the advance time at the rates of 41.3-56.3% in the first irrigation. The application of surge flow with PAM removed this negative effect on advance time, where there was no statistically significant difference according to normal continuous flow (without PAM). PAM applications significantly increased the deep percolation, 80.3-117.1%. Surge flow with PAM had significantly positive effect on the deep percolation compared to continuous flow with PAM but not compared to normal continuous flow. These results suggested that irrigation planning should me made based on the new soil and flow conditions because of PAM usage, and surge flow can be a solution to these problems.

Spectrophotometric determination of substrate-borne polyacrylamide.

PubMed

Lu, Jianhang; Wu, Laosheng

2002-08-28

Polyacrylamides (PAMs) have wide application in many industries and in agriculture. Scientific research and industrial applications manifested a need for a method that can quantify substrate-borne PAM. The N-bromination method (a PAM analytical technique based on N-bromination of amide groups and spectrophotometric determination of the formed starch-triiodide complex), which was originally developed for determining PAM in aqueous solutions, was modified to quantify substrate-borne PAM. In the modified method, the quantity of substrate-borne PAM was converted to a concentration of starch-triiodide complex in aqueous solution that was then measured by spectrophotometry. The method sensitivity varied with substrates due to sorption of reagents and reaction intermediates on the substrates. Therefore, separate calibration for each substrate was required. Results from PAM samples in sand, cellulose, organic matter burnt soils, and clay minerals showed that this method had good accuracy and reproducibility. The PAM recoveries ranged from 95.8% to 103.7%, and the relative standard deviations (n = 4) were <7.5% in all cases. The optimum range of PAM in each sample is 10-80 microg. The technique can serve as an effective tool in improving PAM application and facilitating PAM-related research.

Pro-2-PAM Therapy for Central and Peripheral Cholinesterases

PubMed Central

DeMar, James C.; Clarkson, Edward D.; Ratcliffe, Ruthie H.; Campbell, Amy J.; Thangavelu, Sonia G.; Herdman, Christine A.; Leader, Haim; Schulz, Susan M.; Marek, Elizabeth; Medynets, Marie A.; Ku, Theresa C.; Evans, Sarah A.; Khan, Farhat A.; Owens, Roberta R.; Nambiar, Madhusoodana P.; Gordon, Richard K.

2010-01-01

Novel therapeutics to overcome the toxic effects of organophosphorus (OP) chemical agents are needed due to the documented use of OPs in warfare (e.g. 1980–1988 Iran/Iraq war) and terrorism (e.g. 1995 Tokyo subway attacks). Standard OP exposure therapy in the United States consists of atropine sulfate (to block muscarinic receptors), the acetylcholinesterase (AChE) reactivator (oxime) pralidoxime chloride (2-PAM), and a benzodiazepine anticonvulsant to ameliorate seizures. A major disadvantage is that quaternary nitrogen charged oximes, including 2-PAM, do not cross the blood brain barrier (BBB) to treat brain AChE. Therefore, we have synthesized and evaluated pro-2-PAM (a lipid permeable 2-PAM derivative) that can enter the brain and reactivate CNS AChE, preventing seizures in guinea pigs after exposure to OPs. The protective effects of the pro-2-PAM after OP exposure were shown using a) surgically-implanted radiotelemetry probes for electroencephalogram (EEG) b) neurohistopathology of brain, c) cholinesterase activities in the PNS and CNS, and d) survivability. The PNS oxime 2-PAM was ineffective at reducing seizures/status epilepticus (SE) in diisopropyl-fluorophosphate (DFP)-exposed animals. In contrast, pro-2-PAM significantly suppressed and then eliminated seizure activity. In OP-exposed guinea pigs, there was a significant reduction in neurological damage with pro-2-PAM, but not 2-PAM. Distinct regional areas of the brains showed significantly higher AChE activity 1.5 h after OP exposure in pro-2-PAM treated animals compared to the 2-PAM treated ones. However, blood and diaphragm showed similar AChE activities in animals treated with either oxime, as both 2-PAM and pro 2-PAM are PNS active oximes. In conclusion, pro-2-PAM can cross the BBB, is rapidly metabolized inside the brain to 2-PAM, and protects against OP-induced SE through restoration of brain AChE activity. Pro-2-PAM represents the first non-invasive means of administering a CNS therapeutic for the deleterious effects of OP poisoning by reactivating CNS AChE. PMID:20156430

BicPAMS: software for biological data analysis with pattern-based biclustering.

PubMed

Henriques, Rui; Ferreira, Francisco L; Madeira, Sara C

2017-02-02

Biclustering has been largely applied for the unsupervised analysis of biological data, being recognised today as a key technique to discover putative modules in both expression data (subsets of genes correlated in subsets of conditions) and network data (groups of coherently interconnected biological entities). However, given its computational complexity, only recent breakthroughs on pattern-based biclustering enabled efficient searches without the restrictions that state-of-the-art biclustering algorithms place on the structure and homogeneity of biclusters. As a result, pattern-based biclustering provides the unprecedented opportunity to discover non-trivial yet meaningful biological modules with putative functions, whose coherency and tolerance to noise can be tuned and made problem-specific. To enable the effective use of pattern-based biclustering by the scientific community, we developed BicPAMS (Biclustering based on PAttern Mining Software), a software that: 1) makes available state-of-the-art pattern-based biclustering algorithms (BicPAM (Henriques and Madeira, Alg Mol Biol 9:27, 2014), BicNET (Henriques and Madeira, Alg Mol Biol 11:23, 2016), BicSPAM (Henriques and Madeira, BMC Bioinforma 15:130, 2014), BiC2PAM (Henriques and Madeira, Alg Mol Biol 11:1-30, 2016), BiP (Henriques and Madeira, IEEE/ACM Trans Comput Biol Bioinforma, 2015), DeBi (Serin and Vingron, AMB 6:1-12, 2011) and BiModule (Okada et al., IPSJ Trans Bioinf 48(SIG5):39-48, 2007)); 2) consistently integrates their dispersed contributions; 3) further explores additional accuracy and efficiency gains; and 4) makes available graphical and application programming interfaces. Results on both synthetic and real data confirm the relevance of BicPAMS for biological data analysis, highlighting its essential role for the discovery of putative modules with non-trivial yet biologically significant functions from expression and network data. BicPAMS is the first biclustering tool offering the possibility to: 1) parametrically customize the structure, coherency and quality of biclusters; 2) analyze large-scale biological networks; and 3) tackle the restrictive assumptions placed by state-of-the-art biclustering algorithms. These contributions are shown to be key for an adequate, complete and user-assisted unsupervised analysis of biological data. BicPAMS and its tutorial available in http://www.bicpams.com .

KSC-07pd2017

NASA Image and Video Library

2007-07-19

KENNEDY SPACE CENTER, Fla. -- In the Orbiter Processing Facility bay 3, STS-120 crew members get a look at the main bus switching unit that is part of the payload on their mission. From left are Pilot George Zamka, Mission Specialists Scott Parazynski and Stephanie Wilson, astronaut Dan Tani, who will join the International Space Station crew, and Mission Specialists Paolo Nespoli, Doug Wheelock and Commander Pam Melroy. Nespoli represents the European Space Agency. A main bus switching unit is used for power distribution, circuit protection and fault isolation on the space station's power system. The units route power to proper locations in the space station, such as from solar arrays through umbilicals into the U.S. Lab. The unit will be installed on the external stowage platform 2 attached to the Quest airlock for temporary storage. Discovery is targeted to launch mission STS-120 no earlier than Oct. 20. Photo credit: NASA/Jim Grossmann

SpaceX CRS-10 Post Launch News Conference

NASA Image and Video Library

2017-02-19

In the Press Site auditorium of NASA's Kennedy Space Center in Florida, Pam Underwood, manager of the Operations Integration Division of the Federal Aviation Administration Office of Commercial Space Transportation, speaks to the news media at a post-launch news conference following the liftoff of SpaceX CRS-10, a commercial resupply services mission to the International Space Station. SpaceX CRS-10 lifted off atop a Falcon 9 rocket from Kennedy's Launch Complex 39A at 9:39 a.m. EST.

The STS-92 crew is ready to leave KSC after CEIT

NASA Technical Reports Server (NTRS)

2000-01-01

STS-92 Pilot Pam Melroy poses at the Shuttle Landing Facility before flying back to Houston. She and other crew members completed their Crew Equipment Interface Test activities, looking over their mission payload and related equipment. STS-92 is scheduled to launch Oct. 5 on Shuttle Discovery from Launch Pad 39A on the fifth flight to the International Space Station. Discovery will carry the Integrated Truss Structure (ITS) Z1, the PMA-3, Ku-band Communications System, and Control Moment Gyros (CMGs).

Effect of cationic monomer content on polyacrylamide copolymers by frit-inlet asymmetrical flow field-flow fractionation/multi-angle light scattering.

PubMed

Lee, Hyejin; Kim, Jin Yong; Choi, Woonjin; Moon, Myeong Hee

2017-06-23

In this study, ultrahigh-molecular-weight (MW) (>10 7 Da) cationic polyacrylamides (C-PAMs), which are water-soluble polymers used in waste water treatment, were characterized using frit-inlet asymmetrical flow field-flow fractionation coupled with multi-angle light scattering and differential refractive detection. C-PAMs copolymerized with acryloxyethyltrimethyl ammonium chloride (DAC) were prepared by varying the feed amount of cationic monomer, polymerization method (solution vs. emulsion), and degree of branching. The MW of the copolymers prepared using emulsion polymerization (10 7 -10 9 Da) was generally larger than that of copolymers prepared using solution polymerization (4×10 7 -10 8 Da). When the amount of cationic monomer was increased from 10 to 55mol% in solution polymerization, hydrophobic contraction of the core induced formation of more compact C-PAMs. The copolymers prepared using emulsion polymerization formed highly aggregated or supercoil structures owing to increased intermolecular hydrophobic interaction when less cationic monomer was used. However, the MW decreased with increased cationic group content. In addition, C-PAMs larger than ∼10 8 Da prepared using the emulsion method were separated by steric/hyperlayer elution mode while those in the 10 7 -10 8 Da range were analyzed in either normal or steric/hyperlayer mode depending on the decay patterns of field programming. Moreover, branched copolymers were found to be resolved with different elution modes under the same field decay pattern depending on the degree of branching: steric/hyperlayer for low-branching and normal for high-branching C-PAMs. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigation of selective induction of breast cancer cells to death with treatment of plasma-activated medium

NASA Astrophysics Data System (ADS)

Hashizume, Hiroshi; Tanaka, Hiromasa; Nakamura, Kae; Kano, Hiroyuki; Ishikawa, Kenji; Kikkawa, Fumitaka; Mizuno, Masaaki; Hori, Masaru

2015-09-01

The applications of plasma in medicine have much attention. We previously showed that plasma-activated medium (PAM) induced glioblastoma cells to apoptosis. However, it has not been elucidated the selectivity of PAM in detail. In this study, we investigated the selective effect of PAM on the death of human breast normal and cancer cells, MCF10A and MCF7, respectively, and observed the selective death with fluorescent microscopy. For the investigation of cell viability with PAM treatment, we prepared various PAMs according to the strengths, and treated each of cells with PAMs. Week PAM treatment only decreased the viability of MCF7 cells, while strong PAM treatment significantly affected both viabilities of MCF7 and MCF10A cells. For the fluorescent observation, we prepared the mixture of MCF7 and fluorescent-probed MCF10A cells, and seeded them. After the treatment of PAMs, the images showed that only MCF7 cells damaged in the mixture with week PAM treatment. These results suggested that a specific range existed with the selective effect in the strength of PAM. This work was partly supported by a Grant-in-Aid for Scientific Research on Innovative Areas ``Plasma Medical Innovation'' Grant No. 24108002 and 24108008 from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Mammalian Peptidylglycine α-Amidating Monooxygenase mRNA Expression Can Be Modulated by the La Autoantigen

PubMed Central

Brenet, Fabienne; Dussault, Nadège; Borch, Jonas; Ferracci, Géraldine; Delfino, Christine; Roepstorff, Peter; Miquelis, Raymond; Ouafik, L'Houcine

2005-01-01

Peptidylglycine α-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the COOH-terminal α-amidation of peptidylglycine substrates, yielding amidated products. We have previously reported a putative regulatory RNA binding protein (PAM mRNA-BP) that binds specifically to the 3′ untranslated region (UTR) of PAM-mRNA. Here, the PAM mRNA-BP was isolated and revealed to be La protein using affinity purification onto a 3′ UTR PAM RNA, followed by tandem mass spectrometry identification. We determined that the core binding sequence is approximately 15-nucleotides (nt) long and is located 471 nt downstream of the stop codon. Moreover, we identified the La autoantigen as a protein that specifically binds the 3′ UTR of PAM mRNA in vivo and in vitro. Furthermore, La protein overexpression caused a nuclear retention of PAM mRNAs and resulted in the down-regulation of endogenous PAM activity. Most interestingly, the nuclear retention of PAM mRNA is lost upon expressing the La proteins that lack a conserved nuclear retention element, suggesting a direct association between PAM mRNA and La protein in vivo. Reporter assays using a chimeric mRNA that combined luciferase and the 3′ UTR of PAM mRNA demonstrated a decrease of the reporter activity due to an increase in the nuclear localization of reporter mRNAs, while the deletion of the 15-nt La binding site led to their clear-cut cytoplasmic relocalization. The results suggest an important role for the La protein in the modulation of PAM expression, possibly by mechanisms that involve a nuclear retention and perhaps a processing of pre-PAM mRNA molecules. PMID:16107699

Reversal of Physiological Deficits Caused by Diminished Levels of Peptidylglycine α-Amidating Monooxygenase by Dietary Copper

PubMed Central

Bousquet-Moore, D.; Ma, X. M.; Nillni, E. A.; Czyzyk, T. A.; Pintar, J. E.; Eipper, B. A.; Mains, R. E.

2009-01-01

Amidated peptides are critically involved in many physiological functions. Genetic deletion of peptidylglycine α-amidating monooxygenase (PAM), the only enzyme that can synthesize these peptides, is embryonically lethal. The goal of the present study was the identification of physiological functions impaired by haploinsufficiency of PAM. Regulation of the hypothalamic-pituitary-thyroid axis and body temperature, functions requiring contributions from multiple amidated peptides, were selected for evaluation. Based on serum T4 and pituitary TSH-β mRNA levels, mice heterozygous for PAM (PAM+/−) were euthyroid at baseline. Feedback within the hypothalamic-pituitary-thyroid axis was impaired in PAM+/− mice made hypothyroid using a low iodine/propylthiouracil diet. Despite their normal endocrine response to cold, PAM+/− mice were unable to maintain body temperature as well as wild-type littermates when kept in a 4 C environment. When provided with additional dietary copper, PAM+/− mice maintained body temperature as well as wild-type mice. Pharmacological activation of vasoconstriction or shivering also allowed PAM+/− mice to maintain body temperature. Cold-induced vasoconstriction was deficient in PAM+/− mice. This deficit was eliminated in PAM+/− mice receiving a diet with supplemental copper. These results suggest that dietary deficiency of copper, coupled with genetic deficits in PAM, could result in physiological deficits in humans. PMID:19022883

Power budget enhancement in NG-EPON system employing novel twisted-PAM4

NASA Astrophysics Data System (ADS)

Li, Longsheng; Bi, Meihua; Fu, Yan; Miao, Xin; Zhu, Qingming; Hu, Weisheng

2018-03-01

In this paper, we firstly design a novel modulation format named Twisted-PAM4 (T-PAM4) for the high-speed NG-EPON and the PON-based digital fronthaul system. Compared to other high-order modulation formats like 4-ary pulse amplitude modulation (PAM4), T-PAM4 provides two independent sampling values in each symbol period and enables two-dimensional symbol decision, which significantly improves the receiver sensitivity and hence enlarges the system power budget. Based on this advantage, six types of T-PAM4 are experimentally demonstrated in 28-Gb/s/ λ NG-PON and 32-Gb/s/ λ PON-based digital fronthaul system. The experimental results show that, compared to the ordinary PAM4, the T-PAM4 can bring 5-dB and 4-dB extra power budget in NG-EPON and PON-based fronthaul system respectively. In addition, by experiment, it is also depicted that the T-PAM4 is remarkably robust to system nonlinearity, which would ease the linearity requirement on system components and hence reduce system cost.

Analysis of 1995 speciated volatile organic compound data in the south central U.S.

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

Sather, M.E.; Kemp, M.G.; Yarbrough, J.W.

1997-12-31

An analysis of 1995 speciated volatile organic compound (VOC) data from three areas in the south central US has been performed for Baton Rouge, Louisiana, Houston, Texas, and El Paso, Texas. All three areas are required by the Clean Air Act Amendments of 1990 to collect ambient monitoring data for over 50 VOC species, including ten Clean Air Act Title III toxic compounds, as per the Photochemical Assessment Monitoring Stations (PAMS) requirements. The PAMS program was initiated to provide more detailed VOC data for scientists, modelers, and managers working toward eliminating violations of the ozone National Ambient Air Quality Standardsmore » (NAAQS). This paper presents useful information from a preliminary analysis of the 1995 speciated VOC and related data from Baton Rouge, Houston, and El Paso. All data analyzed were extracted from the US Environmental Protection Agency (EPA) Aerometric Information Retrieval System (AIRS) data base after collection and validation by the states of Louisiana and Texas. Key observations from the analyses include: (1) the presence of propane peaks coincident with ozone peaks during all three ozone episode days at the El Paso site; (2) the dominance of mobile source VOC emissions in the El Paso emission inventory, in contrast to the Baton Rouge and Houston VOC emission inventories, after noting strong correlations between carbon monoxide and major exhaust VOC species of gasoline; and (3) the 1995 ozone episodes at the Houston site were influenced by both morning build-up of ambient VOC concentrations and afternoon puffs of VOC emissions, while the 1995 ozone episodes at the Baton Rouge site were influenced by high early and mid-morning VOC ambient concentrations.« less

[Research progress on wind erosion control with polyacrylamide (PAM).

PubMed

Li, Yuan Yuan; Wang, Zhan Li

2016-03-01

Soil wind erosion is one of the main reasons for soil degradation in the northwest region of China. Polyacrylamide (PAM), as an efficient soil amendment, has gained extensive attention in recent years since it is effective in improving the structure of surface soil due to its special physical and chemical properties. This paper introduced the physical and chemical properties of PAM, reviewed the effects of PAM on soil wind erosion amount and threshold wind velocity, as well as the effect differences of PAM in soil wind erosion control under conditions of various methods and doses. Its effect was proved by comparing with other materials in detail. Furthermore, we analyzed the mecha-nism of wind erosion control with PAM according to its influence on soil physical characteristics. Comprehensive analysis showed that, although some problems existed in wind erosion control with (PAM), PAM as a sand fixation agent, can not only enhance the capacity of the soil resis-tance to wind erosion, but also improve soil physical properties to form better soil conditions. Besides, we proposed that combination of PAM and plant growth would increase the survival rate of plants greatly, control soil wind erosion in wind-erosive areas, and improve the quality of the ecological environment construction. Thus, PAM has practically important significance and wide application prospect in controlling soil wind erosion.

Sensitivity of photoacoustic microscopy

PubMed Central

Yao, Junjie; Wang, Lihong V.

2014-01-01

Building on its high spatial resolution, deep penetration depth and excellent image contrast, 3D photoacoustic microscopy (PAM) has grown tremendously since its first publication in 2005. Integrating optical excitation and acoustic detection, PAM has broken through both the optical diffusion and optical diffraction limits. PAM has 100% relative sensitivity to optical absorption (i.e., a given percentage change in the optical absorption coefficient yields the same percentage change in the photoacoustic amplitude), and its ultimate detection sensitivity is limited only by thermal noise. Focusing on the engineering aspects of PAM, this Review discusses the detection sensitivity of PAM, compares the detection efficiency of different PAM designs, and summarizes the imaging performance of various endogenous and exogenous contrast agents. It then describes representative PAM applications with high detection sensitivity, and outlines paths to further improvement. PMID:25302158

Differentiation of pancreatic ductal adenocarcinoma from chronic pancreatitis by PAM4 immunohistochemistry.

PubMed

Shi, Chanjuan; Merchant, Nipun; Newsome, Guy; Goldenberg, David M; Gold, David V

2014-02-01

PAM4 is a monoclonal antibody that shows high specificity for pancreatic ductal adenocarcinoma (PDAC) and its neoplastic precursor lesions. A PAM4-based serum immunoassay is able to detect 71% of early-stage patients and 91% with advanced disease. However, approximately 20% of patients diagnosed with chronic pancreatitis (CP) are also positive for circulating PAM4 antigen. The specificity of the PAM4 antibody is critical to the interpretation of the serum-based and immunohistochemical assays for detection of PDAC. To determine whether PAM4 can differentiate PDAC from nonneoplastic lesions of the pancreas. Tissue microarrays of PDAC (N = 43) and surgical specimens from CP (N = 32) and benign cystic lesions (N = 19) were evaluated for expression of the PAM4 biomarker, MUC1, MUC4, CEACAM5/6, and CA19-9. PAM4 and monoclonal antibodies (MAbs) to MUC1, MUC4, CEACAM5/6, and CA19-9 were each reactive with the majority of PDAC cases; however, PAM4 was the only monoclonal antibody not to react with adjacent, nonneoplastic parenchyma. Although PAM4 labeled 19% (6 of 32) of CP specimens, reactivity was restricted to pancreatic intraepithelial neoplasia associated with CP; inflamed tissues were negative in all cases. In contrast, MUC1, MUC4, CEACAM5/6, and CA19-9 were detected in 90%, 78%, 97%, and 100% of CP, respectively, with reactivity also present in nonneoplastic inflamed tissue. PAM4 was the only monoclonal antibody able to differentiate PDAC (and pancreatic intraepithelial neoplasia precursor lesions) from benign, nonneoplastic tissues of the pancreas. These results suggest the use of PAM4 for evaluation of tissue specimens, and support its role as an immunoassay for detection of PDAC.

Effects of added polyacrylamide on changes in water states during the composting of kitchen waste.

PubMed

Yang, Yu-Qiang; Chen, Zhuo-Xian; Zhang, Xue-Qing; Hu, Li-Fang; Shen, Dong-Sheng; Long, Yu-Yang

2015-02-01

The effects of adding polyacrylamide (PAM), to attempt to delay the loss of capillary water and achieve a better level of organic matter humification, in the composting of kitchen waste were evaluated. Four treatments, with initial moisture content of 60 % were used: 0.1 % PAM added before the start of composting (R1), 0.1 % PAM added when the thermophilic phase of composting became stable (at >50 °C) (R2), 0.1 % PAM added when the moisture content significantly decreased (R3), and no PAM added (R4). The introduction of PAM in R1 and R2 significantly increased the capillary force and delayed the loss of moisture content and capillary water. The introduction of PAM in R2 and R3 improved the composting process, in terms of the degradation of biochemical fractions and the humification degree. These results show that the optimal time for adding PAM was the initial stage of the thermophilic phase.

[Cryotherapy is useful and safe in the prevention of oral mucositis after high-dose melphalan (L-PAM)].

PubMed

Inagaki, Noriko; Ohue, Yukiko; Shigeta, Hiroe; Tasaka, Taizo

2006-11-01

We prospectively assessed the effectiveness of cryotherapy after high-dose L-PAM to prevent oral mucositis. Cryotherapy with ice tips was commenced 15 minutes before L-PAM administration, and continued until the end of administration. Twenty-six patients were enrolled in this study. Thirteen patients with myeloma were treated with 200 mg/m2 L-PAM followed by autologous peripheral blood stem cell transplantation, and 13 patients (4 AML, 4 MDS, 2 ALL, 2 lymphoma and 1 CML) were treated with 140 mg/m2 L-PAM followed by allogeneic stem cell transplantation. Grade 1 mucositis occurred in four of 13 patients (31%) with 200 mg/m2 L-PAM, and 2 of 13 patients (16%) with 140 mg/m2 L-PAM. Only one patient had grade 2 mucositis, and no grade 3 mucositis were observed. The procedure was well tolerated in all patients. These data suggest that cryotherapy is effective to minimize L-PAM-induced oral mucositis.

The Antinociceptive and Antiinflammatory Properties of 3-furan-2-yl-N-p-tolyl-acrylamide, a Positive Allosteric Modulator of α7 Nicotinic Acetylcholine Receptors in Mice

PubMed Central

Bagdas, Deniz; Targowska-Duda, Katarzyna M.; López, Jhon J.; Perez, Edwin G.; Arias, Hugo R.; Damaj, M. Imad

2016-01-01

BACKGROUND Positive allosteric modulators (PAMs) facilitate endogenous neurotransmission and/or enhance the efficacy of agonists without directly acting on the orthosteric binding sites. In this regard, selective α7 nicotinic acetylcholine receptor type II PAMs display antinociceptive activity in rodent chronic inflammatory and neuropathic pain models. This study investigates whether 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), a new putative α7-selective type II PAM, attenuates experimental inflammatory and neuropathic pains in mice. METHODS We tested the activity of PAM-2 after intraperitoneal administration in 3 pain assays: the carrageenan-induced inflammatory pain, the complete Freund adjuvant induced inflammatory pain, and the chronic constriction injury–induced neuropathic pain in mice. We also tested whether PAM-2 enhanced the effects of the selective α7 agonist choline in the mouse carrageenan test given intrathecally. Because the experience of pain has both sensory and affective dimensions, we also evaluated the effects of PAM-2 on acetic acid–induced aversion by using the conditioned place aversion test. RESULTS We observed that systemic administration of PAM-2 significantly reversed mechanical allodynia and thermal hyperalgesia in inflammatory and neuropathic pain models in a dose- and time-dependent manner without motor impairment. In addition, by attenuating the paw edema in inflammatory models, PAM-2 showed antiinflammatory properties. The antinociceptive effect of PAM-2 was inhibited by the selective competitive antagonist methyllycaconitine, indicating that the effect is mediated by α7 nicotinic acetylcholine receptors. Furthermore, PAM-2 enhanced the antiallodynic and antiinflammatory effects of choline, a selective α7 agonist, in the mouse carrageenan test. PAM-2 was also effective in reducing acetic acid induced aversion in the conditioned place aversion assay. CONCLUSIONS These findings suggest that the administration of PAM-2, a new α7-selective type II PAM, reduces the neuropathic and inflammatory pain sensory and affective behaviors in the mouse. Thus, this drug may have therapeutic applications in the treatment and management of chronic pain. PMID:26280585

Astronauts of Mission STS-120 visit Stennis Space Center

NASA Image and Video Library

2007-12-13

Astronaut Pam Melroy presents a commemorative collage of photos and items flown aboard space shuttle Discovery to Bob Cabana, director of NASA's Stennis Space Center in South Mississippi. Melroy commanded NASA's space shuttle mission STS-120. She and fellow crewmembers (from left) Doug Wheelock, Stephanie Wilson, George Zamka, Scott Parazynski and Paolo Nespoli visited Stennis Dec. 13, 2007, to thank employees for the reliability and safe performance of the space shuttle's main engines, which on Oct. 23 launched them aboard Discovery on their mission to the International Space Station.

Astronauts of Mission STS-120 visit Stennis Space Center

NASA Technical Reports Server (NTRS)

2007-01-01

Astronaut Pam Melroy presents a commemorative collage of photos and items flown aboard space shuttle Discovery to Bob Cabana, director of NASA's Stennis Space Center in South Mississippi. Melroy commanded NASA's space shuttle mission STS-120. She and fellow crewmembers (from left) Doug Wheelock, Stephanie Wilson, George Zamka, Scott Parazynski and Paolo Nespoli visited Stennis Dec. 13, 2007, to thank employees for the reliability and safe performance of the space shuttle's main engines, which on Oct. 23 launched them aboard Discovery on their mission to the International Space Station.

STS-112 crew in front of S0 Truss Structure

NASA Technical Reports Server (NTRS)

2002-01-01

KENNEDY SPACE CENTER, FLA. -- In the Operations and Checkout Building, the STS-112 crew stands under the S0 Integrated Truss Structure, waiting to be transported to the launch pad for mission STS-110. From left are Mission Specialist David Wolf, Pilot Pam ela Melroy; Commander Jeffrey Ashby; and Mission Specialist Piers Sellers. Mission STS-112 will be ferrying the S1 ITS to the International Space Station on its scheduled Aug. 15 flight. The S1 truss will be attached to the S0 truss

PAYLOAD (INDIA SATELLITE [INSAT]) - SHUTTLE

NASA Image and Video Library

1983-01-12

S83-36307 (2 June 1983) --- INSAT 1-B is being prepared for its trip aboard the space shuttle Challenger and its deployment for geosynchronous orbital duties at the Cape Canaveral Air Force Station and at NASA's Kennedy Space Center (KSC). The Indian National Satellite is the second such Indian communications/meteorological spacecraft, the first having been sent into space via a Delta launch vehicle. The STS-8 astronaut crew members and a payload assist module (PAM) will aid the newest INSAT in its deployment steps during NASA?s third Challenger flight in August of this year.

Cross-cultural validation of the parent-patient activation measure in low income Spanish- and English-speaking parents.

PubMed

DeCamp, Lisa Ross; Leifheit, Kathryn; Shah, Harita; Valenzuela-Araujo, Doris; Sloand, Elizabeth; Polk, Sarah; Cheng, Tina L

2016-12-01

(1) To measure healthcare activation among low-income parents by language (English/Spanish); and (2) to assess the psychometrics of the Parent-Patient Activation Measure (P-PAM) in the study population. We surveyed parents/guardians of publicly-insured children who were established patients at a pediatrics clinic for ≥6months. Surveys included the Parent-Patient Activation Measure (P-PAM), a 13-item measure adapted from the well-validated Patient Activation Measure (PAM). Of 316 surveys, 68% were completed in Spanish. Mean activation score in the English-language survey group was 79.1 (SD 16.2); mean score in the Spanish-language group was 70.7 (SD 17.9) (p<0.001). Scale reliability was high (English α=0.90; Spanish α=0.93). The P-PAM had acceptable test-retest reliability, but no previously reported PAM factor structure fit the study data adequately for either language. Healthcare activation among low-income parents was greater for parents surveyed in English compared with those surveyed in Spanish. The P-PAM has acceptable reliability and validity in English and Spanish, but a different factor structure than the PAM. Activation as measured by the P-PAM may not have the same associations with or impact on health/healthcare outcomes in pediatrics compared with adults owing to possible measure differences between the P-PAM and PAM. Published by Elsevier Ireland Ltd.

A study on contraction of pneumatic artificial muscle (PAM) for load-lifting

NASA Astrophysics Data System (ADS)

Najmuddin, W. S. W. A.; Mustaffa, M. T.

2017-10-01

Pneumatic Artificial Muscles (PAMs) have been known for its wide application in various aspects of industrial automation and robotic equipments. Many advantages in terms of high power-to-volume ratio, high power-to-weight ratio, stick-slip-free operation and high degree of safety offer by PAM compare to traditional actuators. However, behind this benefits lie a limitation of significant compatibility of PAM mechanism which have to be considered so as to fully understand how the PAM works during load-lifting. In this study, the mesh suitability experiment and the effect of force load on PAM contraction experiment have been carried out. PAM is constructed and compatibility of bladder and the braided mesh to produce uniform expansion is investigated. Moreover, the first experimental result of finding compatibility is used to verify the contraction value under various loads.

Comparison of contractile and extensile pneumatic artificial muscles

NASA Astrophysics Data System (ADS)

Pillsbury, Thomas E.; Wereley, Norman M.; Guan, Qinghua

2017-09-01

Pneumatic artificial muscles (PAMs) are used in robotic and prosthetic applications due to their high power to weight ratio, controllable compliance, and simple design. Contractile PAMs are typically used in traditional hard robotics in place of heavy electric motors. As the field of soft robotics grows, extensile PAMs are beginning to have increased usage. This work experimentally tests, models, and compares contractile and extensile PAMs to demonstrate the advantages and disadvantages of each type of PAM and applications for which they are best suited.

Passive acoustic mapping of cavitation using eigenspace-based robust Capon beamformer in ultrasound therapy.

PubMed

Lu, Shukuan; Hu, Hong; Yu, Xianbo; Long, Jiangying; Jing, Bowen; Zong, Yujin; Wan, Mingxi

2018-03-01

Pulse-echo imaging technique can only play a role when high intensity focused ultrasound (HIFU) is turned off due to the interference between the primary HIFU signal and the transmission pulse. Passive acoustic mapping (PAM) has been proposed as a tool for true real-time monitoring of HIFU therapy. However, the most-used PAM algorithm based on time exposure acoustic (TEA) limits the quality of cavitation image. Recently, robust Capon beamformer (RCB) has been used in PAM to provide improved resolution and reduced artifacts over TEA-based PAM, but the presented results have not been satisfactory. In the present study, we applied an eigenspace-based RCB (EISRCB) method to further improve the PAM image quality. The optimal weighting vector of the proposed method was found by projecting the RCB weighting vector onto the desired vector subspace constructed from the eigenstructure of the covariance matrix. The performance of the proposed PAM was validated by both simulations and in vitro histotripsy experiments. The results suggested that the proposed PAM significantly outperformed the conventionally used TEA and RCB-based PAM. The comparison results between pulse-echo images of the residual bubbles and cavitation images showed the potential of our proposed PAM in accurate localization of cavitation activity during HIFU therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Plasma-activated medium suppresses choroidal neovascularization in mice: a new therapeutic concept for age-related macular degeneration.

PubMed

Ye, Fuxiang; Kaneko, Hiroki; Nagasaka, Yosuke; Ijima, Ryo; Nakamura, Kae; Nagaya, Masatoshi; Takayama, Kei; Kajiyama, Hiroaki; Senga, Takeshi; Tanaka, Hiromasa; Mizuno, Masaaki; Kikkawa, Fumitaka; Hori, Masaru; Terasaki, Hiroko

2015-01-09

Choroidal neovascularization (CNV) is the main pathogenesis of age-related macular degeneration (AMD), which leads to severe vision loss in many aged patients in most advanced country. CNV compromises vision via hemorrhage and retinal detachment on account of pathological neovascularization penetrating the retina. Plasma medicine represents the medical application of ionized gas "plasma" that is typically studied in the field of physical science. Here we examined the therapeutic ability of plasma-activated medium (PAM) to suppress CNV. The effect of PAM on vascularization was assessed on the basis of human retinal endothelial cell (HREC) tube formation. In mice, laser photocoagulation was performed to induce CNV (laser-CNV), followed by intravitreal injection of PAM. N-Acetylcysteine was used to examine the role of reactive oxygen species in PAM-induced CNV suppression. Fundus imaging, retinal histology examination, and electroretinography (ERG) were also performed to evaluate PAM-induced retinal toxicity. Interestingly, HREC tube formation and laser-CNV were both reduced by treatment with PAM. N-acetylcysteine only partly neutralized the PAM-induced reduction in laser-CNV. In addition, PAM injection had no effect on regular retinal vessels, nor did it show retinal toxicity in vivo. Our findings indicate the potential of PAM as a novel therapeutic agent for suppressing CNV.

Fast focus-scanning head in two-photon photoacoustic microscopy with electrically controlled liquid lens

NASA Astrophysics Data System (ADS)

Yamaoka, Yoshihisa; Kimura, Yuka; Harada, Yoshinori; Takamatsu, Tetsuro; Takahashi, Eiji

2018-02-01

Conventional one-photon photoacoustic microscopy (PAM) utilizes high-frequency components of generated photoacoustic waves to improve the depth resolution. However, to obtain optically-high resolution in PAM in the depth direction, the use of high-frequency ultrasonic waves is to be avoided. It is because that the propagation distance is shortened as the frequency of ultrasonic waves becomes high. To overcome this drawback, we have proposed and developed two-photon photoacoustic microscopy (TP-PAM). Two-photon absorption occurs only at the focus point. TPPAM does not need to use the high-frequency components of photoacoustic waves. Thus, TP-PAM can improve the penetration depth while preserving the spatial resolution. However, the image acquisition time of TP-PAM is longer than that of conventional PAM, because TP-PAM needs to scan the laser spot both in the depth and transverse directions to obtain cross-sectional images. In this paper, we have introduced a focus-tunable electrically-controlled liquid lens in TP-PAM. Instead of a mechanical stepping-motor stage, we employed electrically-controlled liquid lens so that the depth of the focus spot can be quickly changed. In our system, the imaging speed of TP-PAM using the liquid lens and one-axis stepping-motor stage was 10 times faster than that using a two-axis stepping-motor stage only. TP-PAM with focus-scanning head consisting of the liquid lens and stepping-motor stage will be a promising method to investigate the inside of living tissues.

The influence of allosteric modulators and transmembrane mutations on desensitisation and activation of α7 nicotinic acetylcholine receptors

PubMed Central

Chatzidaki, Anna; D'Oyley, Jarryl M.; Gill-Thind, JasKiran K.; Sheppard, Tom D.; Millar, Neil S.

2015-01-01

Acetylcholine activates nicotinic acetylcholine receptors (nAChRs) by binding at an extracellular orthosteric site. Previous studies have described several positive allosteric modulators (PAMs) that are selective for homomeric α7 nAChRs. These include type I PAMs, which exert little or no effect on the rate of receptor desensitisation, and type II PAMs, which cause a dramatic loss of agonist-induced desensitisation. Here we report evidence that transmembrane mutations in α7 nAChRs have diverse effects on receptor activation and desensitisation by allosteric ligands. It has been reported previously that the L247T mutation, located toward the middle of the second transmembrane domain (at the 9′ position), confers reduced levels of desensitisation. In contrast, the M260L mutation, located higher up in the TM2 domain (at the 22′ position), does not show any difference in desensitisation compared to wild-type receptors. We have found that in receptors containing the L247T mutation, both type I PAMs and type II PAMs are converted into non-desensitising agonists. In contrast, in receptors containing the M260L mutation, this effect is seen only with type II PAMs. These findings, indicating that the M260L mutation has a selective effect on type II PAMs, have been confirmed both with previously described PAMs and also with a series of novel α7-selective PAMs. The novel PAMs examined in this study have close chemical similarity but diverse pharmacological properties. For example, they include compounds displaying effects on receptor desensitisation that are typical of classical type I and type II PAMs but, in addition, they include compounds with intermediate properties. PMID:25998276

The influence of allosteric modulators and transmembrane mutations on desensitisation and activation of α7 nicotinic acetylcholine receptors.

PubMed

Chatzidaki, Anna; D'Oyley, Jarryl M; Gill-Thind, JasKiran K; Sheppard, Tom D; Millar, Neil S

2015-10-01

Acetylcholine activates nicotinic acetylcholine receptors (nAChRs) by binding at an extracellular orthosteric site. Previous studies have described several positive allosteric modulators (PAMs) that are selective for homomeric α7 nAChRs. These include type I PAMs, which exert little or no effect on the rate of receptor desensitisation, and type II PAMs, which cause a dramatic loss of agonist-induced desensitisation. Here we report evidence that transmembrane mutations in α7 nAChRs have diverse effects on receptor activation and desensitisation by allosteric ligands. It has been reported previously that the L247T mutation, located toward the middle of the second transmembrane domain (at the 9' position), confers reduced levels of desensitisation. In contrast, the M260L mutation, located higher up in the TM2 domain (at the 22' position), does not show any difference in desensitisation compared to wild-type receptors. We have found that in receptors containing the L247T mutation, both type I PAMs and type II PAMs are converted into non-desensitising agonists. In contrast, in receptors containing the M260L mutation, this effect is seen only with type II PAMs. These findings, indicating that the M260L mutation has a selective effect on type II PAMs, have been confirmed both with previously described PAMs and also with a series of novel α7-selective PAMs. The novel PAMs examined in this study have close chemical similarity but diverse pharmacological properties. For example, they include compounds displaying effects on receptor desensitisation that are typical of classical type I and type II PAMs but, in addition, they include compounds with intermediate properties. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling

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

Maruyama, Akira; Shime, Hiroaki, E-mail: shime@med.hokudai.ac.jp; Takeda, Yohei

2015-02-13

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that exhibit potent immunosuppressive activity. They are increased in tumor-bearing hosts and contribute to tumor development. Toll-like receptors (TLRs) on MDSCs may modulate the tumor-supporting properties of MDSCs through pattern-recognition. Pam2 lipopeptides represented by Pam2CSK4 serve as a TLR2 agonist to exert anti-tumor function by dendritic cell (DC)-priming that leads to NK cell activation and cytotoxic T cell proliferation. On the other hand, TLR2 enhances tumor cell progression/invasion by activating tumor-infiltrating macrophages. How MDSCs respond to TLR2 agonists has not yet been determined. In this study, we found intravenous administration of Pam2CSK4more » systemically up-regulated the frequency of MDSCs in EG7 tumor-bearing mice. The frequency of tumor-infiltrating MDSCs was accordingly increased in response to Pam2CSK4. MDSCs were not increased by Pam2CSK4 stimuli in TLR2 knockout (KO) mice. Adoptive transfer experiments using CFSE-labeled MDSCs revealed that the TLR2-positive MDSCs survived long in tumor-bearing mice in response to Pam2CSK4 treatment. Since the increased MDSC population sustained immune-suppressive properties, our study suggests that Pam2CSK4-triggered TLR2 activation enhances the MDSC potential and suppress antitumor immune response in tumor microenvironment. - Highlights: • Pam2CSK4 administration induces systemic accumulation of CD11b{sup +}Gr1{sup +} MDSCs. • TLR2 is essential for Pam2CSK4-induced accumulation of CD11b{sup +}Gr1{sup +} MDSCs. • Pam2CSK4 supports survival of CD11b{sup +}Gr1{sup +} MDSCs in vivo.« less

Beyond demographics: differences in patient activation across new immigrant, diverse language subgroups.

PubMed

Lubetkin, Erica I; Zabor, Emily C; Brennessel, Debra; Kemeny, M Margaret; Hay, Jennifer L

2014-02-01

The federal government promotes "patient-centered medical homes" to plan care with respect to patients' cultures and values and support patients' self-care efforts. To promote self-care, the medical home would be best utilized by activated, engaged patients. The objective of this study was to measure and compare patient activation scores in English-, Spanish-, and Haitian Creole-speaking patients seen at an inner-city hospital ambulatory care practice. Patient activation was measured using the patient activation measure (PAM). Mean PAM scores and activation levels differed according to survey language (p < 0.001). US-born participants had higher mean PAM scores than persons born outside of the US. Participants living in the US longer had higher mean PAM scores than participants newer to the US. Levels of activation and mean PAM scores increased with greater comfort reading, speaking, and thinking in English. The mean PAM (SD) score of 61.5 (16.5) for Haitian Creole-speaking Caribbean Blacks was significantly lower than the mean PAM score of 68.8 (15.6) for English-speaking Caribbean Blacks (p value = 0.006). Although mean PAM scores did not significantly differ between Haitian Creole and Spanish speakers, PAM stages differed according to language of survey completion (p < 0.001), with a greater percentage of Haitian Creole speakers being categorized as stage 1 (least activated) as well as stage 4 (most activated). Spanish and Haitian Creole speakers have lower mean PAM scores than English speakers. Mean PAM scores did not differ between Hispanics and non-Hispanics or according to race, illustrating the need to examine the role of language and culture on patient activation.

Estimation of Energy Expenditure for Wheelchair Users Using a Physical Activity Monitoring System.

PubMed

Hiremath, Shivayogi V; Intille, Stephen S; Kelleher, Annmarie; Cooper, Rory A; Ding, Dan

2016-07-01

To develop and evaluate energy expenditure (EE) estimation models for a physical activity monitoring system (PAMS) in manual wheelchair users with spinal cord injury (SCI). Cross-sectional study. University-based laboratory environment, a semistructured environment at the National Veterans Wheelchair Games, and the participants' home environments. Volunteer sample of manual wheelchair users with SCI (N=45). Participants were asked to perform 10 physical activities (PAs) of various intensities from a list. The PAMS consists of a gyroscope-based wheel rotation monitor (G-WRM) and an accelerometer device worn on the upper arm or on the wrist. Criterion EE using a portable metabolic cart and raw sensor data from PAMS were collected during each of these activities. Estimated EE using custom models for manual wheelchair users based on either the G-WRM and arm accelerometer (PAMS-Arm) or the G-WRM and wrist accelerometer (PAMS-Wrist). EE estimation performance for the PAMS-Arm (average error ± SD: -9.82%±37.03%) and PAMS-Wrist (-5.65%±32.61%) on the validation dataset indicated that both PAMS-Arm and PAMS-Wrist were able to estimate EE for a range of PAs with <10% error. Moderate to high intraclass correlation coefficients (ICCs) indicated that the EE estimated by PAMS-Arm (ICC3,1=.82, P<.05) and PAMS-Wrist (ICC3,1=.89, P<.05) are consistent with the criterion EE. Availability of PA monitors can assist wheelchair users to track PA levels, leading toward a healthier lifestyle. The new models we developed can estimate PA levels in manual wheelchair users with SCI in laboratory and community settings. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Wind tunnel experimental study on the effect of PAM on soil wind erosion control.

PubMed

He, Ji-Jun; Cai, Qiang-Guo; Tang, Ze-Jun

2008-10-01

In recent years, high-molecular-weight anionic polyacrylamide (PAM) have been widely tested on a variety of soils, primarily in water erosion control. However, little information is available regarding the effectiveness of PAM on preventing soil loss from wind erosion. The research adopted room wind tunnel experiment, two kinds of soils were used which were from the agro-pastoral area of Inner Mongolia, the northwest of China, the clay content of soils were 22.0 and 13.7%, respectively. For these tests, all the treatments were performed under the condition of wind velocity of 14 m s(-1) and a blown angle of 8.75%, according to the actual situation of experimented area. The study results indicated that using PAM on the soil surface could enhance the capability of avoiding the wind erosion, at the same time, the effect of controlling wind soil erosion with 4 g m(-2) PAM was better than 2 g m(-2) PAM's. Economically, the 2 g m(-2) PAM used in soil surface can control wind erosion effectively in this region. The prophase PAM accumulated in soil could not improve the capability of avoiding the wind erosion, owing to the degradation of PAM in the soil and the continual tillage year after year. The texture of soil is a main factor influencing the capability of soil avoiding wind erosion. Soil with higher clay content has the higher capability of preventing soil from wind erosion than one with the opposite one under the together action of PAM and water.

Prediction of consensus binding mode geometries for related chemical series of positive allosteric modulators of adenosine and muscarinic acetylcholine receptors.

PubMed

Sakkal, Leon A; Rajkowski, Kyle Z; Armen, Roger S

2017-06-05

Following insights from recent crystal structures of the muscarinic acetylcholine receptor, binding modes of Positive Allosteric Modulators (PAMs) were predicted under the assumption that PAMs should bind to the extracellular surface of the active state. A series of well-characterized PAMs for adenosine (A 1 R, A 2A R, A 3 R) and muscarinic acetylcholine (M 1 R, M 5 R) receptors were modeled using both rigid and flexible receptor CHARMM-based molecular docking. Studies of adenosine receptors investigated the molecular basis of the probe-dependence of PAM activity by modeling in complex with specific agonist radioligands. Consensus binding modes map common pharmacophore features of several chemical series to specific binding interactions. These models provide a rationalization of how PAM binding slows agonist radioligand dissociation kinetics. M 1 R PAMs were predicted to bind in the analogous M 2 R PAM LY2119620 binding site. The M 5 R NAM (ML-375) was predicted to bind in the PAM (ML-380) binding site with a unique induced-fit receptor conformation. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Waste-Activated Sludge Fermentation for Polyacrylamide Biodegradation Improved by Anaerobic Hydrolysis and Key Microorganisms Involved in Biological Polyacrylamide Removal.

PubMed

Dai, Xiaohu; Luo, Fan; Zhang, Dong; Dai, Lingling; Chen, Yinguang; Dong, Bin

2015-07-06

During the anaerobic digestion of dewatered sludge, polyacrylamide (PAM), a chemical conditioner, can usually be consumed as a carbon and nitrogen source along with other organic matter (e.g., proteins and carbohydrates in the sludge). However, a significant accumulation of acrylamide monomers (AMs) was observed during the PAM biodegradation process. To improve the anaerobic hydrolysis of PAM, especially the amide hydrolysis process, and to avoid the generation of the intermediate product AM, a new strategy is reported herein that uses an initial pH of 9, 200 mg COD/L of PAM and a fermentation time of 17 d. First, response surface methodology (RSM) was applied to optimize PAM removal in the anaerobic digestion of the sludge. The biological hydrolysis of PAM reached 86.64% under the optimal conditions obtained from the RSM. Then, the mechanisms for the optimized parameters that significantly improved the biological hydrolysis of PAM were investigated by the synergistic effect of the main organic compounds in the sludge, the floc size distribution, and the enzymatic activities. Finally, semi-continuous-flow experiments for a microbial community study were investigated based on the determination of key microorganisms involved in the biological hydrolysis of PAM.

Minimizing the average distance to a closest leaf in a phylogenetic tree.

PubMed

Matsen, Frederick A; Gallagher, Aaron; McCoy, Connor O

2013-11-01

When performing an analysis on a collection of molecular sequences, it can be convenient to reduce the number of sequences under consideration while maintaining some characteristic of a larger collection of sequences. For example, one may wish to select a subset of high-quality sequences that represent the diversity of a larger collection of sequences. One may also wish to specialize a large database of characterized "reference sequences" to a smaller subset that is as close as possible on average to a collection of "query sequences" of interest. Such a representative subset can be useful whenever one wishes to find a set of reference sequences that is appropriate to use for comparative analysis of environmentally derived sequences, such as for selecting "reference tree" sequences for phylogenetic placement of metagenomic reads. In this article, we formalize these problems in terms of the minimization of the Average Distance to the Closest Leaf (ADCL) and investigate algorithms to perform the relevant minimization. We show that the greedy algorithm is not effective, show that a variant of the Partitioning Around Medoids (PAM) heuristic gets stuck in local minima, and develop an exact dynamic programming approach. Using this exact program we note that the performance of PAM appears to be good for simulated trees, and is faster than the exact algorithm for small trees. On the other hand, the exact program gives solutions for all numbers of leaves less than or equal to the given desired number of leaves, whereas PAM only gives a solution for the prespecified number of leaves. Via application to real data, we show that the ADCL criterion chooses chimeric sequences less often than random subsets, whereas the maximization of phylogenetic diversity chooses them more often than random. These algorithms have been implemented in publicly available software.

Methods for decoding Cas9 protospacer adjacent motif (PAM) sequences: A brief overview.

PubMed

Karvelis, Tautvydas; Gasiunas, Giedrius; Siksnys, Virginijus

2017-05-15

Recently the Cas9, an RNA guided DNA endonuclease, emerged as a powerful tool for targeted genome manipulations. Cas9 protein can be reprogrammed to cleave, bind or nick any DNA target by simply changing crRNA sequence, however a short nucleotide sequence, termed PAM, is required to initiate crRNA hybridization to the DNA target. PAM sequence is recognized by Cas9 protein and must be determined experimentally for each Cas9 variant. Exploration of Cas9 orthologs could offer a diversity of PAM sequences and novel biochemical properties that may be beneficial for genome editing applications. Here we briefly review and compare Cas9 PAM identification assays that can be adopted for other PAM-dependent CRISPR-Cas systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Low Temperature Plasma for the Treatment of Epithelial Cancer Cells

NASA Astrophysics Data System (ADS)

Mohades, Soheila

Biomedical applications of low temperature plasmas (LTP) may lead to a paradigm shift in treating various diseases by conducting fundamental research on the effects of LTP on cells, tissues, organisms (plants, insects, and microorganisms). This is a rapidly growing interdisciplinary research field that involves engineering, physics, life sciences, and chemistry to find novel solutions for urgent medical needs. Effects of different LTP sources have shown the anti-tumor properties of plasma exposure; however, there are still many unknowns about the interaction of plasma with eukaryotic cells which must be elucidated in order to evaluate the practical potential of plasma in cancer treatment. Plasma, the fourth state of matter, is composed of electrons, ions, reactive molecules (radicals and non-radicals), excited species, radiation, and heat. A sufficient dose (time) of plasma exposure can induce death in cancer cells. The plasma pencil is employed to study the anti-tumor properties of this treatment on epithelial cells. The plasma pencil has been previously used for the inactivation of bacteria, destroying amyloid fibrils, and the killing of various cancer cells. Bladder cancer is the 9th leading cause of cancer. In this dissertation, human urinary bladder tissue with the squamous cell carcinoma disease (SCaBER cells) is treated with LTP utilizing two different approaches: direct plasma exposure and Plasma Activated Media (PAM) as an advancement to the treatment. PAM is produced by exposing a liquid cell culture medium to the plasma pencil. Direct LTP treatment of cancer cells indicates a dose-dependent killing effect at post-treatment times. Similarly, PAM treatment shows an anti-cancer effect by inducing substantial cell death. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have an important role in the biomedical effects of LTP treatment. This study demonstrates the capability of the plasma pencil to transport ROS/RNS into cell culture media leading to their activation. The effectiveness of PAM against SCaBER cells is the highest when it is used immediately after preparation. It is found that the killing effect of PAM decreases gradually over time, depending on the dose of plasma exposure. Hydrogen peroxide is known as one of the most stable and impactful ROS in biological systems. Measurements show that the plasma pencil generates a significant amount of hydrogen peroxide in PAM. Interestingly, the concentration of hydrogen peroxide in PAM decreases gradually over time, which correlates well with the decrease of PAM effectiveness with storage time. While the effects of PAM treatment on cancerous epithelial cell lines have been studied, much less is known about the interaction of PAM with normal epithelial cells. Effects of PAM on non-cancerous Madin-Darby Canine kidney (MDCK) epithelial cells indicates that MDCK cells are much more robust than SCaBER cells against PAM treatment. The dose of PAM, which causes a widespread death in SCaBER cells, does not significantly impact viability and morphology of MDCK cells. Time-lapse imaging of normal cells shows that PAM treatment inhibits cell proliferation and random migration. In addition, immunofluorescence staining shows that PAM treatment causes a significant reduction in the nuclear localization of proliferation marker, Ki-67, without any damage to the morphological properties of cells including adhesions and cytoskeleton function. This dissertation clearly demonstrates the capability of PAM treatment in inducing death in cancerous cells that can be important for cancer therapy. Hydrogen peroxide is identified as an important ROS responsible for the anti-tumor properties of PAM, although much additional work remains to comprehensively understand all the involved ROS/RNS and their role in PAM treatment.

Risk of fatal amebic meningoencephalitis from waterborne Naegleria fowleri

NASA Astrophysics Data System (ADS)

Hallenbeck, William H.; Brenniman, Gary R.

1989-03-01

Primary amebic meningoencephalitis (PAM) is a fatal disease of the central nervous system caused primarily by the free-living ameba, Naegleria fowleri. PAM is primarily associated with swimming in various types of fresh water. World literature was reviewed in order to derive a risk analysis model that would be helpful in the management of PAM. The management of PAM risk is difficult, and the prevention of PAM is almost impossible. However, it is reassuring that the cases and risks estimated by the risk model are usually small, with individual annual risk on the order of 10-6.

Effect of polyacrylamide on soil physical and hydraulic properties

NASA Astrophysics Data System (ADS)

Albalasmeh, Ammar; Gharaibeh, Mamoun; Hamdan, Enas

2017-04-01

The effect of polyacrylamide (PAM), as a soil conditioner, on selected soil physical and hydraulic properties (infiltration rate (f(t)), hydraulic conductivity (HC), soil moisture content, aggregate stability (AS), and soil aggregation) was studied. Two types of anionic PAM were used: Low molecular weight (LPAM) (1×105 g/mol) with medium charge density (33-43) and high molecular weight (HPAM) (1-6×106 g/mol) with medium charge density (33-43). Sandy loam soil was packed into plastic columns; PAM solutions at different concentrations (100, 250, 500, and 1000 mg L-1) were used every two weeks in four wetting and drying cycles. The highest infiltration rate value was 0.16 mm s-1 at 1000 mg/L low molecular weight PAM while the highest value of infiltration rate in high PAM molecular weight was 0.11 mm s-1 compared to the control (0.01 mm s-1). Soil HC was about 3.00 cm h-1 for LPAM at 1000 mg L-1 PAM, while the highest value for HPAM was about 2 cm h-1 for the same concentration, compared to the control. The amount of water that can be held by soil increased with the addition of PAM compared to the control. Differences in water content were more pronounced in LPAM compared to HPAM. The addition of LPAM increased aggregate stability proportional to PAM concentration. Moreover, 1000 mg L-1 produced the highest aggregate stability (19{%}) compared to HPAM and control (7{%} and 5{%}), respectively. As PAM concentration increased, the geometric mean diameter (GMD) increased for both PAM molecular weights compared to control (0.4 mm). At 1000 mg L-1 the GMD values were 0.88 mm and 0.79 mm for LPAM and HPAM, respectively. The addition of PAM improved soil physical and hydraulic properties, with an advantage to LPAM owing that to its ability to penetrate soil aggregates and therefore stabilizing them.

Mapping PAM4 (clivatuzumab), a monoclonal antibody in clinical trials for early detection and therapy of pancreatic ductal adenocarcinoma, to MUC5AC mucin.

PubMed

Gold, David V; Newsome, Guy; Liu, Donglin; Goldenberg, David M

2013-11-20

PAM4, an antibody that has high specificity for pancreatic ductal adenocarcinoma (PDAC), compared to normal pancreas, benign lesions of the pancreas, and cancers originating from other tissues, is being investigated as a biomarker for early detection, as well as antibody-targeted imaging and therapy. Therefore, the identity of the antigen bound by this monoclonal antibody (MAb) can provide information leading to improved use of the antibody. Prior results suggested the antigen is a mucin-type glycoprotein rich in cysteine disulfide bridges that provide stable conformation for the PAM4-epitope. Indirect and sandwich enzyme immunoassays (EIA) were performed to compare and contrast the reactivity of PAM4 with several anti-mucin antibodies having known reactivity to specific mucin species (e.g., MUC1, MUC4, MUC5AC, etc.). Studies designed to block reactivity of PAM4 with its specific antigen also were performed. We demonstrate that MAbs 2-11 M1 and 45 M1, each reactive with MUC5AC, are able to provide signal in a heterologous sandwich immunoassay where PAM4 is the capture antibody. Further, we identify MAbs 21 M1, 62 M1, and 463 M1, each reactive with MUC5AC, as inhibiting the reaction of PAM4 with its specific epitope. MAbs directed to MUC1, MUC3, MUC4, MUC16 and CEACAM6 are not reactive with PAM4-captured antigen, nor are they able to block the reaction of PAM4 with its antigen. These data implicate MUC5AC as a specific mucin species to which PAM4 is reactive. Furthermore, this realization may allow for the improvement of the current PAM4 serum-based immunoassay for detection of early-stage PDAC by the application of anti-MUC5AC MAbs as probes in this sandwich EIA.

The PHOTOSYNTHESIS AFFECTED MUTANT68–LIKE Protein Evolved from a PSII Assembly Factor to Mediate Assembly of the Chloroplast NAD(P)H Dehydrogenase Complex in Arabidopsis[W

PubMed Central

Armbruster, Ute; Rühle, Thilo; Kreller, Renate; Strotbek, Christoph; Zühlke, Jessica; Tadini, Luca; Blunder, Thomas; Hertle, Alexander P.; Qi, Yafei; Rengstl, Birgit; Nickelsen, Jörg; Frank, Wolfgang; Leister, Dario

2013-01-01

In vascular plants, the chloroplast NAD(P)H dehydrogenase complex (NDH-C) is assembled from five distinct subcomplexes, the membrane-spanning (subM) and the luminal (subL) subcomplexes, as well as subA, subB, and subE. The assembly process itself is poorly understood. Vascular plant genomes code for two related intrinsic thylakoid proteins, PHOTOSYNTHESIS-AFFECTED MUTANT68 (PAM68), a photosystem II assembly factor, and PHOTOSYNTHESIS-AFFECTED MUTANT68-LIKE (PAM68L). As we show here, inactivation of Arabidopsis thaliana PAM68L in the pam68l-1 mutant identifies PAM68L as an NDH-C assembly factor. The mutant lacks functional NDH holocomplexes and accumulates three distinct NDH-C assembly intermediates (subB, subM, and subA+L), which are also found in mutants defective in subB assembly (ndf5) or subM expression (CHLORORESPIRATORY REDUCTION4-3 mutant). NDH-C assembly in the cyanobacterium Synechocystis sp PCC 6803 and the moss Physcomitrella patens does not require PAM68 proteins, as demonstrated by the analysis of knockout lines for the single-copy PAM68 genes in these species. We conclude that PAM68L mediates the attachment of subB- and subM-containing intermediates to a complex that contains subA and subL. The evolutionary appearance of subL and PAM68L during the transition from mosses like P. patens to flowering plants suggests that the associated increase in the complexity of the NDH-C might have been facilitated by the recruitment of evolutionarily novel assembly factors like PAM68L. PMID:24096342

Screening of polymers on selected Hawaii soils for erosion reduction and particle settling

NASA Astrophysics Data System (ADS)

Teo, James A.; Ray, Chittaranjan; El-Swaify, Samir A.

2006-01-01

In recent years, high-molecular-weight anionic polyacrylamides (PAMs) have been tested on a variety of soils, primarily in temperate climates. However, little information is available regarding the effectiveness of PAM for preventing soil loss through runoff in tropical settings. Screening tests were performed using three negatively charged PAMs and one positively charged PAM on five Hawaii soils (two Oxisols, one Vertisol, and two Aridisols) to determine erosion loss, sediment settling, and aggregate stability. A laboratory-scale rainfall simulator was used to apply erosive rainfall at intensities from 5 to 8.5 cm h-1 at various PAM doses applied in both dry and solution forms. Soil detachment due to splash and runoff, as well as the runoff and percolate water volumes, were measured for initial and successive storms. The impact of PAM on particle settling and aggregate stability was also evaluated for selected soil-treatment combinations. Among the PAMs, Superfloc A-836 was most effective, and significantly reduced runoff and splash sediment loss for the Wahiawa Oxisol and Pakini Andisol at rates varying between 10 and 50 kg ha-1. Reduced runoff and splash sediment loss were also noted for PAM Aerotil-D when applied in solution form to the Wahiawa Oxisol. Significant reductions in soil loss were not noted for either the Lualualei Vertisol or the Holomua Oxisol. It is believed that the high montmorillonite content of the Lualualei Vertisol and the low cation-exchange capacity of the Holomua Oxisol diminished the effectiveness of the various PAMs tested. The polymers were also found to enhance sediment settling of all soils and helped improve their aggregate stability. This screening study shows the potential use of PAM for tropical soils for applications such as infiltration enhancement, runoff reduction, and enhanced sedimentation of detention ponds.

A histidine-rich linker region in peptidylglycine α-amidating monooxygenase has the properties of a pH sensor.

PubMed

Vishwanatha, Kurutihalli; Bäck, Nils; Mains, Richard E; Eipper, Betty A

2014-05-02

Decreasing luminal pH is thought to play a role in the entry of newly synthesized and endocytosed membrane proteins into secretory granules. The two catalytic domains of peptidylglycine α-amidating monooxygenase (PAM), a type I integral membrane protein, catalyze the sequential reactions that convert peptidyl-Gly substrates into amidated products. We explored the hypothesis that a conserved His-rich cluster (His-Gly-His-His) in the linker region connecting its two catalytic domains senses pH and affects PAM trafficking by mutating these His residues to Ala (Ala-Gly-Ala-Ala; H3A). Purified recombinant wild-type and H3A linker peptides were examined using circular dichroism and tryptophan fluorescence; mutation of the His cluster largely eliminated its pH sensitivity. An enzymatically active PAM protein with the same mutations (PAM-1/H3A) was expressed in HEK293 cells and AtT-20 corticotrope tumor cells. Metabolic labeling followed by immunoprecipitation revealed more rapid loss of newly synthesized PAM-1/H3A than PAM-1; although release of newly synthesized monofunctional PHM/H3A was increased, release of soluble bifunctional PAM/H3A, a product of the endocytic pathway, was decreased. Surface biotinylation revealed rapid loss of PAM-1/H3A, with no detectable return of the mutant protein to secretory granules. Consistent with its altered endocytic trafficking, little PAM-1/H3A was subjected to regulated intramembrane proteolysis followed by release of a small nuclear-targeted cytosolic fragment. AtT-20 cells expressing PAM-1/H3A adopted the morphology of wild-type AtT-20 cells; secretory products no longer accumulated in the trans-Golgi network and secretory granule exocytosis was more responsive to secretagogue.

Decontamination of chemical and biological warfare agents with a single multi-functional material.

PubMed

Amitai, Gabi; Murata, Hironobu; Andersen, Jill D; Koepsel, Richard R; Russell, Alan J

2010-05-01

We report the synthesis of new polymers based on a dimethylacrylamide-methacrylate (DMAA-MA) co-polymer backbone that support both chemical and biological agent decontamination. Polyurethanes containing the redox enzymes glucose oxidase and horseradish peroxidase can convert halide ions into active halogens and exert striking bactericidal activity against gram positive and gram negative bacteria. New materials combining those biopolymers with a family of N-alkyl 4-pyridinium aldoxime (4-PAM) halide-acrylate co-polymers offer both nucleophilic activity for the detoxification of organophosphorus nerve agents and internal sources of halide ions for generation of biocidal activity. Generation of free bromine and iodine was observed in the combined material resulting in bactericidal activity of the enzymatically formed free halogens that caused complete kill of E. coli (>6 log units reduction) within 1 h at 37 degrees C. Detoxification of diisopropylfluorophosphate (DFP) by the polyDMAA MA-4-PAM iodide component was dose-dependent reaching 85% within 30 min. A subset of 4-PAM-halide co-polymers was designed to serve as a controlled release reservoir for N-hydroxyethyl 4-PAM (HE 4-PAM) molecules that reactivate nerve agent-inhibited acetylcholinesterase (AChE). Release rates for HE 4-PAM were consistent with hydrolysis of the HE 4-PAM from the polymer backbone. The HE 4-PAM that was released from the polymer reactivated DFP-inhibited AChE at a similar rate to the oxime antidote 4-PAM. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Naegleria fowleri after 50 years: is it a neglected pathogen?

PubMed

Martínez-Castillo, Moisés; Cárdenas-Zúñiga, Roberto; Coronado-Velázquez, Daniel; Debnath, Anjan; Serrano-Luna, Jesús; Shibayama, Mineko

2016-09-01

It has been 50 years since the first case of primary amoebic meningoencephalitis (PAM), an acute and rapidly fatal disease of the central nervous system (CNS), was reported in Australia. It is now known that the aetiological agent of PAM is Naegleria fowleri, an amoeba that is commonly known as 'the brain-eating amoeba'. N. fowleri infects humans of different ages who are in contact with water contaminated with this micro-organism. N. fowleri is distributed worldwide and is found growing in bodies of freshwater in tropical and subtropical environments. The number of PAM cases has recently increased, and the rate of recovery from PAM has been estimated at only 5 %. Amphotericin B has been used to treat patients with PAM. However, it is important to note that there is no specific treatment for PAM. Moreover, this amoeba is considered a neglected micro-organism. Researchers have exerted great effort to design effective drugs to treat PAM and to understand the pathogenesis of PAM over the past 50 years, such as its pathology, molecular and cellular biology, diagnosis and prevention, and its biological implications, including its pathogenic genotypes, its distribution and its ecology. Given the rapid progression of PAM and its high mortality rate, it is important that investigations continue and that researchers collaborate to gain better understanding of the pathogenesis of this disease and, consequently, to improve the diagnosis and treatment of this devastating infection of the CNS.

A commercialized photoacoustic microscopy system with switchable optical and acoustic resolutions

NASA Astrophysics Data System (ADS)

Pu, Yang; Bi, Renzhe; Olivo, Malini; Zhao, Xiaojie

2018-02-01

A focused-scanning photoacoustic microscopy (PAM) is available to help advancing life science research in neuroscience, cell biology, and in vivo imaging. At this early stage, the only one manufacturer of PAM systems, MicroPhotoAcoustics (MPA; Ronkonkoma, NY), MPA has developed a commercial PAM system with switchable optical and acoustic resolution (OR- and AR-PAM), using multiple patents licensed from the lab of Lihong Wang, who pioneered photoacoustics. The system includes different excitation sources. Two kilohertz-tunable, Q-switched, Diode Pumped Solid-State (DPSS) lasers offering a up to 30kHz pulse repetition rate and 9 ns pulse duration with 532 and 559 nm to achieve functional photoacoustic tomography for sO2 (oxygen saturation of hemoglobin) imaging in OR-PAM. A Ti:sapphire laser from 700 to 900 nm to achieve deep-tissue imaging. OR-PAM provides up to 1 mm penetration depth and 5 μm lateral resolution. while AR-PAM offers up to 3 mm imaging depth and 45 μm lateral resolution. The scanning step sizes for OR- and AR-PAM are 0.625 and 6.25 μm, respectively. Researchers have used the system for a range of applications, including preclinical neural imaging; imaging of cell nuclei in intestine, ear, and leg; and preclinical human imaging of finger cuticle. With the continuation of new technological advancements and discoveries, MPA plans to further advance PAM to achieve faster imaging speed, higher spatial resolution at deeper tissue layer, and address a broader range of biomedical applications.

KSC-00pp0917

NASA Image and Video Library

2000-07-12

In the Orbiter Processing Facility bay 1, STS-92 crew members, along with Boeing workers, look closely at the tools they will be using on their mission. The crew comprises Commander Brian Duffy, Pilot Pam Melroy and Mission Specialists Koichi Wakata, Leroy Chiao, Jeff Wisoff, Michael Lopez-Alegria and Bill McArthur. STS-92 is scheduled to launch Oct. 5 on Shuttle Discovery from Launch Pad 39A on the fifth flight to the International Space Station. Discovery will carry the Integrated Truss Structure (ITS) Z1, Pressurized Mating Adapter 3, Ku-band Communications System, and Control Moment Gyros (CMGs)

Plectranthus amboinicus leaf extract mediated synthesis of zinc oxide nanoparticles and its control of methicillin resistant Staphylococcus aureus biofilm and blood sucking mosquito larvae

NASA Astrophysics Data System (ADS)

Vijayakumar, S.; Vinoj, G.; Malaikozhundan, B.; Shanthi, S.; Vaseeharan, B.

2015-02-01

In this study, zinc oxide nanoparticles were biologically synthesized using the leaf extract of Plectranthus amboinicus (Pam-ZnO NPs). The synthesized Pam-ZnO NPs were characterized by UV-Vis spectrophotometer, FTIR, TEM and XRD analysis. TEM analysis of Pam-ZnO NPs showed the average size of about 20-50 nm. Pam-ZnO NPs control the growth of methicillin-resistant Staphylococcus aureus biofilms (MRSA ATCC 33591) at the concentration of 8-10 μg/ml. Confocal laser scanning microscope (CLSM) images revealed that Pam-ZnO NPs strongly inhibited the biofilm forming ability of S. aureus. In addition, Pam-ZnO NPs showed 100% mortality of fourth instar mosquito larvae of Anopheles stephensi, Culex quinquefasciatus and Culex tritaeniorhynchus at the concentration of 8 and 10 μg/ml. The histopathological studies of Pam-ZnO NPs treated A. stephensi and C. quinquefasciatus larvae revealed the presence of damaged cells and tissues in the mid-gut. The damaged tissues suffered major changes including rupture and disintegration of epithelial layer and cellular vacuolization. The present study conclude that Pam-ZnO NPs showed effective control of S. aureus biofilms and mosquito larvae by damaging the mid gut cells.

Bioelectricity-assisted partial degradation of linear polyacrylamide in a bioelectrochemical system.

PubMed

Cui, Yu-Zhi; Zhang, Jian; Sun, Min; Zhai, Lin-Feng

2015-01-01

The wide application of water-soluble linear polyacrylamides (PAMs) can cause serious environmental pollution. Biological treatment of PAMs receives very limited efficiency due to their recalcitrance to the microbial degradation. Here, we show the bioelectrochemical system (BES) can be used as an effective strategy to improve the biodegradation efficiency of PAMs. A linear PAM with viscosity-average molecular weight of 5 × 10(6) was treated in the anodic chamber of BES reactor, and the change of PAM structure during the degradation process was investigated. The anodic bacteria in the BES demonstrated abilities to utilize the PAM as the sole carbon and nitrogen source to generate electricity. Both the anode-attached and planktonic bacteria contributed to the electricity generation, while the anode-attached community exhibited stronger electron transfer ability than the planktonic one. The closed-circuit and open-circuit operations of the BES reactor obtained chemical oxygen demand (COD) removal efficiencies of 32.5 and 7.4 %, respectively, implying the generation of bioelectricity could enhance the biodegradation of PAM. Structure analysis suggested the carbon chain of PAM was partially degraded in the BES, producing polymeric products with lower molecular weight. The microbial cleavage of the carbon chain was proposed to start from the "head-to-head" linkages and end with the formation of ether bonds.

