77 FR 37060 - Critical Infrastructure and Key Resources (CIKR) Asset Protection Technical Assistance Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-20

...), National Protection and Programs Directorate (NPPD), Office of Infrastructure Protection (IP.../IP/IICD, 245 Murray Lane SW., Mailstop 0602, Arlington, VA 20598-0602. Email requests should go to... Technical Assistance Program (CAPTAP) is offered jointly by the NPPD/IP and the Federal Emergency Management...

47 CFR 64.606 - VRS and IP Relay provider and TRS program certification.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false VRS and IP Relay provider and TRS program... Services and Related Customer Premises Equipment for Persons With Disabilities § 64.606 VRS and IP Relay... including notification in the Federal Register. (2) VRS and IP Relay provider. Any entity desiring to...

Procedural volume and structure of interventional pulmonary fellowships: a survey of fellows and fellowship program directors.

PubMed

Yarmus, Lonny; Feller-Kopman, David; Imad, Melhem; Kim, Stephanie; Lee, Hans J

2013-09-01

Current interventional pulmonary (IP) procedural guidelines for competency are based on expert opinion. There are few objective data to support competency metrics for IP procedures. This survey reports procedural volume during IP fellowships to help define new standards in training and curriculum development. A web-based survey was developed to evaluate IP training procedural volume. The survey was administered to all US and Canadian IP fellowship directors and graduates in training from 2006 to 2011. The survey inquired about all diagnostic and therapeutic procedures performed during the specialized year of IP training. Questions regarding the training program structure were collected and analyzed. There was a 92.5% fellow response rate (37 of 40) and 77% fellowship director response rate (10 of 13) from programs in existence at the time of the survey. Procedural volume was consistent between fellowship directors and graduates (P = .64). Although there was a wide range of procedural volume and types of procedures between different programs, the procedural mean volumes were all significantly higher than the American College of Chest Physicians (ACCP) and American Thoracic Society/European Respiratory Society (ATS/ERS) guideline recommendations (P < .005). US and Canadian IP fellowships produce fellows with variable procedural volumes; however, these are significantly higher than ACCP and ATS/ERS guidelines for most programs and procedures. With a uniform training curriculum being adopted by the majority of IP fellowship programs in the United States and Canada, as well as data showing improved core knowledge in IP fellows undergoing a dedicated year of additional training, further metrics examining the impact of advanced IP training on patient outcomes are needed.

Who Benefits From Supported Employment: A Meta-analytic Study

PubMed Central

Campbell, Kikuko; Drake, Robert E.

2011-01-01

Aims: This meta-analysis sought to identify which subgroups of clients with severe mental illness (SMI) benefited from evidence-based supported employment. Methods: We used meta-analysis to pool the samples from 4 randomized controlled trials comparing the Individual Placement and Support (IPS) model of supported employment to well-regarded vocational approaches using stepwise models and brokered services. Meta-analysis was used to determine the magnitude of effects for IPS/control group differences within specific client subgroups (defined by 2 work history, 7 sociodemographic, and 8 clinical variables) on 3 competitive employment outcomes (obtaining a job, total weeks worked, and job tenure). Results: The findings strongly favored IPS, with large effect sizes across all outcomes: 0.96 for job acquisition, 0.79 for total weeks worked, and 0.74 for job tenure. Overall, 90 (77%) of the 117 effect sizes calculated for the 39 subgroups exceeded 0.70, and all 117 favored IPS. Conclusions: IPS produces better competitive employment outcomes for persons with SMI than alternative vocational programs regardless of background demographic, clinical, and employment characteristics. PMID:19661196

Implementation of evidence-based supported employment in regional Australia.

PubMed

Morris, Adrienne; Waghorn, Geoffrey; Robson, Emma; Moore, Lyndell; Edwards, Emma

2014-06-01

To implement the Individual Placement and Support (IPS) approach at 4 locations in regional New South Wales, Australia. Outcomes attained were compared with a national non-IPS program and with international trials of IPS within and outside the United States. Four IPS programs were established through formal partnerships between mental health services and disability employment services. Ninety-five mental health service clients commenced employment assistance and were tracked for a minimum of 12 months. Two sites achieved good fidelity to IPS principles, and 2 sites achieved fair fidelity. IPS clients had 3.5 times greater odds of attaining 13 weeks' employment than those receiving assistance in the national network of disability employment services. Implementing IPS is challenging in the Australian service delivery context. Factors other than program fidelity appear to contribute to excellent employment outcomes. Further research is needed to identify these factors.

Thermal Analysis of the MC1 Engine Turbopump

NASA Technical Reports Server (NTRS)

Roman, Jose; Turner, Larry D. (Technical Monitor)

2001-01-01

The MC1 Engine turbopump supplied the propellants to the main injector. The turbopump consisted of four parts; lox pump, interpropellant seal package (IPS), RP pump and turbine. The thermal analysis was divided into two 2D finite element models; Housing or stationary parts and rotor or rotating parts. Both models were analyzed at the same boundary conditions using SINDA. The housing model consisted of, lox pump housing, ips housing, RP housing, turbine inlet housing, turbine housing, exit guide vane, heat shield and both bearing outer races. The rotor model consisted of the lox impeller; lox end bearing and id race, RP impeller, and RP bearing and id race, shaft and turbine disk. The objectives of the analysis were to: (1) verified the original design and recommend modifications to it, (2) submitted a thermal environment to support the structural analysis, (3) support the component and engine test program. and (4) to support the X34 vehicle program.

Thermal Analysis of the MCI Engine Turbopump

NASA Technical Reports Server (NTRS)

Roman, Jose

2002-01-01

The MCI Engine turbopump supplied the propellants to the main injector. The turbopump consisted of four parts; lox pump, interpropellant seal package (IPS), RP pump and turbine. The thermal analysis was divided into two 2D finite element models; Housing or stationary parts and rotor or rotating parts. Both models were analyzed at the same boundary conditions using SINDA. The housing model consisted of; lox pump housing, ips housing, RP housing, turbine inlet housing, turbine housing, exit guide vane, heat shield and both bearing outer races. The rotor model consisted of the lox impeller; lox end bearing and id race, RP impeller, and RP bearing and id race, shaft and turbine disk. The objectives of the analysis were to (1) verified the original design and recommend modifications to it, (2) submitted a thermal environment to support the structural analysis, (3) support the component and engine test program and (4) to support the X34 vehicle program.

Mobile-ip Aeronautical Network Simulation Study

NASA Technical Reports Server (NTRS)

Ivancic, William D.; Tran, Diepchi T.

2001-01-01

NASA is interested in applying mobile Internet protocol (mobile-ip) technologies to its space and aeronautics programs. In particular, mobile-ip will play a major role in the Advanced Aeronautic Transportation Technology (AATT), the Weather Information Communication (WINCOMM), and the Small Aircraft Transportation System (SATS) aeronautics programs. This report presents the results of a simulation study of mobile-ip for an aeronautical network. The study was performed to determine the performance of the transmission control protocol (TCP) in a mobile-ip environment and to gain an understanding of how long delays, handoffs, and noisy channels affect mobile-ip performance.

77 FR 74678 - Chemical Security Assessment Tool (CSAT)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-17

...), National Protection and Programs Directorate (NPPD), Office of Infrastructure Protection (IP.../IP/ISCD Chemical Facility Anti-Terrorism Standards Program Manager, 245 Murray Lane SW., Mail Stop... should be appropriately marked and submitted by mail to the DHS/NPPD/IP/ISCD Chemical Facility Anti...

Application of Mobile-ip to Space and Aeronautical Networks

NASA Technical Reports Server (NTRS)

Leung, Kent; Shell, Dan; Ivancic, William D.; Stewart, David H.; Bell, Terry L.; Kachmar, Brian A.

2001-01-01

The National Aeronautics and Space Administration (NASA) is interested in applying mobile Internet protocol (mobile-ip) technologies to its space and aeronautics programs. In particular, mobile-ip will play a major role in the Advanced Aeronautic Transportation Technology (AAT-F), the Weather Information Communication (WINCOMM), and the Small Aircraft Transportation System (SATS) aeronautics programs. This paper describes mobile-ip and mobile routers--in particular, the features, capabilities, and initial performance of the mobile router are presented. The application of mobile-router technology to NASA's space and aeronautics programs is also discussed.

Component Framework for Loosely Coupled High Performance Integrated Plasma Simulations

NASA Astrophysics Data System (ADS)

Elwasif, W. R.; Bernholdt, D. E.; Shet, A. G.; Batchelor, D. B.; Foley, S.

2010-11-01

We present the design and implementation of a component-based simulation framework for the execution of coupled time-dependent plasma modeling codes. The Integrated Plasma Simulator (IPS) provides a flexible lightweight component model that streamlines the integration of stand alone codes into coupled simulations. Standalone codes are adapted to the IPS component interface specification using a thin wrapping layer implemented in the Python programming language. The framework provides services for inter-component method invocation, configuration, task, and data management, asynchronous event management, simulation monitoring, and checkpoint/restart capabilities. Services are invoked, as needed, by the computational components to coordinate the execution of different aspects of coupled simulations on Massive parallel Processing (MPP) machines. A common plasma state layer serves as the foundation for inter-component, file-based data exchange. The IPS design principles, implementation details, and execution model will be presented, along with an overview of several use cases.

78 FR 29375 - Protected Critical Infrastructure Information (PCII) Office Self-Assessment Questionnaire

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-20

...), Office of Infrastructure Protection (IP), Infrastructure Information Collection Division (IICD... Forrest DHS/NPPD/IP/PCII, [email protected] . SUPPLEMENTARY INFORMATION: The PCII Program was... administered by DHS/ NPPD/IP/IICD. The PCII Program is responsible for ensuring compliance with the Regulation...

Pattern-Based Design of Insider Threat Programs

DTIC Science & Technology

2014-12-01

also applied these models to develop best practices and technical controls for mitigating insider threat. In some cases of in- sider threat...departing insiders might take valuable IP with them. One set of practices and controls designed to reduce the risk of insider IP theft is based on case data...describing this set of practices and controls helps to balance the costs of monitoring employee behavior for suspicious actions against the risk of

The effectiveness of augmented versus standard individual placement and support programs in terms of employment: a systematic literature review.

PubMed

Dewa, Carolyn S; Loong, Desmond; Trojanowski, Lucy; Bonato, Sarah

2018-04-01

The Individual Placement and Support (IPS) program is a well-studied vocational rehabilitation program. Although it is more effective than usual care, it is not effective for everyone. This offers an opportunity for program improvement. This systematic literature review examines the state of knowledge regarding the effectiveness of augmented versus standard IPS for people with severe mental illness (SMI). We address the questions, "What IPS augmentations have been tested?" and "What is the evidence for the effectiveness of augmented IPS versus standard IPS in terms of employment?" This systematic literature review used publically available peer-reviewed studies published between January 2002 and January 2016 in either: (1) Medline Current, (2) Medline In-process, (3) PsycINFO, (4) Econlit or (5) Web of Science. 5718 unique citations were identified; seven articles from five studies were included. Of these studies, four were rated as having moderate risk of bias and one as having high risk. The results suggest that augmentations of IPS focusing on cognitive and psychosocial skills training, may have additional effects to standard IPS. Areas in need of further research related to the process and targeting of those interventions are discussed.

77 FR 68795 - Protected Critical Infrastructure Information (PCII) Office Self-Assessment Questionnaire

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-16

...), Office of Infrastructure Protection (IP), Infrastructure Information Collection Division (IICD... forwarded to DHS/NPPD/IP/IICD, 245 Murray Lane, SW., Mail Stop 0602, Arlington,VA 20598-0602. Emailed.../IP PCII Program to assess state and local programs, their compliance with PCII rules and requirements...

77 FR 74677 - Chemical Facility Anti-Terrorism Standards (CFATS)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-17

... Protection (IP), Infrastructure Security Compliance Division (ISCD) will submit the following Information... should be forwarded to DHS/NPPD/IP/ISCD CFATS Program Manager, 245 Murray Lane SW., Mail Stop 0610... should be appropriately marked and submitted by mail to the DHS/NPPD/IP/ISCD CFATS Program Manager, 245...

One Approach for Transitioning the iNET Standards into the IRIG 106 Telemetry Standards

DTIC Science & Technology

2015-05-26

Protocol Suite. Figure 1 illustrates the Open Systems Interconnection ( OSI ) Model, the corresponding TCP/IP Model, and the major components of the TCP...IP Protocol Suite. Figure 2 represents the iNET-specific protocols layered onto the TCP/IP Model. Figure 1. OSI and TCP/IP Model with TCP/IP...Protocol Suite TCP/IP Protocol Suite Major Components IPv4 IPv6 TCP/IP Model OSI Model Application Presentation

Understanding the Relationship Between Female Sex Workers and Their Intimate Partners: Lessons and Initial Findings From Participatory Research in North Karnataka, South India.

PubMed

Bhattacharjee, Parinita; Campbell, Linda; Thalinja, Raghavendra; Nair, Sapna; Doddamane, Mahesh; Ramanaik, Satyanarayana; Isac, Shajy; Beattie, Tara S

2018-04-01

While traditional HIV prevention programs with female sex workers (FSWs) in Karnataka, India, have focused on reducing HIV transmission between FSWs and clients through increased condom use, these programs have not fully addressed the transmission risk between FSWs and their nonpaying intimate partners (IPs). Condom use is infrequent and violence is recurrent in these relationships: Furthermore, there is little evidence on the precise nature of FSW-IP relationships. Our study addresses this knowledge gap to inform HIV programs targeted at FSWs. A series of workshops, using participatory tools, was held to explore FSW-IP relationships; 31 FSWs and 37 IPs participated. Three aspects of FSW-IP relationships were examined: how FSWs and IPs understand and interpret their relationships, factors influencing condom use, and the role of violence and its consequences. FSWs wish to be perceived as their IPs' wives, while IPs expect their FSW partners to accept their dominance in the relationship. Nonuse of condoms signals fidelity and elevates the status of the relationship almost to that of marriage, which helps FSWs enter the category of "good" (married) women. Tolerating and accepting violence in these relationships is normative, as in other marital relationships; IPs justify violence as necessary to establish and maintain their power within the relationship. Both FSWs and IPs value their relationships despite the high degree of risk posed by low condom use and high levels of violence. Implications for program design include addressing current norms around masculinity and gender roles, and improving communication within relationships.

Promising practices in vocational services for the community reintegration of returning veterans: The individual placement and support model and beyond.

PubMed

Wewiorski, Nancy J; Gorman, Jay A; Scoglio, Arielle A J; Fukuda, Seiya; Reilly, Erin; Mueller, Lisa; O'Connor, Maureen; Penk, Walter E; Drebing, Charles E

2018-05-01

Supporting returning veterans' job-seeking, hiring, and retention issues has become an essential goal for effective community reintegration. Given both the particular strengths and challenges associated with veterans transitioning from military to civilian life, multiple models for supported employment have become integrated into Veterans Affairs health care facilities across the nation. In this article, we review the state of vocational rehabilitation for veterans, with a particular focus on individual placement and support-supported employment (IPS-SE), the current vocational services model that is considered the gold standard of vocational rehabilitation. Various modifications to the IPS-SE model are presented, including additions such as cognitive rehabilitation, contingency management, motivational interviewing, supported self-employment, and transitional work. Finally, recommendations are made about future directions and strategies to expand access to IPS-SE-based programs and to effectively meet the needs of returning veterans for employment in jobs of their choice. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

76 FR 81955 - Assessment Questionnaire-IP Sector Specific Agency Risk Self Assessment Tool (IP-SSARSAT)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-29

... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2011-0069] Assessment Questionnaire--IP Sector Specific Agency Risk Self Assessment Tool (IP-SSARSAT) AGENCY: National Protection and Programs Directorate...), Office of Infrastructure Protection (IP), Sector Specific Agency Executive Management Office (SSA EMO...

78 FR 29759 - Chemical Facility Anti-Terrorism Standards Personnel Surety Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-21

...), National Protection and Programs Directorate (NPPD), Office of Infrastructure Protection (IP... requirements and submitted by mail to the DHS/NPPD/IP/ ISCD CFATS Program Manager at the Department of Homeland...

Rationale, Scenarios, and Profiles for the Application of the Internet Protocol Suite (IPS) in Space Operations

NASA Technical Reports Server (NTRS)

Benbenek, Daniel B.; Walsh, William

2010-01-01

This greenbook captures some of the current, planned and possible future uses of the Internet Protocol (IP) as part of Space Operations. It attempts to describe how the Internet Protocol is used in specific scenarios. Of primary focus is low-earth-orbit space operations, which is referred to here as the design reference mission (DRM). This is because most of the program experience drawn upon derives from this type of mission. Application profiles are provided. This includes parameter settings programs have proposed for sending IP datagrams over CCSDS links, the minimal subsets and features of the IP protocol suite and applications expected for interoperability between projects, and the configuration, operations and maintenance of these IP functions. Of special interest is capturing the lessons learned from the Constellation Program in this area, since that program included a fairly ambitious use of the Internet Protocol.

Effective Leadership and Management of an ACS Injury Prevention Program: Current Opinions and Perspectives From Where the Rubber Meets the Road.

PubMed

Wolfe, Elizabeth S; Bryant, Elizabeth A

The American College of Surgeons (ACS) mandates that each verified trauma center must have an injury prevention coordinator (IPC); however, Chapter 18 in the Resources for Optimal Care of the Injured Patient (2014) provides minimal information on how to effectively lead or manage an injury prevention (IP) program. This opinion article addresses 3 fundamental components of an effective IP program: (1) construction of an innovative vision of IP programming using current technology; (2) intentional investment and involvement; and (3) stakeholder leadership, engagement, and sustainability. This article also provides leadership and management methods from other professions both within and outside of the health care field that can be translated into sustainable IP program planning, implementation, and longevity.

75 FR 18850 - National Protection and Programs Directorate; Chemical Facility Anti-Terrorism Standards...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-13

... Programs Directorate (NPPD), Office of Infrastructure Protection (IP), Infrastructure Security Compliance... submitted by mail to the DHS/NPPD/ IP/ISCD CFATS Program Manager at the Department of Homeland Security, 245...

Genome wide approaches to identify protein-DNA interactions.

PubMed

Ma, Tao; Ye, Zhenqing; Wang, Liguo

2018-05-29

Transcription factors are DNA-binding proteins that play key roles in many fundamental biological processes. Unraveling their interactions with DNA is essential to identify their target genes and understand the regulatory network. Genome-wide identification of their binding sites became feasible thanks to recent progress in experimental and computational approaches. ChIP-chip, ChIP-seq, and ChIP-exo are three widely used techniques to demarcate genome-wide transcription factor binding sites. This review aims to provide an overview of these three techniques including their experiment procedures, computational approaches, and popular analytic tools. ChIP-chip, ChIP-seq, and ChIP-exo have been the major techniques to study genome-wide in vivo protein-DNA interaction. Due to the rapid development of next-generation sequencing technology, array-based ChIP-chip is deprecated and ChIP-seq has become the most widely used technique to identify transcription factor binding sites in genome-wide. The newly developed ChIP-exo further improves the spatial resolution to single nucleotide. Numerous tools have been developed to analyze ChIP-chip, ChIP-seq and ChIP-exo data. However, different programs may employ different mechanisms or underlying algorithms thus each will inherently include its own set of statistical assumption and bias. So choosing the most appropriate analytic program for a given experiment needs careful considerations. Moreover, most programs only have command line interface so their installation and usage will require basic computation expertise in Unix/Linux. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Transgenerational programming of longevity and reproduction by post-eclosion dietary manipulation in Drosophila

PubMed Central

Xia, Brian; de Belle, Steven

2016-01-01

Accumulating evidence suggests that early-life diet may program one's health status by causing permanent alternations in specific organs, tissues, or metabolic or homeostatic pathways, and such programming effects may propagate across generations through heritable epigenetic modifications. However, it remains uninvestigated whether postnatal dietary changes may program longevity across generations. To address this question of important biological and public health implications, newly-born flies (F0) were collected and subjected to various post-eclosion dietary manipulations (PDMs) with different protein-carbohydrate (i.e., LP, IP or HP for low-, intermediate- or high-protein) contents or a control diet (CD). Longevity and fecundity analyses were performed with these treated F0 flies and their F1, F2 and F3 offspring, while maintained on CD at all times. The LP and HP PDMs shortened longevity, while the IP PDM extended longevity significantly up to the F3 generation. Furthermore, the LP reduced while the IP PDM increased lifetime fecundity across the F0-F2 generations. Our observations establish the first animal model for studying transgenerational inheritance of nutritional programming of longevity, making it possible to investigate the underlying epigenetic mechanisms and identify gene targets for drug discovery in future studies. PMID:27025190

Supported employment for persons with serious mental illness: current status and future directions.

PubMed

Mueser, K T; McGurk, S R

2014-06-01

The individual placement and supported (IPS) model of supported employment is the most empirically validated model of vocational rehabilitation for persons with schizophrenia or another serious mental illness. Over 18 randomized controlled trials have been conducted throughout the world demonstrating the effectiveness of supported employment at improving competitive work compared to other vocational programs: IPS supported employment is defined by the following principles: 1) inclusion of all clients who want to work; 2) integration of vocational and clinical services; 3) focus on competitive employment; 4) rapid job search and no required prevocational skills training; 5) job development by the employment specialist; 6) attention to client preferences about desired work and disclosure of mental illness to prospective employers; 7) benefits counseling; and 8) follow-along supports after a job is obtained. Supported employment has been successfully implemented in a wide range of cultural and clinical populations, although challenges to implementation are also encountered. Common challenges are related to problems such as the failure to access technical assistance, system issues, negative beliefs and attitudes of providers, funding restrictions, and poor leadership. These challenges can be overcome by tapping expertise in IPS supported employment, including standardized and tested models of training and consultation. Efforts are underway to increase the efficiency of training methods for supported employment and the overall program, and to improve its effectiveness for those clients who do not benefit. Progress in IPS supported employment offers people with a serious mental illness realistic hope for achieving their work goals, and taking greater control over their lives. Copyright © 2014. Published by Elsevier Masson SAS.

Multidisciplinary Mentoring Programs to Enhance Junior Faculty Research Grant Success.

PubMed

Freel, Stephanie A; Smith, Paige C; Burns, Ebony N; Downer, Joanna B; Brown, Ann J; Dewhirst, Mark W

2017-10-01

Junior faculty face challenges in establishing independent research careers. Declining funding combined with a shift to multidisciplinary, collaborative science necessitates new mentorship models and enhanced institutional support. Two multidisciplinary mentorship programs to promote grant success for junior faculty were established at the Duke University School of Medicine beginning in 2011. These four-month programs-the Path to Independence Program (PtIP) for National Institutes of Health (NIH) R applicants and the K Club for NIH K applicants-use multiple senior faculty mentors and professional grant-writing staff to provide a 20-hour joint curriculum comprising a series of lectures, hands-on workshops, career development counseling, peer groups, and an internal study section. In March 2016, the authors analyzed the success rate for all NIH grants submitted by participants since program enrollment. In a 2015 postprogram survey, participants rated their feelings of support and competency across six skill factors. From October 2011 to March 2016, the programs engaged 265 senior faculty mentors, 145 PtIP participants, and 138 K Club participants. Success rates for NIH grant applications were 28% (61 awards/220 decisions) for PtIP participants-an increase over the 2010 Duke University junior faculty baseline of 11%-and 64% (38/59) for K Club participants. Respondents reported significantly increased feelings of support and self-ratings for each competency post program. The authors plan to expand the breadth of both the mentorship pool and faculty served. Broad implementation of similar programs elsewhere could bolster success, satisfaction, and retention of junior faculty investigators.

Approaches to eliminate waste and reduce cost for recycling glass.

PubMed

Chao, Chien-Wen; Liao, Ching-Jong

2011-12-01

In recent years, the issue of environmental protection has received considerable attention. This paper adds to the literature by investigating a scheduling problem in the manufacturing of a glass recycling factory in Taiwan. The objective is to minimize the sum of the total holding cost and loss cost. We first represent the problem as an integer programming (IP) model, and then develop two heuristics based on the IP model to find near-optimal solutions for the problem. To validate the proposed heuristics, comparisons between optimal solutions from the IP model and solutions from the current method are conducted. The comparisons involve two problem sizes, small and large, where the small problems range from 15 to 45 jobs, and the large problems from 50 to 100 jobs. Finally, a genetic algorithm is applied to evaluate the proposed heuristics. Computational experiments show that the proposed heuristics can find good solutions in a reasonable time for the considered problem. Copyright © 2011 Elsevier Ltd. All rights reserved.

Thermo-chemical Ice Penetrator for Icy Moons

NASA Astrophysics Data System (ADS)

Arenberg, J. W.; Lee, G.; Harpole, G.; Zamel, J.; Sen, B.; Ross, F.; Retherford, K. D.