Probing adsorption of polyacrylamide-based polymers on anisotropic Basal planes of kaolinite using quartz crystal microbalance.

PubMed

Alagha, Lana; Wang, Shengqun; Yan, Lujie; Xu, Zhenghe; Masliyah, Jacob

2013-03-26

Quartz crystal microbalance with dissipation (QCM-D) was applied to investigate the adsorption characteristics of polyacrylamide-based polymers (PAMs) on anisotropic basal planes of kaolinite. Kaolinite basal planes were differentiated by depositing kaolinite nanoparticles (KNPs) on silica and alumina sensors in solutions of controlled pH values. Adsorption of an in-house synthesized organic-inorganic Al(OH)3-PAM (Al-PAM) as an example of cationic hybrid PAM and a commercially available partially hydrolyzed polyacrylamide (MF1011) as an example of anionic PAM was studied. Cationic Al-PAM was found to adsorb irreversibly and preferentially on tetrahedral silica basal planes of kaolinite. In contrast, anionic MF1011 adsorbed strongly on aluminum-hydroxy basal planes, while its adsorption on tetrahedral silica basal planes was weak and reversible. Adsorption study revealed that both electrostatic attraction and hydrogen-bonding mechanisms contribute to adsorption of PAMs on kaolinite. The adsorbed Al-PAM layer was able to release trapped water overtime and became more compact, while MF1011 film became more dissipative as backbones stretched out from kaolinite surface with minimal overlapping. Experimental results obtained from this study provide clear insights into the phenomenon that governs flocculation-based solid-liquid separation processes using multicomponent flocculants of anionic and cationic nature.

Waste-Activated Sludge Fermentation for Polyacrylamide Biodegradation Improved by Anaerobic Hydrolysis and Key Microorganisms Involved in Biological Polyacrylamide Removal

PubMed Central

Dai, Xiaohu; Luo, Fan; Zhang, Dong; Dai, Lingling; Chen, Yinguang; Dong, Bin

2015-01-01

During the anaerobic digestion of dewatered sludge, polyacrylamide (PAM), a chemical conditioner, can usually be consumed as a carbon and nitrogen source along with other organic matter (e.g., proteins and carbohydrates in the sludge). However, a significant accumulation of acrylamide monomers (AMs) was observed during the PAM biodegradation process. To improve the anaerobic hydrolysis of PAM, especially the amide hydrolysis process, and to avoid the generation of the intermediate product AM, a new strategy is reported herein that uses an initial pH of 9, 200 mg COD/L of PAM and a fermentation time of 17 d. First, response surface methodology (RSM) was applied to optimize PAM removal in the anaerobic digestion of the sludge. The biological hydrolysis of PAM reached 86.64% under the optimal conditions obtained from the RSM. Then, the mechanisms for the optimized parameters that significantly improved the biological hydrolysis of PAM were investigated by the synergistic effect of the main organic compounds in the sludge, the floc size distribution, and the enzymatic activities. Finally, semi-continuous-flow experiments for a microbial community study were investigated based on the determination of key microorganisms involved in the biological hydrolysis of PAM. PMID:26144551

A low-cost photoacoustic microscopy system with a laser diode excitation

PubMed Central

Wang, Tianheng; Nandy, Sreyankar; Salehi, Hassan S.; Kumavor, Patrick D.; Zhu, Quing

2014-01-01

Photoacoustic microscopy (PAM) is capable of mapping microvasculature networks in biological tissue and has demonstrated great potential for biomedical applications. However, the clinical application of the PAM system is limited due to the use of bulky and expensive pulsed laser sources. In this paper, a low-cost optical-resolution PAM system with a pulsed laser diode excitation has been introduced. The lateral resolution of this PAM system was estimated to be 7 µm by imaging a carbon fiber. The phantoms made of polyethylene tubes filled with blood and a mouse ear were imaged to demonstrate the feasibility of this PAM system for imaging biological tissues. PMID:25401019

Empirical modeling of dynamic behaviors of pneumatic artificial muscle actuators.

PubMed

Wickramatunge, Kanchana Crishan; Leephakpreeda, Thananchai

2013-11-01

Pneumatic Artificial Muscle (PAM) actuators yield muscle-like mechanical actuation with high force to weight ratio, soft and flexible structure, and adaptable compliance for rehabilitation and prosthetic appliances to the disabled as well as humanoid robots or machines. The present study is to develop empirical models of the PAM actuators, that is, a PAM coupled with pneumatic control valves, in order to describe their dynamic behaviors for practical control design and usage. Empirical modeling is an efficient approach to computer-based modeling with observations of real behaviors. Different characteristics of dynamic behaviors of each PAM actuator are due not only to the structures of the PAM actuators themselves, but also to the variations of their material properties in manufacturing processes. To overcome the difficulties, the proposed empirical models are experimentally derived from real physical behaviors of the PAM actuators, which are being implemented. In case studies, the simulated results with good agreement to experimental results, show that the proposed methodology can be applied to describe the dynamic behaviors of the real PAM actuators. Copyright © 2013 ISA. Published by Elsevier Ltd. All rights reserved.

Moderate plasma activated media suppresses proliferation and migration of MDCK epithelial cells

NASA Astrophysics Data System (ADS)

Mohades, Soheila; Laroussi, Mounir; Maruthamuthu, Venkat

2017-05-01

Low-temperature plasma has been shown to have diverse biomedical uses, including its applications in cancer and wound healing. One recent approach in treating mammalian cells with plasma is through the use of plasma activated media (PAM), which is produced by exposing cell culture media to plasma. While the adverse effects of PAM treatment on cancerous epithelial cell lines have been recently studied, much less is known about the interaction of PAM with normal epithelial cells. In this paper, non-cancerous canine kidney MDCK (Madin-Darby Canine Kidney) epithelial cells were treated by PAM and time-lapse microscopy was used to directly monitor their proliferation and random migration upon treatment. While longer durations of PAM treatment led to cell death, we found that moderate levels of PAM treatment inhibited proliferation in these epithelial cells. We also found that PAM treatment reduced random cell migration within epithelial islands. Immunofluorescence staining showed that while there were no major changes in the actin/adhesion apparatus, there was a significant change in the nuclear localization of proliferation marker Ki-67, consistent with our time-lapse results.

Cas9 specifies functional viral targets during CRISPR-Cas adaptation.

PubMed

Heler, Robert; Samai, Poulami; Modell, Joshua W; Weiner, Catherine; Goldberg, Gregory W; Bikard, David; Marraffini, Luciano A

2015-03-12

Clustered regularly interspaced short palindromic repeat (CRISPR) loci and their associated (Cas) proteins provide adaptive immunity against viral infection in prokaryotes. Upon infection, short phage sequences known as spacers integrate between CRISPR repeats and are transcribed into small RNA molecules that guide the Cas9 nuclease to the viral targets (protospacers). Streptococcus pyogenes Cas9 cleavage of the viral genome requires the presence of a 5'-NGG-3' protospacer adjacent motif (PAM) sequence immediately downstream of the viral target. It is not known whether and how viral sequences flanked by the correct PAM are chosen as new spacers. Here we show that Cas9 selects functional spacers by recognizing their PAM during spacer acquisition. The replacement of cas9 with alleles that lack the PAM recognition motif or recognize an NGGNG PAM eliminated or changed PAM specificity during spacer acquisition, respectively. Cas9 associates with other proteins of the acquisition machinery (Cas1, Cas2 and Csn2), presumably to provide PAM-specificity to this process. These results establish a new function for Cas9 in the genesis of prokaryotic immunological memory.

GPR40 partial agonists and AgoPAMs: Differentiating effects on glucose and hormonal secretions in the rodent

PubMed Central

Pachanski, Michele J.; Kirkland, Melissa E.; Kosinski, Daniel T.; Mane, Joel; Cheewatrakoolpong, Boonlert; Xue, Jiyan; Szeto, Daphne; Forrest, Gail; Miller, Corin; Bunzel, Michelle; Plummer, Christopher W.; Chobanian, Harry R.; Miller, Michael W.; Souza, Sarah; Thomas-Fowlkes, Brande S.; Ogawa, Aimie M.; Weinglass, Adam B.; Di Salvo, Jerry; Li, Xiaoyan; Feng, Yue; Tatosian, Daniel A.; Howard, Andrew D.; Colletti, Steven L.

2017-01-01

GPR40 agonists are effective antidiabetic agents believed to lower glucose through direct effects on the beta cell to increase glucose stimulated insulin secretion. However, not all GPR40 agonists are the same. Partial agonists lower glucose through direct effects on the pancreas, whereas GPR40 AgoPAMs may incorporate additional therapeutic effects through increases in insulinotrophic incretins secreted by the gut. Here we describe how GPR40 AgoPAMs stimulate both insulin and incretin secretion in vivo over time in diabetic GK rats. We also describe effects of AgoPAMs in vivo to lower glucose and body weight beyond what is seen with partial GPR40 agonists in both the acute and chronic setting. Further comparisons of the glucose lowering profile of AgoPAMs suggest these compounds may possess greater glucose control even in the presence of elevated glucagon secretion, an unexpected feature observed with both acute and chronic treatment with AgoPAMs. Together these studies highlight the complexity of GPR40 pharmacology and the potential additional benefits AgoPAMs may possess above partial agonists for the diabetic patient. PMID:29053717

Haloarcula hispanica CRISPR authenticates PAM of a target sequence to prime discriminative adaptation

PubMed Central

Li, Ming; Wang, Rui; Xiang, Hua

2014-01-01

The prokaryotic immune system CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated genes) adapts to foreign invaders by acquiring their short deoxyribonucleic acid (DNA) fragments as spacers, which guide subsequent interference to foreign nucleic acids based on sequence matching. The adaptation mechanism avoiding acquiring ‘self’ DNA fragments is poorly understood. In Haloarcula hispanica, we previously showed that CRISPR adaptation requires being primed by a pre-existing spacer partially matching the invader DNA. Here, we further demonstrate that flanking a fully-matched target sequence, a functional PAM (protospacer adjacent motif) is still required to prime adaptation. Interestingly, interference utilizes only four PAM sequences, whereas adaptation-priming tolerates as many as 23 PAM sequences. This relaxed PAM selectivity explains how adaptation-priming maximizes its tolerance of PAM mutations (that escape interference) while avoiding mis-targeting the spacer DNA within CRISPR locus. We propose that the primed adaptation, which hitches and cooperates with the interference pathway, distinguishes target from non-target by CRISPR ribonucleic acid guidance and PAM recognition. PMID:24803673

Analysis of Minimum Efficiency Performance Standards for Residential General Service Lighting in Chile

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

Letschert, Virginie E.; McNeil, Michael A.; Leiva Ibanez, Francisco Humberto

2011-06-01

Minimum Efficiency Performance Standards (MEPS) have been chosen as part of Chile's national energy efficiency action plan. As a first MEPS, the Ministry of Energy has decided to focus on a regulation for lighting that would ban the sale of inefficient bulbs, effectively phasing out the use of incandescent lamps. Following major economies such as the US (EISA, 2007) , the EU (Ecodesign, 2009) and Australia (AS/NZS, 2008) who planned a phase out based on minimum efficacy requirements, the Ministry of Energy has undertaken the impact analysis of a MEPS on the residential lighting sector. Fundacion Chile (FC) and Lawrencemore » Berkeley National Laboratory (LBNL) collaborated with the Ministry of Energy and the National Energy Efficiency Program (Programa Pais de Eficiencia Energetica, or PPEE) in order to produce a techno-economic analysis of this future policy measure. LBNL has developed for CLASP (CLASP, 2007) a spreadsheet tool called the Policy Analysis Modeling System (PAMS) that allows for evaluation of costs and benefits at the consumer level but also a wide range of impacts at the national level, such as energy savings, net present value of savings, greenhouse gas (CO2) emission reductions and avoided capacity generation due to a specific policy. Because historically Chile has followed European schemes in energy efficiency programs (test procedures, labelling program definitions), we take the Ecodesign commission regulation No 244/2009 as a starting point when defining our phase out program, which means a tiered phase out based on minimum efficacy per lumen category. The following data were collected in order to perform the techno-economic analysis: (1) Retail prices, efficiency and wattage category in the current market, (2) Usage data (hours of lamp use per day), and (3) Stock data, penetration of efficient lamps in the market. Using these data, PAMS calculates the costs and benefits of efficiency standards from two distinct but related perspectives: (1) The Life-Cycle Cost (LCC) calculation examines costs and benefits from the perspective of the individual household; and (2) The National Perspective projects the total national costs and benefits including both financial benefits, and energy savings and environmental benefits. The national perspective calculations are called the National Energy Savings (NES) and the Net Present Value (NPV) calculations. PAMS also calculate total emission mitigation and avoided generation capacity. This paper describes the data and methodology used in PAMS and presents the results of the proposed phase out of incandescent bulbs in Chile.« less

Cloning and characterization of a novel amidase from Paracoccus sp. M-1, showing aryl acylamidase and acyl transferase activities.

PubMed

Shen, Weiliang; Chen, Honghong; Jia, Kaizhi; Ni, Jun; Yan, Xin; Li, Shunpeng

2012-05-01

A novel amidase gene, designated pamh, was cloned from Paracoccus sp. M-1. Site-directed mutagenesis and bioinformatic analysis showed that the PamH protein belonged to the amidase signature enzyme family. PamH was expressed in Escherichia coli, purified, and characterized. The molecular mass of PamH was determined to be 52 kDa with an isoelectric point of 5.13. PamH displayed its highest enzymatic activity at 45°C and at pH 8.0 and was stable within a pH range of 5.0-10.0. The PamH enzyme exhibited amidase activity, aryl acylamidase activity, and acyl transferase activity, allowing it to function across a very broad substrate spectrum. PamH was highly active on aromatic and short-chain aliphatic amides (benzamide and propionamide), moderately active on amino acid amides, and possessed weak urease activity. Of the anilides examined, only propanil was a good substrate for PamH. For propanil, the k (cat) and K (m) were 2.8 s(-1) and 158 μM, respectively, and the catalytic efficiency value (k (cat)/K (m)) was 0.018 μM(-1) s(-1). In addition, PamH was able to catalyze the acyl transfer reaction to hydroxylamine for both amide and anilide substrates, including acetamide, propanil, and 4-nitroacetanilide; the highest reaction rate was shown with isobutyramide. These characteristics make PamH an excellent candidate for environmental remediation and an important enzyme for the biosynthesis of novel amides.

Blood-brain barrier penetration of novel pyridinealdoxime methiodide (PAM)-type oximes examined by brain microdialysis with LC-MS/MS

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

Okuno, Sou; Sakurada, Koichi; Ohta, Hikoto

2008-02-15

To develop a new reactivator of inhibited acetylcholinesterase (AChE) that can easily penetrate the blood-brain barrier (BBB), BBB penetration of 6 known and novel pyridinealdoxime methiodide (PAM)-type oximes (alkylPAMs) with relatively high reactivation activities was examined by in vivo rat brain microdialysis with liquid chromatography-mass spectrometry (LC-MS/MS). The 50% lethal dose (LD{sub 50}) of alkylPAMs was intravenously determined for Wistar rats, then the limit of detection, quantification range and linearity of the calibration curve of the alkylPAMs in dialysate and blood were determined by LC-MS/MS. Following 10% LD{sub 50} intravenous administration of the alkylPAMs, 4-[(hydroxyimino) methyl]-1-(2-phenylethyl) pyridinium bromide (4-PAPE) andmore » 4-[(hydroxyimino) methyl]-1-octylpyridinium bromide (4-PAO) appeared in the dialysate. Striatal extracellular fluid/blood concentration ratios were 0.039 {+-} 0.018 and 0.301 {+-} 0.183 (mean {+-} SEM), respectively, 1 h after treatment. This is the first report of BBB penetration of 4-PAPE, and the concentration ratio was smaller than that of 2-PAM.The mean BBB penetration of 4-PAO was approximately 30%, indicating that intravenous administration of 4-PAO may be effective for the reactivation of blocked cholinesterase in the brain. However, the toxicity of 4-PAO (LD{sub 50}; 8.89 mg/kg) was greater than that of 2-PAM. Further investigation is required to determine the effects of these alkylPAMs in organophosphate poisoning.« less

Simple synthesis of nitrogen-rich polymer network and its further amination with PEI for CO2 adsorption

NASA Astrophysics Data System (ADS)

Yin, Fengqin; Zhuang, Linzhou; Luo, Xianyong; Chen, Shuixia

2018-03-01

The nitrogen-rich polymer network (MF/PAM) was synthesized through interpenetration between the molecular chains of melamine-formaldehyde resin(MF) and polyacrylamide (PAM), to which the polyethylene imine (PEI) was grafted to obtain solid amine adsorbent (MF/PAM-g-PEI). Compared with MF, the swelling capacity of MF/PAM was greatly enhanced, it could swell rapidly and directly in water. Although the interpenetration of PAM into MF may reduce the porosity of MF/PAM, the CO2 capture capacity of the solid amine adsorbents (MF/PAM-g-PEI) could still reach 2.8 mmol/g at 273 K. The adsorbents also exhibited promising adsorption kinetics and regeneration performances. The kinetics observation showed that the Avrami model could better descript the CO2 adsorption process compared with the pseudo-first-order model and pseudo-second-order model. Meanwhile, the Avrami kinetic orders (na) range from 1.21 to 1.56, displaying that the both physisorption and chemisorption exist in the adsorption process and the PEI have successfully grafted onto the polymer network, which also can be confirmed by the adsorption activation energy value. After 18 adsorption-desorption recycles, the MF/PAM-g-PEI could preserve its initial capacity without any decrease. Our work provides a new method to achieve promising solid amine adsorbents with higher adsorption capacity and better regeneration performance.

Plectranthus amboinicus leaf extract mediated synthesis of zinc oxide nanoparticles and its control of methicillin resistant Staphylococcus aureus biofilm and blood sucking mosquito larvae.

PubMed

Vijayakumar, S; Vinoj, G; Malaikozhundan, B; Shanthi, S; Vaseeharan, B

2015-02-25

In this study, zinc oxide nanoparticles were biologically synthesized using the leaf extract of Plectranthus amboinicus (Pam-ZnO NPs). The synthesized Pam-ZnO NPs were characterized by UV-Vis spectrophotometer, FTIR, TEM and XRD analysis. TEM analysis of Pam-ZnO NPs showed the average size of about 20-50 nm. Pam-ZnO NPs control the growth of methicillin-resistant Staphylococcus aureus biofilms (MRSA ATCC 33591) at the concentration of 8-10 μg/ml. Confocal laser scanning microscope (CLSM) images revealed that Pam-ZnO NPs strongly inhibited the biofilm forming ability of S. aureus. In addition, Pam-ZnO NPs showed 100% mortality of fourth instar mosquito larvae of Anopheles stephensi, Culex quinquefasciatus and Culex tritaeniorhynchus at the concentration of 8 and 10 μg/ml. The histopathological studies of Pam-ZnO NPs treated A. stephensi and C. quinquefasciatus larvae revealed the presence of damaged cells and tissues in the mid-gut. The damaged tissues suffered major changes including rupture and disintegration of epithelial layer and cellular vacuolization. The present study conclude that Pam-ZnO NPs showed effective control of S. aureus biofilms and mosquito larvae by damaging the mid gut cells. Copyright © 2014 Elsevier B.V. All rights reserved.

Discrimination of Arabic Contrasts by American Learners

ERIC Educational Resources Information Center

Al Mahmoud, Mahmoud S.

2013-01-01

This article reports on second language perception of non-native contrasts. The study specifically tests the perceptual assimilation model (PAM) by examining American learners' ability to discriminate Arabic contrasts. Twenty two native American speakers enrolled in a university level Arabic language program took part in a forced choice AXB…

Measuring patient activation in Italy: Translation, adaptation and validation of the Italian version of the patient activation measure 13 (PAM13-I).

PubMed

Graffigna, Guendalina; Barello, Serena; Bonanomi, Andrea; Lozza, Edoardo; Hibbard, Judith

2015-12-23

The Patient Activation Measure (PAM13) is an instrument that assesses patient knowledge, skills, and confidence for disease self-management. This cross-sectional study was aimed to validate a culturally-adapted Italian Patient Activation Measure (PAM13-I) for patients with chronic conditions. 519 chronic patients were involved in the Italian validation study and responded to PAM13-I. The PAM 13 was translated into Italian by a standardized forward-backward translation. Data quality was assessed by mean, median, item response, missing values, floor and ceiling effects, internal consistency (Cronbach's alpha and average inter-item correlation), item-rest correlations. Rasch Model and differential item functioning assessed scale properties. Mean PAM13-I score was 66.2. Rasch analysis showed that the PAM13-I is a good measure of patient activation. The level of internal consistency was good (α = 0.88). For all items, the distribution of answers was left-skewed, with a small floor effect (range 1.7-4.5 %) and a moderate ceiling effect (range 27.6-55.0 %). The Italian version formed a unidimensional, probabilistic Guttman-like scale explaining 41 % of the variance. The PAM13-I has been demonstrated to be a valid and reliable measure of patient activation and the present study suggests its applicability to the Italian-speaking chronic patient population. The measure has good psychometric properties and appears to be consistent with the developmental nature of the patient activation phenomenon, although it presents a different ranking order of the items comparing to the American version. PAM13-I can be a useful assessment tool to evaluate interventions aimed at improving patient engagement in healthcare and to train doctors in attuning their communication to the level of patients' activation. Future research could be conducted to further confirm the validity of the PAM13-I.

Achievable Strength-Based Signal Detection in Quantity-Constrained PAM OOK Concentration-Encoded Molecular Communication.

PubMed

Mahfuz, Mohammad Upal

2016-10-01

In this paper, the expressions of achievable strength-based detection probabilities of concentration-encoded molecular communication (CEMC) system have been derived based on finite pulsewidth (FP) pulse-amplitude modulated (PAM) on-off keying (OOK) modulation scheme and strength threshold. An FP-PAM system is characterized by its duty cycle α that indicates the fraction of the entire symbol duration the transmitter remains on and transmits the signal. Results show that the detection performance of an FP-PAM OOK CEMC system significantly depends on the statistical distribution parameters of diffusion-based propagation noise and intersymbol interference (ISI). Analytical detection performance of an FP-PAM OOK CEMC system under ISI scenario has been explained and compared based on receiver operating characteristics (ROC) for impulse (i.e., spike)-modulated (IM) and FP-PAM CEMC schemes. It is shown that the effects of diffusion noise and ISI on ROC can be explained separately based on their communication range-dependent statistics. With full duty cycle, an FP-PAM scheme provides significantly worse performance than an IM scheme. The paper also analyzes the performance of the system when duty cycle, transmission data rate, and quantity of molecules vary.

Structural Basis for the Altered PAM Recognition by Engineered CRISPR-Cpf1.

PubMed

Nishimasu, Hiroshi; Yamano, Takashi; Gao, Linyi; Zhang, Feng; Ishitani, Ryuichiro; Nureki, Osamu

2017-07-06

The RNA-guided Cpf1 nuclease cleaves double-stranded DNA targets complementary to the CRISPR RNA (crRNA), and it has been harnessed for genome editing technologies. Recently, Acidaminococcus sp. BV3L6 (AsCpf1) was engineered to recognize altered DNA sequences as the protospacer adjacent motif (PAM), thereby expanding the target range of Cpf1-mediated genome editing. Whereas wild-type AsCpf1 recognizes the TTTV PAM, the RVR (S542R/K548V/N552R) and RR (S542R/K607R) variants can efficiently recognize the TATV and TYCV PAMs, respectively. However, their PAM recognition mechanisms remained unknown. Here we present the 2.0 Å resolution crystal structures of the RVR and RR variants bound to a crRNA and its target DNA. The structures revealed that the RVR and RR variants primarily recognize the PAM-complementary nucleotides via the substituted residues. Our high-resolution structures delineated the altered PAM recognition mechanisms of the AsCpf1 variants, providing a basis for the further engineering of CRISPR-Cpf1. Copyright © 2017 Elsevier Inc. All rights reserved.

Polyacrylamide grafted cellulose as an eco-friendly flocculant: Key factors optimization of flocculation to surfactant effluent.

PubMed

Zhu, Hangcheng; Zhang, Yong; Yang, Xiaogang; Shao, Lan; Zhang, Xiumei; Yao, Juming

2016-01-01

The discharge of effluents from surfactant manufacturers is giving rise to increasingly serious environmental problems. In order to develop the eco-friendly flocculation materials to achieve effective removal of pollutants from the surfactant effluents, the bamboo pulp cellulose from Phyllostachys heterocycla is employed as the skeleton material to synthesize an eco-friendly bamboo pulp cellulose-g-polyacrylamide (BPC-g-PAM) for flocculation. The BPC-g-PAM is used with the metal ions as the coagulant to treat the effluent from a surfactant manufacturer. The response surface methodology coupled with Box-behnken design is employed to optimize the key factors of coagulation-flocculation. The results show that the combination of Fe(3+) with BPC-g-PAM achieves the best coagulation-flocculation performance like, the fast treatment time, minimum coagulant and BPC-g-PAM dosages compared with the other two combinations of Al(3+) with BPC-g-PAM and Ca(2+) with BPC-g-PAM. Therefore, the combination of Fe(3+) with BPC-g-PAM is expected to promote its application for the pollution control in the surfactant manufacturers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cas9 Variants Expand the Target Repertoire in Caenorhabditis elegans

PubMed Central

Bell, Ryan T.; Fu, Becky X. H.; Fire, Andrew Z.

2016-01-01

The proliferation of CRISPR/Cas9-based methods in Caenorhabditis elegans has enabled efficient genome editing and precise genomic tethering of Cas9 fusion proteins. Experimental designs using CRISPR/Cas9 are currently limited by the need for a protospacer adjacent motif (PAM) in the target with the sequence NGG. Here we report the characterization of two modified Cas9 proteins in C. elegans that recognize NGA and NGCG PAMs. We found that each variant could stimulate homologous recombination with a donor template at multiple loci and that PAM specificity was comparable to that of wild-type Cas9. To directly compare effectiveness, we used CRISPR/Cas9 genome editing to generate a set of assay strains with a common single-guide RNA (sgRNA) target sequence, but that differ in the juxtaposed PAM (NGG, NGA, or NGCG). In this controlled setting, we determined that the NGA PAM Cas9 variant can be as effective as wild-type Cas9. We similarly edited a genomic target to study the influence of the base following the NGA PAM. Using four strains with four NGAN PAMs differing only at the fourth position and adjacent to the same sgRNA target, we observed that efficient homologous replacement was attainable with any base in the fourth position, with an NGAG PAM being the most effective. In addition to demonstrating the utility of two Cas9 mutants in C. elegans and providing reagents that permit CRISPR/Cas9 experiments with fewer restrictions on potential targets, we established a means to benchmark the efficiency of different Cas9::PAM combinations that avoids variations owing to differences in the sgRNA sequence. PMID:26680661

OFDM and PAM comparison using a high baudrate low resolution IM/DD interface for 400G Ethernet access.

PubMed

André, Nuno Sequeira; Louchet, Hadrien; Filsinger, Volker; Hansen, Erik; Richter, André

2016-05-30

We compare OFDM and PAM for 400G Ethernet based on a 3-bit high baudrate IM/DD interface at 1550nm. We demonstrate 27Gb/s and 32Gb/s transmission over 10km SSMF using OFDM and PAM respectively. We show that capacity can be improved through adaptation/equalization to achieve 42Gb/s and 64Gb/s for OFDM and PAM respectively. Experimental results are used to create realistic simulations to extrapolate the performance of both modulation formats under varied conditions. For the considered interface we found that PAM has the best performance, OFDM is impaired by quantization noise. When the resolution limitation is relaxed, OFDM shows better performance.

High-throughput ultraviolet photoacoustic microscopy with multifocal excitation

NASA Astrophysics Data System (ADS)

Imai, Toru; Shi, Junhui; Wong, Terence T. W.; Li, Lei; Zhu, Liren; Wang, Lihong V.

2018-03-01

Ultraviolet photoacoustic microscopy (UV-PAM) is a promising intraoperative tool for surgical margin assessment (SMA), one that can provide label-free histology-like images with high resolution. In this study, using a microlens array and a one-dimensional (1-D) array ultrasonic transducer, we developed a high-throughput multifocal UV-PAM (MF-UV-PAM). Our new system achieved a 1.6 ± 0.2 μm lateral resolution and produced images 40 times faster than the previously developed point-by-point scanning UV-PAM. MF-UV-PAM provided a readily comprehensible photoacoustic image of a mouse brain slice with specific absorption contrast in ˜16 min, highlighting cell nuclei. Individual cell nuclei could be clearly resolved, showing its practical potential for intraoperative SMA.

Cross-linkable graphene oxide embedded nanocomposite hydrogel with enhanced mechanics and cytocompatibility for tissue engineering.

PubMed

Liu, Xifeng; Miller, A Lee; Waletzki, Brian E; Lu, Lichun

2018-05-01

Graphene oxide (GO) is an attractive material that can be utilized to enhance the modulus and conductivities of substrates and hydrogels. To covalently cross-link graphene oxide sheets into hydrogels, abundant cross-linkable double bonds were introduced to synthesize the graphene-oxide-tris-acrylate sheet (GO-TrisA). Polyacrylamide (PAM) nanocomposite hydrogels were then fabricated with inherent covalently and permanently cross-linked GO-TrisA sheets. Results showed that the covalently cross-linked GO-TrisA/PAM nanocomposite hydrogel had enhanced mechanical strength, thermo stability compared with GO/PAM hydrogel maintained mainly by hydrogen bonding between PAM chains and GO sheets. In vitro cell study showed that the covalently cross-linked rGO-TrisA/PAM nanocomposite hydrogel had excellent cytocompatibility after in situ reduction. These results suggest that rGO-TrisA/PAM nanocomposite hydrogel holds great potential for tissue engineering applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1247-1257, 2018. © 2018 Wiley Periodicals, Inc.

60 YEARS OF POMC: From POMC and α-MSH to PAM, molecular oxygen, copper, and vitamin C.

PubMed

Kumar, Dhivya; Mains, Richard E; Eipper, Betty A

2016-05-01

A critical role for peptide C-terminal amidation was apparent when the first bioactive peptides were identified. The conversion of POMC into adrenocorticotropic hormone and then into α-melanocyte-stimulating hormone, an amidated peptide, provided a model system for identifying the amidating enzyme. Peptidylglycine α-amidating monooxygenase (PAM), the only enzyme that catalyzes this modification, is essential; mice lacking PAM survive only until mid-gestation. Purification and cloning led to the discovery that the amidation of peptidylglycine substrates proceeds in two steps: peptidylglycine α-hydroxylating monooxygenase catalyzes the copper- and ascorbate-dependent α-hydroxylation of the peptidylglycine substrate; peptidyl-α-hydroxyglycine α-amidating lyase cleaves the N-C bond, producing amidated product and glyoxylate. Both enzymes are contained in the luminal domain of PAM, a type 1 integral membrane protein. The structures of both catalytic cores have been determined, revealing how they interact with metals, molecular oxygen, and substrate to catalyze both reactions. Although not essential for activity, the intrinsically disordered cytosolic domain is essential for PAM trafficking. A phylogenetic survey led to the identification of bifunctional membrane PAM in Chlamydomonas, a unicellular eukaryote. Accumulating evidence points to a role for PAM in copper homeostasis and in retrograde signaling from the lumen of the secretory pathway to the nucleus. The discovery of PAM in cilia, cellular antennae that sense and respond to environmental stimuli, suggests that much remains to be learned about this ancient protein. © 2016 Society for Endocrinology.

Two-dimensional directional synthetic aperture focusing technique using acoustic-resolution photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Jeon, Seungwan; Park, Jihoon; Kim, Chulhong

2018-02-01

Photoacoustic microscopy (PAM) is a hybrid imaging technology using optical illumination and acoustic detection. PAM is divided into two types: optical-resolution PAM (OR-PAM) and acoustic-resolution photoacoustic microscopy (AR-PAM). Among them, AR-PAM has a great advantage in the penetration depth compared to OR-PAM because ARPAM relies on the acoustic focus, which is much less scattered in biological tissue than optical focus. However, because the acoustic focus is not as tight as the optical focus with a same numerical aperture (NA), the AR-PAM requires acoustic NA higher than optical NA. The high NA of the acoustic focus produces good image quality in the focal zone, but significantly degrades spatial resolution and signal-to-noise ratio (SNR) in the out-of-focal zone. To overcome the problem, synthetic aperture focusing technique (SAFT) has been introduced. SAFT improves the degraded image quality in terms of both SNR and spatial resolution in the out-of-focus zone by calculating the time delay of the corresponding signals and combining them. To extend the dimension of correction effect, several 2D SAFTs have been introduced, but there was a problem that the conventional 2D SAFTs cannot improve the degraded SNR and resolution as 1D SAFT can do. In this study, we proposed a new 2D SAFT that can compensate the distorted signals in x and y directions while maintaining the correction performance as the 1D SAFT.

48 CFR 1401.304 - Agency control and compliance procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... and control of the Director, PAM, who is responsible for reviewing and preparing the issuance of all Department-wide and bureau-wide acquisition regulations published in the Federal Register to ensure... Director, PAM, at the time of issuance. (2) The Director, PAM, is also responsible for reviewing and...

Tissue Protecting Antidotes From Anti-Apoptotic Factors of Mycoplasma

DTIC Science & Technology

2005-12-12

agalactiae Pam2C-GDKYFKETE Thioredoxin Pam2C-GPCPGCPPC Thioredoxin-2 Pam2C-PPCPGCPPC M.arginini Pam2C-GETDKEGKIIRIFDNSF Porphyromonas gingivalis...ones such as MALP-2 and FSL-1 from two different Mycoplasma spp, and notion that R- (but not S - counterpart) isomer exhibits biological activities...TLR6 heterodimers. Combinde toxicity of CBLB601 (ug/mouse) and TBI 0 1 2 3 4 5 6 0 5 10 15 20 25 days after 10Gy TBI nu m be r o f s u rv iv ed

Reactivation of model cholinesterases by oximes and intermediate phosphyloximes: A computational study

PubMed Central

Vyas, Shubham; Hadad, Christopher M.

2008-01-01

Phosphyloximes (POX) are generated upon the reactivation of organophosphorus (OP) inhibited cholinesterases (ChEs) by pyridinium oximes. These POXs are known to be potent inhibitors of the ChEs following reactivation. However, they can also decompose to give an OP derivative and a cyano derivative of the oxime when a base abstracts the benzylic proton. Using density functional theory, thermodynamic properties were calculated for the reactivation and decomposition pathways of three different oximes (2-PAM, 3-PAM and 4-PAM) with six different OPs (cyclosarin, paraoxon, sarin, tabun, VR and VX). For reactivation purposes, 2-PAM is predicted to be more efficient than 3- and 4-PAM. Based on atomic charges and relative energies, 2-POXs were found to be more inclined towards the decomposition process. PMID:18582852

Development of sample exchange robot PAM-HC for beamline BL-1A at the photon factory

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

Hiraki, Masahiko, E-mail: masahiko.hiraki@kek.jp; Department of Accelerator Science, SOKENDAI; Matsugaki, Naohiro

A macromolecular crystallography beamline, BL-1A, has been built at the Photon Factory (PF) for low energy experiments and has been operational since 2010. We have installed a sample exchange robot, PAM (PF Automated Mounting system), similar to other macromolecular crystallography beamlines. However, following the installation of a helium chamber to reduce the absorption of the diffraction signal by air, we developed a new sample exchange robot to replace PAM. The new robot, named PAM-HC (Helium Chamber), is designed with the goal of minimizing leakage of helium gas from the chamber. Here, the PAM-HC hardware and the flow of its movementmore » are described. Furthermore, measurements of temperature changes during sample exchange are presented in this paper.« less

Photoacoustic microscopy of human teeth

NASA Astrophysics Data System (ADS)

Rao, Bin; Cai, Xin; Favazza, Christopher; Yao, Junjie; Li, Li; Duong, Steven; Liaw, Lih-Huei; Holtzman, Jennifer; Wilder-Smith, Petra; Wang, Lihong V.

2011-03-01

Photoacoustic microscopy (PAM) utilizes short laser pulses to deposit energy into light absorbers and sensitively detects the ultrasonic waves the absorbers generate in response. PAM directly renders a three-dimensional spatial distribution of sub-surface optical absorbers. Unlike other optical imaging technologies, PAM features label-free optical absorption contrast and excellent imaging depths. Standard dental imaging instruments are limited to X-ray and CCD cameras. Subsurface optical dental imaging is difficult due to the highly-scattering enamel and dentin tissue. Thus, very few imaging methods can detect dental decay or diagnose dental pulp, which is the innermost part of the tooth, containing the nerves, blood vessels, and other cells. Here, we conducted a feasibility study on imaging dental decay and dental pulp with PAM. Our results showed that PAM is sensitive to the color change associated with dental decay. Although the relative PA signal distribution may be affected by surface contours and subsurface reflections from deeper dental tissue, monitoring changes in the PA signals (at the same site) over time is necessary to identify the progress of dental decay. Our results also showed that deep-imaging, near-infrared (NIR) PAM can sensitively image blood in the dental pulp of an in vitro tooth. In conclusion, PAM is a promising tool for imaging both dental decay and dental pulp.

Conjunctival amelanotic malignant melanoma arising in primary acquired melanosis sine pigmento.

PubMed

Jay, V; Font, R L

1998-01-01

The authors describe an amelanotic malignant melanoma of the conjunctiva in association with primary acquired melanosis (PAM) sine pigmento, and highlight the clinical and pathologic features of this rare entity. Histopathologic and immunohistochemical studies were performed on a conjunctival tumor in a 54-year-old white woman. Case report. Histopathologic examination revealed an invasive amelanotic melanoma of the conjunctiva, with anterior orbital extension arising from intraepithelial dysplastic melanocytes that lacked melanin pigment (PAM sine pigmento). Both the malignant melanoma cells and the intraepithelial dysplastic melanocytes in the areas of PAM exhibited S-100 and HMB-45 positivity. The patient underwent an orbital exenteration that disclosed tumor within the anterior orbit inferiorly. Amelanotic invasive malignant melanoma can arise in association with PAM sine pigmento, as seen in our patient who had orbital invasion necessitating exenteration. This aggressive form of conjunctival melanoma is often associated with a poor prognosis and risk of metastatic disease. Absence of conjunctival pigmentation in PAM sine pigmento prevents early clinical detection of this variant of PAM. This lack of pigmentation also makes clinical diagnosis virtually impossible, and diagnosis can only be established histopathologically. Awareness of this nonpigmented variety of PAM is crucial for early recognition and appropriate management of the associated melanoma.

Submicron-resolution photoacoustic microscopy of endogenous light-absorbing biomolecules

NASA Astrophysics Data System (ADS)

Zhang, Chi

Photoacoustic imaging in biomedicine has the unique advantage of probing endogenous light absorbers at various length scales with a 100% relative sensitivity. Among the several modalities of photoacoustic imaging, optical-resolution photoacoustic microscopy (OR-PAM) can achieve high spatial resolution, on the order of optical wavelength, at <1 mm depth in biological tissue (the optical ballistic regime). OR-PAM has been applied successfully to structural and functional imaging of blood vasculature and red blood cells in vivo. Any molecules which absorb sufficient light at certain wavelengths can potentially be imaged by PAM. Compared with pure optical imaging, which typically targets fluorescent markers, label-free PAM avoids the major concerns that the fluorescent labeling probes may disturb the function of biomolecules and may have an insufficient density. This dissertation aims to advance label-free OR-PAM to the subcellular scale. The first part of this dissertation describes the technological advancement of PAM yielding high spatial resolution in 3D. The lateral resolution was improved by using optical objectives with high numerical apertures for optical focusing. The axial resolution was improved by using broadband ultrasonic transducers for ultrasound detection. We achieved 220 nm lateral resolution in transmission mode, 0.43 microm lateral resolution in reflection mode, 7.6 microm axial resolution in normal tissue, and 5.8 microm axial resolution with silicone oil immersion/injection. The achieved lateral resolution and axial resolution were the finest reported at the time. With high-resolution in 3D, PAM was demonstrated to resolve cellular and subcellular structures in vivo, such as red blood cells and melanosomes in melanoma cells. Compared with previous PAM systems, our high-resolution PAM could resolve capillaries in mouse ears more clearly. As an example application, we demonstrated intracellular temperature imaging, assisted by fluorescence signal detection, with sub-degree temperature resolution and sub-micron lateral resolution. The second part of this dissertation describes the exploration of endogenous light-absorbing biomolecules for PAM. We demonstrated cytochromes and myoglobin as new absorption contrasts for PAM and identified the corresponding optimal wavelengths for imaging. Fixed fibroblasts on slides and mouse ear sections were imaged by PAM at 422 nm and 250 nm wavelengths to reveal cytoplasms and nuclei, respectively, as confirmed by standard hematoxylin and eosin (H&E) histology. By imaging a blood-perfused mouse heart at 532 nm down to 150 microm in depth, we derived the myocardial sheet thickness and the cleavage height from an undehydrated heart for the first time. The findings promote PAM at new wavelengths and open up new possibilities for characterizing biological tissue. Of particular interest, dual-wavelength PAM around 250 nm and 420 nm wavelengths is analogous to H&E histology. The last part of this dissertation describes the development of sectioning photoacoustic microscopy (SPAM), based on the advancement in spatial resolution and new contrasts for PAM, with applications in brain histology. Label-free SPAM, assisted by a microtome, acquires serial distortion-free images of a specimen on the surface. By exciting cell nuclei at 266 nm wavelength with high resolution, SPAM could pinpoint cell nuclei sensitively and specifically in the mouse brain section, as confirmed by H&E histology. SPAM was demonstrated to generate high-resolution 3D images, highlighting cell nuclei, of formalin-fixed paraffin-embedded mouse brains without tissue staining or clearing. SPAM can potentially serve as a high-throughput and minimal-artifact substitute for histology, probe many other biomolecules and cells, and become a universal tool for animal or human whole-organ microscopy, with diverse applications in life sciences.

Taming the Wild Text

ERIC Educational Resources Information Center

Allyn, Pam

2012-01-01

As a well-known advocate for promoting wider reading and reading engagement among all children--and founder of a reading program for foster children--Pam Allyn knows that struggling readers often face any printed text with fear and confusion, like Max in the book Where the Wild Things Are. She argues that teachers need to actively create a…

Epidermal fatty acid-binding protein protects nerve growth factor-differentiated PC12 cells from lipotoxic injury

PubMed Central

Liu, Jo-Wen; Montero, Manuel; Bu, Liming; De Leon, Marino

2015-01-01

Epidermal fatty acid-binding protein (E-FABP/FABP5/DA11) binds and transport long-chain fatty acids in the cytoplasm and may play a protecting role during neuronal injury. We examined whether E-FABP protects nerve growth factor-differentiated PC12 cells (NGFDPC12 cells) from lipotoxic injury observed after palmitic acid (C16:0; PAM) overload. NGFDPC12 cells cultures treated with PAM/bovine serum albumin at 0.3 mM/0.15 mM show PAM-induced lipotoxicity (PAM-LTx) and apoptosis. The apoptosis was preceded by a cellular accumulation of reactive oxygen species (ROS) and higher levels of E-FABP. Antioxidants MCI-186 and N-acetyl cysteine prevented E-FABP's induction in expression by PAM-LTx, while tert-butyl hydroperoxide increased ROS and E-FABP expression. Non-metabolized methyl ester of PAM, methyl palmitic acid (mPAM), failed to increase cellular ROS, E-FABP gene expression, or trigger apoptosis. Treatment of NGFDPC12 cultures with siE-FABP showed reduced E-FABP levels correlating with higher accumulation of ROS and cell death after exposure to PAM. In contrast, increasing E-FABP cellular levels by pre-loading the cells with recombinant E-FABP diminished the PAM-induced ROS and cell death. Finally, agonists for PPARβ (GW0742) or PPARγ (GW1929) increased E-FABP expression and enhanced the resistance of NGFDPC12 cells to PAM-LTx. We conclude that E-FABP protects NGFDPC12 cells from lipotoxic injury through mechanisms that involve reduction of ROS. Epidermal fatty acid-binding protein (E-FABP) may protect nerve cells from the damaging exposure to high levels of free fatty acids (FA). We show that E-FABP can neutralize the effects of reactive oxygen species (ROS) generated by the high levels of FA in the cell and protect PC12 cells from lipotoxic injuries common in Type 2 diabetes neuropathy. Potentially, E-FABP gene up-regulation may be mediated through the NFkB pathway and future studies are needed to further evaluate this proposition. PMID:25147052

Motivating Latino caregivers of children with asthma to quit smoking: a randomized trial.

PubMed

Borrelli, Belinda; McQuaid, Elizabeth L; Novak, Scott P; Hammond, S Katharine; Becker, Bruce

2010-02-01

Secondhand smoke exposure is associated with asthma onset and exacerbation. Latino children have higher rates of asthma morbidity than other groups. The current study compared the effectiveness of a newly developed smoking cessation treatment with existing clinical guidelines for smoking cessation. Latino caregivers who smoked (N = 133; 72.9% female; mean age = 36.8 years) and had a child with asthma were randomly assigned to receive 1 of 2 smoking cessation counseling interventions during a home-based asthma program: (a) behavioral action model (BAM; modeled on clinical guidelines for smoking cessation) or (b) precaution adoption model (PAM; feedback on the caregiver's carbon monoxide level and child's secondhand smoke exposure using Motivational Interviewing). Counseling was delivered by a bilingual Latina health educator, and the content was tailored to Latino values and culture. It was not necessary for smokers to want to quit smoking to participate. Smoking cessation was biochemically verified and secondhand smoke exposure was objectively measured through passive nicotine monitors. Intent-to-treat analyses showed that 20.5% of participants in the PAM condition and 9.1% of those in the BAM condition were continuously abstinent at 2 months posttreatment (OR = 2.54; 95% CI = 0.91-7.10), whereas 19.1% of participants in the PAM condition and 12.3% of those in BAM condition were continuously abstinent at 3 months posttreatment (OR = 1.68; 95% CI = 0.64-4.37). Secondhand smoke exposure decreased only in the BAM condition (p < .001), an effect due to less smoking around the child among nonquitters in this condition. Asthma morbidity showed significant decreases in the posttreatment period for the PAM group only (p < .001). Results provide support for targeting specific populations with theory-based interventions.

Implementation of hybrid clustering based on partitioning around medoids algorithm and divisive analysis on human Papillomavirus DNA

NASA Astrophysics Data System (ADS)

Arimbi, Mentari Dian; Bustamam, Alhadi; Lestari, Dian

2017-03-01

Data clustering can be executed through partition or hierarchical method for many types of data including DNA sequences. Both clustering methods can be combined by processing partition algorithm in the first level and hierarchical in the second level, called hybrid clustering. In the partition phase some popular methods such as PAM, K-means, or Fuzzy c-means methods could be applied. In this study we selected partitioning around medoids (PAM) in our partition stage. Furthermore, following the partition algorithm, in hierarchical stage we applied divisive analysis algorithm (DIANA) in order to have more specific clusters and sub clusters structures. The number of main clusters is determined using Davies Bouldin Index (DBI) value. We choose the optimal number of clusters if the results minimize the DBI value. In this work, we conduct the clustering on 1252 HPV DNA sequences data from GenBank. The characteristic extraction is initially performed, followed by normalizing and genetic distance calculation using Euclidean distance. In our implementation, we used the hybrid PAM and DIANA using the R open source programming tool. In our results, we obtained 3 main clusters with average DBI value is 0.979, using PAM in the first stage. After executing DIANA in the second stage, we obtained 4 sub clusters for Cluster-1, 9 sub clusters for Cluster-2 and 2 sub clusters in Cluster-3, with the BDI value 0.972, 0.771, and 0.768 for each main cluster respectively. Since the second stage produce lower DBI value compare to the DBI value in the first stage, we conclude that this hybrid approach can improve the accuracy of our clustering results.

Comparison of the clinical presentations of Naegleria fowleri primary amoebic meningoencephalitis with pneumococcal meningitis: a case-control study.

PubMed

Zahid, Mohammad Faizan; Saad Shaukat, Muhammad Hamza; Ahmed, Bilal; Beg, Mohammad Asim; Kadir, Muhammad Masood; Mahmood, Syed Faisal

2016-08-01

Primary amoebic meningoencephalitis (PAM) is a rare but fatal infection caused by Naegleria fowleri. The infection is acquired by deep nasal irrigation with infected water. Patients present with signs and symptoms similar to pneumococcal meningitis, leading to delayed diagnosis and treatment and hence high mortality. We conducted a case-control study comparing culture proven cases of PAM with pneumococcal meningitis presenting to our center between April 2008 and September 2014. Only patients with blood and/or cerebrospinal fluid cultures positive for Streptococcus pneumoniae during the same time period were included for comparison. There were 19 cases of PAM and pneumococcal meningitis, each. When comparing PAM with pneumococcal meningitis, patients with PAM were more likely to be male (89.5 vs. 36.8 %), younger (mean age: 30 vs. 59 years), present with seizures (42.1 vs. 5.3 %). Both groups of patients presented with similar vital signs and there were no remarkable differences on physical examinations, Glasgow Coma Scale scores, laboratory and radiological investigations and cerebrospinal fluid parameters. PAM was also more likely to present if the city's average maximum temperature was higher in the previous week (mean: 34.6 vs. 30 °C). There was history of fresh water contact in only one patient. On multivariate analysis, PAM was more likely if patients presented when the city's average maximum temperature was high, being young males. PAM and pneumococcal meningitis remain virtually indistinguishable; however, these predictive features should be validated in a prospective study and may lead to a viable algorithm for early management of these patients.

Probing the Production of Amidated Peptides following Genetic and Dietary Copper Manipulations

PubMed Central

Yin, Ping; Bousquet-Moore, Danielle; Annangudi, Suresh P.; Southey, Bruce R.; Mains, Richard E.; Eipper, Betty A.; Sweedler, Jonathan V.

2011-01-01

Amidated neuropeptides play essential roles throughout the nervous and endocrine systems. Mice lacking peptidylglycine α-amidating monooxygenase (PAM), the only enzyme capable of producing amidated peptides, are not viable. In the amidation reaction, the reactant (glycine-extended peptide) is converted into a reaction intermediate (hydroxyglycine-extended peptide) by the copper-dependent peptidylglycine-α-hydroxylating monooxygenase (PHM) domain of PAM. The hydroxyglycine-extended peptide is then converted into amidated product by the peptidyl-α-hydroxyglycine α-amidating lyase (PAL) domain of PAM. PHM and PAL are stitched together in vertebrates, but separated in some invertebrates such as Drosophila and Hydra. In addition to its luminal catalytic domains, PAM includes a cytosolic domain that can enter the nucleus following release from the membrane by γ-secretase. In this work, several glycine- and hydroxyglycine-extended peptides as well as amidated peptides were qualitatively and quantitatively assessed from pituitaries of wild-type mice and mice with a single copy of the Pam gene (PAM+/−) via liquid chromatography-mass spectrometry-based methods. We provide the first evidence for the presence of a peptidyl-α-hydroxyglycine in vivo, indicating that the reaction intermediate becomes free and is not handed directly from PHM to PAL in vertebrates. Wild-type mice fed a copper deficient diet and PAM+/− mice exhibit similar behavioral deficits. While glycine-extended reaction intermediates accumulated in the PAM+/− mice and reflected dietary copper availability, amidated products were far more prevalent under the conditions examined, suggesting that the behavioral deficits observed do not simply reflect a lack of amidated peptides. PMID:22194882

The Bioethics of Music, the Music of Bioethics.

PubMed

Lubet, Alex

2015-12-01

Bioethics is rarely referenced in the scholarship of performing arts medicine (PAM). This essay argues that bioethical concerns loom far larger in the care of PAM patients than might typically be understood. This essay presents Beauchamp and Childress's four principles of bioethics, with examples pertinent to PAM, drawn from the author's research and personal experience.

Application of polyacrylamide (PAM) through lay-flat polyethylene 1 tubing: effects on infiltration, erosion, N and P transport, and corn yield

USDA-ARS?s Scientific Manuscript database

Polyacrylamides (PAMs), when applied as a soil amendment, purportedly improve soil infiltration, decrease erosion, and reduce off-site agrochemical transport. The effect of PAM on infiltration, erosion, agrochemical transport, and crop yield when applied in-furrow to Mid-South production systems has...

DNA interrogation by the CRISPR RNA-guided endonuclease Cas9.

PubMed

Sternberg, Samuel H; Redding, Sy; Jinek, Martin; Greene, Eric C; Doudna, Jennifer A

2014-03-06

The clustered regularly interspaced short palindromic repeats (CRISPR)-associated enzyme Cas9 is an RNA-guided endonuclease that uses RNA-DNA base-pairing to target foreign DNA in bacteria. Cas9-guide RNA complexes are also effective genome engineering agents in animals and plants. Here we use single-molecule and bulk biochemical experiments to determine how Cas9-RNA interrogates DNA to find specific cleavage sites. We show that both binding and cleavage of DNA by Cas9-RNA require recognition of a short trinucleotide protospacer adjacent motif (PAM). Non-target DNA binding affinity scales with PAM density, and sequences fully complementary to the guide RNA but lacking a nearby PAM are ignored by Cas9-RNA. Competition assays provide evidence that DNA strand separation and RNA-DNA heteroduplex formation initiate at the PAM and proceed directionally towards the distal end of the target sequence. Furthermore, PAM interactions trigger Cas9 catalytic activity. These results reveal how Cas9 uses PAM recognition to quickly identify potential target sites while scanning large DNA molecules, and to regulate scission of double-stranded DNA.

[Effects of biochar and PAM application on saline soil hydraulic properties of coastal reclamation region].

PubMed

Cao, Yu Tong; She, Dong Li

2017-11-01

Disc infiltration tests were carried out to study the soil infiltration characteristics under different rates of soil amendments application, and to investigate the effects of biochar and polyacrylamide (PAM) application on saline soil hydraulic properties, pore characteristics and contribution of each pore to soil water flow in coastal reclamation region. The results showed that soil satura-ted hydraulic conductivity increased by 46.4% when biochar was applied at 2% compared with the control, and decreased with increasing PAM application. The total effective soil porosity and r>100 μm pores were increased by 8.3% and 10.2% (P<0.05) with the application of 2% biochar alone. The total effective soil porosity and different radius pores decreased with the PAM application. Particularly, the total effective soil porosity decreased markedly when PAM was applied at 1‰ and the reduction was up to 88%. With the application of biochar and PAM, the contribution of r<100 μm pores to water flow decreased and the pores with r>500 μm played a major role in determining water flows.

DNA interrogation by the CRISPR RNA-guided endonuclease Cas9

NASA Astrophysics Data System (ADS)

Sternberg, Samuel H.; Redding, Sy; Jinek, Martin; Greene, Eric C.; Doudna, Jennifer A.

2014-03-01

The clustered regularly interspaced short palindromic repeats (CRISPR)-associated enzyme Cas9 is an RNA-guided endonuclease that uses RNA-DNA base-pairing to target foreign DNA in bacteria. Cas9-guide RNA complexes are also effective genome engineering agents in animals and plants. Here we use single-molecule and bulk biochemical experiments to determine how Cas9-RNA interrogates DNA to find specific cleavage sites. We show that both binding and cleavage of DNA by Cas9-RNA require recognition of a short trinucleotide protospacer adjacent motif (PAM). Non-target DNA binding affinity scales with PAM density, and sequences fully complementary to the guide RNA but lacking a nearby PAM are ignored by Cas9-RNA. Competition assays provide evidence that DNA strand separation and RNA-DNA heteroduplex formation initiate at the PAM and proceed directionally towards the distal end of the target sequence. Furthermore, PAM interactions trigger Cas9 catalytic activity. These results reveal how Cas9 uses PAM recognition to quickly identify potential target sites while scanning large DNA molecules, and to regulate scission of double-stranded DNA.

Immunological characterization of pulmonary intravascular macrophages

NASA Technical Reports Server (NTRS)

Chitko-McKown, C. G.; Reddy, D. N.; Chapes, S. K.; McKown, R. D.; Blecha, F.; Spooner, B. S. (Principal Investigator)

1992-01-01

Pulmonary intravascular macrophages (PIMs) are lung macrophages found apposed to the endothelium of pulmonary capillaries. In many species, they are responsible for the clearance of blood-borne particulates and pathogens; however, little else is known about their roles as immunologic effector cells. We compared PIMs with pulmonary alveolar macrophages (PAMs) to determine the relative immunological activities of these two cell populations. Our results suggested that both populations possess similar phagocytic and bactericidal activities. In assays measuring cytotoxicity, PIMs were more cytotoxic than PAMs against virally infected target cells; however, differences between these macrophage populations were not as marked when noninfected targets were used. LPS-stimulated PIMs produced more T-cell proliferative cytokines than PAMs, and both populations of nonstimulated macrophages produced similar amounts of the cytokines. In contrast, PAMs produced more TNF alpha and NO2- than PIMs when both populations were stimulated with LPS; however, nonstimulated PAMs and PIMs produced similar amounts of TNF alpha and NO2. These data suggest that bovine PIMs are immunologically active. Differences between the degrees of activity of PIMs and PAMs indicate that these macrophage populations may have different roles in lung surveillance.

Unperturbed volume transition of thermosensitive poly-(N-isopropylacrylamide) microgel particles embedded in a hydrogel matrix.

PubMed

Musch, Judith; Schneider, Stefanie; Lindner, Peter; Richtering, Walter

2008-05-22

The thermoresponsive behavior of poly-(N-isopropylacrylamide) (PNiPAM) microgels embedded in a covalently cross-linked polyacrylamide hydrogel matrix was investigated using ultraviolet-visible (UV-vis) spectroscopy, small-angle neutron scattering (SANS), and confocal laser scanning microscopy. The hydrogel synthesis was performed at two different temperatures, below and above the volume phase transition temperature of PNiPAM, resulting in highly swollen or fully collapsed PNiPAM microgel particles during the incorporation step. UV-vis spectroscopy experiments verify that the incorporation of thermosensitive microgels leads to temperature-sensitive optical properties of the composite materials. SANS measurements at different temperatures show that the thermosensitive swelling behavior of the PNiPAM microgels is fully retained in the composite material. Volume and structure criteria of the embedded microgel particles are compared to those of the free microgels in acrylamide solution. To visualize the temperature responsive behavior of larger PNiPAM particles, confocal fluorescence microscopy images of PNiPAM beads, of 40-microm size, were taken at two different temperatures. The micrographs also demonstrate the retained temperature sensitivity of the embedded microgels.

Feasibility investigation of oily wastewater treatment by combination of zinc and PAM in coagulation/flocculation.

PubMed

Zeng, Yubin; Yang, Changzhu; Zhang, Jingdong; Pu, Wenhong

2007-08-25

Poly-zinc silicate (PZSS) is a new type of coagulant with cationic polymer synthesized by polysilicic acid and zinc sulfate. It has been used in several sorts of wastewaters treatment, but not used in oily wastewater treatment. In this study, we investigated the coagulation/flocculation of oil and suspended solids in heavy oil wastewater (HOW) by PZSS and anion polyacrylamide (A-PAM). The properties of PZSS cooperated with A-PAM were compared with PAC and PFS in dosages, PAMs amount, settling time, pH value and flocs morphology. The results showed that PZSS was more efficient than PAC and PFS. Under the optimum experimental conditions of coagulation/flocculation (dosage: 100mg/L, A-PAM dosage: 1.0mg/L, settling time time: 40min and pH 6.5-9.5), more than 99% of oil was removed and suspended solid value less than 5mg/L by using PZSS cooperated with A-PAM, which could satisfy the demands of the pre-treatment process for HOW to be reused in the steam boiler or recycled into the injecting well.

Understanding the impact of cationic polyacrylamide on anaerobic digestion of waste activated sludge.

PubMed

Wang, Dongbo; Liu, Xuran; Zeng, Guangming; Zhao, Jianwei; Liu, Yiwen; Wang, Qilin; Chen, Fei; Li, Xiaoming; Yang, Qi

2018-03-01

Previous investigations showed that cationic polyacrylamide (cPAM), a flocculant widely used in wastewater pretreatment and waste activated sludge dewatering, deteriorated methane production during anaerobic digestion of sludge. However, details of how cPAM affects methane production are poorly understood, hindering deep control of sludge anaerobic digestion systems. In this study, the mechanisms of cPAM affecting sludge anaerobic digestion were investigated in batch and long-term tests using either real sludge or synthetic wastewaters as the digestion substrates. Experimental results showed that the presence of cPAM not only slowed the process of anaerobic digestion but also decreased methane yield. The maximal methane yield decreased from 139.1 to 86.7 mL/g of volatile suspended solids (i.e., 1861.5 to 1187.0 mL/L) with the cPAM level increasing from 0 to 12 g/kg of total suspended solids (i.e., 0-236.7 mg/L), whereas the corresponding digestion time increased from 22 to 26 d. Mechanism explorations revealed that the addition of cPAM significantly restrained the sludge solubilization, hydrolysis, acidogenesis, and methanogenesis processes. It was found that ∼46% of cAPM was degraded in the anaerobic digestion, and the degradation products significantly affected methane production. Although the theoretically biochemical methane potential of cPAM is higher than that of protein and carbohydrate, only 6.7% of the degraded cPAM was transformed to the final product, methane. Acrylamide, acrylic acid, and polyacrylic acid were found to be the main degradation metabolites, and their amount accounted for ∼50% of the degraded cPAM. Further investigations showed that polyacrylic acid inhibited all the solubilization, hydrolysis, acidogenesis, and methanogenesis processes while acrylamide and acrylic acid inhibited the methanogenesis significantly. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Novel M1 PAM VU0486846 Exerts Efficacy in Cognition Models without Displaying Agonist Activity or Cholinergic Toxicity.

PubMed

Rook, Jerri M; Bertron, Jeanette L; Cho, Hyekyung P; Garcia-Barrantes, Pedro M; Moran, Sean P; Maksymetz, James T; Nance, Kellie D; Dickerson, Jonathan W; Remke, Daniel H; Chang, Sichen; Harp, Joel M; Blobaum, Anna L; Niswender, Colleen M; Jones, Carrie K; Stauffer, Shaun R; Conn, P Jeffrey; Lindsley, Craig W

2018-05-08

Selective activation of the M 1 subtype of muscarinic acetylcholine receptor, via positive allosteric modulation (PAM), is an exciting strategy to improve cognition in schizophrenia and Alzheimer's disease patients. However, highly potent M 1 ago-PAMs, such as MK-7622, PF-06764427, and PF-06827443, can engender excessive activation of M 1 , leading to agonist actions in the prefrontal cortex (PFC) that impair cognitive function, induce behavioral convulsions, and result in other classic cholinergic adverse events (AEs). Here, we report a fundamentally new and highly selective M 1 PAM, VU0486846. VU0486846 possesses only weak agonist activity in M 1 -expressing cell lines with high receptor reserve and is devoid of agonist actions in the PFC, unlike previously reported ago-PAMs MK-7622, PF-06764427, and PF-06827443. Moreover, VU0486846 shows no interaction with antagonist binding at the orthosteric acetylcholine (ACh) site (e.g., neither bitopic nor displaying negative cooperativity with [ 3 H]-NMS binding at the orthosteric site), no seizure liability at high brain exposures, and no cholinergic AEs. However, as opposed to ago-PAMs, VU0486846 produces robust efficacy in the novel object recognition model of cognitive function. Importantly, we show for the first time that an M 1 PAM can reverse the cognitive deficits induced by atypical antipsychotics, such as risperidone. These findings further strengthen the argument that compounds with modest in vitro M 1 PAM activity (EC 50 > 100 nM) and pure-PAM activity in native tissues display robust procognitive efficacy without AEs mediated by excessive activation of M 1 . Overall, the combination of compound assessment with recombinant in vitro assays (mindful of receptor reserve), native tissue systems (PFC), and phenotypic screens (behavioral convulsions) is essential to fully understand and evaluate lead compounds and enhance success in clinical development.

Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase

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

Feng, Lei; Wanninayake, Udayanga; Strom, Susan

The structure of a phenylalanine aminomutase (TcPAM) from Taxus canadensis has been determined at 2.4 {angstrom} resolution. The active site of the TcPAM contains the signature 4-methylidene-1H-imidazol-5(4H)-one prosthesis, observed in all catalysts of the class I lyase-like family. This catalyst isomerizes (S)-{alpha}-phenylalanine to the (R)-{beta}-isomer by exchange of the NH{sub 2}/H pair. The stereochemistry of the TcPAM reaction product is opposite of the (S)-{beta}-tyrosine made by the mechanistically related tyrosine aminomutase (SgTAM) from Streptomyces globisporus. Since TcPAM and SgTAM share similar tertiary- and quaternary-structures and have several highly conserved aliphatic residues positioned analogously in their active sites for substrate recognition,more » the divergent product stereochemistries of these catalysts likely cannot be explained by differences in active site architecture. The active site of the TcPAM structure also is in complex with (E)-cinnamate; the latter functions as both a substrate and an intermediate. To account for the distinct (3R)-{beta}-amino acid stereochemistry catalyzed by TcPAM, the cinnamate skeleton must rotate the C{sub 1}-C{sub {alpha}} and C{sub ipso}-C{sub {beta}} bonds 180{sup o} in the active site prior to exchange and rebinding of the NH{sub 2}/H pair to the cinnamate, an event that is not required for the corresponding acrylate intermediate in the SgTAM reaction. Moreover, the aromatic ring of the intermediate makes only one direct hydrophobic interaction with Leu-104. A L104A mutant of TcPAM demonstrated an 1.5-fold increase in k{sub cat} and a decrease in K{sub M} values for sterically demanding 3'-methyl-{alpha}-phenylalanine and styryl-{alpha}-alanine substrates, compared to the kinetic parameters for TcPAM. These parameters did not change significantly for the mutant with 4'-methyl-{alpha}-phenylalanine compared to those for TcPAM.« less

Photoactivation mechanism of PAmCherry based on crystal structures of the protein in the dark and fluorescent states.

PubMed

Subach, Fedor V; Malashkevich, Vladimir N; Zencheck, Wendy D; Xiao, Hui; Filonov, Grigory S; Almo, Steven C; Verkhusha, Vladislav V

2009-12-15

Photoactivatable fluorescent proteins (PAFPs) are required for super-resolution imaging of live cells. Recently, the first red PAFP, PAmCherry1, was reported, which complements the photo-activatable GFP by providing a red super-resolution color. PAmCherry1 is originally "dark" but exhibits red fluorescence after UV-violet light irradiation. To define the structural basis of PAmCherry1 photoactivation, we determined its crystal structure in the dark and red fluorescent states at 1.50 A and 1.65 A, respectively. The non-coplanar structure of the chromophore in the dark PAmChery1 suggests the presence of an N-acylimine functionality and a single non-oxidized C(alpha)-C(beta) bond in the Tyr-67 side chain in the cyclized Met-66-Tyr-67-Gly-68 tripeptide. MS data of the chromophore-bearing peptide indicates the loss of 20 Da upon maturation, whereas tandem MS reveals the C(alpha)-N bond in Met-66 is oxidized. These data indicate that PAmCherry1 in the dark state possesses the chromophore N-[(E)-(5-hydroxy-1H-imidazol-2-yl)methylidene]acetamide, which, to our knowledge, has not been previously observed in PAFPs. The photoactivated PAmCherry1 exhibits a non-coplanar anionic DsRed-like chromophore but in the trans configuration. Based on the crystallographic analysis, MS data, and biochemical analysis of the PAmCherry1 mutants, we propose the detailed photoactivation mechanism. In this mechanism, the excited-state PAmCherry1 chromophore acts as the oxidant to release CO(2) molecule from Glu-215 via a Koble-like radical reaction. The Glu-215 decarboxylation directs the carbanion formation resulting in the oxidation of the Tyr-67 C(alpha)-C(beta) bond. The double bond extends the pi-conjugation between the phenolic ring of Tyr-67, the imidazolone, and the N-acylimine, resulting in the red fluorescent chromophore.

Receptor model comparisons and wind direction analyses of volatile organic compounds and submicrometer particles in an arid, binational, urban air shed.

PubMed

Mukerjee, Shaibal; Norris, Gary A; Smith, Luther A; Noble, Christopher A; Neas, Lucas M; Ozkaynak, A Halûk; Gonzales, Melissa

2004-04-15

The relationship between continuous measurements of volatile organic compounds sources and particle number was evaluated at a Photochemical Assessment Monitoring Station Network (PAMS) site located near the U.S.-Mexico Border in central El Paso, TX. Sources of volatile organic compounds (VOCs) were investigated using the multivariate receptor model UNMIX and the effective variance least squares receptor model known as Chemical Mass Balance (CMB, Version 8.0). As expected from PAMS measurements, overall findings from data screening as well as both receptor models confirmed that mobile sources were the major source of VOCs. Comparison of hourly source contribution estimates (SCEs) from the two receptor models revealed significant differences in motor vehicle exhaust and evaporative gasoline contributions. However, the motor vehicle exhaust contributions were highly correlated with each other. Motor vehicle exhaust was also correlated with the ultrafine and accumulation mode particle count, which suggests that motor vehicle exhaust is a source of these particles at the measurement site. Wind sector analyses were performed using the SCE and pollutant data to assess source location of VOCs, particle count, and criteria pollutants. Results from this study have application to source apportionment studies and mobile source emission control strategies that are ongoing in this air shed.

Efficient FFT Algorithm for Psychoacoustic Model of the MPEG-4 AAC

NASA Astrophysics Data System (ADS)

Lee, Jae-Seong; Lee, Chang-Joon; Park, Young-Cheol; Youn, Dae-Hee

This paper proposes an efficient FFT algorithm for the Psycho-Acoustic Model (PAM) of MPEG-4 AAC. The proposed algorithm synthesizes FFT coefficients using MDCT and MDST coefficients through circular convolution. The complexity of the MDCT and MDST coefficients is approximately half of the original FFT. We also design a new PAM based on the proposed FFT algorithm, which has 15% lower computational complexity than the original PAM without degradation of sound quality. Subjective as well as objective test results are presented to confirm the efficiency of the proposed FFT computation algorithm and the PAM.

Selective binding and magnetic separation of His-tagged proteins using Fe3O4/PAM/NTA-Ni2+ Magnetic Nanoparticles

NASA Astrophysics Data System (ADS)

Guo, Huiling; Li, Mengyun; Tu, Shu; Sun, Honghao

2018-03-01

Fe3O4 nanoparticles coated with polyacrylamide (PAM) were synthesized. The magnetic core, with an average hydrodynamic size of 235.5 nm, allowed the magnetic nanoparticles (MNPs) rapid separation from solutions under an external magnetic field. NTA-Ni2+ was modified on the surface of Fe3O4/PAM MNPs to selectively trap his-tagged green fluorescent protein (GFP). The results showed that Fe3O4/PAM/NTA-Ni2+ MNPs exhibited remarkable capability of selective binding and separating his-tagged GFP. The adsorption efficiency was 93.37%.

Clinicians' beliefs and attitudes toward patient self-management in the Netherlands; translation and testing of the American Clinician Support for Patient Activation Measure (CS-PAM).

PubMed

Rademakers, Jany; Jansen, Daphne; van der Hoek, Lucas; Heijmans, Monique

2015-04-03

The aim of this study was to test the Dutch version of the Clinician Support for Patient Activation Measure (CS-PAM), to explore the beliefs of Dutch clinicians about patients' self-management, and to establish whether there are differences in this respect between general practitioners and other primary care providers. The CS-PAM was translated in Dutch and data were collected in a sample of 489 general practitioners and other primary care providers. Statistical analyses (RASCH, Cronbach's α) were performed to establish the psychometric properties of the instrument. The psychometric scores of the Dutch CS-PAM were acceptable to good, and the difficulty level and structure was comparable to that of the original instrument. The average score of Dutch clinicians on the CS-PAM was 65.1 (SD 10.7), somewhat lower compared to their colleagues in the US (69; SD 12.1) and the UK (69, SD 12.8). Dutch general practitioners scored significantly lower on the CS-PAM compared to other primary care providers. The Dutch CS-PAM is a reliable instrument to measure beliefs of clinicians regarding patient self-management. Further validation studies are necessary to establish the distribution of scores in specific provider populations and to assess the clinical relevance of the instrument for different outcomes.

The pam1 gene is required for meiotic bouquet formation and efficient homologous synapsis in maize (Zea mays L.).