2016-12-01

The ability to place sensors or to take samples below the ice surface enables a wide variety of potential scientific investigations. Penetrating an ice cap can be accomplished via a mechanical drill, laser drill, kinetic impactor, or heated penetrator. This poster reports on the development of technology for the latter most option, namely a self-heated probe driven by an exothermic chemical reaction: a Thermo-chemical ice penetrator (TChIP). Our penetrator design employs a eutectic mix of alkali metals that produce an exothermic reaction upon contact with an icy surface. This reaction increases once the ice starts melting, so no external power is required. This technology is inspired by a classified Cold-War era program developed at Northrop Grumman for the US Navy. Terrestrial demonstration of this technology took place in the Arctic; however, this device cannot be considered high TRL for application at the icy moons of the solar system due to the environmental differences between Earth's Arctic and the icy moons. These differences demand a TChIP design specific to these cold, low mass, airless worlds. It is expected that this model of TChIP performance will be complex, incorporating all of the forces on the penetrator, gravity, the thermo-chemistry at the interface between penetrator and ice, and multi-phase heat and mass transport, and hydrodynamics. Our initial efforts are aimed at the development of a validated set of tools and simulations to predict the performance of the penetrator for both the environment found on these icy moons and for a terrestrial environment. The purpose of the inclusion of the terrestrial environment is to aid in model validation. Once developed and validated, our models will allow us to design penetrators for a specific scientific application on a specific body. This poster discusses the range of scientific investigations that are enabled by TChIP. We also introduce the development plan to advance TChIP to the point where it can be considered for infusion into a program.

Technology for a Thermo-chemical Ice Penetrator for Icy Moons

NASA Astrophysics Data System (ADS)

Arenberg, Jonathan; Harpole, George; Zamel, James; Sen, Bashwar; Lee, Greg; Ross, Floyd; Retherford, Kurt D.

2016-10-01

The ability to place sensors or to take samples below the ice surface enables a wide variety of potential scientific investigations. Penetrating an ice cap can be accomplished via a mechanical drill, laser drill, kinetic impactor, or heated penetrator. This poster reports on the development of technology for the latter most option, namely a self-heated probe driven by an exothermic chemical reaction: a Thermo-chemical ice penetrator (TChIP). Our penetrator design employs a eutectic mix of alkali metals that produce an exothermic reaction upon contact with an icy surface. This reaction increases once the ice starts melting, so no external power is required. This technology is inspired by a classified Cold-War era program developed at Northrop Grumman for the US Navy. Terrestrial demonstration of this technology took place in the Arctic; however, this device cannot be considered high TRL for application at the icy moons of the solar system due to the environmental differences between Earth's Arctic and the icy moons. These differences demand a TChIP design specific to these cold, low mass, airless worlds. It is expected that this model of TChIP performance will be complex, incorporating all of the forces on the penetrator, gravity, the thermo-chemistry at the interface between penetrator and ice, and multi-phase heat and mass transport, and hydrodynamics. Our initial efforts are aimed at the development of a validated set of tools and simulations to predict the performance of the penetrator for both the environment found on these icy moons and for a terrestrial environment. The purpose of the inclusion of the terrestrial environment is to aid in model validation. Once developed and validated, our models will allow us to design penetrators for a specific scientific application on a specific body. This poster discusses the range of scientific investigations that are enabled by TChIP. We also introduce the development plan to advance TChIP to the point where it can be considered for infusion into a program.

76 FR 17934 - Infrastructure Protection Data Call

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-31

...), National Protection and Programs Directorate (NPPD), Office of Infrastructure Protection (IP), will submit... Collection Request should be forwarded to DHS/NPPD/IP, 245 Murray Lane, SW., Mail Stop 0602, Arlington, VA..., this responsibility is managed by IP within NPPD. Beginning in Fiscal Year 2006, IP engaged in the...

Qualification of Commercial XIPS(R) Ion Thrusters for NASA Deep Space Missions

NASA Technical Reports Server (NTRS)

Goebel, Dan M.; Polk, James E.; Wirz, Richard E.; Snyder, J.Steven; Mikellides, Ioannis G.; Katz, Ira; Anderson, John

2008-01-01

Electric propulsion systems based on commercial ion and Hall thrusters have the potential for significantly reducing the cost and schedule-risk of Ion Propulsion Systems (IPS) for deep space missions. The large fleet of geosynchronous communication satellites that use solar electric propulsion (SEP), which will approach 40 satellites by year-end, demonstrates the significant level of technical maturity and spaceflight heritage achieved by the commercial IPS systems. A program to delta-qualify XIPS(R) ion thrusters for deep space missions is underway at JPL. This program includes modeling of the thruster grid and cathode life, environmental testing of a 25-centimeter electromagnetic (EM) thruster over DAWN-like vibe and temperature profiles, and wear testing of the thruster cathodes to demonstrate the life and benchmark the model results. This paper will present the delta-qualification status of the XIPS thruster and discuss the life and reliability with respect to known failure mechanisms.

Cost-effectiveness of two vocational rehabilitation programs for persons with severe mental illness.

PubMed

Dixon, Lisa; Hoch, Jeffrey S; Clark, Robin; Bebout, Richard; Drake, Robert; McHugo, Greg; Becker, Deborah

2002-09-01

This study sought to determine differences in the cost-effectiveness of two vocational programs: individual placement and support (IPS), in which employment specialists within a mental health center help patients obtain competitive jobs and provide them with ongoing support, and enhanced vocational rehabilitation (EVR), in which stepwise services that involve prevocational experiences are delivered by rehabilitation agencies. A total of 150 unemployed inner-city patients with severe mental disorders who expressed an interest in competitive employment were randomly assigned to IPS or EVR programs and were followed for 18 months. Wages from all forms of employment and the number of weeks and hours of competitive employment were tracked monthly. Estimates were made of direct mental health costs and vocational costs. Incremental cost-effectiveness ratios (ICERs) were calculated for competitive employment outcomes and total wages. No statistically significant differences were found in the overall costs of IPS and EVR. Participation in the IPS program was associated with significantly more hours and weeks of competitive employment. However, the average combined earnings-earnings from competitive and noncompetitive employment-were virtually the same both programs. The ICER estimates indicated that participants in the IPS program worked in competitive employment settings for an additional week over the 18-month period at a cost of $283 ($13 an hour). The analyses suggest that IPS participants engaged in competitive employment at a higher cost. When combined earnings were used as the outcome, data from the statistical analyses were insufficient to enable any firm conclusions to be drawn. The findings illustrate the importance of choice of outcomes in evaluations of employment programs.

New Epigenetic Therapeutic Intervention for Metastatic Breast Cancer

DTIC Science & Technology

2017-04-01

papers as listed in 3.4B. Article Distinct Roles of Brd2 and Brd4 in Potentiating the Transcriptional Program for Th17 Cell Differentiation Graphical...this paper and include the following:d KEY RESOURCES TABLE d CONTACT FOR REAGENT AND RESOURCE SHARING d EXPERIMENTAL MODEL AND SUBJECT DETAILS d METHOD...Brd4, Smc1, Smc3, Nipbl, H3K27ac, H3K4me1 ChIP-seq data This paper GEO: GSE90788 and GSE63778 Other ChIP-seq data Ciofani et al., 2012 GEO: GSE40918

TCP/IP Interface for the Satellite Orbit Analysis Program (SOAP)

NASA Technical Reports Server (NTRS)

Carnright, Robert; Stodden, David; Coggi, John

2009-01-01

The Transmission Control Protocol/ Internet protocol (TCP/IP) interface for the Satellite Orbit Analysis Program (SOAP) provides the means for the software to establish real-time interfaces with other software. Such interfaces can operate between two programs, either on the same computer or on different computers joined by a network. The SOAP TCP/IP module employs a client/server interface where SOAP is the server and other applications can be clients. Real-time interfaces between software offer a number of advantages over embedding all of the common functionality within a single program. One advantage is that they allow each program to divide the computation labor between processors or computers running the separate applications. Secondly, each program can be allowed to provide its own expertise domain with other programs able to use this expertise.

47 CFR 64.606 - Internet-based TRS provider and TRS program certification.

Code of Federal Regulations, 2011 CFR

2011-10-01

... of Internet-based TRS to be provided (i.e., VRS, IP Relay, and/or IP captioned telephone relay... IP Relay providers certified under this section must notify the Commission of substantive changes in...

76 FR 24031 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-29

... Intervention to Promote a Targeted Vaccination program in the Obstetrician- Gynecologist Setting, FOA IP11-009... a Targeted Vaccination Program in the Obstetrician-Gynecologist Setting; FOA IP11-009, initial...

Enacting the Independent Public Schools Program in Western Australia

ERIC Educational Resources Information Center

Gobby, Brad

2013-01-01

The Independent Public Schools (IPS) program began to be implemented in some Western Australian schools in 2010. The IPS program devolves a number of responsibilities to principals and is part of the political objective of removing the constraints of the education bureaucracy by fostering school level decision-making, problem-solving and…

Parent–Adolescent Relationship Education (PARE): Program Delivery to Reduce Risks for Adolescent Pregnancy and STDs

PubMed Central

Lederman, Regina P.; Chan, Wenyaw; Roberts-Gray, Cynthia

2008-01-01

The first author recruited parent–adolescent dyads (N = 192) into after-school prevention education groups at middle schools in southeast Texas. This author placed participants in either (1) an Interactive Program (IP) in which they role-played, practiced resistance skills, and held parent–child discussions or (2) an Attention Control Program (ACP) that used the same curriculum but was delivered in a traditional, didactic format. Questionnaires administered at the beginning and end of the 4-session program and again after booster sessions in 3 subsequent semesters provided measures of social controls (eg, communication with parents) and self controls (eg, protection against risk) on the youths' sexual health behaviors. Linear mixed models adjusted for gender, age, and ethnicity showed that the IP, in comparison with the ACP, achieved significant gains in social control by increasing parental rules about having sex and other risky behaviors and also enhanced students' self-control by increasing their knowledge about prevention and enhancing resistance responses when pressured to have sex. PMID:18316271

Parent-adolescent relationship education (PARE): program delivery to reduce risks for adolescent pregnancy and STDs.

PubMed

Lederman, Regina P; Chan, Wenyaw; Roberts-Gray, Cynthia

2008-01-01

The first author recruited parent-adolescent dyads (N = 192) into after-school prevention education groups at middle schools in southeast Texas. This author placed participants in either (1) an Interactive Program (IP) in which they roleplayed, practiced resistance skills, and held parent-child discussions or (2) an Attention Control Program (ACP) that used the same curriculum but was delivered in a traditional, didactic format. Questionnaires administered at the beginning and end of the 4-session program and again after booster sessions in 3 subsequent semesters provided measures of social controls (eg, communication with parents) and self controls (eg, protection against risk) on the youths' sexual health behaviors. Linear mixed models adjusted for gender, age, and ethnicity showed that the IP, in comparison with the ACP, achieved significant gains in social control by increasing parental rules about having sex and other risky behaviors and also enhanced students' self-control by increasing their knowledge about prevention and enhancing resistance responses when pressured to have sex.

Putting "The System" into a School Autonomy Reform: The Case of the Independent Public Schools Program

ERIC Educational Resources Information Center

Gobby, Brad

2016-01-01

The Australian Federal and state governments have been introducing neoliberal reforms to the governance of their education systems for a number of decades. One of the most recent programs of reform is the Western Australian Independent Public Schools (IPS) initiative. Similar to decentralizing reforms around the world, the IPS program seeks…

Multi-board kernel communication using socket programming for embedded applications

NASA Astrophysics Data System (ADS)

Mishra, Ashish; Girdhar, Neha; Krishnia, Nikita

2016-03-01

It is often seen in large application projects, there is a need to communicate between two different processors or two different kernels. The aim of this paper is to communicate between two different kernels and use efficient method to do so. The TCP/IP protocol is implemented to communicate between two boards via the Ethernet port and use lwIP (lightweight IP) stack, which is a smaller independent implementation of the TCP/IP stack suitable for use in embedded systems. While retaining TCP/IP functionality, lwIP stack reduces the use of memory and even size of the code. In this process of communication we made Raspberry pi as an active client and Field programmable gate array(FPGA) board as a passive server and they are allowed to communicate via Ethernet. Three applications based on TCP/IP client-server network communication have been implemented. The Echo server application is used to communicate between two different kernels of two different boards. Socket programming is used as it is independent of platform and programming language used. TCP transmit and receive throughput test applications are used to measure maximum throughput of the transmission of data. These applications are based on communication to an open source tool called iperf. It is used to measure the throughput transmission rate by sending or receiving some constant piece of data to the client or server according to the test application.

Pediatric injury prevention programs: Identifying markers for success and sustainability.

PubMed

Chaudhary, Sofia; Pomerantz, Wendy J; Miller, Beverly; Pan, Anqi; Agarwal, Maneesha

2017-11-01

Injury is the leading cause of death in children. Although many pediatric hospitals and trauma centers provide injury prevention (IP) programming, there is no national standard. This study aims to identify characteristics of a sustainable and successful IP program by querying programs affiliated with the Injury Free Coalition for Kids (IFCK). The IFCK sites were sent a 30-question survey via e-mail. Questions focused on demographics, scope of IP activities, self-efficacy, and outcome measures including finances, academic productivity, and legislative advocacy. Counts and frequencies were calculated and compared using χ tests. The survey was completed by 38 (90.4%) of 42 sites. The majority were associated with a freestanding children's hospital (57.9%) and Level I pediatric trauma center (86.8%). Most programs (79%) had at least one dedicated full-time equivalent (FTE) staff. Research was most common on child passenger safety and teen driving. Nearly 30% of programs offered educational curricula to health care providers; these sites were more likely to have FTE support (p = 0.036). Steady sources of funding were identified for 60.5% of programs, with 47.8% citing their hospital as the primary source; 73% of respondents were confident in their program's capacity to sustain activities; these were more likely to be larger programs (p = 0.001) with steady sources of funding (p < 0.001). Despite 73.7% of sites having academic affiliations, 60.5% had 5 or fewer publications over the previous 5 years. In the prior 2 years, 55.3% of programs impacted legislative or policy changes. Funding, size of program, and FTE had no statistical correlation with research productivity or number of legislative/policy contributions. This study characterizes the variation among pediatric IP programs within IFCK sites, while highlighting the association between financial and FTE support from programs' institutions with sustainable IP programming. These results can assist programs in identifying differences in relation to their peers.

76 FR 17935 - Protected Critical Infrastructure Information (PCII) Stakeholder Survey

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-31

... Infrastructure Protection (IP) will submit the following Information Collection Request to the Office of... questions about this Information Collection Request should be forwarded to DHS/NPPD/IP, Attn: Emily R... PCII Program is administered by IP's Infrastructure Information Collection Division (IICD). The PCII...

76 FR 59963 - Closed Captioning of Internet Protocol-Delivered Video Programming: Implementation of the Twenty...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-28

...In this document, the Commission proposes rules to implement provisions of the Twenty-First Century Communications and Video Accessibility Act of 2010 (``CVAA'') that mandate rules for closed captioning of certain video programming delivered using Internet protocol (``IP''). The Commission seeks comment on rules that would apply to the distributors, providers, and owners of IP-delivered video programming, as well as the devices that display such programming.

76 FR 17933 - Infrastructure Protection Data Call Survey

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-31

... Survey AGENCY: National Protection and Programs Directorate, DHS. ACTION: 60-Day Notice and request for... mission, IP requests opinions and information in a survey from IP Data Call participants regarding the IP Data Call process and the web-based application used to collect the CIKR data. The survey data...

75 FR 67989 - Agency Information Collection Activities: Office of Infrastructure Protection; Infrastructure...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-04

..., National Protection and Programs Directorate, Office of Infrastructure Protection (IP), will submit the... manner.'' DHS designated IP to lead these efforts. Given that the vast majority of the Nation's critical infrastructure and key resources in most sectors are privately owned or controlled, IP's success in achieving the...

75 FR 13775 - Agency Information Collection Activities: Proposed Collection; Comment Request, 1660-NEW...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-23

... Security Exercise and Evaluation Program (HSEEP) After Action Report (AAR) Improvement Plan (IP) AGENCY... (HSEEP) After Action Report (AAR) Improvement Plan (IP). SUMMARY: The Federal Emergency Management Agency... (HSEEP) After Action Report (AAR) Improvement Plan (IP). DATES: Comments must be submitted on or before...

78 FR 60301 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-01

... Evaluation Program (HSEEP) After Action Report (AAR) Improvement Plan (IP). DATES: Comments must be submitted...) Improvement Plan (IP) provides a standardized method for reporting the results of preparedness exercises and identifying, correcting and sharing as appropriate strengths and areas for improvement. Thus, the HSEEP AAR/IP...

Developing an Interventional Pulmonary Service in a Community-Based Private Practice: A Case Study.

PubMed

French, Kim D; Desai, Neeraj R; Diamond, Edward; Kovitz, Kevin L

2016-04-01

Interventional pulmonology (IP) is a field that uses minimally invasive techniques to diagnose, treat, and palliate advanced lung disease. Technology, formal training, and reimbursement for IP procedures have been slow to catch up with other interventional subspecialty areas. A byproduct of this pattern has been limited IP integration in private practice settings. We describe the key aspects and programmatic challenges of building an IP program in a community-based setting. A philosophical and financial buy-in by stakeholders and a regionalization of services, within and external to a larger practice, are crucial to success. Our experience demonstrates that a successful launch of an IP program increases overall visits as well as procedural volume without cannibalizing existing practice volume. We hope this might encourage others to provide this valuable service to their own communities. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Software for rapid time dependent ChIP-sequencing analysis (TDCA).

PubMed

Myschyshyn, Mike; Farren-Dai, Marco; Chuang, Tien-Jui; Vocadlo, David

2017-11-25

Chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) and associated methods are widely used to define the genome wide distribution of chromatin associated proteins, post-translational epigenetic marks, and modifications found on DNA bases. An area of emerging interest is to study time dependent changes in the distribution of such proteins and marks by using serial ChIP-seq experiments performed in a time resolved manner. Despite such time resolved studies becoming increasingly common, software to facilitate analysis of such data in a robust automated manner is limited. We have designed software called Time-Dependent ChIP-Sequencing Analyser (TDCA), which is the first program to automate analysis of time-dependent ChIP-seq data by fitting to sigmoidal curves. We provide users with guidance for experimental design of TDCA for modeling of time course (TC) ChIP-seq data using two simulated data sets. Furthermore, we demonstrate that this fitting strategy is widely applicable by showing that automated analysis of three previously published TC data sets accurately recapitulates key findings reported in these studies. Using each of these data sets, we highlight how biologically relevant findings can be readily obtained by exploiting TDCA to yield intuitive parameters that describe behavior at either a single locus or sets of loci. TDCA enables customizable analysis of user input aligned DNA sequencing data, coupled with graphical outputs in the form of publication-ready figures that describe behavior at either individual loci or sets of loci sharing common traits defined by the user. TDCA accepts sequencing data as standard binary alignment map (BAM) files and loci of interest in browser extensible data (BED) file format. TDCA accurately models the number of sequencing reads, or coverage, at loci from TC ChIP-seq studies or conceptually related TC sequencing experiments. TC experiments are reduced to intuitive parametric values that facilitate biologically relevant data analysis, and the uncovering of variations in the time-dependent behavior of chromatin. TDCA automates the analysis of TC ChIP-seq experiments, permitting researchers to easily obtain raw and modeled data for specific loci or groups of loci with similar behavior while also enhancing consistency of data analysis of TC data within the genomics field.

75 FR 41213 - National Protection and Programs Directorate; Infrastructure Protection Data Call Survey; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-15

... (IP), Infrastructure Information Collection Division (IICD) published a 60-day comment period notice..., ``IP Data Call.'' This is a correction notice to correct the title of the published 60-day notice to read, ``IP Data Call Survey.'' There are no further updates. This correction notice is issued as...

76 FR 5186 - National Protection and Programs Directorate; Agency Information Collection Activities; Office of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-28

...), Office of Infrastructure Protection (IP), will submit the following information collection request (ICR... Paperwork Reduction Act of 1995 (Pub. L. 104-13, 44 U.S.C. Chapter 35). IP is soliciting comments concerning... INFORMATION CONTACT: If additional information is required, contact DHS/NPPD/IP, Michael Beland, (703) 235...

Heterogeneous IP Ecosystem enabling Reuse (HIER)

DTIC Science & Technology

2017-03-22

Technical Approach and Justification IP reuse is a cornerstone of the commercial electronics market particularly in the digital domain...even in the digital domain. Significant investments in custom ASIC designs have been made by the government, but the IP resulting from such... approach to address requirements for that program. Research Plan The original vision for the HIER activity involved the evaluation

Continued Development of Internet Protocols under the IBM OS/MVS Operating System

DTIC Science & Technology

1985-01-25

developed a prototype TCP/IP implementation for an IBM MVS host under a previous DARPA contract’ as part of the Internet research effort on the design of...participated in the DARPA Internet research program which led to the present TCP and IP protocols. Development of a prototype implementation of TCP/IP

Impact of a New Teaching and Learning Approach in an Introductory Programming Course

ERIC Educational Resources Information Center

Iqbal Malik, Sohail; Coldwell-Neilson, Jo

2017-01-01

High failure and dropout rates are reported in introductory programming (IP) courses in different studies despite extensive research attempting to address the issue. In this study, we introduced an ADRI (Approach, Deployment, Result, Improvement) approach in the teaching and learning process of an IP course to improve learning and success rates.…

Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis

PubMed Central

Malhotra, Deepti; Portales-Casamar, Elodie; Singh, Anju; Srivastava, Siddhartha; Arenillas, David; Happel, Christine; Shyr, Casper; Wakabayashi, Nobunao; Kensler, Thomas W.; Wasserman, Wyeth W.; Biswal, Shyam

2010-01-01

The Nrf2 (nuclear factor E2 p45-related factor 2) transcription factor responds to diverse oxidative and electrophilic environmental stresses by circumventing repression by Keap1, translocating to the nucleus, and activating cytoprotective genes. Nrf2 responses provide protection against chemical carcinogenesis, chronic inflammation, neurodegeneration, emphysema, asthma and sepsis in murine models. Nrf2 regulates the expression of a plethora of genes that detoxify oxidants and electrophiles and repair or remove damaged macromolecules, such as through proteasomal processing. However, many direct targets of Nrf2 remain undefined. Here, mouse embryonic fibroblasts (MEF) with either constitutive nuclear accumulation (Keap1−/−) or depletion (Nrf2−/−) of Nrf2 were utilized to perform chromatin-immunoprecipitation with parallel sequencing (ChIP-Seq) and global transcription profiling. This unique Nrf2 ChIP-Seq dataset is highly enriched for Nrf2-binding motifs. Integrating ChIP-Seq and microarray analyses, we identified 645 basal and 654 inducible direct targets of Nrf2, with 244 genes at the intersection. Modulated pathways in stress response and cell proliferation distinguish the inducible and basal programs. Results were confirmed in an in vivo stress model of cigarette smoke-exposed mice. This study reveals global circuitry of the Nrf2 stress response emphasizing Nrf2 as a central node in cell survival response. PMID:20460467

78 FR 16692 - Chemical Facility Anti-Terrorism Standards (CFATS)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-18

... Protection (IP), Infrastructure Security Compliance Division (ISCD) will submit the following Information... submissions of responses. FOR FURTHER INFORMATION CONTACT: CFATS Program Manager, DHS/NPPD/IP/ ISCD, [email protected

Determination of the Parameter Sets for the Best Performance of IPS-driven ENLIL Model

NASA Astrophysics Data System (ADS)

Yun, Jongyeon; Choi, Kyu-Cheol; Yi, Jonghyuk; Kim, Jaehun; Odstrcil, Dusan

2016-12-01

Interplanetary scintillation-driven (IPS-driven) ENLIL model was jointly developed by University of California, San Diego (UCSD) and National Aeronaucics and Space Administration/Goddard Space Flight Center (NASA/GSFC). The model has been in operation by Korean Space Weather Cetner (KSWC) since 2014. IPS-driven ENLIL model has a variety of ambient solar wind parameters and the results of the model depend on the combination of these parameters. We have conducted researches to determine the best combination of parameters to improve the performance of the IPS-driven ENLIL model. The model results with input of 1,440 combinations of parameters are compared with the Advanced Composition Explorer (ACE) observation data. In this way, the top 10 parameter sets showing best performance were determined. Finally, the characteristics of the parameter sets were analyzed and application of the results to IPS-driven ENLIL model was discussed.

Anxiety and the Imposter Phenomenon among Graduate Students in Online versus Traditional Programs

ERIC Educational Resources Information Center

Fraenza, Christy B.

2014-01-01

High anxiety levels have been associated with high levels of the imposter phenomenon (IP), a negative experience of feeling like a fraud. Because IP can leave a person living in a negative cycle of anxiety that could limit participation in academic pursuits, the purpose of this study was to determine if there were differences in IP between…

ChIPpeakAnno: a Bioconductor package to annotate ChIP-seq and ChIP-chip data

PubMed Central

2010-01-01

Background Chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP-seq) or ChIP followed by genome tiling array analysis (ChIP-chip) have become standard technologies for genome-wide identification of DNA-binding protein target sites. A number of algorithms have been developed in parallel that allow identification of binding sites from ChIP-seq or ChIP-chip datasets and subsequent visualization in the University of California Santa Cruz (UCSC) Genome Browser as custom annotation tracks. However, summarizing these tracks can be a daunting task, particularly if there are a large number of binding sites or the binding sites are distributed widely across the genome. Results We have developed ChIPpeakAnno as a Bioconductor package within the statistical programming environment R to facilitate batch annotation of enriched peaks identified from ChIP-seq, ChIP-chip, cap analysis of gene expression (CAGE) or any experiments resulting in a large number of enriched genomic regions. The binding sites annotated with ChIPpeakAnno can be viewed easily as a table, a pie chart or plotted in histogram form, i.e., the distribution of distances to the nearest genes for each set of peaks. In addition, we have implemented functionalities for determining the significance of overlap between replicates or binding sites among transcription factors within a complex, and for drawing Venn diagrams to visualize the extent of the overlap between replicates. Furthermore, the package includes functionalities to retrieve sequences flanking putative binding sites for PCR amplification, cloning, or motif discovery, and to identify Gene Ontology (GO) terms associated with adjacent genes. Conclusions ChIPpeakAnno enables batch annotation of the binding sites identified from ChIP-seq, ChIP-chip, CAGE or any technology that results in a large number of enriched genomic regions within the statistical programming environment R. Allowing users to pass their own annotation data such as a different Chromatin immunoprecipitation (ChIP) preparation and a dataset from literature, or existing annotation packages, such as GenomicFeatures and BSgenome, provides flexibility. Tight integration to the biomaRt package enables up-to-date annotation retrieval from the BioMart database. PMID:20459804

Accounting for immunoprecipitation efficiencies in the statistical analysis of ChIP-seq data.

PubMed

Bao, Yanchun; Vinciotti, Veronica; Wit, Ernst; 't Hoen, Peter A C

2013-05-30

ImmunoPrecipitation (IP) efficiencies may vary largely between different antibodies and between repeated experiments with the same antibody. These differences have a large impact on the quality of ChIP-seq data: a more efficient experiment will necessarily lead to a higher signal to background ratio, and therefore to an apparent larger number of enriched regions, compared to a less efficient experiment. In this paper, we show how IP efficiencies can be explicitly accounted for in the joint statistical modelling of ChIP-seq data. We fit a latent mixture model to eight experiments on two proteins, from two laboratories where different antibodies are used for the two proteins. We use the model parameters to estimate the efficiencies of individual experiments, and find that these are clearly different for the different laboratories, and amongst technical replicates from the same lab. When we account for ChIP efficiency, we find more regions bound in the more efficient experiments than in the less efficient ones, at the same false discovery rate. A priori knowledge of the same number of binding sites across experiments can also be included in the model for a more robust detection of differentially bound regions among two different proteins. We propose a statistical model for the detection of enriched and differentially bound regions from multiple ChIP-seq data sets. The framework that we present accounts explicitly for IP efficiencies in ChIP-seq data, and allows to model jointly, rather than individually, replicates and experiments from different proteins, leading to more robust biological conclusions.

Running TCP/IP over ATM Networks.

ERIC Educational Resources Information Center

Witt, Michael

1995-01-01

Discusses Internet protocol (IP) and subnets and describes how IP may operate over asynchronous transfer mode (ATM). Topics include TCP (transmission control protocol), ATM cells and adaptation layers, a basic architectural model for IP over ATM, address resolution, mapping IP to a subnet technology, and connection management strategy. (LRW)

Pre-equilibrium Longitudinal Flow in the IP-Glasma Framework for Pb+Pb Collisions at the LHC

NASA Astrophysics Data System (ADS)

McDonald, Scott; Shen, Chun; Fillion-Gourdeau, François; Jeon, Sangyong; Gale, Charles

2017-08-01

In this work, we debut a new implementation of IP-Glasma and quantify the pre-equilibrium longitudinal flow in the IP-Glasma framework. The saturation physics based IP-Glasma model naturally provides a non-zero initial longitudinal flow through its pre-equilibrium Yang-Mills evolution. A hybrid IP-Glasma+MUSIC+UrQMD frame-work is employed to test this new implementation against experimental data and to make further predictions about hadronic flow observables in Pb+Pb collisions at 5.02 TeV. Finally, the non-zero pre-equilibrium longitudinal flow of the IP-Glasma model is quantified, and its origin is briefly discussed.

Comparison of gating dynamics of different IP3R channels with immune algorithm searching for channel parameter distributions

NASA Astrophysics Data System (ADS)

Cai, Xiuhong; Li, Xiang; Qi, Hong; Wei, Fang; Chen, Jianyong; Shuai, Jianwei

2016-10-01

The gating properties of the inositol 1, 4, 5-trisphosphate (IP3) receptor (IP3R) are determined by the binding and unbinding capability of Ca2+ ions and IP3 messengers. With the patch clamp experiments, the stationary properties have been discussed for Xenopus oocyte type-1 IP3R (Oo-IP3R1), type-3 IP3R (Oo-IP3R3) and Spodoptera frugiperda IP3R (Sf-IP3R). In this paper, in order to provide insights about the relation between the observed gating characteristics and the gating parameters in different IP3Rs, we apply the immune algorithm to fit the parameters of a modified DeYoung-Keizer model. By comparing the fitting parameter distributions of three IP3Rs, we suggest that the three types of IP3Rs have the similar open sensitivity in responding to IP3. The Oo-IP3R3 channel is easy to open in responding to low Ca2+ concentration, while Sf-IP3R channel is easily inhibited in responding to high Ca2+ concentration. We also show that the IP3 binding rate is not a sensitive parameter for stationary gating dynamics for three IP3Rs, but the inhibitory Ca2+ binding/unbinding rates are sensitive parameters for gating dynamics for both Oo-IP3R1 and Oo-IP3R3 channels. Such differences may be important in generating the spatially and temporally complex Ca2+ oscillations in cells. Our study also demonstrates that the immune algorithm can be applied for model parameter searching in biological systems.

A Descriptive Model of Information Problem Solving while Using Internet

ERIC Educational Resources Information Center

Brand-Gruwel, Saskia; Wopereis, Iwan; Walraven, Amber

2009-01-01

This paper presents the IPS-I-model: a model that describes the process of information problem solving (IPS) in which the Internet (I) is used to search information. The IPS-I-model is based on three studies, in which students in secondary and (post) higher education were asked to solve information problems, while thinking aloud. In-depth analyses…

Factor Structure of the Revised TOEIC[R] Test: A Multiple-Sample Analysis

ERIC Educational Resources Information Center

In'nami, Yo; Koizumi, Rie

2012-01-01

This study examined the factor structure of the listening and reading sections of the revised Test of English for International Communication (TOEIC[R]) test. The data from the TOEIC IP (institutional program) test taken by 569 English learners were randomly split into two samples (n = 285 vs. 284). Four models (higher-order, correlated,…

A supported employment linkage intervention for people with schizophrenia who want a chance to work.

PubMed

Solar, Ann

2014-06-01

Investigate feasibility and development of a linkage intervention to the evidence-based Individual Placement and Support (IPS) approach to supported employment (SE) for patients with schizophrenia on a mental health unit who want to work in competitive employment. Literature review about the evidence-based IPS approach to SE in schizophrenia and why it might not be implemented in mental health services. Analysis of 10 adult mental health unit multidisciplinary staff interviews for categories in the literature review of IPS implementation barriers and whether these barriers could be overcome. There was lack of full staff knowledge of the IPS approach to SE. However, all staff knew respect for patient choice was paramount, community employment programs existed for the disabled, an outreach linkage process to such a program and ongoing support for people with schizophrenia would be required. There was staff ambivalence about SE for patients with schizophrenia. Despite staff ambivalence about SE for people with schizophrenia there was still enough staff knowledge and openness to shape an IPS linkage intervention from a staff perspective. © The Royal Australian and New Zealand College of Psychiatrists 2014.

A mathematical model of calcium dynamics in HSY cells

PubMed Central

Han, Jung Min; Tanimura, Akihiko; Kirk, Vivien; Sneyd, James

2017-01-01

Saliva is an essential part of activities such as speaking, masticating and swallowing. Enzymes in salivary fluid protect teeth and gums from infectious diseases, and also initiate the digestion process. Intracellular calcium (Ca2+) plays a critical role in saliva secretion and regulation. Experimental measurements of Ca2+ and inositol trisphosphate (IP3) concentrations in HSY cells, a human salivary duct cell line, show that when the cells are stimulated with adenosine triphosphate (ATP) or carbachol (CCh), they exhibit coupled oscillations with Ca2+ spike peaks preceding IP3 spike peaks. Based on these data, we construct a mathematical model of coupled Ca2+ and IP3 oscillations in HSY cells and perform model simulations of three different experimental settings to forecast Ca2+ responses. The model predicts that when Ca2+ influx from the extracellular space is removed, oscillations gradually slow down until they stop. The model simulation of applying a pulse of IP3 predicts that photolysis of caged IP3 causes a transient increase in the frequency of the Ca2+ oscillations. Lastly, when Ca2+-dependent activation of PLC is inhibited, we see an increase in the oscillation frequency and a decrease in the amplitude. These model predictions are confirmed by experimental data. We conclude that, although concentrations of Ca2+ and IP3 oscillate, Ca2+ oscillations in HSY cells are the result of modulation of the IP3 receptor by intracellular Ca2+, and that the period is modulated by the accompanying IP3 oscillations. PMID:28199326

An evaluation of the opportunities for collaborative practice occurring in and the impact of interprofessional education on advanced pharmacy practice experiences.

PubMed

Umland, Elena M; Valenzano, Jonathan; Brown, Caitlin; Giordano, Carolyn

2017-05-01

To evaluate the impact of interprofessional (IP) education (IPE) programs during the first three years of a four-year doctor of pharmacy program on student preparedness and ability to function as a collaborative team member and to garner student feedback on collaboration experienced during the Advanced Pharmacy Practice Experiences (APPEs). Likert scale based statements and open-ended questions were added to the student course evaluations for the APPEs for two graduating classes of students. Quantitative data were analyzed using SPSS (repeated measures ANOVA and MANOVA). Thematic analysis by three reviewers reaching consensus was used to evaluate the qualitative data. Students reported being well prepared for IP collaboration (average ratings ranged from a mean of 3.37-3.46 on a scale of 1-4; 1=not at all prepared and 4=very well prepared). On average, students spent 26-50% of their time working with colleagues from other healthcare professions. In describing their preparedness for IP collaboration, the IP core competency of teams/teamwork was addressed in 50% of the submitted responses. The competencies of values/ethics, roles/responsibilities and IP communication were addressed by 2%, 20% and 28% of the written responses, respectively. Required longitudinal IP programs in the first three years of the pharmacy curriculum contribute to the students' perceived preparedness for collaborative practice during their APPEs. Developing practice sites to increase the opportunities for students to practice collaboratively is key. Further education of and emphasis by preceptors relative to the IPE competencies is desired. Copyright © 2017 Elsevier Inc. All rights reserved.

Representation of Semantic Similarity in the Left Intraparietal Sulcus: Functional Magnetic Resonance Imaging Evidence

PubMed Central

Neyens, Veerle; Bruffaerts, Rose; Liuzzi, Antonietta G.; Kalfas, Ioannis; Peeters, Ronald; Keuleers, Emmanuel; Vogels, Rufin; De Deyne, Simon; Storms, Gert; Dupont, Patrick; Vandenberghe, Rik

2017-01-01

According to a recent study, semantic similarity between concrete entities correlates with the similarity of activity patterns in left middle IPS during category naming. We examined the replicability of this effect under passive viewing conditions, the potential role of visuoperceptual similarity, where the effect is situated compared to regions that have been previously implicated in visuospatial attention, and how it compares to effects of object identity and location. Forty-six subjects participated. Subjects passively viewed pictures from two categories, musical instruments and vehicles. Semantic similarity between entities was estimated based on a concept-feature matrix obtained in more than 1,000 subjects. Visuoperceptual similarity was modeled based on the HMAX model, the AlexNet deep convolutional learning model, and thirdly, based on subjective visuoperceptual similarity ratings. Among the IPS regions examined, only left middle IPS showed a semantic similarity effect. The effect was significant in hIP1, hIP2, and hIP3. Visuoperceptual similarity did not correlate with similarity of activity patterns in left middle IPS. The semantic similarity effect in left middle IPS was significantly stronger than in the right middle IPS and also stronger than in the left or right posterior IPS. The semantic similarity effect was similar to that seen in the angular gyrus. Object identity effects were much more widespread across nearly all parietal areas examined. Location effects were relatively specific for posterior IPS and area 7 bilaterally. To conclude, the current findings replicate the semantic similarity effect in left middle IPS under passive viewing conditions, and demonstrate its anatomical specificity within a cytoarchitectonic reference frame. We propose that the semantic similarity effect in left middle IPS reflects the transient uploading of semantic representations in working memory. PMID:28824405

How Maryland increased infection prevention and control activity in long-term care facilities, 2003-2008.

PubMed

Roup, Brenda J; Scaletta, Joseph M

2011-05-01

In January 2003, the Maryland Department of Health and Mental Hygiene (DHMH) assessed the state of infection prevention and control (IPC) resources and practices in all long-term care facilities (LTC) in the state. Only 8.1% of facilities that responded employed a trained IPC professional (IP) who managed the facility IPC program. Between 2003 and 2008, the DHMH partnered with long-term care industry trade associations and spearheaded regulatory, educational, and financial initiatives to improve this situation. In January 2008, all LTC facilities in the state were resurveyed to determine the impact of these initiatives on IPC activities. The 2008 survey indicated that 44% of LTC facilities used a trained IP who managed the IPC program, a 5-fold increase from 2003. Unpublished DHMH outbreak data indicated that LTC facilities with a trained IP recognized and reported outbreaks to the local health department 2 days sooner than facilities without a trained IP, resulting in fewer cases of disease. Multiple initiatives with concerned stakeholders and LTC partners over the course of 5 years resulted in increased numbers of LTC facilities with trained IPs who recognized and responded to outbreaks sooner than facilities without trained IPs. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Neuronal calcium wave propagation varies with changes in endoplasmic reticulum parameters: a computer model

PubMed Central

Neymotin, Samuel A.; McDougal, Robert A.; Sherif, Mohamed A.; Fall, Christopher P.; Hines, Michael L.; Lytton, William W.

2015-01-01

Calcium (Ca2+) waves provide a complement to neuronal electrical signaling, forming a key part of a neuron’s second messenger system. We developed a reaction-diffusion model of an apical dendrite with diffusible inositol triphosphate (IP3), diffusible Ca2+, IP3 receptors (IP3Rs), endoplasmic reticulum (ER) Ca2+ leak, and ER pump (SERCA) on ER. Ca2+ is released from ER stores via IP3Rs upon binding of IP3 and Ca2+. This results in Ca2+-induced-Ca2+-release (CICR) and increases Ca2+ spread. At least two modes of Ca2+ wave spread have been suggested: a continuous mode based on presumed relative homogeneity of ER within the cell; and a pseudo-saltatory model where Ca2+ regeneration occurs at discrete points with diffusion between them. We compared the effects of three patterns of hypothesized IP3R distribution: 1. continuous homogeneous ER, 2. hotspots with increased IP3R density (IP3R hotspots), 3. areas of increased ER density (ER stacks). All three modes produced Ca2+ waves with velocities similar to those measured in vitro (~50–90µm /sec). Continuous ER showed high sensitivity to IP3R density increases, with time to onset reduced and speed increased. Increases in SERCA density resulted in opposite effects. The measures were sensitive to changes in density and spacing of IP3R hotspots and stacks. Increasing the apparent diffusion coefficient of Ca2+ substantially increased wave speed. An extended electrochemical model, including voltage gated calcium channels and AMPA synapses, demonstrated that membrane priming via AMPA stimulation enhances subsequent Ca2+ wave amplitude and duration. Our modeling suggests that pharmacological targeting of IP3Rs and SERCA could allow modulation of Ca2+ wave propagation in diseases where Ca2+ dysregulation has been implicated. PMID:25734493

Sampled control stability of the ESA instrument pointing system

NASA Astrophysics Data System (ADS)

Thieme, G.; Rogers, P.; Sciacovelli, D.

Stability analysis and simulation results are presented for the ESA Instrument Pointing System (IPS) that is to be used in Spacelab's second launch. Of the two IPS plant dynamic models used in the ESA and NASA activities, one is based on six interconnected rigid bodies that represent the IPS and plant dynamic models used in the ESA and NASA activities, one is based on six interconnected rigid bodies that represent the IPS and its payload, while the other follows the NASA practice of defining an IPS-Spacelab 2 plant configuration through a structural finite element model, which is then used to generate modal data for various pointing directions. In both cases, the IPS dynamic plant model is truncated, then discretized at the sampling frequency and interfaces to a PID-based control law. A stability analysis has been carried out in discrete domain for various instrument pointing directions, taking into account suitable parameter variation ranges. A number of time simulations are presented.

A mixed-mode traffic assignment model with new time-flow impedance function

NASA Astrophysics Data System (ADS)

Lin, Gui-Hua; Hu, Yu; Zou, Yuan-Yang

2018-01-01

Recently, with the wide adoption of electric vehicles, transportation network has shown different characteristics and been further developed. In this paper, we present a new time-flow impedance function, which may be more realistic than the existing time-flow impedance functions. Based on this new impedance function, we present an optimization model for a mixed-mode traffic network in which battery electric vehicles (BEVs) and gasoline vehicles (GVs) are chosen. We suggest two approaches to handle the model: One is to use the interior point (IP) algorithm and the other is to employ the sequential quadratic programming (SQP) algorithm. Three numerical examples are presented to illustrate the efficiency of these approaches. In particular, our numerical results show that more travelers prefer to choosing BEVs when the distance limit of BEVs is long enough and the unit operating cost of GVs is higher than that of BEVs, and the SQP algorithm is faster than the IP algorithm.

Jamming Attack in Wireless Sensor Network: From Time to Space

NASA Astrophysics Data System (ADS)

Sun, Yanqiang; Wang, Xiaodong; Zhou, Xingming

Classical jamming attack models in the time domain have been proposed, such as constant jammer, random jammer, and reactive jammer. In this letter, we consider a new problem: given k jammers, how does the attacker minimize the pair-wise connectivity among the nodes in a Wireless Sensor Network (WSN)? We call this problem k-Jammer Deployment Problem (k-JDP). To the best of our knowledge, this is the first attempt at considering the position-critical jamming attack against wireless sensor network. We mainly make three contributions. First, we prove that the decision version of k-JDP is NP-complete even in the ideal situation where the attacker has full knowledge of the topology information of sensor network. Second, we propose a mathematical formulation based on Integer Programming (IP) model which yields an optimal solution. Third, we present a heuristic algorithm HAJDP, and compare it with the IP model. Numerical results show that our heuristic algorithm is computationally efficient.

75 FR 31458 - Infrastructure Protection Data Call Survey

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-03

...-0022] Infrastructure Protection Data Call Survey AGENCY: National Protection and Programs Directorate... New Information Collection Request, Infrastructure Protection Data Call Survey. DHS previously... territories are able to achieve this mission, IP requests opinions and information in a survey from IP Data...

Digital controller design: Continuous and discrete describing function analysis of the IPS system

NASA Technical Reports Server (NTRS)

1977-01-01

The dynamic equations and the mathematical model of the continuous-data IPS control system are developed. The IPS model considered included one flexible body mode and was hardmounted to the Orbiter/Pallet. The model contains equations describing a torque feed-forward loop (using accelerometers as inputs) which will aid in reducing the pointing errors caused by Orbiter disturbances.

An Analytic Model of Gas Turbine Engine Installations.

DTIC Science & Technology

1984-09-01

CODE . . . . ............. 37 C. CTHiEi PROGRAM FEAL’RES . . . . . . . . . . . . 38 IV. RESULTS AJD RECOXEMNDTZCINS . . . . . . . . . . . 43 A GEN ER...IP(IIST.L.T.1.O) Go 0 7Q GO T3 55 C COMPU:Z FAN PRESSURE AND0 MATCH FAN PERFORMANCE 70 SYSTEM 70 FANC ;=(DP2𔃾.DP£45+DPi2L5.19696 croCf3ZDNIKC) c IF

Hybrid model for wireless mobility management using IPv6

NASA Astrophysics Data System (ADS)

Howie, Douglas P.; Sun, Junzhao; Koivisto, Antti T.

2001-07-01

Within the coming decade, there will be a dramatic increase in the availability of inexpensive, computationally powerful mobile devices running applications which use the Internet Protocol (IP) to access multimedia services over broad-band wireless connections. To this end, there has been extensive research and standardization in the areas of Mobile IP and IPv6. The purpose of this paper is to apply this work to the issues involved in designing a mobility model able to adapt to different wireless mobile IP scenarios. We describe the usefulness of this model in the 4th generation mobile multimedia systems to come. This new model has been synthesized through a comparative analysis of current mobile IP models where particular attention has been given to the problems of mobile IP handoff and mobility management and their impact on QoS. By applying a unique perspective to these problems, our model is used to set a roadmap for future mobile IPv6 testbed construction.

Response functions of Fuji imaging plates to monoenergetic protons in the energy range 0.6-3.2 MeV

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

Bonnet, T.; Denis-Petit, D.; Gobet, F.

2013-01-15

We have measured the responses of Fuji MS, SR, and TR imaging plates (IPs) to protons with energies ranging from 0.6 to 3.2 MeV. Monoenergetic protons were produced with the 3.5 MV AIFIRA (Applications Interdisciplinaires de Faisceaux d'Ions en Region Aquitaine) accelerator at the Centre d'Etudes Nucleaires de Bordeaux Gradignan (CENBG). The IPs were irradiated with protons backscattered off a tantalum target. We present the photo-stimulated luminescence response of the IPs together with the fading measurements for these IPs. A method is applied to allow correction of fading effects for variable proton irradiation duration. Using the IP fading corrections, amore » model of the IP response function to protons was developed. The model enables extrapolation of the IP response to protons up to proton energies of 10 MeV. Our work is finally compared to previous works conducted on Fuji TR IP response to protons.« less

ChIP-PIT: Enhancing the Analysis of ChIP-Seq Data Using Convex-Relaxed Pair-Wise Interaction Tensor Decomposition.

PubMed

Zhu, Lin; Guo, Wei-Li; Deng, Su-Ping; Huang, De-Shuang

2016-01-01

In recent years, thanks to the efforts of individual scientists and research consortiums, a huge amount of chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) experimental data have been accumulated. Instead of investigating them independently, several recent studies have convincingly demonstrated that a wealth of scientific insights can be gained by integrative analysis of these ChIP-seq data. However, when used for the purpose of integrative analysis, a serious drawback of current ChIP-seq technique is that it is still expensive and time-consuming to generate ChIP-seq datasets of high standard. Most researchers are therefore unable to obtain complete ChIP-seq data for several TFs in a wide variety of cell lines, which considerably limits the understanding of transcriptional regulation pattern. In this paper, we propose a novel method called ChIP-PIT to overcome the aforementioned limitation. In ChIP-PIT, ChIP-seq data corresponding to a diverse collection of cell types, TFs and genes are fused together using the three-mode pair-wise interaction tensor (PIT) model, and the prediction of unperformed ChIP-seq experimental results is formulated as a tensor completion problem. Computationally, we propose efficient first-order method based on extensions of coordinate descent method to learn the optimal solution of ChIP-PIT, which makes it particularly suitable for the analysis of massive scale ChIP-seq data. Experimental evaluation the ENCODE data illustrate the usefulness of the proposed model.

GMI-IPS: Python Processing Software for Aircraft Campaigns

NASA Technical Reports Server (NTRS)

Damon, M. R.; Strode, S. A.; Steenrod, S. D.; Prather, M. J.

2018-01-01

NASA's Atmospheric Tomography Mission (ATom) seeks to understand the impact of anthropogenic air pollution on gases in the Earth's atmosphere. Four flight campaigns are being deployed on a seasonal basis to establish a continuous global-scale data set intended to improve the representation of chemically reactive gases in global atmospheric chemistry models. The Global Modeling Initiative (GMI), is creating chemical transport simulations on a global scale for each of the ATom flight campaigns. To meet the computational demands required to translate the GMI simulation data to grids associated with the flights from the ATom campaigns, the GMI ICARTT Processing Software (GMI-IPS) has been developed and is providing key functionality for data processing and analysis in this ongoing effort. The GMI-IPS is written in Python and provides computational kernels for data interpolation and visualization tasks on GMI simulation data. A key feature of the GMI-IPS, is its ability to read ICARTT files, a text-based file format for airborne instrument data, and extract the required flight information that defines regional and temporal grid parameters associated with an ATom flight. Perhaps most importantly, the GMI-IPS creates ICARTT files containing GMI simulated data, which are used in collaboration with ATom instrument teams and other modeling groups. The initial main task of the GMI-IPS is to interpolate GMI model data to the finer temporal resolution (1-10 seconds) of a given flight. The model data includes basic fields such as temperature and pressure, but the main focus of this effort is to provide species concentrations of chemical gases for ATom flights. The software, which uses parallel computation techniques for data intensive tasks, linearly interpolates each of the model fields to the time resolution of the flight. The temporally interpolated data is then saved to disk, and is used to create additional derived quantities. In order to translate the GMI model data to the spatial grid of the flight path as defined by the pressure, latitude, and longitude points at each flight time record, a weighted average is then calculated from the nearest neighbors in two dimensions (latitude, longitude). Using SciPya's Regular Grid Interpolator, interpolation functions are generated for the GMI model grid and the calculated weighted averages. The flight path points are then extracted from the ATom ICARTT instrument file, and are sent to the multi-dimensional interpolating functions to generate GMI field quantities along the spatial path of the flight. The interpolated field quantities are then written to a ICARTT data file, which is stored for further manipulation. The GMI-IPS is aware of a generic ATom ICARTT header format, containing basic information for all flight campaigns. The GMI-IPS includes logic to edit metadata for the derived field quantities, as well as modify the generic header data such as processing dates and associated instrument files. The ICARTT interpolated data is then appended to the modified header data, and the ICARTT processing is complete for the given flight and ready for collaboration. The output ICARTT data adheres to the ICARTT file format standards V1.1. The visualization component of the GMI-IPS uses Matplotlib extensively and has several functions ranging in complexity. First, it creates a model background curtain for the flight (time versus model eta levels) with the interpolated flight data superimposed on the curtain. Secondly, it creates a time-series plot of the interpolated flight data. Lastly, the visualization component creates averaged 2D model slices (longitude versus latitude) with overlaid flight track circles at key pressure levels. The GMI-IPS consists of a handful of classes and supporting functionality that have been generalized to be compatible with any ICARTT file that adheres to the base class definition. The base class represents a generic ICARTT entry, only defining a single time entry and 3D spatial positioning parameters. Other classes inherit from this base class; several classes for input ICARTT instrument files, which contain the necessary flight positioning information as a basis for data processing, as well as other classes for output ICARTT files, which contain the interpolated model data. Utility classes provide functionality for routine procedures such as: comparing field names among ICARTT files, reading ICARTT entries from a data file and storing them in data structures, and returning a reduced spatial grid based on a collection of ICARTT entries. Although the GMI-IPS is compatible with GMI model data, it can be adapted with reasonable effort for any simulation that creates Hierarchical Data Format (HDF) files. The same can be said of its adaptability to ICARTT files outside of the context of the ATom mission. The GMI-IPS contains just under 30,000 lines of code, eight classes, and a dozen drivers and utility programs. It is maintained with GIT source code management and has been used to deliver processed GMI model data for the ATom campaigns that have taken place to date.