PubMed Central

Golubovskaya, Inna N; Harper, Lisa C; Pawlowski, Wojciech P; Schichnes, Denise; Cande, W Zacheus

2002-01-01

The clustering of telomeres on the nuclear envelope (NE) during meiotic prophase to form the bouquet arrangement of chromosomes may facilitate homologous chromosome synapsis. The pam1 (plural abnormalities of meiosis 1) gene is the first maize gene that appears to be required for telomere clustering, and homologous synapsis is impaired in pam1. Telomere clustering on the NE is arrested or delayed at an intermediate stage in pam1. Telomeres associate with the NE during the leptotene-zygotene transition but cluster slowly if at all as meiosis proceeds. Intermediate stages in telomere clustering including miniclusters are observed in pam1 but not in wild-type meiocytes. The tight bouquet normally seen at zygotene is a rare event. In contrast, the polarization of centromeres vs. telomeres in the nucleus at the leptotene-zygotene transition is the same in mutant and wild-type cells. Defects in homologous chromosome synapsis include incomplete synapsis, nonhomologous synapsis, and unresolved interlocks. However, the number of RAD51 foci on chromosomes in pam1 is similar to that of wild type. We suggest that the defects in homologous synapsis and the retardation of prophase I arise from the irregularity of telomere clustering and propose that pam1 is involved in the control of bouquet formation and downstream meiotic prophase I events. PMID:12524364

PLGA-based microcarriers induce mesenchymal stem cell chondrogenesis and stimulate cartilage repair in osteoarthritis.

PubMed

Morille, Marie; Toupet, Karine; Montero-Menei, Claudia N; Jorgensen, Christian; Noël, Danièle

2016-05-01

In the present study, we aimed at evaluating the ability of novel PLGA-P188-PLGA-based microspheres to induce the differentiation of mesenchymal stem/stromal cells (MSC) into chondrocytes. To this aim, we tested microspheres releasing TGFβ3 (PAM-T) in vitro and in situ, in a pathological osteoarthritic (OA) environment. We first evaluated the chondrogenic differentiation of human MSCs seeded onto PAM-T in vitro and confirmed the up-regulation of chondrogenic markers while the secretome of the cells was not changed by the 3D environment. We then injected human MSC seeded onto PAM-T in the knee joints of mice with collagenase-induced OA. After 6 weeks, histological analysis revealed that formation of a cartilage-like tissue occurred at the vicinity of PAM-T that was not observed when MSCs were seeded onto PAM. We also noticed that the endogenous articular cartilage was less degraded. The extent of cartilage protection was further analysed by confocal laser microscopy. When MSCs seeded onto PAM-T were injected early after OA induction, protection of cartilage against degradation was evidenced and this effect was associated to a higher survival of MSCs in presence of TGFβ3. This study points to the interest of using MSCs seeded onto PAM for cartilage repair and stimulation of endogenous cartilage regeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

New technology in postfire rehab

Treesearch

Joe Sabel

2007-01-01

PAM-12™ is a recycled office paper byproduct made into a spreadable mulch with added Water Soluble Polyacrylamide (WSPAM), a previously difficult polymer to apply. PAM-12 is extremely versatile and can be applied through several methods. In a field test, PAM-12 outperformed straw in every targeted performance area: erosion control, improving soil hydrophobicity, and...

Characterization of ultrahigh-molecular weight cationic polyacrylamide using frit-inlet asymmetrical flow field-flow fractionation and multi-angle light scattering.

PubMed

Woo, Sohee; Lee, Ju Yong; Choi, Woonjin; Moon, Myeong Hee

2016-01-15

In this study, frit inlet asymmetrical flow field-flow fractionation (FlFFF) with multi-angle light scattering (MALS) and differential refractive index (DRI) detection is utilized for size separation, determination of molecular weight (MW), and conformation of ultrahigh-MW (10(7)-10(9) g/mol) cationic polyacrylamides (C-PAMs), a class of water-soluble copolymers based on acrylamide and vinyl-type comonomers with quaternary ammonium cations that are widely used in wastewater treatment and in paper industries. Linear and branched C-PAM copolymers prepared in two different polymerization methods (solution and emulsion) from varying amounts of crosslinking agent and initiator were size fractionated by FlFFF with field-programming. It was found experimentally that the linear copolymers from both polymerization methods were less than 10(8) g/mol in MW with compact, nearly spherical structures, while the branched C-PAM copolymers from the emulsion polymerization showed a significant increase in average MW up to ∼ 10(9)g/mol, which was about 20-fold greater than those from the solution method, and the branched copolymers had more compact or shrunken conformations. While both linear and branched copolymers less than 10(8) g/mol MW were well resolved in an increasing order of MW (normal mode), it was noted that branched copolymers prepared through emulsion polymerization exhibited significantly larger MWs of 10(8-)10(9) g/mol and eluted in the steric/hyperlayer mode, in which the elution order is reversed in an extreme run condition (strong initial field strength followed by a fast field decay during programming). Copyright © 2015 Elsevier B.V. All rights reserved.

Scaling single-wavelength optical interconnects to 180 Gb/s with PAM-M and pulse shaping

NASA Astrophysics Data System (ADS)

Dris, Stefanos; Bakopoulos, Paraskevas; Argyris, Nikolaos; Spatharakis, Christos; Avramopoulos, Hercules

2016-03-01

Faced with surging datacenter traffic demand, system designers are turning to multi-level optical modulation with direct detection as the means of reaching 100 Gb/s in a single optical lane; a further upgrade to 400 Gb/s is envisaged through wavelength-multiplexing of multiple 100 Gb/s strands. In terms of modulation formats, PAM-4 and PAM-8 are considered the front-runners, striking a good balance between bandwidth-efficiency and implementation complexity. In addition, the emergence of energy-efficient, high-speed CMOS digital-to-analog converters (DACs) opens up new possibilities: Spectral shaping through digital filtering will allow squeezing even more data through low-cost, low-bandwidth electro-optic components. In this work we demonstrate an optical interconnect based on an EAM that is driven directly with sub-volt electrical swing by a 65 GSa/s arbitrary waveform generator (AWG). Low-voltage drive is particularly attractive since it allows direct interfacing with the switch/server ASIC, eliminating the need for dedicated, power-hungry and expensive electrical drivers. Single-wavelength throughputs of 180 and 120 Gb/s are experimentally demonstrated with 60 Gbaud optical PAM-8 and PAM-4 respectively. Successful transmission over 1250 m SMF is achieved with direct-detection, using linear equalization via offline digital signal processing in order to overcome the strong bandwidth limitation of the overall link (~20 GHz). The suitability of Nyquist pulse shaping for optical interconnects is also investigated experimentally with PAM-4 and PAM-8, at a lower symbol rate of 40 Gbaud (limited by the sampling rate of the AWG). To the best of our knowledge, the rates achieved are the highest ever using optical PAM-M formats.

PAMs ameliorates the imiquimod-induced psoriasis-like skin disease in mice by inhibition of translocation of NF-κB and production of inflammatory cytokines.

PubMed

Dou, Rongkun; Liu, Zongying; Yuan, Xue; Xiangfei, Danzhou; Bai, Ruixue; Bi, Zhenfei; Yang, Piao; Yang, Yalan; Dong, Yinsong; Su, Wei; Li, Diqiang; Mao, Canquan

2017-01-01

Psoriasis is a chronic and persistent inflammatory skin disease seriously affecting the quality of human life. In this study, we reported an ancient formula of Chinese folk medicine, the natural plant antimicrobial solution (PAMs) for its anti-inflammatory effects and proposed the primary mechanisms on inhibiting the inflammatory response in TNF-α/IFN-γ-induced HaCaT cells and imiquimod-induced psoriasis-like skin disease mouse model. Two main functional components of hydroxysafflor Yellow A and allantoin in PAMs were quantified by HPLC to be 94.2±2.2 and 262.9±12.5 μg/mL respectively. PAMs could significantly reduce the gene expression and inflammatory cytokines production of Macrophage-Derived Chemokine (MDC), IL-8 and IL-6 in TNF-α/IFN-γ-induced HaCaT cells. PAMs also significantly ameliorates the psoriatic-like symptoms in a mouse model with the evaluation scores for both the single (scales, thickness, erythema) and cumulative features were in the order of blank control < Dexamethasone < PAMs < 50% ethanol < model groups. The results were further confirmed by hematoxylin-eosin staining, RT-qPCR and immunohistochemistry. The down-regulated gene expression of IL-8, TNF-α, ICAM-1 and IL-23 in mouse tissues was consistent with the results from those of the HaCaT cells. The inhibition of psoriasis-like skin inflammation by PAMs was correlated with the inactivation of the translocation of P65 protein into cellular nucleus, indicating the inhibition of the inflammatory NF-κB signaling pathway. Taken together, these findings suggest that PAMs may be a promising drug candidate for the treatment of inflammatory skin disorders, such as psoriasis.

High-Throughput Characterization of Cascade type I-E CRISPR Guide Efficacy Reveals Unexpected PAM Diversity and Target Sequence Preferences.

PubMed

Fu, Becky Xu Hua; Wainberg, Michael; Kundaje, Anshul; Fire, Andrew Z

2017-08-01

Interactions between Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) RNAs and CRISPR-associated (Cas) proteins form an RNA-guided adaptive immune system in prokaryotes. The adaptive immune system utilizes segments of the genetic material of invasive foreign elements in the CRISPR locus. The loci are transcribed and processed to produce small CRISPR RNAs (crRNAs), with degradation of invading genetic material directed by a combination of complementarity between RNA and DNA and in some cases recognition of adjacent motifs called PAMs (Protospacer Adjacent Motifs). Here we describe a general, high-throughput procedure to test the efficacy of thousands of targets, applying this to the Escherichia coli type I-E Cascade (CRISPR-associated complex for antiviral defense) system. These studies were followed with reciprocal experiments in which the consequence of CRISPR activity was survival in the presence of a lytic phage. From the combined analysis of the Cascade system, we found that (i) type I-E Cascade PAM recognition is more expansive than previously reported, with at least 22 distinct PAMs, with many of the noncanonical PAMs having CRISPR-interference abilities similar to the canonical PAMs; (ii) PAM positioning appears precise, with no evidence for tolerance to PAM slippage in interference; and (iii) while increased guanine-cytosine (GC) content in the spacer is associated with higher CRISPR-interference efficiency, high GC content (>62.5%) decreases CRISPR-interference efficiency. Our findings provide a comprehensive functional profile of Cascade type I-E interference requirements and a method to assay spacer efficacy that can be applied to other CRISPR-Cas systems. Copyright © 2017 by the Genetics Society of America.

Performance Comparison of 112-Gb/s DMT, Nyquist PAM4, and Partial-Response PAM4 for Future 5G Ethernet-Based Fronthaul Architecture

NASA Astrophysics Data System (ADS)

Eiselt, Nicklas; Muench, Daniel; Dochhan, Annika; Griesser, Helmut; Eiselt, Michael; Olmos, Juan Jose Vegas; Monroy, Idelfonso Tafur; Elbers, Joerg-Peter

2018-05-01

For a future 5G Ethernet-based fronthaul architecture, 100G trunk lines of a transmission distance up to 10 km standard single mode fiber (SSMF) in combination with cheap grey optics to daisy chain cell site network interfaces are a promising cost- and power-efficient solution. For such a scenario, different intensity modulation and direct detect (IMDD) Formats at a data rate of 112 Gb/s, namely Nyquist four-level pulse amplitude modulation (PAM4), discrete multi-tone Transmission (DMT) and partial-response (PR) PAM4 are experimentally investigated, using a low-cost electro-absorption modulated laser (EML), a 25G driver and current state-of-the-art high Speed 84 GS/s CMOS digital-to-analog converter (DAC) and analog-to-digital converter (ADC) test chips. Each modulation Format is optimized independently for the desired scenario and their digital signal processing (DSP) requirements are investigated. The performance of Nyquist PAM4 and PR PAM4 depend very much on the efficiency of pre- and post-equalization. We show the necessity for at least 11 FFE-taps for pre-emphasis and up to 41 FFE coefficients at the receiver side. In addition, PR PAM4 requires an MLSE with four states to decode the signal back to a PAM4 signal. On the contrary, bit- and power-loading (BL, PL) is crucial for DMT and an FFT length of at least 512 is necessary. With optimized parameters, all Modulation formats result in a very similar performances, demonstrating a transmission distance of up to 10 km over SSMF with bit error rates (BERs) below a FEC threshold of 4.4E-3, allowing error free transmission.

Novel R2R3-MYB transcription factors from Prunus americana regulate differential patterns of anthocyanin accumulation in tobacco and citrus

PubMed Central

Dasgupta, Kasturi; Stover, Ed; Oliveira, Maria Luiza; Thomson, James

2017-01-01

ABSTRACT The level of anthocyanins in plants vary widely among cultivars, developmental stages and environmental stimuli. Previous studies have reported that the expression of various MYBs regulate anthocyanin pigmentation during growth and development. Here we examine the activity of 3 novel R2R3-MYB transcription factor (TF) genes, PamMybA.1, PamMybA.3 and PamMybA.5 from Prunus americana. The anthocyanin accumulation patterns mediated by CaMV double35S promoter (db35Sp) controlled expression of the TFs in transgenic tobacco were compared with citrus-MoroMybA, Arabidopsis-AtMybA1 and grapevine-VvMybA1 transgenics during their entire growth cycles. The db35Sp-PamMybA.1 and db35Sp-PamMybA.5 constructs induced high levels of anthocyanin accumulation in both transformed tobacco calli and the regenerated plants. The red/purple color pigmentation induced in the PamMybA.1 and PamMybA.5 lines was not uniformly distributed, but appeared as patches in the leaves, whereas the flowers showed intense uniform pigmentation similar to the VvMybA1 expressing lines. MoroMybA and AtMybA1 showed more uniform pink coloration in both vegetative and reproductive tissues. Plant morphology, anthocyanin content, seed viability, and transgene inheritance were examined for the PamMybA.5 transgenic plants and compared with the controls. We conclude that these TFs alone are sufficient for activating anthocyanin production in plants and may be used as visible reporter genes for plant transformation. Evaluating these TFs in a heterologous crop species such as citrus further validated that these genes can be useful for the metabolic engineering of anthocyanin production and cultivar enhancement. PMID:28051907

32 CFR Appendix A to Part 505 - References

Code of Federal Regulations, 2013 CFR

2013-07-01

... 1974 (5 U.S.C. 552a, as amended). (b) OMB Circular No. A-130, Management of Federal Information Resources. (c) AR 25-55, The Department of the Army Freedom of Information Program. (d) DA PAM 25-51, The..., Information Assurance (h) AR 25-400-2, The Army Records Information Management System (ARIMS). (i) AR 27-10...

32 CFR Appendix A to Part 505 - References

Code of Federal Regulations, 2014 CFR

2014-07-01

... 1974 (5 U.S.C. 552a, as amended). (b) OMB Circular No. A-130, Management of Federal Information Resources. (c) AR 25-55, The Department of the Army Freedom of Information Program. (d) DA PAM 25-51, The..., Information Assurance (h) AR 25-400-2, The Army Records Information Management System (ARIMS). (i) AR 27-10...

32 CFR Appendix A to Part 505 - References

Code of Federal Regulations, 2012 CFR

2012-07-01

... 1974 (5 U.S.C. 552a, as amended). (b) OMB Circular No. A-130, Management of Federal Information Resources. (c) AR 25-55, The Department of the Army Freedom of Information Program. (d) DA PAM 25-51, The..., Information Assurance (h) AR 25-400-2, The Army Records Information Management System (ARIMS). (i) AR 27-10...

32 CFR Appendix A to Part 505 - References

Code of Federal Regulations, 2011 CFR

2011-07-01

... 1974 (5 U.S.C. 552a, as amended). (b) OMB Circular No. A-130, Management of Federal Information Resources. (c) AR 25-55, The Department of the Army Freedom of Information Program. (d) DA PAM 25-51, The..., Information Assurance (h) AR 25-400-2, The Army Records Information Management System (ARIMS). (i) AR 27-10...

An Operational Utility Assessment: Measuring the Effectiveness of the Experimental Forward Operating Base Program

DTIC Science & Technology

2014-06-01

SPACES product brochure . Retrieved from https://www.iristechnology.com/manuals/BR-Iris-SPACES.pdf Jameson, LLC. (2014, April 11). EMI hardened LED...Army. (2010). TRADOC generating force study (TRADOC Pamphlet 525-8-1). Retrieved from http://www.tradoc.army.mil/tpubs/pams/tp525-8-1.pdf U.S. Army

Plasma peptidylglycine alpha-amidating monooxygenase (PAM) and ceruloplasmin are affected by age and copper status in rats and mice

PubMed Central

Prohaska, Joseph R.; Broderius, Margaret

2009-01-01

In an attempt to identify a sensitive and improved marker of mammalian copper status during neonatal development experiments compared two plasma cuproenzymes, peptidylglycine α-amidating monooxygenase (PAM ), an enzyme involved in peptide posttranslational activation, to ceruloplasmin (Cp), a ferroxidase involved in iron mobilization. Dietary Cu deficiency (Cu−) was studied in dams and offspring at postnatal age 3 (P3), P12, and P28. Rodent Cp activity rose during lactation whereas PAM activity fell. Reduction in Cp activity was more severe than reduction in PAM activity in Cu− offspring and dams. Cp activity was greater in rats than mice whereas PAM activity was similar in adults but greater in mouse than rat pups. Both cuproenzymes changed during neonatal development and when dietary copper was limiting. With proper controls, each enzyme can be used to assess copper status. PMID:16448835

Naegleria fowleri: Diagnosis, Pathophysiology of Brain Inflammation, and Antimicrobial Treatments.

PubMed

Pugh, J Jeffrey; Levy, Rebecca A

2016-09-21

Primary amoebic meningoencephalitis (PAM) is a very rare disease with a high mortality rate. PAM is caused by Naegleria fowleri, an amoeba which resides in freshwater lakes and ponds and can survive in inadequately chlorinated pools ( Lopez, C.; Budge, P.; Chen, J., et al. Primary amebic meningoencephalitis: a case report and literature review . Pediatr. Emerg. Care 2012 , 28 , 272 - 276 ). In the past 50 years, there have been over 130 cases of Naegleria induced PAM in the United States with only three known survivors; one survivor was diagnosed and treated at Arkansas Children's Hospital. Successful treatment of PAM started with a rapid diagnosis, extensive antimicrobial therapy including an investigational medication miltefosine, supportive care, an intraventricular shunt, and hypothermia. These treatments address different aspects of the disease process. Increased understanding of the diagnosis and treatment of PAM is important especially for patients who present with meningitis-like findings during the summer months.

A passive and active microwave-vector radiative transfer (PAM-VRT) model

NASA Astrophysics Data System (ADS)

Yang, Jun; Min, Qilong

2015-11-01

A passive and active microwave vector radiative transfer (PAM-VRT) package has been developed. This fast and accurate forward microwave model, with flexible and versatile input and output components, self-consistently and realistically simulates measurements/radiation of passive and active microwave sensors. The core PAM-VRT, microwave radiative transfer model, consists of five modules: gas absorption (two line-by-line databases and four fast models); hydrometeor property of water droplets and ice (spherical and nonspherical) particles; surface emissivity (from Community Radiative Transfer Model (CRTM)); vector radiative transfer of successive order of scattering (VSOS); and passive and active microwave simulation. The PAM-VRT package has been validated against other existing models, demonstrating good accuracy. The PAM-VRT not only can be used to simulate or assimilate measurements of existing microwave sensors, but also can be used to simulate observation results at some new microwave sensors.

PAM-4 Signaling over VCSELs with 0.13µm CMOS Chip Technology

NASA Astrophysics Data System (ADS)

Cunningham, J. E.; Beckman, D.; Zheng, Xuezhe; Huang, Dawei; Sze, T.; Krishnamoorthy, A. V.

2006-12-01

We present results for VCSEL based links operating PAM-4 signaling using a commercial 0.13µm CMOS technology. We perform a complete link analysis of the Bit Error Rate, Q factor, random and deterministic jitter by measuring waterfall curves versus margins in time and amplitude. We demonstrate that VCSEL based PAM 4 can match or even improve performance over binary signaling under conditions of a bandwidth limited, 100meter multi-mode optical link at 5Gbps. We present the first sensitivity measurements for optical PAM-4 and compare it with binary signaling. Measured benefits are reconciled with information theory predictions.

PAM-4 Signaling over VCSELs with 0.13microm CMOS Chip Technology.

PubMed

Cunningham, J E; Beckman, D; Zheng, Xuezhe; Huang, Dawei; Sze, T; Krishnamoorthy, A V

2006-12-11

We present results for VCSEL based links operating PAM-4 signaling using a commercial 0.13microm CMOS technology. We perform a complete link analysis of the Bit Error Rate, Q factor, random and deterministic jitter by measuring waterfall curves versus margins in time and amplitude. We demonstrate that VCSEL based PAM-4 can match or even improve performance over binary signaling under conditions of a bandwidth limited, 100meter multi-mode optical link at 5Gbps. We present the first sensitivity measurements for optical PAM-4 and compare it with binary signaling. Measured benefits are reconciled with information theory predictions.

Monitoring photodynamic therapy with photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Shao, Peng; Chapman, David W.; Moore, Ronald B.; Zemp, Roger J.

2015-10-01

We present our work on examining the feasibility of monitoring photodynamic therapy (PDT)-induced vasculature change with acoustic-resolution photoacoustic microscopy (PAM). Verteporfin, an FDA-approved photosensitizer for clinical PDT, was utilized. With a 60-μm-resolution PAM system, we demonstrated the capability of PAM to monitor PDT-induced vasculature variations in a chick chorioallantoic membrane model with topical application and in a rat ear with intravenous injection of the photosensitizer. We also showed oxygen saturation change in target blood vessels due to PDT. Success of the present approach may potentially lead to the application of PAM imaging in evaluating PDT efficacy, guiding treatment, and predicting responders from nonresponders.

The measurement of hemoglobin oxygen saturation using multiwavelength photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Deng, Zilin; Yang, Xiaoquan; Yu, Lejun; Gong, Hui

2010-02-01

Hemoglobin oxygen saturation (SO2) is one of the most critical functional parameters to the metabolism. In this paper, we mainly introduced some initial results of measuring blood oxygen using multi-wavelength photoacoustic microscopy (PAM). In phantom study, we demonstrate the photoacoustic signal amplitude increases linearly with the concentration of red or blue ink. Then the calculated concentration of red ink in double-ink mixtures with PAM has a 5% difference with the result measured with spectrophotometric analysis. In ex vivo experiment, the measured result exhibt 15% difference between the PAM and spectrophotometric analysis. Experiment results suggest that PAM could be used to determine the SO2 quantitatively.

Engineered Cpf1 variants with altered PAM specificities.

PubMed

Gao, Linyi; Cox, David B T; Yan, Winston X; Manteiga, John C; Schneider, Martin W; Yamano, Takashi; Nishimasu, Hiroshi; Nureki, Osamu; Crosetto, Nicola; Zhang, Feng

2017-08-01

The RNA-guided endonuclease Cpf1 is a promising tool for genome editing in eukaryotic cells. However, the utility of the commonly used Acidaminococcus sp. BV3L6 Cpf1 (AsCpf1) and Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1) is limited by their requirement of a TTTV protospacer adjacent motif (PAM) in the DNA substrate. To address this limitation, we performed a structure-guided mutagenesis screen to increase the targeting range of Cpf1. We engineered two AsCpf1 variants carrying the mutations S542R/K607R and S542R/K548V/N552R, which recognize TYCV and TATV PAMs, respectively, with enhanced activities in vitro and in human cells. Genome-wide assessment of off-target activity using BLISS indicated that these variants retain high DNA-targeting specificity, which we further improved by introducing an additional non-PAM-interacting mutation. Introducing the identified PAM-interacting mutations at their corresponding positions in LbCpf1 similarly altered its PAM specificity. Together, these variants increase the targeting range of Cpf1 by approximately threefold in human coding sequences to one cleavage site per ∼11 bp.

Borotungstic Acid (BWA)-Polyacrylamide (PAM) Solid Polymer Electrolytes for Electrochemical Capacitors

NASA Astrophysics Data System (ADS)

Foong, Yee Wei

Solid polymer electrolytes (SPEs) are key enablers for thin and flexible electrochemical capacitors in wearable technologies. Polyacrylamide (PAM) is one such promising hygroscopic polymer host, but its performance had not been optimized. This thesis enhanced PAM with borotungstic acid (BWA) as the heteropolyacid conductors. The BWA-PAM electrolyte achieved a high initial conductivity of ca. 27 mS cm-1, but suffered from a short service life (< 40% conductivity retention after 28 days) due to dehydration. BWA-PAM modified with acidic (H3PO4) and neutral (glycerol) plasticizers showed improved conductivity of ca. 30 mS cm-1 and service life (≥ 70% conductivity retention after 28 days). The high BWA and H3PO4 content accelerated the hydrolysis of PAM to polyacrylic acid, resulting in the undesirable precipitation of NH4+-substituted BWA; whereas, glycerol was found to suppress this reaction. The solid CNT-graphite cells with the optimized electrolytes demonstrated a capacitance of ca. 19.5 mF cm -2; a high rate capability (≥ 75% capacitance retention) at 1Vs -1; excellent cycle life (≥ 90% retention of its initial capacitance); and maintained ca. -85° phase angle over 10,000 charging-discharging cycles.

National Program for Inspection of Non-Federal Dams. Chase Pond Dam (NH 00255), NHWRB Number 253.02, Merrimack River Basin, Wilmot, New Hampshire. Phase I Inspection Report.

DTIC Science & Technology

1980-03-01

STANDAROS-1963-A L ~.°.. o...... 1....MERRIMACK RIVER BASIN -!. WILMOT , NEW HAMPSHIRE ’,- CHASE POND DAM NH 00255 NHWRB NO. 253.02 r PHASE I...Continue on fewsorsp side #0 .o..oemay and Ientify by black Muthot) - DAMS, NSPECTION, PAM S’AFETY, Merrimack River Basin. * Wilmot , New Hampshire...MERRIMACK RIVER BASIN R WILMOT , NEW HAMPSHIRE - - PHASE I INSPECTION REPORT NATIONAL DAM INSPECTION PROGRAM :: : I

Reducing sediment and phosphorus in tributary waters with alum and polyacrylamide.

PubMed

Mason, L B; Amrhein, C; Goodson, C C; Matsumoto, M R; Anderson, M A

2005-01-01

The Salton Sea is the largest inland water body in California, covering an area of 980 km(2). Inflow to the Salton Sea (1.6 km(3) yr(-1)) is predominately nutrient-rich agricultural wastewater, which has led to eutrophication. Because internal phosphorus release from the bottom sediments is comparatively low and external phosphorus loading to the Salton Sea is high, reduction of tributary phosphorus is expected to reduce algal blooms, increase dissolved oxygen, and reduce odors. Removing both dissolved phosphorus and phosphorus-laden sediment from agricultural drainage water (ADW) should decrease eutrophication. Both alum and polyacrylamide (PAM) are commonly used in wastewater treatment to remove phosphorus and sediment and were tested for use in tributary waters. Laboratory jar tests determined PAM effectiveness (2 mg L(-1)) for turbidity reduction as cationic > anionic = nonionic. Although cationic PAM was the most effective at reducing turbidity at higher speeds, there was no observed difference between the neutral and anionic PAMs at velocity gradients of 18 to 45 s(-1). Alum (4 mg L(-1) Al) reduced turbidity in low energy systems (velocity gradients < 10 s(-1)) by 95% and was necessary to reduce soluble phosphorus, which comprises 47 to 100% of the total P concentration in the tributaries. When PAM was added with alum, the anionic PAM became ineffective in aiding flocculation. The nonionic PAM (2 mg L(-1)) + alum (4 mg L(-1) Al) is recommended to reduce suspended solids in higher energy systems and reduce soluble P by 93%.

Professional Development Needs of Science and Technology Librarians: Results of the 2012 SLA/PAM Professional Development Committee Survey

ERIC Educational Resources Information Center

Tchangalova, Nedelina; Lam, Margaret N.

2013-01-01

This article reports and analyzes the survey results on the continuing education needs of librarians with current job responsibilities in the science, technology, and engineering subject fields. The intended purpose of the survey results is to assist conference coordinators in the development of a continuing education program at future Special…

PF-06827443 Displays Robust Allosteric Agonist and Positive Allosteric Modulator Activity in High Receptor Reserve and Native Systems.

PubMed

Moran, Sean P; Cho, Hyekyung P; Maksymetz, James; Remke, Daniel H; Hanson, Ryan M; Niswender, Colleen M; Lindsley, Craig W; Rook, Jerri M; Conn, P Jeffrey

2018-04-25

Positive allosteric modulators (PAMs) of the M 1 subtype of muscarinic acetylcholine receptor have attracted intense interest as an exciting new approach for improving the cognitive deficits in schizophrenia and Alzheimer's disease. Recent evidence suggests that the presence of intrinsic agonist activity of some M 1 PAMs may reduce efficacy and contribute to adverse effect liability. However, the M 1 PAM PF-06827443 was reported to have only weak agonist activity at human M 1 receptors but produced M 1 -dependent adverse effects. We now report that PF-06827443 is an allosteric agonist in cell lines expressing rat, dog, and human M 1 and use of inducible cell lines shows that agonist activity of PF-06827443 is dependent on receptor reserve. Furthermore, PF-06827443 is an agonist in native tissue preparations and induces behavioral convulsions in mice similar to other ago-PAMs. These findings suggest that PF-06827443 is a robust ago-PAM, independent of species, in cell lines and native systems.

Preparation, Biological Evaluation and Dosimetry Studies of 175Yb-Bis-Phosphonates for Palliative Treatment of Bone Pain.

PubMed

Fakhari, Ashraf; Jalilian, Amir R; Yousefnia, Hassan; Shanehsazzadeh, Saeed; Samani, Ali Bahrami; Daha, Fariba Johari; Ardestani, Mehdi Shafiee; Khalaj, Ali

2015-10-05

Optimized production and quality control of ytterbium-175 (Yb-175) labeled pamidronate and alendronate complexes as efficient agents for bone pain palliation has been presented. Yb-175 labeled pamidronate and alendronate (175Yb-PMD and 175Yb-ALN) complexes were prepared successfully at optimized conditions with acceptable radiochemical purity, stability and significant hydroxyapatite absorption. The biodistribution of complexes were evaluated up to 48 h, which demonstrated significant bone uptake ratios for 175Yb-PAM at all-time intervals. It was also detected that 175Yb-PAM mostly washed out and excreted through the kidneys. The performance of 175Yb-PAM in an animal model was better or comparable to other 175Yb-bone seeking complexes previously reported. Based on calculations, the total body dose for 175Yb-ALN is 40% higher as compared to 175Yb-PAM (especially kidneys) indicating that 175Yb-PAM is probably a safer agent than 175Yb-ALN.

Preparation, Biological Evaluation and Dosimetry Studies of 175Yb-Bis-Phosphonates for Palliative Treatment of Bone Pain

PubMed Central

Fakhari, Ashraf; Jalilian, Amir R.; Yousefnia, Hassan; Shanehsazzadeh, Saeed; Samani, Ali Bahrami; Daha, Fariba Johari; Ardestani, Mehdi Shafiee; Khalaj, Ali

2015-01-01

Objective: Optimized production and quality control of ytterbium-175 (Yb-175) labeled pamidronate and alendronate complexes as efficient agents for bone pain palliation has been presented. Methods: Yb-175 labeled pamidronate and alendronate (175Yb-PMD and 175Yb-ALN) complexes were prepared successfully at optimized conditions with acceptable radiochemical purity, stability and significant hydroxyapatite absorption. The biodistribution of complexes were evaluated up to 48 h, which demonstrated significant bone uptake ratios for 175Yb-PAM at all-time intervals. It was also detected that 175Yb-PAM mostly washed out and excreted through the kidneys. Results: The performance of 175Yb-PAM in an animal model was better or comparable to other 175Yb-bone seeking complexes previously reported. Conclusion: Based on calculations, the total body dose for 175Yb-ALN is 40% higher as compared to 175Yb-PAM (especially kidneys) indicating that 175Yb-PAM is probably a safer agent than 175Yb-ALN. PMID:27529886

Quantitative imaging of bilirubin by photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Zhou, Yong; Zhang, Chi; Yao, Da-Kang; Wang, Lihong V.

2013-03-01

Noninvasive detection of both bilirubin concentration and its distribution is important for disease diagnosis. Here we implemented photoacoustic microscopy (PAM) to detect bilirubin distribution. We first demonstrate that our PAM system can measure the absorption spectra of bilirubin and blood. We also image bilirubin distributions in tissuemimicking samples, both without and with blood mixed. Our results show that PAM has the potential to quantitatively image bilirubin in vivo for clinical applications.

One step synthesis of polyacrylamide functionalized graphene and its application in Pb(II) removal

NASA Astrophysics Data System (ADS)

Xu, Zhiwei; Zhang, Yaoyao; Qian, Xiaoming; Shi, Jie; Chen, Lei; Li, Baodong; Niu, Jiarong; Liu, Liangsen

2014-10-01

Polyacrylamide grafted graphene (PAM-g-graphene) from graphite oxide (GO) was successfully prepared by γ-ray irradiation with acrylamide monomers in aqueous at room temperature in this paper. Our strategy involves the PAM chains graft on the surface and between the layers of GO by in situ radical polymerization which led to the exfoliation of GO into individual sheets. Results show that the degree of grafting of PAM-g-graphene samples is 24.2%, and the thickness is measured to be 2.59 nm. Moreover, the as-prepared PAM-g-graphene with some amino from PAM and little oxygen functional groups exhibit superior adsorption of Pb(II) ions. The adsorption processes reach equilibrium in just 30 min and the adsorption isotherms are described well by Langmuir and Freundlich classical isotherms models. The determined adsorption capacity of PAM-g-graphene is 819.67 mg g-1 (pH 6) for Pb(II), which is 20 times and 8 times capacities of that for graphene nanosheets and carbon nanotubes according to reports, respectively. This chemically modified graphene synthesized by this fast one-step approach, featuring a good versatility and adaptability, excellent adsorption capacity and rapid extraction, may provide a new idea for the global problem of heavy metal pollutants' removal in water.

Accelerated Biofluid Filling in Complex Microfluidic Networks by Vacuum-Pressure Accelerated Movement (V-PAM).

PubMed

Yu, Zeta Tak For; Cheung, Mei Ki; Liu, Shirley Xiaosu; Fu, Jianping

2016-09-01

Rapid fluid transport and exchange are critical operations involved in many microfluidic applications. However, conventional mechanisms used for driving fluid transport in microfluidics, such as micropumping and high pressure, can be inaccurate and difficult for implementation for integrated microfluidics containing control components and closed compartments. Here, a technology has been developed termed Vacuum-Pressure Accelerated Movement (V-PAM) capable of significantly enhancing biofluid transport in complex microfluidic environments containing dead-end channels and closed chambers. Operation of the V-PAM entails a pressurized fluid loading into microfluidic channels where gas confined inside can rapidly be dissipated through permeation through a thin, gas-permeable membrane sandwiched between microfluidic channels and a network of vacuum channels. Effects of different structural and operational parameters of the V-PAM for promoting fluid filling in microfluidic environments have been studied systematically. This work further demonstrates the applicability of V-PAM for rapid filling of temperature-sensitive hydrogels and unprocessed whole blood into complex irregular microfluidic networks such as microfluidic leaf venation patterns and blood circulatory systems. Together, the V-PAM technology provides a promising generic microfluidic tool for advanced fluid control and transport in integrated microfluidics for different microfluidic diagnosis, organs-on-chips, and biomimetic studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polyacrylamide hydrogel as a template in situ synthesis of CdS nanoparticles with high photocatalytic activity and photostability

NASA Astrophysics Data System (ADS)

Yang, Jiangbing; Gao, Jianping; Wang, Xiaoxue; Mei, Shunkang; Zhao, Ruiru; Hao, Chaoyue; Wu, Yongli; Zhai, Xiangang; Liu, Yu

2017-10-01

Porous polyacrylamide hydrogel (PAM) was prepared by polymerization at room temperature. Cadmium sulfide/polyacrylamide hydrogels (CdS/PAM) was synthesized by in situ loading CdS nanoparticles and used for photocatalytic decomposition of water for the first time. The size distribution of the loaded CdS nanoparticles is 3-12 nm. We studied the enhanced photocatalytic activity and photo-corrosion inhibition of CdS/PAM the compared with pure CdS and probed the mechanism of the improvement. In particular, the CdS/PAM prepared in 0.003 M CdCl2 solution exhibited the highest hydrogen production efficiency of 2.929 mmol g-1 h-1, about 79 times that of pure CdS. The results demonstrate that the formation of new N-Cd bond and high transmittance of CdS/PAM dramatically enhance photocatalytic activity. The electron cloud of nitrogen atom can attract holes and repel photogenerated electrons, which lowers the carrier recombination probability. The results also reveal that the excellent hydrophilicity of hydrogel plays an important role in the inhibition of photocorrosion. In addition, CdS/PAM is easily recycled and processed. The present work will pave a good way for the application of smart hydrogels in the field of photocatalytic hydrogen production. [Figure not available: see fulltext.

Pressure application measurement (PAM): a novel behavioural technique for measuring hypersensitivity in a rat model of joint pain.

PubMed

Barton, Nicola J; Strickland, Iain T; Bond, Susan M; Brash, Harry M; Bate, Simon T; Wilson, Alex W; Chessell, Iain P; Reeve, Alison J; McQueen, Daniel S

2007-06-15

Chronic joint pain affects physical well being and can lead to severe psychological and social problems, therefore successful long-term management is highly sought-after. No current behavioural measures of pain used in pre-clinical models mimic the clinical dolorimeter, which provides an objective measure of joint hypersensitivity. In this study we aim to use a novel behavioural readout alongside an established measure to mimic the multifactorial measurements taken in the clinic. Using the pressure application measurement (PAM) device a gradually increasing squeeze was applied across the knee joint of rats until the animal gave an indication of pain or discomfort. PAM and the incapacitance tester were used to detect joint hypersensitivity in a well-established rodent model of adjuvant-induced arthritis. Subsequently, the analgesic effects of prednisolone (1, 3 or 10 mg kg(-1)), morphine (3 mg kg(-1)) and celecoxib (15 mg kg(-1)) were assessed. Both PAM and the incapacitance tester detected a reversal of hypersensitivity 1h post-drug administration. Furthermore, the two readouts were highly correlated, and power analysis indicated that PAM was highly reproducible. In conclusion, PAM provides a novel, accurate behavioural tool for detecting a primary mechanical hypersensitivity in a rat model of chronic inflammatory joint pain.

Enhancement of the optical, thermal and electrical properties of PEO/PAM:Li polymer electrolyte films doped with Ag nanoparticles

NASA Astrophysics Data System (ADS)

Morsi, M. A.; El-Khodary, Sherif A.; Rajeh, A.

2018-06-01

Both lithium bromide (LiBr) and biosynthesized silver nanoparticles (Ag NPs) with average size 2-30 nm have been incorporated into the polymeric matrix of polyethylene oxide and polyacrylamide (PEO/PAM) blend by the casting method. FT-IR analysis indicates the formation of hydrogen bond between the blend components. Also, LiBr and Ag NPs interact with the functional groups of PEO/PAM matrix. The results of XRD analysis depict the semi-crystalline nature of these polymer samples and the degree of crystallinity is decreased due to the addition process. The values of optical energy gap from UV-Vis. data are decreased from 3.55 eV for blend to 3.26 for the nanocomposite sample in the indirect transition. LiBr/Ag NPs assist the improvement of the thermal stability of the PEO/PAM blend, as evidenced by TGA and DTA techniques. Upon the addition of LiBr and Ag NPs, an improvement for the conductivity, dielectric permittivity (έ) and dielectric loss (ἕ) of PEO/PAM solid polymer electrolytes are observed. It's clear that the improvement of the electrical conductivity and dielectric parameters for PEO/PAM: Li+/Ag NPs polymer electrolyte system makes it as a promising candidate for solid-state Li battery applications.

An Archaeal Immune System Can Detect Multiple Protospacer Adjacent Motifs (PAMs) to Target Invader DNA*

PubMed Central

Fischer, Susan; Maier, Lisa-Katharina; Stoll, Britta; Brendel, Jutta; Fischer, Eike; Pfeiffer, Friedhelm; Dyall-Smith, Mike; Marchfelder, Anita

2012-01-01

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system provides adaptive and heritable immunity against foreign genetic elements in most archaea and many bacteria. Although this system is widespread and diverse with many subtypes, only a few species have been investigated to elucidate the precise mechanisms for the defense of viruses or plasmids. Approximately 90% of all sequenced archaea encode CRISPR/Cas systems, but their molecular details have so far only been examined in three archaeal species: Sulfolobus solfataricus, Sulfolobus islandicus, and Pyrococcus furiosus. Here, we analyzed the CRISPR/Cas system of Haloferax volcanii using a plasmid-based invader assay. Haloferax encodes a type I-B CRISPR/Cas system with eight Cas proteins and three CRISPR loci for which the identity of protospacer adjacent motifs (PAMs) was unknown until now. We identified six different PAM sequences that are required upstream of the protospacer to permit target DNA recognition. This is only the second archaeon for which PAM sequences have been determined, and the first CRISPR group with such a high number of PAM sequences. Cells could survive the plasmid challenge if their CRISPR/Cas system was altered or defective, e.g. by deletion of the cas gene cassette. Experimental PAM data were supplemented with bioinformatics data on Haloferax and Haloquadratum. PMID:22767603

Risk for transmission of Naegleria fowleri from solid organ transplantation.

PubMed

Roy, S L; Metzger, R; Chen, J G; Laham, F R; Martin, M; Kipper, S W; Smith, L E; Lyon, G M; Haffner, J; Ross, J E; Rye, A K; Johnson, W; Bodager, D; Friedman, M; Walsh, D J; Collins, C; Inman, B; Davis, B J; Robinson, T; Paddock, C; Zaki, S R; Kuehnert, M; DaSilva, A; Qvarnstrom, Y; Sriram, R; Visvesvara, G S

2014-01-01

Primary amebic meningoencephalitis (PAM) caused by the free-living ameba (FLA) Naegleria fowleri is a rare but rapidly fatal disease of the central nervous system (CNS) affecting predominantly young, previously healthy persons. No effective chemotherapeutic prophylaxis or treatment has been identified. Recently, three transplant-associated clusters of encephalitis caused by another FLA, Balamuthia mandrillaris, have occurred, prompting questions regarding the suitability of extra-CNS solid organ transplantation from donors with PAM. During 1995-2012, 21 transplant recipients of solid organs donated by five patients with fatal cases of PAM were reported in the United States. None of the recipients developed PAM, and several recipients tested negative for N. fowleri by serology. However, historical PAM case reports and animal experiments with N. fowleri, combined with new postmortem findings from four patients with PAM, suggest that extra-CNS dissemination of N. fowleri can occur and might pose a risk for disease transmission via transplantation. The risks of transplantation with an organ possibly harboring N. fowleri should be carefully weighed for each individual recipient against the potentially greater risk of delaying transplantation while waiting for another suitable organ. In this article, we present a case series and review existing data to inform such risk assessments. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Risk for Transmission of Naegleria fowleri from Solid Organ Transplantation

PubMed Central

Roy, SL; Metzger, R; Chen, JG; Laham, FR; Martin, M; Kipper, SW; Smith, LE; Lyon, GM; Haffner, J; Ross, JE; Rye, AK; Johnson, W; Bodager, D; Friedman, M; Walsh, DJ; Collins, C; Inman, B; Davis, BJ; Robinson, T; Paddock, C; Zaki, SR; Kuehnert, M; DaSilva, A; Qvarnstrom, Y; Sriram, R; Visvesvara, GS

2015-01-01

Primary amebic meningoencephalitis (PAM) caused by the free-living ameba Naegleria fowleri is a rare but rapidly fatal disease of the central nervous system (CNS) affecting predominantly young, previously healthy persons. No effective chemotherapeutic prophylaxis or treatment has been identified. Recently, three transplant-associated clusters of encephalitis caused by another free-living ameba, Balamuthia mandrillaris, have occurred, prompting questions regarding the suitability of extra-CNS solid organ transplantation from donors with PAM. During 1995–2012, 21 transplant recipients of solid organs donated by five patients with fatal cases of PAM were reported in the United States. None of the recipients developed PAM and several recipients tested negative for N. fowleri by serology. However, historical PAM case reports and animal experiments with N. fowleri, combined with new post-mortem findings from four PAM patients, suggest that extra-CNS dissemination of N. fowleri can occur and might pose a risk for disease transmission via transplantation. The risks of transplantation with an organ possibly harboring N. fowleri should be carefully weighed for each individual recipient against the potentially greater risk of delaying transplantation while waiting for another suitable organ. In this article we present a case series and review existing data to inform such risk assessments. PMID:24279908

Structural and water diffusion of poly(acryl amide)/poly(vinyl alcohol) blend films: Experiment and molecular dynamics simulations.

PubMed

Wang, Yanen; Wei, Qinghua; Wang, Shuzhi; Chai, Weihong; Zhang, Yingfeng

2017-01-01

To study the effects of composition ratios and temperature on the diffusion of water molecules in PVA/PAM blend films, five simulation models of PVA/PAM with ten water molecules at different composition ratios (4/0, 3/1, 2/2, 1/3, 0/4) were constructed and simulated by using a molecular dynamics (MD) simulation. The diffusion behavior of water molecules in blends were investigated from the aspects of the diffusion coefficient, free volume, pair correlation function (PCF) and trajectories of water molecules, respectively. And the hydrophilicity of blend composite was studied based on the contact angle and equilibrium water content (EWC) of the blend films. The simulation results show that the diffusion coefficient of water molecules and fractional free volume (FFV) of blend membranes increase with the addition of PAM, and a higher temperature can also improve the diffusion of water molecules. Additionally, the analysis of PCFs reveals the main reason why the diffusion coefficient of water in blend system increases with the addition of PAM. The measurement results of contact angle and EWC of blend films indicate that the hydrophilicity of blend films decreases with the addition of PAM, but the EWC of blends increases with the addition of PAM. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization of pulse amplitude and pulse rate modulation for a human vestibular implant during acute electrical stimulation

NASA Astrophysics Data System (ADS)

Nguyen, T. A. K.; DiGiovanna, J.; Cavuscens, S.; Ranieri, M.; Guinand, N.; van de Berg, R.; Carpaneto, J.; Kingma, H.; Guyot, J.-P.; Micera, S.; Perez Fornos, A.

2016-08-01

Objective. The vestibular system provides essential information about balance and spatial orientation via the brain to other sensory and motor systems. Bilateral vestibular loss significantly reduces quality of life, but vestibular implants (VIs) have demonstrated potential to restore lost function. However, optimal electrical stimulation strategies have not yet been identified in patients. In this study, we compared the two most common strategies, pulse amplitude modulation (PAM) and pulse rate modulation (PRM), in patients. Approach. Four subjects with a modified cochlear implant including electrodes targeting the peripheral vestibular nerve branches were tested. Charge-equivalent PAM and PRM were applied after adaptation to baseline stimulation. Vestibulo-ocular reflex eye movement responses were recorded to evaluate stimulation efficacy during acute clinical testing sessions. Main results. PAM evoked larger amplitude eye movement responses than PRM. Eye movement response axes for lateral canal stimulation were marginally better aligned with PRM than with PAM. A neural network model was developed for the tested stimulation strategies to provide insights on possible neural mechanisms. This model suggested that PAM would consistently cause a larger ensemble firing rate of neurons and thus larger responses than PRM. Significance. Due to the larger magnitude of eye movement responses, our findings strongly suggest PAM as the preferred strategy for initial VI modulation.

Improving Population Health Management Strategies: Identifying Patients Who Are More Likely to Be Users of Avoidable Costly Care and Those More Likely to Develop a New Chronic Disease.

PubMed

Hibbard, Judith H; Greene, Jessica; Sacks, Rebecca M; Overton, Valerie; Parrotta, Carmen

2017-08-01

To explore using the Patient Activation Measure (PAM) for identifying patients more likely to have ambulatory care-sensitive (ACS) utilization and future increases in chronic disease. Secondary data are extracted from the electronic health record of a large accountable care organization. This is a retrospective cohort design. The key predictor variable, PAM score, is measured in 2011, and is used to predict outcomes in 2012-2014. Outcomes include ACS utilization and the likelihood of a new chronic disease. Our sample of 98,142 adult patients was drawn from primary care clinic users. To be included, patients had to have a PAM score in 2011 and at least one clinic visit in each of the three subsequent years. PAM level is a significant predictor of ACS utilization. Less activated patients had significantly higher odds of ACS utilization compared to those with high PAM scores. Similarly, patients with low PAM scores were more likely to have a new chronic disease diagnosis over each of the years of observation. Assessing patient activation may help to identify patients who could benefit from greater support. Such an approach may help ACOs reach population health management goals. © Health Research and Educational Trust.

Synergistic effects of plasma-activated medium and chemotherapeutic drugs in cancer treatment

NASA Astrophysics Data System (ADS)

Chen, Chao-Yu; Cheng, Yun-Chien; Cheng, Yi-Jing

2018-04-01

Chemotherapy is an important treatment method for metastatic cancer, but the drug-uptake efficiency of cancer cells needs to be enhanced in order to diminish the side effects of chemotherapeutic drugs and improve survival. The use of a nonequilibrium low-temperature atmospheric-pressure plasma jet (APPJ) has been demonstrated to exert selective effects in cancer therapy and to be able to enhance the uptake of molecules by cells, which makes an APPJ a good candidate adjuvant in combination chemotherapy. This study estimated the effects of direct helium-based APPJ (He-APPJ) exposure (DE) and He-APPJ-activated RPMI medium (PAM) on cell viability and migration. Both of these treatments decreased cell viability and inhibited cell migration, but to different degrees in different cell types. The use of PAM as a culture medium resulted in the dialkylcarbocyanine (DiI) fluorescent dye entering the cells more efficiently. PAM was combined with the anticancer drug doxorubicin (Doxo) to treat human heptocellular carcinoma HepG2 cells and human adenocarcinomic alveolar basal epithelial A549 cells. The results showed that the synergistic effects of combined PAM and Doxo treatment resulted in stronger lethality in cancer cells than did PAM or Doxo treatment alone. To sum up, PAM has potential as an adjuvant in combination with other drugs to improve curative cancer therapies.

Industrial safety and applied health physics. Annual report for 1980

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

Not Available

1981-11-01

Information is reported in sections entitled: radiation monitoring; Environmental Management Program; radiation and safety surveys; industrial safety and special projects; Office of Operational Safety; and training, lectures, publications, and professional activities. There were no external or internal exposures to personnel which exceeded the standards for radiation protection as defined in DOE Manual Chapter 0524. Only 35 employees received whole body dose equivalents of 10 mSv (1 rem) or greater. There were no releases of gaseous waste from the Laboratory which were of a level that required an incident report to DOE. There were no releases of liquid radioactive waste frommore » the Laboratory which were of a level that required an incident report to DOE. The quantity of those radionuclides of primary concern in the Clinch River, based on the concentration measured at White Oak Dam and the dilution afforded by the Clinch River, averaged 0.16 percent of the concentration guide. The average background level at the Perimeter Air Monitoring (PAM) stations during 1980 was 9.0 ..mu..rad/h (0.090 ..mu..Gy/h). Soil samples were collected at all perimeter and remote monitoring stations and analyzed for eleven radionuclides including plutonium and uranium. Plutonium-239 content ranged from 0.37 Bq/kg (0.01 pCi/g) to 1.5 Bq/kg (0.04 pCi/g), and the uranium-235 content ranged from 0.7 Bq/kg (0.02 pCi/g) to 16 Bq/kg (0.43 pCi/g). Grass samples were collected at all perimeter and remote monitoring stations and analyzed for twelve radionuclides including plutonium and uranium. Plutonium-239 content ranged from 0.04 Bq/kg (0.001 pCi/g) to 0.07 Bq/kg (0.002 pCi/g), and the uranium-235 content ranged from 0.37 Bq/kg (0.01 pCi/g) to 12 Bq/kg (0.33 pCi/g).« less

Antibodies to variant surface antigens of Plasmodium falciparum infected erythrocytes associated with protection from treatment failure and development of anaemia in pregnancy

PubMed Central

Feng, Gaoqian; Aitken, Elizabeth; Yosaatmadja, Francisca; Kalilani, Linda; Meshnick, Steven R; Jaworowski, Anthony; Simpson, Julie A; Rogerson, Stephen J

2009-01-01

Background In pregnancy associated malaria (PAM), Plasmodium falciparum infected erythrocytes (IEs) express variant surface antigens (VSA-PAM) that evade existing immunity and mediate placental sequestration. Antibodies to VSA-PAM develop with gravidity and block placental adhesion or opsonise IEs for phagocytic clearance, protecting women from anemia and low birth weight Methods and findings Using sera from 141 parasitemic pregnant Malawian women enrolled in a randomized trial of antimalarials and VSA-PAM-expressing CS2 IEs, we quantitated levels of IgG to VSA-PAM by flow cytometry and opsonizing antibodies by measuring uptake of IEs by THP1 promonocytes. After controlling for gravidity and antimalarial treatment, IgG against VSA-PAM was associated with decreased anemia at delivery (OR=0.66, 95% confidence interval [CI] 0.46, 0.93; P=0.018) and weakly associated with decreased parasitological failure (OR=0.78; 95% CI, 0.60, 1.03; P=0.075), especially re-infection (OR=0.73; CI, 0.53,1.01; P=0.057). Opsonizing antibodies to CS2 IE were associated with less maternal anemia. (OR=0.31, 95% CI, 0.13, 0.74; P=0.008) and treatment failure (OR=0.48; 95% CI, 0.25, 0.90; P=0.023), primarily due to recrudescent infection (OR=0.49; 95% CI, 0.21, 1.12; P=0.089). Conclusion Both IgG antibody to VSA-PAM and opsonizing antibody, a functional measure of immunity correlate with parasite clearance and less anemia in pregnancy malaria. PMID:19500037

Measuring patient activation in The Netherlands: translation and validation of the American short form Patient Activation Measure (PAM13).

PubMed

Rademakers, Jany; Nijman, Jessica; van der Hoek, Lucas; Heijmans, Monique; Rijken, Mieke

2012-07-31

The American short form Patient Activation Measure (PAM) is a 13-item instrument which assesses patient (or consumer) self-reported knowledge, skills and confidence for self-management of one's health or chronic condition. In this study the PAM was translated into a Dutch version; psychometric properties of the Dutch version were established and the instrument was validated in a panel of chronically ill patients. The translation was done according to WHO guidelines. The PAM 13-Dutch was sent to 4178 members of the Dutch National Panel of people with Chronic illness or Disability (NPCD) in April 2010 (study A) and again to a sub sample of this group (N = 973) in June 2010 (study B). Internal consistency, test-retest reliability and cross-validation with the SBSQ-D (a measure for Health literacy) were computed. The Dutch results were compared to similar Danish and American data. The psychometric properties of the PAM 13-Dutch were generally good. The level of internal consistency is good (α = 0.88) and item-rest correlations are moderate to strong. The Dutch mean PAM score (61.3) is comparable to the American (61.9) and lower than the Danish (64.2). The test-retest reliability was moderate. The association with Health literacy was weak to moderate. The PAM-13 Dutch is a reliable instrument to measure patient activation. More research is needed into the validity of the Patient Activation Measure, especially with respect to a more comprehensive measure of Health literacy.

Assessing the Risk of Primary Amoebic Meningoencephalitis from Swimming in the Presence of Environmental Naegleria fowleri

PubMed Central

Cabanes, Pierre-André; Wallet, France; Pringuez, Emmanuelle; Pernin, Pierre

2001-01-01

Free-living Naegleria fowleri amoebae cause primary amoebic meningoencephalitis (PAM). Because of the apparent conflict between their ubiquity and the rarity of cases observed, we sought to develop a model characterizing the risk of PAM after swimming as a function of the concentration of N. fowleri. The probability of death from PAM as a function of the number of amoebae inhaled is modeled according to results obtained from animals infected with amoeba strains. The calculation of the probability of inhaling one or more amoebae while swimming is based on a double hypothesis: that the distribution of amoebae in the water follows a Poisson distribution and that the mean quantity of water inhaled while swimming is 10 ml. The risk of PAM for a given concentration of amoebae is then obtained by summing the following products: the probability of inhaling n amoebae × the probability of PAM associated with inhaling these n amoebae. We chose the lognormal model to assess the risk of PAM because it yielded the best analysis of the studentized residuals. Nonetheless, the levels of risk thereby obtained cannot be applied to humans without correction, because they are substantially greater than those indicated by available epidemiologic data. The curve was thus adjusted by a factor calculated with the least-squares method. This provides the PAM risk in humans as a function of the N. fowleri concentration in the river. For example, the risk is 8.5 × 10−8 at a concentration of 10 N. fowleri amoebae per liter. PMID:11425704

Cleavage of the main carbon chain backbone of high molecular weight polyacrylamide by aerobic and anaerobic biological treatment.

PubMed

Song, Wenzhe; Zhang, Yu; Gao, Yingxin; Chen, Dong; Yang, Min

2017-12-01

High molecular weight partially hydrolyzed polyacrylamide (PAM) can be bio-hydrolyzed on the amide side group, however, solid evidence regarding the biological cleavage of its main carbon chain backbone is limited. In this study, viscometry, flow field-flow fractionation multi-angle light scattering (FFF-MALS), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) analysis were used to investigate the biodegradability of PAM with a nominal molecular weight of 2 × 10 7  Da (Da) in two suspended aerobic (25 and 40 °C) and two upflow anaerobic blanket reactors (35 and 55 °C) operated for 470 d under a hydraulic residence time (HRT) of 2 d. Both anaerobic and aerobic biological treatment reduced the viscosity from 2.02 cp in the influent to 1.45-1.60 cp, and reduced the molecular weight of PAM using FFF-MALS from 2.17 × 10 7  Da to less than one-third its original size. The removals of both the amide group and carbon chain backbone in the PAM molecule were further supported by the FTIR analysis. In comparison with the other conditions, thermophilic anaerobic treatment exhibited higher efficiency for PAM biodegradation. Batch test excluded the influence of temperature on the molecular weight of PAM over the range 25-55 °C, suggesting that cleavage of the main carbon chain backbone was attributed to biological degradation. Our results suggested that high molecular weight PAM was biodegradable, but mineralization did not occur. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vivo study of endometriosis in mice by photoacoustic microscopy.

PubMed

Ding, Yichen; Zhang, Mingzhu; Lang, Jinghe; Leng, Jinhua; Ren, Qiushi; Yang, Jie; Li, Changhui

2015-01-01

Endometriosis (EM) impacts the healthcare and the quality of life for women of reproductive age. However, there is no reliable noninvasive diagnosis method for either animal study or clinical use. In this work, a novel imaging method, photoacoustic microscopy (PAM) was employed to study the EM on the mouse model. Our results demonstrated the PAM noninvasively provided the high contrast and 3D imaging of subcutaneously implanted EM tissue in the nude mouse in vivo. The statistical study also indicated PAM had high sensitivity and specificity in the diagnosis of EM in this animal study. In addition, we also discussed the potential clinical application for PAM in the diagnosis of EM. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Discovery of a novel, CNS penetrant M4 PAM chemotype based on a 6-fluoro-4-(piperidin-1-yl)quinoline-3-carbonitrile core.

PubMed

Bewley, Blake R; Spearing, Paul K; Weiner, Rebecca L; Luscombe, Vincent B; Zhan, Xiaoyan; Chang, Sichen; Cho, Hyekyung P; Rodriguez, Alice L; Niswender, Colleen M; Conn, P Jeffrey; Bridges, Thomas M; Engers, Darren W; Lindsley, Craig W

2017-09-15

This Letter details the discovery and subsequent optimization of a novel M 4 PAM scaffold based on an 6-fluoro-4-(piperidin-1-yl)quinoline-3-carbonitrile core, which represents a distinct departure from the classical M 4 PAM chemotypes. Optimized compounds in this series demonstrated improved M 4 PAM potency on both human and rat M 4 (4 to 5-fold relative to HTS hit), and displayed attractive physicochemical and DMPK profiles, including good CNS penetration (rat brain:plasma K p =5.3, K p,uu =2.4; MDCK-MDR1 (P-gp) ER=1.1). Copyright © 2017 Elsevier Ltd. All rights reserved.

PAM-4 delivery based on pre-distortion and CMMA equalization in a ROF system at 40 GHz

NASA Astrophysics Data System (ADS)

Zhou, Wen; Zhang, Jiao; Han, Xifeng; Kong, Miao; Gou, Pengqi

2018-06-01

In this paper, we proposed a PAM-4 delivery in a ROF system at 40-GHz. PAM-4 transmission data can be generated via look-up table (LUT) pre-distortion, then delivered over 25km single-mode fiber and 0.5m wireless link. At the receiver side, the received signal can be processed with cascaded multi-module algorithm (CMMA) equalization to improve the decision precision. Our measured results show that 10Gbaud PAM-4 transmission in a ROF system at 40-GHz can be achieved with BER of 1.6 × 10-3. To our knowledge, this is the first time to introduce LUT pre-distortion and CMMA equalization in a ROF system to improve signal performance.

Pneumatic artificial muscle actuators for compliant robotic manipulators

NASA Astrophysics Data System (ADS)

Robinson, Ryan Michael

Robotic systems are increasingly being utilized in applications that require interaction with humans. In order to enable safe physical human-robot interaction, light weight and compliant manipulation are desirable. These requirements are problematic for many conventional actuation systems, which are often heavy, and typically use high stiffness to achieve high performance, leading to large impact forces upon collision. However, pneumatic artificial muscles (PAMs) are actuators that can satisfy these safety requirements while offering power-to-weight ratios comparable to those of conventional actuators. PAMs are extremely lightweight actuators that produce force in response to pressurization. These muscles demonstrate natural compliance, but have a nonlinear force-contraction profile that complicates modeling and control. This body of research presents solutions to the challenges associated with the implementation of PAMs as actuators in robotic manipulators, particularly with regard to modeling, design, and control. An existing PAM force balance model was modified to incorporate elliptic end geometry and a hyper-elastic constitutive relationship, dramatically improving predictions of PAM behavior at high contraction. Utilizing this improved model, two proof-of-concept PAM-driven manipulators were designed and constructed; design features included parallel placement of actuators and a tendon-link joint design. Genetic algorithm search heuristics were employed to determine an optimal joint geometry; allowing a manipulator to achieve a desired torque profile while minimizing the required PAM pressure. Performance of the manipulators was evaluated in both simulation and experiment employing various linear and nonlinear control strategies. These included output feedback techniques, such as proportional-integral-derivative (PID) and fuzzy logic, a model-based control for computed torque, and more advanced controllers, such as sliding mode, adaptive sliding mode, and adaptive neural network control. Results demonstrated the benefits of an accurate model in model-based control, and the advantages of adaptive neural network control when a model is unavailable or variations in payload are expected. Lastly, a variable recruitment strategy was applied to a group of parallel muscles actuating a common joint. Increased manipulator efficiency was observed when fewer PAMs were activated, justifying the use of variable recruitment strategies. Overall, this research demonstrates the benefits of pneumatic artificial muscles as actuators in robotics applications. It demonstrates that PAM-based manipulators can be well-modeled and can achieve high tracking accuracy over a wide range of payloads and inputs while maintaining natural compliance.

Solids and nutrient removal from flushed swine manure using polyacrylamides

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

Vanotti, M.B.; Hunt, P.G.

1999-12-01

Most of the organic nutrients and reduced carbon (C) materials in liquid swine manure are contained in fine suspended particles that are not separated by available mechanical separators. Treatment with polyacrylamide (PAM) polymers prior to mechanical removal or gravity settling has the potential for enhancing solids-liquid separation, thus concentrating nitrogen (N), phosphorus (P), and organic C. In this work, the authors determined PAM charge and density characteristics most desirable for swine wastewater applications and established the optimum chemical requirement. Treatments were applied to flushed manure from two swine operations in North Carolina. Cationic PAMs significantly increased solids separation while performancemore » of neutral and anionic types was not different from a control. Cationic PAMs with moderate-charge density (20%) were more effective than polymers with higher charge density. Flocs were large and effectively retained with a 1-mm screen. Optimum PAM rate varied with the amount of total suspended solids (TSS) in the liquid manure; 26 and 79 mg PAM/L for samples containing 1.5 and 4.1 g TSS/L, respectively. Corresponding TSS removal efficiencies were 90 to 94%. In contrast, screening without PAM treatment captured only 5 to 14% of the suspended solids. Polymer usage rate was consistent and averaged 2.0{degree} based on weight of dry solids produced. Volatile suspended solids (VSS) were highly correlated with TSS and comprised 79.5% of TSS. Chemical oxygen demand (COD) and organic nutrient concentrations in the effluent were also significantly decreased by PAM treatment. The decrease of COD concentration, an important consideration for odor control, was linearly related with removal of suspended solids, at a rate of 2.0 g COD/g TSS and 2.6 g COD/g VSS. Removal efficiency of organic N and P followed approximately a 1:1 relationship with removal efficiency of TSS. Chemical cost to capture 90% of the suspended solids was estimated to be $0.026 per hog per day ($2.79 per finished hog). Results obtained indicate that PAM treatment is very effective for removal of manure solids, COD, and organic nutrients from flushed swine effluents. The technology provides an attractive alternative to existing liquid manure handling methods for conserving nutrients and avoiding excessive nutrient application in areas where swine production is concentrated.« less

PAM4 silicon photonic microring resonator-based transceiver circuits

NASA Astrophysics Data System (ADS)

Palermo, Samuel; Yu, Kunzhi; Roshan-Zamir, Ashkan; Wang, Binhao; Li, Cheng; Seyedi, M. Ashkan; Fiorentino, Marco; Beausoleil, Raymond

2017-02-01

Increased data rates have motivated the investigation of advanced modulation schemes, such as four-level pulseamplitude modulation (PAM4), in optical interconnect systems in order to enable longer transmission distances and operation with reduced circuit bandwidth relative to non-return-to-zero (NRZ) modulation. Employing this modulation scheme in interconnect architectures based on high-Q silicon photonic microring resonator devices, which occupy small area and allow for inherent wavelength-division multiplexing (WDM), offers a promising solution to address the dramatic increase in datacenter and high-performance computing system I/O bandwidth demands. Two ring modulator device structures are proposed for PAM4 modulation, including a single phase shifter segment device driven with a multi-level PAM4 transmitter and a two-segment device driven by two simple NRZ (MSB/LSB) transmitters. Transmitter circuits which utilize segmented pulsed-cascode high swing output stages are presented for both device structures. Output stage segmentation is utilized in the single-segment device design for PAM4 voltage level control, while in the two-segment design it is used for both independent MSB/LSB voltage levels and impedance control for output eye skew compensation. The 65nm CMOS transmitters supply a 4.4Vppd output swing for 40Gb/s operation when driving depletion-mode microring modulators implemented in a 130nm SOI process, with the single- and two-segment designs achieving 3.04 and 4.38mW/Gb/s, respectively. A PAM4 optical receiver front-end is also described which employs a large input-stage feedback resistor transimpedance amplifier (TIA) cascaded with an adaptively-tuned continuous-time linear equalizer (CTLE) for improved sensitivity. Receiver linearity, critical in PAM4 systems, is achieved with a peak-detector-based automatic gain control (AGC) loop.

Full duplex fiber link for alternative wired and wireless access based on SSB optical millimeter-wave with 4-PAM signal

NASA Astrophysics Data System (ADS)

Ma, Jianxin; Zhang, Junjie

2015-03-01

A novel full-duplex fiber-wireless link based on single sideband (SSB) optical millimeter (mm)-wave with 10 Gbit/s 4-pulse amplitude modulation (PAM) signal is proposed to provide alternative wired and 40 GHz wireless accesses for the user terminals. The SSB optical mm-wave with 4-PAM signal consists of two tones: one bears the 4-PAM signal and the other is unmodulated with high power. After transmission over the fiber to the hybrid optical network unit (HONU), the SSB optical mm-wave signal can be decomposed by fiber Bragg gratings (FBGs) as the SSB optical mm-wave signal with reduced carrier-to-sideband ratio (the baseband 4-PAM optical signal) and the uplink optical carrier for the wireless (wired) access. This makes the HONU free from the laser source. For the uplink, since the wireless access signal is converted to the baseband by power detection, both the transmitter in the HONU and the receiver in optical line terminal (OLT) are co-shared for both wireless and wired accesses, which makes the full duplex link much simpler. In our scheme, the optical electrical field of the square-root increment level 4-PAM signal assures an equal level spacing receiving for both the downlink wired and wireless accesses. Since the downlink wireless signal is down-converted to the baseband by power detection, RF local oscillator is unnecessary. To confirm the feasibility of our proposed scheme, a simulation full duplex link with 40 GHz SSB optical mm-wave with 10 Gbit/s 4-PAM signal is built. The simulation results show that both down- and up-links for either wired or wireless access can keep good performance even if the link length of the SSMF is extended to 40 km.

Practice change in community pharmacy: using change-management principles when implementing a pharmacy asthma management service in NSW, Australia.

PubMed

Feletto, Eleonora; Lui, Grace Wan Ying; Armour, Carol; Saini, Bandana

2013-02-01

This study aimed to investigate the application of a research-based change-management tool, the Pharmacy Change Readiness Wheel (PCRW), in practice, and the impact it had on the implementation of an asthma service (Pharmacy Asthma Management Service or PAMS). All pharmacists implementing the PAMS in the state of New South Wales, Australia, were provided training using a custom-designed module explaining change readiness as it applied to the PAMS. This training and a self-administered PCRW checklist were completed before PAMS implementation. Following PAMS service delivery, semi-structured phone interviews were conducted with the pharmacists and any additional staff involved regarding their experiences of change management. Interviews were transcribed verbatim and content analysed. Thirty seven of the forty five pharmacies who delivered PAMS returned the PCRW checklist (82% response rate) and participants from 29 pharmacies were interviewed (29 pharmacists and six additional staff). Perception of readiness for change before service delivery was remarkably high. From the interviews conducted after service delivery it was evident that systematic management of the practice change using theoretical concepts had not really been undertaken and that many challenges were faced in the implementation of practice change (PAMS). The results of the content analysis from the interviews revealed that factors external or internal to the pharmacy or those related to the individual pharmacist could affect implementation of practice change. Change is not as straightforward as it may appear and is a multi-step process over time. Pharmacists were unaware of this. A change-management framework should be applied to specific services with enough flexibility so that pharmacists can individualise them for their pharmacies. © 2012 The Authors. IJPP © 2012 Royal Pharmaceutical Society.

CYP51 is an essential drug target for the treatment of primary amoebic meningoencephalitis (PAM)

PubMed Central

Debnath, Anjan; Calvet, Claudia M.; Aksenov, Alexander; Abagyan, Ruben; Nes, W. David; McKerrow, James H.

2017-01-01

Primary Amoebic Meningoencephalitis (PAM) is caused by Naegleria fowleri, a free-living amoeba that occasionally infects humans. While considered “rare” (but likely underreported) the high mortality rate and lack of established success in treatment makes PAM a particularly devastating infection. In the absence of economic inducements to invest in development of anti-PAM drugs by the pharmaceutical industry, anti-PAM drug discovery largely relies on drug ‘repurposing’—a cost effective strategy to apply known drugs for treatment of rare or neglected diseases. Similar to fungi, N. fowleri has an essential requirement for ergosterol, a building block of plasma and cell membranes. Disruption of sterol biosynthesis by small-molecule inhibitors is a validated interventional strategy against fungal pathogens of medical and agricultural importance. The N. fowleri genome encodes the sterol 14-demethylase (CYP51) target sharing ~35% sequence identity to fungal orthologues. The similarity of targets raises the possibility of repurposing anti-mycotic drugs and optimization of their usage for the treatment of PAM. In this work, we (i) systematically assessed the impact of anti-fungal azole drugs, known as conazoles, on sterol biosynthesis and viability of cultured N. fowleri trophozotes, (ii) identified the endogenous CYP51 substrate by mass spectrometry analysis of N. fowleri lipids, and (iii) analyzed the interactions between the recombinant CYP51 target and conazoles by UV-vis spectroscopy and x-ray crystallography. Collectively, the target-based and parasite-based data obtained in these studies validated CYP51 as a potentially ‘druggable’ target in N. fowleri, and conazole drugs as the candidates for assessment in the animal model of PAM. PMID:29284029

The Role of Patient Activation in Contraceptive Use.