Research on TCP/IP network communication based on Node.js

NASA Astrophysics Data System (ADS)

Huang, Jing; Cai, Lixiong

2018-04-01

In the face of big data, long connection and high synchronization, TCP/IP network communication will cause performance bottlenecks due to its blocking multi-threading service model. This paper presents a method of TCP/IP network communication protocol based on Node.js. On the basis of analyzing the characteristics of Node.js architecture and asynchronous non-blocking I/O model, the principle of its efficiency is discussed, and then compare and analyze the network communication model of TCP/IP protocol to expound the reasons why TCP/IP protocol stack is widely used in network communication. Finally, according to the large data and high concurrency in the large-scale grape growing environment monitoring process, a TCP server design based on Node.js is completed. The results show that the example runs stably and efficiently.

Social costs of expanding access to evidence-based supported employment: concepts and interpretive review of evidence.

PubMed

Salkever, David

2013-02-01

A recent policy analysis argued that expanding access to evidence-based supported employment can provide savings in major components of social costs. This article extends the scope of this policy analysis by placing the argument within a recently developed economic framework for social cost-effectiveness analysis that defines a program's social cost impact as its effect on net consumption of all goods and services. A total of 27 studies over the past two decades are reviewed to synthesize evidence of the social cost impacts of expanding access to the individual placement and support model of supported employment (IPS-SE). Most studies have focused primarily on agency costs of providing IPS-SE services, cost offsets when clients shift from "traditional" rehabilitation to IPS-SE, and impacts on clients' earnings. Because costs and cost offsets are similar in magnitude, incremental costs of expanding services to persons who would otherwise receive traditional services are probably small or even negative. The population served by an expansion could be sizable, but the feasibility of a policy targeting IPS-SE expansion in this way has yet to be demonstrated. IPS-SE has positive impacts on competitive job earnings, but these may not fully translate into social cost offsets. Additional empirical support is needed for the argument that large-scale expansion would yield substantial mental health treatment cost offsets. Other gaps in evidence of policy impacts include take-up rate estimates, cost impact estimates from longer-term studies (exceeding two years), and longer-term studies of whether IPS-SE prevents younger clients from becoming recipients of Supplemental Security Income or Social Security Disability Insurance

78 FR 75573 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-12

..., facsimile number (202) 646-3347, or email address [email protected] (HSEEP) After Action Report (AAR) Improvement Plan (IP). Type of Information Collection: Revision of a... Exercise and Evaluation Program (HSEEP) After Action Report (AAR) Improvement Plan (IP). Abstract: The...

Research and Simulation on Application of the Mobile IP Network

NASA Astrophysics Data System (ADS)

Yibing, Deng; Wei, Hu; Minghui, Li; Feng, Gao; Junyi, Shen

The paper analysed the mobile node, home agent, and foreign agent of mobile IP network firstly, some key technique, such as mobile IP network basical principle, protocol work principle, agent discovery, registration, and IP packet transmission, were discussed. Then a network simulation model was designed, validating the characteristic of mobile IP network, and some advantages, which were brought by mobile network, were testified. Finally, the conclusion is gained: mobile IP network could realize the expectation of consumer that they can communicate with others anywhere.

Provider-identified barriers and facilitators to implementing a supported employment program in spinal cord injury.

PubMed

Cotner, Bridget A; Ottomanelli, Lisa; O'Connor, Danielle R; Trainor, John K

2018-06-01

In a 5-year study, individual placement and support (IPS) significantly increased employment rate of United States Veterans with spinal cord injury (SCI), a historically underemployed population. In a follow-up study, data on barriers and facilitators to IPS implementation were identified. Over 24 months of implementation, 82 key medical and vocational staff underwent semi-structured interviews (n = 130). Interviews were digitally recorded and qualitatively analyzed (ATLAS.ti v0.7) using a constant comparative method to generate themes. Some barriers to implementation occurred throughout the study, such as Veterans' lack of motivation and providers' difficulty integrating vocational and medical rehabilitation. Other barriers emerged at specific stages, for example, early barriers included a large geographic service area and a large patient caseload, and late barriers included need for staff education. Facilitators were mostly constant throughout implementation and included leadership support and successful integration of vocational staff into the medical care team. Implementation strategies need to be adjusted as implementation progresses and matures. The strategies that succeeded in this setting, which were situated in a real-world context of providing IPS as a part of SCI medical care, may inform implementation of IPS for other populations with physical disabilities. Implications for Rehabilitation Key facilitators to IPS in SCI implementation are integrating vocational staff with expertise in IPS and SCI on clinical rehabilitation teams and providing leadership support. Ongoing barriers to IPS in SCI include patient specific and program administration factors such as caseload size and staffing patterns. Varying implementation strategies are needed to address barriers as they arise and facilitate successful implementation.

Kinetic Description of the Impedance Probe

NASA Astrophysics Data System (ADS)

Oberrath, Jens; Lapke, Martin; Mussenbrock, Thomas; Brinkmann, Ralf

2011-10-01

Active plasma resonance spectroscopy is a well known diagnostic method. Many concepts of this method are theoretically investigated and realized as a diagnostic tool, one of which is the impedance probe (IP). The application of such a probe in plasmas with pressures of a few Pa raises the question whether kinetic effects have to be taken into account or not. To address this question a kinetic model is necessary. A general kinetic model for an electrostatic concept of active plasma spectroscopy was presented by R.P. Brinkmann and can be used to describe the multipole resonance probe (MRP). In principle the IP is interpretable as a special case of the MRP in lower order. Thus, we are able to describe the IP by the kinetic model of the MRP. Based on this model we derive a solution to investigate the influence of kinetic effects to the resonance behavior of the IP. Active plasma resonance spectroscopy is a well known diagnostic method. Many concepts of this method are theoretically investigated and realized as a diagnostic tool, one of which is the impedance probe (IP). The application of such a probe in plasmas with pressures of a few Pa raises the question whether kinetic effects have to be taken into account or not. To address this question a kinetic model is necessary. A general kinetic model for an electrostatic concept of active plasma spectroscopy was presented by R.P. Brinkmann and can be used to describe the multipole resonance probe (MRP). In principle the IP is interpretable as a special case of the MRP in lower order. Thus, we are able to describe the IP by the kinetic model of the MRP. Based on this model we derive a solution to investigate the influence of kinetic effects to the resonance behavior of the IP. The authors acknowledge the support by the Deutsche Forschungsgemeinschaft (DFG) via the Ruhr University Research School and the Federal Ministry of Education and Research in frame of the PluTO project.

MultiNet TCP/P/IP for VAX/VMS update

NASA Technical Reports Server (NTRS)

Vance, L. Stuart

1991-01-01

Outlines of device support; DECnet interoperability; installation; MultiNet services; domain name server; Telnet; FTP; SMTP; DECwindows over TCP/IP; BSD r services; remote printing; RPC services and NFS server; NFS client; netcontrol; diagnostics; programming support; and MultiNet features are presented in viewgraph format.

Intergenerational Programmes: Public Policy and Research Implications--An International Perspective.

ERIC Educational Resources Information Center

Hatton-Yeo, Alan, Ed.; Ohsako, Toshio, Ed.

This document consists of 12 papers that, together, summarize the key issues underpinning future research and policy development related to intergenerational programs (IPs). "Introduction" (Alan Hatton-Yeo) discusses the project out of which the papers developed. "A General Assessment of IP Initiatives in the Countries…

American British Canadian, Australian Armies Standardization Program Catalog of War Games

DTIC Science & Technology

1991-05-21

Defense Netwrrk (ADNET), Command, Control Communication, Intelligence, Prioritization (C3IP) Links, FM2 Grid (read-in optimization) in Terrain Database...at a given echelon such as division and below. Force level models may be interactive with players performing various cnmard, control , and staff...and may require compliance with appropriate configuration control procedures. Also, release to contractors may be prohibited. FOR THE WASHINGTON

Evaluating Text-Based Information on the World Wide Web

ERIC Educational Resources Information Center

Wopereis, Iwan G. J. H.; van Merrienboer, Jeroen J. G.

2011-01-01

This special section contributes to an inclusive cognitive model of information problem solving (IPS) activity, touches briefly IPS learning, and brings to the notice methodological pitfalls related to uncovering IPS processes. Instead of focusing on the IPS process as a whole, the contributing articles turn their attention to what is regarded the…

Amino Acids Inhibitory Effects and Mechanism on 2-Amino-1-Methyl-6-Phenylimidazo [4,5-b]Pyridine (PhIP) Formation in the Maillard Reaction Model Systems.

PubMed

Linghu, Ziyi; Karim, Faris; Smith, J Scott

2017-12-01

This study was to investigate the inhibitory effects of amino acids (AAs) on the formation of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) and to evaluate the inhibition mechanism of PhIP in Maillard model systems. Different AAs were individually added into model systems heat-treated at 180 °C/1 h. The PhIP, phenylacetaldehyde (PheAce), and pyrazines derivatives were determined using HPLC and GC-MS. AAs significantly reduced (P < 0.05) PhIP levels in a dose-dependent response, ranking as: Trp = Lys > Pro > Leu > Met > Val > Ile > Thr > Phe > Asp, at the highest molar ratio. The PheAce content was gradually reduced with increasing AAs levels, suggesting that AAs may inhibit PhIP formation through scavenging the available PheAce. A correlation between PhIP inhibition and PheAce-scavenging activity of AAs was observed when PheAce and AAs were heated. The variety and quantity of pyrazines formed are highly depending on the type of AAs. © 2017 Institute of Food Technologists®.

A comparative study of interprofessional education in global health care

PubMed Central

Herath, Chulani; Zhou, Yangfeng; Gan, Yong; Nakandawire, Naomie; Gong, Yanghong; Lu, Zuxun

2017-01-01

Abstract Background: The World Health Organization (WHO) and its partners identify interprofessional (IP) collaboration in education and practice as an innovative strategy that plays an important role in mitigating the global health workforce crisis. Evidence on the practice of global health level in interprofessional education (IPE) is scarce and hampered due to the absence of aggregate information. Therefore, this systematic review was conducted to examine the incidences of IPE and summarize the main features about the IPE programs in undergraduate and postgraduate education in developed and developing countries. Methods: The PubMed, Embase, Web of Science, and Google Scholar were searched from their inception to January 31, 2016 for relevant studies regarding the development of IPE worldwide, IPE undergraduate and postgraduate programs, IP interaction in health education, IPE content, clinical placements, and teaching methods. Countries in which a study was conducted were classified as developed and developing countries according to the definition by the United Nations (UN) in 2014. Results: A total of 65 studies from 41 countries met our inclusion criteria, including 45 studies from 25 developed countries and 20 studies from 16 developing countries. Compared with developing countries, developed countries had more IPE initiatives. IPE programs were mostly at the undergraduate level. Overall, the university was the most common academic institution that provided IPE programs. The contents of the curricula were mainly designed to provide IP knowledge, skills, and values that aimed at developing IP competencies. IPE clinical placements were typically based in hospitals, community settings, or both. The didactic and interactive teaching methods varied significantly within and across universities where they conducted IPE programs. Among all health care disciplines, nursing was the discipline that conducted most of the IPE programs. Conclusion: This systematic review illustrated that the IPE programs vary substantially across countries. Many countries, especially the academic institutions are benefiting from the implementation of IPE programs. There is a need to strengthen health education policies at global level aiming at initiating IPE programs in relevant institutions. PMID:28930816

Using Importance-Performance Analysis To Evaluate Teaching Effectiveness.

ERIC Educational Resources Information Center

Attarian, Aram

This paper introduces Importance-Performance (IP) analysis as a method to evaluate teaching effectiveness in a university outdoor program. Originally developed for use in the field of marketing, IP analysis is simple and easy to administer, and provides the instructor with a visual representation of what teaching attributes are important, how…

Nuclear inositol 1,4,5-trisphosphate is a necessary and conserved signal for the induction of both pathological and physiological cardiomyocyte hypertrophy.

PubMed

Arantes, Lilian A M; Aguiar, Carla J; Amaya, Maria Jimena; Figueiró, Núbia C G; Andrade, Lídia M; Rocha-Resende, Cibele; Resende, Rodrigo R; Franchini, K G; Guatimosim, Silvia; Leite, M Fatima

2012-10-01

It is well established that inositol 1,4,5-trisphosphate (IP3) dependent Ca(2+) signaling plays a crucial role in cardiomyocyte hypertrophy. However, it is not yet known whether nuclear IP3 represents a Ca(2+) mobilizing pathway involved in this process. The goal of the current work was to investigate the specific role of nuclear IP3 in cardiomyocyte hypertrophic response. In this work, we used an adenovirus construct that selectively buffers IP3 in the nuclear region of neonatal cardiomyocytes. We showed for the first time that nuclear IP3 mediates endothelin-1 (ET-1) induced hypertrophy. We also found that both calcineurin (Cn)/nuclear factor of activated T Cells (NFAT) and histone deacetylase-5 (HDAC5) pathways require nuclear IP3 to mediate pathological cardiomyocyte growth. Additionally, we found that nuclear IP3 buffering inhibited insulin-like growth factor-1 (IGF-1) induced hypertrophy and prevented reexpression of fetal gene program. Together, these results demonstrated that nuclear IP3 is an essential and a conserved signal for both pathological and physiological forms of cardiomyocyte hypertrophy. Copyright © 2012. Published by Elsevier Ltd.

Modeling human neurological disorders with induced pluripotent stem cells.

PubMed

Imaizumi, Yoichi; Okano, Hideyuki

2014-05-01

Human induced pluripotent stem (iPS) cells obtained by reprogramming technology are a source of great hope, not only in terms of applications in regenerative medicine, such as cell transplantation therapy, but also for modeling human diseases and new drug development. In particular, the production of iPS cells from the somatic cells of patients with intractable diseases and their subsequent differentiation into cells at affected sites (e.g., neurons, cardiomyocytes, hepatocytes, and myocytes) has permitted the in vitro construction of disease models that contain patient-specific genetic information. For example, disease-specific iPS cells have been established from patients with neuropsychiatric disorders, including schizophrenia and autism, as well as from those with neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. A multi-omics analysis of neural cells originating from patient-derived iPS cells may thus enable investigators to elucidate the pathogenic mechanisms of neurological diseases that have heretofore been unknown. In addition, large-scale screening of chemical libraries with disease-specific iPS cells is currently underway and is expected to lead to new drug discovery. Accordingly, this review outlines the progress made via the use of patient-derived iPS cells toward the modeling of neurological disorders, the testing of existing drugs, and the discovery of new drugs. The production of human induced pluripotent stem (iPS) cells from the patients' somatic cells and their subsequent differentiation into specific cells have permitted the in vitro construction of disease models that contain patient-specific genetic information. Furthermore, innovations of gene-editing technologies on iPS cells are enabling new approaches for illuminating the pathogenic mechanisms of human diseases. In this review article, we outlined the current status of neurological diseases-specific iPS cell research and described recently obtained knowledge in the form of actual examples. © 2013 International Society for Neurochemistry.

Staffing and structure of infection prevention and control programs.

PubMed

Stone, Patricia W; Dick, Andrew; Pogorzelska, Monika; Horan, Teresa C; Furuya, E Yoko; Larson, Elaine

2009-06-01

The nature of infection prevention and control is changing; however, little is known about current staffing and structure of infection prevention and control programs. Our objectives were to provide a snapshot of the staffing and structure of hospital-based infection prevention and control programs in the United States. A Web-based survey was sent to 441 hospitals that participate in the National Healthcare Safety Network. The response rate was 66% (n = 289); data were examined on 821 professionals. Infection preventionist (IP) staffing was significantly negatively related to bed size, with higher staffing in smaller hospitals (P < .001). Median staffing was 1 IP per 167 beds. Forty-seven percent of IPs were certified, and 24 percent had less than 2 years of experience. Most directors or hospital epidemiologists were reported to have authority to close beds for outbreaks always or most of the time (n = 225, 78%). Only 32% (n = 92) reported using an electronic surveillance system to track infections. This study is the first to provide a comprehensive description of current infection prevention and control staffing, organization, and support in a select group of hospitals across the nation. Further research is needed to identify effective staffing levels for various hospital types as well as examine how the IP role is changing over time.

Staffing and structure of infection prevention and control programs

PubMed Central

Stone, Patricia W.; Dick, Andrew; Pogorzelska, Monika; Horan, Teresa C.; Furuya, E. Yoko; Larson, Elaine

2009-01-01

Background The nature of infection prevention and control is changing; however, little is known about current staffing and structure of infection prevention and control programs. Methods Our objectives were to provide a snapshot of the staffing and structure of hospital-based infection prevention and control programs in the United States. A Web-based survey was sent to 441 hospitals that participate in the National Healthcare Safety Network. Results The response rate was 66% (n = 289); data were examined on 821 professionals. Infection preventionist (IP) staffing was significantly negatively related to bed size, with higher staffing in smaller hospitals (P < .001). Median staffing was 1 IP per 167 beds. Forty-seven percent of IPs were certified, and 24 percent had less than 2 years of experience. Most directors or hospital epidemiologists were reported to have authority to close beds for outbreaks always or most of the time (n = 225, 78%). Only 32% (n = 92) reported using an electronic surveillance system to track infections. Conclusion This study is the first to provide a comprehensive description of current infection prevention and control staffing, organization, and support in a select group of hospitals across the nation. Further research is needed to identify effective staffing levels for various hospital types as well as examine how the IP role is changing over time. PMID:19201510

BinQuasi: a peak detection method for ChIP-sequencing data with biological replicates.

PubMed

Goren, Emily; Liu, Peng; Wang, Chao; Wang, Chong

2018-04-19

ChIP-seq experiments that are aimed at detecting DNA-protein interactions require biological replication to draw inferential conclusions, however there is no current consensus on how to analyze ChIP-seq data with biological replicates. Very few methodologies exist for the joint analysis of replicated ChIP-seq data, with approaches ranging from combining the results of analyzing replicates individually to joint modeling of all replicates. Combining the results of individual replicates analyzed separately can lead to reduced peak classification performance compared to joint modeling. Currently available methods for joint analysis may fail to control the false discovery rate at the nominal level. We propose BinQuasi, a peak caller for replicated ChIP-seq data, that jointly models biological replicates using a generalized linear model framework and employs a one-sided quasi-likelihood ratio test to detect peaks. When applied to simulated data and real datasets, BinQuasi performs favorably compared to existing methods, including better control of false discovery rate than existing joint modeling approaches. BinQuasi offers a flexible approach to joint modeling of replicated ChIP-seq data which is preferable to combining the results of replicates analyzed individually. Source code is freely available for download at https://cran.r-project.org/package=BinQuasi, implemented in R. pliu@iastate.edu or egoren@iastate.edu. Supplementary material is available at Bioinformatics online.

Protocol for the Individual Placement and Support (IPS) in Pain Trial: A randomized controlled trial investigating the effectiveness of IPS for patients with chronic pain.

PubMed

Linnemørken, Lene Therese B; Sveinsdottir, Vigdis; Knutzen, Thomas; Rødevand, Linn; Hernæs, Kjersti Helene; Reme, Silje Endresen

2018-02-13

Work disability involves large costs to the society as well as to the individual. Work disability is common among people with chronic pain conditions, yet few effective interventions exist. Individual Placement and Support (IPS) is an evidence-based work rehabilitation model originally developed to help people with severe mental illness obtain and maintain employment. The effectiveness of IPS for patients with severe mental illness is well documented, but the model has never before been tested for patients with chronic pain. The aim of the IPS in Pain trial is to investigate the effectiveness of IPS as an integrated part of the interdisciplinary treatment for patients with chronic pain in a hospital outpatient clinic. The study is a randomized controlled trial comparing pain treatment with integrated IPS to treatment as usual in unemployed patients suffering from various chronic pain conditions. The primary outcome of the study is labor market participation during 12 months after enrollment, and secondary outcomes include physical and mental health and well-being, collected at baseline, 6, and 12 months. Finally, there will be an additional long-term follow-up for the primary outcome, which will be collected through a brief phone interview at 24 months. The IPS in Pain trial will be the first report of the effectiveness of the IPS model of supported employment applied in an outpatient setting for chronic pain patients. It will thus provide important information about the effectiveness of repurposing IPS to a new patient group in great need of job support. Clinicaltrials.gov: NCT02697656 . Registered January 15th, 2016.

Human Biomarker Discovery and Predictive Models for Disease Progression for Idiopathic Pneumonia Syndrome Following Allogeneic Stem Cell Transplantation*

PubMed Central

Schlatzer, Daniela M.; Dazard, Jean-Eudes; Ewing, Rob M.; Ilchenko, Serguei; Tomcheko, Sara E.; Eid, Saada; Ho, Vincent; Yanik, Greg; Chance, Mark R.; Cooke, Kenneth R.

2012-01-01

Allogeneic hematopoietic stem cell transplantation (SCT) is the only curative therapy for many malignant and nonmalignant conditions. Idiopathic pneumonia syndrome (IPS) is a frequently fatal complication that limits successful outcomes. Preclinical models suggest that IPS represents an immune mediated attack on the lung involving elements of both the adaptive and the innate immune system. However, the etiology of IPS in humans is less well understood. To explore the disease pathway and uncover potential biomarkers of disease, we performed two separate label-free, proteomics experiments defining the plasma protein profiles of allogeneic SCT patients with IPS. Samples obtained from SCT recipients without complications served as controls. The initial discovery study, intended to explore the disease pathway in humans, identified a set of 81 IPS-associated proteins. These data revealed similarities between the known IPS pathways in mice and the condition in humans, in particular in the acute phase response. In addition, pattern recognition pathways were judged to be significant as a function of development of IPS, and from this pathway we chose the lipopolysaccaharide-binding protein (LBP) protein as a candidate molecular diagnostic for IPS, and verified its increase as a function of disease using an ELISA assay. In a separately designed study, we identified protein-based classifiers that could predict, at day 0 of SCT, patients who: 1) progress to IPS and 2) respond to cytokine neutralization therapy. Using cross-validation strategies, we built highly predictive classifier models of both disease progression and therapeutic response. In sum, data generated in this report confirm previous clinical and experimental findings, provide new insights into the pathophysiology of IPS, identify potential molecular classifiers of the condition, and uncover a set of markers potentially of interest for patient stratification as a basis for individualized therapy. PMID:22337588

Inhibition of pulmonary fibrosis by the chemokine IP-10/CXCL10.

PubMed

Tager, Andrew M; Kradin, Richard L; LaCamera, Peter; Bercury, Scott D; Campanella, Gabriele S V; Leary, Carol P; Polosukhin, Vasiliy; Zhao, Long-Hai; Sakamoto, Hideo; Blackwell, Timothy S; Luster, Andrew D

2004-10-01

Pulmonary fibrosis is an enigmatic and devastating disease with few treatment options, now thought to result from abnormal wound healing in the lung in response to injury. We have previously noted a role for the chemokine interferon gamma-inducible protein of 10 kD (IP-10)/CXC chemokine ligand 10 in the regulation of cutaneous wound healing, and consequently investigated whether IP-10 regulates pulmonary fibrosis. We found that IP-10 is highly expressed in a mouse model of pulmonary fibrosis induced by bleomycin. IP-10-deficient mice exhibited increased pulmonary fibrosis after administration of bleomycin, suggesting that IP-10 limits the development of fibrosis in this model. Substantial fibroblast chemoattractant and proliferative activities were generated in the lung after bleomycin exposure. IP-10 significantly inhibited fibroblast responses to the chemotactic, but not the proliferative activity generated, suggesting that IP-10 may attenuate fibroblast accumulation in bleomycin-induced pulmonary fibrosis by limiting fibroblast migration. Consistent with this inhibitory activity of IP-10 on fibroblast migration, fibroblast accumulation in the lung after bleomycin exposure was dramatically increased in IP-10-deficient mice compared with wild-type mice. Conversely, transgenic mice overexpressing IP-10 were protected from mortality after bleomycin exposure, and demonstrated decreased fibroblast accumulation in the lung after challenge compared with wild-type mice. Our findings suggest that interruption of fibroblast recruitment may represent a novel therapeutic strategy for pulmonary fibrosis, which could have applicability to a wide range of fibrotic illnesses.

Communication and respect for people with dementia: student learning (CARDS) - the development and evaluation of a pilot of an education intervention for pre-qualifying healthcare students.