PubMed

Bello, Jennifer K; Lapin, Brittany; Poston, Lindsay; Hirshfeld, Meredith; Hosack, Allison

2016-01-01

Many unintended pregnancies occur due to to contraceptive misuse and nonuse, which is partly due to to lack of knowledge and low self-efficacy related to contraception. We conducted an exploratory, cross-sectional study among low-income women to examine the relationship between knowledge, skills, and confidence in managing one's health, measured using the Patient Activation Measure (PAM) and factors that influence contraceptive use. A survey and chart review were conducted among 18- to 45-year-old women from a community health center in Chicago, Illinois, to measure the relationship between activation, self-confidence in avoiding pregnancy, contraception use, and contraceptive counseling. Associations between PAM and outcomes were evaluated using the χ(2) test and adjusted logistic regression models. Among 112 participants (61% Latina, 15% Black, 14% White), we found no differences in PAM by age, race/ethnicity, or parity. Women with higher PAM were more likely to be confident they could avoid pregnancy compared with women with lower PAM (50% vs. 7%; p = .02). Higher PAM remained a significant predictor for self-confidence after risk adjustment (odds ratio, 3.13; 95% CI, 1.11-8.78; p = .031). Greater confidence in avoiding pregnancy was associated with using a moderately or highly effective contraceptive method (43% vs. 14%; p = .047). Women with lower PAM were less likely to receive contraceptive counseling in the prior month (0% vs. 57%; p < .01). Patient activation may be an important construct for understanding factors that influence women's contraceptive use, including self-confidence in avoiding pregnancy until it is desired and receiving contraceptive services in primary care. Copyright © 2016 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Identification of Global and Ligand-Specific Calcium Sensing Receptor Activation Mechanisms.

PubMed

Keller, Andrew N; Kufareva, Irina; Josephs, Tracy M; Diao, Jiayin; Mai, Vyvyan T; Conigrave, Arthur D; Christopoulos, Arthur; Gregory, Karen J; Leach, Katie

2018-06-01

Calcium sensing receptor (CaSR) positive allosteric modulators (PAMs) are therapeutically important. However, few are approved for clinical use, in part due to complexities in assessing allostery at a receptor where the endogenous agonist (extracellular calcium) is present in all biologic fluids. Such complexity impedes efforts to quantify and optimize allosteric drug parameters (affinity, cooperativity, and efficacy) that dictate PAM structure-activity relationships (SARs). Furthermore, an underappreciation of the structural mechanisms underlying CaSR activation hinders predictions of how PAM SAR relates to in vitro and in vivo activity. Herein, we combined site-directed mutagenesis and calcium mobilization assays with analytical pharmacology to compare modes of PAM binding, positive modulation, and agonism. We demonstrate that 3-(2-chlorophenyl)- N -((1 R )-1-(3-methoxyphenyl)ethyl)-1-propanamine (NPS R568) binds to a 7 transmembrane domain (7TM) cavity common to class C G protein-coupled receptors and used by ( αR )-(-)- α -methyl- N -[3-[3-[trifluoromethylphenyl]propyl]-1-napthalenemethanamine (cinacalcet) and 1-benzothiazol-2-yl-1-(2,4-dimethylphenyl)-ethanol (AC265347); however, there are subtle distinctions in the contribution of select residues to the binding and transmission of cooperativity by PAMs. Furthermore, we reveal some common activation mechanisms used by different CaSR activators, but also demonstrate some differential contributions of residues within the 7TM bundle and extracellular loops to the efficacy of the PAM-agonist, AC265347, versus cooperativity. Finally, we show that PAMS potentiate the affinity of divalent cations. Our results support the existence of both global and ligand-specific CaSR activation mechanisms and reveal that allosteric agonism is mediated in part via distinct mechanisms to positive modulation. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Biological effects of paenilamicin, a secondary metabolite antibiotic produced by the honey bee pathogenic bacterium Paenibacillus larvae.

PubMed

Garcia-Gonzalez, Eva; Müller, Sebastian; Hertlein, Gillian; Heid, Nina; Süssmuth, Roderich D; Genersch, Elke

2014-10-01

Paenibacillus larvae is the etiological agent of American Foulbrood (AFB) a world-wide distributed devastating disease of the honey bee brood. Previous comparative genome analysis and more recently, the elucidation of the bacterial genome, provided evidence that this bacterium harbors putative functional nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) and therefore, might produce nonribosomal peptides (NRPs) and polyketides (PKs). Such biosynthesis products have been shown to display a wide-range of biological activities such as antibacterial, antifungal or cytotoxic activity. Herein we present an in silico analysis of the first NRPS/PKS hybrid of P. larvae and we show the involvement of this cluster in the production of a compound named paenilamicin (Pam). For the characterization of its in vitro and in vivo bioactivity, a knock-out mutant strain lacking the production of Pam was constructed and subsequently compared to wild-type species. This led to the identification of Pam by mass spectrometry. Purified Pam-fractions showed not only antibacterial but also antifungal and cytotoxic activities. The latter suggested a direct effect of Pam on honey bee larval death which could, however, not be corroborated in laboratory infection assays. Bee larvae infected with the non-producing Pam strain showed no decrease in larval mortality, but a delay in the onset of larval death. We propose that Pam, although not essential for larval mortality, is a virulence factor of P. larvae influencing the time course of disease. These findings are not only of significance in elucidating and understanding host-pathogen interactions but also within the context of the quest for new compounds with antibiotic activity for drug development. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

50Gb/s PAM-4 oxide VCSEL development progress at Broadcom

NASA Astrophysics Data System (ADS)

Wang, Jingyi; Murty, M. V. Ramana; Wang, Charlie; Hui, David; Lehman Harren, Ann; Chang, Hsu-Hao; Feng, Zheng-Wen; Fanning, Thomas R.; Sridhara, Aaditya; Taslim, Sumitro-Joyo; Cai, Xinle; Chu, Jason; Giovane, Laura M.

2017-02-01

This paper will review the device design and performance of Broadcom's 50Gb/s PAM-4 VCSEL to enable the next generation of transceivers using a PAM-4 advanced modulation scheme at 25-28 GBd. The VCSEL has been optimized to minimize noise and improve dynamic performance for cleaner eyes. Preliminary wear out lifetime studies indicate that the time to 1% failure exceeds 10 years, making the VCSELs suitable for data communication applications.

Multispectral photoacoustic microscopy of lipids using a pulsed supercontinuum laser.

PubMed

Buma, Takashi; Conley, Nicole C; Choi, Sang Won

2018-01-01

We demonstrate optical resolution photoacoustic microscopy (OR-PAM) of lipid-rich tissue between 1050-1714 nm using a pulsed supercontinuum laser based on a large-mode-area photonic crystal fiber. OR-PAM experiments of lipid-rich samples show the expected optical absorption peaks near 1210 and 1720 nm. These results show that pulsed supercontinuum lasers are promising for OR-PAM applications such as label-free histology of lipid-rich tissue and imaging small animal models of disease.

Comparison of the efficacy of HI6 and 2-PAM against soman, tabun, sarin, and VX in the rabbit

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

Koplovitz, I.; Stewart, J.R.

1994-12-31

This study compared the efficacy of H16 and 2-PAM against nerve agent (soman tabun sarin and VX) -induced lethality in the atropinesterase-free rabbits pretreated with vehicle (controls) or pyridostigmine. Treatment was administered at signs or 2 min after agent challenge and consisted ofoxime (l00umol/lkg) + atropine 13 mg(kg) (alone or together with diazepam). Twenty-four-h LD50 values were calculated for soman- and tabun-intoxicated animals, whereas 24-h survival was noted in animals given 10 LD50s of sarin or VX. In pyridostigmine and control rabbits intoxicated with soman and treated with oxime + atropine (alone or together with diazepam), HI6 was 35 timesmore » more effective than 2-PAM. In contrast 1116 was less effective than 2-PAM against tabun poisoning. In pyridostigmine-pretreated animals exposed to tabun, efficacy was increased more than 3-fold when compare to tabun-challenged animals treated with atropine + H16 alone. Both oximes were highly effective against satin and VX. These findings suggest that Hifi could replace 2-PAM as therapy for nerve agent poisoning because it is superior to 2-PAM against soman, and when used in pyridostigmine-pretreated animals it affords excellent protection against all four nerve agents when used in combination with atropine (alone or together with diazepam) therapy.« less

Chemical Degradation of Polyacrylamide during Hydraulic Fracturing

NASA Astrophysics Data System (ADS)

Xiong, B.; Tasker, T.; Miller, Z.; Roman-White, S.; Farina, B.; Piechowicz, B.; Burgos, W.; Joshi, P.; Zhu, L.; Gorski, C.; Zydney, A.; Kumar, M.

2017-12-01

Polyacrylamide (PAM) based friction reducers are a primary ingredient of slickwater hydraulic fracturing fluids. Little is known regarding the fate of these polymers under downhole conditions, which could have important environmental impacts including strategies for reuse or treatment of flowback water. The objective of this study was to evaluate the chemical degradation of high molecular weight PAM, including the effects of shale, oxygen, temperature, pressure, and salinity. Data were obtained with a slickwater fracturing fluid exposed to both a shale sample collected from a Marcellus shale outcrop and to Marcellus core samples at high pressures/temperatures (HPT) simulating downhole conditions. Based on size exclusion chromatography analyses, the peak molecular weight of the PAM was reduced by two orders of magnitude, from roughly 10 MDa to 200 kDa under typical HPT fracturing conditions. The rate of degradation was independent of pressure and salinity but increased significantly at high temperatures and in the presence of oxygen dissolved in fracturing fluid. Results were consistent with a free radical chain scission mechanism, supported by measurements of sub-M hydroxyl radical concentrations. The shale sample adsorbed some PAM ( 30%), but importantly it catalyzed the chemical degradation of PAM, likely due to dissolution of Fe2+ at low pH. These results provide the first evidence of radical-induced degradation of PAM under HPT hydraulic fracturing conditions without additional oxidative breaker.

High-speed and high-SNR photoacoustic microscopy based on a galvanometer mirror in non-conducting liquid

PubMed Central

Kim, Jin Young; Lee, Changho; Park, Kyungjin; Han, Sangyeob; Kim, Chulhong

2016-01-01

Optical-resolution photoacoustic microscopy (OR-PAM), a promising microscopic imaging technique with high ultrasound resolution and superior optical sensitivity, can provide anatomical, functional, and molecular information at scales ranging from the microvasculature to single red blood cells. In particular, real-time OR-PAM imaging with a high signal-to-noise ratio (SNR) is a prerequisite for widespread use in preclinical and clinical applications. Although several technical approaches have been pursued to simultaneously improve the imaging speed and SNR of OR-PAM, they are bulky, complex, not sensitive, and/or not actually real-time. In this paper, we demonstrate a simple and novel OR-PAM technique which is based on a typical galvanometer immersed in non-conducting liquid. Using an opto-ultrasound combiner, this OR-PAM system achieves a high SNR and fast imaging speed. It takes only 2 seconds to acquire a volumetric image with a wide field of view (FOV) of 4 × 8 mm2 along the X and Y axes, respectively. The measured lateral and axial resolutions are 6.0 and 37.7 μm, respectively. Finally, as a demonstration of the system’s capability, we successfully imaged the microvasculature in a mouse ear in vivo. Our new method will contribute substantially to the popularization and commercialization of OR-PAM in various preclinical and clinical applications. PMID:27708379

Translation, adaptation and validation of the American short form Patient Activation Measure (PAM13) in a Danish version.

PubMed

Maindal, Helle Terkildsen; Sokolowski, Ineta; Vedsted, Peter

2009-06-29

The Patient Activation Measure (PAM) is a measure that assesses patient knowledge, skill, and confidence for self-management. This study validates the Danish translation of the 13-item Patient Activation Measure (PAM13) in a Danish population with dysglycaemia. 358 people with screen-detected dysglycaemia participating in a primary care health education study responded to PAM13. The PAM13 was translated into Danish by a standardised forward-backward translation. Data quality was assessed by mean, median, item response, missing values, floor and ceiling effects, internal consistency (Cronbach's alpha and average inter-item correlation) and item-rest correlations. Scale properties were assessed by Rasch Rating Scale models. The item response was high with a small number of missing values (0.8-4.2%). Floor effect was small (range 0.6-3.6%), but the ceiling effect was above 15% for all items (range 18.6-62.7%). The alpha-coefficient was 0.89 and the average inter-item correlation 0.38. The Danish version formed a unidimensional, probabilistic Guttman-like scale explaining 43.2% of the variance. We did however, find a different item sequence compared to the original scale. A Danish version of PAM13 with acceptable validity and reliability is now available. Further development should focus on single items, response categories in relation to ceiling effects and further validation of reproducibility and responsiveness.

Chemical Degradation of Polyacrylamide during Hydraulic Fracturing.

PubMed

Xiong, Boya; Miller, Zachary; Roman-White, Selina; Tasker, Travis; Farina, Benjamin; Piechowicz, Bethany; Burgos, William D; Joshi, Prachi; Zhu, Liang; Gorski, Christopher A; Zydney, Andrew L; Kumar, Manish

2018-01-02

Polyacrylamide (PAM) based friction reducers are a primary ingredient of slickwater hydraulic fracturing fluids. Little is known regarding the fate of these polymers under downhole conditions, which could have important environmental impacts including decisions on strategies for reuse or treatment of flowback water. The objective of this study was to evaluate the chemical degradation of high molecular weight PAM, including the effects of shale, oxygen, temperature, pressure, and salinity. Data were obtained with a slickwater fracturing fluid exposed to both a shale sample collected from a Marcellus outcrop and to Marcellus core samples at high pressures/temperatures (HPT) simulating downhole conditions. Based on size exclusion chromatography analyses, the peak molecular weight of the PAM was reduced by 2 orders of magnitude, from roughly 10 MDa to 200 kDa under typical HPT fracturing conditions. The rate of degradation was independent of pressure and salinity but increased significantly at high temperatures and in the presence of oxygen dissolved in fracturing fluids. Results were consistent with a free radical chain scission mechanism, supported by measurements of sub-μM hydroxyl radical concentrations. The shale sample adsorbed some PAM (∼30%), but importantly it catalyzed the chemical degradation of PAM, likely due to dissolution of Fe 2+ at low pH. These results provide the first evidence of radical-induced degradation of PAM under HPT hydraulic fracturing conditions without additional oxidative breaker.

Study of methanogen communities associated with different rumen protozoal populations

PubMed Central

Belanche, Alejandro; de la Fuente, Gabriel; Newbold, Charles J

2014-01-01

Protozoa-associated methanogens (PAM) are considered one of the most active communities in the rumen methanogenesis. This experiment investigated whether methanogens are sequestrated within rumen protozoa, and structural differences between rumen free-living methanogens and PAM. Rumen protozoa were harvested from totally faunated sheep, and six protozoal fractions (plus free-living microorganisms) were generated by sequential filtration. Holotrich-monofaunated sheep were also used to investigate the holotrich-associated methanogens. Protozoal size determined the number of PAM as big protozoa had 1.7–3.3 times more methanogen DNA than smaller protozoa, but also more endosymbiotic bacteria (2.2- to 3.5-fold times). Thus, similar abundance of methanogens with respect to total bacteria were observed across all protozoal fractions and free-living microorganisms, suggesting that methanogens are not accumulated within rumen protozoa in a greater proportion to that observed in the rumen as a whole. All rumen methanogen communities had similar diversity (22.2 ± 3.4 TRFs). Free-living methanogens composed a conserved community (67% similarity within treatment) in the rumen with similar diversity but different structures than PAM (P < 0.05). On the contrary, PAM constituted a more variable community (48% similarity), which differed between holotrich and total protozoa (P < 0.001). Thus, PAM constitutes a community, which requires further investigation as part of methane mitigation strategies. PMID:25195951

Benefits and Risks of using Linear Anionic Polyacrylamide (LA-PAM) for Seepage Reduction in Unlined Water Delivery Canals

NASA Astrophysics Data System (ADS)

Susfalk, R. B.; Martin, C.; Sada, D.; Young, M.; Gates, T.; Shanafield, M.; Fitzgerald, B.; Smith, D.

2008-12-01

As water resources continue to be constrained in the arid western United States, there is a need to improve the efficiency in how water is transported from its sources to end-users. In particular, there is a growing need for cost-effective technologies capable of reducing undesirable seepage from water delivery canals where traditional canal sealing methods, such as concrete and geomembranes, are not suitable or cost-prohibitive. One alternative is the use of a linear, anionic polyacrylamide (LA-PAM) applied as granular solid to a flowing canal. The benefits and risks of LA-PAM use in unlined water delivery canals will be discussed in context of a diverse set of experiments that were conducted in the laboratory, at the furrow-scale, and in working water delivery canals. When properly used, the application of LA-PAM reduced seepage rates between 28 and 87 percent at a cost of 78 to 213 km-1. LA-PAM provided a cost-effective tool for canal operators to better manage the volume, timing, and extent of water losses from their canals. However, these benefits must be weighed against potential risks associated with LA-PAM use. Potential risks included the release of small concentrations of residual acrylamide (AMD) monomer, a cumulative neurotoxin and a suspected human carcinogen, and potential impacts on aquatic communities and downstream users.

Synthetic light-needle photoacoustic microscopy for extended depth of field (Conference Presentation)

NASA Astrophysics Data System (ADS)

Yang, Jiamiao; Gong, Lei; Xu, Xiao; Hai, Pengfei; Suzuki, Yuta; Wang, Lihong V.

2017-03-01

Photoacoustic microscopy (PAM) has been extensively applied in biomedical study because of its ability to visualize tissue morphology and physiology in vivo in three dimensions (3D). However, conventional PAM suffers from a rapidly decreasing resolution away from the focal plane because of the limited depth of focus of an objective lens, which deteriorates the volumetric imaging quality inevitably. Here, we propose a novel method to synthesize an ultra-long light needle to extend a microscope's depth of focus beyond its physical limitations with wavefront engineering method. Furthermore, it enables an improved lateral resolution that exceeds the diffraction limit of the objective lens. The virtual light needle can be flexibly synthesized anywhere throughout the imaging volume without mechanical scanning. Benefiting from these advantages, we developed a synthetic light needle photoacoustic microscopy (SLN-PAM) to achieve an extended depth of field (DOF), sub-diffraction and motionless volumetric imaging. The DOF of our SLN-PAM system is up to 1800 µm, more than 30-fold improvement over that gained by conventional PAM. Our system also achieves the lateral resolution of 1.8 µm (characterized at 532 nm and 0.1 NA objective), about 50% higher than the Rayleigh diffraction limit. Its superior imaging performance was demonstrated by 3D imaging of both non-biological and biological samples. This extended DOF, sub-diffraction and motionless 3D PAM will open up new opportunities for potential biomedical applications.

Structure and Engineering of Francisella novicida Cas9

PubMed Central

Hirano, Hisato; Gootenberg, Jonathan S.; Horii, Takuro; Abudayyeh, Omar O.; Kimura, Mika; Hsu, Patrick D.; Nakane, Takanori; Ishitani, Ryuichiro; Hatada, Izuho; Zhang, Feng; Nishimasu, Hiroshi; Nureki, Osamu

2016-01-01

Summary The RNA-guided endonuclease Cas9 cleaves double-stranded DNA targets complementary to the guide RNA, and has been applied to programmable genome editing. Cas9-mediated cleavage requires a protospacer adjacent motif (PAM) juxtaposed with the DNA target sequence, thus constricting the range of targetable sites. Here, we report the 1.7 Å resolution crystal structures of Cas9 from Francisella novicida (FnCas9), one of the largest Cas9 orthologs, in complex with a guide RNA and its PAM-containing DNA targets. A structural comparison of FnCas9 with other Cas9 orthologs revealed striking conserved and divergent features among distantly related CRISPR-Cas9 systems. We found that FnCas9 recognizes the 5′-NGG-3′ PAM, and used the structural information to create a variant that can recognize the more relaxed 5′-YG-3′ PAM. Furthermore, we demonstrated that pre-assembled FnCas9 ribonucleoprotein complexes can be microinjected into mouse zygotes to edit endogenous sites with the 5′-YG-3′ PAMs, thus expanding the target space of the CRISPR-Cas9 toolbox. PMID:26875867

Effect of the presence of cationic polyacrylamide on the surface properties of aqueous alumina suspension-stability mechanism

NASA Astrophysics Data System (ADS)

Wiśniewska, Małgorzata; Chibowski, Stanisław; Urban, Teresa

2014-11-01

The effects of solution pH and the content of cationic groups in polyacrylamide (PAM) macromolecules on the stability mechanism of aqueous alumina suspension were investigated. The following experimental techniques were applied: spectrophotometry, potentiometric titration, microelectrophoresis, viscosimetry and turbidimetry. They enable determination of polymer adsorbed amount, surface charge density and zeta potential of solid particles in the presence and absence of PAM, as well as thickness of polymer adsorption layer, size of macromolecules in the solution and stability of the Al2O3-polymer systems, respectively. The obtained results indicate that adsorption of PAM increases with the increasing pH, whereas the thickness of polymeric adsorption layer decreases. Additionally, the greater the number of cationic groups in the PAM chains is, the higher adsorption was found. The polymer presence influences on the alumina suspension stability. At pH 3 and 6 the slight deterioration of stability conditions of solid particle covered with polyacrylamide was observed. At pH 9 the systems containing polymer are unstable, similarly to the suspension without PAM, but the mechanism of their destabilization is different.

Controlled clustering of carboxylated SPIONs through polyethylenimine

NASA Astrophysics Data System (ADS)

Nesztor, Dániel; Bali, Krisztina; Tóth, Ildikó Y.; Szekeres, Márta; Tombácz, Etelka

2015-04-01

Clusters of magnetite nanoparticles (MNPs) were synthesized using poly(acrylic acid-co-maleic acid) coated MNPs (PAM@MNP) and branched polyethylenimine (PEI). Materials were characterized by potentiometric titration, zeta potential and dynamic light scattering (DLS) measurements. PEI and PAM@MNP are oppositely charged as characterized by zeta potential measurements (+8, -34 mV respectively) and titration (10.30 mmol -NH3+/g PEI; 0.175 mmol -COO-/g PAM@MNP) at pH 6.5±0.2; therefore magnetic clusters are formed by electrostatic adhesion. Two different preparation methods and the effect of PEI and electrolyte (NaCl) concentration on the cluster formation was studied. Choosing an optimal concentration of PEI (charge ratio of PEI to PAM@MNP: 0.17) and electrolyte (10 mM), a concentrated (10 g MNP/L) product containing PEI-PAM@MNP nanoclusters with size of 165±10 nm was prepared. Its specific absorption rate (SAR) measured in AC magnetic field (110 kHz, 25 mT) is 12 W/g Fe. The clustered product is expected to have enhanced contrast efficiency in MRI.

Structure and Engineering of Francisella novicida Cas9.

PubMed

Hirano, Hisato; Gootenberg, Jonathan S; Horii, Takuro; Abudayyeh, Omar O; Kimura, Mika; Hsu, Patrick D; Nakane, Takanori; Ishitani, Ryuichiro; Hatada, Izuho; Zhang, Feng; Nishimasu, Hiroshi; Nureki, Osamu

2016-02-25

The RNA-guided endonuclease Cas9 cleaves double-stranded DNA targets complementary to the guide RNA and has been applied to programmable genome editing. Cas9-mediated cleavage requires a protospacer adjacent motif (PAM) juxtaposed with the DNA target sequence, thus constricting the range of targetable sites. Here, we report the 1.7 Å resolution crystal structures of Cas9 from Francisella novicida (FnCas9), one of the largest Cas9 orthologs, in complex with a guide RNA and its PAM-containing DNA targets. A structural comparison of FnCas9 with other Cas9 orthologs revealed striking conserved and divergent features among distantly related CRISPR-Cas9 systems. We found that FnCas9 recognizes the 5'-NGG-3' PAM, and used the structural information to create a variant that can recognize the more relaxed 5'-YG-3' PAM. Furthermore, we demonstrated that the FnCas9-ribonucleoprotein complex can be microinjected into mouse zygotes to edit endogenous sites with the 5'-YG-3' PAM, thus expanding the target space of the CRISPR-Cas9 toolbox. Copyright © 2016 Elsevier Inc. All rights reserved.

Series Pneumatic Artificial Muscles (sPAMs) and Application to a Soft Continuum Robot.

PubMed

Greer, Joseph D; Morimoto, Tania K; Okamura, Allison M; Hawkes, Elliot W

2017-01-01

We describe a new series pneumatic artificial muscle (sPAM) and its application as an actuator for a soft continuum robot. The robot consists of three sPAMs arranged radially round a tubular pneumatic backbone. Analogous to tendons, the sPAMs exert a tension force on the robot's pneumatic backbone, causing bending that is approximately constant curvature. Unlike a traditional tendon driven continuum robot, the robot is entirely soft and contains no hard components, making it safer for human interaction. Models of both the sPAM and soft continuum robot kinematics are presented and experimentally verified. We found a mean position accuracy of 5.5 cm for predicting the end-effector position of a 42 cm long robot with the kinematic model. Finally, closed-loop control is demonstrated using an eye-in-hand visual servo control law which provides a simple interface for operation by a human. The soft continuum robot with closed-loop control was found to have a step-response rise time and settling time of less than two seconds.

Series Pneumatic Artificial Muscles (sPAMs) and Application to a Soft Continuum Robot

PubMed Central

Greer, Joseph D.; Morimoto, Tania K.; Okamura, Allison M.; Hawkes, Elliot W.

2017-01-01

We describe a new series pneumatic artificial muscle (sPAM) and its application as an actuator for a soft continuum robot. The robot consists of three sPAMs arranged radially round a tubular pneumatic backbone. Analogous to tendons, the sPAMs exert a tension force on the robot’s pneumatic backbone, causing bending that is approximately constant curvature. Unlike a traditional tendon driven continuum robot, the robot is entirely soft and contains no hard components, making it safer for human interaction. Models of both the sPAM and soft continuum robot kinematics are presented and experimentally verified. We found a mean position accuracy of 5.5 cm for predicting the end-effector position of a 42 cm long robot with the kinematic model. Finally, closed-loop control is demonstrated using an eye-in-hand visual servo control law which provides a simple interface for operation by a human. The soft continuum robot with closed-loop control was found to have a step-response rise time and settling time of less than two seconds. PMID:29379672

Design of flat pneumatic artificial muscles

NASA Astrophysics Data System (ADS)

Wirekoh, Jackson; Park, Yong-Lae

2017-03-01

Pneumatic artificial muscles (PAMs) have gained wide use in the field of robotics due to their ability to generate linear forces and motions with a simple mechanism, while remaining lightweight and compact. However, PAMs are limited by their traditional cylindrical form factors, which must increase radially to improve contraction force generation. Additionally, this form factor results in overly complicated fabrication processes when embedded fibers and sensor elements are required to provide efficient actuation and control of the PAMs while minimizing the bulkiness of the overall robotic system. In order to overcome these limitations, a flat two-dimensional PAM capable of being fabricated using a simple layered manufacturing process was created. Furthermore, a theoretical model was developed using Von Karman’s formulation for large deformations and the energy methods. Experimental characterizations of two different types of PAMs, a single-cell unit and a multi-cell unit, were performed to measure the maximum contraction lengths and forces at input pressures ranging from 0 to 150 kPa. Experimental data were then used to verify the fidelity of the theoretical model.

In vivo time-serial evaluation of laser-induced choroidal neovascularization in rats simultaneously using photoacoustic microscopy and optical coherence tomography

NASA Astrophysics Data System (ADS)

Dai, Cuixia; Li, Lin; Liu, Wenlu; Wang, Fenghua; Zhou, Chuanqing

2018-02-01

Determination of the precise location and degree of condition of the Choroidal neovascularization (CNV) lesion is essential for diagnosation Neovascular age-related macular degeneration (AMD) and evaluation the efficacy of treatment. Given the complimentary contrast mechanisms of Photoacoustic microscopy (PAM) and Optical coherence tomography (OCT), the combination of PAM and OCT imaging could potentially provide much sensitive and specific detection of CNV. In this paper, we validated the opportunity to evaluate the information of laser-induced CNV and presented the in vivo time-serial evaluation of the CNV by simultaneously using PAM and OCT techniques. In vivo PAM and OCT examination was performed after laser photocoagulation applied to the rat fundus at days 1, 3, 5, 7, 14. Time-serial results showed that CNV in rats increased to its maximum at day 7 and decreased at day 14. Evolution of CNV information was given in PAM images with a high contrast and details of high axial resolution OCT images were simultaneously given to show the hyperreflective reaction progress.

Tropical cyclone Pam field survey in Vanuatu

NASA Astrophysics Data System (ADS)

Fritz, Hermann M.; Pilarczyk, Jessica E.; Kosciuch, Thomas; Hong, Isabel; Rarai, Allan; Harrison, Morris J.; Jockley, Fred R.; Horton, Benjamin P.

2016-04-01

Severe tropical cyclone Pam (Cat. 5, SSHS) crossed the Vanuatu archipelago with sustained winds of 270 km/h on March 13 and 14, 2015 and made landfall on Erromango. Pam is the most intense tropical cyclone to make landfall on Vanuatu since the advent of satellite imagery based intensity estimates in the 1970s. Pam caused one of the worst natural disaster in Vanuatu's recorded history. Eleven fatalities were directly attributed to cyclone Pam and mostly due to lack of shelter from airborne debris. On March 6 Pam formed east of the Santa Cruz Islands causing coastal inundation on Tuvalu's Vaitupu Island located some 1100 km east of the cyclone center. Pam intensified while tracking southward along Vanuatu severely affecting the Shefa and Tafea Provinces. An international storm surge reconnaissance team was deployed to Vanuatu from June 3 to 17, 2015 to complement earlier local surveys. Cyclone Pam struck a remote island archipelago particularly vulnerable to the combined cyclonic multi-hazards encompassing extreme wind gusts, massive rainfall and coastal flooding due to a combination of storm surge and storm wave impacts. The team surveyed coastal villages on Epi, the Shepherd Islands (Tongoa and Mataso), Efate (including Lelepa), Erromango, and Tanna. The survey spanned 320 km parallel to the cyclone track between Epi and Tanna encompassing more than 45 sites including the hardest hit settlements. Coastal flooding profiles were surveyed from the shoreline to the limit of inundation. Maximum coastal flood elevations and overland flow depths were measured based on water marks on buildings, scars on trees, rafted debris and corroborated with eyewitness accounts. We surveyed 91 high water marks with characteristic coastal flood levels in the 3 to 7 m range and composed of storm surge with superimposed storm waves. Inundation distances were mostly limited to a few hundred meters but reached 800 m on Epi Island. Wrack lines containing pumice perfectly delineated the inundation at many sites and were mapped as line features. Coral boulders of more than 1 m diameter were measured on Erromango. Along each island that was sampled, Cyclone Pam deposited a 1 - 20 cm thick sedimentary layer consisting of foraminfera-bearing sand and pumice cobbles. Infrastructure damage on traditional and modern structures was assessed. Eyewitnesses were interviewed at most sites to document the chronology of the wind and coastal flooding events, survival strategies, cyclone and tsunami awareness, evacuation procedures, shelter locations and ancestral knowledge. Field observations were compared with surveyed eyewitness accounts of historic events such as severe tropical cyclone Uma in 1987. The measured cyclone Pam high water marks will facilitate the interpretation of the collected sedimentary evidence and serve as benchmarks for modeling studies.

PAM-4 signal delivery in one radio-over-fiber system

NASA Astrophysics Data System (ADS)

Wang, Hada; Zhou, Wen; Yu, Jianjun

2017-10-01

We propose and experimentally demonstrate four-level pulse-amplitude-modulation (PAM-4) signal delivery in a radio-over-fiber system for the first time. Over 8-Gbit/s PAM-4 signals have been transmitted over 20-km single-mode fiber-28 and 1-m wireless distance. The signal after transmission is detected directly by an envelope detector at the receiver side. The maximal bit rate could be increased if the bandpass amplifier and envelope detector have more bandwidth.

Searching for the Cases of Acute Organophosphorus Pesticides Poisoning by JOIS

NASA Astrophysics Data System (ADS)

Futagami, Kojiro; Fujii, Toshiyuki; Horioka, Masayoshi; Asakura, Hajime; Fukagawa, Mitsuro

Cholinesterase reactivator PAM (Pralidoxime) is used in the treatment of organophosphates poisoning with anticholinergic agent atropine. However, some reports demonstrated recently that PAM has inefficacy in some cases of so-called low toxicity organophosphates poisoning. So, to atempt to discuss the efficacy of PAM in clinical treatment, we searched for the case reports of these poisoning by JOIS. In this time, we compared with the specificity of each data bases and presented some examples in this on-line information retrieval.

112 Gb/s transmission with a directly-modulated laser using FFT-based synthesis of orthogonal PAM and DMT signals.

PubMed

Ling, William A; Matsui, Yasuhiro; Daghighian, Henry M; Lyubomirsky, Ilya

2015-07-27

We report the experimental measurement of 112 Gb/s transmission back-to-back and through 12 km of S-SMF with a single directly-modulated laser (DML) using the novel modulation format Orthogonal PAM-DMT. This work demonstrates a record DML-based 112 Gb/s receiver sensitivity of -7.1 dBm at a BER of 10(-3), outperforming conventional PAM and DMT by approximately 2.5 dB.

Skylab IMSS checklist application study for emergency medical care. [emergency medical care operations involving the use and operation of the portable ambulance module

NASA Technical Reports Server (NTRS)

Carl, J. G.; Furukawa, S.

1975-01-01

A manual is presented that provides basic technical documentation to support the operation and utilization of the Portable Ambulance Module (PAM) in the field. The PAM is designed to be used for emergency resuscitation and victim monitoring. The functions of all the controls, displays, and stowed equipment of the unit are defined. Supportive medical and physiological data in those areas directly related to the uses of the PAM unit are presented.

PAM multiplicity marks genomic target sites as inhibitory to CRISPR-Cas9 editing.

PubMed

Malina, Abba; Cameron, Christopher J F; Robert, Francis; Blanchette, Mathieu; Dostie, Josée; Pelletier, Jerry

2015-12-08

In CRISPR-Cas9 genome editing, the underlying principles for selecting guide RNA (gRNA) sequences that would ensure for efficient target site modification remain poorly understood. Here we show that target sites harbouring multiple protospacer adjacent motifs (PAMs) are refractory to Cas9-mediated repair in situ. Thus we refine which substrates should be avoided in gRNA design, implicating PAM density as a novel sequence-specific feature that inhibits in vivo Cas9-driven DNA modification.

PAM multiplicity marks genomic target sites as inhibitory to CRISPR-Cas9 editing

PubMed Central

Malina, Abba; Cameron, Christopher J. F.; Robert, Francis; Blanchette, Mathieu; Dostie, Josée; Pelletier, Jerry

2015-01-01

In CRISPR-Cas9 genome editing, the underlying principles for selecting guide RNA (gRNA) sequences that would ensure for efficient target site modification remain poorly understood. Here we show that target sites harbouring multiple protospacer adjacent motifs (PAMs) are refractory to Cas9-mediated repair in situ. Thus we refine which substrates should be avoided in gRNA design, implicating PAM density as a novel sequence-specific feature that inhibits in vivo Cas9-driven DNA modification. PMID:26644285

Algorithmic Trading with Developmental and Linear Genetic Programming

NASA Astrophysics Data System (ADS)

Wilson, Garnett; Banzhaf, Wolfgang

A developmental co-evolutionary genetic programming approach (PAM DGP) and a standard linear genetic programming (LGP) stock trading systemare applied to a number of stocks across market sectors. Both GP techniques were found to be robust to market fluctuations and reactive to opportunities associated with stock price rise and fall, with PAMDGP generating notably greater profit in some stock trend scenarios. Both algorithms were very accurate at buying to achieve profit and selling to protect assets, while exhibiting bothmoderate trading activity and the ability to maximize or minimize investment as appropriate. The content of the trading rules produced by both algorithms are also examined in relation to stock price trend scenarios.

Sedimentary record of Tropical Cyclone Pam from Vanuatu: implications for long-term event records in the tropical South Pacific

NASA Astrophysics Data System (ADS)

Pilarczyk, Jessica; Kosciuch, Thomas; Hong, Isabel; Fritz, Hermann; Horton, Benjamin; Wallace, Davin; Dike, Clayton; Rarai, Allan; Harrison, Morris; Jockley, Fred

2017-04-01

Vanuatu has a history of tropical cyclones impacting its coastlines, including Tropical Cyclone (TC) Pam, a rare Category 5 event that made landfall in March 2015. Reliable records of tropical cyclones impacting Vanuatu are limited to the last several decades, with only fragmentary evidence of events extending as far back as the 1890's. Geological investigations are a means for expanding the short historical record of tropical cyclones by hundreds to thousands of years, permitting the study of even the rare, but intense events. However, geological records of past tropical cyclones are limited in their ability to quantify the intensity of past events. Modern analogues of landfalling tropical cyclones present an opportunity to characterize overwash sediments deposited by a storm of known intensity. In this study, we document the sedimentological and micropaleontological characteristics of sediments deposited by TC Pam in order to assess sediment provenance associated with a landfalling Category 5 storm. Within three months of TC Pam making landfall on Vanuatu we surveyed high-water marks associated with the storm surge and documented the foraminiferal assemblages and grain size distributions contained within the overwash sediments from Manuro (mixed-carbonate site on Efate Island) and Port Resolution Bay (volcaniclastic site on Tanna Island). The combined use of foraminiferal taxonomy and taphonomy (surface condition of foraminifera) was most useful in distinguishing the TC Pam sediments from the underlying layer. TC Pam sediments were characterized by an influx of calcareous marine foraminifera that were dominantly unaltered relative to those that were abraded and fragmented. Similar to studies that use mollusk taphonomy to identify overwash deposits, we found that TC Pam sediments were associated with an influx of angular fragments that were broken during transport by the storm surge. A statistical comparison of foraminifera from six modern environments on Efate Island (open bay, forereef, reef crest, reef flat, mangrove, and beach) with TC Pam sediments revealed a shallow nearshore to supratidal (reef crest to beach) source, spanning depths ranging from 1.3 to -4.9 m above MSL. On Efate Island, the TC Pam sediments consisted of a medium-grained (1.20Φ), moderately well-sorted (0.55Φ), mixed-carbonate sand. At this location, the sand extended 130 m inland, where it abruptly transitioned to a pumice layer that extended 400 m inland. In contrast, TC Pam deposited a medium-grained (1.81Φ), moderately well-sorted volcanic sand at Port Resolution Bay, where the sand extended up to 320 m inland. We used a combination of measured flow heights obtained at the Port Resolution Bay site and laboratory derived grain size settling velocities to calculate the distance of sediment transport caused by TC Pam's storm surge. Based on the distribution of settling velocities from our samples, transport distances for material deposited in the trench suggests a source for the overwash sand ranging from the supratidal berm to 290 m seaward in the nearshore at Port Resolution Bay.

Comparative study of signalling methods for high-speed backplane transceiver

NASA Astrophysics Data System (ADS)

Wu, Kejun

2017-11-01

A combined analysis of transient simulation and statistical method is proposed for comparative study of signalling methods applied to high-speed backplane transceivers. This method enables fast and accurate signal-to-noise ratio and symbol error rate estimation of a serial link based on a four-dimension design space, including channel characteristics, noise scenarios, equalisation schemes, and signalling methods. The proposed combined analysis method chooses an efficient sampling size for performance evaluation. A comparative study of non-return-to-zero (NRZ), PAM-4, and four-phase shifted sinusoid symbol (PSS-4) using parameterised behaviour-level simulation shows PAM-4 and PSS-4 has substantial advantages over conventional NRZ in most of the cases. A comparison between PAM-4 and PSS-4 shows PAM-4 gets significant bit error rate degradation when noise level is enhanced.

Label-free photoacoustic microscopy of peripheral nerves

NASA Astrophysics Data System (ADS)

Matthews, Thomas Paul; Zhang, Chi; Yao, Da-Kang; Maslov, Konstantin; Wang, Lihong V.

2014-01-01

Peripheral neuropathy is a common neurological problem that affects millions of people worldwide. Diagnosis and treatment of this condition are often hindered by the difficulties in making objective, noninvasive measurements of nerve fibers. Photoacoustic microscopy (PAM) has the ability to obtain high resolution, specific images of peripheral nerves without exogenous contrast. We demonstrated the first proof-of-concept imaging of peripheral nerves using PAM. As validated by both standard histology and photoacoustic spectroscopy, the origin of photoacoustic signals is myelin, the primary source of lipids in the nerves. An extracted sciatic nerve sandwiched between two layers of chicken tissue was imaged by PAM to mimic the in vivo case. Ordered fibrous structures inside the nerve, caused by the bundles of myelin-coated axons, could be observed clearly. With further technical improvements, PAM can potentially be applied to monitor and diagnose peripheral neuropathies.

Mapping the pulmonary environment of animals protected from virulent H1N1 influenza infection using the TLR-2 agonist Pam₂Cys.

PubMed

Mifsud, Edin J; Tan, Amabel C L; Reading, Patrick C; Jackson, David C

2016-02-01

We have previously shown that intranasal administration of the Toll-like receptor-2 agonist, S-(2,3-bis(palmitoyloxy)propyl) cysteine (Pam2Cys), provides immediate and antigen independent protection against challenge with influenza virus. Here we characterize the cellular pulmonary environments of mice which had either been treated with Pam2Cys or placebo and then challenged with influenza virus. We show that Pam2Cys treatment results in the influx of innate immune cells into the lungs and that depletion of phagocytic cells from this influx using clodronate-loaded liposomes caused a reduction in the number of interstitial macrophages and monocytes. This resulted in abolition of the protective effect indicating the importance of this cellular subset in Pam2Cys-mediated protection.

A pacifier-activated music player with mother's voice improves oral feeding in preterm infants.

PubMed

Chorna, Olena D; Slaughter, James C; Wang, Lulu; Stark, Ann R; Maitre, Nathalie L

2014-03-01

We conducted a randomized trial to test the hypothesis that mother's voice played through a pacifier-activated music player (PAM) during nonnutritive sucking would improve the development of sucking ability and promote more effective oral feeding in preterm infants. Preterm infants between 34 0/7 and 35 6/7 weeks' postmenstrual age, including those with brain injury, who were taking at least half their feedings enterally and less than half orally, were randomly assigned to receive 5 daily 15-minute sessions of either PAM with mother's recorded voice or no PAM, along with routine nonnutritive sucking and maternal care in both groups. Assignment was masked to the clinical team. Ninety-four infants (46 and 48 in the PAM intervention and control groups, respectively) completed the study. The intervention group had significantly increased oral feeding rate (2.0 vs. 0.9 mL/min, P < .001), oral volume intake (91.1 vs. 48.1 mL/kg/d, P = .001), oral feeds/day (6.5 vs. 4.0, P < .001), and faster time-to-full oral feedings (31 vs. 38 d, P = .04) compared with controls. Weight gain and cortisol levels during the 5-day protocol were not different between groups. Average hospital stays were 20% shorter in the PAM group, but the difference was not significant (P = .07). A PAM using mother's voice improves oral feeding skills in preterm infants without adverse effects on hormonal stress or growth.

Commercial versus synthesized polymers for soil erosion control and growth of Chinese cabbage.

PubMed

Lee, Sang Soo; Chang, Scott X; Chang, Yoon-Young; Ok, Yong Sik

2013-01-01

Soil erosion leads to environmental degradation and reduces soil productivity. The use of anionic polyacrylamide (PAM) and synthesized biopolymer (BP) using lignin, corn starch, acrylamide, and acrylic acid were tested to evaluate soil erosion, water quality, and growth of Chinese cabbage (Brassica campestris L.). Each treatment of PAM and BP was applied at 200 kg ha(-1) to loamy sand soil and subjected to a slope of 36% with a 20 mm h(-1) simulated rainfall. Application of BP decreased soil pH compared to the untreated check (CK); however, the soil pH was not altered with PAM. The decrease in pH might most likely be due to availability of anionic sites to be protonated on soils having pH >6 and soil buffering capacity. Both PAM and BP applications may not induce eutrophication with stable levels of total contents of N and P. With PAM and BP, the average values of suspended soil (SS) and turbidity were reduced by up to 96.0 and 99.9%, respectively, compared to CK. Reduction of SS can be attributed to increasing soil stability and shear strength by clay flocculation. There was no toxicity effects resulting from germination tests and the dry weight was increased by 17.7% (vs. CK) when PAM and BP were applied. These results are attributed to increases in water retention and plant-available water. The use of polymeric soil amendments is an environmentally friendly way to mitigate soil erosion and nonpoint source pollution.

A Pacifier-Activated Music Player With Mother’s Voice Improves Oral Feeding in Preterm Infants

PubMed Central

Chorna, Olena D.; Slaughter, James C.; Wang, Lulu; Stark, Ann R.

2014-01-01

OBJECTIVES: We conducted a randomized trial to test the hypothesis that mother’s voice played through a pacifier-activated music player (PAM) during nonnutritive sucking would improve the development of sucking ability and promote more effective oral feeding in preterm infants. METHODS: Preterm infants between 34 0/7 and 35 6/7 weeks’ postmenstrual age, including those with brain injury, who were taking at least half their feedings enterally and less than half orally, were randomly assigned to receive 5 daily 15-minute sessions of either PAM with mother’s recorded voice or no PAM, along with routine nonnutritive sucking and maternal care in both groups. Assignment was masked to the clinical team. RESULTS: Ninety-four infants (46 and 48 in the PAM intervention and control groups, respectively) completed the study. The intervention group had significantly increased oral feeding rate (2.0 vs 0.9 mL/min, P < .001), oral volume intake (91.1 vs 48.1 mL/kg/d, P = .001), oral feeds/day (6.5 vs 4.0, P < .001), and faster time-to-full oral feedings (31 vs 38 d, P = .04) compared with controls. Weight gain and cortisol levels during the 5-day protocol were not different between groups. Average hospital stays were 20% shorter in the PAM group, but the difference was not significant (P = .07). CONCLUSIONS: A PAM using mother’s voice improves oral feeding skills in preterm infants without adverse effects on hormonal stress or growth. PMID:24534413

Pregnancy-associated malaria and malaria in infants: an old problem with present consequences.

PubMed

Moya-Alvarez, Violeta; Abellana, Rosa; Cot, Michel

2014-07-11

Albeit pregnancy-associated malaria (PAM) poses a potential risk for over 125 million women each year, an accurate review assessing the impact on malaria in infants has yet to be conducted. In addition to an effect on low birth weight (LBW) and prematurity, PAM determines foetal exposure to Plasmodium falciparum in utero and is correlated to congenital malaria and early development of clinical episodes during infancy. This interaction plausibly results from an ongoing immune tolerance process to antigens in utero, however, a complete explanation of this immune process remains a question for further research, as does the precise role of protective maternal antibodies. Preventive interventions against PAM modify foetal exposure to P. falciparum in utero, and have thus an effect on perinatal malaria outcomes. Effective intermittent preventive treatment in pregnancy (IPTp) diminishes placental malaria (PM) and its subsequent malaria-associated morbidity. However, emerging resistance to sulphadoxine-pyrimethamine (SP) is currently hindering the efficacy of IPTp regimes and the efficacy of alternative strategies, such as intermittent screening and treatment (IST), has not been accurately evaluated in different transmission settings. Due to the increased risk of clinical malaria for offspring of malaria infected mothers, PAM preventive interventions should ideally start during the preconceptual period. Innovative research examining the effect of PAM on the neurocognitive development of the infant, as well as examining the potential influence of HLA-G polymorphisms on malaria symptoms, is urged to contribute to a better understanding of PAM and infant health.

Effective PCR-based detection of Naegleria fowleri from cultured sample and PAM-developed mouse.

PubMed

Kang, Heekyoung; Seong, Gi-Sang; Sohn, Hae-Jin; Kim, Jong-Hyun; Lee, Sang-Eun; Park, Mi Yeoun; Lee, Won-Ja; Shin, Ho-Joon

2015-10-01

Increasing numbers of Primary Amoebic Meningoencephalitis (PAM) cases due to Naegleria fowleri are becoming a serious issue in subtropical and tropical countries as a Neglected Tropical Disease (NTD). To establish a rapid and effective diagnostic tool, a PCR-based detection technique was developed based on previous PCR methods. Four kinds of primer pairs, Nfa1, Nae3, Nf-ITS, and Naegl, were employed in the cultured amoebic trophozoites and a mouse with PAM experimentally developed by N. fowleri inoculation (PAM-mouse). For the extraction of genomic DNA from N. fowleri trophozoites (1×10(6)), simple boiling with 10μl of PBS (pH 7.4) at 100°C for 30min was found to be the most rapid and efficient procedure, allowing amplification of 2.5×10(2) trophozoites using the Nfa-1 primer. The primers Nfa1 and Nae3 amplified only N. fowleri DNA, whereas the ITS primer detected N. fowleri and N. gruberi DNA. Using the PAM-mouse brain tissue, the Nfa1 primer was able to amplify the N. fowleri DNA 4 days post infection with 1ng/μl of genomic DNA being detectable. Using the PAM-mouse CSF, amplification of the N. fowleri DNA with the Nae3 primer was possible 5 days post infection showing a better performance than the Nfa1 primer at day 6. Copyright © 2015 Elsevier GmbH. All rights reserved.

Corifungin, a New Drug Lead against Naegleria, Identified from a High-Throughput Screen

PubMed Central

Debnath, Anjan; Tunac, Josefino B.; Galindo-Gómez, Silvia; Silva-Olivares, Angélica; Shibayama, Mineko

2012-01-01

Primary amebic meningoencephalitis (PAM) is a rapidly fatal infection caused by the free-living ameba Naegleria fowleri. The drug of choice in treating PAM is the antifungal antibiotic amphotericin B, but its use is associated with severe adverse effects. Moreover, few patients treated with amphotericin B have survived PAM. Therefore, fast-acting and efficient drugs are urgently needed for the treatment of PAM. To facilitate drug screening for this pathogen, an automated, high-throughput screening methodology was developed and validated for the closely related species Naegleria gruberi. Five kinase inhibitors and an NF-kappaB inhibitor were hits identified in primary screens of three compound libraries. Most importantly for a preclinical drug discovery pipeline, we identified corifungin, a water-soluble polyene macrolide with a higher activity against Naegleria than that of amphotericin B. Transmission electron microscopy of N. fowleri trophozoites incubated with different concentrations of corifungin showed disruption of cytoplasmic and plasma membranes and alterations in mitochondria, followed by complete lysis of amebae. In vivo efficacy of corifungin in a mouse model of PAM was confirmed by an absence of detectable amebae in the brain and 100% survival of mice for 17 days postinfection for a single daily intraperitoneal dose of 9 mg/kg of body weight given for 10 days. The same dose of amphotericin B did not reduce ameba growth, and mouse survival was compromised. Based on these results, the U.S. FDA has approved orphan drug status for corifungin for the treatment of PAM. PMID:22869574

2013 Center for Army Leadership Annual Survey of Army Leadership (CASAL): Main Findings

DTIC Science & Technology

2014-04-01

enhances Esprit de Corps. The Center for Army Profession and Ethic (CAPE) has fielded education and training materials (including doctrine, pamphlets ...videos, brochures , and lesson plans available online) to assist Army leaders in executing this program (The FY14 America’s Army-Our Profession...contribution of warrant officer courses for improving leadership capabilities are not unexpected. However, Department of the Army Pamphlet (DA PAM) 600-3

STS-41 Space Shuttle mission report

NASA Technical Reports Server (NTRS)

Camp, David W.; Germany, D. M.; Nicholson, Leonard S.

1990-01-01

The STS-41 Space Shuttle Program Mission Report contains a summary of the vehicle subsystem activities on this thirty-sixth flight of the Space Shuttle and the eleventh flight of the Orbiter vehicle, Discovery (OV-103). In addition to the Discovery vehicle, the flight vehicle consisted of an External Tank (ET) (designated as ET-39/LWT-32), three Space Shuttle main engines (SSME's) (serial numbers 2011, 2031, and 2107), and two Solid Rocket Boosters (SRB's), designated as BI-040. The primary objective of the STS-41 mission was to successfully deploy the Ulysses/inertial upper stage (IUS)/payload assist module (PAM-S) spacecraft. The secondary objectives were to perform all operations necessary to support the requirements of the Shuttle Backscatter Ultraviolet (SSBUV) Spectrometer, Solid Surface Combustion Experiment (SSCE), Space Life Sciences Training Program Chromosome and Plant Cell Division in Space (CHROMEX), Voice Command System (VCS), Physiological Systems Experiment (PSE), Radiation Monitoring Experiment - 3 (RME-3), Investigations into Polymer Membrane Processing (IPMP), Air Force Maui Optical Calibration Test (AMOS), and Intelsat Solar Array Coupon (ISAC) payloads. The sequence of events for this mission is shown in tabular form. Summarized are the significant problems that occurred in the Orbiter subsystems during the mission. The official problem tracking list is presented. In addition, each Orbiter problem is cited in the subsystem discussion.

Advanced Systems for Monitoring Underwater Sounds

NASA Technical Reports Server (NTRS)

Lane, Michael; Van Meter, Steven; Gilmore, Richard Grant; Sommer, Keith

2007-01-01

The term "Passive Acoustic Monitoring System" (PAMS) describes a developmental sensing-and-data-acquisition system for recording underwater sounds. The sounds (more precisely, digitized and preprocessed versions from acoustic transducers) are subsequently analyzed by a combination of data processing and interpretation to identify and/or, in some cases, to locate the sources of those sounds. PAMS was originally designed to locate the sources such as fish of species that one knows or seeks to identify. The PAMS unit could also be used to locate other sources, for example, marine life, human divers, and/or vessels. The underlying principles of passive acoustic sensing and analyzing acoustic-signal data in conjunction with temperature and salinity data are not new and not unique to PAMS. Part of the uniqueness of the PAMS design is that it is the first deep-sea instrumentation design to provide a capability for studying soniferous marine animals (especially fish) over the wide depth range described below. The uniqueness of PAMS also lies partly in a synergistic combination of advanced sensing, packaging, and data-processing design features with features adapted from proven marine instrumentation systems. This combination affords a versatility that enables adaptation to a variety of undersea missions using a variety of sensors. The interpretation of acoustic data can include visual inspection of power-spectrum plots for identification of spectral signatures of known biological species or artificial sources. Alternatively or in addition, data analysis could include determination of relative times of arrival of signals at different acoustic sensors arrayed at known locations. From these times of arrival, locations of acoustic sources (and errors in those locations) can be estimated. Estimates of relative locations of sources and sensors can be refined through analysis of the attenuation of sound in the intervening water in combination with water-temperature and salinity data acquired by instrumentation systems other than PAMS. A PAMS is packaged as a battery-powered unit, mated with external sensors, that can operate in the ocean at any depth from 2 m to 1 km. A PAMS includes a pressure housing, a deep-sea battery, a hydrophone (which is one of the mating external sensors), and an external monitor and keyboard box. In addition to acoustic transducers, external sensors can include temperature probes and, potentially, underwater cameras. The pressure housing contains a computer that includes a hard drive, DC-to- DC power converters, a post-amplifier board, a sound card, and a universal serial bus (USB) 4-port hub.

CRISPR interference and priming varies with individual spacer sequences

PubMed Central

Xue, Chaoyou; Seetharam, Arun S.; Musharova, Olga; Severinov, Konstantin; J. Brouns, Stan J.; Severin, Andrew J.; Sashital, Dipali G.

2015-01-01

CRISPR–Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated) systems allow bacteria to adapt to infection by acquiring ‘spacer’ sequences from invader DNA into genomic CRISPR loci. Cas proteins use RNAs derived from these loci to target cognate sequences for destruction through CRISPR interference. Mutations in the protospacer adjacent motif (PAM) and seed regions block interference but promote rapid ‘primed’ adaptation. Here, we use multiple spacer sequences to reexamine the PAM and seed sequence requirements for interference and priming in the Escherichia coli Type I-E CRISPR–Cas system. Surprisingly, CRISPR interference is far more tolerant of mutations in the seed and the PAM than previously reported, and this mutational tolerance, as well as priming activity, is highly dependent on spacer sequence. We identify a large number of functional PAMs that can promote interference, priming or both activities, depending on the associated spacer sequence. Functional PAMs are preferentially acquired during unprimed ‘naïve’ adaptation, leading to a rapid priming response following infection. Our results provide numerous insights into the importance of both spacer and target sequences for interference and priming, and reveal that priming is a major pathway for adaptation during initial infection. PMID:26586800

A practical optical-resolution photoacoustic microscopy prototype using a 300 mW visible laser diode

NASA Astrophysics Data System (ADS)

Zeng, Lvming; Piao, Zhonglie; Huang, Shenghai; Jia, Wangcun; Chen, Zhongping

2016-03-01

Optical-resolution photoacoustic microscopy (OR-PAM) is an emerging technique for microvasculature imaging at high spatial resolution and contrast. In this work, we present a practical visible laser-diode-based OR-PAM (LD-OR-PAM) prototype for vasculature imaging, which has the desirable properties of being portable, low-cost, and label-free. The prototype employs a 300 mW pulsed laser diode in a 3.8 mm diameter package, emitting 174 ns pulses at 405 +/- 5 nm wavelength and a pulse energy of 52 nJ. An aspheric objective with a numerical aperture of 0.60 is used to achieve microscope optical illumination. The laser diode excitation has a compact size of 4.5 × 1.8 × 1.8 cm3 assembled with a cooling block. The lateral resolution was tested to be 0.95 μm on ~7 μm carbon fibers. The subcutaneous microvasculature on a mouse back was label-free imaged ex vivo, which demonstrates the potential of the LD-OR-PAM prototype for in vivo imaging skin chromosphores such as hemoglobin. Our ultimate aim is to provide a practical and affordable OR-PAM system as a routine instrument for standard clinical applications.

Surveillance for malaria outbreak on malaria-eliminating islands in Tafea Province, Vanuatu after Tropical Cyclone Pam in 2015.

PubMed

Chan, C W; Iata, H; Yaviong, J; Kalkoa, M; Yamar, S; Taleo, G; Isozumi, R; Fukui, M; Aoyama, F; Pomer, A; Dancause, K N; Kaneko, A

2017-01-01

The risk of malaria outbreak surfaced in Vanuatu after Tropical Cyclone (TC) Pam in March 2015. In June and July 2015 we conducted malariometric surveys on the islands of Tanna, Aneityum, and Erromango in Tafea Province, where malaria elimination had been targeted, to determine if malaria incidence had increased after TC Pam. No Plasmodium infection was detected by microscopy and PCR in 3009 survey participants. Only 6·3% (190/3007) of participants had fever. Spleen rates in children aged ⩽12 years from Aneityum and Tanna were low, at 3·6% (14/387) and 5·3% (27/510), respectively. Overall bed net use was high at 72·8% (2175/2986); however, a significantly higher (P < 0·001) proportion of participants from Aneityum (85·9%, 796/927) reported net use than those from Tanna (67·1%, 751/1119) and Erromango (66·8%, 628/940). A recent decrease in malaria incidence in Tafea Province through comprehensive intervention measures had reduced the indigenous parasite reservoir and limited the latter's potential to spur an outbreak after TC Pam. The path towards malaria elimination in Tafea Province was not adversely affected by TC Pam.

Engineered Cpf1 variants with altered PAM specificities increase genome targeting range

PubMed Central

Gao, Linyi; Cox, David B.T.; Yan, Winston X.; Manteiga, John C.; Schneider, Martin W.; Yamano, Takashi; Nishimasu, Hiroshi; Nureki, Osamu; Crosetto, Nicola; Zhang, Feng

2017-01-01

The RNA-guided endonuclease Cpf1 is a promising tool for genome editing in eukaryotic cells1–7. However, the utility of the commonly used Acidaminococcus sp. BV3L6 Cpf1 (AsCpf1) and Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1) is limited by their requirement of a TTTV protospacer adjacent motif (PAM) in the DNA substrate. To address this limitation, we performed a structure-guided mutagenesis screen to increase the targeting range of Cpf1. We engineered two AsCpf1 variants carrying the mutations S542R/K607R and S542R/K548V/N552R, which recognize TYCV and TATV PAMs, respectively, with enhanced activities in vitro and in human cells. Genome-wide assessment of off-target activity using BLISS7 assay indicated that these variants retain high DNA targeting specificity, which we further improved by introducing an additional non-PAM-interacting mutation. Introducing the identified mutations at their corresponding positions in LbCpf1 similarly altered its PAM specificity. Together, these variants increase the targeting range of Cpf1 by approximately three-fold in human coding sequences to one cleavage site per ~11 bp. PMID:28581492

Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity.

PubMed

Zhang, Rui; Kramer, Jake S; Smith, Josiah D; Allen, Brittany N; Leeper, Caitlin N; Li, Xiaolei; Morton, Logan D; Gallazzi, Fabio; Ulery, Bret D

2018-06-01

Current vaccine research has shifted from traditional vaccines (i.e., whole-killed or live-attenuated) to subunit vaccines (i.e., protein, peptide, or DNA) as the latter is much safer due to delivering only the bioactive components necessary to produce a desirable immune response. Unfortunately, subunit vaccines are very weak immunogens requiring delivery vehicles and the addition of immunostimulatory molecules termed adjuvants to convey protective immunity. An interesting type of delivery vehicle is peptide amphiphile micelles (PAMs), unique biomaterials where the vaccine is part of the nanomaterial itself. Due to the modularity of PAMs, they can be readily modified to deliver both vaccine antigens and adjuvants within a singular construct. Through the co-delivery of a model antigenic epitope (Ovalbumin 319-340 -OVA BT ) and a known molecular adjuvant (e.g., 2,3-dipalmitoyl-S-glyceryl cysteine-Pam 2 C), greater insight into the mechanisms by which PAMs can exert immunostimulatory effects was gained. It was found that specific combinations of antigen and adjuvant can significantly alter vaccine immunogenicity both in vitro and in vivo. These results inform fundamental design rules that can be leveraged to fabricate optimal PAM-based vaccine formulations for future disease-specific applications. Graphical Abstract.

Photoacoustic microscopy of complex regional pain syndrome type I (CRPS-1) after stellate ganglion blocks in vivo

NASA Astrophysics Data System (ADS)

Zhou, Yong; Yi, Xiaobin; Xing, Wenxin; Hu, Song; Maslov, Konstantin I.; Wang, Lihong V.

2015-03-01

We used photoacoustic microscopy (PAM) to assist diagnoses and monitor the progress and treatment outcome of complex regional pain syndrome type 1 (CRPS-1). Blood vasculature and oxygen saturation (sO2) were imaged by PAM in eight adult patients with CRPS-1. Patients' hands and cuticles were imaged both before and after stellate ganglion block (SGB) for comparison. For all patients, both the vascular structure and sO2 could be assessed by PAM. In addition, more vessels and stronger signals were observed after SGB.

Surface morphology and morphometry of rat alveolar macrophages after ozone exposure

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

Dormans, J.A.; Rombout, P.J.; van Loveren, H.

1990-09-01

As the ultrastructural data on the effects of ozone on pulmonary alveolar macrophages (PAM) are lacking, transmission (TEM) and scanning (SEM) electron microscopy were performed on rat PAM present in alveolar lavages following exposure to ozone. Rats were continuously exposed for 7 d to ozone concentrations ranging from 0.25 to 1.50 mg/m3 for 7 d followed by a 5-d recovery period. Additionally, morphometry on lung sections was performed to quantitate PAM. In a second experiment rats were continuously exposed to 1.50 mg O3/m3 for 1, 3, 5, or 7 d. To study the influence of concurrent ozone exposure and lungmore » infection, due to Listeria monocytogenes, rats were exposed for 7 d to 1.50 mg O3/m3 after a Listeria infection. The surface area of lavaged control PAM was uniformly covered with ruffles as shown by SEM and TEM. Exposure to 0.5 mg ozone/m3 for 7 d resulted in cells partly covered with microvilli and blebs in addition to normal ruffles. The number of large size PAM increased with an increase in ozone concentration. After 1 d of exposure, normal-appearing as well as many small macrophages with ruffles and scattered lymphocytes were seen. Lavage samples taken after 5 or 7 d of exposure showed an identical cell composition to that taken after 3 d of exposure. After Listeria infection alone, lavage samples consisted of mainly lymphocytes and some macrophages. Small quantitative changes, such as an increase in the number of polymorphonuclear neutrophils and large-size PAM, occurred in lavages after ozone exposure and infection with L. monocytogenes. Morphometric examination of lung sections revealed a concentration-related increase in the number of PAM, even in animals exposed to 0.25 mg ozone/m3 for 7 d. Centriacinar regions were more severely affected than other regions of lung tissue.« less

Maternal allergy increases susceptibility to offspring allergy in association with TH2-biased epigenetic alterations in a mouse model of peanut allergy.

PubMed

Song, Ying; Liu, Changda; Hui, Yiqun; Srivastava, Kamal; Zhou, Zhenwen; Chen, Jia; Miller, Rachel L; Finkelman, Fred D; Li, Xiu-Min

2014-12-01

Although maternal atopy is a risk factor for the development of peanut allergy, this phenomenon has not been well characterized experimentally, and the mechanisms underlying offspring risk are unclear. We sought to determine whether offspring of mothers with peanut allergy (O-PAM mice) are more susceptible to peanut allergy than offspring of naive mothers (O-NM mice) in a murine model and, if so, whether the susceptibility is linked to TH2-biased epigenetic alterations. Five-week-old O-PAM and O-NM mice were intragastrically sensitized to and challenged with peanut. Serum peanut-specific IgE levels, plasma histamine levels, anaphylactic reactions, and splenocyte and MLN cell cytokine production were measured. DNA methylation levels of the Il4 gene promoter from splenocytes and MLN cells from sensitized offspring and splenocytes from unsensitized neonatal offspring were determined by means of pyrosequencing. O-PAM mice exhibited 3-fold higher peanut-specific IgE levels after peanut sensitization, as well as 5-fold higher histamine levels and significantly higher anaphylactic symptom scores after challenge than O-NM mice (P < .05-.01). Cultured splenocytes and MLNs from O-PAM mice produced significantly more TH2 cytokines than cells from O-NM mice (P < .05-.01). Cells from O-PAM mice exhibited significantly reduced DNA methylation at CpG sites of the Il4 gene promoter than cells from O-NM mice. DNA methylation levels were inversely correlated with IL-4 and IgE production. O-PAM neonatal splenocyte hypomethylation of the Il4 gene promoter was also present. This study is the first to demonstrate that increased susceptibility to peanut allergy in O-PAM mice is associated with epigenetic alteration of the Il4 gene promoter. This finding might provide insight into preventing the development of early-life allergy. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

In Vitro and In Vivo Identification of Novel Positive Allosteric Modulators of the Human Dopamine D2 and D3 Receptor.

PubMed

Wood, Martyn; Ates, Ali; Andre, Veronique Marie; Michel, Anne; Barnaby, Robert; Gillard, Michel

2016-02-01

Agonists at dopamine D2 and D3 receptors are important therapeutic agents in the treatment of Parkinson's disease. Compared with the use of agonists, allosteric potentiators offer potential advantages such as temporal, regional, and phasic potentiation of natural signaling, and that of receptor subtype selectivity. We report the identification of a stereoselective interaction of a benzothiazol racemic compound that acts as a positive allosteric modulator (PAM) of the rat and human dopamine D2 and D3 receptors. The R isomer did not directly stimulate the dopamine D2 receptor but potentiated the effects of dopamine. In contrast the S isomer attenuated the effects of the PAM and the effects of dopamine. In radioligand binding studies, these compounds do not compete for binding of orthosteric ligands, but indeed the R isomer increased the number of high-affinity sites for [(3)H]-dopamine without affecting K(d). We went on to identify a more potent PAM for use in native receptor systems. This compound potentiated the effects of D2/D3 signaling in vitro in electrophysiologic studies on dissociated striatal neurons and in vivo on the effects of L-dopa in the 6OHDA (6-hydroxydopamine) contralateral turning model. These PAMs lacked activity at a wide variety of receptors, lacked PAM activity at related Gi-coupled G protein-coupled receptors, and lacked activity at D1 receptors. However, the PAMs did potentiate [(3)H]-dopamine binding at both D2 and D3 receptors. Together, these studies show that we have identified PAMs of the D2 and D3 receptors both in vitro and in vivo. Such compounds may have utility in the treatment of hypodopaminergic function. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Exploring with PAM: Prospecting ANTS Missions for Solar System Surveys

NASA Astrophysics Data System (ADS)

Clark, P. E.; Rilee, M. L.; Curtis, S. A.

2003-03-01

ANTS (Autonomous Nano Technology Swarm of hundreds of picoclass autonomous spacecraft) have many applications. A version designed for surveying and the resource potential of the asteroid belt, called PAM (Prospecting ANTS Mission), is examined here.

32 CFR 536.28 - Claims acknowledgment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... submission jurisdictionally deficient based on the requirements discussed in DA Pam 27-162, paragraphs 2-5... (HIPAA), 42 U.S.C. 1320d-1320d-8. See the parallel discussion at DA Pam 27-162, paragraph 2-7. ...

Quantification of photoacoustic microscopy images for ovarian cancer detection

NASA Astrophysics Data System (ADS)

Wang, Tianheng; Yang, Yi; Alqasemi, Umar; Kumavor, Patrick D.; Wang, Xiaohong; Sanders, Melinda; Brewer, Molly; Zhu, Quing

2014-03-01

In this paper, human ovarian tissues with malignant and benign features were imaged ex vivo by using an opticalresolution photoacoustic microscopy (OR-PAM) system. Several features were quantitatively extracted from PAM images to describe photoacoustic signal distributions and fluctuations. 106 PAM images from 18 human ovaries were classified by applying those extracted features to a logistic prediction model. 57 images from 9 ovaries were used as a training set to train the logistic model, and 49 images from another 9 ovaries were used to test our prediction model. We assumed that if one image from one malignant ovary was classified as malignant, it is sufficient to classify this ovary as malignant. For the training set, we achieved 100% sensitivity and 83.3% specificity; for testing set, we achieved 100% sensitivity and 66.7% specificity. These preliminary results demonstrate that PAM could be extremely valuable in assisting and guiding surgeons for in vivo evaluation of ovarian tissue.

Extracting body image symptom dimensions among eating disorder patients: the Profile Analysis via Multidimensional Scaling (PAMS) approach.

PubMed

Olatunji, Bunmi O; Kim, Se-Kang; Wall, David

2015-09-01

The present study employs Profile Analysis via Multidimensional Scaling (PAMS), a procedure for extracting dimensions, in order to identify core eating disorder symptoms in a clinical sample. A large sample of patients with eating disorders (N=5193) presenting for treatment completed the Eating Disorders Inventory-2 (EDI-2; Garner, 1991), and PAMS was then employed to estimate individual profile weights that reflect the degree to which an individual's observed symptom profile approximates the pattern of the dimensions. The findings revealed three symptom dimensions: Body Thinness, Body Perfectionism, and Body Awareness. Subsequent analysis using individual level data illustrate that the PAMS profiles properly operate as prototypical profiles that encapsulate all individuals' response patterns. The implications of these dimensional findings for the assessment and diagnosis of eating disorders are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Photo-induced ultrasound microscopy for photo-acoustic imaging of non-absorbing specimens

NASA Astrophysics Data System (ADS)

Tcarenkova, Elena; Koho, Sami V.; Hänninen, Pekka E.

2017-08-01

Photo-Acoustic Microscopy (PAM) has raised high interest in in-vivo imaging due to its ability to preserve the near-diffraction limited spatial resolution of optical microscopes, whilst extending the penetration depth to the mm-range. Another advantage of PAM is that it is a label-free technique - any substance that absorbs PAM excitation laser light can be viewed. However, not all sample structures desired to be observed absorb sufficiently to provide contrast for imaging. This work describes a novel imaging method that makes it possible to visualize optically transparent samples that lack intrinsic photo-acoustic contrast, without the addition of contrast agents. A thin, strongly light absorbing layer next to sample is used to generate a strong ultrasonic signal. This signal, when recorded from opposite side, contains ultrasonic transmission information of the sample and thus the method can be used to obtain an ultrasound transmission image on any PAM.

Swimming with death: Naegleria fowleri infections in recreational waters.

PubMed

Heggie, Travis W

2010-07-01

Naegleria fowleri is a free-living amoeba commonly found in warm freshwater environments such as hot springs, lakes, natural mineral water, and resort spas frequented by tourists. N. fowleri is the etiologic agent of primary amoebic meningoencephalitis (PAM), an acute fatal disease of the central nervous system that results in death in approximately seven days. Previously thought to be a rare condition, the number of reported PAM cases is increasing each year. PAM is difficult to diagnose because the clinical signs of the disease are similar to bacterial meningitis. Thus, the key to diagnosis is physician awareness and clinical suspicion. With the intent of creating awareness among travel medicine practitioners and the tourism industry, this review focuses on the presenting features of N. fowleri and PAM and offers insight into the prevention and treatment of the disease. Copyright © 2010 Elsevier Ltd. All rights reserved.