PubMed

Wood, Julia Helen; Alushi, Ledia; Hammond, John A

2016-04-01

Dementia is an international health priority and healthcare students need to be prepared to work with people living with dementia. There is a paucity of the literature describing appropriate educational interventions for pre-qualifying healthcare students and even fewer that are evaluated. Based on available evidence, an education program was developed aiming to increase students' knowledge and confidence in working with people with dementia (PWD). An introductory program (IP) of classroom sessions and workshops was followed by a volunteer care home experience (CHE) (4 × 3 h). Piloted with physiotherapy (IP n = 55; CHE n = 6) and nursing students (IP n = 20; CHE n = 7), using a survey design, knowledge, and perceived confidence for working with PWD were measured at four time points; baseline, after the IP, after the CHE, and six months later. The data were analyzed using paired t-tests or non-parametric equivalents. Knowledge scores increased after the IP (Time 1-2, p < 0.001, n = 48) and increases were retained after six months (Time 1-4, p < 0.001, n = 40). Perceived confidence increased at six months follow up (Time 1-4, p < 0.001, n = 40) with peaks after the IP (Time 1-2, p < 0.001, n = 47) and CHE (Time 2-3, p = 0.004, n = 13). Physiotherapy and nursing students did not differ on knowledge, but nursing students were more confident at baseline and after the IP. Prior experience equated with greater confidence but no more knowledge. Findings indicate that students' knowledge and confidence to work with PWD improves after this educational intervention, with confidence improving more when supplemented by experience.

X-Windows Socket Widget Class

NASA Technical Reports Server (NTRS)

Barry, Matthew R.

2006-01-01

The X-Windows Socket Widget Class ("Class" is used here in the object-oriented-programming sense of the word) was devised to simplify the task of implementing network connections for graphical-user-interface (GUI) computer programs. UNIX Transmission Control Protocol/Internet Protocol (TCP/IP) socket programming libraries require many method calls to configure, operate, and destroy sockets. Most X Windows GUI programs use widget sets or toolkits to facilitate management of complex objects. The widget standards facilitate construction of toolkits and application programs. The X-Windows Socket Widget Class encapsulates UNIX TCP/IP socket-management tasks within the framework of an X Windows widget. Using the widget framework, X Windows GUI programs can treat one or more network socket instances in the same manner as that of other graphical widgets, making it easier to program sockets. Wrapping ISP socket programming libraries inside a widget framework enables a programmer to treat a network interface as though it were a GUI.

Programmed cell death 6 interacting protein (PDCD6IP) and Rabenosyn-5 (ZFYVE20) are potential urinary biomarkers for upper gastrointestinal cancer.

PubMed

Husi, Holger; Skipworth, Richard J E; Cronshaw, Andrew; Stephens, Nathan A; Wackerhage, Henning; Greig, Carolyn; Fearon, Kenneth C H; Ross, James A

2015-06-01

Cancer of the upper digestive tract (uGI) is a major contributor to cancer-related death worldwide. Due to a rise in occurrence, together with poor survival rates and a lack of diagnostic or prognostic clinical assays, there is a clear need to establish molecular biomarkers. Initial assessment was performed on urine samples from 60 control and 60 uGI cancer patients using MS to establish a peak pattern or fingerprint model, which was validated by a further set of 59 samples. We detected 86 cluster peaks by MS above frequency and detection thresholds. Statistical testing and model building resulted in a peak profiling model of five relevant peaks with 88% overall sensitivity and 91% specificity, and overall correctness of 90%. High-resolution MS of 40 samples in the 2-10 kDa range resulted in 646 identified proteins, and pattern matching identified four of the five model peaks within significant parameters, namely programmed cell death 6 interacting protein (PDCD6IP/Alix/AIP1), Rabenosyn-5 (ZFYVE20), protein S100A8, and protein S100A9, of which the first two were validated by Western blotting. We demonstrate that MS analysis of human urine can identify lead biomarker candidates in uGI cancers, which makes this technique potentially useful in defining and consolidating biomarker patterns for uGI cancer screening. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Securing Voice over IP Conferencing with Decentralized Group Encryption

DTIC Science & Technology

2007-09-04

media stream. Call data can then be encrypted and decrypted. Zfone is available as a plug-in for a number of VoIP programs, including Gizmo [13...Terminal. http://www.l- 3com.com/csw/product/specs/Airborne/TCDLAir.asp. [13] The Gizmo Project. http://gizmoproject.com. [14] The OpenSSL

The effectiveness of incorporating a real-time oculometer system in a commercial flight training program

NASA Technical Reports Server (NTRS)

Jones, D. H.; Coates, G. D.; Kirby, R. H.

1983-01-01

The effectiveness of incroporating a real-time oculometer system into a Boeing 737 commercial flight training program was studied. The study combined a specialized oculometer system with sophisticated video equipment that would allow instructor pilots (IPs) to monitor pilot and copilot trainees' instrument scan behavior in real-time, and provide each trainee with video tapes of his/her instrument scanning behavior for each training session. The IPs' performance ratings and trainees' self-ratings were compared to the performance ratings by IPs and trainees in a control group. The results indicate no difference in IP ratings or trainees' self-ratings for the control and experimental groups. The results indicated that the major beneficial role of a real-time oculometer system for pilots and copilots having a significant amount of flight experience would be for problem solving or refinement of instrument scanning behavior rather than a general instructional scheme. It is suggested that this line of research be continued with the incorporation of objective data (e.g., state of the aircraft data), measures of cost effectiveness and with trainees having less flight experience.

Vectors to Increase Production Efficiency of Inducible Pluripotent Stem Cell (iPSC) | NCI Technology Transfer Center | TTC

Cancer.gov

This invention describes the discovery that specific p53 isoform increase the number of inducible pluripotent stem cells (iPS). It is known that the activity of p53 regulates the self-renewal and pluripotency of normal and cancer stem cells, and also affects re-programming efficiency of iPS cells. This p53 isoform-based technology provides a more natural process of increasing iPS cell production than previous methods of decreasing p53. NCI seeks licensees for this technology.

Calcium waves in a grid of clustered channels with synchronous IP3 binding and unbinding.

PubMed

Rückl, M; Rüdiger, S

2016-11-01

Calcium signals in cells occur at multiple spatial scales and variable temporal duration. However, a physical explanation for transitions between long-lasting global oscillations and localized short-term elevations (puffs) of cytoplasmic Ca 2+ is still lacking. Here we introduce a phenomenological, coarse-grained model for the calcium variable, which is represented by ordinary differential equations. Due to its small number of parameters, and its simplicity, this model allows us to numerically study the interplay of multi-scale calcium concentrations with stochastic ion channel gating dynamics even in larger systems. We apply this model to a single cluster of inositol trisphosphate (IP 3 ) receptor channels and find further evidence for the results presented in earlier work: a single cluster may be capable of producing different calcium release types, where long-lasting events are accompanied by unbinding of IP 3 from the receptor (Rückl et al., PLoS Comput. Biol. 11, e1003965 (2015)). Finally, we show the practicability of the model in a grid of 64 clusters which is computationally intractable with previous high-resolution models. Here long-lasting events can lead to synchronized oscillations and waves, while short events stay localized. The frequency of calcium releases as well as their coherence can thereby be regulated by the amplitude of IP 3 stimulation. Finally the model allows for a new explanation of oscillating [IP 3 ], which is not based on metabolic production and degradation of IP 3 .

Neural Mechanisms Underlying the Computation of Hierarchical Tree Structures in Mathematics

PubMed Central

Nakai, Tomoya; Sakai, Kuniyoshi L.

2014-01-01

Whether mathematical and linguistic processes share the same neural mechanisms has been a matter of controversy. By examining various sentence structures, we recently demonstrated that activations in the left inferior frontal gyrus (L. IFG) and left supramarginal gyrus (L. SMG) were modulated by the Degree of Merger (DoM), a measure for the complexity of tree structures. In the present study, we hypothesize that the DoM is also critical in mathematical calculations, and clarify whether the DoM in the hierarchical tree structures modulates activations in these regions. We tested an arithmetic task that involved linear and quadratic sequences with recursive computation. Using functional magnetic resonance imaging, we found significant activation in the L. IFG, L. SMG, bilateral intraparietal sulcus (IPS), and precuneus selectively among the tested conditions. We also confirmed that activations in the L. IFG and L. SMG were free from memory-related factors, and that activations in the bilateral IPS and precuneus were independent from other possible factors. Moreover, by fitting parametric models of eight factors, we found that the model of DoM in the hierarchical tree structures was the best to explain the modulation of activations in these five regions. Using dynamic causal modeling, we showed that the model with a modulatory effect for the connection from the L. IPS to the L. IFG, and with driving inputs into the L. IFG, was highly probable. The intrinsic, i.e., task-independent, connection from the L. IFG to the L. IPS, as well as that from the L. IPS to the R. IPS, would provide a feedforward signal, together with negative feedback connections. We indicate that mathematics and language share the network of the L. IFG and L. IPS/SMG for the computation of hierarchical tree structures, and that mathematics recruits the additional network of the L. IPS and R. IPS. PMID:25379713

Localization and socialization: Experimental insights into the functional architecture of IP3 receptors

NASA Astrophysics Data System (ADS)

Diambra, Luis; Marchant, Jonathan S.

2009-09-01

Inositol 1,4,5-trisphosphate (IP3)-evoked Ca2+ signals display great spatiotemporal malleability. This malleability depends on diversity in both the cellular organization and in situ functionality of IP3 receptors (IP3Rs) that regulate Ca2+ release from the endoplasmic reticulum (ER). Recent experimental data imply that these considerations are not independent, such that—as with other ion channels—the local organization of IP3Rs impacts their functionality, and reciprocally IP3R activity impacts their organization within native ER membranes. Here, we (i) review experimental data that lead to our understanding of the "functional architecture" of IP3Rs within the ER, (ii) propose an updated terminology to span the organizational hierarchy of IP3Rs observed in intact cells, and (iii) speculate on the physiological significance of IP3R socialization in Ca2+ dynamics, and consequently the emerging need for modeling studies to move beyond gridded, planar, and static simulations of IP3R clustering even over short experimental timescales.

Validating a conceptual model for an inter-professional approach to shared decision making: a mixed methods study

PubMed Central

Légaré, France; Stacey, Dawn; Gagnon, Susie; Dunn, Sandy; Pluye, Pierre; Frosch, Dominick; Kryworuchko, Jennifer; Elwyn, Glyn; Gagnon, Marie-Pierre; Graham, Ian D

2011-01-01

Rationale, aims and objectives Following increased interest in having inter-professional (IP) health care teams engage patients in decision making, we developed a conceptual model for an IP approach to shared decision making (SDM) in primary care. We assessed the validity of the model with stakeholders in Canada. Methods In 15 individual interviews and 7 group interviews with 79 stakeholders, we asked them to: (1) propose changes to the IP-SDM model; (2) identify barriers and facilitators to the model's implementation in clinical practice; and (3) assess the model using a theory appraisal questionnaire. We performed a thematic analysis of the transcripts and a descriptive analysis of the questionnaires. Results Stakeholders suggested placing the patient at its centre; extending the concept of family to include significant others; clarifying outcomes; highlighting the concept of time; merging the micro, meso and macro levels in one figure; and recognizing the influence of the environment and emotions. The most common barriers identified were time constraints, insufficient resources and an imbalance of power among health professionals. The most common facilitators were education and training in inter-professionalism and SDM, motivation to achieve an IP approach to SDM, and mutual knowledge and understanding of disciplinary roles. Most stakeholders considered that the concepts and relationships between the concepts were clear and rated the model as logical, testable, having clear schematic representation, and being relevant to inter-professional collaboration, SDM and primary care. Conclusions Stakeholders validated the new IP-SDM model for primary care settings and proposed few modifications. Future research should assess if the model helps implement SDM in IP clinical practice. PMID:20695950

Validating a conceptual model for an inter-professional approach to shared decision making: a mixed methods study.

PubMed

Légaré, France; Stacey, Dawn; Gagnon, Susie; Dunn, Sandy; Pluye, Pierre; Frosch, Dominick; Kryworuchko, Jennifer; Elwyn, Glyn; Gagnon, Marie-Pierre; Graham, Ian D

2011-08-01

Following increased interest in having inter-professional (IP) health care teams engage patients in decision making, we developed a conceptual model for an IP approach to shared decision making (SDM) in primary care. We assessed the validity of the model with stakeholders in Canada. In 15 individual interviews and 7 group interviews with 79 stakeholders, we asked them to: (1) propose changes to the IP-SDM model; (2) identify barriers and facilitators to the model's implementation in clinical practice; and (3) assess the model using a theory appraisal questionnaire. We performed a thematic analysis of the transcripts and a descriptive analysis of the questionnaires. Stakeholders suggested placing the patient at its centre; extending the concept of family to include significant others; clarifying outcomes; highlighting the concept of time; merging the micro, meso and macro levels in one figure; and recognizing the influence of the environment and emotions. The most common barriers identified were time constraints, insufficient resources and an imbalance of power among health professionals. The most common facilitators were education and training in inter-professionalism and SDM, motivation to achieve an IP approach to SDM, and mutual knowledge and understanding of disciplinary roles. Most stakeholders considered that the concepts and relationships between the concepts were clear and rated the model as logical, testable, having clear schematic representation, and being relevant to inter-professional collaboration, SDM and primary care. Stakeholders validated the new IP-SDM model for primary care settings and proposed few modifications. Future research should assess if the model helps implement SDM in IP clinical practice. © 2010 Blackwell Publishing Ltd.

Inversion of time-domain induced polarization data based on time-lapse concept

NASA Astrophysics Data System (ADS)

Kim, Bitnarae; Nam, Myung Jin; Kim, Hee Joon

2018-05-01

Induced polarization (IP) surveys, measuring overvoltage phenomena of the medium, are widely and increasingly performed not only for exploration of mineral resources but also for engineering applications. Among several IP survey methods such as time-domain, frequency-domain and spectral IP surveys, this study introduces a noble inversion method for time-domain IP data to recover the chargeability structure of target medium. The inversion method employs the concept of 4D inversion of time-lapse resistivity data sets, considering the fact that measured voltage in time-domain IP survey is distorted by IP effects to increase from the instantaneous voltage measured at the moment the source current injection starts. Even though the increase is saturated very fast, we can consider the saturated and instantaneous voltages as a time-lapse data set. The 4D inversion method is one of the most powerful method for inverting time-lapse resistivity data sets. Using the developed IP inversion algorithm, we invert not only synthetic but also field IP data to show the effectiveness of the proposed method by comparing the recovered chargeability models with those from linear inversion that was used for the inversion of the field data in a previous study. Numerical results confirm that the proposed inversion method generates reliable chargeability models even though the anomalous bodies have large IP effects.

Thin Film Phase Transition Materials Development Program

DTIC Science & Technology

1985-04-01

and ̂ from f are consistent with a real, positive film thickness d. These conditions are written IP( td /4) = 0, d > 0, (49) where IP denotes...surface of the substrate of the form . aAC(a) + bBD (a) >< cAB(a) + dCD(a) where (a) represents a phase adsorbed on the substrate surface, and the

Training Interpreter Paraprofessionals to Assist in the Language Assessment of English Language Learners in Utah.

ERIC Educational Resources Information Center

Yoakum, Susie; Manuel-Dupont, Sonia

1997-01-01

Describes development of an interpreter paraprofessional (IP) program by Utah State University and Granite (Utah) school district in response to the unavailability of certified interpreters to assist in special education assessment of students who are English Language Learners. Stresses the importance of providing IPs with job-relevant training,…

Infusing Integrated Behavioral Health in an MSW Program: Curricula, Field, and Interprofessional Educational Activities

ERIC Educational Resources Information Center

Zerden, Lisa de Saxe; Jones, Anne; Brigham, Rebecca; Kanfer, Meryl; Zomorodi, Margaret

2017-01-01

An essential aspect of integrated care is the coordination of medical and behavioral health needs concurrently. This has sparked renewed emphasis on interprofessional (IP) education and practice. The impetus for IP efforts was crystalized in large part because of health care reforms, and federal funding to expand the behavioral health work force.…

76 FR 45796 - Information Collection Being Submitted to the Office of Management and Budget for Review and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-01

... organizational structure, including the names of its executives, officers, partners, and board of directors; A... Control Number: 3060-1145. Title: Structure and Practices of the Video Relay Service Program, CG Docket No... end times; (5) incoming telephone number and IP address (if call originates with an IP-based device...

Supported employment for persons with mental illness: systematic review of the effectiveness of individual placement and support in the UK.

PubMed

Heffernan, John; Pilkington, Paul

2011-08-01

High levels of unemployment among persons with mental illness are a significant social disability. The individual placement and support (IPS) model of vocational support has been shown to be effective in establishing persons with mental health problems back into competitive employment in North America. Evidence outside North America is more limited. To examine the evidence for the effectiveness of the IPS model of supported employment within the United Kingdom. Systematic review of studies of the effectiveness of IPS conducted principally in the United Kingdom. The evidence base was small. Overall quality of evidence was fair. There is evidence that interventions with high fidelity to the IPS model increase the proportion of patients engaged in work or education/training over the short- to medium-term (6-18 months follow-up). More research is needed to improve the evidence base in relation to IPS within a UK context. Evaluation should focus on both the nature and quality of the employment gained, patient and service factors.

Interferon-γ–Inducible Protein 10 (IP-10) as a Screening Tool to Optimize Human Immunodeficiency Virus RNA Monitoring in Resource-Limited Settings

PubMed Central

Pastor, Lucía; Casellas, Aina; Carrillo, Jorge; Maculuve, Sonia; Jairoce, Chenjerai; Paredes, Roger; Blanco, Julià; Naniche, Denise

2017-01-01

Abstract Background Achieving effective antiretroviral treatment (ART) monitoring is a key determinant to ensure viral suppression and reach the UNAIDS 90-90-90 targets. The gold standard for detecting virological failure is plasma human immunodeficiency virus (HIV) RNA (viral load [VL]) testing; however, its availability is very limited in low-income countries due to cost and operational constraints. Methods HIV-1–infected adults on first-line ART attending routine visits at the Manhiça District Hospital, Mozambique, were previously evaluated for virologic failure. Plasma levels of interferon-γ–inducible protein 10 (IP-10) were quantified by enzyme-linked immunosorbent assay. Logistic regression was used to build an IP-10–based model able to identify individuals with VL >150 copies/mL. From the 316 individuals analyzed, 253 (80%) were used for model training and 63 (20%) for validation. Receiver operating characteristic curves were employed to evaluate model prediction. Results From the individuals included in the training set, 34% had detectable VL. Mean age was 41 years, 70% were females, and median time on ART was 3.4 years. IP-10 levels were significantly higher in subjects with detectable VL (108.2 pg/mL) as compared to those with undetectable VL (38.0 pg/mL) (P < .0001, U test). IP-10 univariate model demonstrated high classification performance (area under the curve = 0.85 [95% confidence interval {CI}, .80–.90]). Using a cutoff value of IP-10 ≥44.2 pg/mL, the model identified detectable VL with 91.9% sensitivity (95% CI, 83.9%–96.7%) and 59.9% specificity (95% CI, 52.0%–67.4%), values confirmed in the validation set. Conclusions IP-10 is an accurate biomarker to screen individuals on ART for detectable viremia. Further studies should evaluate the benefits of IP-10 as a triage approach to monitor ART in resource-limited settings. PMID:29020145

Modeling Ca2+ Feedback on a Single Inositol 1,4,5-Trisphosphate Receptor and Its Modulation by Ca2+ Buffers

PubMed Central

Shuai, Jianwei; Pearson, John E.; Parker, Ian

2008-01-01

The inositol 1,4,5-trisphosphate receptor/channel (IP3R) is a major regulator of intracellular Ca2+ signaling, and liberates Ca2+ ions from the endoplasmic reticulum in response to binding at cytosolic sites for both IP3 and Ca2+. Although the steady-state gating properties of the IP3R have been extensively studied and modeled under conditions of fixed [IP3] and [Ca2+], little is known about how Ca2+ flux through a channel may modulate the gating of that same channel by feedback onto activating and inhibitory Ca2+ binding sites. We thus simulated the dynamics of Ca2+ self-feedback on monomeric and tetrameric IP3R models. A major conclusion is that self-activation depends crucially on stationary cytosolic Ca2+ buffers that slow the collapse of the local [Ca2+] microdomain after closure. This promotes burst-like reopenings by the rebinding of Ca2+ to the activating site; whereas inhibitory actions are substantially independent of stationary buffers but are strongly dependent on the location of the inhibitory Ca2+ binding site on the IP3R in relation to the channel pore. PMID:18641077

Common genetic variation drives molecular heterogeneity in human iPSCs.

PubMed

Kilpinen, Helena; Goncalves, Angela; Leha, Andreas; Afzal, Vackar; Alasoo, Kaur; Ashford, Sofie; Bala, Sendu; Bensaddek, Dalila; Casale, Francesco Paolo; Culley, Oliver J; Danecek, Petr; Faulconbridge, Adam; Harrison, Peter W; Kathuria, Annie; McCarthy, Davis; McCarthy, Shane A; Meleckyte, Ruta; Memari, Yasin; Moens, Nathalie; Soares, Filipa; Mann, Alice; Streeter, Ian; Agu, Chukwuma A; Alderton, Alex; Nelson, Rachel; Harper, Sarah; Patel, Minal; White, Alistair; Patel, Sharad R; Clarke, Laura; Halai, Reena; Kirton, Christopher M; Kolb-Kokocinski, Anja; Beales, Philip; Birney, Ewan; Danovi, Davide; Lamond, Angus I; Ouwehand, Willem H; Vallier, Ludovic; Watt, Fiona M; Durbin, Richard; Stegle, Oliver; Gaffney, Daniel J

2017-06-15

Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells.

A randomized pilot clinical trial to evaluate the efficacy of Community Reinforcement and Family Training for Treatment Retention (CRAFT-T) for improving outcomes for patients completing opioid detoxification.

PubMed

Brigham, Gregory S; Slesnick, Natasha; Winhusen, Theresa M; Lewis, Daniel F; Guo, Xiamei; Somoza, Eugene

2014-05-01

Detoxification with psychosocial counseling remains a standard opioid-use disorder treatment practice but is associated with poor outcomes. This study tested the efficacy of a newly developed psychosocial intervention, Community Reinforcement Approach and Family Training for Treatment Retention (CRAFT-T), relative to psychosocial treatment as usual (TAU), for improving treatment outcomes. A randomized, 14-week trial with follow-up visits at 6 and 9 months post-randomization conducted at two substance use disorder (SUD) treatment programs. Opioid-dependent adults (i.e., identified patient - IP) enrolled in a residential buprenorphine-detoxification program and their identified concerned significant other (CSO) was randomized to CRAFT-T (n=28 dyads) or TAU (n=24 dyads). CRAFT-T consisted of two sessions with the IP and CSO together and 10 with the CSO alone, over 14 weeks. TAU for the CSOs was primarily educational and referral to self-help. All IPs received treatment as usually provided by the SUD program in which they were enrolled. The primary outcome was time to first IP drop from treatment lasting 30 days or more. Opioid and other drug use were key secondary outcomes. CRAFT-T resulted in a moderate but non-significant effect on treatment retention (p=0.058, hazard ratio=0.57). When the CSO was parental family, CRAFT-T had a large and significant effect on treatment retention (p<0.01, hazard ratio=.040). CRAFT-T had a significant positive effect on IP opioid and other drug use (p<0.0001). CRAFT-T is a promising treatment for opioid use disorder but replication is needed to confirm these results. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Individual Placement and Support in Spinal Cord Injury: A Longitudinal Observational Study of Employment Outcomes.

PubMed

Ottomanelli, Lisa; Goetz, Lance L; Barnett, Scott D; Njoh, Eni; Dixon, Thomas M; Holmes, Sally Ann; LePage, James P; Ota, Doug; Sabharwal, Sunil; White, Kevin T

2017-08-01

To determine the effects of a 24-month program of Individual Placement and Support (IPS) supported employment (SE) on employment outcomes for veterans with spinal cord injury (SCI). Longitudinal, observational multisite study of a single-arm, nonrandomized cohort. SCI centers in the Veterans Health Administration (n=7). Veterans with SCI (N=213) enrolled during an episode of either inpatient hospital care (24.4%) or outpatient care (75.6%). More than half the sample (59.2%) had a history of traumatic brain injury (TBI). IPS SE for 24 months. Competitive employment. Over the 24-month period, 92 of 213 IPS participants obtained competitive jobs for an overall employment rate of 43.2%. For the subsample of participants without TBI enrolled as outpatients (n=69), 36 obtained competitive jobs for an overall employment rate of 52.2%. Overall, employed participants averaged 38.2±29.7 weeks of employment, with an average time to first employment of 348.3±220.0 days. Nearly 25% of first jobs occurred within 4 to 6 months of beginning the program. Similar employment characteristics were observed in the subsample without TBI history enrolled as outpatients. Almost half of the veterans with SCI participating in the 24-month IPS program as part of their ongoing SCI care achieved competitive employment, consistent with their expressed preferences at the start of the study. Among a subsample of veterans without TBI history enrolled as outpatients, employment rates were >50%. Time to first employment was highly variable, but quite long in many instances. These findings support offering continued IPS services as part of ongoing SCI care to achieve positive employment outcomes. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Modeling Alzheimer’s disease with human induced pluripotent stem (iPS) cells

PubMed Central

Mungenast, Alison E.; Siegert, Sandra; Tsai, Li-Huei

2018-01-01

In the last decade, induced pluripotent stem (iPS) cells have revolutionized the utility of human in vitro models of neurological disease. The iPS-derived and differentiated cells allow researchers to study the impact of a distinct cell type in health and disease as well as performing therapeutic drug screens on a human genetic background. In particular, clinical trials for Alzheimer’s disease (AD) have been often failing. Two of the potential reasons are first, the species gap involved in proceeding from initial discoveries in rodent models to human studies, and second, an unsatisfying patient stratification, meaning subgrouping patients based on the disease severity due to the lack of phenotypic and genetic markers. iPS cells overcome this obstacles and will improve our understanding of disease subtypes in AD. They allow researchers conducting in depth characterization of neural cells from both familial and sporadic AD patients as well as preclinical screens on human cells. In this review, we briefly outline the status quo of iPS cell research in neurological diseases along with the general advantages and pitfalls of these models. We summarize how genome-editing techniques such as CRISPR/Cas will allow researchers to reduce the problem of genomic variability inherent to human studies, followed by recent iPS cell studies relevant to AD. We then focus on current techniques for the differentiation of iPS cells into neural cell types that are relevant to AD research. Finally, we discuss how the generation of three-dimensional cell culture systems will be important for understanding AD phenotypes in a complex cellular milieu, and how both two- and three-dimensional iPS cell models can provide platforms for drug discovery and translational studies into the treatment of AD. PMID:26657644

Modeling Alzheimer's disease with human induced pluripotent stem (iPS) cells.

PubMed

Mungenast, Alison E; Siegert, Sandra; Tsai, Li-Huei

2016-06-01

In the last decade, induced pluripotent stem (iPS) cells have revolutionized the utility of human in vitro models of neurological disease. The iPS-derived and differentiated cells allow researchers to study the impact of a distinct cell type in health and disease as well as performing therapeutic drug screens on a human genetic background. In particular, clinical trials for Alzheimer's disease (AD) have been failing. Two of the potential reasons are first, the species gap involved in proceeding from initial discoveries in rodent models to human studies, and second, an unsatisfying patient stratification, meaning subgrouping patients based on the disease severity due to the lack of phenotypic and genetic markers. iPS cells overcome this obstacles and will improve our understanding of disease subtypes in AD. They allow researchers conducting in depth characterization of neural cells from both familial and sporadic AD patients as well as preclinical screens on human cells. In this review, we briefly outline the status quo of iPS cell research in neurological diseases along with the general advantages and pitfalls of these models. We summarize how genome-editing techniques such as CRISPR/Cas9 will allow researchers to reduce the problem of genomic variability inherent to human studies, followed by recent iPS cell studies relevant to AD. We then focus on current techniques for the differentiation of iPS cells into neural cell types that are relevant to AD research. Finally, we discuss how the generation of three-dimensional cell culture systems will be important for understanding AD phenotypes in a complex cellular milieu, and how both two- and three-dimensional iPS cell models can provide platforms for drug discovery and translational studies into the treatment of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

Chromatin immunoprecipitation (ChIP) method for non-model fruit flies (Diptera: Tephritidae) and evidence of histone modifications.

PubMed

Nagalingam, Kumaran; Lorenc, Michał T; Manoli, Sahana; Cameron, Stephen L; Clarke, Anthony R; Dudley, Kevin J

2018-01-01

Interactions between DNA and proteins located in the cell nucleus play an important role in controlling physiological processes by specifying, augmenting and regulating context-specific transcription events. Chromatin immunoprecipitation (ChIP) is a widely used methodology to study DNA-protein interactions and has been successfully used in various cell types for over three decades. More recently, by combining ChIP with genomic screening technologies and Next Generation Sequencing (e.g. ChIP-seq), it has become possible to profile DNA-protein interactions (including covalent histone modifications) across entire genomes. However, the applicability of ChIP-chip and ChIP-seq has rarely been extended to non-model species because of a number of technical challenges. Here we report a method that can be used to identify genome wide covalent histone modifications in a group of non-model fruit fly species (Diptera: Tephritidae). The method was developed by testing and refining protocols that have been used in model organisms, including Drosophila melanogaster. We demonstrate that this method is suitable for a group of economically important pest fruit fly species, viz., Bactrocera dorsalis, Ceratitis capitata, Zeugodacus cucurbitae and Bactrocera tryoni. We also report an example ChIP-seq dataset for B. tryoni, providing evidence for histone modifications in the genome of a tephritid fruit fly for the first time. Since tephritids are major agricultural pests globally, this methodology will be a valuable resource to study taxa-specific evolutionary questions and to assist with pest management. It also provides a basis for researchers working with other non-model species to undertake genome wide DNA-protein interaction studies.

A Cluster Analytic Approach to Identifying Predictors and Moderators of Psychosocial Treatment for Bipolar Depression: Results from STEP-BD

PubMed Central

Deckersbach, Thilo; Peters, Amy T.; Sylvia, Louisa G.; Gold, Alexandra K.; da Silva Magalhaes, Pedro Vieira; Henry, David B.; Frank, Ellen; Otto, Michael W.; Berk, Michael; Dougherty, Darin D.; Nierenberg, Andrew A.; Miklowitz, David J.

2016-01-01

Background We sought to address how predictors and moderators of psychotherapy for bipolar depression – identified individually in prior analyses – can inform the development of a metric for prospectively classifying treatment outcome in intensive psychotherapy (IP) versus collaborative care (CC) adjunctive to pharmacotherapy in the Systematic Treatment Enhancement Program (STEP-BD) study. Methods We conducted post-hoc analyses on 135 STEP-BD participants using cluster analysis to identify subsets of participants with similar clinical profiles and investigated this combined metric as a moderator and predictor of response to IP. We used agglomerative hierarchical cluster analyses and k-means clustering to determine the content of the clinical profiles. Logistic regression and Cox proportional hazard models were used to evaluate whether the resulting clusters predicted or moderated likelihood of recovery or time until recovery. Results The cluster analysis yielded a two-cluster solution: 1) “less-recurrent/severe” and 2) “chronic/recurrent.” Rates of recovery in IP were similar for less-recurrent/severe and chronic/recurrent participants. Less-recurrent/severe patients were more likely than chronic/recurrent patients to achieve recovery in CC (p = .040, OR = 4.56). IP yielded a faster recovery for chronic/recurrent participants, whereas CC led to recovery sooner in the less-recurrent/severe cluster (p = .034, OR = 2.62). Limitations Cluster analyses require list-wise deletion of cases with missing data so we were unable to conduct analyses on all STEP-BD participants. Conclusions A well-powered, parametric approach can distinguish patients based on illness history and provide clinicians with symptom profiles of patients that confer differential prognosis in CC vs. IP. PMID:27289316

Inhibition of fatty acid amide hydrolase produces analgesia by multiple mechanisms

PubMed Central

Chang, Leon; Luo, Lin; Palmer, James A; Sutton, Steven; Wilson, Sandy J; Barbier, Ann J; Breitenbucher, James Guy; Chaplan, Sandra R; Webb, Michael

2006-01-01

The reversible fatty acid amide hydrolase (FAAH) inhibitor OL135 reverses mechanical allodynia in the spinal nerve ligation (SNL) and mild thermal injury (MTI) models in the rat. The purpose of this study was to investigate the role of the cannabinoid and opioid systems in mediating this analgesic effect. Elevated brain concentrations of anandamide (350 pmol g−1 of tissue vs 60 pmol g−1 in vehicle-treated controls) were found in brains of rats given OL135 (20 mg kg−1) i.p. 15 min prior to 20 mg kg−1 i.p. anandamide. Predosing rats with OL135 (2–60 mg kg−1 i.p.) 30 min before administration of an irreversible FAAH inhibitor (URB597: 0.3 mg kg−1 intracardiac) was found to protect brain FAAH from irreversible inactivation. The level of enzyme protection was correlated with the OL135 concentrations in the same brains. OL135 (100 mg kg−1 i.p.) reduced by 50% of the maximum possible efficacy (MPE) mechanical allodynia induced by MTI in FAAH+/+mice (von Frey filament measurement) 30 min after dosing, but was without effect in FAAH−/− mice. OL135 given i.p. resulted in a dose-responsive reversal of mechanical allodynia in both MTI and SNL models in the rat with an ED50 between 6 and 9 mg kg−1. The plasma concentration at the ED50 in both models was 0.7 μM (240 ng ml−1). In the rat SNL model, coadministration of the selective CB2 receptor antagonist SR144528 (5 mg kg−1 i.p.), with 20 mg kg−1 OL135 blocked the OL135-induced reversal of mechanical allodynia, but the selective CB1 antagonist SR141716A (5 mg kg−1 i.p.) was without effect. In the rat MTI model neither SR141716A or SR144528 (both at 5 mg kg−1 i.p.), or a combination of both antagonists coadministered with OL135 (20 mg kg−1) blocked reversal of mechanical allodynia assessed 30 min after dosing. In both the MTI model and SNL models in rats, naloxone (1 mg kg−1, i.p. 30 min after OL135) reversed the analgesia (to 15% of control levels in the MTI model, to zero in the SNL) produced by OL135. PMID:16501580

Experiences with the implementation of Individual Placement and Support for people with severe mental illness: a qualitative study among stakeholders.

PubMed

Vukadin, Miljana; Schaafsma, Frederieke G; Westerman, Marjan J; Michon, Harry W C; Anema, Johannes R

2018-05-24

Individual Placement and Support (IPS) is an evidence-based approach to help people with severe mental illness achieve competitive employment. This article provides insight into an organizational and a financial implementation strategy for IPS in the Netherlands by exploring the perceived facilitators and barriers among participating stakeholders. The goal of this multifaceted strategy was to improve IPS implementation by improving the collaboration between all organizations involved, and realising secured IPS funding with a 'pay for performance' element. A qualitative, explorative study among practitioners (n = 8) and decision makers (n = 7) in mental health care and vocational rehabilitation was performed using semi-structured interviews to collect rich information about the possible facilitators and barriers with regard to the organizational and financial implementation strategy for IPS. Important perceived facilitators were the key principles of the IPS model, regular meetings of stakeholders in mental health care and vocational rehabilitation, stakeholders' experienced ownership of IPS and collaboration, the mandate and influence of the decision makers involved and secured IPS funding. Important perceived barriers included the experienced rigidity of the IPS model fidelity scale and lack of independent fidelity reviewers, the temporary and fragmented character of the secured funding, lack of communication between decision makers and practitioners and negative attitudes and beliefs among mental health clinicians. Changes in legislation were experienced as a facilitator as well as a barrier. The results of this study suggest that the collaboration and IPS funding were experienced as improved by applying an organizational and a financial implementation strategy. However, considerable effort is still necessary to overcome the remaining barriers identified and to make the implementation of IPS a success in practice.

Developing research and recruitment while fostering stakeholder engagement in a National Institutes of Mental Health-funded Interventions and Practice Research Infrastructure Programs grant for depression.

PubMed

Stirman, Shannon Wiltsey; Goldstein, Lizabeth A; Wrenn, Glenda; Barrett, Marna; Gibbons, Mary Beth Connolly; Casiano, Delane; Thompson, Donald; Green, Patricia P; Heintz, Laura; Barber, Jacques P; Crits-Christoph, Paul

2010-01-01

In the context of a National Institutes of Mental Health-funded Interventions and Practice Research Infrastructure Programs (IP-RISP) grant for the treatment of depression, a partnership was developed between a community mental health organization and a team of researchers. This paper describes the collaborative process, key challenges, and strategies employed to meet the goals of the first phase of the grant, which included development of a working and sustainable partnership and building capacity for recruitment and research. This paper was developed through the use of qualitative interviews and discussion with a variety of IP-RISP partners. Communication with multiple stakeholders through varied channels, feedback from stakeholders on research procedures, and employing a research liaison at the clinic have been key strategies in the first phase of the grant. The strategies we employed allowed multiple stakeholders to contribute to the larger mission of the IP-RISP and helped to establish an ongoing research program within the mental health organization.

Impact of daily chlorhexidine baths and hand hygiene compliance on nosocomial infection rates in critically ill patients.

PubMed

Martínez-Reséndez, Michel Fernando; Garza-González, Elvira; Mendoza-Olazaran, Soraya; Herrera-Guerra, Alexis; Rodríguez-López, Juan Manuel; Pérez-Rodriguez, Edelmiro; Mercado-Longoria, Roberto; Camacho-Ortiz, Adrián

2014-07-01

Up to 25% of all nosocomial infections (NIs) develop in critically ill patients. Our objective was to evaluate chlorhexidine (CHX) bathing and hand hygiene (HH) compliance in the reduction of NIs in the intensive care unit. The study comprised three 6-month periods: preintervention (PIP; soap/water bathing), intervention (IP; bathing with CHX-impregnated wipes), and postintervention (PoIP; soap/water bathing). An HH program was implemented during the IP and PoIP. Primary outcomes were global and specific NI rates. A total of 1007 patients were included. Infection rates per 100 discharges were higher in the PIP compared with the IP and also higher in the PoIP compared with the IP (P = .0004 and .0109, respectively). Global infection rates per 1000 hospital-days were higher in the PIP than in the IP (P = .0268). The rates of ventilator-associated pneumonia (VAP) and catheter-associated urinary tract infection (CAUTI) were higher in the PIP than in the IP (P = .036 and .0001, respectively). Isolation of Acinetobacter baumannii from VAP specimens (P = .0204) and isolation of Candida spp from CAUTI specimens (P = .0005) decreased as well. The combined intervention reduced global and specific infection rates, including rates of VAP associated with A baumannii and CAUTI associated with Candida spp. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Interfacing the Controllogics PLC over Ethernet/IP.

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

Kasemir, K. U.; Dalesio, L. R.

2001-01-01

The Allen-Bradley ControlLogix [1] line of programmable logic controllers (PLCs) offers several interfaces: Ethernet, ControlNet, DeviceNet, RS-232 and others. The ControlLogix Ethernet interface module 1756-ENET uses EtherNet/IP, the ControlNet protocol [2], encapsulated in Ethernet packages, with specific service codes [3]. A driver for the Experimental Physics and Industrial Control System (EPICS) has been developed that utilizes this EtherNet/IP protocol for controllers running the vxWorks RTOS as well as a Win32 and Unix/Linux test program. Features, performance and limitations of this interface are presented.

VON and Its Use in NASA's International Space Station Science Operation

NASA Technical Reports Server (NTRS)

Bradford, Robert N.; Chamberlain, Jim

1999-01-01

This presentation will provide a brief overview of a International Space Station (ISS) remote user (scientist/experimenter) operation. Specifically, the presentation will show how Voice over IP (VoIP) is integrated into the ISS science payload operation and in the mission voice system. Included will be the details on how a scientist, using VON, will talk to the ISS onboard crew and ground based cadre from a scientist's home location (lab, office or garage) over tile public Internet and science nets. Benefit(s) to tile ISS Program (and taxpayer) and of VoIP versus other implementations also will be presented.

Interferon-gamma inducible protein 10 (IP10) induced cisplatin resistance of HCC after liver transplantation through ER stress signaling pathway

PubMed Central

Geng, Wei; Lo, Chung-Mau; Ng, Kevin T.P.; Ling, Chang-Chun; Qi, Xiang; Li, Chang-Xian; Zhai, Yuan; Liu, Xiao-Bing; Ma, Yuen-Yuen; Man, Kwan

2015-01-01

Tumor recurrence remains an obstacle after liver surgery, especially in living donor liver transplantation (LDLT) for patients with hepatocellular carcinoma (HCC). The acute-phase liver graft injury might potentially induce poor response to chemotherapy in recurrent HCC after liver transplantation. We here intended to explore the mechanism and to identify a therapeutic target to overcome such chemoresistance. The associations among graft injury, overexpression of IP10 and multidrug resistant genes were investigated in a rat liver transplantation model, and further validated in clinical cohort. The role of IP10 on HCC cell proliferation and tumor growth under chemotherapy was studied both in vitro and in vivo. The underlying mechanism was revealed by detecting the activation of endoplasmic reticulum (ER) stress signaling pathways. Moreover, the effect of IP10 neutralizing antibody sensitizing cisplatin treatment was further explored. In rat liver transplantation model, significant up-regulation of IP10 associated with multidrug resistant genes was found in small-for-size liver graft. Clinically, high expression of circulating IP10 was significant correlated with tumor recurrence in HCC patients underwent LDLT. Overexpression of IP10 promoted HCC cell proliferation and tumor growth under cisplatin treatment by activation of ATF6/Grp78 signaling. IP10 neutralizing antibody sensitized cisplatin treatment in nude mice. The overexpression of IP10, which induced by liver graft injury, may lead to cisplatin resistance via ATF6/Grp78 ER stress signaling pathway. IP10 neutralizing antibody could be a potential adjuvant therapy to sensitize cisplatin treatment. PMID:26336986

Accretion Flows in Magnetic White Dwarf Systems

NASA Technical Reports Server (NTRS)

Imamura, James N.

2005-01-01

We received Type A and B funding under the NASA Astrophysics Data Program for the analysis and interpretation of hard x-ray data obtained by the Rossi X-ray Timing Explorer and other NASA sponsored missions for Intermediate Polars (IPS) and Polars. For some targets, optical data was available. We reduced and analyzed the X-ray spectra and the X-ray and optical (obtained at the Cerro Tololo Inter-American Observatory) timing data using detailed shock models (which we constructed) to place constraints on the properties of the accreting white dwarfs, the high energy emission mechanisms of white dwarfs, and the large-scale accretion flows of Polars and IPS. IPS and Polars are white dwarf mass-transfer binaries, members of the larger class of cata,clysmic variables. They differ from the bulk of the cataclysmic variables in that they contain strongly magnetic white dwarfs; the white dwarfs in Polars have B, = 7 to 230 MG and those in IPS have B, less than 10 MG. The IPS and Polars are both examples of funneled accretion flows in strong magnetic field systems. The IPS are similar to x-ray pulsars in that accretion disks form in the systems which are disrupted by the strong stellar magnetic fields of the white dwarfs near the stellar surface from where the plasma is funneled to the surface of the white dwarf. The localized hot spots formed at the footpoints of the funnels coupled with the rotation of the white dwarf leads to coherent pulsed x-ray emission. The Polars offer an example of a different accretion topology; the magnetic field of the white dwarf controls the accretion flow from near the inner Lagrangian point of the system directly to the stellar surface. Accretion disks do not form. The strong magnetic coupling generally leads to synchronous orbital/rotational motion in the Polars. The physical system in this sense resembles the Io/Jupiter system. In both IPS and Polars, pulsed emission from the infrared to x-rays is produced as the funneled flows merge onto the white dwarfs through the formation of strong radiating shock waves. A comparative study of the IPS and Polars can elucidate the primary effects of the magnetic fields on the dynamics and thermodynamics in accreting white dwarf systems.

Modeling impacts of human footprint and soil variability on the potential distribution of invasive plant species in different biomes

NASA Astrophysics Data System (ADS)

Wan, Ji-Zhong; Wang, Chun-Jing; Yu, Fei-Hai

2017-11-01

Human footprint and soil variability may be important in shaping the spread of invasive plant species (IPS). However, until now, there is little knowledge on how human footprint and soil variability affect the potential distribution of IPS in different biomes. We used Maxent modeling to project the potential distribution of 29 IPS with wide distributions and long introduction histories in China based on various combinations of climatic correlates, soil characteristics and human footprint. Then, we evaluated the relative importance of each type of environmental variables (climate, soil and human footprint) as well as the difference in range and similarity of the potential distribution of IPS between different biomes. Human footprint and soil variables contributed to the prediction of the potential distribution of IPS, and different types of biomes had varying responses and degrees of impacts from the tested variables. Human footprint and soil variability had the highest tendency to increase the potential distribution of IPS in Montane Grasslands and Shrublands. We propose to integrate the assessment in impacts of human footprint and soil variability on the potential distribution of IPS in different biomes into the prevention and control of plant invasion.

Intraperitoneal administration of tumor-targeting Salmonella typhimurium A1-R inhibits disseminated human ovarian cancer and extends survival in nude mice

PubMed Central

Zhang, Yong; Zhao, Ming; Yano, Shuya; Uehara, Fuminari; Yamamoto, Mako; Hiroshima, Yukihiko; Toneri, Makoto; Bouvet, Michael; Matsubara, Hisahiro; Tsuchiya, Hiroyuki; Hoffman, Robert M.

2015-01-01

Peritoneal disseminated cancer is highly treatment resistant. We here report the efficacy of intraperitoneal (i.p.) administration of tumor-targeting Salmonella typhimurium A1-R in a nude mouse model of disseminated human ovarian cancer. The mouse model was established by intraperitoneal injection of the human ovarian cancer cell line SKOV3-GFP. Seven days after implantation, mice were treated with S. typhimurium A1-R via intravenous (i.v.) or i.p. administration at the same dose, 5×107 CFU, once per week. Both i.v. and i.p. treatments effected prolonged survival compared with the untreated control group (P=0.025 and P<0.001, respectively). However, i.p. treatment was less toxic than i.v. treatment. Tumor-specific targeting of S. typhimurium A1-R was confirmed with bacterial culture from tumors and various organs and tumor or organ colony formation after i.v. or i.p. injection. Selective tumor targeting was most effective with i.p. administration. The results of the present study show S. typhimurium A1-R has promising clinical potential for disseminated ovarian cancer, especially via i.p. administration. PMID:25957417

Individual Placement and Support: a community mental health center approach to vocational rehabilitation.

PubMed

Becker, D R; Drake, R E

1994-04-01

Individual Placement and Support (IPS) is a vocational rehabilitation intervention for people with severe mental disabilities. IPS draws from components and philosophies of several other models. Employment specialists, who are part of the community mental health center team, provide services in the community. IPS emphasizes client preferences, rapid job finding, continuous assessment, competitive employment, integrated work settings, and follow-along supports. Initial research on IPS shows favorable results.

The Impact of an Online Orientation Program on the Impostor Phenomenon, Self-Efficacy, and Anxiety

ERIC Educational Resources Information Center

Ives, Sujata Kolhatkar

2010-01-01

The imposter phenomenon (IP), defined as the fear that others may perceive one to be an intellectual "phony", and its association to one's self-efficacy (SE) and anxiety, requires further research. This dissertation investigates the IP, SE, and anxiety and their interrelationships at the beginning and at the end of an orientation program…

Changes in the Medicare home health care market: the impact of reimbursement policy.

PubMed

Choi, Sunha; Davitt, Joan K

2009-03-01

The Balanced Budget Act of 1997 introduced 2 new reimbursement structures, the Interim Payment System (IPS, 1997-2000) and the Prospective Payment System (PPS, begun October 2000) for Medicare home health agencies (HHAs) under the fee-for-service program. This article describes and compares the impact of these changes on the Medicare home health market from a period before the BBA through the IPS and PPS in relation to agency characteristics. A secondary analysis of 1996, 1999, and 2002 Provider of Services data was conducted on all Medicare-certified HHAs. Frequencies and rates of change were calculated by agency characteristics to describe changes in the number of active agencies through those years. Logistic regression models were used to compare factors associated with market exits under different payment systems. The results indicate dramatic but disproportional changes in response to the IPS and the PPS among Medicare home health care agencies. Agency closures were greater and market entries fewer during the IPS, but more branch offices/subunits were closed during the PPS. Proprietary and freestanding agencies experienced greater volatility throughout, with the greatest number of closures seen in Region VI (Dallas). These results demonstrate the direct impact of policy changes on the home health care market and highlight the need to evaluate policy changes to understand both intended and unintended impacts on health markets. Future research should analyze the effect of these policy changes on other healthcare providers and systems and their impact on health outcomes for Medicare beneficiaries.

Maximizing MST's inductive capability with a Bp programmable power supply

NASA Astrophysics Data System (ADS)

Chapman, B. E.; Holly, D. J.; Jacobson, C. M.; McCollam, K. J.; Morin, J. C.; Sarff, J. S.; Squitieri, A.

2016-10-01

A major goal of the MST program is the advancement of inductive control for the development of both the RFP's fusion potential and, synergistically, the predictive capability of fusion science. This entails programmable power supplies (PPS's) for the Bt and Bp circuits. A Bt PPS is already in place, allowing advanced RFP operation and the production of tokamak plasmas, and a Bp PPS prototype is under construction. To explore some of the new capabilities to be provided by the Bp PPS, the existing Bt PPS has been temporarily connected to the Bp circuit. One key result is new-found access to very low Ip (20 kA) and very low Lundquist number, S (104). At this low S, simulation of RFP plasmas with the MHD code NIMROD is readily achievable, and work toward validation of extended MHD models using NIMROD is underway with direct comparisons to these MST plasmas. The full Bp PPS will also provide higher Ip and S than presently possible, allowing MST to produce plasmas with S spanning as much as five orders of magnitude, a dramatic extension of MST's capability. In these initial tests, the PPS has also increased five-fold MST's Ip flattop duration, to about 100 ms. This, coupled with the recently demonstrated PPS ability to drive large-amplitude sinusoidal oscillations in Ip, will allow tests of extended-duration oscillating field current drive, the goal of which is ac sustainment of a quasi-dc plasma current. Work supported by US DOE.