Performance improvement by orthogonal pulse amplitude modulation and discrete multitone modulation signals in hybrid fiber-visible laser light communication system

NASA Astrophysics Data System (ADS)

Zhang, Fangliu; He, Jing; Deng, Rui; Chen, Qinghui; Chen, Lin

2016-10-01

A modulation format, orthogonal pulse amplitude modulation and discrete multitone modulation (O-PAM-DMT), is experimentally demonstrated in a hybrid fiber-visible laser light communication (fiber-VLLC) system using a cost-effective directly modulated laser and blue laser diode. In addition, low overhead is achieved by utilizing only one training sequence to implement synchronization and channel estimation. Through adjusting the ratio of PAM and DMT signal, three types of O-PAM-DMT signals are investigated. After transmission over a 20-km standard single-mode fiber and 5-m free-space VLLC, the receiver sensitivity for 4.36-Gbit/s O-PAM-DMT signals can be improved by 0.4, 1.4, and 2.7 dB, respectively, at a bit error rate of 1×10-3, compared with a conventional DMT signal.

2-propen-1-amine derivatives and their synthetic intermediates: activity against pathogenic trypanosomatids.

PubMed

de Souza, A O; Hemerly, F P; Gomes-Cardoso, L; Santa-Rita, R M; Leon, L L; de Castro, S L; Durán, N

2004-12-01

The potential activity of three new derivatives of 3-(4'-Y-[1,1'-biphenyl]-4-yl)-3-(4-X-phenyl)-N,N-dimethyl-2-propen-1-amine (2-PAMs) was assayed against Trypanosoma cruzi and Leishmania amazonensis. They showed higher activity against trypomastigotes and epimastigotes of T. cruzi than the standard drugs, crystal violet and nifurtimox. Besides these derivatives, a series of eleven 2-PAMs derivatives and the corresponding intermediates, biphenyl methanones (BPMs) were assayed against promastigotes of L. amazonensis, showing that the 2-PAMs were remarkably more active than the BPMs. The PAMs 2c, 2e and 2j were about 2-fold more active that pentamidine isothionate and between 27.2- and 46.4-fold less toxic to V79 mammalian cells. The present results encourage further studies, especially against intracellular parasites and in experimental animals.

In vitro characterization of pralidoxime transport and acetylcholinesterase reactivation across MDCK cells and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs).

PubMed

Gallagher, Erin; Minn, Il; Chambers, Janice E; Searson, Peter C

2016-07-11

Current therapies for organophosphate poisoning involve administration of oximes, such as pralidoxime (2-PAM), that reactivate the enzyme acetylcholinesterase. Studies in animal models have shown a low concentration in the brain following systemic injection. To assess 2-PAM transport, we studied transwell permeability in three Madin-Darby canine kidney (MDCKII) cell lines and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs). To determine whether 2-PAM is a substrate for common brain efflux pumps, experiments were performed in the MDCKII-MDR1 cell line, transfected to overexpress the P-gp efflux pump, and the MDCKII-FLuc-ABCG2 cell line, transfected to overexpress the BCRP efflux pump. To determine how transcellular transport influences enzyme reactivation, we developed a modified transwell assay where the inhibited acetylcholinesterase enzyme, substrate, and reporter are introduced into the basolateral chamber. Enzymatic activity was inhibited using paraoxon and parathion. The permeability of 2-PAM is about 2 × 10(-6) cm s(-1) in MDCK cells and about 1 × 10(-6) cm s(-1) in BC1-hBMECs. Permeability is not influenced by pre-treatment with atropine. In addition, 2-PAM is not a substrate for the P-gp or BCRP efflux pumps. The low permeability explains poor brain penetration of 2-PAM and therefore the slow enzyme reactivation. This elucidates one of the reasons for the necessity of sustained intravascular (IV) infusion in response to organophosphate poisoning.

Steer by ear: Myoelectric auricular control of powered wheelchairs for individuals with spinal cord injury.

PubMed

Schmalfuß, L; Rupp, R; Tuga, M R; Kogut, A; Hewitt, M; Meincke, J; Klinker, F; Duttenhoefer, W; Eck, U; Mikut, R; Reischl, M; Liebetanz, D

2015-01-01

Providing mobility solutions for individuals with tetraplegia remains challenging. Existing control devices have shortcomings such as varying or poor signal quality or interference with communication. To overcome these limitations, we present a novel myoelectric auricular control system (ACS) based on bilateral activation of the posterior auricular muscles (PAMs). Ten able-bodied subjects and two individuals with tetraplegia practiced PAM activation over 4 days using visual feedback and software-based training for 1 h/day. Initially, half of these subjects were not able to voluntarily activate their PAMs. This ability was tested with regard to 8 parameters such as contraction rate, lateralized activation, wheelchair speed and path length in a virtual obstacle course. In session 5, all subjects steered an electric wheelchair with the ACS. Performance of all subjects in controlling their PAMs improved steadily over the training period. By day 5, all subjects successfully generated basic steering commands using the ACS in a powered wheelchair, and subjects with tetraplegia completed a complex real-world obstacle course. This study demonstrates that the ability to activate PAM on both sides together or unilaterally can be learned and used intuitively to steer a wheelchair. With the ACS we can exploit the untapped potential of the PAMs by assigning them a new, complex function. The inherent advantages of the ACS, such as not interfering with oral communication, robustness, stability over time and proportional and continuous signal generation, meet the specific needs of wheelchair users and render it a realistic alternative to currently available assistive technologies.

Disease activity in and quality of life of patients with psoriatic arthritis mutilans: the Nordic PAM Study.

PubMed

Lindqvist, U; Gudbjornsson, B; Iversen, L; Laasonen, L; Ejstrup, L; Ternowitz, T; Ståhle, M

2017-11-01

To describe the social status and health-related quality of life of patients with psoriatic arthritis mutilans (PAM) in the Nordic countries. Patients with at least one mutilated joint confirmed by radiology were studied. Disease activity involving joints and skin, physician-assessed disease activity, and patient's education and work status were recorded. Data from the 36-item Short Form Health Survey, Health Assessment Questionnaire and Dermatology Life Quality Index questionnaire were gathered and correlated with disease duration, pain, and general well-being (visual analogue scale). The controls were 58 Swedish patients with long-standing psoriatic arthritis sine PAM. Sixty-seven patients were included. Patients with PAM had a protracted disease history (33 ± 14 years) and disease onset at a relatively early age (30 ± 12 years). Overall inflammatory activity at inclusion was mild to moderate. The mean number of mutilated joints was 8.2 and gross deformity was found in 16% of patients. Forty per cent were treated with biological and 32% with conventional synthetic disease-modifying anti-rheumatic drugs. Forty-two per cent had retired early or were on sick leave. Impaired functional capacity with little or no ability to perform self-care or everyday tasks was reported by 21% of the patients. Patients between 45 and 60 years of age reported the most impaired quality of life in comparison to the control group. PAM seriously affects social functioning. Whether early recognition of PAM and new forms of therapy can improve disease outcome and quality of life remains to be studied.

DVD pickup head based optical resolution photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Wang, Po-Hsun; Li, Meng-Lin

2012-02-01

Optical resolution photoacoustic microscopy (OR-PAM) has been shown as a promising tool for label-free microvascular and single-cell imaging in clinical and bioscientific applications. However, most OR-PAM systems are realized by using a bulky laser for photoacoustic excitation. The large volume and high price of the laser may restrain the popularity of OR-PAM. In this study, we develop a low-cost and compact OR-PAM system based on a commercially available DVD pickup head. We showed that the DVD pickup head have the required laser energy and focusing optics for OR-PAM. The firmware of a DVD burner was modified to enable its laser diode to provide a 13-ns laser pulse with 1.3-nJ energy at 650 nm. Two excitation wavelengths at 650 and 780 nm were available. The laser beam was focused onto the target after passing through a 0.6-mm thick DVD transparent polycarbonate coating, and then aligned to be confocal with a 50-MHz focused ultrasonic transducer in forward mode. To keep the target on focus, a scan involving auto-tracking procedure was performed. The lateral resolution was verified via cross-sectional imaging of a 6-μm carbon fiber. The measured -6 dB width of the carbon fiber was 6.66 μm which was in agreement with optical diffraction limit. The proposed OR-PAM has potential as an economically viable and compact blood screening tool available outside of large laboratories due to its low cost and portability. Furthermore, a better spatial resolution could be provided by using a blue ray DVD pickup head.

Development and validation of a UV-spectrophotometric method for the determination of pheniramine maleate and its stability studies

NASA Astrophysics Data System (ADS)

Raghu, M. S.; Basavaiah, K.; Ramesh, P. J.; Abdulrahman, Sameer A. M.; Vinay, K. B.

2012-03-01

A sensitive, precise, and cost-effective UV-spectrophotometric method is described for the determination of pheniramine maleate (PAM) in bulk drug and tablets. The method is based on the measurement of absorbance of a PAM solution in 0.1 N HCl at 264 nm. As per the International Conference on Harmonization (ICH) guidelines, the method was validated for linearity, accuracy, precision, limits of detection (LOD) and quantification (LOQ), and robustness and ruggedness. A linear relationship between absorbance and concentration of PAM in the range of 2-40 μg/ml with a correlation coefficient (r) of 0.9998 was obtained. The LOD and LOQ values were found to be 0.18 and 0.39 μg/ml PAM, respectively. The precision of the method was satisfactory: the value of relative standard deviation (RSD) did not exceed 3.47%. The proposed method was applied successfully to the determination of PAM in tablets with good accuracy and precision. Percentages of the label claims ranged from 101.8 to 102.01% with the standard deviation (SD) from 0.64 to 0.72%. The accuracy of the method was further ascertained by recovery studies via a standard addition procedure. In addition, the forced degradation of PAM was conducted in accordance with the ICH guidelines. Acidic and basic hydrolysis, thermal stress, peroxide, and photolytic degradation were used to assess the stability-indicating power of the method. A substantial degradation was observed during oxidative and alkaline degradations. No degradation was observed under other stress conditions.

Differential gene expression profiling of Actinobacillus pleuropneumoniae during induction of primary alveolar macrophage apoptosis in piglets.

PubMed

Wang, Lei; Qin, Wanhai; Ruidong, Zhai; Liu, Shiting; Zhang, Hu; Sun, Changjiang; Feng, Xin; Gu, Jingmin; Du, Chongtao; Han, Wenyu; Langford, P R; Lei, Liancheng

2015-01-01

Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is the causative agent of porcine pleuropneumonia, a disease that causes serious problems for the swine industry. Successful infection by this bacterium requires breaking the first line of defence in the lungs, the primary alveolar macrophages (PAMs). Therefore, exploring A. pleuropneumoniae-PAM interactions will provide vital groundwork for the scientific control of this infectious disease, which has been little studied up to now. In this work, PAMs were isolated from piglets and co-incubated with A. pleuropneumoniae serovar 5b strain L20 in vitro, and their interaction, PAM cell death, and differential gene expression of A. pleuropneumoniae in response to PAM cell death were observed and analysed using confocal microscopy, electron microscopy, RT-PCR, Western blot, flow cytometry and the use of a gene expression profile chip. A. pleuropneumoniae quickly adhered to and invaded PAMs, inducing apoptosis, which was confirmed using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The highest percentage of apoptosis in cells was confirmed using flow cytometry when the cells were infected at a multiplicity of infection (MOI) of 10 and incubated for 5 h, with higher expression of activated caspase-3 as measured by Western blot. Using microarray gene chips with 2868 probes containing nearly all of the genomic sequence of A. pleuropneumoniae serotype 5b strain L20, a total of 185 bacterial genes were found to be differentially expressed (including 92 up-regulated and 93 down-regulated genes) and involved in the process of apoptosis, as compared with the expression of control bacteria cultured without PAMs in BHI medium (mean expression ratios >1.5-fold, p < 0.05). The up-regulated genes are involved in energy metabolism, gene transcription and translation, virulence related gene such as LPS, Trimeric Autotransporter Adhesin, RTX and similar genes. The down-regulated genes are involved in amino acid, cofactor, and vitamin metabolism, and also include ABC transporters. These data demonstrate that A. pleuropneumoniae induces apoptosis of PAMs and undergoes complex changes in gene transcription, including expression changes in known and potential virulence factors. Some potentially novel virulence targets have been identified, suggesting new strategies for the development of vaccines and medicines for both preventive and clinical use. Copyright © 2014 Elsevier Ltd. All rights reserved.

USDA-ARS perspective on PAM

USDA-ARS?s Scientific Manuscript database

Polyacrylamide (PAM) described herein is a synthetic organic polymer used globally by a number of important industries. It also has a number of valuable applications in irrigated agriculture, including its use in furrow irrigation to control erosion and sediment loss in runoff, manage infiltration,...

Surviving Naegleria fowleri infections: A successful case report and novel therapeutic approach.

PubMed

Heggie, Travis W; Küpper, Thomas

Naegleria fowleri is a deadly human pathogen recognized as the causative agent of Primary Amoebic Meningitis (PAM). N. fowleri is commonly found in warm freshwater environments such as natural or man-made lakes, hot springs, and resort spas frequented by tourists. PAM infections have a mortality rate between 95 and 99% with minimal progress being made toward a successful treatment therapy. We report the case of a 12-year old American female who survived a PAM infection and propose a new drug therapy which includes the antimicrobial drug Miltefosine. Copyright © 2017 Elsevier Ltd. All rights reserved.

Introduction of the new concept: Potential Aerosol Mass (PAM) for Inorganic and Organic Secondary Aerosol

NASA Astrophysics Data System (ADS)

Kang, E.; Root, M. J.; Brune, W. H.

2006-12-01

A new concept, the Potential Aerosol Mass (PAM), is being developed and tested in the laboratory with the goal of deploying instruments to measure PAM in the atmosphere. PAM can be defined as the maximum aerosol mass that precursor gases can be oxidized to form. In the PAM concept, all precursor gases are oxidized to low volatile compounds with excessive amount of oxidants in a small continuous-flow Teflon cylinder, resulting in aerosol formation. Excessive amounts of OH and O3 are produced by a UV light that shines into the Teflon chamber. For our studies, the aerosol mass is then detected with a real-time aerosol mass measurement instrument, the Rupprecht and Patashnick Tapered Element Oscillating Microbalance (TEOM) and Filter Dynamic Measurement System (FDMS). As a test of the system, SO2 was oxidized to sulfate; the measured and calculated conversion ratios of sulfate aerosol mass to SO2 mass agree to within 10%. We will discuss the results of a series of laboratory tests that have been conducted with α-pinene to determine the variables that most affect its Secondary Organic Aerosol (SOA) yield. We will also discuss the results of some atmospheric measurement tests made at a site on the Penn State University campus.

Polyacrylamide sorption opportunity on interlayer and external pore surfaces of contaminant barrier clays.

PubMed

Inyang, Hilary I; Bae, Sunyoung

2005-01-01

Physico-chemical interactions among polymer molecules in aqueous solution and clay mineralogical/textural characteristics influence the sorption of polymer molecules on clay barrier minerals. Amendment of potentially unstable barrier clays with aqueous polymers can improve barrier material resistance to environmental stresses during service. In this research, the ability of molecular coils of polyacrylamide (PAM) to overlap in solution and to enter interlayer space in Na-montmorillonite (specific surface=31.82+/-0.22 m2 g(-1)) and kaolinite (specific surface=18+/-2 m2 g(-1)) were analyzed theoretically and experimentally, using solution viscosity measurements, and X-ray diffractometry. Experimental data on two theoretical indices: relative size ratio (RSR); and molecular availability (Ma) that are formulated to scale polymer molecular sorption on clay interlayer, indicate that the sorption of PAM A (Mw=4000000) and PAM B (Mw=7000000) does not produce any significant change in the d-spacing of both clay minerals. Although the negative Ma values of -3.51 g l(-1) for PAM A and -3.88 g l(-1) for PAM B indicate high levels of entanglement of polymer molecular coils in solution, sorption data confirm that the entangled coils are still able to sorb onto Na-montmorillonite highly and kaolinite to a lesser extent.

AMPA receptor positive allosteric modulators attenuate morphine tolerance and dependence.

PubMed

Hu, Xiaoyu; Tian, Xuebi; Guo, Xiao; He, Ying; Chen, Haijun; Zhou, Jia; Wang, Zaijie Jim

2018-04-25

Development of opioid tolerance and dependence hinders the use of opioids for the treatment of chronic pain. In searching for the mechanism and potential intervention for opioid tolerance and dependence, we studied the action of two positive allosteric modulators of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR PAMs). In mice treated with morphine (100 mg/kg, s.c.), acute morphine tolerance and dependence developed in 4-6 h. Treatment with aniracetam, a well-established AMPAR PAM, was able to completely prevent and reverse the development of acute antinociceptive tolerance to morphine. Partial, but significant, effects of aniracetam on acute morphine induced-physical dependence were also observed. Moreover, aniracetam significantly reversed the established morphine tolerance and dependence in a chronic model of morphine tolerance and dependence produced by intermittent morphine (10 mg/kg, s.c. for 5d). In addition, HJC0122, a new AMPAR PAM was found to have similar effects as aniracetam but with a higher potency. These previously undisclosed actions of AMPAR PAMs are intriguing and may shed lights on understanding the APMA signaling pathway in opioid addiction. Moreover, these data suggest that AMPAR PAMs may have utility in preventing and treating morphine tolerance and dependence. Copyright © 2018. Published by Elsevier Ltd.

Thermal Image of Coffee-Seed Germ Obtained by Photoacoustic Microscopy

NASA Astrophysics Data System (ADS)

Domínguez-Pacheco, A.; Hernández Aguilar, C.; Cruz-Orea, Alfredo; Isaac Alemán, E.; Martínez Ortiz, E.

2013-09-01

Photoacoustic microscopy (PAM) has been shown to be a suitable technique to obtain thermal images of a wide variety of samples from semiconductors to biological material. In PAM, the incidence of a modulated laser beam on a sample within a photoacoustic (PA) cell, hermetically sealed, produces a PA signal which depends on the thermal and optical properties of the studied sample. By making a sweep of the modulated laser beam on the sample surface, it is possible to obtain the PA signal as a function of their x- y coordinates, and from this signal, it is possible to reconstruct thermal images of the sample. In this study, thermal images of a coffee-seed germ were obtained, with a difference of 12 h between them, by using the PAM technique. Thermal differences observed between images give information which reflects degradation due to the fact that germ cells undergo changes as a function of time. The thermal images obtained by the PAM technique could be applied to biological materials that have a complex constitution (not homogeneous) in their structures, and thermal differences can be observed. PAM is a non-destructive technique, which is an important feature for this type of study. Other applications of this technique can be performed in the agricultural and biotechnological areas.

PAM-OBG: A monoamine oxidase B specific prodrug that inhibits MGMT and generates DNA interstrand crosslinks, potentiating temozolomide and chemoradiation therapy in intracranial glioblastoma

PubMed Central

Sharpe, Martyn A.; Raghavan, Sudhir; Baskin, David S.

2018-01-01

Via extensive analyses of genetic databases, we have characterized the DNA-repair capacity of glioblastoma with respect to patient survival. In addition to elevation of O6-methylguanine DNA methyltransferase (MGMT), down-regulation of three DNA repair pathways; canonical mismatch repair (MMR), Non-Homologous End-Joining (NHEJ), and Homologous Recombination (HR) are correlated with poor patient outcome. We have designed and tested both in vitro and in vivo, a monoamine oxidase B (MAOB) specific prodrug, PAM-OBG, that is converted by glioma MAOB into the MGMT inhibitor O6-benzylguanine (O6BG) and the DNA crosslinking agent acrolein. In cultured glioma cells, we show that PAM-OBG is converted to O6BG, inhibiting MGMT and sensitizing cells to DNA alkylating agents such as BCNU, CCNU, and Temozolomide (TMZ). In addition, we demonstrate that the acrolein generated is highly toxic in glioma treated with an inhibitor of Nucleotide Excision Repair (NER). In mouse intracranial models of primary human glioma, we show that PAM-OBG increases survival of mice treated with either BCNU or CCNU by a factor of six and that in a chemoradiation model utilizing six rounds of TMZ/2Gy radiation, pre-treatment with PAM-OBG more than doubled survival time. PMID:29844863

PAM-OBG: A monoamine oxidase B specific prodrug that inhibits MGMT and generates DNA interstrand crosslinks, potentiating temozolomide and chemoradiation therapy in intracranial glioblastoma.

PubMed

Sharpe, Martyn A; Raghavan, Sudhir; Baskin, David S

2018-05-08

Via extensive analyses of genetic databases, we have characterized the DNA-repair capacity of glioblastoma with respect to patient survival. In addition to elevation of O 6 -methylguanine DNA methyltransferase (MGMT), down-regulation of three DNA repair pathways; canonical mismatch repair (MMR), Non-Homologous End-Joining (NHEJ), and Homologous Recombination (HR) are correlated with poor patient outcome. We have designed and tested both in vitro and in vivo , a monoamine oxidase B (MAOB) specific prodrug, PAM-OBG, that is converted by glioma MAOB into the MGMT inhibitor O 6 -benzylguanine (O 6 BG) and the DNA crosslinking agent acrolein. In cultured glioma cells, we show that PAM-OBG is converted to O 6 BG, inhibiting MGMT and sensitizing cells to DNA alkylating agents such as BCNU, CCNU, and Temozolomide (TMZ). In addition, we demonstrate that the acrolein generated is highly toxic in glioma treated with an inhibitor of Nucleotide Excision Repair (NER). In mouse intracranial models of primary human glioma, we show that PAM-OBG increases survival of mice treated with either BCNU or CCNU by a factor of six and that in a chemoradiation model utilizing six rounds of TMZ/2Gy radiation, pre-treatment with PAM-OBG more than doubled survival time.

Detection of physical activities using a physical activity monitor system for wheelchair users.

PubMed

Hiremath, Shivayogi V; Intille, Stephen S; Kelleher, Annmarie; Cooper, Rory A; Ding, Dan

2015-01-01

Availability of physical activity monitors for wheelchair users can potentially assist these individuals to track regular physical activity (PA), which in turn could lead to a healthier and more active lifestyle. Therefore, the aim of this study was to develop and validate algorithms for a physical activity monitoring system (PAMS) to detect wheelchair based activities. The PAMS consists of a gyroscope based wheel rotation monitor (G-WRM) and an accelerometer device (wocket) worn on the upper arm or on the wrist. A total of 45 persons with spinal cord injury took part in the study, which was performed in a structured university-based laboratory environment, a semi-structured environment at the National Veterans Wheelchair Games, and in the participants' home environments. Participants performed at least ten PAs, other than resting, taken from a list of PAs. The classification performance for the best classifiers on the testing dataset for PAMS-Arm (G-WRM and wocket on upper arm) and PAMS-Wrist (G-WRM and wocket on wrist) was 89.26% and 88.47%, respectively. The outcomes of this study indicate that multi-modal information from the PAMS can help detect various types of wheelchair-based activities in structured laboratory, semi-structured organizational, and unstructured home environments. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

How Does Plasma Activated Media Treatment Differ From Direct Cold Plasma Treatment.

PubMed

Attri, Pankaj; Park, Ji Hoon; Ali, Anser; Choi, Eun Ha

2018-04-06

The aim of the paper is to investigate the optimum condition for generation of plasma activated media (PAM), where it can deactivate the cancer cells while minimum damage for normal cells. Over past few years, cold atmospheric plasma-activated media (PAM) have shown its promising application in plasma medicine for treatment of cancer. PAM has a tremendous ability for selective anti-cancer capacity in vitro and in vivo. We have analyzed the radicals in air using the optical emission spectroscopy and in culture media using chemical analysis. Further, we have tested the toxicity of PAM using MTT assay. We observed that more cancer cell death is for the Ar plasma followed by the Ar-N2 plasma, and the least cell death was observed for the Ar-O2 plasma at all treatment times both by direct treatment and through PAM treatment. The concentration of the RNS species is high for Ar-N2 plasma in gas as well as inside the culture media compared to that for pure Ar plasma. However, the difference is significantly less between the Ar plasma treatments and the Ar-N2 plasma treatments, showing that ROS is the main factor contributing to cell death. Among all three feeding gas plasmas the best system is Ar-O2 plasma for direct treatments towards the cancer cells. In addition, the best system for PAM preparation is Ar-N2 at low time treatments (1 min and 2 min) because it has no effect on normal cells, but kills the cancer cells. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Oleic acid derived metabolites in mouse neuroblastoma N18TG2 cells.

PubMed

Merkler, David J; Chew, Geoffrey H; Gee, Andrew J; Merkler, Kathleen A; Sorondo, Jean-Paul O; Johnson, Mitchell E

2004-10-05

Oleamide is an endogenous sleep-inducing lipid that has been isolated from the cerebrospinal fluid of sleep-deprived mammals. Oleamide is the best-understood member of the primary fatty acid amide family. One key unanswered question regarding oleamide and all other primary acid amides is the pathway by which these molecules are produced. One proposed pathway involves oleoyl-CoA and N-oleoylglycine as intermediates: oleic acid --> oleoyl-CoA --> N-oleoylglycine --> oleamide. The first and third reactions are known reactions, catalyzed by acyl-CoA synthetase and peptidylglycine alpha-amidating monooxygenase (PAM). Oleoyl-CoA formation from oleic acid has been demonstrated in vitro and in vivo while, to date, N-oleoylglycine cleavage to oleamide has been established only in vitro. PAM catalyzes the final step in alpha-amidated peptide biosynthesis, and its proposed role in primary fatty acid amide biosynthesis has been controversial. Mouse neuroblastoma N(18)TG(2) cells are an excellent model system for the study of oleamide biosynthesis because these cells convert [(14)C]-oleic acid to [(14)C]-oleamide and express PAM in a regulated fashion. We report herein that growth of the N(18)TG(2) cells in the presence of [(14)C]-oleic acid under conditions known to stimulate PAM expression generates an increase in [(14)C]-oleamide or in the presence of a PAM inhibitor generates [(14)C]-N-oleoylglycine. This represents the first identification of N-oleoylglycine from a biological source. In addition, N(18)TG(2) cell growth in the presence of N-oleoylglycine yields oleamide. These results strongly indicate that N-oleoylglycine is an intermediate in oleamide biosynthesis and provide further evidence that PAM does have a role in primary fatty acid amide production in vivo.

Characterization of Potential Aerosol Mass using an Oxidation Chamber coupled to an Aerodyne HR-ToF-AMS during DAURE, SHARP, and FLAME-3

NASA Astrophysics Data System (ADS)

Ortega, A. M.; Brune, W. H.; Cubison, M.; Lefer, B. L.; Schallharter, S.; Metzger, A.; Mueller, M.; Hansel, A.; Jimenez, J. L.

2009-12-01

The Potential Aerosol Mass (PAM) oxidation chamber (Kang et al., ACP 2007) used in front of an aerosol instrument provides an indication of the secondary inorganic and organic aerosol formation potential in an airmass. The chamber, a flow tube with small residence time, rapidly oxidizes ambient air through exposure to high concentrations of ozone (O3) and hydroxy (OH) and hydroperoxy (HO2) radicals. Here we use a recently-modified PAM chamber in conjunction with an Aerodyne High Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS; DeCarlo et al., Anal. Chem. 2006) during two ambient studies and one source study: the Determination of the Sources of the Atmospheric Aerosol in Urban and Rural Environments in Spain (DAURE) in February 2009, the Study of Houston Atmospheric Radical Precursors (SHARP) in April 2009, and the Fire Lab at Missoula Experiment phase 3 (FLAME-3) in Sep. 2009. The AMS samples alternatively between ambient air and chamber-processed air every 2.5 min., and a cycling of the UV light intensity (OH exposure) is also used with a maximum equivalent exposure of about 7 days. Large variations in the organic PAM were observed in the different studies. In particular very large PAM values were observed in several evenings in Houston when the site was impacted by emissions from petrochemical facilities. Optimum OH exposure for maximum PAM was observed at intermediate OH levels. For all experiments we compare the amount of SOA formed in the PAM chamber to the yield predicted by the measured precursors (from PTRMS instruments).

KK-92A, a novel GABAB receptor positive allosteric modulator, attenuates nicotine self-administration and cue-induced nicotine seeking in rats.

PubMed

Li, Xia; Sturchler, Emmanuel; Kaczanowska, Katarzyna; Cameron, Michael; Finn, M G; Griffin, Patrick; McDonald, Patricia; Markou, Athina

2017-05-01

GABA B receptors (GABA B R) play a critical role in GABAergic neurotransmission in the brain and are thought to be one of the most promising targets for the treatment of drug addiction. GABA B R positive allosteric modulators (PAMs) have shown promise as potential anti-addictive therapies, as they lack the sedative and muscle relaxant properties of full GABA B receptor agonists such as baclofen. The present study was aimed at developing novel, selective, and potent GABA B R PAMs with efficacy on abuse-related effects of nicotine. We synthetized ~100 analogs of BHF177, a GABA B R PAM that has been shown to inhibit nicotine taking and seeking, and tested their activity in multiple cell-based functional assays. Among these compounds, KK-92A displayed superior PAM properties at the GABA B R. Interestingly, our results revealed the existence of pathway-selective differential modulation of GABA B R signaling by the structurally related GABA B R allosteric modulators BHF177 and KK-92A. In vivo, similarly to BHF177, KK-92A inhibited intravenous nicotine self-administration under both fixed- and progressive-ratio schedules of reinforcement in rats. In contrast to BHF177, KK-92A had no effect on food self-administration. Furthermore, KK-92A decreased cue-induced nicotine-seeking behavior without affecting food seeking. These results indicate that KK-92A is a selective GABA B R PAM with efficacy in inhibition of the primary reinforcing and incentive motivational effects of nicotine, and attenuation of nicotine seeking, further confirming that GABA B R PAMs may be useful antismoking medications.

Adaptor Protein-1 Complex Affects the Endocytic Trafficking and Function of Peptidylglycine α-Amidating Monooxygenase, a Luminal Cuproenzyme*

PubMed Central

Bonnemaison, Mathilde L.; Bäck, Nils; Duffy, Megan E.; Ralle, Martina; Mains, Richard E.; Eipper, Betty A.

2015-01-01

The adaptor protein-1 complex (AP-1), which transports cargo between the trans-Golgi network and endosomes, plays a role in the trafficking of Atp7a, a copper-transporting P-type ATPase, and peptidylglycine α-amidating monooxygenase (PAM), a copper-dependent membrane enzyme. Lack of any of the four AP-1 subunits impairs function, and patients with MEDNIK syndrome, a rare genetic disorder caused by lack of expression of the σ1A subunit, exhibit clinical and biochemical signs of impaired copper homeostasis. To explore the role of AP-1 in copper homeostasis in neuroendocrine cells, we used corticotrope tumor cells in which AP-1 function was diminished by reducing expression of its μ1A subunit. Copper levels were unchanged when AP-1 function was impaired, but cellular levels of Atp7a declined slightly. The ability of PAM to function was assessed by monitoring 18-kDa fragment-NH2 production from proopiomelanocortin. Reduced AP-1 function made 18-kDa fragment amidation more sensitive to inhibition by bathocuproine disulfonate, a cell-impermeant Cu(I) chelator. The endocytic trafficking of PAM was altered, and PAM-1 accumulated on the cell surface when AP-1 levels were reduced. Reduced AP-1 function increased the Atp7a presence in early/recycling endosomes but did not alter the ability of copper to stimulate its appearance on the plasma membrane. Co-immunoprecipitation of a small fraction of PAM and Atp7a supports the suggestion that copper can be transferred directly from Atp7a to PAM, a process that can occur only when both proteins are present in the same subcellular compartment. Altered luminal cuproenzyme function may contribute to deficits observed when the AP-1 function is compromised. PMID:26170456

Capacity upgrade in short-reach optical fibre networks: simultaneous 4-PAM 20 Gbps data and polarization-modulated PPS clock signal using a single VCSEL carrier

NASA Astrophysics Data System (ADS)

Isoe, G. M.; Wassin, S.; Gamatham, R. R. G.; Leitch, A. W. R.; Gibbon, T. B.

2017-11-01

In this work, a four-level pulse amplitude modulation (4-PAM) format with a polarization-modulated pulse per second (PPS) clock signal using a single vertical cavity surface emitting laser (VCSEL) carrier is for the first time experimentally demonstrated. We propose uncomplex alternative technique for increasing capacity and flexibility in short-reach optical communication links through multi-signal modulation onto a single VCSEL carrier. A 20 Gbps 4-PAM data signal is directly modulated onto a single mode 10 GHz bandwidth VCSEL carrier at 1310 nm, therefore, doubling the network bit rate. Carrier spectral efficiency is further maximized by exploiting the inherent orthogonal polarization switching of the VCSEL carrier with changing bias in transmission of a PPS clock signal. We, therefore, simultaneously transmit a 20 Gbps 4-PAM data signal and a polarization-based PPS clock signal using a single VCSEL carrier. It is the first time a signal VCSEL carrier is reported to simultaneously transmit a directly modulated 20 Gbps 4-PAM data signal and a polarization-based PPS clock signal. We further demonstrate on the design of a software-defined digital signal processing (DSP)-assisted receiver as an alternative to costly receiver hardware. Experimental results show that a 3.21 km fibre transmission with simultaneous 20 Gbps 4-PAM data signal and polarization-based PPS clock signal introduced a penalty of 3.76 dB. The contribution of polarization-based PPS clock signal to this penalty was found out to be 0.41 dB. Simultaneous distribution of data and timing clock signals over shared network infrastructure significantly increases the aggregated data rate at different optical network units (ONUs), without costly investment.

Exploring the Biotic Pump Hypothesis along Non-linear Transects in Tropical South America

NASA Astrophysics Data System (ADS)

Molina, R.; Bettin, D. M.; Salazar, J. F.; Villegas, J. C.

2014-12-01

Forests might actively transport atmospheric moisture from the oceans, according to the biotic pump of atmospheric moisture (BiPAM) hypothesis. The BiPAM hypothesis appears to be supported by the fact that precipitation drops exponentially with distance from ocean along non-forested land transects, but not on their forested counterparts. Yet researchers have discussed the difficulty in defining proper transects for BiPAM studies. Previous studies calculate precipitation gradients either along linear transects maximizing distance to the ocean, or along polylines following specific atmospheric pathways (e.g., aerial rivers). In this study we analyzed precipitation gradients along curvilinear streamlines of wind in tropical South America. Wind streamlines were computed using long-term quarterly averages of meridional and zonal wind components from the ERA-Interim and NCEP/NCAR reanalyses. Total precipitation along streamlines was obtained from four data sources: TRMM, UDEL, ERA-Interim, and NCEP/NCAR. Precipitation on land versus distance from the ocean was analyzed along selected streamlines for each data source. As predicted by BiPAM, precipitation gradients did not decrease exponentially along streamlines in the vicinity of the Amazon forest, but dropped rapidly as distance from the forest increased. Remarkably, precipitation along streamlines in some areas outside the Amazon forest did not decrease exponentially either. This was possibly owing to convergence of moisture conveyed by low level jets (LLJs) in those areas (e.g., streamlines driven by the Caribbean and CHOCO jets on the Pacific coast of Colombia). Significantly, BiPAM held true even along long transects displaying strong sinuosity. In fact, the general conclusions of previous studies remain valid. Yet effects of LLJs on precipitation gradients need to be thoroughly considered in future BiPAM studies.

Investigating the properties and interaction mechanism of nano-silica in polyvinyl alcohol/polyacrylamide blends at an atomic level.

PubMed

Wei, Qinghua; Wang, Yanen; Wang, Shuzhi; Zhang, Yingfeng; Chen, Xiongbiao

2017-11-01

The nano-silica can be incorporated into polymers for improved mechanical properties. Notably, the interaction between nano-silica and polymer is of a microscopic phenomenon and thus, hard to observe and study by using experimental methods. Based on molecular dynamics, this paper presents a study on the properties and the interaction mechanism of nano-silica in the polyvinyl alcohol (PVA)/polyacrylamide (PAM) blends at an atomic level. Specifically, six blends of PVA/PAM with varying concentrations of nano-silica (0-13wt%) and two interfacial interaction models of polymers on the silica surface were designed and analyzed at an atomic level in terms of concentration profile, mechanical properties, fractional free volume (FFV), dynamic properties of polymers and X-ray diffraction patterns. The concentration profile results and micromorphologies of equilibrium models suggest PAM molecular chains are easier to be adsorbed on the silica surface than PVA molecular chains in blends. The incorporation of nano-silica into the PVA/PAM blends can increase the blend mechanical properties, densities, and semicrystalline character. Meanwhile, the FFV and the mobility of polymer chain decrease with the silica concentration, which agrees with the results of mechanical properties, densities, and semicrystalline character. Our results also illustrate that an analysis of binding energies and pair correlation functions (PCF) allows for the discovery of the interaction mechanism of nano-silica in PVA/PAM blends; and that hydrogen bond interactions between polar functional groups of polymer molecular chains and the hydroxyl groups of the silica surface are involved in adsorption of the polymers on the silica surface, thus affecting the interaction mechanism of nano-silica in PVA/PAM blend systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pralidoxime inhibits paraoxon-induced depression of rocuronium-neuromuscular block in a time-dependent fashion.

PubMed

Narimatsu, Eichi; Niiya, Tomohisa; Takahashi, Kazunobu; Yamauchi, Masanori; Yamakage, Michiaki

2012-07-01

The composite effects of organophosphorus (OP)-cholinesterase (ChE) inhibitors and oximes on the actions of nondepolarizing neuromuscular blockers in acute OP-ChE inhibitor intoxication have not been evaluated in detail. We investigated the effects of paraoxon (Pox) (an OP-ChE inhibitor) and pralidoxime (PAM) (an oxime) on the nondepolarizing neuromuscular blocking action of rocuronium. Isometric twitch tensions of rat left phrenic nerve-hemidiaphragm preparations elicited by indirect (phrenic nerve) supramaximal stimulation at 0.1 Hz were evaluated. Analysis of variance with post hoc testing was used for statistical comparison, and P < .05 was accepted as significant. Rocuronium reduced the indirectly elicited twitch tensions in normal (50% inhibitory concentration [IC(50)], 9.84 [9.64-10.04] μM, mean [95% confidence interval]) and all pretreated diaphragms (P < .01, n = 6) in a concentration-dependent fashion. Paraoxon caused a rightward shift in the rocuronium concentration-twitch tension curve (IC(50), 15.48 [15.24-15.72] μM). The rightward shift was completely inhibited by previous copretreatment (IC(50), 9.98 [9.77-10.20] μM) and partially inhibited by simultaneous copretreatment (IC(50), 11.68 [11.45-11.91] μM) with PAM but was not inhibited by subsequent copretreatment (IC(50), 13.69 [13.39-13.99] μM) with PAM (P < .01, n = 6). Atropine did not influence the rightward shift (P < .01, n = 6). Paraoxon depressed rocuronium-induced neuromuscular block by inhibiting ChEs, and the action of Pox was inhibited by PAM. Pralidoxime acts more intensely when applied earlier. The time-dependent effect of PAM indicates that the preceding presence of PAM in proximity to ChEs before Pox is necessary for definite suppression of the Pox-induced ChE inhibition. Copyright © 2012 Elsevier Inc. All rights reserved.

PAM50 gene signatures and breast cancer prognosis with adjuvant anthracycline- and taxane-based chemotherapy: correlative analysis of C9741 (Alliance)

PubMed Central

Liu, Minetta C; Pitcher, Brandelyn N; Mardis, Elaine R; Davies, Sherri R; Friedman, Paula N; Snider, Jacqueline E; Vickery, Tammi L; Reed, Jerry P; DeSchryver, Katherine; Singh, Baljit; Gradishar, William J; Perez, Edith A; Martino, Silvana; Citron, Marc L; Norton, Larry; Winer, Eric P; Hudis, Clifford A; Carey, Lisa A; Bernard, Philip S; Nielsen, Torsten O; Perou, Charles M; Ellis, Matthew J; Barry, William T

2016-01-01

PAM50 intrinsic breast cancer subtypes are prognostic independent of standard clinicopathologic factors. CALGB 9741 demonstrated improved recurrence-free (RFS) and overall survival (OS) with 2-weekly dose-dense (DD) versus 3-weekly therapy. A significant interaction between intrinsic subtypes and DD-therapy benefit was hypothesized. Suitable tumor samples were available from 1,471 (73%) of 2,005 subjects. Multiplexed gene-expression profiling generated the PAM50 subtype call, proliferation score, and risk of recurrence score (ROR-PT) for the evaluable subset of 1,311 treated patients. The interaction between DD-therapy benefit and intrinsic subtype was tested in a Cox proportional hazards model using two-sided alpha=0.05. Additional multivariable Cox models evaluated the proliferation and ROR-PT scores as continuous measures with selected clinical covariates. Improved outcomes for DD therapy in the evaluable subset mirrored results from the complete data set (RFS; hazard ratio=1.20; 95% confidence interval=0.99–1.44) with 12.3-year median follow-up. Intrinsic subtypes were prognostic of RFS (P<0.0001) irrespective of treatment assignment. No subtype-specific treatment effect on RFS was identified (interaction P=0.44). Proliferation and ROR-PT scores were prognostic for RFS (both P<0.0001), but no association with treatment benefit was seen (P=0.14 and 0.59, respectively). Results were similar for OS. The prognostic value of PAM50 intrinsic subtype was greater than estrogen receptor/HER2 immunohistochemistry classification. PAM50 gene signatures were highly prognostic but did not predict for improved outcomes with DD anthracycline- and taxane-based therapy. Clinical validation studies will assess the ability of PAM50 and other gene signatures to stratify patients and individualize treatment based on expected risks of distant recurrence. PMID:28691057

The impact of patient education and shared decision making on hospital readmissions for COPD

PubMed Central

Collinsworth, Ashley W; Brown, Rachel M; James, Cameron S; Stanford, Richard H; Alemayehu, Daniel; Priest, Elisa L

2018-01-01

Purpose Education on the self-management of COPD has been shown to improve patients’ quality of life and reduce hospital admissions. This study aimed to assess the feasibility of a pilot, pragmatic COPD Chronic Care (CCC) education program led by registered respiratory therapists and determine the CCC’s impact on hospital readmissions, patient activation, and health status. Patients and methods This was a prospective, randomized, pilot study of inpatients with COPD admitted to a US community hospital between August 2014 and February 2016. In total, 308 patients were randomized 1:1 to receive standard care with or without the CCC program. Outcomes included the number of patients completing the program, frequency and time to first all-cause and COPD-related hospital readmissions, and changes in the Patient Activation Measure (PAM) and COPD Assessment Test (CAT). Results Overall, 37% (n=52) of patients in the CCC group and 29% (n=48) of patients in the control group remained in the study for 6 months and completed all follow-up phone calls. In total, 74% (n=105) of patients in the CCC group and 69% (n=115) of patients in the control group had at least one readmission (P=0.316). The time to first all-cause and COPD-related readmission appeared shorter for patients in the CCC group compared with the control group (mean [standard deviation]: 50.2 [54.5] vs 59.9 [63.1] days and 95.1 [80.2] vs 113.7 [82.4] days, respectively; both P=0.231). Patients experienced significant improvement from baseline in mean PAM (both groups) and CAT (CCC group) scores. Conclusion Utilizing respiratory therapists to lead a chronic care education program for COPD in a community hospital was feasible. Although CCC patients showed improvements in perceived symptom severity, they were readmitted sooner than control group patients. However, the program did not impact the frequency of hospital readmissions. A more comprehensive disease management program may be needed to improve outcomes. PMID:29731620

The impact of patient education and shared decision making on hospital readmissions for COPD.

PubMed

Collinsworth, Ashley W; Brown, Rachel M; James, Cameron S; Stanford, Richard H; Alemayehu, Daniel; Priest, Elisa L

Education on the self-management of COPD has been shown to improve patients' quality of life and reduce hospital admissions. This study aimed to assess the feasibility of a pilot, pragmatic COPD Chronic Care (CCC) education program led by registered respiratory therapists and determine the CCC's impact on hospital readmissions, patient activation, and health status. This was a prospective, randomized, pilot study of inpatients with COPD admitted to a US community hospital between August 2014 and February 2016. In total, 308 patients were randomized 1:1 to receive standard care with or without the CCC program. Outcomes included the number of patients completing the program, frequency and time to first all-cause and COPD-related hospital readmissions, and changes in the Patient Activation Measure (PAM) and COPD Assessment Test (CAT). Overall, 37% (n=52) of patients in the CCC group and 29% (n=48) of patients in the control group remained in the study for 6 months and completed all follow-up phone calls. In total, 74% (n=105) of patients in the CCC group and 69% (n=115) of patients in the control group had at least one readmission ( P =0.316). The time to first all-cause and COPD-related readmission appeared shorter for patients in the CCC group compared with the control group (mean [standard deviation]: 50.2 [54.5] vs 59.9 [63.1] days and 95.1 [80.2] vs 113.7 [82.4] days, respectively; both P =0.231). Patients experienced significant improvement from baseline in mean PAM (both groups) and CAT (CCC group) scores. Utilizing respiratory therapists to lead a chronic care education program for COPD in a community hospital was feasible. Although CCC patients showed improvements in perceived symptom severity, they were readmitted sooner than control group patients. However, the program did not impact the frequency of hospital readmissions. A more comprehensive disease management program may be needed to improve outcomes.

The therapeutic strategies against Naegleria fowleri.

PubMed

Bellini, Natália Karla; Santos, Thomás Michelena; da Silva, Marco Túlio Alves; Thiemann, Otavio Henrique

2018-04-01

Naegleria fowleri is a pathogenic amoeboflagellate most prominently known for its role as the etiological agent of the Primary Amoebic Meningoencephalitis (PAM), a disease that afflicts the central nervous system and is fatal in more than 95% of the reported cases. Although being fatal and with potential risks for an increase in the occurrence of the pathogen in populated areas, the organism receives little public health attention. A great underestimation in the number of PAM cases reported is assumed, taking into account the difficulty in obtaining an accurate diagnosis. In this review, we summarize different techniques and methods used in the identification of the protozoan in clinical and environmental samples. Since it remains unclear whether the protozoan infection can be successfully treated with the currently available drugs, we proceed to discuss the current PAM therapeutic strategies and its effectiveness. Finally, novel compounds for potential treatments are discussed as well as research on vaccine development against PAM. Copyright © 2018 Elsevier Inc. All rights reserved.

Progress Report for the Robotic Intelligence Evaluation. Program Year 1: Developing Test Methodology for Anti-Rollover Systems

DTIC Science & Technology

2006-06-01

Scientific Research. 5PAM-Crash is a trademark of the ESI Group . 6MATLAB and SIMULINK are registered trademarks of the MathWorks. 14 maneuvers...Laboratory (ARL) to develop methodologies to evaluate robotic behavior algorithms that control the actions of individual robots or groups of robots...methodologies to evaluate robotic behavior algorithms that control the actions of individual robots or groups of robots acting as a team to perform a

International Conference on Chemical Kinetics: Program and Abstracts Held in Gaithersburg, Maryland on 17-19 June 1985.

DTIC Science & Technology

1985-06-01

relative to reactant and with the free energy of reaction. The correlation equations were derived from hyperbolic paraboloid models of the energy...obtained the differen- tial equations which define the best dividing surfaces of this type for both microcanonical and canonical cases. We have...is now generalized to non-uniform reaction systems. For kinetics-diffusion problems the equations of the generalized PAM were (similar in form to

Mapping of a microbial protein domain involved in binding and activation of the TLR2/TLR1 heterodimer.

PubMed

Liang, Shuang; Hosur, Kavita B; Lu, Shanyun; Nawar, Hesham F; Weber, Benjamin R; Tapping, Richard I; Connell, Terry D; Hajishengallis, George

2009-03-01

The pentameric B subunit of type IIb Escherichia coli enterotoxin (LT-IIb-B(5)), a doughnut-shaped oligomeric protein from enterotoxigenic E. coli, activates the TLR2/TLR1 heterodimer (TLR2/1). We investigated the molecular basis of the LT-IIb-B(5) interaction with TLR2/1 to define the structure-function relationship of LT-IIb-B(5) and, moreover, to gain an insight into how TLR2/1 recognizes large, nonacylated protein ligands that cannot fit within its lipid-binding pockets, as previously shown for the Pam(3)CysSerLys(4) (Pam(3)CSK(4)) lipopeptide. We first identified four critical residues in the upper region of the LT-IIb-B(5) pore. Corresponding point mutants (M69E, A70D, L73E, S74D) were defective in binding TLR2 or TLR1 and could not activate APCs, despite retaining full ganglioside-binding capacity. Point mutations in the TLR2/1 dimer interface, as determined in the crystallographic structure of the TLR2/1-Pam(3)CSK(4) complex, resulted in diminished activation by both Pam(3)CSK(4) and LT-IIb-B(5). Docking analysis of the LT-IIb-B(5) interaction with this apparently predominant activation conformation of TLR2/1 revealed that LT-IIb-B(5) might primarily contact the convex surface of the TLR2 central domain. Although the TLR1/LT-IIb-B(5) interface is relatively smaller, the leucine-rich repeat motifs 9-12 in the central domain of TLR1 were found to be critical for cooperative TLR2-induced cell activation by LT-IIb-B(5). Moreover, the putative LT-IIb-B(5) binding site overlaps partially with that of Pam(3)CSK(4); consistent with this, Pam(3)CSK(4) suppressed TLR2 binding of LT-IIb-B(5), albeit not as potently as self-competitive inhibition. We identified the upper pore region of LT-IIb-B(5) as a TLR2/1 interactive domain, which contacts the heterodimeric receptor at a site that is distinct from, although it overlaps with, that of Pam(3)CSK(4).

Survival, differentiation, and neuroprotective mechanisms of human stem cells complexed with neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo model of Parkinson's disease.

PubMed

Daviaud, Nicolas; Garbayo, Elisa; Sindji, Laurence; Martínez-Serrano, Alberto; Schiller, Paul C; Montero-Menei, Claudia N

2015-06-01

Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson's disease (PD). We recently reported the repair and functional recovery after treatment with human marrow-isolated adult multilineage inducible (MIAMI) cells adhered to neurotrophin-3 (NT3) releasing pharmacologically active microcarriers (PAMs) in hemiparkinsonian rats. In order to comprehend this effect, the goal of the present work was to elucidate the survival, differentiation, and neuroprotective mechanisms of MIAMI cells and human neural stem cells (NSCs), both adhering to NT3-releasing PAMs in an ex vivo organotypic model of nigrostriatal degeneration made from brain sagittal slices. It was shown that PAMs led to a marked increase in MIAMI cell survival and neuronal differentiation when releasing NT3. A significant neuroprotective effect of MIAMI cells adhering to PAMs was also demonstrated. NSCs barely had a neuroprotective effect and differentiated mostly into dopaminergic neuronal cells when adhering to PAM-NT3. Moreover, those cells were able to release dopamine in a sufficient amount to induce a return to baseline levels. Reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay analyses identified vascular endothelial growth factor (VEGF) and stanniocalcin-1 as potential mediators of the neuroprotective effect of MIAMI cells and NSCs, respectively. It was also shown that VEGF locally stimulated tissue vascularization, which might improve graft survival, without excluding a direct neuroprotective effect of VEGF on dopaminergic neurons. These results indicate a prospective interest of human NSC/PAM and MIAMI cell/PAM complexes in tissue engineering for PD. Stem cell-based regenerative therapies hold great potential for the treatment of degenerative disorders such as Parkinson's disease (PD). The present work elucidates and compares the survival, differentiation, and neuroprotective mechanisms of marrow-isolated adult multilineage inducible cells and human neural stem cells both adhered to neurotrophin-3-releasing pharmacologically active microcarriers in an ex vivo organotypic model of PD made from brain sagittal slices. ©AlphaMed Press.

Identification of cysteine protease inhibitors as new drug leads against Naegleria fowleri.

PubMed

Zyserman, Ingrid; Mondal, Deboprosad; Sarabia, Francisco; McKerrow, James H; Roush, William R; Debnath, Anjan

2018-05-01

Primary amebic meningoencephalitis (PAM) is a rapidly fatal infection caused by the free-living ameba Naegleria fowleri. PAM occurs principally in healthy children of less than 13 years old with a history of recent exposure to warm fresh water. While as yet not a reportable disease, the Centers for Disease Control and Prevention (CDC) documents a total of 143 cases in the United States. Only four patients have survived. Infection results from water containing N. fowleri entering the nose, followed by migration of the amebae to the brain. Within the brain, N. fowleri infection results in extensive necrosis, leading to death in 3-7 days. Mortality among patients with PAM is greater than 95%. The drugs of choice in treating PAM are the antifungal amphotericin B, and the antileishmanial, miltefosine. However neither drug is FDA-approved for this indication and the use of amphotericin B is associated with severe adverse effects. Moreover, very few patients treated with amphotericin B have survived PAM. Therefore, development of new, safe and effective drugs is a critical unmet need to avert future deaths of children. The molecular mechanisms underlying the pathogenesis of PAM are poorly understood but it is known that cysteine proteases of N. fowleri play a role in the progression of PAM. We therefore assessed the in vitro activity of the synthetic vinyl sulfone cysteine protease inhibitor, K11777, and 33 analogs with valine, phenylalanine or pyridylalanine at P2 position, against cysteine protease activity in the lysate of N. fowleri. Inhibitors with phenylalanine or pyridylalanine at P2 position were particularly effective in inhibiting the cysteine protease activity of N. fowleri cell lysate with IC 50 ranging between 3 nM and 6.6 μM. Three of the 34 inhibitors also showed inhibitory activity against N. fowleri in a cell viability assay and were 1.6- to 2.5-fold more potent than the standard of care drug miltefosine. Our study provides the first evidence of the activity of synthetic, small molecule cysteine protease inhibitors against N. fowleri. Copyright © 2018 Elsevier Inc. All rights reserved.

Frequent Surfing on Social Health Networks is Associated With Increased Knowledge and Patient Health Activation.

PubMed

Grosberg, Dafna; Grinvald, Haya; Reuveni, Haim; Magnezi, Racheli

2016-08-10

The advent of the Internet has driven a technological revolution that has changed our lives. As part of this phenomenon, social networks have attained a prominent role in health care. A variety of medical services is provided over the Internet, including home monitoring, interactive communications between the patient and service providers, and social support, among others. This study emphasizes some of the practical implications of Web-based health social networks for patients and for health care systems. The objective of this study was to assess how participation in a social network among individuals with a chronic condition contributed to patient activation, based on the Patient Activation Measure (PAM). A prospective, cross-sectional survey with a retrospective component was conducted. Data were collected from Camoni, a Hebrew-language Web-based social health network, participants in the diabetes mellitus, pain, hypertension, and depression/anxiety forums, during November 2012 to 2013. Experienced users (enrolled at least 6 months) and newly enrolled received similar versions of the same questionnaire including sociodemographics and PAM. Among 686 participants, 154 of 337 experienced and 123 of 349 newly enrolled completed the questionnaire. Positive correlations (P<.05) were found between frequency and duration of site visits and patient activation, social relationships, and chronic disease knowledge. Men surfed longer than women (χ²3=10.104, P<.05). Experienced users with diabetes surfed more than those with other illnesses and had significantly higher PAM scores (mean, M=69.3, standard deviation, SD=19.1, PAM level 4; Z=-4.197, P<.001) than new users (M=62.8, SD=18.7, PAM level 3). Disease knowledge directly predicted PAM for all users (β=.26 and .21, respectively). Frequency and duration of social health network use were correlated with increased knowledge about a chronic disease. Experienced surfers had higher PAM than newly enrolled, suggesting that continued site use may contribute to increased activation. Web-based social health networks offer an opportunity to expand patient knowledge and increase involvement in personal health, thereby increasing patient activation. Further studies are needed to examine these changes on other aspects of chronic illnesses such as quality of life and costs.

Studies of ambient noise in shallow water environments off Mexico and Alaska: characteristics, metrics and time-synchronization applications

NASA Astrophysics Data System (ADS)

Guerra, Melania

Sound in the ocean originates from multiple mechanisms, both natural and anthropogenic. Collectively, underwater ambient noise accumulates valuable information about both its sources and the oceanic environment that propagates this noise. Characterizing the features of ambient noise source mechanisms is challenging, but essential, for properly describing an acoustic environment. Disturbances to a local acoustic environment may affect many aquatic species that have adapted to be heavily dependent on this particular sense for survival functions. In the case of marine mammals, which are federally protected, demand exists for understanding such potential impacts, which drives important scientific efforts that utilize passive acoustic monitoring (PAM) tools to inform regulatory decisions. This dissertation presents two independent studies that use PAM data to investigate the characteristics of source mechanisms that dominate ambient noise in two diverse shallow water environments. The study in Chapter 2 directly addresses the concern of how anthropogenic activities can degrade the effectiveness of PAM. In the Alaskan Beaufort Sea, an environment where ambient noise is normally dominated by natural causes, seismic surveys create impulsive sounds to map the composition of the bottom. By inspecting single-sensor PAM data, the spectral characteristics of seismic survey airgun reverberation are measured, and their contribution to the overall ambient noise is quantified. This work is relevant to multiple ongoing mitigation protocols that rely on PAM to acoustically detect marine mammal presence during industrial operations. Meanwhile, Chapter 3 demonstrates that by analyzing data from multiple PAM sensors, features embedded in both directional and omnidirectional ambient noise can be used to develop new time-synchronization processing techniques for aligning autonomous elements of an acoustic array, a tool commonly used in PAM for detecting and tracking marine mammals. Using the time-synchronization procedures shown here, arrays may be built out of stand-alone recorders that simplify the deployment logistics and can be arranged in multiple configurations. Given increasing economic pressures worldwide, anthropogenic activities in the ocean are only expected to expand, and their ambient noise contributions will continue to rise. These studies provide baseline knowledge and practical tools to help properly assess the impact of such source mechanisms in shallow-water acoustic environments.

Cryotherapy for conjunctival primary acquired melanosis and malignant melanoma. Experience with 62 cases.

PubMed

Jakobiec, F A; Rini, F J; Fraunfelder, F T; Brownstein, S

1988-08-01

Sixty-two patients were treated by some combination of cryotherapy and surgery with an average follow-up of 3.3 years for one of the following diseases: focal or diffuse flat conjunctival primary acquired melanosis (PAM) with atypia but without a nodule of melanoma (10 cases); unifocal malignant melanoma with or without focal or diffuse PAM (30 cases); and multinodular/multicentric melanoma with and without PAM (22 cases). Of the ten patients who had PAM with atypia, invasive nodules of malignant melanoma did not develop. A second treatment was required to control the disease in four of the ten patients with extensive or diffuse lesions, and one has mild persistent disease. Of the 30 patients with unifocal nodules of malignant melanoma, 27 remained free of recurrence after one treatment, and 2 are asymptomatic after two treatments. One patient with a thick nodule at presentation required a parotidectomy and radical neck dissection for cervical metastases after recurrence in the conjunctival sac. In the group of 22 patients with multinodular malignant melanoma, only two did not have recurrent disease after one treatment. Of those who received multiple therapies, seven remained free of recurrence for at least 2 years after the last treatment; regional or distant metastases developed in nine; four required exenteration; and eight died. Conjunctival adjunctive cryotherapy avoids exenteration in extensive lesions of pure PAM and in unifocal melanoma, but even after multiple therapies, multinodular malignant melanoma had a 45% rate of metastasis. Metastasis was related to the presence of PAM sine pigmento in four patients (microscopically but not clinically detectable PAM); to the location of the nodules (9 of 10 patients who experienced metastases had forniceal, palpebral, and/or caruncular nodules); to the thickness or depth of invasion of the nodules (greater than 2 mm); and to the development of intralymphatic spread ("in-transit" local metastasis) within the conjunctival sac in six patients. No metastases were encountered among patients with strictly limbal nodules and among five patients with invasive nodules composed of spindle cells in part or in toto. Therapeutic success in this spectrum of melanocytic proliferations is closely correlated with the clinical extent of the disease when initiating definitive therapy.

Conformational effects on the torsional barriers in m-methylanisole studied by microwave spectroscopy

NASA Astrophysics Data System (ADS)

Ferres, Lynn; Stahl, Wolfgang; Nguyen, Ha Vinh Lam

2018-03-01

The microwave spectrum of m-methylanisole (also known as 3-methylanisole, or 3-methoxytoluene) was measured using a pulsed molecular jet Fourier transform microwave spectrometer operating in the frequency range of 2-26.5 GHz. Quantum chemical calculations predicted two conformers with the methoxy group in trans or cis position related to the ring methyl group, both of which were assigned in the experimental spectrum. Due to the internal rotation of the ring methyl group, all rotational transitions introduced large A-E splittings up to several GHz, which were analyzed with a newly developed program, called aixPAM, working in the principal axis system. There are significant differences in the V3 potential barriers of 55.7693(90) cm-1 and 36.6342(84) cm-1 determined by fitting 223 and 320 torsional components of the cis and the trans conformer, respectively. These values were compared with those found in other m-substituted toluenes as well as in o- and p-methylanisole. A comparison between the aixPAM and the XIAM code (using a combined axis system) was also performed.

Microlithiasis of Seminal Vesicles and Severe Oligoasthenospermia in Pulmonary Alveolar Microlithiasis (PAM): Report of An Unusual Sporadic Case.

PubMed

Castellana, Giuseppe; Carone, Domenico; Castellana, Marco

2015-01-01

Pulmonary alveolar microlithiasis (PAM) is classified as an elective dysmetabolic thesaurotic pneumoalveolitis and characterized by the presence within the alveoli of the lungs of myriad of tiny calculi. The classic presentation of the chest radiography is unmistakable with multiple small "sand-like" opacities diffusely involving both lung fields. We present a case of male infertility for hypoposia and severe oligoasthenospermia in a young patient with recurrent haematuria and small calcifications in the seminal vesicles similar to pulmonary microliths. PAM was diagnosed on routine chest radiography, com- puter tomography (CT), transbronchial biopsy and bronchoalveolar lavage (BAL).

40 CFR 58.12 - Operating schedules.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) AMBIENT AIR QUALITY SURVEILLANCE Monitoring Network § 58.12 Operating schedules. State and local... part. Area-specific PAMS operating schedules must be included as part of the PAMS network description... remains once every six days. No less frequently than as part of each 5-year network assessment, the most...

40 CFR 58.12 - Operating schedules.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) AMBIENT AIR QUALITY SURVEILLANCE Monitoring Network § 58.12 Operating schedules. State and local... part. Area-specific PAMS operating schedules must be included as part of the PAMS network description... remains once every six days. No less frequently than as part of each 5-year network assessment, the most...

Sedimentological characteristics of the 2015 Tropical Cyclone Pam overwash deposits from Vanuatu, South Pacific

NASA Astrophysics Data System (ADS)

Hong, I.; Pilarczyk, J.; Horton, B.; Fritz, H. M.; Kosciuch, T. J.; Wallace, D. J.; Dike, C.; Rarai, A.; Harrison, M. J.; Jockley, F. R.

2016-12-01

Historical observations and overwash sediments deposited by prehistoric tropical cyclones (TC) enable the assessment of long-term patterns of tropical cyclone variability. Prehistoric TC reconstructions, however, are limited in their ability to quantify the intensity of past events. Modern analogues present an opportunity to characterize overwash sediments deposited by a TC of known intensity. On 13 March 2015, TC Pam made landfall on Vanuatu as a Category 5 storm with 10-minute sustained wind speeds as high as 250 km/h. Less than three months after landfall, we (1) measured the height and inland extent of TC Pam's storm surge; and (2) described the sedimentological characteristics of the TC Pam overwash deposits focusing on two of the hardest hit islands, Efate and Tanna. TC Pam's storm surge inundated Vanuatu with maximum high water marks of 5.6 m above mean sea level (MSL) on the island of Efate and 5.5 m above MSL on the island of Tanna. We measured surge heights of 4.2 m above MSL at our study area Manuro on Efate and 3.3 m above MSL at our study area Port Resolution Bay on Tanna. TC Pam deposited a medium-grained (mean: 1.20 Φ), moderately well-sorted (sorting: 0.55 Φ) mixed-carbonate sand with trace amounts of volcanic sediments and coral fragments at Manuro. The sand extends 130 m inland, abruptly transitioning into pumice that extends 400 m inland into Lake Otas. A sharp contact separates the base of the sand and the underlying organic-rich sand unit. In contrast, TC Pam deposited a medium-grained (mean: 1.81 Φ), moderately well-sorted (sorting: 0.67 Φ) volcanic sand at Port Resolution Bay. The sand extends up to 320 m inland. A sharp contact separates the base of the sand and the underlying rooted sandy soil. We found both a coarsening upward and fining upward sequences in trench M1 at Manuro and upward fining in trenches RB 3 and RB 2 at Port Resolution Bay. We used a combination of measured flow heights obtained at the Port Resolution Bay site and laboratory derived grain size settling velocities to calculate the distance of sediment transport caused by TC Pam's storm surge. Based on the distribution of settling velocities from our samples, transport distances for material deposited in the trench suggests a source for the overwash sand ranging from the supratidal berm to 290 m seaward in the nearshore at Port Resolution Bay.

Co-occurrence of methanogenesis and N2 fixation in oil sands tailings.

PubMed

Collins, C E Victoria; Foght, Julia M; Siddique, Tariq

2016-09-15

Oil sands tailings ponds in northern Alberta, Canada have been producing biogenic gases via microbial metabolism of hydrocarbons for decades. Persistent methanogenic activity in tailings ponds without any known replenishment of nutrients such as fixed nitrogen (N) persuaded us to investigate whether N2 fixation or polyacrylamide (PAM; used as a tailings flocculant) could serve as N sources. Cultures comprising mature fine tailings (MFT) plus methanogenic medium supplemented with or deficient in fixed N were incubated under an N2 headspace. Some cultures were further amended with citrate, which is used in oil sands processing, as a relevant carbon source, and/or with PAM. After an initial delay, N-deficient cultures with or without PAM produced methane (CH4) at the same rate as N-containing cultures, indicating a mechanism of overcoming apparent N-deficiency. Acetylene reduction and (15)N2 incorporation in all N-deficient cultures (with or without PAM) suggested active N2 fixation concurrently with methanogenesis but inability to use PAM as a N source. 16S rRNA gene pyrosequencing revealed little difference between archaeal populations regardless of N content. However, bacterial sequences in N-deficient cultures showed enrichment of Hyphomicrobiaceae and Clostridium members that might contain N2-fixing species. The results are important in understanding long-term production of biogenic greenhouse gases in oil sands tailings. Copyright © 2016 Elsevier B.V. All rights reserved.

Multi-mode multi-band power amplifier module with high low-power efficiency

NASA Astrophysics Data System (ADS)

Xuguang, Zhang; Jie, Jin

2015-10-01

Increasingly, mobile communications standards require high power efficiency and low currents in the low power mode. This paper proposes a fully-integrated multi-mode and multi-band power amplifier module (PAM) to meet these requirements. A dual-path PAM is designed for high-power mode (HPM), medium-power mode (MPM), and low-power mode (LPM) operations without any series switches for different mode selection. Good performance and significant current saving can be achieved by using an optimized load impedance design for each power mode. The PAM is tapeout with the InGaP/GaAs heterojunction bipolar transistor (HBT) process and the 0.18-μm complementary metal-oxide semiconductor (CMOS) process. The test results show that the PAM achieves a very low quiescent current of 3 mA in LPM. Meanwhile, across the 1.7-2.0 GHz frequency, the PAM performs well. In HPM, the output power is 28 dBm with at least 39.4% PAE and -40 dBc adjacent channel leakage ratio 1 (ACLR1). In MPM, the output power is 17 dBm, with at least 21.3% PAE and -43 dBc ACLR1. In LPM, the output power is 8 dBm, with at least 18.2% PAE and -40 dBc ACLR1. Project supported by the National Natural Science Foundation of China (No. 61201244).

Whole-organ atlas imaged by label-free high-resolution photoacoustic microscopy assisted by a microtome

NASA Astrophysics Data System (ADS)

Wong, Terence T. W.; Zhang, Ruiying; Hsu, Hsun-Chia; Maslov, Konstantin I.; Shi, Junhui; Chen, Ruimin; Shung, K. Kirk; Zhou, Qifa; Wang, Lihong V.

2018-02-01

In biomedical imaging, all optical techniques face a fundamental trade-off between spatial resolution and tissue penetration. Therefore, obtaining an organelle-level resolution image of a whole organ has remained a challenging and yet appealing scientific pursuit. Over the past decade, optical microscopy assisted by mechanical sectioning or chemical clearing of tissue has been demonstrated as a powerful technique to overcome this dilemma, one of particular use in imaging the neural network. However, this type of techniques needs lengthy special preparation of the tissue specimen, which hinders broad application in life sciences. Here, we propose a new label-free three-dimensional imaging technique, named microtomy-assisted photoacoustic microscopy (mPAM), for potentially imaging all biomolecules with 100% endogenous natural staining in whole organs with high fidelity. We demonstrate the first label-free mPAM, using UV light for label-free histology-like imaging, in whole organs (e.g., mouse brains), most of them formalin-fixed and paraffin- or agarose-embedded for minimal morphological deformation. Furthermore, mPAM with dual wavelength illuminations is also employed to image a mouse brain slice, demonstrating the potential for imaging of multiple biomolecules without staining. With visible light illumination, mPAM also shows its deep tissue imaging capability, which enables less slicing and hence reduces sectioning artifacts. mPAM could potentially provide a new insight for understanding complex biological organs.

Impact of Pregnancy-Associated Malaria on Infant Malaria Infection in Southern Benin

PubMed Central

Borgella, Sophie; Fievet, Nadine; Huynh, Bich-Tram; Ibitokou, Samad; Hounguevou, Gbetognon; Affedjou, Jacqueline; Sagbo, Jean-Claude; Houngbegnon, Parfait; Guezo-Mévo, Blaise; Massougbodji, Achille; Luty, Adrian J. F.

2013-01-01

Background Infants of mothers with placental Plasmodium falciparum infections at delivery are themselves more susceptible to malaria attacks or to infection in early life. Methodology/ Principal Findings To assess the impact of either the timing or the number of pregnancy-associated malaria (PAM) infections on the incidence of parasitemia or malaria attacks in infancy, we followed 218 mothers through pregnancy (monthly visits) up to delivery and their infants from birth to 12 months of age (fortnightly visits), collecting detailed clinical and parasitological data. After adjustment on location, mother’s age, birth season, bed net use, and placental malaria, infants born to a mother with PAM during the third trimester of pregnancy had a significantly increased risk of infection (OR [95% CI]: 4.2 [1.6; 10.5], p = 0.003) or of malaria attack (4.6 [1.7; 12.5], p = 0.003). PAM during the first and second trimesters had no such impact. Similarly significant results were found for the effect of the overall number of PAM episodes on the time to first parasitemia and first malaria attack (HR [95% CI]: 2.95 [1.58; 5.50], p = 0.001 and 3.19 [1.59; 6.38], p = 0.001) respectively. Conclusions/ Significance This study highlights the importance of protecting newborns by preventing repeated episodes of PAM in their mothers. PMID:24236190

Proficiency feasibility of multi-walled carbon nanotubes in the presence of polymeric surfactant on enhanced oil recovery

NASA Astrophysics Data System (ADS)

Nezhad, Javad Razavi; Jafari, Arezou; Abdollahi, Mahdi

2018-01-01

Enhanced heavy oil recovery methods are widely utilized to increase oil recovery. For this purpose, polymer and surfactant flooding have been used extensively. Recently, polymeric surfactant flooding has become an attractive alternative to sole polymer flooding due to their capability of providing an increase in solution viscosity and a decrease in interfacial tension, which are both beneficial for efficiency of the process. Applying nanoparticles as an additive to polymer solutions is a method to improve viscosity and alter rock wettability. Therefore, in this research, multi-walled carbon nanotube (MWCNT) was mixed with a polymeric surfactant of polyacrylamide-graft-lignin copolymer (PAM-g-L) synthesized via radical grafting reaction. Moreover, several solutions with different concentrations of nanoparticles with PAM-g-L were prepared. The solutions were injected into a micromodel to evaluate the PAM-g-L flooding efficiency in presence of the multi-walled carbon nanotubes. The results of micromodel flooding showed that increasing MWCNT concentration results in lower sweep efficiencies; and consequently, oil production will decrease. Therefore, MWCNT along with PAM-g-L has an unacceptable performance in enhanced heavy oil recovery. But data of wettability tests revealed that MWCNT can change the wettability from oil-wet to water-wet. In addition, the combination of the PAM-g-L and MWCNT in a solution will cause more water-wet condition.