Regulation of 1, 4, 5-triphosphate receptor channel gating dynamics by mutant presenilin in Alzheimer's disease cells

NASA Astrophysics Data System (ADS)

Wei, Fang; Li, Xiang; Cai, Meichun; Liu, Yanping; Jung, Peter; Shuai, Jianwei

2017-06-01

In neurons of patients with Alzheimer's disease, the intracellular Ca2+ concentration is increased by its release from the endoplasmic reticulum via the inositol 1, 4, 5-triphosphate receptor (IP3R). In this paper, we discuss the IP3R gating dynamics in familial Alzheimer's disease (FAD) cells induced with presenilin mutation PS1. By fitting the parameters of an IP3R channel model to experimental data of the open probability, the mean open time and the mean closed time of IP3R channels, in control cells and FAD mutant cells, we suggest that the interaction of presenilin mutation PS1 with IP3R channels leads the decrease in the unbinding rates of IP3 and the activating Ca2+ from IP3Rs. As a result, the increased affinities of IP3 and activating Ca2+ for IP3R channels induce the increase in the Ca2+ signal in FAD mutant cells. Specifically, the PS1 mutation decreases the IP3 dissociation rate of IP3R channels significantly in FAD mutant cells. Our results suggest possible novel targets for FAD therapeutic intervention.

Specification and Design of a Fault Recovery Model for the Reliable Multicast Protocol

NASA Technical Reports Server (NTRS)

Montgomery, Todd; Callahan, John R.; Whetten, Brian

1996-01-01

The Reliable Multicast Protocol (RMP) provides a unique, group-based model for distributed programs that need to handle reconfiguration events at the application layer. This model, called membership views, provides an abstraction in which events such as site failures, network partitions, and normal join-leave events are viewed as group reformations. RMP provides access to this model through an application programming interface (API) that notifies an application when a group is reformed as the result of a some event. RMP provides applications with reliable delivery of messages using an underlying IP Multicast media to other group members in a distributed environment even in the case of reformations. A distributed application can use various Quality of Service (QoS) levels provided by RMP to tolerate group reformations. This paper explores the implementation details of the mechanisms in RMP that provide distributed applications with membership view information and fault recovery capabilities.

A simulation of the instrument pointing system for the Astro-1 mission

NASA Technical Reports Server (NTRS)

Whorton, M.; West, M.; Rakoczy, J.

1991-01-01

NASA has recently completed a shuttle-borne stellar ultraviolet astronomy mission known as Astro-1. A three axis instrument pointing system (IPS) was employed to accurately point the science instruments. In order to analyze the pointing control system and verify pointing performance, a simulation of the IPS was developed using the multibody dynamics software TREETOPS. The TREETOPS IPS simulation is capable of accurately modeling the multibody IPS system undergoing large angle, nonlinear motion. The simulation is documented and example cases are presented demonstrating disturbance rejection, fine pointing operations, and multiple target pointing and slewing of the IPS.

Briefer assessment of social network drinking: A test of the Important People Instrument-5 (IP-5).

PubMed

Hallgren, Kevin A; Barnett, Nancy P

2016-12-01

The Important People instrument (IP; Longabaugh et al., 2010) is one of the most commonly used measures of social network drinking. Although its reliability and validity are well-supported, the length of the instrument may limit its use in many settings. The present study evaluated whether a briefer, 5-person version of the IP (IP-5) adequately reproduces scores from the full IP. College freshmen (N = 1,053) reported their own past-month drinking, alcohol-related consequences, and information about drinking in their close social networks at baseline and 1 year later. From this we derived network members' drinking frequency, percentage of drinkers, and percentage of heavy drinkers, assessed for up to 10 (full IP) or 5 (IP-5) network members. We first modeled the expected concordance between full-IP scores and scores from simulated shorter IP instruments by sampling smaller subsets of network members from full IP data. Then, using quasi-experimental methods, we administered the full IP and IP-5 and compared the 2 instruments' score distributions and concurrent and year-lagged associations with participants' alcohol consumption and consequences. Most of the full-IP variance was reproduced from simulated shorter versions of the IP (ICCs ≥ 0.80). The full IP and IP-5 yielded similar score distributions, concurrent associations with drinking (r = 0.22 to 0.52), and year-lagged associations with drinking. The IP-5 retains most of the information about social network drinking from the full IP. The shorter instrument may be useful in clinical and research settings that require frequent measure administration, yielding greater temporal resolution for monitoring social network drinking. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Inositol pyrophosphates mediate the DNA-PK/ATM-p53 cell death pathway by regulating CK2 phosphorylation of Tti1/Tel2

PubMed Central

Rao, Feng; Cha, Jiyoung; Xu, Jing; Xu, Risheng; Vandiver, M. Scott; Tyagi, Richa; Tokhunts, Robert; Koldobskiy, Michael A.; Fu, Chenglai; Barrow, Roxanne; Wu, Mingxuan; Fiedler, Dorothea; Barrow, James C.; Snyder, Solomon H.

2014-01-01

The apoptotic actions of p53 require its phosphorylation by a family of phosphoinositide-3-kinase-related-kinases (PIKKs), which include DNA-PKcs and ATM. These kinases are stabilized by the TTT (Tel2, Tti1, Tti2) co-chaperone family, whose actions are mediated by CK2 phosphorylation. The inositol pyrophosphates, such as 5-diphosphoinositol pentakisphosphate (IP7), are generated by a family of inositol hexakisphosphate kinases (IP6Ks) of which IP6K2 has been implicated in p53-associated cell death. In the present study we report a novel apoptotic signaling cascade linking CK2, TTT, the PIKKs, and p53. We demonstrate that IP7, formed by IP6K2, binds CK2 to enhance its phosphorylation of the TTT complex thereby stabilizing DNA-PKcs and ATM. This process stimulates p53 phosphorylation at serine-15 to activate the cell death program in human cancer cells and in murine B cells. PMID:24657168

Reusable, extensible, and modifiable R scripts and Kepler workflows for comprehensive single set ChIP-seq analysis.

PubMed

Cormier, Nathan; Kolisnik, Tyler; Bieda, Mark

2016-07-05

There has been an enormous expansion of use of chromatin immunoprecipitation followed by sequencing (ChIP-seq) technologies. Analysis of large-scale ChIP-seq datasets involves a complex series of steps and production of several specialized graphical outputs. A number of systems have emphasized custom development of ChIP-seq pipelines. These systems are primarily based on custom programming of a single, complex pipeline or supply libraries of modules and do not produce the full range of outputs commonly produced for ChIP-seq datasets. It is desirable to have more comprehensive pipelines, in particular ones addressing common metadata tasks, such as pathway analysis, and pipelines producing standard complex graphical outputs. It is advantageous if these are highly modular systems, available as both turnkey pipelines and individual modules, that are easily comprehensible, modifiable and extensible to allow rapid alteration in response to new analysis developments in this growing area. Furthermore, it is advantageous if these pipelines allow data provenance tracking. We present a set of 20 ChIP-seq analysis software modules implemented in the Kepler workflow system; most (18/20) were also implemented as standalone, fully functional R scripts. The set consists of four full turnkey pipelines and 16 component modules. The turnkey pipelines in Kepler allow data provenance tracking. Implementation emphasized use of common R packages and widely-used external tools (e.g., MACS for peak finding), along with custom programming. This software presents comprehensive solutions and easily repurposed code blocks for ChIP-seq analysis and pipeline creation. Tasks include mapping raw reads, peakfinding via MACS, summary statistics, peak location statistics, summary plots centered on the transcription start site (TSS), gene ontology, pathway analysis, and de novo motif finding, among others. These pipelines range from those performing a single task to those performing full analyses of ChIP-seq data. The pipelines are supplied as both Kepler workflows, which allow data provenance tracking, and, in the majority of cases, as standalone R scripts. These pipelines are designed for ease of modification and repurposing.

Merging the Structural Motifs of Functionalized Amino Acids and α-Aminoamides: Compounds with Significant Anticonvulsant Activities

PubMed Central

Salomé, Christophe; Salomé-Grosjean, Elise; Stables, James P.; Kohn, Harold

2010-01-01

Functional amino acids (FAAs) and α-aminoamides (AAAs) are two classes of antiepileptic drugs (AEDs) that exhibit pronounced anticonvulsant activities. We combined key structural pharmacophores present in FAAs and AAAs to generate a new series of compounds and document that select compounds exhibit activity superior to either the prototypical FAA (lacosamide) or the prototypical AAA (safinamide) in the maximal electroshock (MES) seizure model in rats. A representative compound, (R)-N-4′-((3″-fluoro)benzyloxy)benzyl 2-acetamido-3-methoxypropionamide ((R)-10), was tested in the MES (mice, ip), MES (rat, po), psychomotor 6 Hz (32 mA) (mice, ip), and hippocampal kindled (rat, ip) seizure tests providing excellent protection with ED50 values of 13, 14, ~10 mg/kg, and 12 mg/kg, respectively. In the rat sciatic nerve ligation model (ip), (R)-10 (12 mg/kg) provided an 11.2-fold attenuation of mechanical allodynia. In the mouse biphasic formalin pain model (ip), (R)-10 (15 mg/kg) reduced pain responses in the acute and the chronic inflammatory phases. PMID:20394379

Merging the structural motifs of functionalized amino acids and alpha-aminoamides: compounds with significant anticonvulsant activities.

PubMed

Salomé, Christophe; Salomé-Grosjean, Elise; Stables, James P; Kohn, Harold

2010-05-13

Functional amino acids (FAAs) and alpha-aminoamides (AAAs) are two classes of antiepileptic drugs (AEDs) that exhibit pronounced anticonvulsant activities. We combined key structural pharmacophores present in FAAs and AAAs to generate a new series of compounds and document that select compounds exhibit activity superior to either the prototypical FAA (lacosamide) or the prototypical AAA (safinamide) in the maximal electroshock (MES) seizure model in rats. A representative compound, (R)-N-4'-((3''-fluoro)benzyloxy)benzyl 2-acetamido-3-methoxypropionamide ((R)-10), was tested in the MES (mice, ip), MES (rat, po), psychomotor 6 Hz (32 mA) (mice, ip), and hippocampal kindled (rat, ip) seizure tests providing excellent protection with ED(50) values of 13, 14, approximately 10 mg/kg, and 12 mg/kg, respectively. In the rat sciatic nerve ligation model (ip), (R)-10 (12 mg/kg) provided an 11.2-fold attenuation of mechanical allodynia. In the mouse biphasic formalin pain model (ip), (R)-10 (15 mg/kg) reduced pain responses in the acute and the chronic inflammatory phases.

Modeling of the Modulation by Buffers of Ca2+ Release through Clusters of IP3 Receptors

PubMed Central

Zeller, S.; Rüdiger, S.; Engel, H.; Sneyd, J.; Warnecke, G.; Parker, I.; Falcke, M.

2009-01-01

Abstract Intracellular Ca2+ release is a versatile second messenger system. It is modeled here by reaction-diffusion equations for the free Ca2+ and Ca2+ buffers, with spatially discrete clusters of stochastic IP3 receptor channels (IP3Rs) controlling the release of Ca2+ from the endoplasmic reticulum. IP3Rs are activated by a small rise of the cytosolic Ca2+ concentration and inhibited by large concentrations. Buffering of cytosolic Ca2+ shapes global Ca2+ transients. Here we use a model to investigate the effect of buffers with slow and fast reaction rates on single release spikes. We find that, depending on their diffusion coefficient, fast buffers can either decouple clusters or delay inhibition. Slow buffers have little effect on Ca2+ release, but affect the time course of the signals from the fluorescent Ca2+ indicator mainly by competing for Ca2+. At low [IP3], fast buffers suppress fluorescence signals, slow buffers increase the contrast between bulk signals and signals at open clusters, and large concentrations of buffers, either fast or slow, decouple clusters. PMID:19686646

Design and implementation of a VoIP broadcasting service over embedded systems in a heterogeneous network environment.

PubMed

Leu, Jenq-Shiou; Lin, Wei-Hsiang; Hsieh, Wen-Bin; Lo, Chien-Chih

2014-01-01

As the digitization is integrated into daily life, media including video and audio are heavily transferred over the Internet nowadays. Voice-over-Internet Protocol (VoIP), the most popular and mature technology, becomes the focus attracting many researches and investments. However, most of the existing studies focused on a one-to-one communication model in a homogeneous network, instead of one-to-many broadcasting model among diverse embedded devices in a heterogeneous network. In this paper, we present the implementation of a VoIP broadcasting service on the open source-Linphone-in a heterogeneous network environment, including WiFi, 3G, and LAN networks. The proposed system featuring VoIP broadcasting over heterogeneous networks can be integrated with heterogeneous agile devices, such as embedded devices or mobile phones. VoIP broadcasting over heterogeneous networks can be integrated into modern smartphones or other embedded devices; thus when users run in a traditional AM/FM signal unreachable area, they still can receive the broadcast voice through the IP network. Also, comprehensive evaluations are conducted to verify the effectiveness of the proposed implementation.

Design and Implementation of a VoIP Broadcasting Service over Embedded Systems in a Heterogeneous Network Environment

PubMed Central

Lin, Wei-Hsiang; Hsieh, Wen-Bin; Lo, Chien-Chih

2014-01-01

As the digitization is integrated into daily life, media including video and audio are heavily transferred over the Internet nowadays. Voice-over-Internet Protocol (VoIP), the most popular and mature technology, becomes the focus attracting many researches and investments. However, most of the existing studies focused on a one-to-one communication model in a homogeneous network, instead of one-to-many broadcasting model among diverse embedded devices in a heterogeneous network. In this paper, we present the implementation of a VoIP broadcasting service on the open source—Linphone—in a heterogeneous network environment, including WiFi, 3G, and LAN networks. The proposed system featuring VoIP broadcasting over heterogeneous networks can be integrated with heterogeneous agile devices, such as embedded devices or mobile phones. VoIP broadcasting over heterogeneous networks can be integrated into modern smartphones or other embedded devices; thus when users run in a traditional AM/FM signal unreachable area, they still can receive the broadcast voice through the IP network. Also, comprehensive evaluations are conducted to verify the effectiveness of the proposed implementation. PMID:25300280

The Role of Genome Accessibility in Transcription Factor Binding in Bacteria.

PubMed

Gomes, Antonio L C; Wang, Harris H

2016-04-01

ChIP-seq enables genome-scale identification of regulatory regions that govern gene expression. However, the biological insights generated from ChIP-seq analysis have been limited to predictions of binding sites and cooperative interactions. Furthermore, ChIP-seq data often poorly correlate with in vitro measurements or predicted motifs, highlighting that binding affinity alone is insufficient to explain transcription factor (TF)-binding in vivo. One possibility is that binding sites are not equally accessible across the genome. A more comprehensive biophysical representation of TF-binding is required to improve our ability to understand, predict, and alter gene expression. Here, we show that genome accessibility is a key parameter that impacts TF-binding in bacteria. We developed a thermodynamic model that parameterizes ChIP-seq coverage in terms of genome accessibility and binding affinity. The role of genome accessibility is validated using a large-scale ChIP-seq dataset of the M. tuberculosis regulatory network. We find that accounting for genome accessibility led to a model that explains 63% of the ChIP-seq profile variance, while a model based in motif score alone explains only 35% of the variance. Moreover, our framework enables de novo ChIP-seq peak prediction and is useful for inferring TF-binding peaks in new experimental conditions by reducing the need for additional experiments. We observe that the genome is more accessible in intergenic regions, and that increased accessibility is positively correlated with gene expression and anti-correlated with distance to the origin of replication. Our biophysically motivated model provides a more comprehensive description of TF-binding in vivo from first principles towards a better representation of gene regulation in silico, with promising applications in systems biology.

Trunk-acceleration based assessment of gait parameters in older persons: a comparison of reliability and validity of four inverted pendulum based estimations.

PubMed

Zijlstra, Agnes; Zijlstra, Wiebren

2013-09-01

Inverted pendulum (IP) models of human walking allow for wearable motion-sensor based estimations of spatio-temporal gait parameters during unconstrained walking in daily-life conditions. At present it is unclear to what extent different IP based estimations yield different results, and reliability and validity have not been investigated in older persons without a specific medical condition. The aim of this study was to compare reliability and validity of four different IP based estimations of mean step length in independent-living older persons. Participants were assessed twice and walked at different speeds while wearing a tri-axial accelerometer at the lower back. For all step-length estimators, test-retest intra-class correlations approached or were above 0.90. Intra-class correlations with reference step length were above 0.92 with a mean error of 0.0 cm when (1) multiplying the estimated center-of-mass displacement during a step by an individual correction factor in a simple IP model, or (2) adding an individual constant for bipedal stance displacement to the estimated displacement during single stance in a 2-phase IP model. When applying generic corrections or constants in all subjects (i.e. multiplication by 1.25, or adding 75% of foot length), correlations were above 0.75 with a mean error of respectively 2.0 and 1.2 cm. Although the results indicate that an individual adjustment of the IP models provides better estimations of mean step length, the ease of a generic adjustment can be favored when merely evaluating intra-individual differences. Further studies should determine the validity of these IP based estimations for assessing gait in daily life. Copyright © 2013 Elsevier B.V. All rights reserved.

Equivalent intraperitoneal doses of ibuprofen supplemented in drinking water or in diet: a behavioral and biochemical assay using antinociceptive and thromboxane inhibitory dose–response curves in mice

PubMed Central

El Gayar, Nesreen H.; Georgy, Sonia S.

2016-01-01

Background. Ibuprofen is used chronically in different animal models of inflammation by administration in drinking water or in diet due to its short half-life. Though this practice has been used for years, ibuprofen doses were never assayed against parenteral dose–response curves. This study aims at identifying the equivalent intraperitoneal (i.p.) doses of ibuprofen, when it is administered in drinking water or in diet. Methods. Bioassays were performed using formalin test and incisional pain model for antinociceptive efficacy and serum TXB2 for eicosanoid inhibitory activity. The dose–response curve of i.p. administered ibuprofen was constructed for each test using 50, 75, 100 and 200 mg/kg body weight (b.w.). The dose–response curves were constructed of phase 2a of the formalin test (the most sensitive phase to COX inhibitory agents), the area under the ‘change in mechanical threshold’-time curve in the incisional pain model and serum TXB2 levels. The assayed ibuprofen concentrations administered in drinking water were 0.2, 0.35, 0.6 mg/ml and those administered in diet were 82, 263, 375 mg/kg diet. Results. The 3 concentrations applied in drinking water lay between 73.6 and 85.5 mg/kg b.w., i.p., in case of the formalin test; between 58.9 and 77.8 mg/kg b.w., i.p., in case of the incisional pain model; and between 71.8 and 125.8 mg/kg b.w., i.p., in case of serum TXB2 levels. The 3 concentrations administered in diet lay between 67.6 and 83.8 mg/kg b.w., i.p., in case of the formalin test; between 52.7 and 68.6 mg/kg b.w., i.p., in case of the incisional pain model; and between 63.6 and 92.5 mg/kg b.w., i.p., in case of serum TXB2 levels. Discussion. The increment in pharmacological effects of different doses of continuously administered ibuprofen in drinking water or diet do not parallel those of i.p. administered ibuprofen. It is therefore difficult to assume the equivalent parenteral daily doses based on mathematical calculations. PMID:27547547

KChIP2 genotype dependence of transient outward current (Ito) properties in cardiomyocytes isolated from male and female mice

PubMed Central

Waldschmidt, Lara; Junkereit, Vera; Bähring, Robert

2017-01-01

The transient outward current (Ito) in cardiomyocytes is largely mediated by Kv4 channels associated with Kv Channel Interacting Protein 2 (KChIP2). A knockout model has documented the critical role of KChIP2 in Ito expression. The present study was conducted to characterize in both sexes the dependence of Ito properties, including current magnitude, inactivation kinetics, recovery from inactivation and voltage dependence of inactivation, on the number of functional KChIP2 alleles. For this purpose we performed whole-cell patch-clamp experiments on isolated left ventricular cardiomyocytes from male and female mice which had different KChIP2 genotypes; i.e., wild-type (KChIP2+/+), heterozygous knockout (KChIP2+/-) or complete knockout of KChIP2 (KChIP2-/-). We found in both sexes a KChIP2 gene dosage effect (i.e., a proportionality between number of alleles and phenotype) on Ito magnitude, however, concerning other Ito properties, KChIP2+/- resembled KChIP2+/+. Only in the total absence of KChIP2 (KChIP2-/-) we observed a slowing of Ito kinetics, a slowing of recovery from inactivation and a negative shift of a portion of the voltage dependence of inactivation. In a minor fraction of KChIP2-/- myocytes Ito was completely lost. The distinct KChIP2 genotype dependences of Ito magnitude and inactivation kinetics, respectively, seen in cardiomyocytes were reproduced with two-electrode voltage-clamp experiments on Xenopus oocytes expressing Kv4.2 and different amounts of KChIP2. Our results corroborate the critical role of KChIP2 in controlling Ito properties. They demonstrate that the Kv4.2/KChIP2 interaction in cardiomyocytes is highly dynamic, with a clear KChIP2 gene dosage effect on Kv4 channel surface expression but not on inactivation gating. PMID:28141821

KChIP2 genotype dependence of transient outward current (Ito) properties in cardiomyocytes isolated from male and female mice.

PubMed

Waldschmidt, Lara; Junkereit, Vera; Bähring, Robert

2017-01-01

The transient outward current (Ito) in cardiomyocytes is largely mediated by Kv4 channels associated with Kv Channel Interacting Protein 2 (KChIP2). A knockout model has documented the critical role of KChIP2 in Ito expression. The present study was conducted to characterize in both sexes the dependence of Ito properties, including current magnitude, inactivation kinetics, recovery from inactivation and voltage dependence of inactivation, on the number of functional KChIP2 alleles. For this purpose we performed whole-cell patch-clamp experiments on isolated left ventricular cardiomyocytes from male and female mice which had different KChIP2 genotypes; i.e., wild-type (KChIP2+/+), heterozygous knockout (KChIP2+/-) or complete knockout of KChIP2 (KChIP2-/-). We found in both sexes a KChIP2 gene dosage effect (i.e., a proportionality between number of alleles and phenotype) on Ito magnitude, however, concerning other Ito properties, KChIP2+/- resembled KChIP2+/+. Only in the total absence of KChIP2 (KChIP2-/-) we observed a slowing of Ito kinetics, a slowing of recovery from inactivation and a negative shift of a portion of the voltage dependence of inactivation. In a minor fraction of KChIP2-/- myocytes Ito was completely lost. The distinct KChIP2 genotype dependences of Ito magnitude and inactivation kinetics, respectively, seen in cardiomyocytes were reproduced with two-electrode voltage-clamp experiments on Xenopus oocytes expressing Kv4.2 and different amounts of KChIP2. Our results corroborate the critical role of KChIP2 in controlling Ito properties. They demonstrate that the Kv4.2/KChIP2 interaction in cardiomyocytes is highly dynamic, with a clear KChIP2 gene dosage effect on Kv4 channel surface expression but not on inactivation gating.

Sub-corotating region of Saturn's magnetosphere: Cassini observations of the azimuthal field and implications for the ionospheric Pederesen Current (Invited)

NASA Astrophysics Data System (ADS)

Smith, E. J.; Dougherty, M. K.; Zhou, X.

2010-12-01

A consensus model of Saturn’s magnetosphere that has broad acceptance consists of four regions in which the plasma and field are corotating, sub-corotating or undergoing Vasyliunas or Dungey convection. In this model, the sub-corotating magnetosphere contains a large scale circuital current system comprised of radial, field-aligned and ionospheric currents. A quantitative rendering of this system developed by S. Cowley and E. Bunch relates the azimuthal field component, B phi, that causes the field to spiral to the ionospheric Pedersen current , Ip. Cassini measurements of B phi over the four year interval between 2005 and 2008 that are widely distributed in radial distance, latitude and local time have been used to compute Ip from a Bunce-Cowley formula. A striking north-south asymmetry of the global magnetosphere has been found. In the southern hemisphere, the magnitude and variation of Ip with invariant colatitude, θ, agree qualitatively with the model but Ip (θ) is shifted poleward by about 10°. In the northern hemisphere, however, the data fail to reproduce the profile of Ip (θ) predicted by the model but are dominated by two high latitude currents having the wrong polarities. Possible causes of this asymmetry are seasonal variations (summer in the southern hemisphere) and/or asymmetric plasma outflow from the inner magnetosphere such as the plumes extending southward from Enceladus. Another finding is a significant local time dependence of Ip(θ) rather than the axisymmetry assumed in the model. There is a close correspondence with the model in the noon sector. The currents in the midnight and dawn sectors are significantly larger than in the noon sector and the current in the dusk sector is dramatically weaker.

The Future of Geospatial Standards

NASA Astrophysics Data System (ADS)

Bermudez, L. E.; Simonis, I.

2016-12-01

The OGC is an international not-for-profit standards development organization (SDO) committed to making quality standards for the geospatial community. A community of more than 500 member organizations with more than 6,000 people registered at the OGC communication platform drives the development of standards that are freely available for anyone to use and to improve sharing of the world's geospatial data. OGC standards are applied in a variety of application domains including Environment, Defense and Intelligence, Smart Cities, Aviation, Disaster Management, Agriculture, Business Development and Decision Support, and Meteorology. Profiles help to apply information models to different communities, thus adapting to particular needs of that community while ensuring interoperability by using common base models and appropriate support services. Other standards address orthogonal aspects such as handling of Big Data, Crowd-sourced information, Geosemantics, or container for offline data usage. Like most SDOs, the OGC develops and maintains standards through a formal consensus process under the OGC Standards Program (OGC-SP) wherein requirements and use cases are discussed in forums generally open to the public (Domain Working Groups, or DWGs), and Standards Working Groups (SWGs) are established to create standards. However, OGC is unique among SDOs in that it also operates the OGC Interoperability Program (OGC-IP) to provide real-world testing of existing and proposed standards. The OGC-IP is considered the experimental playground, where new technologies are researched and developed in a user-driven process. Its goal is to prototype, test, demonstrate, and promote OGC Standards in a structured environment. Results from the OGC-IP often become requirements for new OGC standards or identify deficiencies in existing OGC standards that can be addressed. This presentation will provide an analysis of the work advanced in the OGC consortium including standards and testbeds, where we can extract a trend for the future of geospatial standards. We see a number of key elements in focus, but simultaneously a broadening of standards to address particular communities' needs.