Source apportionment of VOCs in the Los Angeles area using positive matrix factorization

NASA Astrophysics Data System (ADS)

Brown, Steven G.; Frankel, Anna; Hafner, Hilary R.

Eight 3-h speciated hydrocarbon measurements were collected daily by the South Coast Air Quality Management District (SCAQMD) as part of the Photochemical Assessment Monitoring Stations (PAMS) program during the summers of 2001-03 at two sites in the Los Angeles air basin, Azusa and Hawthorne. Over 30 hydrocarbons from over 500 samples at Azusa and 600 samples at Hawthorne were subsequently analyzed using the multivariate receptor model positive matrix factorization (PMF). At Azusa and Hawthorne, five and six factors were identified, respectively, with a good comparison between predicted and measured mass. At Azusa, evaporative emissions (a median of 31% of the total mass), motor vehicle exhaust (22%), liquid/unburned gasoline (27%), coatings (17%), and biogenic emissions (3%) factors were identified. Factors identified at Hawthorne were evaporative emissions (a median of 34% of the total mass), motor vehicle exhaust (24%), industrial process losses (15%), natural gas (13%), liquid/unburned gasoline (13%), and biogenic emissions (1%). Together, the median contribution from mobile source-related factors (exhaust, evaporative emissions, and liquid/unburned gasoline) was 80% and 71% at Azusa and Hawthorne, respectively, similar to previous source apportionment results using the chemical mass balance (CMB) model. There is a difference in the distribution among mobile source factors compared to the CMB work, with an increase in the contribution from evaporative emissions, though the cause (changes in emissions or differences between models) is unknown.

STS-112 Flight Day 3 Highlights

NASA Technical Reports Server (NTRS)

2002-01-01

During the third flight day of STS-112 (Commander Jeff Ashby, Pilot Pam Melroy and Mission Specialists Sandy Magnus, Piers Sellers, David Wolf and Fyodor Yurchikhin), the Space Shuttle Atlantis begins its final approach to the International Space Station (ISS) with which it will dock. The Chinese mainland is seen, at night, at a height of 242 statute miles. In one section of video from a camera onboard the ISS, Atlantis can be seen to be almost directly below the station, at a distance of several hundred feet. The orbiter's docking system is shown, as it is slowly guided by Ashby towards the forward docking port on the ISS's Destiny Laboratory Module and its forward docking port. Above the docking port, the S0 truss structure can be seen, to which the S1 truss structure in Atlantis' payload bay will be attached during this mission. Also seen are the Unity airlock and other modules. Following the completion of docking, in which an excellent shot of the docking system in hard dock is visible, the hatches between the two crafts are opened and the members of Atlantis are greeted by the very excited members of Expedition 5, who have been aboard the ISS for several months.

NOx promotion of SO2 conversion to sulfate: An important mechanism for the occurrence of heavy haze during winter in Beijing.

PubMed

Ma, Jinzhu; Chu, Biwu; Liu, Jun; Liu, Yongchun; Zhang, Hongxing; He, Hong

2018-02-01

In this study, concentrations of NO x , SO 2 , O 3 and fine particles (PM 2.5 ) were measured at three monitoring stations in Beijing during 2015. For extreme haze episodes during 25 Nov. - 3 Dec. 2015, observation data confirmed that high concentrations of NO x promoted the conversion of SO 2 to sulfate. Annual data confirmed that this is an important mechanism for the occurrence of heavy haze during winter in Beijing. Furthermore, in situ perturbation experiments in a potential aerosol mass (PAM) reactor were carried out at Shengtaizhongxin (STZX) station during both clean and polluted days. The concentrations of SO 4 2- , NH 4 + , NO 3 - and organic aerosol were positively related to the concentration of added NO 2 . These results provide definitive evidence that NO 2 can promote the conversion of SO 2 to sulfate. At the same time, we found that NO 2 can promote the formation of NH 4 + and organic compounds in the aerosols. Our results illustrate that strengthened controls of nitrogen oxides is a key step in reducing the fine particles level in China. Copyright © 2017 Elsevier Ltd. All rights reserved.

The STS-92 crew is ready to leave KSC after CEIT

NASA Technical Reports Server (NTRS)

2000-01-01

The STS-92 crew strides across the runway at KSC's Shuttle Landing Facility, heading toward the aircraft that will take them back to Houston. They were at KSC for Crew Equipment Interface Test (CEIT) activities, looking over their mission payload and related equipment. From left are Mission Specialists Bill McArthur and Jeff Wisoff, Pilot Pam Melroy, Mission Specialist Michael Lopez-Alegria, Commander Brian Duffy and Mission Specialist Koichi Wakata, who is with the Japanese space agency. Not seen is Mission Specialist Leroy Chiao, who was also at KSC for the CEIT. STS-92 is scheduled to launch Oct. 5 on Shuttle Discovery from Launch Pad 39A on the fifth flight to the International Space Station. Discovery will carry the Integrated Truss Structure (ITS) Z1, the PMA-3, Ku-band Communications System, and Control Moment Gyros (CMGs).

ITAS - A Better Way of Coding.

DTIC Science & Technology

1980-03-01

ray tube, eliminates the tedium and time delays associated with conventional language programing. G ! vii SECTION I The Problem Our objective was to...8217 Input Gan+ Delay •Del ay Gai Figure 1 - An Itagram of a first order recursive digital filter. 3 ktmuIeN PAM NO FILMED MAR Using a light pen, the user... the computer in a positive active role, i.e. the user has to determine why an answer is wrong and take action to correct the fault. This is accomplished

Unveiling the Dual Role of the Dopaminergic System on Locomotion and the Innate Value for an Aversive Olfactory Stimulus in Drosophila.

PubMed

Fuenzalida-Uribe, Nicolás; Campusano, Jorge M

2018-02-10

The communication between sensory systems and the specific brain centers that process this information is crucial to develop adequate behavioral responses. Modulatory systems, including dopaminergic circuits, regulate this communication to finely tune the behavioral response associated to any given stimulus. For instance, the Mushroom Body (MB), an insect brain integration center that receives and processes several sensory stimuli and organizes the execution of motor programs, communicates with MB output neurons (MBONs) to develop behavioral responses associated to olfactory stimuli. This communication is modulated by dopaminergic neural systems. Here we show that silencing dopaminergic neurons increases the aversive response observed in adult flies exposed to Benzaldehyde (Bz) or octanol. We studied the contribution of two dopaminergic clusters that innervate different zones of MB, Protocerebral anterior medial (PAM) and Protocerebral posterior lateral 1 (PPL1), on the innate value to the aversive stimulus and the associated locomotor behavior. In order to do this, we manipulated the synaptic transmission of these neural clusters through the expression of Tetanus toxin, Kir2.1 and Transient receptor potential cation channel A1 (TrpA1) channels. Our results show that neurons in PPL1 and PAM differentially modulate the innate value to Bz in adult flies. On the other hand, blocking neurotransmission or genetic silencing of PAM neurons results in decreased locomotor behavior in flies, an effect not observed when silencing PPL1. Our results suggest that as in mammals, specific dopaminergic pathways differentially modulate locomotor behavior and the innate value for an odorant, a limbic-like response in Drosophila. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Label-free imaging of cellular malformation using high resolution photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Chen, Zhongjiang; Li, Bingbing; Yang, Sihua

2014-09-01

A label-free high resolution photoacoustic microscopy (PAM) system for imaging cellular malformation is presented. The carbon fibers were used to testify the lateral resolution of the PAM. Currently, the lateral resolution is better than 2.7 μm. The human normal red blood cells (RBCs) were used to prove the imaging capability of the system, and a single red blood cell was mapped with high contrast. Moreover, the iron deficiency anemia RBCs were clearly distinguished from the cell morphology by using the PAM. The experimental results demonstrate that the photoacoustic microscopy system can accomplish label-free photoacoustic imaging and that it has clinical potential for use in the detection of erythrocytes and blood vessels malformation.

Lack of gender-specific antibody recognition of products from domains of a var gene implicated in pregnancy-associated Plasmodium falciparum malaria.

PubMed

Jensen, Anja T R; Zornig, Hanne D; Buhmann, Caecilie; Salanti, Ali; Koram, Kwadwo A; Riley, Eleanor M; Theander, Thor G; Hviid, Lars; Staalsoe, Trine

2003-07-01

Gender-specific and parity-dependent acquired antibody recognition is characteristic of variant surface antigens (VSA) expressed by chondroitin sulfate A (CSA)-adherent Plasmodium falciparum involved in pregnancy-associated malaria (PAM). However, antibody recognition of recombinant products of a specific VSA gene (2O2var1) implicated in PAM and transcribed by a CSA-adhering parasite line did not have these characteristics. Furthermore, we could not demonstrate preferential transcription of 2O2var1 in the CSA-adhering line versus the unselected, parental isolate. Our data call for circumspection regarding the molecular identity of the parasite ligand mediating adhesion to CSA in PAM.

In vivo integrated photoacoustic and confocal microscopy of hemoglobin oxygen saturation and oxygen partial pressure.

PubMed

Wang, Yu; Hu, Song; Maslov, Konstantin; Zhang, Yu; Xia, Younan; Wang, Lihong V

2011-04-01

We developed dual-modality microscope integrating photoacoustic microscopy (PAM) and fluorescence confocal microscopy (FCM) to noninvasively image hemoglobin oxygen saturation (sO₂) and oxygen partial pressure (pO₂) in vivo in single blood vessels with high spatial resolution. While PAM measures sO₂ by imaging hemoglobin optical absorption at two wavelengths, FCM quantifies pO₂ using phosphorescence quenching. The variations of sO₂ and pO₂ values in multiple orders of vessel branches under hyperoxic (100% oxygen) and normoxic (21% oxygen) conditions correlate well with the oxygen-hemoglobin dissociation curve. In addition, the total concentration of hemoglobin is imaged by PAM at an isosbestic wavelength.

Post-assembly Modification of Tetrazine-Edged Fe(II)4L6 Tetrahedra.

PubMed

Roberts, Derrick A; Pilgrim, Ben S; Cooper, Jonathan D; Ronson, Tanya K; Zarra, Salvatore; Nitschke, Jonathan R

2015-08-19

Post-assembly modification (PAM) is a powerful tool for the modular functionalization of self-assembled structures. We report a new family of tetrazine-edged Fe(II)4L6 tetrahedral cages, prepared using different aniline subcomponents, which undergo rapid and efficient PAM by inverse electron-demand Diels-Alder (IEDDA) reactions. Remarkably, the electron-donating or -withdrawing ability of the para-substituent on the aniline moiety influences the IEDDA reactivity of the tetrazine ring 11 bonds away. This effect manifests as a linear free energy relationship, quantified using the Hammett equation, between σ(para) and the rate of the IEDDA reaction. The rate of PAM can thus be adjusted by varying the aniline subcomponent.

From the Field: Speech Therapy Outcome Measures--Interview with Dr. Pam Enderby

ERIC Educational Resources Information Center

Montgomery, Judy K.

2015-01-01

This article is an interview with Dr. Pam Enderby--a speech language therapist and professor at the Institute of General Practice and Primary Care at the University of Sheffield, Community Sciences Centre, Northern General Hospital, in the United Kingdom--conducted by Judy Montgomery, Editor in Chief, of "Communication Disorders…

Combined Atropine and 2-PAM Cl Effects on Tracking Performance and Visual, Physiological, and Psychological Functions

DTIC Science & Technology

1988-12-01

tracking task reveals the magnitude Akitrihm. Spare. and Environmental Medicine • December. I$ II I ANTIDOTE EFFECTS--PEN ETAR ET AL. and duration of the... marihuana on dynamic visual acu- blood pressure following the combination of 2-PAM Cl ity: I. Threshold measurements. Perception Psychophys. 1975

Efficacy of Pro-PAM (N-methyl-1,6-dihydropyridine-2-carbaldoxime Hydrochloride) as a Treatment for Organophosphate Poisoning

DTIC Science & Technology

1978-02-01

con- sciousness; and had anticonvulsant effects in people poisoned by parathion (Namba and Hiraki , 1958; Karlog et al., 1958; Funches, 1960; Schuchter...Pharmacodyn. Therap. 132, 180-188. UNCLASSIFIED UNCLASSIFIED /10 REFERENCES (Con’t) Namba, T. and Hiraki , K. (1958) PAM (Pyridine-2-Aldoxime Methiodide

Agronomic and water quality impacts of incorporating polyacrylamide in furrow irrigation water in Arkansas cotton -- 2014

USDA-ARS?s Scientific Manuscript database

The combined erosion-halting and infiltration-increasing effects of PAM appeared to be an ideal practice for Midsouth cotton producers interested in improving irrigation efficiency and nutrient management; however, there has been limited research to evaluate PAM in the Midsouth. The objective of thi...

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

Lu, Jun; Byrne, Noel; Wang, John

Clinical studies indicate that partial agonists of the G-protein-coupled, free fatty acid receptor 1 GPR40 enhance glucose-dependent insulin secretion and represent a potential mechanism for the treatment of type 2 diabetes mellitus. Full allosteric agonists (AgoPAMs) of GPR40 bind to a site distinct from partial agonists and can provide additional efficacy. We report the 3.2-Å crystal structure of human GPR40 (hGPR40) in complex with both the partial agonist MK-8666 and an AgoPAM, which exposes a novel lipid-facing AgoPAM-binding pocket outside the transmembrane helical bundle. Comparison with an additional 2.2-Å structure of the hGPR40–MK-8666 binary complex reveals an induced-fit conformational couplingmore » between the partial agonist and AgoPAM binding sites, involving rearrangements of the transmembrane helices 4 and 5 (TM4 and TM5) and transition of the intracellular loop 2 (ICL2) into a short helix. These conformational changes likely prime GPR40 to a more active-like state and explain the binding cooperativity between these ligands.« less

Time skewing and amplitude nonlinearity mitigation by feedback equalization for 56 Gbps VCSEL-based PAM-4 links

NASA Astrophysics Data System (ADS)

You, Yue; Zhang, Wenjia; Sun, Lin; Du, Jiangbing; Liang, Chenyu; Yang, Fan; He, Zuyuan

2018-03-01

The vertical cavity surface emitting laser (VCSEL)-based multimode optical transceivers enabled by pulse amplitude modulation (PAM)-4 will be commercialized in near future to meet the 400-Gbps standard short reach optical interconnects. It is still challenging to achieve over 56/112-Gbps with the multilevel signaling as the multimode property of the device and link would introduce the nonlinear temporal response for the different levels. In this work, we scrutinize the distortions that relates to the multilevel feature of PAM-4 modulation, and propose an effective feedback equalization scheme for 56-Gbps VCSEL-based PAM-4 optical interconnects system to mitigate the distortions caused by eye timing-skew and nonlinear power-dependent noise. Level redistribution at Tx side is theoretically modeled and constructed to achieve equivalent symbol error ratios (SERs) of four levels and improved BER performance. The cause of the eye skewing and the mitigation approach are also simulated at 100-Gbps and experimentally investigated at 56-Gbps. The results indicate more than 2-dB power penalty improvement has been achieved by using such a distortion aware equalizer.

The role of Cas8 in type I CRISPR interference.

PubMed

Cass, Simon D B; Haas, Karina A; Stoll, Britta; Alkhnbashi, Omer S; Sharma, Kundan; Urlaub, Henning; Backofen, Rolf; Marchfelder, Anita; Bolt, Edward L

2015-05-05

CRISPR (clustered regularly interspaced short palindromic repeat) systems provide bacteria and archaea with adaptive immunity to repel invasive genetic elements. Type I systems use 'cascade' [CRISPR-associated (Cas) complex for antiviral defence] ribonucleoprotein complexes to target invader DNA, by base pairing CRISPR RNA (crRNA) to protospacers. Cascade identifies PAMs (protospacer adjacent motifs) on invader DNA, triggering R-loop formation and subsequent DNA degradation by Cas3. Cas8 is a candidate PAM recognition factor in some cascades. We analysed Cas8 homologues from type IB CRISPR systems in archaea Haloferax volcanii (Hvo) and Methanothermobacter thermautotrophicus (Mth). Cas8 was essential for CRISPR interference in Hvo and purified Mth Cas8 protein responded to PAM sequence when binding to nucleic acids. Cas8 interacted physically with Cas5-Cas7-crRNA complex, stimulating binding to PAM containing substrates. Mutation of conserved Cas8 amino acid residues abolished interference in vivo and altered catalytic activity of Cas8 protein in vitro. This is experimental evidence that Cas8 is important for targeting Cascade to invader DNA. © 2015 Authors.

Exploring Orthogonal Hydrogen Bonding towards Designing Organic-Salt-Based Supramolecular Gelators: Synthesis, Structures, and Anticancer Properties.

PubMed

Chakraborty, Poulami; Dastidar, Parthasarathi

2018-05-18

A series of primary ammonium monocarboxylate (PAM) salts derived from β-alanine derivatives of pyrene and naphthalene acetic acid, along with the parent acids, were explored to probe the plausible role of orthogonal hydrogen bonding resulting from amide⋅⋅⋅amide and PAM synthons on gelation. Single-crystal X-ray diffraction (SXRD) studies were performed on two parent acids and five PAM salts in the series. The data revealed that orthogonal hydrogen bonding played an important role in gelation. Structure-property correlation based on SXRD and powder X-ray diffraction data also supported the working hypothesis upon which these gelators were designed. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell migration assay on a highly aggressive human breast cancer cell line, MDA-MB-231, revealed that one of the PAM salts in the series, namely, PAA.B2, displayed anticancer properties, and internalization of the gelator salt in the same cell line was confirmed by cell imaging. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Functional photoacoustic microscopy of pH

NASA Astrophysics Data System (ADS)

Chatni, M. Rameez; Yao, Junjie; Danielli, Amos; Favazza, Christopher P.; Maslov, Konstantin I.; Wang, Lihong V.

2012-02-01

pH is a tightly regulated indicator of metabolic activity. In mammalian systems, imbalance of pH regulation may result from or result in serious illness. Even though the regulation system of pH is very robust, tissue pH can be altered in many diseases such as cancer, osteoporosis and diabetes mellitus. Traditional high-resolution optical imaging techniques, such as confocal microscopy, routinely image pH in cells and tissues using pH sensitive fluorescent dyes, which change their fluorescence properties with the surrounding pH. Since strong optical scattering in biological tissue blurs images at greater depths, high-resolution pH imaging is limited to penetration depths of 1mm. Here, we report photoacoustic microscopy (PAM) of commercially available pH-sensitive fluorescent dye in tissue phantoms. Using both opticalresolution photoacoustic microscopy (OR-PAM), and acoustic resolution photoacoustic microscopy (AR-PAM), we explored the possibility of recovering the pH values in tissue phantoms. In this paper, we demonstrate that PAM was capable of recovering pH values up to a depth of 2 mm, greater than possible with other forms of optical microscopy.

Solar Radiation Stress in Natural Acidophilic Biofilms of Euglena mutabilis Revealed by Metatranscriptomics and PAM Fluorometry.

PubMed

Puente-Sánchez, Fernando; Olsson, Sanna; Gómez-Rodriguez, Manuel; Souza-Egipsy, Virginia; Altamirano-Jeschke, Maria; Amils, Ricardo; Parro, Victor; Aguilera, Angeles

2016-02-01

The daily photosynthetic performance of a natural biofilm of the extreme acidophilic Euglena mutabilis from Río Tinto (SW, Spain) under full solar radiation was analyzed by means of pulse amplitude-modulated (PAM) fluorescence measurements and metatrascriptomic analysis. Natural E. mutabilis biofilms undergo large-scale transcriptomic reprogramming during midday due to a dynamic photoinhibition and solar radiation stress. Photoinhibition is due to UV radiation and not to light intensity, as revealed by PAM fluorometry analysis. In order to minimize the negative effects of solar radiation, our data supports the presence of a circadian rhythm in this euglenophyte that increases their opportunity to survive. Differential gene expression throughout the day (at 12:00, 20:00 and night) was monitored by massive Illumina parallel sequencing of metatranscriptomic libraries. The transcription pattern was altered in genes involved in Photosystem II stability and repair, UV damaged DNA repair, non-photochemical quenching and oxidative stress, supporting the photoinhibition detected by PAM fluorometry at midday. Copyright © 2016 Elsevier GmbH. All rights reserved.

Cas4 Facilitates PAM-Compatible Spacer Selection during CRISPR Adaptation.

PubMed

Kieper, Sebastian N; Almendros, Cristóbal; Behler, Juliane; McKenzie, Rebecca E; Nobrega, Franklin L; Haagsma, Anna C; Vink, Jochem N A; Hess, Wolfgang R; Brouns, Stan J J

2018-03-27

CRISPR-Cas systems adapt their immunological memory against their invaders by integrating short DNA fragments into clustered regularly interspaced short palindromic repeat (CRISPR) loci. While Cas1 and Cas2 make up the core machinery of the CRISPR integration process, various class I and II CRISPR-Cas systems encode Cas4 proteins for which the role is unknown. Here, we introduced the CRISPR adaptation genes cas1, cas2, and cas4 from the type I-D CRISPR-Cas system of Synechocystis sp. 6803 into Escherichia coli and observed that cas4 is strictly required for the selection of targets with protospacer adjacent motifs (PAMs) conferring I-D CRISPR interference in the native host Synechocystis. We propose a model in which Cas4 assists the CRISPR adaptation complex Cas1-2 by providing DNA substrates tailored for the correct PAM. Introducing functional spacers that target DNA sequences with the correct PAM is key to successful CRISPR interference, providing a better chance of surviving infection by mobile genetic elements. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Synthesis and characterization of novel polymers from non-petroleum sources for use in enhanced oil recovery. Progress report, July 1,1981-June 30, 1982. [Starch-g-polyacrylamide; polysaccharides and acrylamides; Schardinger-. beta. -dextrin and acrylamide

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

Butler, G.B.; Hogen-Esch, T.E.

1982-01-01

Annual progress reports are presented for the following tasks: (1) synthesis and structural characterization of polysaccharide-based graft copolymers for use in tertiary oil recovery; (2) determination of physical properties of the polymers and their solutions, and screening of the polymers to determine their utility in oil recovery. Over the past year synthesis and characterization studies have continued in the following five areas: (1) starch-g-polyacrylamide (ST-g-PAM) copolymers; (2) graft copolymers of other polysaccharides (gum arabic, yellow dextrin, pectin, okra polysaccharide, and guar gum) and acrylamides; (3) a naturally occurring polysaccharide extracted from okra (Akro); (4) graft copolymers of Schardinger-..beta..-dextrin and acrylamidemore » (SD-g-PAM); (5) chemical degradation of ST-g-PAM and SD-g-PAM copolymers. For physical properties studies, the following areas were investigated: (1) characterization of copolymers by ultracentrifugation, size exclusion chromatography and nucleophore membrane filtration; (2) rheological studies on copolymers; and (3) statistical analysis of variables in graft copolymerization. (ATT)« less

Centre d'Observacio de l'Univers: first year of activities

NASA Astrophysics Data System (ADS)

Ribas, S. J.

2011-11-01

The Centre d'Observacio de l'Univers is one of the parts of the Parc Astronomic Montsec (PAM). PAM is an initiative of the Catalan government, through the Consorci del Montsec (Montsec Consortium), to take advantage of the capabilities and potential of the Montsec region to develop scientific research, training, and outreach activities, particularly in the field of astronomy. The choice of the Montsec mountains to install the PAM was motivated by the magnificent conditions for observing the sky at night; the sky above Montsec is the best (natural sky free of light pollution) in Catalonia for astronomical observations. The PAM has two main parts: the Observatori Astronomic del Montsec (OAdM) and the Centre d'Observacio del'Univers (COU). The OAdM is a professional observatory with an 80 cm catadioptric telescope (Joan Oro Telescope). The COU is a large multipurpose center which is intended to become an educational benchmark for teaching and communicate astronomy and other sciences in Catalonia. Since the opening more than 50000 visitors went to this center to enjoy science with Montsec dark skies and an special natural environment.

Flocculation characteristics of polyacrylamide grafted cellulose from Phyllostachys heterocycla: An efficient and eco-friendly flocculant.

PubMed

Liu, Hongyi; Yang, Xiaogang; Zhang, Yong; Zhu, Hangcheng; Yao, Juming

2014-08-01

This work presents a synthesis process and flocculation characteristics of an eco-friendly flocculant based on bamboo pulp cellulose (BPC) from Phyllostachys heterocycla. Ployacrylamide (PAM) was grafted onto the BPC by free-radical graft copolymerization in homogeneous aqueous solution. The optimal synthesis conditions of the bamboo pulp cellulose-graft-ployacrylamide flocculant (BPC-g-PAM) and its performance on wastewater treatments were investigated. A UV-based method was used to rapidly determine the degree of substitution (DS) of BPC. The results showed that, under the optimal synthesis conditions, the obtained BPC-g-PAM held a grafting ratio of 43.8% and DS of 1.31. Turbidity removal of the product reached 98.0% accompanying with the significant flocculation and sedimentation in target suspensions. The flocculation mechanism was explored by means of zeta potential method. For negatively charged contaminants, like kaolin clay particles, the BPC-g-PAM could remove the contaminants efficiently via bridging and charge neutralization in acidic or neutral environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Improvement of an automated protein crystal exchange system PAM for high-throughput data collection

PubMed Central

Hiraki, Masahiko; Yamada, Yusuke; Chavas, Leonard M. G.; Wakatsuki, Soichi; Matsugaki, Naohiro

2013-01-01

Photon Factory Automated Mounting system (PAM) protein crystal exchange systems are available at the following Photon Factory macromolecular beamlines: BL-1A, BL-5A, BL-17A, AR-NW12A and AR-NE3A. The beamline AR-NE3A has been constructed for high-throughput macromolecular crystallography and is dedicated to structure-based drug design. The PAM liquid-nitrogen Dewar can store a maximum of three SSRL cassettes. Therefore, users have to interrupt their experiments and replace the cassettes when using four or more of them during their beam time. As a result of investigation, four or more cassettes were used in AR-NE3A alone. For continuous automated data collection, the size of the liquid-nitrogen Dewar for the AR-NE3A PAM was increased, doubling the capacity. In order to check the calibration with the new Dewar and the cassette stand, calibration experiments were repeatedly performed. Compared with the current system, the parameters of the novel system are shown to be stable. PMID:24121334

On the benefit of DMT modulation in nonlinear VLC systems.

PubMed

Qian, Hua; Cai, Sunzeng; Yao, Saijie; Zhou, Ting; Yang, Yang; Wang, Xudong

2015-02-09

In a visible light communication (VLC) system, the nonlinear characteristic of the light emitting diode (LED) in transmitter is a limiting factor of system performance. Modern modulation signals with large peak-to-power-ratio (PAPR) suffers uneven distortion. The nonlinear response directly impacts the intensity modulation and direct detection VLC system with pulse-amplitude modulation (PAM). The amplitude of the PAM signal is distorted unevenly and large signal is vulnerable to noise. Orthogonal linear transformations, such as discrete multi-tone (DMT) modulation, can spread the nonlinear effects evenly to each data symbol, thus perform better than PAM signals. In this paper, we provide theoretical analysis on the benefit of DMT modulation in nonlinear VLC system. We show that the DMT modulation is a better choice than the PAM modulation for the VLC system as the DMT modulation is more robust against nonlinearity. We also show that the post-distortion nonlinear elimination method, which is applied at the receiver, can be a reliable solution to the nonlinear VLC system. Simulation results show that the post-distortion greatly improves the system performance for the DMT modulation.

Programmable RNA recognition and cleavage by CRISPR/Cas9.

PubMed

O'Connell, Mitchell R; Oakes, Benjamin L; Sternberg, Samuel H; East-Seletsky, Alexandra; Kaplan, Matias; Doudna, Jennifer A

2014-12-11

The CRISPR-associated protein Cas9 is an RNA-guided DNA endonuclease that uses RNA-DNA complementarity to identify target sites for sequence-specific double-stranded DNA (dsDNA) cleavage. In its native context, Cas9 acts on DNA substrates exclusively because both binding and catalysis require recognition of a short DNA sequence, known as the protospacer adjacent motif (PAM), next to and on the strand opposite the twenty-nucleotide target site in dsDNA. Cas9 has proven to be a versatile tool for genome engineering and gene regulation in a large range of prokaryotic and eukaryotic cell types, and in whole organisms, but it has been thought to be incapable of targeting RNA. Here we show that Cas9 binds with high affinity to single-stranded RNA (ssRNA) targets matching the Cas9-associated guide RNA sequence when the PAM is presented in trans as a separate DNA oligonucleotide. Furthermore, PAM-presenting oligonucleotides (PAMmers) stimulate site-specific endonucleolytic cleavage of ssRNA targets, similar to PAM-mediated stimulation of Cas9-catalysed DNA cleavage. Using specially designed PAMmers, Cas9 can be specifically directed to bind or cut RNA targets while avoiding corresponding DNA sequences, and we demonstrate that this strategy enables the isolation of a specific endogenous messenger RNA from cells. These results reveal a fundamental connection between PAM binding and substrate selection by Cas9, and highlight the utility of Cas9 for programmable transcript recognition without the need for tags.

Practical controller design for ultra-precision positioning of stages with a pneumatic artificial muscle actuator

NASA Astrophysics Data System (ADS)

Tang, T. F.; Chong, S. H.

2017-06-01

This paper presents a practical controller design method for ultra-precision positioning of pneumatic artificial muscle actuator stages. Pneumatic artificial muscle (PAM) actuators are safe to use and have numerous advantages which have brought these actuators to wide applications. However, PAM exhibits strong non-linear characteristics, and these limitations lead to low controllability and limit its application. In practice, the non-linear characteristics of PAM mechanism are difficult to be precisely modeled, and time consuming to model them accurately. The purpose of the present study is to clarify a practical controller design method that emphasizes a simple design procedure that does not acquire plants parameters modeling, and yet is able to demonstrate ultra-precision positioning performance for a PAM driven stage. The practical control approach adopts continuous motion nominal characteristic trajectory following (CM NCTF) control as the feedback controller. The constructed PAM driven stage is in low damping characteristic and causes severe residual vibration that deteriorates motion accuracy of the system. Therefore, the idea to increase the damping characteristic by having an acceleration feedback compensation to the plant has been proposed. The effectiveness of the proposed controller was verified experimentally and compared with a classical PI controller in point-to-point motion. The experiment results proved that the CM NCTF controller demonstrates better positioning performance in smaller motion error than the PI controller. Overall, the CM NCTF controller has successfully to reduce motion error to 3µm, which is 88.7% smaller than the PI controller.

Ti 3 C 2 T x (MXene)–polyacrylamide nanocomposite films

DOE PAGES

Naguib, Michael; Saito, Tomonori; Lai, Sophia; ...

2016-07-20

Polymer nanocomposite films are of great interest due to their enhanced properties over base polymers. By incorporating 2D titanium carbide a representative of a new family of 2D materials, MXenes, as nanofillers into a water soluble polyacrylamide (PAM) matrix, the resulting films benefit from the flexibility, robustness, and processability of PAM, as well as the conductivity and mechanical properties of MXene fillers. We report on manufacturing and characterization of MXene-PAM nanocomposite films. Dimethylsulfoxide (DMSO) intercalation in-between the Ti 3C 2-based MXene layers led to full delamination of the MXene layers and hence a uniform dispersion of hydrophilic MXene nanosheets inmore » aqueous PAM solutions was achieved. Moreover, the polymer composite solutions of up to 75 wt.% MXene loading were sonicated and cast onto large Teflon trays and dried at room temperature to produce shiny black films. The observation of reduced 0002 peaks of Ti 3C 2T x phase in X-ray diffraction patterns and TEM images indicate the presence of well dispersed nanoflakes. The as-prepared composite films are flexible and the conductivity was increased significantly to 3 x 10 -3 S cm -1 for 6 wt. % MXene-PAM films. With high MXene loading, some non-uniformity between the top and bottom surfaces was observed. This could be due to the segregation of MXene layers in composite films during drying. Finally, the power law dependence of conductivity above the percolation threshold is presented through detailed conductivity measurements.« less

A 'new lease of life': FnCpf1 possesses DNA cleavage activity for genome editing in human cells.

PubMed

Tu, Mengjun; Lin, Li; Cheng, Yilu; He, Xiubin; Sun, Huihui; Xie, Haihua; Fu, Junhao; Liu, Changbao; Li, Jin; Chen, Ding; Xi, Haitao; Xue, Dongyu; Liu, Qi; Zhao, Junzhao; Gao, Caixia; Song, Zongming; Qu, Jia; Gu, Feng

2017-11-02

Cpf1 nucleases were recently reported to be highly specific and programmable nucleases with efficiencies comparable to those of SpCas9. AsCpf1 and LbCpf1 require a single crRNA and recognize a 5'-TTTN-3' protospacer adjacent motif (PAM) at the 5' end of the protospacer for genome editing. For widespread application in precision site-specific human genome editing, the range of sequences that AsCpf1 and LbCpf1 can recognize is limited due to the size of this PAM. To address this limitation, we sought to identify a novel Cpf1 nuclease with simpler PAM requirements. Specifically, here we sought to test and engineer FnCpf1, one reported Cpf1 nuclease (FnCpf1) only requires 5'-TTN-3' as a PAM but does not exhibit detectable levels of nuclease-induced indels at certain locus in human cells. Surprisingly, we found that FnCpf1 possesses DNA cleavage activity in human cells at multiple loci. We also comprehensively and quantitatively examined various FnCpf1 parameters in human cells, including spacer sequence, direct repeat sequence and the PAM sequence. Our study identifies FnCpf1 as a new member of the Cpf1 family for human genome editing with distinctive characteristics, which shows promise as a genome editing tool with the potential for both research and therapeutic applications. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Programmable RNA recognition and cleavage by CRISPR/Cas9

PubMed Central

O’Connell, Mitchell R.; Oakes, Benjamin L.; Sternberg, Samuel H.; East-Seletsky, Alexandra; Kaplan, Matias; Doudna, Jennifer A.

2014-01-01

The CRISPR-associated protein Cas9 is an RNA-guided DNA endonuclease that uses RNA:DNA complementarity to identify target sites for sequence-specific doublestranded DNA (dsDNA) cleavage1-5. In its native context, Cas9 acts on DNA substrates exclusively because both binding and catalysis require recognition of a short DNA sequence, the protospacer adjacent motif (PAM), next to and on the strand opposite the 20-nucleotide target site in dsDNA4-7. Cas9 has proven to be a versatile tool for genome engineering and gene regulation in many cell types and organisms8, but it has been thought to be incapable of targeting RNA5. Here we show that Cas9 binds with high affinity to single-stranded RNA (ssRNA) targets matching the Cas9-associated guide RNA sequence when the PAM is presented in trans as a separate DNA oligonucleotide. Furthermore, PAM-presenting oligonucleotides (PAMmers) stimulate site-specific endonucleolytic cleavage of ssRNA targets, similar to PAM-mediated stimulation of Cas9-catalyzed DNA cleavage7. Using specially designed PAMmers, Cas9 can be specifically directed to bind or cut RNA targets while avoiding corresponding DNA sequences, and we demonstrate that this strategy enables the isolation of a specific endogenous mRNA from cells. These results reveal a fundamental connection between PAM binding and substrate selection by Cas9, and highlight the utility of Cas9 for programmable and tagless transcript recognition. PMID:25274302

A ‘new lease of life’: FnCpf1 possesses DNA cleavage activity for genome editing in human cells

PubMed Central

Tu, Mengjun; Lin, Li; Cheng, Yilu; He, Xiubin; Sun, Huihui; Xie, Haihua; Fu, Junhao; Liu, Changbao; Li, Jin; Chen, Ding; Xi, Haitao; Xue, Dongyu; Liu, Qi; Zhao, Junzhao; Gao, Caixia; Song, Zongming; Qu, Jia

2017-01-01

Abstract Cpf1 nucleases were recently reported to be highly specific and programmable nucleases with efficiencies comparable to those of SpCas9. AsCpf1 and LbCpf1 require a single crRNA and recognize a 5′-TTTN-3′ protospacer adjacent motif (PAM) at the 5′ end of the protospacer for genome editing. For widespread application in precision site-specific human genome editing, the range of sequences that AsCpf1 and LbCpf1 can recognize is limited due to the size of this PAM. To address this limitation, we sought to identify a novel Cpf1 nuclease with simpler PAM requirements. Specifically, here we sought to test and engineer FnCpf1, one reported Cpf1 nuclease (FnCpf1) only requires 5′-TTN-3′ as a PAM but does not exhibit detectable levels of nuclease-induced indels at certain locus in human cells. Surprisingly, we found that FnCpf1 possesses DNA cleavage activity in human cells at multiple loci. We also comprehensively and quantitatively examined various FnCpf1 parameters in human cells, including spacer sequence, direct repeat sequence and the PAM sequence. Our study identifies FnCpf1 as a new member of the Cpf1 family for human genome editing with distinctive characteristics, which shows promise as a genome editing tool with the potential for both research and therapeutic applications. PMID:28977650

Real-time observation of DNA target interrogation and product release by the RNA-guided endonuclease CRISPR Cpf1 (Cas12a).

PubMed

Singh, Digvijay; Mallon, John; Poddar, Anustup; Wang, Yanbo; Tippana, Ramreddy; Yang, Olivia; Bailey, Scott; Ha, Taekjip

2018-05-22

CRISPR-Cas9, which imparts adaptive immunity against foreign genomic invaders in certain prokaryotes, has been repurposed for genome-engineering applications. More recently, another RNA-guided CRISPR endonuclease called Cpf1 (also known as Cas12a) was identified and is also being repurposed. Little is known about the kinetics and mechanism of Cpf1 DNA interaction and how sequence mismatches between the DNA target and guide-RNA influence this interaction. We used single-molecule fluorescence analysis and biochemical assays to characterize DNA interrogation, cleavage, and product release by three Cpf1 orthologs. Our Cpf1 data are consistent with the DNA interrogation mechanism proposed for Cas9. They both bind any DNA in search of protospacer-adjacent motif (PAM) sequences, verify the target sequence directionally from the PAM-proximal end, and rapidly reject any targets that lack a PAM or that are poorly matched with the guide-RNA. Unlike Cas9, which requires 9 bp for stable binding and ∼16 bp for cleavage, Cpf1 requires an ∼17-bp sequence match for both stable binding and cleavage. Unlike Cas9, which does not release the DNA cleavage products, Cpf1 rapidly releases the PAM-distal cleavage product, but not the PAM-proximal product. Solution pH, reducing conditions, and 5' guanine in guide-RNA differentially affected different Cpf1 orthologs. Our findings have important implications on Cpf1-based genome engineering and manipulation applications.

Measuring acoustic habitats

PubMed Central

Merchant, Nathan D; Fristrup, Kurt M; Johnson, Mark P; Tyack, Peter L; Witt, Matthew J; Blondel, Philippe; Parks, Susan E

2015-01-01

1. Many organisms depend on sound for communication, predator/prey detection and navigation. The acoustic environment can therefore play an important role in ecosystem dynamics and evolution. A growing number of studies are documenting acoustic habitats and their influences on animal development, behaviour, physiology and spatial ecology, which has led to increasing demand for passive acoustic monitoring (PAM) expertise in the life sciences. However, as yet, there has been no synthesis of data processing methods for acoustic habitat monitoring, which presents an unnecessary obstacle to would-be PAM analysts. 2. Here, we review the signal processing techniques needed to produce calibrated measurements of terrestrial and aquatic acoustic habitats. We include a supplemental tutorial and template computer codes in matlab and r, which give detailed guidance on how to produce calibrated spectrograms and statistical analyses of sound levels. Key metrics and terminology for the characterisation of biotic, abiotic and anthropogenic sound are covered, and their application to relevant monitoring scenarios is illustrated through example data sets. To inform study design and hardware selection, we also include an up-to-date overview of terrestrial and aquatic PAM instruments. 3. Monitoring of acoustic habitats at large spatiotemporal scales is becoming possible through recent advances in PAM technology. This will enhance our understanding of the role of sound in the spatial ecology of acoustically sensitive species and inform spatial planning to mitigate the rising influence of anthropogenic noise in these ecosystems. As we demonstrate in this work, progress in these areas will depend upon the application of consistent and appropriate PAM methodologies. PMID:25954500

Measuring acoustic habitats.

PubMed

Merchant, Nathan D; Fristrup, Kurt M; Johnson, Mark P; Tyack, Peter L; Witt, Matthew J; Blondel, Philippe; Parks, Susan E

2015-03-01

1. Many organisms depend on sound for communication, predator/prey detection and navigation. The acoustic environment can therefore play an important role in ecosystem dynamics and evolution. A growing number of studies are documenting acoustic habitats and their influences on animal development, behaviour, physiology and spatial ecology, which has led to increasing demand for passive acoustic monitoring (PAM) expertise in the life sciences. However, as yet, there has been no synthesis of data processing methods for acoustic habitat monitoring, which presents an unnecessary obstacle to would-be PAM analysts. 2. Here, we review the signal processing techniques needed to produce calibrated measurements of terrestrial and aquatic acoustic habitats. We include a supplemental tutorial and template computer codes in matlab and r, which give detailed guidance on how to produce calibrated spectrograms and statistical analyses of sound levels. Key metrics and terminology for the characterisation of biotic, abiotic and anthropogenic sound are covered, and their application to relevant monitoring scenarios is illustrated through example data sets. To inform study design and hardware selection, we also include an up-to-date overview of terrestrial and aquatic PAM instruments. 3. Monitoring of acoustic habitats at large spatiotemporal scales is becoming possible through recent advances in PAM technology. This will enhance our understanding of the role of sound in the spatial ecology of acoustically sensitive species and inform spatial planning to mitigate the rising influence of anthropogenic noise in these ecosystems. As we demonstrate in this work, progress in these areas will depend upon the application of consistent and appropriate PAM methodologies.

Dynamic bending of bionic flexible body driven by pneumatic artificial muscles(PAMs) for spinning gait of quadruped robot

NASA Astrophysics Data System (ADS)

Lei, Jingtao; Yu, Huangying; Wang, Tianmiao

2016-01-01

The body of quadruped robot is generally developed with the rigid structure. The mobility of quadruped robot depends on the mechanical properties of the body mechanism. It is difficult for quadruped robot with rigid structure to achieve better mobility walking or running in the unstructured environment. A kind of bionic flexible body mechanism for quadruped robot is proposed, which is composed of one bionic spine and four pneumatic artificial muscles(PAMs). This kind of body imitates the four-legged creatures' kinematical structure and physical properties, which has the characteristic of changeable stiffness, lightweight, flexible and better bionics. The kinematics of body bending is derived, and the coordinated movement between the flexible body and legs is analyzed. The relationship between the body bending angle and the PAM length is obtained. The dynamics of the body bending is derived by the floating coordinate method and Lagrangian method, and the driving force of PAM is determined. The experiment of body bending is conducted, and the dynamic bending characteristic of bionic flexible body is evaluated. Experimental results show that the bending angle of the bionic flexible body can reach 18°. An innovation body mechanism for quadruped robot is proposed, which has the characteristic of flexibility and achieve bending by changing gas pressure of PAMs. The coordinated movement of the body and legs can achieve spinning gait in order to improve the mobility of quadruped robot.

Selective Adsorption of Pb(II) from Aqueous Solution by Triethylenetetramine-Grafted Polyacrylamide/Vermiculite

PubMed Central

Gu, Shiqing; Wang, Lan; Mao, Xinyou; Yang, Liping; Wang, Chuanyi

2018-01-01

Amine groups play significant roles in polymeric composites for heavy metals removal. However, generating a composite with a large number of functional and stable amine groups based on clay is still a challenge. In this work, a new amine-functionalized adsorbent based on acid-activated vermiculite (a-Verm) was prepared by organic modification of silane coupling agent as bridge, followed by in situ polymerization of acrylamide (AM) and further grafting of triethylene tetramine (TETA). The obtained polymeric composite g-PAM/OVerm was characterized by scanning electron microscope (SEM), energy dispersive spectrometer (EDS), Fourier transform infrared (FTIR), thermal analysis (TG/DTG), X-ray photoelectron spectroscopy (XPS) and Brunauer–Emmett–Teller (BET) analyses, confirming that amine groups were successfully grafted onto the surface of Verm. The efficacy g-PAM/OVerm for removing Pb(II) was tested. The adsorption equilibrium data on g-PAM/OVerm was in good accordance with the Langmuir adsorption isotherms, and the adsorption maximal value of Pb(II) was 219.4 mg·g−1. The adsorption kinetic data fit the pseudo-second-order kinetic model well. Additionally, g-PAM/OVerm has better selectivity for Pb(II) ion in comparison with Zn(II), Cd(II) and Cu(II) ions. The present work shows that g-PAM/OVerm holds great potential for removing Pb(II) from wastewater, and provides a new and efficient method for the removal of heavy metal ions from industrial wastewater. PMID:29597288

Expression of PAM50 Genes in Lung Cancer: Evidence that Interactions between Hormone Receptors and HER2/HER3 Contribute to Poor Outcome.

PubMed

Siegfried, Jill M; Lin, Yan; Diergaarde, Brenda; Lin, Hui-Min; Dacic, Sanja; Pennathur, Arjun; Weissfeld, Joel L; Romkes, Marjorie; Nukui, Tomoko; Stabile, Laura P

2015-11-01

Non-small cell lung cancers (NSCLCs) frequently express estrogen receptor (ER) β, and estrogen signaling is active in many lung tumors. We investigated the ability of genes contained in the prediction analysis of microarray 50 (PAM50) breast cancer risk predictor gene signature to provide prognostic information in NSCLC. Supervised principal component analysis of mRNA expression data was used to evaluate the ability of the PAM50 panel to provide prognostic information in a stage I NSCLC cohort, in an all-stage NSCLC cohort, and in The Cancer Genome Atlas data. Immunohistochemistry was used to determine status of ERβ and other proteins in lung tumor tissue. Associations with prognosis were observed in the stage I cohort. Cross-validation identified seven genes that, when analyzed together, consistently showed survival associations. In pathway analysis, the seven-gene panel described one network containing the ER and progesterone receptor, as well as human epidermal growth factor receptor (HER)2/HER3 and neuregulin-1. NSCLC cases also showed a significant association between ERβ and HER2 protein expression. Cases positive for HER2 expression were more likely to express HER3, and ERβ-positive cases were less likely to be both HER2 and HER3 negative. Prognostic ability of genes in the PAM50 panel was verified in an ERβ-positive cohort representing all NSCLC stages. In The Cancer Genome Atlas data sets, the PAM50 gene set was prognostic in both adenocarcinoma and squamous cell carcinoma, whereas the seven-gene panel was prognostic only in squamous cell carcinoma. Genes in the PAM50 panel, including those linking ER and HER2, identify lung cancer patients at risk for poor outcome, especially among ERβ-positive cases and squamous cell carcinoma. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Native pears of Sardinia affect Penicillium expansum pathogenesis.

PubMed

Cubaiu, L; Azara, E; Ladu, G; Venditti, T; D'Hallewin, G

2013-01-01

Penicillium expansum causes blue mould rot, a serious post-harvest disease of pome fruits and is the main producer of the mycotoxin patulin. The occurrence of natural resistance against different hostpathogens, has been evidenced in some pear accessions of the Sardinian germoplasm. The aim of this research was to correlate P. expansum growth and patulin production on these indigenous pear accessions. In vitro and in vivo experiments were carried out with seven accessions ('Sarmentina', 'Vacchesa', 'De Puleu', 'De su Duca', 'Natalina', 'Oliena', 'Laconi 5') belonging to the CNR-ISPA ex situ collection and one national control cultivar ('Abate'). A wild type P. expansum from our collection was isolated from blue mould-decayed Sardinian pear fruit and selected for its aggressiveness and patulin production. The in vivo assay was carried out using 5 x 2 cm (Ø x thickness) sterilized fruit discs wounded and inoculated by a 10(5)UFC/mL concentration of P. expansum. Fruit discs were incubated at 23 degrees C for 7 days before analysis. The in vitro experiments, aimed at monitoring over time P. expansum mycelial growth and patulin accumulation, were performed with a standard medium (PDA) and a pear puree Agar Medium (PAM). Petri dishes with PDA and PAM were inoculated centrally with P. expansum conidia (10(5)UFC/ml) and then incubated at 23 degrees C for 7 days. Mycelial growth on Sardinian PAMs was inhibited in comparison to 'Abate' PAM and PDA. In particular, the accessions 'Sarmentina' and 'Vacchesa' showed the maximum inhibitory activity both in vitro and in vivo. Patulin production was detected by high-pressure liquid chromatography-mass spectrometry. The mycotoxin concentration in Sardinian PAMs was lower than that detected in PDA medium, pointing out a positive correlation between fungal growth inhibition and patulin production. The lowest concentration of patulin was found in 'Sarmentina' PAM. Based on these findings, some of Sardinian pear accessions seems to affect P. expansum pathogenesis and inhibit patulin production. Further researches are necessary to assess the mechanism of this biocontrol activity.

Frequent Surfing on Social Health Networks is Associated With Increased Knowledge and Patient Health Activation

PubMed Central

Grosberg, Dafna; Grinvald, Haya; Reuveni, Haim

2016-01-01

Background The advent of the Internet has driven a technological revolution that has changed our lives. As part of this phenomenon, social networks have attained a prominent role in health care. A variety of medical services is provided over the Internet, including home monitoring, interactive communications between the patient and service providers, and social support, among others. This study emphasizes some of the practical implications of Web-based health social networks for patients and for health care systems. Objective The objective of this study was to assess how participation in a social network among individuals with a chronic condition contributed to patient activation, based on the Patient Activation Measure (PAM). Methods A prospective, cross-sectional survey with a retrospective component was conducted. Data were collected from Camoni, a Hebrew-language Web-based social health network, participants in the diabetes mellitus, pain, hypertension, and depression/anxiety forums, during November 2012 to 2013. Experienced users (enrolled at least 6 months) and newly enrolled received similar versions of the same questionnaire including sociodemographics and PAM. Results Among 686 participants, 154 of 337 experienced and 123 of 349 newly enrolled completed the questionnaire. Positive correlations (P<.05) were found between frequency and duration of site visits and patient activation, social relationships, and chronic disease knowledge. Men surfed longer than women (χ²3=10.104, P<.05). Experienced users with diabetes surfed more than those with other illnesses and had significantly higher PAM scores (mean, M=69.3, standard deviation, SD=19.1, PAM level 4; Z=−4.197, P<.001) than new users (M=62.8, SD=18.7, PAM level 3). Disease knowledge directly predicted PAM for all users (β=.26 and .21, respectively). Frequency and duration of social health network use were correlated with increased knowledge about a chronic disease. Experienced surfers had higher PAM than newly enrolled, suggesting that continued site use may contribute to increased activation. Conclusions Web-based social health networks offer an opportunity to expand patient knowledge and increase involvement in personal health, thereby increasing patient activation. Further studies are needed to examine these changes on other aspects of chronic illnesses such as quality of life and costs. PMID:27511272

Modeling the formation and aging of secondary organic aerosols during CalNex 2010

NASA Astrophysics Data System (ADS)

Hayes, P. L.; Ortega, A. M.; Ahmadov, R.; McKeen, S. A.; Washenfelder, R. A.; Alvarez, S.; Rappenglueck, B.; Holloway, J. S.; Gilman, J. B.; Kuster, W. C.; De Gouw, J. A.; Zotter, P.; Prevot, A. S.; Kleindienst, T. E.; Offenberg, J. H.; Jimenez, J. L.

2012-12-01

Several traditional and recently proposed models are applied to predict the concentrations and properties of secondary organic aerosols (SOA) and organic gases at the Pasadena ground site during the CalNex campaign. The models are constrained with and compared against results from available observations. The CalNex campaign and specifically the Pasadena ground site featured a large and sophisticated suite of aerosol and gas phase instrumentation, and thus, it provides a unique opportunity to test SOA models under conditions of strong urban emissions at a range of low photochemical ages. The oxidation of volatile organic compounds (VOCs) using an updated traditional model cannot explain the observed ambient SOA, and under-predicts the measurements by a factor of ~40. Similarly, after accounting for the multi-generation oxidation of VOCs using a volatility basis set (VBS) approach as described by Tsimpidi et al. (2010), SOA is still under-predicted by a factor of ~8. For SOA formed from VOCs (V-SOA) the dominant precursors are aromatics (xylenes, toluene, and trimethylbenzenes). The model SOA formed from the oxidation of primary semivolatile and intermediate volatility organic compounds (P-S/IVOCs, producing SI-SOA) is also predicted using the parameterizations of Robinson et al. (2007) and Grieshop et al. (2009), and the properties of V-SOA + SI-SOA are compared against the measured O:C and volatility. We also compare the results of the different models against fossil/non-fossil carbon measurements as well as tracers of different SOA precursors. Potential Aerosol Mass (PAM) measurements of the SOA forming potential of the Pasadena air masses are also compared against that predicted by the models. The PAM analysis allows for model/measurement comparisons of SOA properties over a range of photochemical ages spanning almost two weeks. Using the V-SOA model, at low photochemical ages (< 1 day) the modeled PAM V-SOA is less than the measured PAM SOA, similar to the ambient results. In contrast, at high photochemical ages (i.e., more than about three days) the modeled PAM V-SOA is substantially greater than that measured, which is likely due fragmentation reactions that are not included in that model. We derive a parameterization of the measured PAM SOA as a function of the input photochemical age and the PAM photochemical age that serves as a comparison with other SOA models.

Hypothermia Is Neuroprotective after Severe Hypoxic-Ischaemic Brain Injury in Neonatal Rats Pre-Exposed to PAM3CSK4.

PubMed

Falck, Mari; Osredkar, Damjan; Maes, Elke; Flatebø, Torun; Wood, Thomas Ragnar; Walløe, Lars; Sabir, Hemmen; Thoresen, Marianne

2018-06-01

Preclinical research on the neuroprotective effect of hypothermia (HT) after perinatal asphyxia has shown variable results, depending on comorbidities and insult severity. Exposure to inflammation increases vulnerability of the neonatal brain to hypoxic-ischaemic (HI) injury, and could be one explanation for those neonates whose injury is unexpectedly severe. Gram-negative type inflammatory exposure by lipopolysaccharide administration prior to a mild HI insult results in moderate brain injury, and hypothermic neuroprotection is negated. However, the neuroprotective effect of HT is fully maintained after gram-positive type inflammatory exposure by PAM3CSK4 (PAM) pre-administration in the same HI model. Whether HT is neuroprotective in severe brain injury with gram-positive inflammatory pre-exposure has not been investigated. 59 seven-day-old rat pups were subjected to a unilateral HI insult, with left carotid artery ligation followed by 90-min hypoxia (8% O2 at Trectal 36°C). An additional 196 pups received intraperitoneal 0.9% saline (control) or PAM1 mg/kg, 8 h before undergoing the same HI insult. After randomisation to 5 h normothermia (NT37°C) or HT32°C, pups survived 1 week before they were sacrificed by perfusion fixation. Brains were harvested for hemispheric and hippocampal area loss analyses at postnatal day 14, as well as immunostaining for neuron count in the HIP CA1 region. Normothermic PAM animals (PAM-NT) had a comparable median area loss (hemispheric: 60% [95% CI 33-66]; hippocampal: 61% [95% CI 29-67]) to vehicle animals (Veh-NT) (hemispheric: 58% [95% CI 11-64]; hippocampal: 60% [95% CI 19-68]), which is defined as severe brain injury. Furthermore, mortality was low and similar in the two groups (Veh-NT 4.5% vs. PAM-NT 6.6%). HT reduced hemispheric and hippocampal injury in the Veh group by 13 and 28%, respectively (hemispheric: p = 0.048; hippocampal: p = 0.042). HT also provided neuroprotection in the PAM group, reducing hemispheric injury by 22% (p = 0.03) and hippocampal injury by 37% (p = 0.027). In these experiments with severe brain injury, Toll-like receptor-2 triggering prior to HI injury does not have an additive injurious effect, and there is a small but significant neuroprotective effect of HT. HT appears to be neuroprotective over a continuum of injury severity in this model, and the effect size tapers off with increasing area loss. Our results indicate that gram-positive inflammatory exposure prior to HI injury does not negate the neuroprotective effect of HT in severe brain injury. © 2018 S. Karger AG, Basel.

Characterization of plasticized PEO-PAM blend polymer electrolyte system

NASA Astrophysics Data System (ADS)

Dave, Gargi; Kanchan, Dinesh

2017-05-01

Present study reports characterization studies of NaCF3SO3 based PEO-PAM Blend Polymer Electrolyte (BPE) system with varying amount of EC+PC as plasticizer prepared by solution cast technique. Structural analysis and surface topography have been performed using FTIR and SEM studies. To understand, thermal properties, DSC studies have been undertaken in the present paper

Evaluating the Invariance of Cognitive Profile Patterns Derived from Profile Analysis via Multidimensional Scaling (PAMS): A Bootstrapping Approach

ERIC Educational Resources Information Center

Kim, Se-Kang

2010-01-01

The aim of the current study is to validate the invariance of major profile patterns derived from multidimensional scaling (MDS) by bootstrapping. Profile Analysis via Multidimensional Scaling (PAMS) was employed to obtain profiles and bootstrapping was used to construct the sampling distributions of the profile coordinates and the empirical…

A fast MEMS scanning photoacoustic microscopy system and its application in glioma study

NASA Astrophysics Data System (ADS)

Bi, Renzhe; Balasundaram, Ghayathri; Jeon, Seungwan; Pu, Yang; Tay, Hui Chien; Kim, Chulhong; Olivo, Malini

2018-02-01

We present a water-proof Microelectromechanical systems (MEMS) based scanning optical resolution Photoacoustic Microscopy (OR-PAM) system and its application in glioma tumor mouse model study. The presented OR-PAM system has high optical resolution ( 3 μm) and high scanning speed (up to 50 kHz A-scan rate), which is ideal for cerebral vascular imaging. In this study, the mice with glioma tumor are treated with vascular disrupting agent (VDA). OR-PAM system is utilized to image the cerebral with the whole skull intact before and after the injection of VDA. By image registration, the response of every single blood vessel can be traced. This will provide us deeper understanding of the drug effect.

Comparison of PAM Systems for Acoustic Monitoring and Further Risk Mitigation Application.

PubMed

Ludwig, Stefan; Kreimeyer, Roman; Knoll, Michaela

2016-01-01

We present results of the SIRENA 2011 research cruises conducted by the NATO Undersea Research Centre (NURC) and joined by the Research Department for Underwater Acoustics and Geophysics (FWG), Bundeswehr Technical Centre (WTD 71) and the Universities of Kiel and Pavia. The cruises were carried out in the Ligurian Sea. The main aim of the FWG was to test and evaluate the newly developed towed hydrophone array as a passive acoustic monitoring (PAM) tool for risk mitigation applications. The system was compared with the PAM equipment used by the other participating institutions. Recorded sounds were used to improve an automatic acoustic classifier for marine mammals, and validated acoustic detections by observers were compared with the results of the classifier.

Explanation of random experiment sheduling and its application to space station analysis

NASA Technical Reports Server (NTRS)

Moore, J. E.

1970-01-01

The capability of the McDonnell-Douglas Phase B space station concept to complete the Blue Book Experiment program is analyzed and the Random experiment program with Resource Impact (REPRI) which was used to generate the data is described. The results indicate that station manpower and electrical power are the two resources which will constrain the amount of the Blue Book program that the station can complete. The station experiment program and its resource requirements are sensitive to levels of manpower and electrical power 13.5 men and 11 kilowatts. Continuous artificial gravity experiments have much less impact on the experiment program than experiments using separate artificial gravity periods. Station storage volume presently allocated for the FPE's and their supplies (1600 cu ft) is more than adequate. The REPRI program uses the Monte Carlo technique to generate a set of feasible experiment schedules for a space station. The schedules are statistically analyzed to determine the impact of the station experiment program resource requirements on the station concept. Also, the sensitivity of the station concept to one or more resources is assessed.

All-optical photoacoustic microscopy (AOPAM) system for remote characterization of biological tissues

NASA Astrophysics Data System (ADS)

Sampathkumar, Ashwin; Chitnis, Parag V.; Silverman, Ronald H.

2014-03-01

Conventional photoacoustic microscopy (PAM) employs light pulses to produce a photoacoustic (PA) effect and detects the resulting acoustic waves using an ultrasound transducer acoustically coupled to the target. The resolution of conventional PAM is limited by the sensitivity and bandwidth of the ultrasound transducer. We investigated a versatile, all-optical PAM (AOPAM) system for characterizing in vivo as well as ex vivo biological specimens. The system employs non-contact interferometric detection of PA signals that overcomes limitations of conventional PAM. A 532-nm pump laser with a pulse duration of 5 ns excites the PA effect in tissue. Resulting acoustic waves produce surface displacements that are sensed using a 532-nm continuous-wave (CW) probe laser in a Michelson interferometer with a 1- GHz bandwidth. The pump and probe beams are coaxially focused using a 50X objective giving a diffraction-limited spot size of 0.48 μm. The phase-encoded probe beam is demodulated using homodyne methods. The detected timedomain signal is time reversed using k-space wave-propagation methods to produce a spatial distribution of PA sources in the target tissue. A minimum surface-displacement sensitivity of 0.19 pm was measured. PA-induced surface displacements are very small; therefore, they impose stringent detection requirements and determine the feasibility of implementing an all-optical PAM in biomedical applications. 3D PA images of ex vivo porcine retina specimens were generated successfully. We believe the AOPAM system potentially is well suited for assessing retinal diseases and other near-surface biomedical applications such as sectionless histology and evaluation of skin burns and pressure or friction ulcers.

Ozone Enhances Pulmonary Innate Immune Response to a Toll-Like Receptor–2 Agonist

PubMed Central

Oakes, Judy L.; O’Connor, Brian P.; Warg, Laura A.; Burton, Rachel; Hock, Ashley; Loader, Joan; LaFlamme, Daniel; Jing, Jian; Hui, Lucy; Schwartz, David A.

2013-01-01

Previous work demonstrated that pre-exposure to ozone primes innate immunity and increases Toll-like receptor–4 (TLR4)–mediated responses to subsequent stimulation with LPS. To explore the pulmonary innate immune response to ozone exposure further, we investigated the effects of ozone in combination with Pam3CYS, a synthetic TLR2/TLR1 agonist. Whole-lung lavage (WLL) and lung tissue were harvested from C57BL/6 mice after exposure to ozone or filtered air, followed by saline or Pam3CYS 24 hours later. Cells and cytokines in the WLL, the surface expression of TLRs on macrophages, and lung RNA genomic expression profiles were examined. We demonstrated an increased WLL cell influx, increased IL-6 and chemokine KC (Cxcl1), and decreased macrophage inflammatory protein (MIP)-1α and TNF-α in response to Pam3CYS as a result of ozone pre-exposure. We also observed the increased cell surface expression of TLR4, TLR2, and TLR1 on macrophages as a result of ozone alone or in combination with Pam3CYS. Gene expression analysis of lung tissue revealed a significant increase in the expression of genes related to injury repair and the cell cycle as a result of ozone alone or in combination with Pam3CYS. Our results extend previous findings with ozone/LPS to other TLR ligands, and suggest that the ozone priming of innate immunity is a general mechanism. Gene expression profiling of lung tissue identified transcriptional networks and genes that contribute to the priming of innate immunity at the molecular level. PMID:23002100

Positive and negative metacognitions about alcohol use among university students: Psychometric properties of the PAMS and NAMS French versions.

PubMed

Gierski, Fabien; Spada, Marcantonio M; Fois, Eveline; Picard, Aurélie; Naassila, Mickaël; Van der Linden, Martial

2015-08-01

Metacognitions about the positive and negative effects of alcohol use have been associated with various patterns of drinking. The aim of the present study was to validate French versions of the Positive Alcohol Metacognitions Scale (PAMS) and the Negative Alcohol Metacognitions Scale (NAMS) developed by Spada and Wells (2008, Addict. Behav. 33, 515) and to investigate the relationship between metacognitions and patterns of alcohol use among university students. Responses of 1600 university students who participated in an internet survey-based study on alcohol use were submitted to confirmatory (N=800, mean age 20.40 years, 45.50% male) and exploratory (N=800, mean age 20.34 years, 45.38% male) factor analyses in two separate samples. Alcohol use, binge drinking and mood were also assessed. In line with the original versions of the scales, results provided support for a two-factor structure of the French PAMS and NAMS. Both scales revealed adequate internal reliability. Good temporal stability was found for the two factors of the NAMS, whereas one factor of the PAMS showed weakness across time. Predictive validity revealed that negative alcohol metacognitions about the uncontrollability of alcohol use were found to be consistently associated with alcohol use and binge drinking, whereas positive metacognitions about alcohol use were found to be differentially associated with alcohol use and binge drinking. The French versions of the PAMS and NAMS exhibited suitable psychometric properties. This study also emphasized the role of metacognitions about alcohol use in drinking behaviour among university students. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Fatal Naegleria fowleri infection acquired in Minnesota: possible expanded range of a deadly thermophilic organism.

PubMed

Kemble, Sarah K; Lynfield, Ruth; DeVries, Aaron S; Drehner, Dennis M; Pomputius, William F; Beach, Michael J; Visvesvara, Govinda S; da Silva, Alexandre J; Hill, Vincent R; Yoder, Jonathan S; Xiao, Lihua; Smith, Kirk E; Danila, Richard

2012-03-01

Primary amebic meningoencephalitis (PAM), caused by the free-living ameba Naegleria fowleri, has historically been associated with warm freshwater exposures at lower latitudes of the United States. In August 2010, a Minnesota resident, aged 7 years, died of rapidly progressive meningoencephalitis after local freshwater exposures, with no history of travel outside the state. PAM was suspected on the basis of amebae observed in cerebrospinal fluid. Water and sediment samples were collected at locations where the patient swam during the 2 weeks preceding illness onset. Patient and environmental samples were tested for N. fowleri with use of culture and real-time polymerase chain reaction (PCR); isolates were genotyped. Historic local ambient temperature data were obtained. N. fowleri isolated from a specimen of the patient's brain and from water and sediment samples was confirmed using PCR as N. fowleri genotype 3. Surface water temperatures at the times of collection of the positive environmental samples ranged from 22.1°C to 24.5°C. August 2010 average air temperature near the exposure site was 25°C, 3.6°C above normal and the third warmest for August in the Minneapolis area since 1891. This first reported case of PAM acquired in Minnesota occurred 550 miles north of the previously reported northernmost case in the Americas. Clinicians should be aware that N. fowleri-associated PAM can occur in areas at much higher latitude than previously described. Local weather patterns and long-term climate change could impact the frequency of PAM.

75 FR 81212 - Certain Pasta From Italy: Notice of Final Results of the Thirteenth Antidumping Duty...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-27

....r.L. (Granoro). The period of review (POR) is July 1, 2008, through June 30, 2009. Granoro and... Lensi S.r.L. (Lensi), Industria Alimentare Colavita, S.p.A. (Indalco), PAM S.p.A. (PAM), and Fasolino... dry pasta in packages of five pounds four ounces or less, whether or not enriched or fortified or...

Single channel 112Gbit/sec PAM4 at 56Gbaud with digital signal processing for data centers applications.

PubMed

Sadot, Dan; Dorman, G; Gorshtein, Albert; Sonkin, Eduard; Vidal, Or

2015-01-26

112Gbit/sec DSP-based single channel transmission of PAM4 at 56Gbaud over 15GHz of effective analog bandwidth is experimentally demonstrated. The DSP enables use of mature 25G optoelectronics for 2-10km datacenter intra-connections, and 8Tbit/sec over 80km interconnections between data centers.

Harvesting Chlorella vulgaris by magnetic flocculation using Fe₃O₄ coating with polyaluminium chloride and polyacrylamide.

PubMed

Zhao, Yuan; Liang, Wenyan; Liu, Lijun; Li, Feizhen; Fan, Qianlong; Sun, Xiaoli

2015-12-01

The harvesting of Chlorella vulgaris was investigated by magnetic flocculation, where the natural magnetite was used as magnetic seeds and the polyaluminium chloride (PACl) and polyacrylamide (PAM) were used as the coating polymer on the Fe3O4 surface. The composite modes of PACl, PAM, and Fe3O4 and their effects on harvesting were studied. The results showed that adding the composite PACl/Fe3O4 first (at (0.625 mmol Al/L)/(10 g/L)) followed by the addition PAM (at 3mg/L) was the optimum dosing strategy. Following this strategy, 99% of cells could be harvested in less than 0.5 min, and it could overcome negative impacts from pH and algal organic matter. Compared to PACl, ζ-potentials of PACl/Fe3O4 were found to be increased substantially from -4.9-8.5 mV to 1.5-19.5 mV at pH range 2.1-12.3. The charge neutralization of PACl/Fe3O4 and sweeping of PAM play an important role in magnetic harvesting of microalgal cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

FRAP and Photoconversion in Multiple Arbitrary Regions of Interest Using a Programmable Array Microscope (PAM)

PubMed Central

Hagen, Guy M.; Caarls, Wouter; Lidke, Keith A.; de Vries, Anthony H. B.; Fritsch, Cornelia; Barisas, B. George; Arndt-Jovin, Donna J.; Jovin, Thomas M.

2011-01-01

Photomanipulation (photobleaching, photoactivation, or photoconversion) is an essential tool in fluorescence microscopy. Fluorescence recovery after photobleaching (FRAP) is commonly used for the determination of lateral diffusion constants of membrane proteins, and can be conveniently implemented in confocal laser scanning microscopy (CLSM). Such determinations provide important information on molecular dynamics in live cells. However, the CLSM platform is inherently limited for FRAP because of its inflexible raster (spot) scanning format. We have implemented FRAP and photoactivation protocols using structured illumination and detection in a programmable array microscope (PAM). The patterns are arbitrary in number and shape, dynamic and adjustable to and by the sample characteristics. We have used multi-spot PAM-FRAP to measure the lateral diffusion of the erbB3 (HER3) receptor tyrosine kinase labeled by fusion with mCitrine on untreated cells and after treatment with reagents that perturb the cytoskeleton or plasma membrane or activate co-expressed erbB1 (HER1, the EGF receptor EGFR). We also show the versatility of the PAM for photoactivation in arbitrary regions of interest, in cells expressing erbB3 fused with the photoconvertible fluorescent protein dronpa. PMID:19208387

Hyaluronan–cisplatin conjugate nanoparticles embedded in Eudragit S100-coated pectin/alginate microbeads for colon drug delivery

PubMed Central

Tsai, Shiao-Wen; Yu, Ding-Syuan; Tsao, Shu-Wei; Hsu, Fu-Yin

2013-01-01

Hyaluronan–cisplatin conjugate nanoparticles (HCNPs) were chosen as colon-targeting drug-delivery carriers due to the observation that a variety of malignant tumors overexpress hyaluronan receptors. HCNPs were prepared by mixing cisplatin with a hyaluronan solution, followed by dialysis to remove trace elements. The cells treated with HCNPs showed significantly lower viability than those treated with cisplatin alone. HCNPs were entrapped in Eudragit S100-coated pectinate/alginate microbeads (PAMs) by using an electrospray method and a polyelectrolyte multilayer-coating technique in aqueous solution. The release profile of HCNPs from Eudragit S100-coated HCNP-PAMs was pH-dependent. The percentage of 24-hour drug release was approximately 25.1% and 39.7% in pH 1.2 and pH 4.5 media, respectively. However, the percentage of drug released quickly rose to 75.6% at pH 7.4. Moreover, the result of an in vivo nephrotoxicity study demonstrated that Eudragit S100-coated HCNP-PAMs treatment could mitigate the nephrotoxicity that resulted from cisplatin. From these results, it can be concluded that Eudragit S100-coated HCNP-PAMs are promising carriers for colonspecific drug delivery. PMID:23861585

Primary Amoebic Meningoencephalitis: Neurochemotaxis and Neurotropic Preferences of Naegleria fowleri.

PubMed

Baig, Abdul Mannan

2016-08-17

Naegleria fowleri causes one of the most devastating necrotic meningoencephalitis in humans. The infection caused by this free-living amoeba is universally fatal within a week of onset of the signs and symptoms of the disease called primary amoebic meningoencephalitis (PAM). In all the affected patients, there is always a history of entry of water into the nose. Even though the diagnostic and treatment protocols have been revised and improved, the obstinate nature of the disease can be gauged by the fact that the mortality rate has persisted around ∼95% over the past 60 years. Some of the unanswered questions regarding PAM are is there a neurochemical basis of the chemotaxis of N. fowleri to the brain? What immune evasion means occurs preceding the neurotropic invasion? What is the contribution of the acute inflammatory response in the fatal cases? Can a combination of anti-amoebic drugs with antagonism of the acute inflammation help save the patient's life? As prevention remains the most valuable safeguard against N. fowleri, a quicker diagnosis, better understanding of the pathogenesis of PAM coupled with testing of newer and safer drugs could improve the chances of survival in patients affected with PAM.

Flocculation of both anionic and cationic dyes in aqueous solutions by the amphoteric grafting flocculant carboxymethyl chitosan-graft-polyacrylamide.

PubMed

Yang, Zhen; Yang, Hu; Jiang, Ziwen; Cai, Tao; Li, Haijiang; Li, Haibo; Li, Aimin; Cheng, Rongshi

2013-06-15

In the current work, a series of amphoteric grafting chitosan-based flocculants (carboxymethyl chitosan-graft-polyacrylamide, denoted as CMC-g-PAM) was designed and prepared successfully. The flocculants were applied to eliminate various dyes from aqueous solutions. Among different graft copolymers, CMC-g-PAM11 with a PAM grafting ratio of 74% demonstrated the most efficient performance for removal of both the anionic dye (Methyl Orange, MO) and the cationic dye (Basic Bright Yellow, 7GL) under the corresponding favored conditions (80 mg/L of the flocculant at pH 4.0, and 160 mg/L at pH 11.0). In comparison with its precursors, chitosan and carboxymethyl chitosan, CMC-g-PAM11 showed higher removal efficiencies and wider flocculation windows. More importantly, the graft copolymer produced notably more compacted flocs based on image analysis in combination with fractal theory, which was of great significance in practical water treatment. Furthermore, the flocculation mechanism was discussed in detail. The grafted polyacrylamide chains were found to contribute much to the improved bridging and sweeping flocculation effects, but reduced charge neutralization flocculation for the effect of charge screening. Copyright © 2013 Elsevier B.V. All rights reserved.

Detection, mapping, and quantification of single walled carbon nanotubes in histological specimens with photoacoustic microscopy.

PubMed

Avti, Pramod K; Hu, Song; Favazza, Christopher; Mikos, Antonios G; Jansen, John A; Shroyer, Kenneth R; Wang, Lihong V; Sitharaman, Balaji

2012-01-01

In the present study, the efficacy of multi-scale photoacoustic microscopy (PAM) was investigated to detect, map, and quantify trace amounts [nanograms (ng) to micrograms (µg)] of SWCNTs in a variety of histological tissue specimens consisting of cancer and benign tissue biopsies (histological specimens from implanted tissue engineering scaffolds). Optical-resolution (OR) and acoustic-resolution (AR)--Photoacoustic microscopy (PAM) was employed to detect, map and quantify the SWCNTs in a variety of tissue histological specimens and compared with other optical techniques (bright-field optical microscopy, Raman microscopy, near infrared (NIR) fluorescence microscopy). Both optical-resolution and acoustic-resolution PAM, allow the detection and quantification of SWCNTs in histological specimens with scalable spatial resolution and depth penetration. The noise-equivalent detection sensitivity to SWCNTs in the specimens was calculated to be as low as ∼7 pg. Image processing analysis further allowed the mapping, distribution, and quantification of the SWCNTs in the histological sections. The results demonstrate the potential of PAM as a promising imaging technique to detect, map, and quantify SWCNTs in histological specimens, and could complement the capabilities of current optical and electron microscopy techniques in the analysis of histological specimens containing SWCNTs.

Distinct forms of mitochondrial TOM-TIM supercomplexes define signal-dependent states of preprotein sorting.

PubMed

Chacinska, Agnieszka; van der Laan, Martin; Mehnert, Carola S; Guiard, Bernard; Mick, David U; Hutu, Dana P; Truscott, Kaye N; Wiedemann, Nils; Meisinger, Chris; Pfanner, Nikolaus; Rehling, Peter

2010-01-01

Mitochondrial import of cleavable preproteins occurs at translocation contact sites, where the translocase of the outer membrane (TOM) associates with the presequence translocase of the inner membrane (TIM23) in a supercomplex. Different views exist on the mechanism of how TIM23 mediates preprotein sorting to either the matrix or inner membrane. On the one hand, two TIM23 forms were proposed, a matrix transport form containing the presequence translocase-associated motor (PAM; TIM23-PAM) and a sorting form containing Tim21 (TIM23(SORT)). On the other hand, it was reported that TIM23 and PAM are permanently associated in a single-entity translocase. We have accumulated distinct transport intermediates of preproteins to analyze the translocases in their active, preprotein-carrying state. We identified two different forms of active TOM-TIM23 supercomplexes, TOM-TIM23(SORT) and TOM-TIM23-PAM. These two supercomplexes do not represent separate pathways but are in dynamic exchange during preprotein translocation and sorting. Depending on the signals of the preproteins, switches between the different forms of supercomplex and TIM23 are required for the completion of preprotein import.

Fatal primary amoebic meningoencephalitis in a Norwegian tourist returning from Thailand

PubMed Central

Reiakvam, Olaug Marie; Stensvold, Christen Rune; Hermansen, Nils Olav; Holberg-Petersen, Mona; Antal, Ellen-Ann; Gaustad, Knut; Førde, Ingrid Schage; Heger, Bernt

2016-01-01

Introduction: Primary amoebic meningoencephalitis (PAM) is a rare disease caused by the free-living amoeba Naegleria fowleri. Infection occurs by insufflation of water containing amoebae into the nasal cavity, and is usually associated with bathing in freshwater. Nasal irrigation is a more rarely reported route of infection. Case presentation: A fatal case of PAM in a previously healthy Norwegian woman, acquired during a holiday trip to Thailand, is described. Clinical findings were consistent with rapidly progressing meningoencephalitis. The cause of infection was discovered by chance, owing to the unexpected detection of N. fowleri DNA by a PCR assay targeting fungi. A conclusive diagnosis was established based on sequencing of N. fowleri DNA from brain biopsies, supported by histopathological findings. Nasal irrigation using contaminated tap water is suspected as the source of infection. Conclusion: The clinical presentation of PAM is very similar to severe bacterial meningitis. This case is a reminder that when standard investigations fail to identify a cause of infection in severe meningoencephalitis, it is of crucial importance to continue a broad search for a conclusive diagnosis. PAM should be considered as a diagnosis in patients with symptoms of severe meningoencephalitis returning from endemic areas. PMID:28348761

Fatal primary amoebic meningoencephalitis in a Norwegian tourist returning from Thailand.

PubMed

Stubhaug, Tore Taksdal; Reiakvam, Olaug Marie; Stensvold, Christen Rune; Hermansen, Nils Olav; Holberg-Petersen, Mona; Antal, Ellen-Ann; Gaustad, Knut; Førde, Ingrid Schage; Heger, Bernt

2016-06-01

Primary amoebic meningoencephalitis (PAM) is a rare disease caused by the free-living amoeba Naegleria fowleri . Infection occurs by insufflation of water containing amoebae into the nasal cavity, and is usually associated with bathing in freshwater. Nasal irrigation is a more rarely reported route of infection. A fatal case of PAM in a previously healthy Norwegian woman, acquired during a holiday trip to Thailand, is described. Clinical findings were consistent with rapidly progressing meningoencephalitis. The cause of infection was discovered by chance, owing to the unexpected detection of N. fowleri DNA by a PCR assay targeting fungi. A conclusive diagnosis was established based on sequencing of N. fowleri DNA from brain biopsies, supported by histopathological findings. Nasal irrigation using contaminated tap water is suspected as the source of infection. The clinical presentation of PAM is very similar to severe bacterial meningitis. This case is a reminder that when standard investigations fail to identify a cause of infection in severe meningoencephalitis, it is of crucial importance to continue a broad search for a conclusive diagnosis. PAM should be considered as a diagnosis in patients with symptoms of severe meningoencephalitis returning from endemic areas.

Primary Acquired Melanosis: Clinical, Histopathologic and Optical Coherence Tomographic Correlation

PubMed Central

Alzahrani, Yahya A.; Kumar, Smita; Abdul Aziz, Hassan; Plesec, Thomas; Singh, Arun D.

2016-01-01

Aim To assess the use of anterior segment optical coherence tomography (OCT) as an adjuvant diagnostic tool in primary acquired melanosis (PAM) by correlating clinical, histopathologic and anterior segment OCT findings. Methods Twenty-four patients (24 eyes) with PAM of the conjunctiva, cornea or both were imaged with an anterior segment OCT device (RTVue, model-RT100; Optovue Inc., Fremont, Calif., USA). Results Histopathologic diagnosis following excisional or incisional biopsy was confirmed in 13 out of 24 patients (54.6%). OCT images showed a characteristic uniformly thick basal epithelial hyperreflective band (about 20 μm thick) and normal thickness of the overlying epithelial layer in all patients (100%). The hyperreflective band on OCT correlated with the basal epithelial melanocytic pigmentation noted on histopathologic examination but did not vary in thickness between cases with or without atypia. Conclusions The characteristic basal epithelial hyperreflective band with normal overlying epithelium in the absence of cysts observed in all cases by anterior segment OCT correlated with clinical and histopathologic features of conjunctival and corneal PAM. Anterior segment OCT may be helpful as a noninvasive diagnostic tool for PAM. Improvement in resolution is necessary to detect melanocytic hyperplasia and aytpia suggestive of malignant potential. PMID:27390743

Challenges in the development of an M4 PAM preclinical candidate: The discovery, SAR, and in vivo characterization of a series of 3-aminoazetidine-derived amides.

PubMed

Tarr, James C; Wood, Michael R; Noetzel, Meredith J; Bertron, Jeanette L; Weiner, Rebecca L; Rodriguez, Alice L; Lamsal, Atin; Byers, Frank W; Chang, Sichen; Cho, Hyekyung P; Jones, Carrie K; Niswender, Colleen M; Wood, Michael W; Brandon, Nicholas J; Duggan, Mark E; Conn, P Jeffrey; Bridges, Thomas M; Lindsley, Craig W

2017-07-01

This letter details the continued chemical optimization of a novel series of M 4 positive allosteric modulators (PAMs) based on a 5-amino-thieno[2,3-c]pyridazine core by incorporating a 3-amino azetidine amide moiety. The analogs described within this work represent the most potent M 4 PAMs reported for this series to date. The SAR to address potency, clearance, subtype selectivity, CNS exposure, and P-gp efflux are described. This work culminated in the discovery of VU6000918, which demonstrated robust efficacy in a rat amphetamine-induced hyperlocomotion reversal model at a minimum efficacious dose of 0.3mg/kg. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reactivation of VX-inhibited cholinesterase by 2-PAM and HS-6 in rats.

PubMed

Harris, L W; Stitcher, D L

1983-01-01

Atropinized rats intoxicated with ethyl-S-2-diisopropyl aminoethyl methyl phosphonothioate (VX), 15 mg/kg iv, were divided into three groups and were treated with normal saline, iv, 30 mg/kg of 2-PAM C1, iv, and 30 mg/kg of HS-6, iv. One hr after administration of therapy they were decapitated and cholinesterase (ChE) activity was determined on blood, brain and diaphragm tissue. Both 2-PAM C1 and HS-6 markedly reactivated VX-inhibited blood and diaphragm ChE. Brain ChE activity was not significantly reactivated by either oxime. The effectiveness of these oximes in restoration of VX-inactivated ChE in vivo offers an explanation as to why conventional atropine/oxime therapy is so effective against VX intoxication.

Transmission of 2 × 56 Gb/s PAM-4 signal over 100 km SSMF using 18 GHz DMLs.

PubMed

Zhou, Shiwei; Li, Xiang; Yi, Lilin; Yang, Qi; Fu, Songnian

2016-04-15

We experimentally demonstrate C-band 2 × 56 Gb/s pulse-amplitude modulation (PAM)-4 signal transmission over 100 km standard single-mode fiber (SSMF) using 18 GHz direct-modulated lasers (DMLs) and direct detection, without inline optical amplifier. A delay interferometer (DI) at the transmitter side is used to extend the transmission reach from 40 to 100 km. A digital Volterra filter at the receiver side is used to mitigate the nonlinear distortions. We obtain an average bit error ratio (BER) of 1.5 × 10(-3) for 2 × 56 Gb/s PAM-4 signal after 100 km SSMF transmission at the optimal input power, which is below the 7% forward error correction (FEC) threshold (3.8 × 10(-3)).

3.375-Gb/s RGB-LED based WDM visible light communication system employing PAM-8 modulation with phase shifted Manchester coding.

PubMed

Chi, Nan; Zhang, Mengjie; Zhou, Yingjun; Zhao, Jiaqi

2016-09-19

Optical background noise and second-order nonlinear distortions are two main challenges faced by indoor high-speed VLC system. In this paper, a novel phase shifted Manchester (PS-Manchester) coding based on PAM-8 is proposed and experimentally demonstrated to mitigate these noise and distortions. With the aid of PS-Manchester coding and WDM, a total data rate of 3.375-Gb/s can be successfully achieved in the RGB-LED based VLC system. The BER is under 7% HD-FEC limit of 3.8x10^-3 after 1-m indoor free space transmission. To the best of our knowledge, this is the highest data rate ever achieved in PAM VLC systems.

Growth of melanoma brain tumors monitored by photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Staley, Jacob; Grogan, Patrick; Samadi, Abbas K.; Cui, Huizhong; Cohen, Mark S.; Yang, Xinmai

2010-07-01

Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.

7 CFR 1740.1 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-01-01

... PUBLIC TELEVISION STATION DIGITAL TRANSITION GRANT PROGRAM Public Television Station Digital Transition... Station Digital Transition Grant Program (Grant Program) is to enable public television stations serving rural areas to transition from broadcasting in analog to digital, as required under the Federal...

7 CFR 1740.1 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-01-01

... PUBLIC TELEVISION STATION DIGITAL TRANSITION GRANT PROGRAM Public Television Station Digital Transition... Station Digital Transition Grant Program (Grant Program) is to enable public television stations serving rural areas to transition from broadcasting in analog to digital, as required under the Federal...

Pulse amplitude modulated chlorophyll fluorometer

DOEpatents

Greenbaum, Elias; Wu, Jie

2015-12-29

Chlorophyll fluorometry may be used for detecting toxins in a sample because of changes in micro algae. A portable lab on a chip ("LOAC") based chlorophyll fluorometer may be used for toxin detection and environmental monitoring. In particular, the system may include a microfluidic pulse amplitude modulated ("PAM") chlorophyll fluorometer. The LOAC PAM chlorophyll fluorometer may analyze microalgae and cyanobacteria that grow naturally in source drinking water.

A Modified Moore Approach to Teaching Mathematical Statistics: An Inquiry Based Learning Technique to Teaching Mathematical Statistics

ERIC Educational Resources Information Center

McLoughlin, M. Padraig M. M.

2008-01-01

The author of this paper submits the thesis that learning requires doing; only through inquiry is learning achieved, and hence this paper proposes a programme of use of a modified Moore method in a Probability and Mathematical Statistics (PAMS) course sequence to teach students PAMS. Furthermore, the author of this paper opines that set theory…

A comprehensive evaluation of the efficacy of leading oxime therapies in guinea pigs exposed to organophosphorus chemical warfare agents or pesticides

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

Wilhelm, Christina M., E-mail: wilhelmc@battelle.org; Snider, Thomas H., E-mail: snidert@battelle.org; Babin, Michael C., E-mail: babinm@battelle.org

The currently fielded pre-hospital therapeutic regimen for the treatment of organophosphorus (OP) poisoning in the United States (U.S.) is the administration of atropine in combination with an oxime antidote (2-PAM Cl) to reactivate inhibited acetylcholinesterase (AChE). Depending on clinical symptoms, an anticonvulsant, e.g., diazepam, may also be administered. Unfortunately, 2-PAM Cl does not offer sufficient protection across the range of OP threat agents, and there is some question as to whether it is the most effective oxime compound available. The objective of the present study is to identify an oxime antidote, under standardized and comparable conditions, that offers protection atmore » the FDA approved human equivalent dose (HED) of 2-PAM Cl against tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX, and the pesticides paraoxon, chlorpyrifos oxon, and phorate oxon. Male Hartley guinea pigs were subcutaneously challenged with a lethal level of OP and treated at approximately 1 min post challenge with atropine followed by equimolar oxime therapy (2-PAM Cl, HI-6 DMS, obidoxime Cl{sub 2}, TMB-4, MMB4-DMS, HLö-7 DMS, MINA, and RS194B) or therapeutic-index (TI) level therapy (HI-6 DMS, MMB4-DMS, MINA, and RS194B). Clinical signs of toxicity were observed for 24 h post challenge and blood cholinesterase [AChE and butyrylcholinesterase (BChE)] activity was analyzed utilizing a modified Ellman's method. When the oxime is standardized against the HED of 2-PAM Cl for guinea pigs, the evidence from clinical observations, lethality, quality of life (QOL) scores, and cholinesterase reactivation rates across all OPs indicated that MMB4 DMS and HLö-7 DMS were the two most consistently efficacious oximes. - Highlights: • First comprehensive evaluation of leading AChE oxime reactivators • All oximes are compared against current U.S. therapy 2-PAM Cl. • Relative therapeutic oxime efficacies against OP CWNA and pesticides • Contribution to more effective antidotes for civilian and military populations.« less

The toll-like receptor 2 agonist Pam3CSK4 is neuroprotective after spinal cord injury.

PubMed

Stivers, Nicole S; Pelisch, Nicolas; Orem, Ben C; Williams, Joshua; Nally, Jacqueline M; Stirling, David P

2017-08-01

Microglia/macrophage activation and recruitment following spinal cord injury (SCI) is associated with both detrimental and reparative functions. Stimulation of the innate immune receptor Toll-like receptor-2 (TLR2) has shown to be beneficial following SCI, and it increases axonal regeneration following optic nerve crush. However, the mechanism(s) remain unclear. As microglia express high levels of TLR2, we hypothesized that modulating the microglial response to injury using a specific TLR2 agonist, Pam3CSK4, would prevent secondary-mediated white matter degeneration following SCI. To test this hypothesis, we documented acute changes in microglia, axons, and oligodendroglia over time using two-photon excitation and an ex vivo laser-induced SCI (LiSCI) model. We utilized double transgenic mice that express GFP in either microglia or oligodendroglia, and YFP in axons, and we applied the lipophilic fluorescent dye (Nile Red) to visualize myelin. We found that treatment with Pam3CSK4 initiated one hour after injury induced a significant increase in the extent and timing of the microglial response to injury compared to vehicle controls. This enhanced response was observed 2 to 4h following SCI and was most prominent in areas closer to the ablation site. In addition, Pam3CSK4 treatment significantly reduced axonal dieback rostral and caudal to the ablation at 6h post-SCI. This protective effect of Pam3CSK4 was also mirrored when assessing secondary bystander axonal damage (i.e., axons spared by the primary injury that then succumb to secondary degeneration), and when assessing the survival of oligodendroglia. Following these imaging experiments, custom microarray analysis of the ex vivo spinal cord preparations revealed that Pam3CSK4-treatment induced an alternative (mixed M1:M2) microglial activation profile. In summary, our data suggest that by providing a second "sterile" activation signal to microglia through TLR2/TLR1 signaling, the microglial response to injury can be modulated in situ and is highly neuroprotective. Copyright © 2017 Elsevier Inc. All rights reserved.

Mapping of a Microbial Protein Domain Involved in Binding and Activation of the TLR2/TLR1 Heterodimer 1

PubMed Central

Liang, Shuang; Hosur, Kavita B.; Lu, Shanyun; Nawar, Hesham F.; Weber, Benjamin R.; Tapping, Richard I.; Connell, Terry D.; Hajishengallis, George

2009-01-01

LT-IIb-B5, a doughnut-shaped oligomeric protein from enterotoxigenic Escherichia coli, is known to activate the TLR2/TLR1 heterodimer (TLR2/1). We investigated the molecular basis of the LT-IIb-B5 interaction with TLR2/1 in order to define the structure-function relationship of LT-IIb-B5 and, moreover, to gain an insight into how TLR2/1 recognizes large, non-acylated protein ligands that cannot fit within its lipid-binding pockets, as previously shown for the Pam3CSK4 lipopeptide. We first identified four critical residues in the upper region of the LT-IIb-B5 pore: Corresponding point mutants (M69E, A70D, L73E, S74D) were defective in binding TLR2 or TLR1 and could not activate antigen-presenting cells, despite retaining full ganglioside-binding capacity. Point mutations in the TLR2/1 dimer interface, as determined in the crystallographic structure of the TLR2/1-Pam3CSK4 complex, resulted in diminished activation by both Pam3CSK4 and LT-IIb-B5. Docking analysis of the LT-IIb-B5 interaction with this apparently “predominant” activation conformation of TLR2/1 revealed that LT-IIb-B5 may primarily contact the convex surface of the TLR2 central domain. Although the TLR1/LT-IIb-B5 interface is relatively smaller, the leucine-rich repeat motifs 9–12 in the central domain of TLR1 were found to be critical for cooperative TLR2-induced cell activation by LT-IIb-B5. Moreover, the putative LT-IIb-B5 binding site overlaps partially with that of Pam3CSK4; consistent with this, Pam3CSK4 suppressed TLR2 binding of LT-IIb-B5, albeit not as potently as self-competitive inhibition. In conclusion, we identified the upper pore region of LT-IIb-B5 as a TLR2/1 interactive domain, which contacts the heterodimeric receptor at a site that is distinct from, though overlaps with, that of Pam3CSK4. PMID:19234193

Biological applications of an LCoS-based programmable array microscope (PAM)

NASA Astrophysics Data System (ADS)

Hagen, Guy M.; Caarls, Wouter; Thomas, Martin; Hill, Andrew; Lidke, Keith A.; Rieger, Bernd; Fritsch, Cornelia; van Geest, Bert; Jovin, Thomas M.; Arndt-Jovin, Donna J.

2007-02-01

We report on a new generation, commercial prototype of a programmable array optical sectioning fluorescence microscope (PAM) for rapid, light efficient 3D imaging of living specimens. The stand-alone module, including light source(s) and detector(s), features an innovative optical design and a ferroelectric liquid-crystal-on-silicon (LCoS) spatial light modulator (SLM) instead of the DMD used in the original PAM design. The LCoS PAM (developed in collaboration with Cairn Research, Ltd.) can be attached to a port of a(ny) unmodified fluorescence microscope. The prototype system currently operated at the Max Planck Institute incorporates a 6-position high-intensity LED illuminator, modulated laser and lamp light sources, and an Andor iXon emCCD camera. The module is mounted on an Olympus IX71 inverted microscope with 60-150X objectives with a Prior Scientific x,y, and z high resolution scanning stages. Further enhancements recently include: (i) point- and line-wise spectral resolution and (ii) lifetime imaging (FLIM) in the frequency domain. Multiphoton operation and other nonlinear techniques should be feasible. The capabilities of the PAM are illustrated by several examples demonstrating single molecule as well as lifetime imaging in live cells, and the unique capability to perform photoconversion with arbitrary patterns and high spatial resolution. Using quantum dot coupled ligands we show real-time binding and subsequent trafficking of individual ligand-growth factor receptor complexes on and in live cells with a temporal resolution and sensitivity exceeding those of conventional CLSM systems. The combined use of a blue laser and parallel LED or visible laser sources permits photoactivation and rapid kinetic analysis of cellular processes probed by photoswitchable visible fluorescent proteins such as DRONPA.

Nrf2 Regulates the Sensitivity of Mouse Keratinocytes to Nitrogen Mustard via Multidrug Resistance-Associated Protein 1 (Mrp1)

PubMed Central

Udasin, Ronald G.; Wen, Xia; Bircsak, Kristin M.; Aleksunes, Lauren M.; Shakarjian, Michael P.; Kong, Ah-Ng Tony; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

2016-01-01

Sulfur mustard and nitrogen mustard (mechlorethamine, HN2) are potent vesicants developed as chemical warfare agents. These electrophilic, bifunctional alkylating agents cause skin injury, including inflammation, edema, and blistering. HN2 covalently modifies macromolecules such as DNA, RNA, and proteins or is scavenged by glutathione, forming adducts that can contribute to toxicity. Multidrug resistance-associated protein 1 (Mrp1/MRP1) is a transmembrane ATPase known to efflux glutathione-conjugated electrophiles. In the present studies, we examined the effects of modulating Mrp1-mediated transport activity on the sensitivity of primary and PAM212 mouse keratinocytes to HN2. Primary keratinocytes, and to a lesser extent, PAM212 cells, express Mrp1 mRNA and protein and possess Mrp1 functional activity, as measured by calcein efflux. Sulforaphane, an activator of Nrf2, increased Mrp1 mRNA, protein, and functional activity in primary keratinocytes and PAM212 cells and decreased their sensitivity to HN2-induced growth inhibition (IC50 = 1.4 and 4.8 µM in primary keratinocytes and 1 and 13 µM in PAM212 cells, in the absence and presence of sulforaphane, respectively). The Mrp1 inhibitor, MK-571, reversed the effects of sulforaphane on HN2-induced growth inhibition in both primary keratinocytes and PAM212 cells. In primary keratinocytes from Nrf2−/− mice, sulforaphane had no impact on Mrp1 expression or activity, or on sensitivity to HN2, demonstrating that its effects depend on Nrf2. These data suggest that Mrp1-mediated efflux is important in regulating HN2-induced keratinocyte growth inhibition. Enhancing HN2 efflux from keratinocytes may represent a novel strategy for mitigating vesicant-induced cytotoxicity. PMID:26454883

A Comprehensive Evaluation of the Efficacy of Leading Oxime Therapies in Guinea Pigs Exposed to Organophosphorus Chemical Warfare Agents or Pesticides

PubMed Central

Wilhelm, Christina M.; Snider, Thomas H.; Babin, Michael C.; Jett, David A.; Platoff, Gennady E.; Yeung, David T.

2014-01-01

The currently fielded pre-hospital therapeutic regimen for the treatment of organophosphorus (OP) poisoning in the United States (U.S.) is the administration of atropine in combination with an oxime antidote (2-PAM Cl) to reactivate inhibited acetylcholinesterase (AChE). Depending on clinical symptoms, an anticonvulsant, e.g., diazepam, may also be administered. Unfortunately, 2-PAM Cl does not offer sufficient protection across the range of OP threat agents, and there is some question as to whether it is the most effective oxime compound available. The objective of the present study is to identify an oxime antidote, under standardized and comparable conditions, that offers protection at the FDA approved human equivalent dose (HED) of 2-PAM Cl against tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX, and the pesticides paraoxon, chlorpyrifos oxon, and phorate oxon. Male Hartley guinea pigs were subcutaneously challenged with a lethal level of OP and treated at approximately 1 min post challenge with atropine followed by equimolar oxime therapy (2-PAM Cl, HI-6 DMS, obidoxime Cl2, TMB-4, MMB4-DMS, HLö-7 DMS, MINA, and RS194B) or therapeutic-index (TI) level therapy (HI-6 DMS, MMB4-DMS, MINA, and RS194B). Clinical signs of toxicity were observed for 24 hours post challenge and blood cholinesterase [AChE and butyrylcholinesterase (BChE)] activity was analyzed utilizing a modified Ellman’s method. When the oxime is standardized against the HED of 2-PAM Cl for guinea pigs, the evidence from clinical observations, lethality, quality of life (QOL) scores, and cholinesterase reactivation rates across all OPs indicated that MMB4 DMS and HLö-7 DMS were the two most consistently efficacious oximes. PMID:25448441

Molecular and functional characterization of the American cockroach, Periplaneta americana, Rab5: the first exopterygotan low molecular weight ovarian GTPase during oogenesis.

PubMed

Elmogy, Mohamed; Mohamed, Amr A; Tufail, Muhammad; Uno, Tomohide; Takeda, Makio

2017-05-26

The small Rab GTPases are key regulators of membrane vesicle trafficking. Ovaries of Periplaneta americana (Linnaeus) (Blattodea: Blattidae) have small molecular weight GTP/ATP-binding proteins during early and late vitellogenic periods of oogenesis. However, the identification and characterization of the detected proteins have not been yet reported. Herein, we cloned a cDNA encoding Rab5 from the American cockroach, P. americana, ovaries (PamRab5). It comprises 796 bp, encoding a protein of 213 amino acid residues with a predicted molecular weight of 23.5 kDa. PamRab5 exists as a single-copy gene in the P. americana genome, as revealed by Southern blot analysis. An approximate 2.6 kb ovarian mRNA was transcribed especially at high levels in the previtellogenic ovaries, detected by Northern blot analysis. The muscle and head tissues also showed high levels of PamRab5 transcript. PamRab5 protein was localized, via immunofluorescence labeling, to germline-derived cells of the oocytes, very early during oocyte differentiation. Immunoblotting detected a ∼25 kDa signal as a membrane-associated form revealed after application of detergent in the extraction buffer, and 23 kDa as a cytosolic form consistent with the predicted molecular weight from amino acid sequence in different tissues including ovary, muscles and head. The PamRab5 during late vitellogenic periods is required to regulate the endocytotic machinery during oogenesis in this cockroach. This is the first report on Rab5 from a hemimetabolan, and presents an inaugural step in probing the molecular premises of insect oocyte endocytotic trafficking important for oogenesis and embryonic development. © 2017 Institute of Zoology, Chinese Academy of Sciences.

Architecture of the TIM23 inner mitochondrial translocon and interactions with the matrix import motor.

PubMed

Ting, See-Yeun; Schilke, Brenda A; Hayashi, Masaya; Craig, Elizabeth A

2014-10-10

Translocation of proteins from the cytosol across the mitochondrial inner membrane is driven by action of the matrix-localized multi-subunit import motor, which is associated with the TIM23 translocon. The architecture of the import apparatus is not well understood. Here, we report results of site-specific in vivo photocross-linking along with genetic and coimmunoprecipitation analyses dissecting interactions between import motor subunits and the translocon. The translocon is composed of the two integral membrane proteins Tim23 and Tim17, each containing four membrane-spanning segments. We found that Tim23 having a photoactivatable cross-linker in the matrix exposed loop between transmembrane domains 1 and 2 (loop 1) cross-linked to Tim44. Alterations in this loop destabilized interaction of Tim44 with the translocon. Analogously, Tim17 having a photoactivatable cross-linker in the matrix exposed loop between transmembrane segments 1 and 2 (loop 1) cross-linked to Pam17. Alterations in this loop caused destabilization of the interaction of Pam17 with the translocon. Substitution of individual photoactivatable residues in Tim44 and Pam17 in regions we previously identified as important for translocon association resulted in cross-linking to Tim23 and Tim17, respectively. Our results are consistent with a model in which motor association is achieved via interaction of Tim23 with Tim44, which serves as a scaffold for association of other motor components, and of Tim17 with Pam17. As both Tim44 and Pam17 have been implicated as regulatory subunits of the motor, this positioning is conducive for responding to conformational changes in the translocon upon a translocating polypeptide entering the channel. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Evaluation of the neuroactive steroid ganaxolone on social and repetitive behaviors in the BTBR mouse model of autism.

PubMed

Kazdoba, Tatiana M; Hagerman, Randi J; Zolkowska, Dorota; Rogawski, Michael A; Crawley, Jacqueline N

2016-01-01

Abnormalities in excitatory/inhibitory neurotransmission are hypothesized to contribute to autism spectrum disorder (ASD) etiology. BTBR T (+) Itpr3 (tf) /J (BTBR), an inbred mouse strain, displays social deficits and repetitive self-grooming, offering face validity to ASD diagnostic symptoms. Reduced GABAergic neurotransmission in BTBR suggests that GABAA receptor positive allosteric modulators (PAMs) could improve ASD-relevant BTBR phenotypes. The neuroactive steroid ganaxolone acts as a PAM, displaying anticonvulsant properties in rodent epilepsy models and an anxiolytic-like profile in the elevated plus-maze. We evaluated ganaxolone in BTBR and C57BL/6J mice in standardized assays for sociability and repetitive behaviors. Open field and anxiety-related behaviors were tested as internal controls and for comparison with the existing neuroactive steroid literature. Ganaxolone improved aspects of social approach and reciprocal social interactions in BTBR, with no effect on repetitive self-grooming, and no detrimental effects in C57BL/6J. Ganaxolone increased overall exploratory activity in BTBR and C57BL/6J in the open field, social approach, and elevated plus-maze, introducing a confound for the interpretation of social improvements. Allopregnanolone and diazepam similarly increased total entries in the elevated plus-maze, indicating that behavioral activation may be a general property of GABAA receptor PAMs in these strains. Ganaxolone shows promise for improving sociability. In addition, ganaxolone, as well as other GABAA receptor PAMs, enhanced overall BTBR activity. The translational implications of specific sociability improvements and nonspecific behavioral activation by ganaxolone in the BTBR model remain to be determined. Future studies to explore whether PAMs provide a novel profile with unique benefits for ASD treatment will be worthwhile.

Efficacy of Recommended Pre-Hospital Human Equivalent Doses of Atropine and Pralidoxime against the Toxic Effects of Carbamate Poisoning in the Hartley Guinea Pig

PubMed Central

Brittain, Matthew K.; McGarry, Kevin G.; Moyer, Robert A.; Babin, Michael C.; Jett, David A.; Platoff, Gennady E.; Yeung, David T.

2016-01-01

Purpose Aldicarb and methomyl are carbamate pesticides commonly implicated in human poisonings. The primary toxic mechanism of action for carbamate poisoning is cholinesterase (ChE) inhibition. As such, it is logical to assume that the currently accepted therapies for organophosphate poisoning [muscarinic antagonist atropine and the oxime acetylcholinesterase reactivator pralidoxime chloride (2-PAM Cl),], could afford therapeutic protection. However, oximes have been shown to be contraindicated for poisoning by some carbamates. Methods A protective ratio study was conducted in guinea pigs to evaluate the efficacy of atropine and 2-PAM Cl. ChE activity was determined in both the blood and cerebral cortex.. Results Co-administration of atropine free base (0.4 mg/kg) and 2-PAM Cl (25.7 mg/kg) demonstrated protective ratios of 2 and 3 against aldicarb and methomyl, respectively, relative to saline. The data reported here show that this protection was primarily mediated by the action of atropine. The reactivator 2-PAM Cl had neither positive nor negative effects on survival. Both blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were significantly reduced at 15 minutes post-challenge but gradually returned to normal within 24 h. Analysis of cerebral cortex showed that BChE, but not AChE, activity was reduced in animals that succumbed prior to 24 h after challenge. Conclusion The results suggest that co-administration of atropine and 2-PAM Cl at the currently recommended human equivalent doses for use in the pre-hospital setting to treat organophosphorus nerve agent and pesticide poisoning would likely also be effective against aldicarb or methomyl poisoning. PMID:27102179

Evaluation of the neuroactive steroid ganaxolone on social and repetitive behaviors in the BTBR mouse model of autism

PubMed Central

Kazdoba, Tatiana M.; Hagerman, Randi J.; Zolkowska, Dorota; Rogawski, Michael A.; Crawley, Jacqueline N.

2015-01-01

Rationale Abnormalities in excitatory/inhibitory neurotransmission are hypothesized to contribute to autism spectrum disorder (ASD) etiology. BTBR, an inbred mouse strain, displays social deficits and repetitive self-grooming, offering face validity to ASD diagnostic symptoms. Reduced GABAergic neurotransmission in BTBR suggests that GABAA receptor positive allosteric modulators (PAMs) could improve ASD-relevant BTBR phenotypes. The neuroactive steroid ganaxolone acts as a PAM, displaying anticonvulsant properties in rodent epilepsy models and an anxiolytic-like profile in the elevated plus-maze. Objectives We evaluated ganaxolone in BTBR and C57BL/6J mice in standardized assays for sociability and repetitive behaviors. Open field and anxiety-related behaviors were tested as internal controls and for comparison with the existing neuroactive steroid literature. Results Ganaxolone improved aspects of social approach and reciprocal social interactions in BTBR, with no effect on repetitive self-grooming, and no detrimental effects in C57BL/6J. Ganaxolone increased overall exploratory activity in BTBR and C57BL/6J in the open field, social approach, and elevated plus-maze, introducing a confound for the interpretation of social improvements. Allopregnanolone and diazepam similarly increased total entries in the elevated plus-maze, indicating that behavioral activation may be a general property of GABAA receptor PAMs in these strains. Conclusions Ganaxolone shows promise for improving sociability. In addition, ganaxolone, as well as other GABAA receptor PAMs, enhanced overall BTBR activity. The translational implications of specific sociability improvements and non-specific behavioral activation by ganaxolone in the BTBR model remains to be determined. Future studies to explore whether PAMs provide a novel profile with unique benefits for ASD treatment will be worthwhile. PMID:26525567

Selective Activation of M4 Muscarinic Acetylcholine Receptors Reverses MK-801-Induced Behavioral Impairments and Enhances Associative Learning in Rodents

PubMed Central

2015-01-01

Positive allosteric modulators (PAMs) of the M4 muscarinic acetylcholine receptor (mAChR) represent a novel approach for the treatment of psychotic symptoms associated with schizophrenia and other neuropsychiatric disorders. We recently reported that the selective M4 PAM VU0152100 produced an antipsychotic drug-like profile in rodents after amphetamine challenge. Previous studies suggest that enhanced cholinergic activity may also improve cognitive function and reverse deficits observed with reduced signaling through the N-methyl-d-aspartate subtype of the glutamate receptor (NMDAR) in the central nervous system. Prior to this study, the M1 mAChR subtype was viewed as the primary candidate for these actions relative to the other mAChR subtypes. Here we describe the discovery of a novel M4 PAM, VU0467154, with enhanced in vitro potency and improved pharmacokinetic properties relative to other M4 PAMs, enabling a more extensive characterization of M4 actions in rodent models. We used VU0467154 to test the hypothesis that selective potentiation of M4 receptor signaling could ameliorate the behavioral, cognitive, and neurochemical impairments induced by the noncompetitive NMDAR antagonist MK-801. VU0467154 produced a robust dose-dependent reversal of MK-801-induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions, including the touchscreen pairwise visual discrimination task in wild-type mice, but failed to reverse these stimulant-induced deficits in M4 KO mice. VU0467154 also enhanced the acquisition of both contextual and cue-mediated fear conditioning when administered alone in wild-type mice. These novel findings suggest that M4 PAMs may provide a strategy for addressing the more complex affective and cognitive disruptions associated with schizophrenia and other neuropsychiatric disorders. PMID:25137629

Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort: differences by age, race, and tumor characteristics.

PubMed

Sweeney, Carol; Bernard, Philip S; Factor, Rachel E; Kwan, Marilyn L; Habel, Laurel A; Quesenberry, Charles P; Shakespear, Kaylynn; Weltzien, Erin K; Stijleman, Inge J; Davis, Carole A; Ebbert, Mark T W; Castillo, Adrienne; Kushi, Lawrence H; Caan, Bette J

2014-05-01

Data are lacking to describe gene expression-based breast cancer intrinsic subtype patterns for population-based patient groups. We studied a diverse cohort of women with breast cancer from the Life After Cancer Epidemiology and Pathways studies. RNA was extracted from 1 mm punches from fixed tumor tissue. Quantitative reverse-transcriptase PCR was conducted for the 50 genes that comprise the PAM50 intrinsic subtype classifier. In a subcohort of 1,319 women, the overall subtype distribution based on PAM50 was 53.1% luminal A, 20.5% luminal B, 13.0% HER2-enriched, 9.8% basal-like, and 3.6% normal-like. Among low-risk endocrine-positive tumors (i.e., estrogen and progesterone receptor positive by immunohistochemistry, HER2 negative, and low histologic grade), only 76.5% were categorized as luminal A by PAM50. Continuous-scale luminal A, luminal B, HER2-enriched, and normal-like scores from PAM50 were mutually positively correlated. Basal-like score was inversely correlated with other subtypes. The proportion with non-luminal A subtype decreased with older age at diagnosis, P Trend < 0.0001. Compared with non-Hispanic Whites, African American women were more likely to have basal-like tumors, age-adjusted OR = 4.4 [95% confidence intervals (CI), 2.3-8.4], whereas Asian and Pacific Islander women had reduced odds of basal-like subtype, OR = 0.5 (95% CI, 0.3-0.9). Our data indicate that over 50% of breast cancers treated in the community have luminal A subtype. Gene expression-based classification shifted some tumors categorized as low risk by surrogate clinicopathologic criteria to higher-risk subtypes. Subtyping in a population-based cohort revealed distinct profiles by age and race. ©2014 AACR.

CasA mediates Cas3-catalyzed target degradation during CRISPR RNA-guided interference.

PubMed

Hochstrasser, Megan L; Taylor, David W; Bhat, Prashant; Guegler, Chantal K; Sternberg, Samuel H; Nogales, Eva; Doudna, Jennifer A

2014-05-06

In bacteria, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) DNA-targeting complex Cascade (CRISPR-associated complex for antiviral defense) uses CRISPR RNA (crRNA) guides to bind complementary DNA targets at sites adjacent to a trinucleotide signature sequence called the protospacer adjacent motif (PAM). The Cascade complex then recruits Cas3, a nuclease-helicase that catalyzes unwinding and cleavage of foreign double-stranded DNA (dsDNA) bearing a sequence matching that of the crRNA. Cascade comprises the CasA-E proteins and one crRNA, forming a structure that binds and unwinds dsDNA to form an R loop in which the target strand of the DNA base pairs with the 32-nt RNA guide sequence. Single-particle electron microscopy reconstructions of dsDNA-bound Cascade with and without Cas3 reveal that Cascade positions the PAM-proximal end of the DNA duplex at the CasA subunit and near the site of Cas3 association. The finding that the DNA target and Cas3 colocalize with CasA implicates this subunit in a key target-validation step during DNA interference. We show biochemically that base pairing of the PAM region is unnecessary for target binding but critical for Cas3-mediated degradation. In addition, the L1 loop of CasA, previously implicated in PAM recognition, is essential for Cas3 activation following target binding by Cascade. Together, these data show that the CasA subunit of Cascade functions as an essential partner of Cas3 by recognizing DNA target sites and positioning Cas3 adjacent to the PAM to ensure cleavage.

Colon Cancer Survival With Herbal Medicine and Vitamins Combined With Standard Therapy in a Whole-Systems Approach: Ten-Year Follow-up Data Analyzed With Marginal Structural Models and Propensity Score Methods

PubMed Central

McCulloch, Michael; Broffman, Michael; van der Laan, Mark; Hubbard, Alan; Kushi, Lawrence; Abrams, Donald I.; Gao, Jin; Colford, John M.

2014-01-01

Although localized colon cancer is often successfully treated with surgery, advanced disease requires aggressive systemic therapy that has lower effectiveness. Approximately 30% to 75% of patients with colon cancer use complementary and alternative medicine (CAM), but there is limited formal evidence of survival efficacy. In a consecutive case series with 10-year follow-up of all colon cancer patients (n = 193) presenting at a San Francisco Bay-Area center for Chinese medicine (Pine Street Clinic, San Anselmo, CA), the authors compared survival in patients choosing short-term treatment lasting the duration of chemotherapy/radiotherapy with those continuing long-term. To put these data into the context of treatment responses seen in conventional medical practice, they also compared survival with Pan-Asian medicine + vitamins (PAM+V) with that of concurrent external controls from Kaiser Permanente Northern California and California Cancer Registries. Kaplan-Meier, traditional Cox regression, and more modern methods were used for causal inference—namely, propensity score and marginal structural models (MSMs), which have not been used before in studies of cancer survival and Chinese herbal medicine. PAM+V combined with conventional therapy, compared with conventional therapy alone, reduced the risk of death in stage I by 95%, stage II by 64%, stage III by 29%, and stage IV by 75%. There was no significant difference between short-term and long-term PAM+V. Combining PAM+V with conventional therapy improved survival, compared with conventional therapy alone, suggesting that prospective trials combining PAM+V with conventional therapy are justified. PMID:21964510

A high capacity data centre network: simultaneous 4-PAM data at 20 Gbps and 2 GHz phase modulated RF clock signal over a single VCSEL carrier

NASA Astrophysics Data System (ADS)

Isoe, G. M.; Wassin, S.; Gamatham, R. R. G.; Leitch, A. W. R.; Gibbon, T. B.

2017-11-01

Optical fibre communication technologies are playing important roles in data centre networks (DCNs). Techniques for increasing capacity and flexibility for the inter-rack/pod communications in data centres have drawn remarkable attention in recent years. In this work, we propose a low complexity, reliable, alternative technique for increasing DCN capacity and flexibility through multi-signal modulation onto a single mode VCSEL carrier. A 20 Gbps 4-PAM data signal is directly modulated on a single mode 10 GHz bandwidth VCSEL carrier at 1310 nm, therefore, doubling the network bit rate. Carrier spectral efficiency is further maximized by modulating its phase attribute with a 2 GHz reference frequency (RF) clock signal. We, therefore, simultaneously transmit a 20 Gbps 4-PAM data signal and a phase modulated 2 GHz RF signal using a single mode 10 GHz bandwidth VCSEL carrier. It is the first time a single mode 10 GHz bandwidth VCSEL carrier is reported to simultaneously transmit a directly modulated 4-PAM data signal and a phase modulated RF clock signal. A receiver sensitivity of -10. 52 dBm was attained for a 20 Gbps 4-PAM VCSEL transmission. The 2 GHz phase modulated RF clock signal introduced a power budget penalty of 0.21 dB. Simultaneous distribution of both data and timing signals over shared infrastructure significantly increases the aggregated data rate at different optical network units within the DCN, without expensive optics investment. We further demonstrate on the design of a software-defined digital signal processing assisted receiver to efficiently recover the transmitted signal without employing costly receiver hardware.

The α7 nicotinic receptor dual allosteric agonist and positive allosteric modulator GAT107 reverses nociception in mouse models of inflammatory and neuropathic pain

PubMed Central

Wilkerson, Jenny L; Kulkarni, Abhijit; Toma, Wisam; AlSharari, Shakir; Gul, Zulfiye; Lichtman, Aron H; Papke, Roger L; Damaj, M Imad

2016-01-01

Background and Purpose Orthosteric agonists and positive allosteric modulators (PAMs) of the α7 nicotinic ACh receptor (nAChR) represent novel therapeutic approaches for pain modulation. Moreover, compounds with dual function as allosteric agonists and PAMs, known as ago‐PAMs, add further regulation of receptor function. Experimental Approach Initial studies examined the α7 ago‐PAM, GAT107, in the formalin, complete Freund's adjuvant (CFA), LPS inflammatory pain models, the chronic constriction injury neuropathic pain model and the tail flick and hot plate acute thermal nociceptive assays. Additional studies examined the locus of action of GAT107 and immunohistochemical markers in the dorsal horn of the spinal cord in the CFA model. Key Results Complementary pharmacological and genetic approaches confirmed that the dose‐dependent antinociceptive effects of GAT107 were mediated through α7 nAChR. However, GAT107 was inactive in the tail flick and hot plate assays. In addition, GAT107 blocked conditioned place aversion elicited by acetic acid injection. Furthermore, intrathecal, but not intraplantar, injections of GAT107 reversed nociception in the CFA model, suggesting a spinal component of action. Immunohistochemical evaluation revealed an increase in the expression of astrocyte‐specific glial fibrillary acidic protein and phosphorylated p38MAPK within the spinal cords of mice treated with CFA, which was attenuated by intrathecal GAT107 treatment. Importantly, GAT107 did not elicit motor impairment and continued to produce antinociceptive effects after subchronic administration in both phases of the formalin test. Conclusions and Implications Collectively, these results provide the first proof of principle that α7 ago‐PAMs represent an effective pharmacological strategy for treating inflammatory and neuropathic pain. PMID:27243753

Inhibitory effects of palmitoylcarnitine and lysophosphatidylcholine on the sodium current of cardiac ventricular cells.

PubMed

Sato, T; Kiyosue, T; Arita, M

1992-01-01

We investigated the effects of ischemia-related amphipathic compounds, palmitoylcarnitine (PamCar, 0.5-50 microM) and lysophosphatidylcholine (lysoPtdCho, 5-50 microM) on sodium current (INa) of guinea-pig ventricular myocytes. The cells were perfused with low-Na+ (60 mM) Tyrode's solution, and Ca2+ and K+ currents were blocked by external Co2+ (3 mM) and internal Cs+ (140 mM), respectively. INa was elicited by depolarizing voltage steps from a holding potential of -100 mV at a temperature of 33 degrees C. PamCar (5 microM) decreased the peak INa (attained at -20 mV or -30 mV) from 6.1 +/- 2.1 nA to 3.9 +/- 1.4 nA (n = 11), or by 36.1% within 2 min, and shifted the curve of steady-state INa inactivation by 5.4 mV in the positive direction (from -76.3 +/- 4.6 mV, control to -70.9 +/- 4.0 mV, in PamCar, n = 4). Partial restoration of the amplitude and the shift of the steady-state inactivation curve of INa was attained after washout of PamCar. In contrast, lysoPtdCho at concentrations over 10 microM irreversibly depressed the INa within 0.5-3 min and the reduction of INa was followed by cell contracture or cell death (n = 9). The survival time, defined as a period from the start of lysoPtdCho application to the time of the last successful recording of the INa (before evolution of sudden changes in the holding current), depended on the concentrations of lysoPtdCho. Both PamCar and lysoPtdCho retarded the time course of activation and inactivation of INa.(ABSTRACT TRUNCATED AT 250 WORDS)

A structure-activity analysis of the variation in oxime efficacy against nerve agents

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

Maxwell, Donald M.; Koplovitz, Irwin; Worek, Franz

2008-09-01

A structure-activity analysis was used to evaluate the variation in oxime efficacy of 2-PAM, obidoxime, HI-6 and ICD585 against nerve agents. In vivo oxime protection and in vitro oxime reactivation were used as indicators of oxime efficacy against VX, sarin, VR and cyclosarin. Analysis of in vivo oxime protection was conducted with oxime protective ratios (PR) from guinea pigs receiving oxime and atropine therapy after sc administration of nerve agent. Analysis of in vitro reactivation was conducted with second-order rate contants (k{sub r2}) for oxime reactivation of agent-inhibited acetylcholinesterase (AChE) from guinea pig erythrocytes. In vivo oxime PR and inmore » vitro k{sub r2} decreased as the volume of the alkylmethylphosphonate moiety of nerve agents increased from VX to cyclosarin. This effect was greater with 2-PAM and obidoxime (> 14-fold decrease in PR) than with HI-6 and ICD585 (< 3.7-fold decrease in PR). The decrease in oxime PR and k{sub r2} as the volume of the agent moiety conjugated to AChE increased was consistent with a steric hindrance mechanism. Linear regression of log (PR-1) against log (k{sub r2} {center_dot} [oxime dose]) produced two offset parallel regression lines that delineated a significant difference between the coupling of oxime reactivation and oxime protection for HI-6 and ICD585 compared to 2-PAM and obidoxime. HI-6 and ICD585 appeared to be 6.8-fold more effective than 2-PAM and obidoxime at coupling oxime reactivation to oxime protection, which suggested that the isonicotinamide group that is common to both of these oximes, but absent from 2-PAM and obidoxime, is important for oxime efficacy.« less

Imidazenil prevention of alprazolam-induced acquisition deficit in patas monkeys is devoid of tolerance

PubMed Central

Auta, James; Guidotti, Alessandro; Costa, Erminio

2000-01-01

The partial allosteric modulators (PAMs) of γ-aminobutyric acid-gated Cl− current intensities at γ-aminobutyric acid type A receptors have high affinity but low intrinsic efficacy on benzodiazepine recognition sites. Unlike the full allosteric modulators (FAM), like alprazolam, triazolam, and diazepam, PAMs are virtually devoid of unwanted side effects, including tolerance. Imidazenil (IMD) is a PAM that elicits potent anxiolytic and anticonvulsant actions in rodents and nonhuman primates and retains its anticonvulsant and anxiolytic effects, even in rodents that are tolerant to FAMs. IMD antagonizes the side effects of FAMs in rodents and nonhuman primates. Using patas monkeys and a multiple schedule with repeated acquisition and performance of chain responses, we report that IMD administration for 17 days antagonized without showing tolerance ALP-induced disruption of acquisition. PMID:10696114

Photoacoustic microscopy of bilirubin in tissue phantoms

NASA Astrophysics Data System (ADS)

Zhou, Yong; Zhang, Chi; Yao, Da-Kang; Wang, Lihong V.

2012-12-01

Determining both bilirubin's concentration and its spatial distribution are important in disease diagnosis. Here, for the first time, we applied quantitative multiwavelength photoacoustic microscopy (PAM) to detect bilirubin concentration and distribution simultaneously. By measuring tissue-mimicking phantoms with different bilirubin concentrations, we showed that the root-mean-square error of prediction has reached 0.52 and 0.83 mg/dL for pure bilirubin and for blood-mixed bilirubin detection (with 100% oxygen saturation), respectively. We further demonstrated the capability of the PAM system to image bilirubin distribution both with and without blood. Finally, by underlaying bilirubin phantoms with mouse skins, we showed that bilirubin can be imaged with consistent accuracy down to >400 μm in depth. Our results show that PAM has potential for noninvasive bilirubin monitoring in vivo, as well as for further clinical applications.

Low-cost and miniaturized 100-Gb/s (2 × 50 Gb/s) PAM-4 TO-packaged ROSA for data center networks.

PubMed

Kang, Sae-Kyoung; Huh, Joon Young; Lee, Jie Hyun; Lee, Joon Ki

2018-03-05

We design and implement a cost-effective and compact 100-Gb/s (2 × 50 Gb/s) PAM-4 receiver optical sub-assembly (ROSA) by using a TO-can package instead of an expensive box-type package. It consists of an optical demultiplexer, two PIN-PDs and a 2-channel linear transimpedance amplifier. The components are passively aligned and assembled using alignment marks engraved on each part. With a real-time PAM-4 DSP chip, we measured the back-to-back receiver sensitivities of the 100-Gb/s ROSA based on TO-56 to be less than -13.2 dBm for both channels at a bit error rate of 2.4e-4. The crosstalk penalty due to the adjacent channel interference was observed around 0.1 dB.

DU Processing Efficiency and Reclamation: Plasma Arc Melting

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

Imhoff, Seth D.; Aikin, Jr., Robert M.; Swenson, Hunter

The work described here corresponds to one piece of a larger effort to increase material usage efficiency during DU processing operations. In order to achieve this goal, multiple technologies and approaches are being tested. These technologies occupy a spectrum of technology readiness levels (TRLs). Plasma arc melting (PAM) is one of the technologies being investigated. PAM utilizes a high temperature plasma to melt materials. Depending on process conditions, there are potential opportunities for recycling and material reclamation. When last routinely operational, the LANL research PAM showed extremely promising results for recycling and reclamation of DU and DU alloys. The currentmore » TRL is lower due to machine idleness for nearly two decades, which has proved difficult to restart. This report describes the existing results, promising techniques, and the process of bringing this technology back to readiness at LANL.« less

Designing Biological Systems for Sustainability and Programmed Environmental Interface (2011 JGI User Meeting)

ScienceCinema

Silver, Pamela

2018-02-13

The U.S. Department of Energy Joint Genome Institute (JGI) invited scientists interested in the application of genomics to bioenergy and environmental issues, as well as all current and prospective users and collaborators, to attend the annual DOE JGI Genomics of Energy & Environment Meeting held March 22-24, 2011 in Walnut Creek, Calif. The emphasis of this meeting was on the genomics of renewable energy strategies, carbon cycling, environmental gene discovery, and engineering of fuel-producing organisms. The meeting features presentations by leading scientists advancing these topics. Pam Silver of Harvard University gives a presentation on "Designing Biological Systems for Sustainability and Programmed Environmental Interface" at the 6th annual Genomics of Energy & Environment Meeting on March 23, 2011.

Isolation and molecular typing of Naegleria fowleri from the brain of a cow that died of primary amebic meningoencephalitis.

PubMed

Visvesvara, Govinda S; De Jonckheere, Johan F; Sriram, Rama; Daft, Barbara

2005-08-01

Naegleria fowleri causes an acute and rapidly fatal central nervous system infection called primary amebic meningoencephalitis (PAM) in healthy children and young adults. We describe here the identification of N. fowleri isolated from the brain of one of several cows that died of PAM based on sequencing of the internal transcribed spacers, including the 5.8S rRNA genes.

Identifying Insurgent Infrastructure

DTIC Science & Technology

1990-01-07

104, Underorounds. 7. DA PAM 550-104, Underoroundag p. 52. 8. DA PAM 550-106, Communist Insuroent InfragtructurA, p. 145. Also, LTC Rolando Garcia ...1985), p. 6-2. 30. LTC Rolando Garcia , Philippine Constabulary, interviews by author, 7 and 13 November 1989, Fort Leavenworth, KS. The CPP model was...Assistant U.S. Attorney, U.S. Department of Justice, Western District of Missouri. Inter-view by author. Kansas City, Missouri. 16 October 1989. Garcia

Charging Toward an Even Brighter Future

DTIC Science & Technology

2011-01-01

counterparts, but rather seeking to be treated with equal recognition in all aspects such as protocol , etiquette , housing, and evaluation reporting...grade as well as GS-12 or higher. When consid- ered with other regulations such as DA PAM 600-60 (A Guide to Protocol and Etiquette for Official...PAM 600-60 (A Guide to Protocol and Etiquette for Official Enter- tainment) contains a table which lists the precedence of civilian and military

Copper-mediated homogeneous living radical polymerization of acrylamide with waxy potato starch-based macroinitiator.

PubMed

Fan, Yifei; Cao, Huatang; van Mastrigt, Frank; Pei, Yutao; Picchioni, Francesco

2018-07-15

Cu 0 -mediated living radical polymerization (Cu 0 -mediated LRP) was employed in this research for the synthesis of starch-g-polyacrylamide (St-g-PAM). The use of a controlled radical grafting technique is necessary, as compared to the traditional free-radical polymerization methods, in order to obtain a well-defined structure of the final product. This is in turn essential for studying the relationship between such structure and the end-properties. Waxy potato starch-based water-soluble macroinitiator was first synthesized by esterification with 2-bromopropionyl bromide in the mixture of dimethylacetamide and lithium chloride. With the obtained macroinitiator, St-g-PAM was homogeneously synthesized by aqueous Cu 0 -mediated LRP using CuBr/hexamethylated tris(2-aminoethyl)amine (Me 6 Tren) as catalyst. The successful synthesis of the macroinitiator and St-g-PAM was proved by NMR, FT-IR, SEM, XRD and TGA analysis. The molecular weight and polydispersity of PAM chains were analyzed by gel permeation chromatography (GPC) after hydrolyzing the starch backbone. Monomer conversion was monitored by gas chromatography (GC), on the basis of which the kinetics were determined. A preliminarily rheological study was performed on aqueous solutions of the prepared materials. Copyright © 2018 Elsevier Ltd. All rights reserved.

An evaluation of the mobility of pathogen indicators, Escherichia coli and bacteriophage MS-2, in a highly weathered tropical soil under unsaturated conditions

USGS Publications Warehouse

Wong, T.-P.; Byappanahalli, M.; Yoneyama, B.; Ray, C.

2008-01-01

Laboratory column experiments were conducted to study the effects of anionic polyacrylamide (PAM) polymer and surfactant linear alkylbenzene sulfonate (LAS) on the movement of Escherichia coli and the FRNA phage MS-2. The study was designed to evaluate if PAM or PAM + LAS would enhance the mobility of human pathogens in tropical soils under unsaturated conditions. No breakthrough of phage was observed in a 10 cm column after passing 100 pore volumes of solution containing 1 ?? 108 plaque-forming units (PFU)/ml. In later experiments, after passing 10-20 pore volumes of influent containing 1 ?? 108/ml MS-2 or E. coli through 15 cm columns, the soil was sliced and the organisms eluted. Phage moved slightly deeper in the polymer-treated column than in the control column. There was no measurable difference in the movement of E. coli in either polymer-treated or control columns. The properties of the soil (high amounts of metal oxides, kaolinitic clay), unsaturated flow conditions, and relatively high ionic strengths of the leaching solution attributed to significant retention of these indicators. The impacts of PAM and LAS on the mobility of E. coli or MS-2 phage in the chosen soils were not significant. ?? IWA Publishing 2008.

Case Series of Naegleria fowleri Primary Ameobic Meningoencephalitis from Karachi, Pakistan.

PubMed

Ghanchi, Najia K; Jamil, Bushra; Khan, Erum; Ansar, Zeeshan; Samreen, Azra; Zafar, Afia; Hasan, Zahra

2017-11-01

Naegleria fowleri causes primary amoebic meningoencephalitis (PAM) which is almost always fatal. Naegleria fowleri is waterborne, and its infections are usually associated with aquatic activities but it can also be transmitted via the domestic water supply. An increasing number of N. fowleri cases have been reported from Pakistan. Improved methods for diagnosis are required. We report the utility of polymerase chain reaction (PCR) for the diagnosis of N. fowleri in patients suspected of PAM. One hundred and sixteen cases suspected of having PAM were examined. Cerebrospinal fluid (CSF) specimens were tested at the Aga Khan University Hospital, Karachi. Nineteen CSF specimens were positive for N. fowleri using PCR. Naegleria fowleri positive patients had a median age of 28 years and were 84% male and 16% female. Overall, CSF wet preparation microscopy was performed in 85 (73%) cases and identified that seven specimens were positive for motile trophozoites. The CSF wet preparation results were available for 15 of the 19 N. fowleri PCR positive CSF samples; seven (40%) wet preparations were positive. Our data highlight the threat of N. fowleri infection as a cause of PAM. It also emphasizes the utility of the PCR-based diagnosis of the amoeba for early diagnosis and management of the disease.

In Vivo Near Infrared Virtual Intraoperative Surgical Photoacoustic Optical Coherence Tomography

PubMed Central

Lee, Donghyun; Lee, Changho; Kim, Sehui; Zhou, Qifa; Kim, Jeehyun; Kim, Chulhong

2016-01-01

Since its first implementation in otolaryngological surgery nearly a century ago, the surgical microscope has improved the accuracy and the safety of microsurgeries. However, the microscope shows only a magnified surface view of the surgical region. To overcome this limitation, either optical coherence tomography (OCT) or photoacoustic microscopy (PAM) has been independently combined with conventional surgical microscope. Herein, we present a near-infrared virtual intraoperative photoacoustic optical coherence tomography (NIR-VISPAOCT) system that combines both PAM and OCT with a conventional surgical microscope. Using optical scattering and absorption, the NIR-VISPAOCT system simultaneously provides surgeons with real-time comprehensive biological information such as tumor margins, tissue structure, and a magnified view of the region of interest. Moreover, by utilizing a miniaturized beam projector, it can back-project 2D cross-sectional PAM and OCT images onto the microscopic view plane. In this way, both microscopic and cross-sectional PAM and OCT images are concurrently displayed on the ocular lens of the microscope. To verify the usability of the NIR-VISPAOCT system, we demonstrate simulated surgeries, including in vivo image-guided melanoma resection surgery and in vivo needle injection of carbon particles into a mouse thigh. The proposed NIR-VISPAOCT system has potential applications in neurosurgery, ophthalmological surgery, and other microsurgeries. PMID:27731390

Adhesion of and to soil in runoff as influenced by polyacrylamide.

PubMed

Bech, Tina B; Sbodio, Adrian; Jacobsen, Carsten S; Suslow, Trevor

2014-11-01

Polyacrylamide (PAM) is used in agriculture to reduce soil erosion and has been reported to reduce turbidity, nutrients, and pollutants in surface runoff water. The objective of this work was to determine the effect of PAM on the concentration of enteric bacteria in surface runoff by comparing four enteric bacteria representing phenotypically different motility and hydrophobicity from three soils. Results demonstrated that bacterial surface runoff was differentially influenced by the PAM treatment. Polyacrylamide treatment increased surface runoff for adhered and planktonic cells from a clay soil; significantly decreased surface runoff of adhered bacteria, while no difference was observed for planktonic bacteria from the sandy loam; and significantly decreased the surface runoff of planktonic cells, while no difference was observed for adhered bacteria from the clay loam. Comparing strains from a final water sample collected after 48 h showed a greater loss of while serovar Poona was almost not detected. Thus, (i) the PAM efficiency in reducing the concentration of enteric bacteria in surface runoff was influenced by soil type and (ii) variation in the loss of enteric bacteria highlights the importance of strain-specific properties that may not be captured with general fecal indicator bacteria. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Solids, organic load and nutrient concentration reductions in swine waste slurry using a polyacrylamide (PAM)-aided solids flocculation treatment.

PubMed

Walker, Paul; Kelley, Tim

2003-11-01

Increased swine production results in concentration of wastes generated within a limited geographical area, which may lead to land application rates exceeding the local or regional assimilatory capacity. This may result in pollutant transfer through surface water or soil-groundwater systems, environmental degradation, and/or odor concerns. Existing swine waste pit storage and lagoon treatment technologies may be inadequate to store or treat waste prior to land application without these concerns resulting. Efficient swine waste solids separation may reduce environmental health concerns and generate a value-added bioresource (solids). This study evaluated the efficiency of a polyacrylamide (PAM) flocculant-aided solids separation treatment to reduce pollution indicator concentrations in raw (untreated) swine waste slurry. Swine waste slurry solids separation efficiency through gravity settling (sedimentation) was evaluated before and after the addition of a proprietary polymeric (PAM) flocculant. Results indicated that polymer amendments at concentrations of 62.5-750 mg/l improved slurry solids separation efficiency and significantly reduced concentrations of other associated aquatic pollution indicators in a majority of analyses conducted (33 of 50 total analyses conducted). Results also suggested that PAM-aided solids separation from swine waste slurry might facilitate further treatment and/or disposal and therefore reduce associated environmental degradation potential.

Cross-cultural adaptation and construct validity of the Korean version of a physical activity measure for community-dwelling elderly.

PubMed

Choi, Bongsam

2018-01-01

[Purpose] This study aimed to cross-cultural adapt and validate the Korean version of an physical activity measure (K-PAM) for community-dwelling elderly. [Subjects and Methods] One hundred and thirty eight community-dwelling elderlies, 32 males and 106 female, participated in the study. All participants were asked to fill out a fifty-one item questionnaire measuring perceived difficulty in the activities of daily living (ADL) for the elderly. One-parameter model of item response theory (Rasch analysis) was applied to determine the construct validity and to inspect item-level psychometric properties of 51 ADL items of the K-PAM. [Results] Person separation reliability (analogous to Cronbach's alpha) for internal consistency was ranging 0.93 to 0.94. A total of 16 items was misfit to the Rasch model. After misfit item deletion, 35 ADL items of the K-PAM were placed in an empirically meaningful hierarchy from easy to hard. The item-person map analysis delineated that the item difficulty was well matched for the elderlies with moderate and low ability except for high ceilings. [Conclusion] Cross-cultural adapted K-PAM was shown to be sufficient for establishing construct validity and stable psychometric properties confirmed by person separation reliability and fit statistics.

Breast imaging using the Twente photoacoustic mammoscope (PAM): new clinical measurements

NASA Astrophysics Data System (ADS)

Heijblom, Michelle; Piras, Daniele; Ten Tije, Ellen; Xia, Wenfeng; van Hespen, Johan; Klaase, Joost; van den Engh, Frank; van Leeuwen, Ton; Steenbergen, Wiendelt; Manohar, Srirang

2011-07-01

Worldwide, yearly about 450,000 women die from the consequences of breast cancer. Current imaging modalities are not optimal in discriminating benign from malignant tissue. Visualizing the malignancy-associated increased hemoglobin concentration might significantly improve early diagnosis of breast cancer. Since photoacoustic imaging can visualize hemoglobin in tissue with optical contrast and ultrasound-like resolution, it is potentially an ideal method for early breast cancer imaging. The Twente Photoacoustic Mammoscope (PAM) has been developed specifically for breast imaging. Recently, a large clinical study has been started in the Medisch Spectrum Twente in Oldenzaal using PAM. In PAM, the breast is slightly compressed between a window for laser light illumination and a flat array ultrasound detector. The measurements are performed using a Q-switched Nd:YAG laser, pulsed at 1064 nm and a 1 MHz unfocused ultrasound detector array. Three-dimensional data are reconstructed using a delay and sum reconstruction algorithm. Those reconstructed images are compared with conventional imaging and histopathology. In the first phase of the study 12 patients with a malignant lesion and 2 patients with a benign cyst have been measured. The results are used to guide developments in photoacoustic mammography in order to pave the way towards an optimal technique for early diagnosis of breast cancer.

Detection, Mapping, and Quantification of Single Walled Carbon Nanotubes in Histological Specimens with Photoacoustic Microscopy

PubMed Central

Mikos, Antonios G.; Jansen, John A.; Shroyer, Kenneth R.; Wang, Lihong V.; Sitharaman, Balaji

2012-01-01

Aims In the present study, the efficacy of multi-scale photoacoustic microscopy (PAM) was investigated to detect, map, and quantify trace amounts [nanograms (ng) to micrograms (µg)] of SWCNTs in a variety of histological tissue specimens consisting of cancer and benign tissue biopsies (histological specimens from implanted tissue engineering scaffolds). Materials and Methods Optical-resolution (OR) and acoustic-resolution (AR) - Photoacoustic microscopy (PAM) was employed to detect, map and quantify the SWCNTs in a variety of tissue histological specimens and compared with other optical techniques (bright-field optical microscopy, Raman microscopy, near infrared (NIR) fluorescence microscopy). Results Both optical-resolution and acoustic-resolution PAM, allow the detection and quantification of SWCNTs in histological specimens with scalable spatial resolution and depth penetration. The noise-equivalent detection sensitivity to SWCNTs in the specimens was calculated to be as low as ∼7 pg. Image processing analysis further allowed the mapping, distribution, and quantification of the SWCNTs in the histological sections. Conclusions The results demonstrate the potential of PAM as a promising imaging technique to detect, map, and quantify SWCNTs in histological specimens, and could complement the capabilities of current optical and electron microscopy techniques in the analysis of histological specimens containing SWCNTs. PMID:22496892

Short and long time effects of low temperature Plasma Activated Media on 3D multicellular tumor spheroids

NASA Astrophysics Data System (ADS)

Judée, Florian; Fongia, Céline; Ducommun, Bernard; Yousfi, Mohammed; Lobjois, Valérie; Merbahi, Nofel

2016-02-01

This work investigates the regionalized antiproliferative effects of plasma-activated medium (PAM) on colon adenocarcinoma multicellular tumor spheroid (MCTS), a model that mimics 3D organization and regionalization of a microtumor region. PAM was generated by dielectric barrier plasma jet setup crossed by helium carrier gas. MCTS were transferred in PAM at various times after plasma exposure up to 48 hours and effect on MCTS growth and DNA damage were evaluated. We report the impact of plasma exposure duration and delay before transfer on MCTS growth and DNA damage. Local accumulation of DNA damage revealed by histone H2AX phosphorylation is observed on outermost layers and is dependent on plasma exposure. DNA damage is completely reverted by catalase addition indicating that H2O2 plays major role in observed genotoxic effect while growth inhibitory effect is maintained suggesting that it is due to others reactive species. SOD and D-mannitol scavengers also reduced DNA damage by 30% indicating that and OH* are involved in H2O2 formation. Finally, PAM is able to retain its cytotoxic and genotoxic activity upon storage at +4 °C or -80 °C. These results suggest that plasma activated media may be a promising new antitumor strategy for colorectal cancer tumors.

Space Station - An integrated approach to operational logistics support

NASA Technical Reports Server (NTRS)

Hosmer, G. J.

1986-01-01

Development of an efficient and cost effective operational logistics system for the Space Station will require logistics planning early in the program's design and development phase. This paper will focus on Integrated Logistics Support (ILS) Program techniques and their application to the Space Station program design, production and deployment phases to assure the development of an effective and cost efficient operational logistics system. The paper will provide the methodology and time-phased programmatic steps required to establish a Space Station ILS Program that will provide an operational logistics system based on planned Space Station program logistics support.

Feasibility and Effectiveness of Online Physical Activity Advice Based on a Personal Activity Monitor: Randomized Controlled Trial

PubMed Central

Slootmaker, Sander M; Schuit, Albertine J; Seidell, Jacob C; Van Mechelen, Willem

2009-01-01

Background Inactive people are often not aware of the fact that they are insufficiently active. Providing insight into their actual physical activity (PA) levels may raise awareness and could, in combination with tailored PA advice, stimulate a physically active lifestyle. Objective This study evaluated the feasibility and effectiveness of a 3-month intervention in which Dutch office workers were provided with a personal activity monitor (PAM) coupled to simple and concise Web-based tailored PA advice (PAM COACH). Method Participants were randomly assigned to the 3-month PAM intervention (n = 51) or received a single written information brochure with brief general PA recommendations (n = 51). Study outcome measures were changes in PA (recall of minutes per week spent on PA, as measured by the Activity Questionnaire for Adolescents and Adults), determinants of PA, aerobic fitness, and body composition. Follow-up measurements were performed immediately after the 3-month intervention and at 8-months, 5 months after the end of the 3-month intervention period. Results A total of 102 workers, 23 to 39 years old, completed the baseline measurement at the worksite. 48 completed the 3-month follow up and 38 the 8-month follow-up in the intervention group, 50 completed the 3-month follow up and 42 the 8-month follow up in the control group. 35 out of 48 (73%) participants in the PAM intervention group reported wearing the PAM regularly, and the PAM COACH was used almost once a week; 24 out of 46 (52%) PAM users set a personal goal, and 33 (72%) entered their favorite activities on the website. Main reasons for not using these items were lack of interest or not being able to find the item on the website. The majority of PAM users (34 out of 46, 74%) read the advice, of whom 14 (39%) found it unappealing. After the 3-month intervention, no significant intervention effect was observed (adjusted difference in min/week) for sedentary behavior (β = 10, 95% CI = −435 to 455), light-intensity PA (β = −129, 95% CI = −337 to 79), moderate-intensity PA (β = −13, 95% CI = −89 to 63), vigorous-intensity PA (β= −6, 95% CI = −75 to 62), and moderate- to vigorous-intensity PA (β = −23, 95% CI = −121 to 76). No significant intervention effect was observed in the PA outcomes at the 8-month follow-up. For the determinants of PA, aerobic fitness, and body composition, no statistically significant intervention effect was observed in the total study population immediately after the 3-month intervention or the 8-month follow-up. Conclusions The intervention appeared to be easily applicable to real-life settings. The intervention was ineffective in improving PA behavior or its determinants in healthy office workers. More attention should have been given to the quality and appropriateness of the tailored advice. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 93896459; http://www.controlled-trials.com/ISRCTN93896459/ (Archived by WebCite at http://www.webcitation.org/5iR3mf7ex) PMID:19674956

A fluorescence-based bioassay for aquatic macrophytes and its suitability for effect analysis of non-photosystem II inhibitors.

PubMed

Küster, Anette; Pohl, Korinna; Altenburger, Rolf

2007-09-01

BACKGROUND, GOALS AND SCOPE: During the last years the miniaturization of toxicity test systems for rapid and parallel measurements of large quantities of samples has often been discussed. For unicellular algae as well as for aquatic macrophytes, fluorescence-based miniaturized test systems have been introduced to analyze photosystem II (PSII) inhibitors. Nevertheless, high-throughput screening should also guarantee the effect detection of a broad range of toxicants in order to ensure routinely applicable, high-throughput measuring device experiments which can cover a broad range of toxicants and modes of action others than PSII inhibition. Thus, the aim of this study was to establish a fast and reproducible measuring system for non-PSII inhibitors for aquatic macrophyte species to overcome major limitations for use. A newly developed imaging pulse-amplitude-modulated chlorophyll fluorometer (I-PAM) was applied as an effect detector in short-term bioassays with the aquatic macrophyte species Lemna minor. This multiwell-plate based measuring device enabled the incubation and measurement of up to 24 samples in parallel. The chemicals paraquat-dichloride, alizarine and triclosan were chosen as representatives for the toxicant groups of non-PSII herbicides, polycyclic aromatic hydrocarbons (PAHs) and pharmaceuticals and personal care products (PPCPs), which are often detected in the aquatic environment. The I-PAM was used (i) to establish and validate the sensitivity of the test system to the three non-PSII inhibitors, (ii) to compare the test systems with standardized and established biotests for aquatic macrophytes, and (iii) to define necessary time scales in aquatic macrophyte testing. For validation of the fluorescence-based assay, the standard growth test with L. minor (ISO/DIS 20079) was performed in parallel for each chemical. The results revealed that fluorescence-based measurements with the I-PAM allow rapid and parallel analysis of large amounts of aquatic macrophyte samples. The I-PAM enabled the recording of concentration-effect-curves with L. minor samples on a 24-well plate with single measurements. Fluorescence-based concentration-effect-curves could be detected for all three chemicals after only 1 h of incubation. After 4-5 h incubation time, the maximum inhibition of fluorescence showed an 80-100% effect for the chemicals tested. The EC50 after 24 h incubation were estimated to be 0.06 mg/L, 0.84 mg/L and 1.69 mg/L for paraquat-dichloride, alizarine and triclosan, respectively. The results obtained with the I-PAM after 24 h for the herbicide paraquat-dichloride and the polycyclic aromatic hydrocarbon alizarine were in good accordance with median effective concentrations (EC50s) obtained by the standardized growth test for L. minor after 7 d incubation (0.09 mg/L and 0.79 mg/L for paraquat-dichloride and alizarine, respectively). Those results were in accordance with literature findings for the two chemicals. In contrast, fluorescence-based EC50 of the antimicrobial agent triclosan proved to be two orders of magnitude greater when compared to the standard growth test with 7 d incubation time (0.026 mg/L) as well as with literature findings. Typically, aquatic macrophyte testing is very time consuming and relies on laborious experimental set-ups. The I-PAM measuring device enabled fast effect screening for the three chemicals tested. While established test systems for aquatic macrophytes need incubation times of > or = 7 d, the I-PAM can detect inhibitory effects much earlier (24 h), even if inhibition of chemicals is not specifically associated with PSII. Thus, the fluorescence-based bioassay with the I-PAM offers a promising approach for the miniaturization and high-throughput testing of chemicals with aquatic macrophytes. For the chemical triclosan, however, the short-term effect prediction with the I-PAM has been shown to be less sensitive than with long-term bioassays, which might be due to physicochemical substance properties such as lipophilicity. The results of this study show that the I-PAM represents a promising tool for decreasing the incubation times of aquatic macrophyte toxicity testing to about 24 h as a supplement to existing test batteries. The applicability of this I-PAM bioassay on emergent and submerged aquatic macrophyte species should be investigated in further studies. Regarding considerations that physicochemical properties of the tested substances might play an important role in microplate bioassays, the I-PAM bioassay should either be accompanied by evaluating physicochemical properties modeled from structural information prior to an experimental investigation, or by intensified chemical analyses to identify and determine nominal concentrations of the toxicants tested. The chemicals paraquat-dichloride, alizarine and triclosan were chosen as representatives for the toxicant groups of non-PSII herbicides, PAHs and PPCPs which are often detected in the aquatic environment. Nevertheless, in order to ensure a routinely applicable measuring device, experiments with a broader range of toxicants and samples of surface and/or waste waters are necessary.

Experimental demonstration of PAM-DWMT for passive optical network

NASA Astrophysics Data System (ADS)

Lin, Bangjiang; Zhang, Kaiwei; Tang, Xuan; Ghassemlooy, Zabih; Lin, Chun; Zhou, Zhenlei

2018-07-01

We experimentally demonstrate a discrete wavelet multitone (DWMT) modulation scheme based on pulse amplitude modulation (PAM) for next generation passive optical network (PON), which offers high tolerance against chromatic dispersion, high spectral efficiency, low peak to average power ratio (PAPR) and low side lobes. The experimental results show the chromatic dispersion induced power penalties are negligible after 20km fiber transmission. Compared with orthogonal frequency division multiplexing (OFDM), DWMT offers a better receiver sensitivity.

Isolation and Molecular Typing of Naegleria fowleri from the Brain of a Cow That Died of Primary Amebic Meningoencephalitis

PubMed Central

Visvesvara, Govinda S.; De Jonckheere, Johan F.; Sriram, Rama; Daft, Barbara

2005-01-01

Naegleria fowleri causes an acute and rapidly fatal central nervous system infection called primary amebic meningoencephalitis (PAM) in healthy children and young adults. We describe here the identification of N. fowleri isolated from the brain of one of several cows that died of PAM based on sequencing of the internal transcribed spacers, including the 5.8S rRNA genes. PMID:16081978

The Design, Synthesis and Screening of Potential Pyridinium Oxime Prodrugs

DTIC Science & Technology

1984-02-01

In vitro and in vivo ( mice ) screening of these compounds indicates some promise as AChE regenerators, prompting the preparation of gram quantities of...PAM 6 (E-I) have been synthesized and characterized. In vitro (immobilized-AChE) and in vivo ( mice ) screening of these compounds showed promising...screening assay. An ED5 0 determination (diisopropylfluorophosphate [DFPJ challenge/ mice ) showed 5-I-2-PAM (5) to be significantly more effective than 2

Local Minima Free Parameterized Appearance Models

PubMed Central

Nguyen, Minh Hoai; De la Torre, Fernando

2010-01-01

Parameterized Appearance Models (PAMs) (e.g. Eigentracking, Active Appearance Models, Morphable Models) are commonly used to model the appearance and shape variation of objects in images. While PAMs have numerous advantages relative to alternate approaches, they have at least two drawbacks. First, they are especially prone to local minima in the fitting process. Second, often few if any of the local minima of the cost function correspond to acceptable solutions. To solve these problems, this paper proposes a method to learn a cost function by explicitly optimizing that the local minima occur at and only at the places corresponding to the correct fitting parameters. To the best of our knowledge, this is the first paper to address the problem of learning a cost function to explicitly model local properties of the error surface to fit PAMs. Synthetic and real examples show improvement in alignment performance in comparison with traditional approaches. PMID:21804750

Photoacoustic microscopy of bilirubin in tissue phantoms

PubMed Central

Zhou, Yong; Zhang, Chi; Yao, Da-Kang

2012-01-01

Abstract. Determining both bilirubin’s concentration and its spatial distribution are important in disease diagnosis. Here, for the first time, we applied quantitative multiwavelength photoacoustic microscopy (PAM) to detect bilirubin concentration and distribution simultaneously. By measuring tissue-mimicking phantoms with different bilirubin concentrations, we showed that the root-mean-square error of prediction has reached 0.52 and 0.83  mg/dL for pure bilirubin and for blood-mixed bilirubin detection (with 100% oxygen saturation), respectively. We further demonstrated the capability of the PAM system to image bilirubin distribution both with and without blood. Finally, by underlaying bilirubin phantoms with mouse skins, we showed that bilirubin can be imaged with consistent accuracy down to >400  μm in depth. Our results show that PAM has potential for noninvasive bilirubin monitoring in vivo, as well as for further clinical applications. PMID:23235894

Photoacoustic imaging of teeth for dentine imaging and enamel characterization

NASA Astrophysics Data System (ADS)

Periyasamy, Vijitha; Rangaraj, Mani; Pramanik, Manojit

2018-02-01

Early detection of dental caries, cracks and lesions is needed to prevent complicated root canal treatment and tooth extraction procedures. Resolution of clinically used x-ray imaging is low, hence optical imaging techniques such as optical coherence tomography, fluorescence imaging, and Raman imaging are widely experimented for imaging dental structures. Photoacoustic effect is used in photon induced photoacoustic streaming technique to debride the root canal. In this study, the extracted teeth were imaged using photoacoustic tomography system at 1064 nm. The degradation of enamel and dentine is an indicator of onset of dental caries. Photoacoustic microscopy (PAM) was used to study the tooth enamel. Images were acquired using acoustic resolution PAM system. This was done to identify microscopic cracks and dental lesion at different anatomical sites (crown and cementum). The PAM tooth profile is an indicator of calcium distribution which is essential for demineralization studies.

Use of a single bipolar electrode in the posterior arytenoid muscles for bilateral monitoring of the recurrent laryngeal nerves in thyroid surgery.

PubMed

Haerle, Stephan; Sidler, D; Linder, Th; Mueller, W

2008-12-01

The aims were to assess the technical feasibility of using a single electrode in the posterior arytenoid muscles (PAM) for intraoperative monitoring of the recurrent laryngeal nerve (RLN) in thyroid surgery, to validate the new method against the insertion of electrodes placed in the vocal cord muscle, and to report the results of the clinical application of the new concept. A total of 52 patients were enrolled. The handling and safety of RLN monitoring was tested by simultaneous registration of the EMG response from vocal fold electrodes and PAM electrodes. Acoustically and electromyographically we found nearly the same values for the arytenoid muscles as for the vocal folds, although the signals taken from the vocal folds were slightly stronger. PAM recording using a single bipolar electrode is technically feasible and as reliable compared to the standard vocal cord monitoring.

Region-of-interest breast images with the Twente Photoacoustic Mammoscope (PAM)

NASA Astrophysics Data System (ADS)

Manohar, Srirang; Vaartjes, Sanne E.; van Hespen, Johan G. C.; Klaase, Joost M.; van den Engh, Frank M.; The, Andy K. H.; Steenbergen, Wiendelt; van Leeuwen, Ton G.

2007-02-01

The Twente Photoacoustic Mammoscope (PAM) is based on generating laser-induced ultrasound from absorbing structures in the breast. The heart of the instrument is a flat PVDF based detector matrix comprising 590 active elements. The exciting source is an Nd:YAG laser operating at 1064 nm with 5 ns pulses. The instrument is built around a hospital bed. A study protocol was designed to explore the feasibility of using the photoacoustic technique as embodied in PAM to detect cancer in the breasts of patients with suspect/symptomatic breasts. The protocol was approved by a Medical Ethics testing committee and the instrument approved for laser and electrical safety. The protocol was executed at the Medisch Spectrum Twente by using the mammoscope to obtain photoacoustic region-of-interest (ROI) images of the suspect/symptomatic breasts. We report on one case and compare the photoacoustic images obtained with x-ray mammograms and ultrasound images.

Generation-3 programmable array microscope (PAM) with digital micro-mirror device (DMD)

NASA Astrophysics Data System (ADS)

De Beule, Pieter A. A.; de Vries, Anthony H. B.; Arndt-Jovin, Donna J.; Jovin, Thomas M.

2011-03-01

We report progress on the construction of an optical sectioning programmable array microscope (PAM) implemented with a digital micro-mirror device (DMD) spatial light modulator (SLM) utilized for both fluorescence illumination and detection. The introduction of binary intensity modulation at the focal plane of a microscope objective in a computer controlled pixilated mode allows the recovery of an optically sectioned image. Illumination patterns can be changed very quickly, in contrast to static Nipkow disk or aperture correlation implementations, thereby creating an optical system that can be optimized to the optical specimen in a convenient manner, e.g. for patterned photobleaching, photobleaching reduction, or spatial superresolution. We present a third generation (Gen-3) dual path PAM module incorporating the 25 kHz binary frame rate TI 1080p DMD and a newly developed optical system that offers diffraction limited imaging with compensation of tilt angle distortion.

Effect of the electric field pattern on the generation of fast electrons in front of lower hybrid launchers

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

Valade, Laurent, E-mail: laurent.valade@cea.fr; Ekedahl, Annika; Colas, Laurent

2015-12-10

The effect of the detailed waveguide spectrum on the electron acceleration has been studied for the 3.7 GHz LHCD launchers in Tore Supra, i.e. the ITER-like passive-active multijunction (PAM) launcher and the fully-active-multijunction (FAM) launcher, using test electron modelling technique. The detailed launched antenna wave spectrum is used as input to the code that computes the dynamics of the electrons in the electric field. Comparison with the LHCD launchers in EAST, operating at 2.45 GHz and 4.6 GHz, has also been made. The simulations show that the PAM-design generates lower flux of fast electrons than FAM-launchers, this could be themore » consequence of the wider waveguide of PAM-launcher (14.65 mm for Tore-Supra) than FAM-launcher (8 mm for Tore-Supra)« less

Microcapillary imaging of lamina cribrosa in porcine eyes using photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Moothanchery, Mohesh; Chuangsuwanich, Thanadet; Yan, Alvan Tsz Chung; Schmetterer, Leopold; Girard, Michael J. A.; Pramanik, Manojit

2018-02-01

In order to understand the pathophysiology of glaucoma, Lamina cribrosa (LC) perfusion needs to be the subject of thorough investigation. It is currently difficult to obtain high resolution images of the embedded microcapillary network of the LC using conventional imaging techniques. In this study, an optical resolution photoacoustic microscopy (OR-PAM) system was used for imaging lamina cribrosa of an ex vivo porcine eye. Extrinsic contrast agent was used to perfuse the eye via its ciliary arteries. The OR-PAM system have a lateral resolution of 4 μm and an axial resolution of 30 μm. The high resolution system could able resolve a perfused LC microcapillary network to show vascular structure within the LC thickness. OR-PAM could be a promising imaging modality to study the LC perfusion and hence could be used to elucidate the hemodynamic aspect of glaucoma.

Anticonvulsant effects of structurally diverse GABA(B) positive allosteric modulators in the DBA/2J audiogenic seizure test: Comparison to baclofen and utility as a pharmacodynamic screening model.

PubMed

Brown, Jordan W; Moeller, Achim; Schmidt, Martin; Turner, Sean C; Nimmrich, Volker; Ma, Junli; Rueter, Lynne E; van der Kam, Elizabeth; Zhang, Min

2016-02-01

The GABA(B) receptor has been indicated as a promising target for multiple CNS-related disorders. Baclofen, a prototypical orthosteric agonist, is used clinically for the treatment of spastic movement disorders, but is associated with unwanted side-effects, such as sedation and motor impairment. Positive allosteric modulators (PAM), which bind to a topographically-distinct site apart from the orthosteric binding pocket, may provide an improved side-effect profile while maintaining baclofen-like efficacy. GABA, the major inhibitory neurotransmitter in the CNS, plays an important role in the etiology and treatment of seizure disorders. Baclofen is known to produce anticonvulsant effects in the DBA/2J mouse audiogenic seizure test (AGS), suggesting it may be a suitable assay for assessing pharmacodynamic effects. Little is known about the effects of GABA(B) PAMs, however. The studies presented here sought to investigate the AGS test as a pharmacodynamic (PD) screening model for GABA(B) PAMs by comparing the profile of structurally diverse PAMs to baclofen. GS39783, rac-BHFF, CMPPE, A-1295120 (N-(3-(4-(4-chloro-3-fluorobenzyl)-6-methoxy-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide), and A-1474713 (N-(3-(4-(4-chlorobenzyl)-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide) all produced robust, dose-dependent anticonvulsant effects; a similar profile was observed with baclofen. Pre-treatment with the GABA(B) antagonist SCH50911 completely blocked the anticonvulsant effects of baclofen and CMPPE in the AGS test, indicating such effects are likely mediated by the GABA(B) receptor. In addition to the standard anticonvulsant endpoint of the AGS test, video tracking software was employed to assess potential drug-induced motor side-effects during the acclimation period of the test. This analysis was sensitive to detecting drug-induced changes in total distance traveled, which was used to establish a therapeutic index (TI = hypoactivity/anticonvulsant effects). Calculated TIs for A-1295120, CMPPE, rac-BHFF, GS39783, and A-1474713 were 5.31x, 5.00x, 4.74x, 3.41x, and 1.83x, respectively, whereas baclofen was <1. The results presented here suggest the DBA/2J mouse AGS test is a potentially useful screening model for detecting PD effects of GABA(B) PAMs and can provide an initial read-out on target-related motor side-effects. Furthermore, an improved TI was observed for PAMs compared to baclofen, indicating the PAM approach may be a viable therapeutic alternative to baclofen. Copyright © 2015 Elsevier Ltd. All rights reserved.

KENNEDY SPACE CENTER, FLA. - Lisa Malone, deputy director of External Relations and Business Development at KSC, emcees a ceremony in the Space Station Processing Facility to highlight the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope) arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Speakers at the ceremony included KSC Director Roy Bridges Jr.; NASA's Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, and William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - Lisa Malone, deputy director of External Relations and Business Development at KSC, emcees a ceremony in the Space Station Processing Facility to highlight the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope) arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Speakers at the ceremony included KSC Director Roy Bridges Jr.; NASA's Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, and William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

Space station program phase B definition: Nuclear reactor-powered space station cost and schedules

NASA Technical Reports Server (NTRS)

1971-01-01

Tabulated data are presented on the costs, schedules, and technical characteristics for the space station phases C and D program. The work breakdown structure, schedule data, program ground rules, program costs, cost-estimating rationale, funding schedules, and supporting data are included.

Photochemical aging of aerosol particles in different air masses arriving at Baengnyeong Island, Korea

NASA Astrophysics Data System (ADS)

Kang, Eunha; Lee, Meehye; Brune, William H.; Lee, Taehyoung; Park, Taehyun; Ahn, Joonyoung; Shang, Xiaona

2018-05-01

Atmospheric aerosol particles are a serious health risk, especially in regions like East Asia. We investigated the photochemical aging of ambient aerosols using a potential aerosol mass (PAM) reactor at Baengnyeong Island in the Yellow Sea during 4-12 August 2011. The size distributions and chemical compositions of aerosol particles were measured alternately every 6 min from the ambient air or through the highly oxidizing environment of a potential aerosol mass (PAM) reactor. Particle size and chemical composition were measured by using the combination of a scanning mobility particle sizer (SMPS) and a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS). Inside the PAM reactor, O3 and OH levels were equivalent to 4.6 days of integrated OH exposure at typical atmospheric conditions. Two types of air masses were distinguished on the basis of the chemical composition and the degree of aging: air transported from China, which was more aged with a higher sulfate concentration and O : C ratio, and the air transported across the Korean Peninsula, which was less aged with more organics than sulfate and a lower O : C ratio. For both episodes, the particulate sulfate mass concentration increased in the 200-400 nm size range when sampled through the PAM reactor. A decrease in organics was responsible for the loss of mass concentration in 100-200 nm particles when sampled through the PAM reactor for the organics-dominated episode. This loss was especially evident for the m/z 43 component, which represents less oxidized organics. The m/z 44 component, which represents further oxidized organics, increased with a shift toward larger sizes for both episodes. It is not possible to quantify the maximum possible organic mass concentration for either episode because only one OH exposure of 4.6 days was used, but it is clear that SO2 was a primary precursor of secondary aerosol in northeast Asia, especially during long-range transport from China. In addition, inorganic nitrate evaporated in the PAM reactor as sulfate was added to the particles. These results suggest that the chemical composition of aerosols and their degree of photochemical aging, particularly for organics, are also crucial in determining aerosol mass concentrations.

Mitigation of water repellency in burned soils applying hydrophillic polymers

NASA Astrophysics Data System (ADS)

Neris, Jonay; de la Torre, Sara; Vidal-Vazquez, Eva; Lado, Marcos

2017-04-01

In this study, the effect of fire on water repellency was analyzed in soils from different parent materials, as well as the suitability of anionic polyacrylamide (PAM) to reduce water repellency in these soils. Samples were collected in four different sites where wildfires took place: two in the Canary Islands, with soils developed on volcanic materials, and two in Galicia (NW Spain), with soils developed on plutonic rocks. In Galicia, two soil samples were collected in each site, one in the burnt area and one in an adjacent unburnt area. In the Canary Islands, four samples were collected from each site, three inside the burnt area where the soils were affected by different fire intensities, and one in an unburnt adjacent area. Samples were air-dried and sieved by a 2-mm mesh sieve. Water repellency was measured using the Water Drop Penetration Time test. An amount of 10 g of soil was placed in a tray. Five drops of deionized water were place on the soil surface with a pipette, and the time for each drop to fully penetrate into the soil was recorded. PAM solution was applied to the burnt soils simulating a field application rate of 1gm-2. The polymer used was Superfloc A-110 (Kemira Water Solutions BV, Holland) with 1x107 Da molecular weigth and 15% hydrolysis. PAM was sprayed on the soil surface as solution with a concentration 0.2 g/L. After the application, the samples were dried and the WDPT test was performed. Three replicates for each treatment and soil were used, and the treatments included: dry soil, dry soil after a wetting treatment, dry PAM-treated soil. The results showed that water repellency was modified by fire differently in the various soils. In hydrophilic soils and soils with low water repellency, water repellency was increased after the action of fire. In soils with noticeable initial water repellency, this was reduced or eliminated after the fire. Wetting repellent soils caused a decrease in water repellency most probably because of the spatial redistribution of hydrophobic organic compounds that caused water repellency. The addition of PAM further reduced in all of the cases. The application of PAM could be an effective method for mitigation of water repellency in burnt soils.

T227. THE METABOTROPIC GLUTAMATE RECEPTOR SUBTYPE 1 REGULATES STRIATAL DOPAMINE RELEASE VIA AN ENDOCANNABINOID-DEPENDENT MECHANISM: IMPLICATIONS FOR THE TREATMENT OF SCHIZOPHRENIA

PubMed Central

Yohn, Samantha; Covey, Daniel; Foster, Daniel; Moehle, Mark; Galbraith, Jordan; Cheer, Joseph; Lindsley, Craig; Jeffrey Conn, P

2018-01-01

Abstract Background Clinical and preclinical studies suggest that selective activators of the muscarinic M4 receptor have exciting potential as a novel approach for treatment of schizophrenia. M4 reduces striatal dopamine (DA) though release of endocannabinoids (eCB), providing a mechanism for local effects on DA signaling in the striatum. M4 signals through Gαi/o and does not couple to Gαq/11 or induce calcium (Ca++) mobilization. This raises the possibility that M4-induced eCB release and inhibition of DA release may require co-activation of another receptor that activates Gαq/11. If so, this receptor could provide a novel target that may be more proximal to inhibition of DA release. Interestingly, the group 1 metabotropic glutamate (mGlu) receptors (mGlu1 and Glu5), couple to Gαq/11 and activate eCB signaling in multiple brain regions. Methods We tested the hypothesis that M4-induced reductions in DA release and subsequent antipsychotic-effect requires co-activation of group 1 mGlu receptors. The effect of M4 activation on electrically-evoked DA release in striatal slices was assessed using fast-scan cyclic voltammetry (FSCV) in the absence or presence of selective negative allosteric modulators (NAMs) of group 1 mGlu receptor subtypes. To evaluate the potential role of mGlu1, we determined the effects of a selective mGlu1 positive allosteric modulators (PAMs) on striatal DA release and antipsychotic-like activity in rodent models that are dependent on increased DA transmission. Since reductions in DA signaling, including D1 signaling have been implicated in reduced motivation, we also determined the effects of an mGlu1 PAM, M4 PAM, and the typical antipsychotic haloperidol on motivational responding in a progressive ratio (PR) schedule. Results We now present exciting new data in which we found that activation of mGlu1 through application of exogenous agonists or selective stimulation of thalamostriatal afferents induces a reduction of striatal DA release and that selective mGlu1 PAMs have robust antipsychotic-like effects in rodent models. Interestingly, our studies also suggest that mGlu1 activation is required for M4 PAM-induced inhibition of DA release and antipsychotic-like effects. However, in contrast to available antipsychotic agents, the present results and previous studies suggest that mGlu1 and M4 PAMs reduce DA signaling through local release of an eCB from striatal SPNs and activation of CB2 receptors on neighboring DA terminals to reduce DA release. While these studies suggest that the effects of M4 PAMs on DA release require activation of mGlu1, we have also found that these targets have important differences. Most notably, M4 PAMs also directly inhibits D1 signaling in D1-SPN terminals in the substatnia nigra pars reticulata (SNr). Unlike M4, mGlu1 does not directly inhibit DA D1 receptor signaling and does not induce behavioral changes that could be associated with negative symptoms. Discussion Our findings are especially interesting in light of recent findings that multiple loss of function single nucleotide polymorphisms (SNPs) in the human gene encoding mGlu1 (GRM1) are associated with schizophrenia, and points to GRM1/mGlu1 as a gene within the “druggable genome” that could be targeted for treatment of schizophrenia. Recent clinical imaging studies suggesting that symptoms in schizophrenia patients are associated with selective increases in striatal DA signaling and while extrastriatal regions display hypo-dopaminergic function; thus, mGlu1 and M4 PAMs may provide a mechanism for selective inhibition of DA release in striatal regions that are important for antipsychotic efficacy, without further disruptions in extrastriatal DA signaling.

Creating and parameterizing patient-specific deep brain stimulation pathway-activation models using the hyperdirect pathway as an example.

PubMed

Gunalan, Kabilar; Chaturvedi, Ashutosh; Howell, Bryan; Duchin, Yuval; Lempka, Scott F; Patriat, Remi; Sapiro, Guillermo; Harel, Noam; McIntyre, Cameron C

2017-01-01

Deep brain stimulation (DBS) is an established clinical therapy and computational models have played an important role in advancing the technology. Patient-specific DBS models are now common tools in both academic and industrial research, as well as clinical software systems. However, the exact methodology for creating patient-specific DBS models can vary substantially and important technical details are often missing from published reports. Provide a detailed description of the assembly workflow and parameterization of a patient-specific DBS pathway-activation model (PAM) and predict the response of the hyperdirect pathway to clinical stimulation. Integration of multiple software tools (e.g. COMSOL, MATLAB, FSL, NEURON, Python) enables the creation and visualization of a DBS PAM. An example DBS PAM was developed using 7T magnetic resonance imaging data from a single unilaterally implanted patient with Parkinson's disease (PD). This detailed description implements our best computational practices and most elaborate parameterization steps, as defined from over a decade of technical evolution. Pathway recruitment curves and strength-duration relationships highlight the non-linear response of axons to changes in the DBS parameter settings. Parameterization of patient-specific DBS models can be highly detailed and constrained, thereby providing confidence in the simulation predictions, but at the expense of time demanding technical implementation steps. DBS PAMs represent new tools for investigating possible correlations between brain pathway activation patterns and clinical symptom modulation.

Photoinhibition in common atlantic macroalgae measured on site in Gran Canaria

NASA Astrophysics Data System (ADS)

Häder, D.-P.; Porst, M.; Lebert, M.

2001-03-01

The photosynthetic quantum yield was analysed in four common atlantic macroalgae, the Rhodophytes Gelidium arbuscula and Halopithys incurvus and the Phaeophytes Halopteris scoparia and Lobophora variegata in Gran Canaria, Canary Islands at their growth site. The fluorescence parameters were measured using a portable pulse amplitude modulated (PAM) fluorometer (PAM 2000) instrument and a diving PAM under water without removing the thalli from their growth sites. Solar radiation was monitored continuously above and under water during the whole experimental period using two three-channel dosimeters (European light dosimeter network; ELDONET) (Real Time Computer, Möhrendorf, Germany). These instruments measure solar radiation in three wavelength ranges, ultraviolet (UV)-A, UV-B and photosynthetic active radiation (PAR). In all four algae the effective photosynthetic quantum yield decreased significantly from the optimal values measured after dark adaptation due to exposure to 15 min solar radiation, but at least partially recovered subsequently in the shade within several hours. Increasing the exposure period to 30 min intensified the photoinhibition. In some algae no recovery was observed after this treatment and in others no significant recovery could be detected. Exposure to unfiltered solar radiation caused a significantly higher photoinhibition than PAR-only radiation or PAR plus UV-A. A substantial inhibition was found in all algae at their growth sites in the water column when the sun was at high angles, as measured with the diving PAM.

Different effects of 25-kDa amelogenin on the proliferation, attachment and migration of various periodontal cells

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

Li, Xiting; Shu, Rong, E-mail: shurong123@hotmail.com; Liu, Dali

Previous studies have assumed that amelogenin is responsible for the therapeutic effect of the enamel matrix derivative (EMD) in periodontal tissue healing and regeneration. However, it is difficult to confirm this hypothesis because both the EMD and the amelogenins are complex mixtures of multiple proteins. Further adding to the difficulties is the fact that periodontal tissue regeneration involves various types of cells and a sequence of associated cellular events including the attachment, migration and proliferation of various cells. In this study, we investigated the potential effect of a 25-kDa recombinant porcine amelogenin (rPAm) on primarily cultured periodontal ligament fibroblasts (PDLF),more » gingival fibroblasts (GF) and gingival epithelial cells (GEC). The cells were treated with 25-kDa recombinant porcine amelogenin at a concentration of 10 {mu}g/mL. We found that rPAm significantly promoted the proliferation and migration of PDLF, but not their adhesion. Similarly, the proliferation and adhesion of GF were significantly enhanced by treatment with rPAm, while migration was greatly inhibited. Interestingly, this recombinant protein inhibited the growth rate, cell adhesion and migration of GEC. These data suggest that rPAm may play an essential role in periodontal regeneration through the activation of periodontal fibroblasts and inhibition of the cellular behaviors of gingival epithelial cells.« less

Primitive Auditory Memory Is Correlated with Spatial Unmasking That Is Based on Direct-Reflection Integration

PubMed Central

Li, Huahui; Kong, Lingzhi; Wu, Xihong; Li, Liang

2013-01-01

In reverberant rooms with multiple-people talking, spatial separation between speech sources improves recognition of attended speech, even though both the head-shadowing and interaural-interaction unmasking cues are limited by numerous reflections. It is the perceptual integration between the direct wave and its reflections that bridges the direct-reflection temporal gaps and results in the spatial unmasking under reverberant conditions. This study further investigated (1) the temporal dynamic of the direct-reflection-integration-based spatial unmasking as a function of the reflection delay, and (2) whether this temporal dynamic is correlated with the listeners’ auditory ability to temporally retain raw acoustic signals (i.e., the fast decaying primitive auditory memory, PAM). The results showed that recognition of the target speech against the speech-masker background is a descending exponential function of the delay of the simulated target reflection. In addition, the temporal extent of PAM is frequency dependent and markedly longer than that for perceptual fusion. More importantly, the temporal dynamic of the speech-recognition function is significantly correlated with the temporal extent of the PAM of low-frequency raw signals. Thus, we propose that a chain process, which links the earlier-stage PAM with the later-stage correlation computation, perceptual integration, and attention facilitation, plays a role in spatially unmasking target speech under reverberant conditions. PMID:23658664

The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a γδ T cell population in humanized mice

PubMed Central

Zheng, Jian; Liu, Yinping; Sia, Sin Fun; Liu, Ming; Qin, Gang; Xiang, Zheng; Lam, Kwok-Tai

2011-01-01

There are few antiviral drugs for treating influenza, and the emergence of antiviral resistance has further limited the available therapeutic options. Furthermore, antivirals are not invariably effective in severe influenza, such as that caused by H5N1 viruses. Thus, there is an urgent need to develop alternative therapeutic strategies. Here, we show that human Vγ9Vδ2 T cells expanded by the aminobisphosphonate pamidronate (PAM) kill influenza virus–infected cells and inhibit viral replication in vitro. In Rag2−/−γc−/− immunodeficient mice reconstituted with human peripheral mononuclear cells (huPBMCs), PAM reduces disease severity and mortality caused by human seasonal H1N1 and avian H5N1 influenza virus, and controls the lung inflammation and viral replication. PAM has no such effects in influenza virus–infected Rag2−/−γc−/− mice reconstituted with Vγ9Vδ2 T cell–depleted huPBMCs. Our study provides proof-of-concept of a novel therapeutic strategy for treating influenza by targeting the host rather than the virus, thereby reducing the opportunity for the emergence of drug-resistant viruses. As PAM has been commonly used to treat osteoporosis and Paget’s disease, this new application of an old drug potentially offers a safe and readily available option for treating influenza. PMID:21708931

A study of photochemical againg of ambient air using Potential Aerosol Mass (PAM) chamber under the different sources and types of emissions

NASA Astrophysics Data System (ADS)

Lee, T.; Son, J.; Kim, J.; Kim, S.; Sung, K.; Park, G.; Link, M.; Park, T.; Kim, K.; Kang, S.; Ban, J.; Kim, D. S.

2016-12-01

Recent research proposed that Secondary Aerosol (SA) is important class of predicting future climate change scenarios, health effect, and a general air quality. However, there has been lack of studies to investigate SA formation all over the world. This study tried to focus on understanding potential secondary aerosol formation and its local impact by the photochemical aging of inorganic and organic aerosols in the ambient air using the Potential Aerosol Mass (PAM) chamber under the different sources and types of emissions. PAM chamber manufactured by Aerodyne make an oxidizing environment that simulates oxidation processes on timescales of 12-15 hrs in the atmosphere. Chemical compositions of ambient aerosol and aerosol that was aged in the PAM chamber were alternately measured every 2-minutes using the High Resolution-Time of Flight-Aerosol Mass Spectrometer (HR-ToF-AMS). HR-ToF-AMS provides non-refractory aerosol mass concentrations including nitrate, sulfate, hydrocarbon-like and oxygenated organic aerosol in real time. This study includes a residence area of mixture of sources, a forest site of dominant source of biogenic VOCs, an underground parking lot of dominant vehicle emission, and laboratory experiment of vehicle emissions under different fuels and speeds using the chassis dynamometer. As a result, it was revealed that gasoline and LPG vehicle relatively made more potential SA than diesel vehicle.

Evaluation of the RBC Pig-a and PIGRET assays using single doses of hydroxyurea and melphalan in rats.

PubMed

Adachi, Hideki; Uematsu, Yasuaki; Yamada, Toru

2016-11-15

To evaluate the suitability of the rat Pig-a assay on reticulocytes (PIGRET assay) as a short-term test, red blood cell (RBC) Pig-a and PIGRET assays after single doses with hydroxyurea (HU) and melphalan (L-PAM) were conducted and the results of both assays were compared. HU was administered once orally to male SD rats at 250, 500 and 1000mg/kg, and both assays were conducted using peripheral blood withdrawn from the jugular vein at 1, 2 and 4 weeks after dosing. L-PAM was administered at 1.25, 2.5 and 5mg/kg in the same manner. L-PAM produced significant dose-dependent increases in mutant frequencies in the PIGRET assay after single oral doses, but did not produce dose-dependent increases in mutant frequencies in the RBC Pig-a assay. These results suggest that the PIGRET assay is more sensitive for the evaluation of the mutagenic potential of L-PAM than the RBC Pig-a assay. In contrast, HU, a clastogenic but not DNA-reactive compound, gave negative results in both assays. The results with these 2 chemicals indicate that the single-dose PIGRET assay in rats has the potential to properly detect DNA-reactive compounds that directly cause DNA damage in a short-term assay. Copyright © 2016 Elsevier B.V. All rights reserved.

Measurement of photosynthesis using PAM technology in a purple sulfur bacterium Thermochromatium tepidum (Chromatiaceae).

PubMed

Ritchie, Raymond J; Mekjinda, Nutsara

2015-01-01

We demonstrate that Blue-diode-based pulse amplitude modulation (PAM) technology can be used to measure the photosynthetic electron transport rate (ETR) of purple sulfur bacteria (Thermochromatium tepidum, Chromatiaceae). Previous studies showed that PAM technology could be used to estimate photosynthesis in purple nonsulfur bacteria and so PAM technology can be used to estimate photosynthesis of both kinds of purple photosynthetic bacteria. The absorptance of Thermochromatium films on glass fiber disks was measured and used to calculate actual ETR. ETR vs Irradiance (P vs E) curves fitted the waiting-in-line model (ETR = (ETRmax × E/Eopt) × exp (1−E/Eopt)). Yield (Y) was only ≈ 0.3–0.4. Thermochromatium saturates at 325 ± 13.8 μmol photons m(−2) s(−1) or ≈15% sunlight and shows photoinhibition at high irradiances. A pond of Thermochromatium would exhibit classic surface inhibition. Photosynthesis is extremely low in the absence of an electron source: ETR increases in the presence of acetate (5 mol m(−3)) provided as an organic carbon source and also increases in the presence of sulfite (3 mol m(−3)) but not sulfide and is only marginally increased by the presence of Fe(2+). Nonphotochemical quenching does occur in Thermochromatium but at very low levels compared to oxygenic photo-organisms or Rhodopseudomonads.

Adaptive cellular structures and devices with internal features for enhanced structural performance

NASA Astrophysics Data System (ADS)

Pontecorvo, Michael Eugene

This dissertation aims to develop a family of cellular and repeatable devices that exhibit a variety of force-displacement behaviors. It is envisioned that these cellular structures might be used either as stand-alone elements, or combined and repeated to create multiple types of structures (i.e. buildings, ship hulls, vehicle subfloors, etc.) with the ability to passively or actively perform multiple functions (harmonic energy dissipation, impact mitigation, modulus change) over a range of loading types, amplitudes, and frequencies. To accomplish this goal, this work combines repeatable structural frameworks, such as that provided by a hexagonal cellular structure, with internal structural elements such as springs, viscous dampers, buckling plates, bi-stable von Mises trusses (VMTs), and pneumatic artificial muscles (PAMs). The repeatable framework serves to position damping and load carrying elements throughout the structure, and the configuration of the internal elements allow each cell to be tuned to exhibit a desired force-displacement response. Therefore, gradient structures or structures with variable load paths can be created for an optimal global response to a range of loads. This dissertation focuses on the development of cellular structures for three functions: combined load-carrying capability with harmonic energy dissipation, impact mitigation, and cell modulus variation. One or more conceptual designs are presented for devices that can perform each of these functions, and both experimental measurements and simulations are used to gain a fundamental understanding of each device. Chapter 2 begins with a presentation of a VMT model that is the basis for many of the elements. The equations of motion for the VMT are derived and the static and dynamic behavior of the VMT are discussed in detail. Next, two metrics for the energy dissipation of the VMT - hysteresis loop area and loss factor - are presented. The responses of the VMT to harmonic displacement and force inputs are contrasted in relation to these metrics. The key innovation to the early structural elements presented here is the combination of the VMT with the pin-jointed hexagonal cell. Chapter 3 explores several prototypes of repeatable structural elements for simultaneous load-carrying capability and energy dissipation that are based on this innovation. The final demonstration prototype presented in this chapter is a column-like element that is based on a hexagonal cell containing two horizontal springs and one vertical damper. The unit is enclosed by a pair of buckling plates that serve to give the prototype a high initial stiffness and load carrying capability. The prototype is tested in both displacement and force input and its behavior is compared to simulation. Chapter 4 builds on the conceptual designs of Chapter 3 with the introduction of a plate-like element, that contains two compact VMTs connected by a horizontally oriented damper. Pre-loaded springs are used in the prototype to perform the same load carrying function as the buckling plates in the column-like prototype with increased predictability. The plate-like prototype is studied under impact to demonstrate its effectiveness as a protective layer. It is shown to reduce peak impact loads transmitted to the base of the device by over 60%. In most cases, the prototype compares well with a conventional protective rubber layer, and in cases of extreme impact loads, it exceeds the performance of the rubber layer. In addition to impact testing, the prototype is also experimentally tested under harmonic displacement input, and is simulated under both harmonic displacement and force input. The experiments illustrate that while the VMT parameters of a single layer can be optimized to a particular harmonic load amplitude, having two layers with softer and stiffer VMTs allows the system to show good energy dissipation characteristics at different harmonic load amplitude levels. Chapter 5 examines using PAM inclusions within planar hexagonal cells as variable stiffness springs to create a variable modulus cellular structure. The proposed concept is envisioned as a first step toward a structural unit cell whose in-plane modulus in a given direction can be tuned based on the orientation of PAMs within the cell and the pressure supplied to the individual muscles. To begin, a pin-jointed cell is considered, loaded in the horizontal direction, with three PAMs (one vertical PAM and two horizontal PAMs) oriented in an "H" configuration between the vertices of the cell. A method for calculation of the hexagonal cell modulus is introduced, as is an expression for the balance of tensile forces between the horizontal and vertical PAMs. An aluminum hexagonal unit cell is fabricated and simulation of the hexagonal cell with PAM inclusions is then compared to experimental measurement of the unit cell modulus in the horizontal direction over a pressure range up to 682 kPa. An increase in cell modulus of 200% and a corresponding change in cell angle of 1.53 degrees are demonstrated experimentally. A design study via simulation predicts that differential pressurization of the PAMs up to 1992 kPa can increase the cell modulus in the horizontal direction by a factor of 6.66 with a change in cell angle of only 2.75 degrees. Additionally, simulation predicts that variation of unpressurized cell equilibrium angle and vertical wall length coefficient can result in changes in cell modulus greater than 1000%. A drawback of the pin-jointed cell with PAM inclusions is that it is inherently underconstrained. To solve this problem, the pin-jointed cell walls are replaced with a continuous Delrin hexagon which gives the cell kinematic stability and allows for experimental measurement of modulus in both the horizontal and vertical directions. The Delrin cell is designed to have a modulus on the same order as that of the pin-jointed cell at zero pressure and is experimentally measured without the PAM inclusions. These measurements validate the use of a combined flexural/hinging analytical model that accurately simulates the cell modulus. This analysis is then combined with the PAM force equations to model the complete hexagonal cell with PAM inclusions. Simulation and experimental measurement of the cell modulus with the PAM inclusions are compared in both the horizontal and vertical directions over an expanded pressure range up to 1302 kPa. The interplay between the contraction ratio and pressure in orthogonal sets of PAMs is highlighted as the primary driver of overall cell modulus.

Space station structures and dynamics test program

NASA Technical Reports Server (NTRS)

Moore, Carleton J.; Townsend, John S.; Ivey, Edward W.

1987-01-01

The design, construction, and operation of a low-Earth orbit space station poses unique challenges for development and implementation of new technology. The technology arises from the special requirement that the station be built and constructed to function in a weightless environment, where static loads are minimal and secondary to system dynamics and control problems. One specific challenge confronting NASA is the development of a dynamics test program for: (1) defining space station design requirements, and (2) identifying the characterizing phenomena affecting the station's design and development. A general definition of the space station dynamic test program, as proposed by MSFC, forms the subject of this report. The test proposal is a comprehensive structural dynamics program to be launched in support of the space station. The test program will help to define the key issues and/or problems inherent to large space structure analysis, design, and testing. Development of a parametric data base and verification of the math models and analytical analysis tools necessary for engineering support of the station's design, construction, and operation provide the impetus for the dynamics test program. The philosophy is to integrate dynamics into the design phase through extensive ground testing and analytical ground simulations of generic systems, prototype elements, and subassemblies. On-orbit testing of the station will also be used to define its capability.

Television in the After School Hours. A Study of Programming and Advertising for Children on Independent Stations Across the United States.

ERIC Educational Resources Information Center

Barcus, F. Earle

A study analyzed the programing and advertising matter in the after-school hours on independent commercial television stations unaffiliated with the major networks. These stations, primarily UHF, relied almost entirely on syndicated programing that is often reruns of former network programs. These programs draw large after-school audiences. By…

KENNEDY SPACE CENTER, FLA. - Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; Alan Thirkettle, International Space Station Program manager for Node 2, European Space Agency (ESA); and NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, sign documents officially transferring ownership of Node 2 between the ESA and NASA. The signing was part of a ceremony highlighting the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module (above right) of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. Emceed by Lisa Malone (far left), deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; NASA’s William Gerstenmaier, International Space Station Program manager; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; Alan Thirkettle, International Space Station Program manager for Node 2, European Space Agency (ESA); and NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, sign documents officially transferring ownership of Node 2 between the ESA and NASA. The signing was part of a ceremony highlighting the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module (above right) of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. Emceed by Lisa Malone (far left), deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; NASA’s William Gerstenmaier, International Space Station Program manager; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

KENNEDY SPACE CENTER, FLA. - Alan Thirkettle (center), International Space Station Program manager for Node 2, European Space Agency (ESA); and NASA’s Michael C. Kostelnik (right), deputy associate administrator for International Space Station and Shuttle Programs, sign documents officially transferring ownership of Node 2 between the ESA and NASA. At left, also part of the signing, is Andrea Lorenzoni (left), International Space Station Program manager for Node 2, Italian Space Agency. NASA's Node 2, built by ESA in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. Emceed by Lisa Malone, deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; NASA’s William Gerstenmaier, International Space Station Program manager; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - Alan Thirkettle (center), International Space Station Program manager for Node 2, European Space Agency (ESA); and NASA’s Michael C. Kostelnik (right), deputy associate administrator for International Space Station and Shuttle Programs, sign documents officially transferring ownership of Node 2 between the ESA and NASA. At left, also part of the signing, is Andrea Lorenzoni (left), International Space Station Program manager for Node 2, Italian Space Agency. NASA's Node 2, built by ESA in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. Emceed by Lisa Malone, deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; NASA’s William Gerstenmaier, International Space Station Program manager; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

The impact of Telephonic Health Coaching on Health Outcomes in a High-risk Population.

PubMed

Lawson, Karen L; Jonk, Yvonne; O'Connor, Heidi; Riise, Kirsten Sundgaard; Eisenberg, David M; Kreitzer, Mary Jo

2013-05-01

Health coaching is a client-centric process to increase motivation and self-efficacy that supports sustainable lifestyle behavior changes and active management of health conditions. This study describes an intervention offered as a benefit to health plan members and examines health and behavioral outcomes of participants. High-risk health plan enrollees were invited to participate in a telephonic health coaching intervention addressing the whole person and focusing on motivating health behavior changes. Outcomes of self-reported lifestyle behaviors, perceived health, stress levels, quality of life, readiness to make changes, and patient activation levels were reported at baseline and upon program completion. Retrospectively, these data were extracted from administrative and health coaching records of participants during the first 2 full years of the program. Less than 7% of the 114 615 potential candidates self-selected to actively participate in health coaching, those with the highest chronic disease load being the most likely to participate. Of 6940 active participants, 1082 fully completed health inventories, with 570 completing Patient Activation Measure (PAM). The conditions most often represented in the active participants were depression, congestive heart failure, diabetes, hyperlipidemia, hypertension, osteoporosis, asthma, and low back pain. In 6 months or less, 89% of participants met at least one goal. Significant improvements occurred in stress levels, healthy eating, exercise levels, and physical and emotional health, as well as in readiness to make change and PAM scores. The types of client-selected goals most often met were physical activity, eating habits, stress management, emotional health, sleep, and pain management, resulting in improved overall quality of life regardless of condition. Positive shifts in activation levels and readiness to change suggest that health coaching is an intervention deserving of future prospective research studies to assess the utilization, efficacy, and potential cost-effectiveness of health coaching programs for a range of populations.

KENNEDY SPACE CENTER, FLA. - Center Director Roy Bridges Jr. speaks to the media and guests gathered in the Space Station Processing Facility for a ceremony to highlight the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope) arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone (far left), deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: NASA's Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, and William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - Center Director Roy Bridges Jr. speaks to the media and guests gathered in the Space Station Processing Facility for a ceremony to highlight the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope) arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone (far left), deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: NASA's Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, and William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

KENNEDY SPACE CENTER, FLA. - Alan Thirkettle, International Space Station Program manager for Node 2, European Space Agency (ESA), speaks to guests and the media gathered in the Space Station Processing Facility at a ceremony highlighting the arrival of two major components of the International Space Station. NASA's Node 2, built by ESA in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone, deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs and William Gerstenmaier, International Space Station Program manager; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - Alan Thirkettle, International Space Station Program manager for Node 2, European Space Agency (ESA), speaks to guests and the media gathered in the Space Station Processing Facility at a ceremony highlighting the arrival of two major components of the International Space Station. NASA's Node 2, built by ESA in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone, deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs and William Gerstenmaier, International Space Station Program manager; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

KENNEDY SPACE CENTER, FLA. - NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, speaks to guests and the media gathered in the Space Station Processing Facility for a ceremony to highlight the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope) arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone, deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, speaks to guests and the media gathered in the Space Station Processing Facility for a ceremony to highlight the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope) arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone, deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

KENNEDY SPACE CENTER, FLA. - Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency, speaks to guests and the media gathered in the Space Station Processing Facility at a ceremony highlighting the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone, deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs and William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency, speaks to guests and the media gathered in the Space Station Processing Facility at a ceremony highlighting the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone, deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs and William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

KENNEDY SPACE CENTER, FLA. - Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan, speaks to guests and the media gathered in the Space Station Processing Facility at a ceremony highlighting the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone (far left), deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr. (second from left); NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs and William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; and Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan, speaks to guests and the media gathered in the Space Station Processing Facility at a ceremony highlighting the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone (far left), deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr. (second from left); NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs and William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; and Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency.

KENNEDY SPACE CENTER, FLA. - Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency, speaks to guests and the media gathered in the Space Station Processing Facility at a ceremony highlighting the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone (far left), deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, and William Gerstenmaier, International Space Station Program manager ; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency, speaks to guests and the media gathered in the Space Station Processing Facility at a ceremony highlighting the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone (far left), deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, and William Gerstenmaier, International Space Station Program manager ; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

KENNEDY SPACE CENTER, FLA. - NASA's Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, speaks to guests and the media gathered in the Space Station Processing Facility for a ceremony to highlight the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope) arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone (far left), deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr. (second from left); William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - NASA's Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, speaks to guests and the media gathered in the Space Station Processing Facility for a ceremony to highlight the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope) arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone (far left), deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr. (second from left); William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

KENNEDY SPACE CENTER, FLA. - Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan, speaks to guests and the media gathered in the Space Station Processing Facility at a ceremony highlighting the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module (above right) of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone (far left), deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr. (second from left); NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs and William Gerstenmaier, International Space Station Program manager ; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; and Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan, speaks to guests and the media gathered in the Space Station Processing Facility at a ceremony highlighting the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module (above right) of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone (far left), deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr. (second from left); NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs and William Gerstenmaier, International Space Station Program manager ; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; and Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency.

KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, media and guests listen intently to remarks during a ceremony to highlight the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope) arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone, deputy director of External Relations and Business Development at KSC, the ceremony included these speakers: KSC Director Roy Bridges Jr.; NASA's Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, and William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, media and guests listen intently to remarks during a ceremony to highlight the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope) arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone, deputy director of External Relations and Business Development at KSC, the ceremony included these speakers: KSC Director Roy Bridges Jr.; NASA's Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, and William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

KENNEDY SPACE CENTER, FLA. - Center Director Roy Bridges Jr. speaks to the media and guests gathered in the Space Station Processing Facility for a ceremony to highlight the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope) arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone (left) , deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: NASA's Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, and William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - Center Director Roy Bridges Jr. speaks to the media and guests gathered in the Space Station Processing Facility for a ceremony to highlight the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope) arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone (left) , deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: NASA's Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, and William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

KENNEDY SPACE CENTER, FLA. - Center Director Roy Bridges Jr. speaks to the media and guests gathered in the Space Station Processing Facility for a ceremony to highlight the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope) arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone (left), deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: NASA's Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, and William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - Center Director Roy Bridges Jr. speaks to the media and guests gathered in the Space Station Processing Facility for a ceremony to highlight the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope) arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone (left), deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: NASA's Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs, and William Gerstenmaier, International Space Station Program manager; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

KENNEDY SPACE CENTER, FLA. - Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan, speaks to guests and the media gathered in the Space Station Processing Facility at a ceremony highlighting the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone, deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs and William Gerstenmaier, International Space Station Program manager ; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; and Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan, speaks to guests and the media gathered in the Space Station Processing Facility at a ceremony highlighting the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone, deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs and William Gerstenmaier, International Space Station Program manager ; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; and Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency.

KENNEDY SPACE CENTER, FLA. - Alan Thirkettle, International Space Station Program manager for Node 2, European Space Agency (ESA), speaks to guests and the media gathered in the Space Station Processing Facility at a ceremony highlighting the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone, deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs and William Gerstenmaier, International Space Station Program manager; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - Alan Thirkettle, International Space Station Program manager for Node 2, European Space Agency (ESA), speaks to guests and the media gathered in the Space Station Processing Facility at a ceremony highlighting the arrival of two major components of the International Space Station. NASA's Node 2, built by the European Space Agency (ESA) in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone, deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs and William Gerstenmaier, International Space Station Program manager; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

KENNEDY SPACE CENTER, FLA. - At a ceremony highlighting the arrival of two major components of the International Space Station, William Gerstenmaier, International Space Station Program manager, points to one of the components as he speaks to guests and the media gathered in the Space Station Processing Facility. NASA's Node 2, built by the European Space Agency (ESA) in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone, deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

NASA Image and Video Library

2003-06-18

KENNEDY SPACE CENTER, FLA. - At a ceremony highlighting the arrival of two major components of the International Space Station, William Gerstenmaier, International Space Station Program manager, points to one of the components as he speaks to guests and the media gathered in the Space Station Processing Facility. NASA's Node 2, built by the European Space Agency (ESA) in Italy, arrived at KSC on June 1. It will be the next pressurized module installed on the Station. The pressurized module of the Japanese Experiment Module (JEM), named "Kibo" (Hope), arrived at KSC on June 4. It is Japan's primary contribution to the Station. The ceremony held today included the official transfer of ownership signing of Node 2 between the ESA and NASA.. Emceed by Lisa Malone, deputy director of External Relations and Business Development at KSC, the ceremony also included these speakers: Center Director Roy Bridges Jr.; NASA’s Michael C. Kostelnik, deputy associate administrator for International Space Station and Shuttle Programs; Alan Thirkettle, International Space Station Program manager for Node 2, ESA; Andrea Lorenzoni, International Space Station Program manager for Node 2, Italian Space Agency; and Kuniaki Shiraki, JEM Project manager, National Aerospace and Development Agency of Japan.

Physicochemical Properties, Antioxidant and Cytotoxic Activities of Crude Extracts and Fractions from Phyllanthus amarus

PubMed Central

Nguyen, Van Tang; Sakoff, Jennette A.; Scarlett, Christopher J.

2017-01-01

Background: Phyllanthus amarus (P. amarus) has been used as a medicinal plant for the prevention and treatment of chronic ailments such as diabetes, hepatitis, and cancer. Methods: The physicochemical properties, antioxidant and cytotoxic activities of crude extracts and fractions from P. amarus were determined using spectrophotometric method. Results: The P. amarus methanol (PAM) extract had lower levels of residual moisture (7.40%) and water activity (0.24) and higher contents of saponins, phenolics, flavonoids, and proanthocyanidins (1657.86 mg escin equivalents, 250.45 mg gallic acid equivalents, 274.73 mg rutin equivalents and 61.22 mg catechin equivalents per g dried extract, respectively) than those of the P. amarus water (PAW) extract. The antioxidant activity of PAM extract was significantly higher (p < 0.05) than that of the PAW extract, PAM fractions, and phyllanthin (known as a major compound in the P. amarus). Higher cytotoxic activity of PAM extract based on MTT assay on different cell lines including MiaPaCa-2 (pancreas), HT29 (colon), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2-C (neuroblastoma), MCF-7 (breast), MCF-10A (normal breast), and U87, SJ-G2, SMA (glioblastoma) was observed in comparison to the PAW extract and PAM fractions. The cytotoxic potential of the PAW extract (200 μg/mL), based on the CCK-8 assay on a pancreatic cancer cell line (MiaCaPa2) was significantly lower (p < 0.05) than those of gemcitabine (50 nM) and a saponin-enriched extract from quillajia bark at 200 μg/mL (a commercial product), but was significantly higher than that of phyllanthin at 2 μg/mL. Conclusions: The results achieved from this study reveal that the PA extracts are a potential source for the development of natural antioxidant products and/or novel anticancer drugs. PMID:28930257

Focusing on the adult attachment style in schizophrenia in community mental health centres: validation of the Psychosis Attachment Measure (PAM) in a German-speaking sample.

PubMed

Kvrgic, Sara; Beck, Eva-Marina; Cavelti, Marialuisa; Kossowsky, Joe; Stieglitz, Rolf-Dieter; Vauth, Roland

2012-07-01

Assessing attachment style in people with schizophrenia may be important to identify a risk factor in building a strong therapeutic relationship and so indirectly to understand the development of mal-compliance as one of the major obstacles in the treatment of schizophrenia. The present study analysed the psychometric properties of the German version of the Psychosis Attachment Measure (PAM), which assesses avoidant and anxious attachment style. A sample of 127 patients suffering from chronic schizophrenia or schizoaffective disorder participated in this study. In testing discriminant validity, we assessed psychopathology, depression, therapeutic relationship and service engagement. Internal consistency, test-retest reliability and factor structure were analysed. The German version of PAM exhibited acceptable to good internal and test-retest reliabilities and the two-factor structure of the English version could be replicated. Avoidant attachment style was related to higher levels of positive symptoms and to a poorer therapeutic relationship. In the context of external validation, a regression analysis revealed that a poor therapeutic relationship correlated with avoidant attachment style, independent of anxious attachment style and depressive symptoms. Anxious attachment was associated with higher treatment adherence. Both insecure attachment styles (avoidant and anxious) were found to be correlated with higher levels of depression, but only attachment anxiety had an independent predictive value for self-reported depression in regression analysis. The German version of PAM displayed satisfactory psychometric properties and seems to be a reliable measure for assessing attachment style in individuals with schizophrenia. Validation of PAM led to the finding that only the avoidant attachment style might be a risk factor when building a strong therapeutic relationship in schizophrenia. In future studies, other factors influencing therapeutic relationship should be taken into account. Anxious attachment style may be a risk factor for depression, but it also has an enhancing effect on treatment adherence.

Sex-Dependent Anti-Stress Effect of an α5 Subunit Containing GABAA Receptor Positive Allosteric Modulator

PubMed Central

Piantadosi, Sean C.; French, Beverly J.; Poe, Michael M.; Timić, Tamara; Marković, Bojan D.; Pabba, Mohan; Seney, Marianne L.; Oh, Hyunjung; Orser, Beverley A.; Savić, Miroslav M.; Cook, James M.; Sibille, Etienne

2016-01-01

Rationale: Current first-line treatments for stress-related disorders such as major depressive disorder (MDD) act on monoaminergic systems and take weeks to achieve a therapeutic effect with poor response and low remission rates. Recent research has implicated the GABAergic system in the pathophysiology of depression, including deficits in interneurons targeting the dendritic compartment of cortical pyramidal cells. Objectives: The present study evaluates whether SH-053-2’F-R-CH3 (denoted “α5-PAM”), a positive allosteric modulator selective for α5-subunit containing GABAA receptors found predominantly on cortical pyramidal cell dendrites, has anti-stress effects. Methods: Female and male C57BL6/J mice were exposed to unpredictable chronic mild stress (UCMS) and treated with α5-PAM acutely (30 min prior to assessing behavior) or chronically before being assessed behaviorally. Results: Acute and chronic α5-PAM treatments produce a pattern of decreased stress-induced behaviors (denoted as “behavioral emotionality”) across various tests in female, but not in male mice. Behavioral Z-scores calculated across a panel of tests designed to best model the range and heterogeneity of human symptomatology confirmed that acute and chronic α5-PAM treatments consistently produce significant decreases in behavioral emotionality in several independent cohorts of females. The behavioral responses to α5-PAM could not be completely accounted for by differences in drug brain disposition between female and male mice. In mice exposed to UCMS, expression of the Gabra5 gene was increased in the frontal cortex after acute treatment and in the hippocampus after chronic treatment with α5-PAM in females only, and these expression changes correlated with behavioral emotionality. Conclusion: We showed that acute and chronic positive modulation of α5 subunit-containing GABAA receptors elicit anti-stress effects in a sex-dependent manner, suggesting novel therapeutic modalities. PMID:27920723

The Metabotropic Glutamate Receptor 4-Positive Allosteric Modulator VU0364770 Produces Efficacy Alone and in Combination with l-DOPA or an Adenosine 2A Antagonist in Preclinical Rodent Models of Parkinson's Disease

PubMed Central

Jones, Carrie K.; Bubser, Michael; Thompson, Analisa D.; Dickerson, Jonathan W.; Turle-Lorenzo, Nathalie; Amalric, Marianne; Blobaum, Anna L.; Bridges, Thomas M.; Morrison, Ryan D.; Jadhav, Satyawan; Engers, Darren W.; Italiano, Kimberly; Bode, Jacob; Daniels, J. Scott; Lindsley, Craig W.; Hopkins, Corey R.; Conn, P. Jeffrey

2012-01-01

Parkinson's disease (PD) is a debilitating neurodegenerative disorder associated with severe motor impairments caused by the loss of dopaminergic innervation of the striatum. Previous studies have demonstrated that positive allosteric modulators (PAMs) of metabotropic glutamate receptor 4 (mGlu4), including N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide, can produce antiparkinsonian-like effects in preclinical models of PD. However, these early mGlu4 PAMs exhibited unsuitable physiochemical properties for systemic dosing, requiring intracerebroventricular administration and limiting their broader utility as in vivo tools to further understand the role of mGlu4 in the modulation of basal ganglia function relevant to PD. In the present study, we describe the pharmacologic characterization of a systemically active mGlu4 PAM, N-(3-chlorophenyl)picolinamide (VU0364770), in several rodent PD models. VU0364770 showed efficacy alone or when administered in combination with l-DOPA or an adenosine 2A (A2A) receptor antagonist currently in clinical development (preladenant). When administered alone, VU0364770 exhibited efficacy in reversing haloperidol-induced catalepsy, forelimb asymmetry-induced by unilateral 6-hydroxydopamine (6-OHDA) lesions of the median forebrain bundle, and attentional deficits induced by bilateral 6-OHDA nigrostriatal lesions in rats. In addition, VU0364770 enhanced the efficacy of preladenant to reverse haloperidol-induced catalepsy when given in combination. The effects of VU0364770 to reverse forelimb asymmetry were also potentiated when the compound was coadministered with an inactive dose of l-DOPA, suggesting that mGlu4 PAMs may provide l-DOPA-sparing activity. The present findings provide exciting support for the potential role of selective mGlu4 PAMs as a novel approach for the symptomatic treatment of PD and a possible augmentation strategy with either l-DOPA or A2A antagonists. PMID:22088953

Intermittent hypoxia activates peptidylglycine α-amidating monooxygenase in rat brain stem via reactive oxygen species-mediated proteolytic processing

PubMed Central

Sharma, Suresh D.; Raghuraman, Gayatri; Lee, Myeong-Seon; Prabhakar, Nanduri R.; Kumar, Ganesh K.

2009-01-01

Intermittent hypoxia (IH) associated with sleep apneas leads to cardiorespiratory abnormalities that may involve altered neuropeptide signaling. The effects of IH on neuropeptide synthesis have not been investigated. Peptidylglycine α-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the α-amidation of neuropeptides, which confers biological activity to a large number of neuropeptides. PAM consists of O2-sensitive peptidylglycine α-hydroxylating monooxygenase (PHM) and peptidyl-α-hydroxyglycine α-amidating lyase (PAL) activities. Here, we examined whether IH alters neuropeptide synthesis by affecting PAM activity and, if so, by what mechanisms. Experiments were performed on the brain stem of adult male rats exposed to IH (5% O2 for 15 s followed by 21% O2 for 5 min; 8 h/day for up to 10 days) or continuous hypoxia (0.4 atm for 10 days). Analysis of brain stem extracts showed that IH, but not continuous hypoxia, increased PHM, but not PAL, activity of PAM and that the increase of PHM activity was associated with a concomitant elevation in the levels of α-amidated forms of substance P and neuropeptide Y. IH increased the relative abundance of 42- and 35-kDa forms of PHM (∼1.6- and 2.7-fold, respectively), suggesting enhanced proteolytic processing of PHM, which appears to be mediated by an IH-induced increase of endoprotease activity. Kinetic analysis showed that IH increases Vmax but has no effect on Km. IH increased generation of reactive oxygen species in the brain stem, and systemic administration of antioxidant prevented IH-evoked increases of PHM activity, proteolytic processing of PHM, endoprotease activity, and elevations in substance P and neuropeptide Y amide levels. Taken together, these results demonstrate that IH activates PHM in rat brain stem via reactive oxygen species-dependent posttranslational proteolytic processing and further suggest that PAM activation may contribute to IH-mediated peptidergic neurotransmission in rat brain stem. PMID:18818385

Intermittent hypoxia activates peptidylglycine alpha-amidating monooxygenase in rat brain stem via reactive oxygen species-mediated proteolytic processing.

PubMed

Sharma, Suresh D; Raghuraman, Gayatri; Lee, Myeong-Seon; Prabhakar, Nanduri R; Kumar, Ganesh K

2009-01-01

Intermittent hypoxia (IH) associated with sleep apneas leads to cardiorespiratory abnormalities that may involve altered neuropeptide signaling. The effects of IH on neuropeptide synthesis have not been investigated. Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) catalyzes the alpha-amidation of neuropeptides, which confers biological activity to a large number of neuropeptides. PAM consists of O(2)-sensitive peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) activities. Here, we examined whether IH alters neuropeptide synthesis by affecting PAM activity and, if so, by what mechanisms. Experiments were performed on the brain stem of adult male rats exposed to IH (5% O(2) for 15 s followed by 21% O(2) for 5 min; 8 h/day for up to 10 days) or continuous hypoxia (0.4 atm for 10 days). Analysis of brain stem extracts showed that IH, but not continuous hypoxia, increased PHM, but not PAL, activity of PAM and that the increase of PHM activity was associated with a concomitant elevation in the levels of alpha-amidated forms of substance P and neuropeptide Y. IH increased the relative abundance of 42- and 35-kDa forms of PHM ( approximately 1.6- and 2.7-fold, respectively), suggesting enhanced proteolytic processing of PHM, which appears to be mediated by an IH-induced increase of endoprotease activity. Kinetic analysis showed that IH increases V(max) but has no effect on K(m). IH increased generation of reactive oxygen species in the brain stem, and systemic administration of antioxidant prevented IH-evoked increases of PHM activity, proteolytic processing of PHM, endoprotease activity, and elevations in substance P and neuropeptide Y amide levels. Taken together, these results demonstrate that IH activates PHM in rat brain stem via reactive oxygen species-dependent posttranslational proteolytic processing and further suggest that PAM activation may contribute to IH-mediated peptidergic neurotransmission in rat brain stem.

Salinity management using an anionic polymer in a pecan field with calcareous-sodic soil.

PubMed

Ganjegunte, Girisha K; Sheng, Zhuping; Braun, Robert J

2011-01-01

Soil salinity and sodicity have long been recognized as the major concerns for irrigated agriculture in the Trans-Pecos Basin, where fields are being flood irrigated with Rio Grande River water that has elevated salinity. Reclamation of these salt-affected lands is difficult due to fine-texture, high shrink-swell soils with low permeability. Conventional practice of subsoiling to improve soil permeability is expensive and has had limited success on the irrigated soils that have appreciable amounts of readily weatherable Ca minerals. If these native Ca sources can be effectively used to counter sodicity, it can improve soil permeability and reduce amelioration costs. This study evaluated the effects of 3 yr of polyacrylamide (PAM) application at 10 mg L concentration during the first irrigation of the season to evaluate soil permeability, in situ Ca mineral dissolution, and leaching of salts from the effective root zone in a pecan field of El Paso County, TX. Results indicated that PAM application improved water movement throughout the effective root zone that resulted in Na leaching. Polymer application significantly decreased CaCO (estimated based on inorganic C analysis) concentrations in the top 45 cm compared with baseline levels, indicating solubilization and redistribution of calcite. The PAM application also reduced soil electrical conductivity (EC) in the top 60 cm (4.64-2.76 dS m) and sodium adsorption ratio (SAR) from 13.1 to 5.7 mmol L in the top 75-cm depths. As evidence of improved soil conditions, pecan nut yields increased by 34% in PAM-treated fields over the control. Results suggested that PAM application helped in effective use of native Ca sources present in soils of the study site and reduced Na by improving soil permeability. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Reparameterization of PAM50 Expression Identifies Novel Breast Tumor Dimensions and Leads to Discovery of a Genome-Wide Significant Breast Cancer Locus at 12q15.

PubMed

Madsen, Michael J; Knight, Stacey; Sweeney, Carol; Factor, Rachel; Salama, Mohamed; Stijleman, Inge J; Rajamanickam, Venkatesh; Welm, Bryan E; Arunachalam, Sasi; Jones, Brandt; Rachamadugu, Rakesh; Rowe, Kerry; Cessna, Melissa H; Thomas, Alun; Kushi, Lawrence H; Caan, Bette J; Bernard, Philip S; Camp, Nicola J

2018-06-01

Background: Breast tumor subtyping has failed to provide impact in susceptibility genetics. The PAM50 assay categorizes breast tumors into: Luminal A, Luminal B, HER2-enriched and Basal-like. However, tumors are often more complex than simple categorization can describe. The identification of heritable tumor characteristics has potential to decrease heterogeneity and increase power for gene finding. Methods: We used 911 sporadic breast tumors with PAM50 expression data to derive tumor dimensions using principal components (PC). Dimensions in 238 tumors from high-risk pedigrees were compared with the sporadic tumors. Proof-of-concept gene mapping, informed by tumor dimension, was performed using Shared Genomic Segment (SGS) analysis. Results: Five dimensions (PC1-5) explained the majority of the PAM50 expression variance: three captured intrinsic subtype, two were novel (PC3, PC5). All five replicated in 745 TCGA tumors. Both novel dimensions were significantly enriched in the high-risk pedigrees (intrinsic subtypes were not). SGS gene-mapping in a pedigree identified a 0.5 Mb genome-wide significant region at 12q15 This region segregated through 32 meioses to 8 breast cancer cases with extreme PC3 tumors ( P = 2.6 × 10 -8 ). Conclusions: PC analysis of PAM50 gene expression revealed multiple independent, quantitative measures of tumor diversity. These tumor dimensions show evidence for heritability and potential as powerful traits for gene mapping. Impact: Our study suggests a new approach to describe tumor expression diversity, provides new avenues for germline studies, and proposes a new breast cancer locus. Similar reparameterization of expression patterns may inform other studies attempting to model the effects of tumor heterogeneity. Cancer Epidemiol Biomarkers Prev; 27(6); 644-52. ©2018 AACR . ©2018 American Association for Cancer Research.