Induced polarization and its interaction with electromagnetic coupling in low-frequency geophysical exploration

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

Gruszka, T.P.

1987-01-01

Starting from the dynamic equations of electromagnetics we derive mutual impedance formulas that include the effects of induced polarization (IP) and electromagnetic (EM) coupling. The mutual impedance formulas are given for four geometries: a fullspace, a cylinder in a fullspace, a halfspace, and a layer over a halfspace. IP effects are characterized by a Cole-Cole model, the properties of which are fully investigated. From the general mutual impedance formulas specific limiting forms are defined to characterize the IP and EM effects. Using these limiting forms a framework is developed to justify the addition or multiplication of the two effects. Themore » additive and multiplicative models are compared in the cylinder and layer geometries with the conclusion that the additive model proves to be more accurate over a wider range of frequencies than the multiplicative model. The nature of the IP and EM effects is illustrated in all four geometries showing the effects of relevant parameters. In all cases it is shown that the real part of the mutual impedance contains important IP information that is less influenced by EM effects. Finally the effects of boundaries are illustrated by the cylinder and layer geometries and a theory is developed to incorporate EM effects and IP effects from multiple regions which utilizes frequency dependent real dilution factors. The author also included a brief review of some EM removal schemes and dilution theory approximations.« less

Systems Modeling of Ca2+ Homeostasis and Mobilization in Platelets Mediated by IP3 and Store-Operated Ca2+ Entry

PubMed Central

Dolan, Andrew T.; Diamond, Scott L.

2014-01-01

Resting platelets maintain a stable level of low cytoplasmic calcium ([Ca2+]cyt) and high dense tubular system calcium ([Ca2+]dts). During thrombosis, activators cause a transient rise in inositol trisphosphate (IP3) to trigger calcium mobilization from stores and elevation of [Ca2+]cyt. Another major source of [Ca2+]cyt elevation is store-operated calcium entry (SOCE) through plasmalemmal calcium channels that open in response to store depletion as [Ca2+]dts drops. A 34-species systems model employed kinetics describing IP3-receptor, DTS-plasmalemma puncta formation, SOCE via assembly of STIM1 and Orai1, and the plasmalemma and sarco/endoplasmic reticulum Ca2+-ATPases. Four constraints were imposed: calcium homeostasis before activation; stable in zero extracellular calcium; IP3-activatable; and functional SOCE. Using a Monte Carlo method to sample three unknown parameters and nine initial concentrations in a 12-dimensional space near measured or expected values, we found that model configurations that were responsive to stimuli and demonstrated significant SOCE required high inner membrane electric potential (>−70 mV) and low resting IP3 concentrations. The absence of puncta in resting cells was required to prevent spontaneous store depletion in calcium-free media. Ten-fold increases in IP3 caused saturated calcium mobilization. This systems model represents a critical step in being able to predict platelets’ phenotypes during hemostasis or thrombosis. PMID:24806937

Use of IPsec by Manned Space Missions

NASA Technical Reports Server (NTRS)

Pajevski, Michael J.

2009-01-01

NASA's Constellation Program is developing its next generation manned space systems for missions to the International Space Station (ISS) and the Moon. The Program is embarking on a path towards standards based Internet Protocol (IP) networking for space systems communication. The IP based communications will be paired with industry standard security mechanisms such as Internet Protocol Security (IPsec) to ensure the integrity of information exchanges and prevent unauthorized release of sensitive information in-transit. IPsec has been tested in simulations on the ground and on at least one Earth orbiting satellite, but the technology is still unproven in manned space mission situations and significant obstacles remain.

Model calibration for ice sheets and glaciers dynamics: a general theory of inverse problems in glaciology

NASA Astrophysics Data System (ADS)

Giudici, Mauro; Baratelli, Fulvia; Vassena, Chiara; Cattaneo, Laura

2014-05-01

Numerical modelling of the dynamic evolution of ice sheets and glaciers requires the solution of discrete equations which are based on physical principles (e.g. conservation of mass, linear momentum and energy) and phenomenological constitutive laws (e.g. Glen's and Fourier's laws). These equations must be accompanied by information on the forcing term and by initial and boundary conditions (IBC) on ice velocity, stress and temperature; on the other hand the constitutive laws involves many physical parameters, which possibly depend on the ice thermodynamical state. The proper forecast of the dynamics of ice sheets and glaciers (forward problem, FP) requires a precise knowledge of several quantities which appear in the IBCs, in the forcing terms and in the phenomenological laws and which cannot be easily measured at the study scale in the field. Therefore these quantities can be obtained through model calibration, i.e. by the solution of an inverse problem (IP). Roughly speaking, the IP aims at finding the optimal values of the model parameters that yield the best agreement of the model output with the field observations and data. The practical application of IPs is usually formulated as a generalised least squares approach, which can be cast in the framework of Bayesian inference. IPs are well developed in several areas of science and geophysics and several applications were proposed also in glaciology. The objective of this paper is to provide a further step towards a thorough and rigorous theoretical framework in cryospheric studies. Although the IP is often claimed to be ill-posed, this is rigorously true for continuous domain models, whereas for numerical models, which require the solution of algebraic equations, the properties of the IP must be analysed with more care. First of all, it is necessary to clarify the role of experimental and monitoring data to determine the calibration targets and the values of the parameters that can be considered to be fixed, whereas only the model output should depend on the subset of the parameters that can be identified with the calibration procedure and the solution to the IP. It is actually difficult to guarantee the existence and uniqueness of a solution to the IP for complex non-linear models. Also identifiability, a property related to the solution to the FP, and resolution should be carefully considered. Moreover, instability of the IP should not be confused with ill-conditioning and with the properties of the method applied to compute a solution. Finally, sensitivity analysis is of paramount importance to assess the reliability of the estimated parameters and of the model output, but it is often based on the one-at-a-time approach, through the application of the adjoint-state method, to compute local sensitivity, i.e. the uncertainty on the model output due to small variations of the input parameters, whereas first-order approaches that consider the whole possible variability of the model parameters should be considered. This theoretical framework and the relevant properties are illustrated by means of a simple numerical example of isothermal ice flow, based on the shallow ice approximation.

Enabling IP Header Compression in COTS Routers via Frame Relay on a Simplex Link

NASA Technical Reports Server (NTRS)

Nguyen, Sam P.; Pang, Jackson; Clare, Loren P.; Cheng, Michael K.

2010-01-01

NASA is moving toward a networkcentric communications architecture and, in particular, is building toward use of Internet Protocol (IP) in space. The use of IP is motivated by its ubiquitous application in many communications networks and in available commercial off-the-shelf (COTS) technology. The Constellation Program intends to fit two or more voice (over IP) channels on both the forward link to, and the return link from, the Orion Crew Exploration Vehicle (CEV) during all mission phases. Efficient bandwidth utilization of the links is key for voice applications. In Voice over IP (VoIP), the IP packets are limited to small sizes to keep voice latency at a minimum. The common voice codec used in VoIP is G.729. This new algorithm produces voice audio at 8 kbps and in packets of 10-milliseconds duration. Constellation has designed the VoIP communications stack to use the combination of IP/UDP/RTP protocols where IP carries a 20-byte header, UDP (User Datagram Protocol) carries an 8-byte header, and RTP (Real Time Transport Protocol) carries a 12-byte header. The protocol headers total 40 bytes and are equal in length to a 40-byte G.729 payload, doubling the VoIP latency. Since much of the IP/UDP/RTP header information does not change from IP packet to IP packet, IP/UDP/RTP header compression can avoid transmission of much redundant data as well as reduce VoIP latency. The benefits of IP header compression are more pronounced at low data rate links such as the forward and return links during CEV launch. IP/UDP/RTP header compression codecs are well supported by many COTS routers. A common interface to the COTS routers is through frame relay. However, enabling IP header compression over frame relay, according to industry standard (Frame Relay IP Header Compression Agreement FRF.20), requires a duplex link and negotiations between the compressor router and the decompressor router. In Constellation, each forward to and return link from the CEV in space is treated independently as a simplex link. Without negotiation, the COTS routers are prevented from entering into the IP header compression mode, and no IP header compression would be performed. An algorithm is proposed to enable IP header compression in COTS routers on a simplex link with no negotiation or with a one-way messaging. In doing so, COTS routers can enter IP header compression mode without the need to handshake through a bidirectional link as required by FRF.20. This technique would spoof the routers locally and thereby allow the routers to enter into IP header compression mode without having the negotiations between routers actually occur. The spoofing function is conducted by a frame relay adapter (also COTS) with the capability to generate control messages according to the FRF.20 descriptions. Therefore, negotiation is actually performed between the FRF.20 adapter and the connecting COTS router locally and never occurs over the space link. Through understanding of the handshaking protocol described by FRF.20, the necessary FRF.20 negotiations messages can be generated to control the connecting router, not only to turn on IP header compression but also to adjust the compression parameters. The FRF.20 negotiation (or control) message is composed in the FRF.20 adapter by interpreting the incoming router request message. Many of the fields are simply transcribed from request to response while the control field indicating response and type are modified.

DROMPA: easy-to-handle peak calling and visualization software for the computational analysis and validation of ChIP-seq data.

PubMed

Nakato, Ryuichiro; Itoh, Tahehiko; Shirahige, Katsuhiko

2013-07-01

Chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) can identify genomic regions that bind proteins involved in various chromosomal functions. Although the development of next-generation sequencers offers the technology needed to identify these protein-binding sites, the analysis can be computationally challenging because sequencing data sometimes consist of >100 million reads/sample. Herein, we describe a cost-effective and time-efficient protocol that is generally applicable to ChIP-seq analysis; this protocol uses a novel peak-calling program termed DROMPA to identify peaks and an additional program, parse2wig, to preprocess read-map files. This two-step procedure drastically reduces computational time and memory requirements compared with other programs. DROMPA enables the identification of protein localization sites in repetitive sequences and efficiently identifies both broad and sharp protein localization peaks. Specifically, DROMPA outputs a protein-binding profile map in pdf or png format, which can be easily manipulated by users who have a limited background in bioinformatics. © 2013 The Authors Genes to Cells © 2013 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

IPS-Empress II inlay-retained fixed partial denture reinforced with zirconia bar: three-dimensional finite element and in-vitro studies.

PubMed

Kermanshah, Hamid; Geramy, Allahyar; Ebrahimi, Shahram Farzin; Bitaraf, Tahereh

2012-12-01

This study evaluated von Mises stress distribution, flexural strength and interface micrographs of IPS-Empress II (IPS) inlay-retained fixed partial dentures (IRFPD) reinforced with Zirconia bars (Zb). In the Finite element analysis, six three-dimensional models of IRFPD were designed using Solid Works 2006. Five models were reinforced with different Zb and a model without Zb was considered as a control. The bridges were loaded by 200 and 500 N forces at the middle of the pontic on the occlusal surface. Subsequently, von Mises stress and displacement of the models were evaluated along a defined path. In the experimental part, 21 bar shape specimens were fabricated from lithium disilicate and zirconia ceramic in three different designs. The zirconia-IPS interfaces and the fractured surfaces of flexural test were observed using SEM. In the connector area, von Mises stress and displacement of the models with Zb under a load of 500 N were decreased compared to the model without the Zb; however, this difference was not considerable at a load of 200 N. In the mesial connector, Von Mises stress and displacement was decreased from 12.5 Mpa for the control model tested at 500 N to 7.0 Mpa for the model with Zb and from 0.0050-0.0041 mm, respectively. SEM analyses showed that, before fracture, interfacial gaps were not observed along the interfaces, but initiated cracks propagated along the interfaces after flexural loading. IPS IRFPD reinforced by Zb can tolerate higher stresses while still functioning effectively and the interfaces may have desirable adaption.

Program Evaluation of Outcomes Based Orthotic and Prosthetic Education

DTIC Science & Technology

2006-12-01

Rheumatoid Arthritis; synovial joints ; tendon sheaths. b. Osteoarthritis; weight bearing joints ; loading areas. c. Osteoporosis; cancellous bone...flexion. 32. The desirable length of a thumb post is: a. to the thumb IP joint . b. proximal to the IP joint . c. to the nail bed. d. just...assist hyperextension of the thoracic spine. b. eliminate motion. c. prevent lumbar flexion. d. reduce axial load on lumbar vertebrae. 44

Communication-Gateway Software For NETEX, DECnet, And TCP/IP

NASA Technical Reports Server (NTRS)

Keith, B.; Ferry, D.; Fendler, E.

1990-01-01

Communications gateway software, GATEWAY, provides process-to-process communication between remote applications programs in different protocol domains. Communicating peer processes may be resident on any paired combination of NETEX, DECnet, or TCP/IP hosts. Provides necessary mapping from one protocol to another and facilitates practical intermachine communications in cost-effective manner by eliminating need to standardize on single protocol or to implement multiple protocols in host computers. Written in Ada.

Fault recovery in the reliable multicast protocol

NASA Technical Reports Server (NTRS)

Callahan, John R.; Montgomery, Todd L.; Whetten, Brian

1995-01-01

The Reliable Multicast Protocol (RMP) provides a unique, group-based model for distributed programs that need to handle reconfiguration events at the application layer. This model, called membership views, provides an abstraction in which events such as site failures, network partitions, and normal join-leave events are viewed as group reformations. RMP provides access to this model through an application programming interface (API) that notifies an application when a group is reformed as the result of a some event. RMP provides applications with reliable delivery of messages using an underlying IP Multicast (12, 5) media to other group members in a distributed environment even in the case of reformations. A distributed application can use various Quality of Service (QoS) levels provided by RMP to tolerate group reformations. This paper explores the implementation details of the mechanisms in RMP that provide distributed applications with membership view information and fault recovery capabilities.

Dose-dependent role of novel agents emodin and BTB14431 in colonic cancer treatment in rats.

PubMed

Braumann, Chris; Koplin, Gerold; Geier, Caroline; Höhn, Philipp; Pohlenz, Jana; Dubiel, Wolfgang; Rogalla, Stephan

2017-12-01

BTB14431 is an in silico homolog to emodin. Both were found to possess anti-tumor effects in vitro. The aim of this work was to analyze the tumor suppressing effects of both molecules in an intraperitoneal (ip) and intravenous (iv) treated rat model (WAG-Rij). A tumor cell suspension (CC531) was applied at the cecum after laparotomy and at the back. The rats where treated twice a day over 1 week with BTB14431, emodin and isotone sodium chloride solution (control). Treatment was applied iv or ip in a variety of dosages. Peripheral blood samples were taken before tumor application and on day 7. Twenty-one days after the last day of therapy animals were euthanized and tumor growth was evaluated. Data showed an insignificant decrease of tumor growth after iv and ip treatment with low doses of BTB14431 and emodin. Differential blood analysis showed apoptosis. Increased doses of emodin clearly raised mortality rate. Apoptosis was verified but no tumor-suppressing effects could be observed for iv and ip treatment with both agents in contrast to in vitro studies in our model. Establishing a successful ip treatment model for emotion and BTB14331 requires further studies.

76 FR 18555 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-04

... announced below concerns Economic Studies of Vaccines and Immunization Policies, Programs, and Practices... to ``Economic Studies of Vaccines and Immunization Policies, Programs, and Practices, FOA IP11-007...

Effect of Withania somnifera on forced swimming test induced immobility in mice and its interaction with various drugs.

PubMed

Shah, P C; Trivedi, N A; Bhatt, J D; Hemavathi, K G

2006-01-01

The objective of the present study was to evaluate the antidepressant action of Withania somnifera (WS) as well as its interaction with the conventional antidepressant drugs and to delineate the possible mechanism of its antidepressant action using forced swimming model in mice. Effect of different doses of WS, fluoxetine and imipramine were studied on forced swimming test induced mean immobility time (MIT). Moreover effect of WS 100 mg/kg, i.p. was observed at different time intervals. Effect produced by combination of sub therapeutic doses of WS with imipramine (2.5 mg/kg, i.p.) as well as fluoxetine (2.5 mg/kg, i.p.) were also observed. Effect of WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) were observed in mice pretreated with reserpine (2 mg/kg, i.p.) and clonidine (0.15 mg/kg, i.p.). Effects of prazosin (3 mg/kg, i.p.) or haloperidol (0.1 mg/kg, i.p.) pre-treatment were also observed on WS induced decrease in MIT. WS produced dose dependent decrease in MIT. Maximum effect in MIT was observed after 30 min of treatment with WS 100 mg/kg, i.p. Combination of WS (37.5 mg/kg, i.p.) with imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) also produced significant decrease in the MIT. Clonidine and reserpine induced increase in MIT, was significantly reversed by treatment with WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.). Pre-treatment with prazosin but not haloperidol, significantly antagonized the WS (100 mg/kg, i.p.) induced decrease in MIT. It is concluded that, WS produced significant decrease in MIT in mice which could be mediated partly through a adrenoceptor as well as alteration in the level of central biogenic amines.

A resource for characterizing genome-wide binding and putative target genes of transcription factors expressed during secondary growth and wood formation in Populus.

PubMed

Liu, Lijun; Ramsay, Trevor; Zinkgraf, Matthew; Sundell, David; Street, Nathaniel Robert; Filkov, Vladimir; Groover, Andrew

2015-06-01

Identifying transcription factor target genes is essential for modeling the transcriptional networks underlying developmental processes. Here we report a chromatin immunoprecipitation sequencing (ChIP-seq) resource consisting of genome-wide binding regions and associated putative target genes for four Populus homeodomain transcription factors expressed during secondary growth and wood formation. Software code (programs and scripts) for processing the Populus ChIP-seq data are provided within a publically available iPlant image, including tools for ChIP-seq data quality control and evaluation adapted from the human Encyclopedia of DNA Elements (ENCODE) project. Basic information for each transcription factor (including members of Class I KNOX, Class III HD ZIP, BEL1-like families) binding are summarized, including the number and location of binding regions, distribution of binding regions relative to gene features, associated putative target genes, and enriched functional categories of putative target genes. These ChIP-seq data have been integrated within the Populus Genome Integrative Explorer (PopGenIE) where they can be analyzed using a variety of web-based tools. We present an example analysis that shows preferential binding of transcription factor ARBORKNOX1 to the nearest neighbor genes in a pre-calculated co-expression network module, and enrichment for meristem-related genes within this module including multiple orthologs of Arabidopsis KNOTTED-like Arabidopsis 2/6. © 2015 Society for Experimental Biology and John Wiley & Sons Ltd This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Research study on IPS digital controller design

NASA Technical Reports Server (NTRS)

Kuo, B. C.; Folkerts, C.

1976-01-01

The performance is investigated of the simplified continuous-data model of the Instrument Pointing System (IPS). Although the ultimate objective is to study the digital model of the system, knowledge on the performance of the continuous-data model is important in the sense that the characteristics of the digital system should approach those of the continuous-data system as the sampling period approaches zero.

Practice makes perfect: A systematic review of the expertise development of pharmacist and nurse independent prescribers in the United Kingdom.

PubMed

Abuzour, Aseel S; Lewis, Penny J; Tully, Mary P

2018-01-01

Prescribing is a complex and error-prone task that demands expertise. McLellan et al.'s theory of expertise development model ("the model"), developed to assess medical literature on prescribing by medical students, proposes that in order to develop, individuals should deliberately engage their knowledge, skills and attitudes within a social context. Its applicability to independent prescribers (IP) is unknown. A systematic review was conducted to explore whether the model is applicable to non-medical independent prescribing and to assess the factors underpinning expertise development reported in the literature. Six electronic databases (EMBASE, Medline, AMED, CINAHL, IPA and PsychInfo) were searched for articles published between 2006 and 2016, reporting empirical data on pharmacist and nurse IPs education or practice. Data were extracted using themes from the model and analysed using framework analysis. Thirty-four studies met the inclusion criteria. Knowledge, pre-registration education, experience, support and confidence were some of the intrinsic and extrinsic factors influencing IPs. Difficulty in transferring theory to practice was attributed to lack of basic pharmacology and bioscience content in pre-registration nursing rather than the prescribing programme. Students saw interventions using virtual learning or learning in practice as more useful with long-term benefits e.g. students were able to use their skills in history taking following the virtual learning intervention 6-months after the programme. All studies demonstrated how engaging knowledge and skills affected individuals' attitude by, for example, increasing professional dignity. IPs were able to develop their expertise when integrating their competencies in a workplace context with support from colleagues and adherence to guidelines. This is the first study to synthesize data systematically on expertise development from studies on IPs using the model. The model showed the need for stronger foundations in scientific knowledge amongst some IPs, where continuous workplace practice can improve skills and strengthen attitudes. This could facilitate a smoother transfer of learnt theory to practice, in order for IPs to be experts within their fields and not merely adequately competent. Copyright © 2017 Elsevier Inc. All rights reserved.

Optimization of OSPF Routing in IP Networks

NASA Astrophysics Data System (ADS)

Bley, Andreas; Fortz, Bernard; Gourdin, Eric; Holmberg, Kaj; Klopfenstein, Olivier; Pióro, Michał; Tomaszewski, Artur; Ümit, Hakan

The Internet is a huge world-wide packet switching network comprised of more than 13,000 distinct subnetworks, referred to as Autonomous Systems (ASs) autonomous system AS . They all rely on the Internet Protocol (IP) internet protocol IP for transport of packets across the network. And most of them use shortest path routing protocols shortest path routing!protocols , such as OSPF or IS-IS, to control the routing of IP packets routing!of IP packets within an AS. The idea of the routing is extremely simple — every packet is forwarded on IP links along the shortest route between its source and destination nodes of the AS. The AS network administrator can manage the routing of packets in the AS by supplying the so-called administrative weights of IP links, which specify the link lengths that are used by the routing protocols for their shortest path computations. The main advantage of the shortest path routing policy is its simplicity, allowing for little administrative overhead. From the network engineering perspective, however, shortest path routing can pose problems in achieving satisfactory traffic handling efficiency. As all routing paths depend on the same routing metric routing!metric , it is not possible to configure the routing paths for the communication demands between different pairs of nodes explicitly or individually; the routing can be controlled only indirectly and only as a whole by modifying the routing metric. Thus, one of the main tasks when planning such networks is to find administrative link weights that induce a globally efficient traffic routing traffic!routing configuration of an AS. It turns out that this task leads to very difficult mathematical optimization problems. In this chapter, we discuss and describe exact integer programming models and solution approaches as well as practically efficient smart heuristics for such shortest path routing problems shortest path routing!problems .

ACTS 118x: High Speed TCP Interoperability Testing

NASA Technical Reports Server (NTRS)

Brooks, David E.; Buffinton, Craig; Beering, Dave R.; Welch, Arun; Ivancic, William D.; Zernic, Mike; Hoder, Douglas J.

1999-01-01

With the recent explosion of the Internet and the enormous business opportunities available to communication system providers, great interest has developed in improving the efficiency of data transfer over satellite links using the Transmission Control Protocol (TCP) of the Internet Protocol (IP) suite. The NASA's ACTS experiments program initiated a series of TCP experiments to demonstrate scalability of TCP/IP and determine to what extent the protocol can be optimized over a 622 Mbps satellite link. Through partnerships with the government technology oriented labs, computer, telecommunication, and satellite industries NASA Glenn was able to: (1) promote the development of interoperable, high-performance TCP/IP implementations across multiple computing / operating platforms; (2) work with the satellite industry to answer outstanding questions regarding the use of standard protocols (TCP/IP and ATM) for the delivery of advanced data services, and for use in spacecraft architectures; and (3) conduct a series of TCP/IP interoperability tests over OC12 ATM over a satellite network in a multi-vendor environment using ACTS. The experiments' various network configurations and the results are presented.

Data exploration, quality control and statistical analysis of ChIP-exo/nexus experiments

PubMed Central

Welch, Rene; Chung, Dongjun; Grass, Jeffrey; Landick, Robert

2017-01-01

Abstract ChIP-exo/nexus experiments rely on innovative modifications of the commonly used ChIP-seq protocol for high resolution mapping of transcription factor binding sites. Although many aspects of the ChIP-exo data analysis are similar to those of ChIP-seq, these high throughput experiments pose a number of unique quality control and analysis challenges. We develop a novel statistical quality control pipeline and accompanying R/Bioconductor package, ChIPexoQual, to enable exploration and analysis of ChIP-exo and related experiments. ChIPexoQual evaluates a number of key issues including strand imbalance, library complexity, and signal enrichment of data. Assessment of these features are facilitated through diagnostic plots and summary statistics computed over regions of the genome with varying levels of coverage. We evaluated our QC pipeline with both large collections of public ChIP-exo/nexus data and multiple, new ChIP-exo datasets from Escherichia coli. ChIPexoQual analysis of these datasets resulted in guidelines for using these QC metrics across a wide range of sequencing depths and provided further insights for modelling ChIP-exo data. PMID:28911122

Data exploration, quality control and statistical analysis of ChIP-exo/nexus experiments.

PubMed

Welch, Rene; Chung, Dongjun; Grass, Jeffrey; Landick, Robert; Keles, Sündüz

2017-09-06

ChIP-exo/nexus experiments rely on innovative modifications of the commonly used ChIP-seq protocol for high resolution mapping of transcription factor binding sites. Although many aspects of the ChIP-exo data analysis are similar to those of ChIP-seq, these high throughput experiments pose a number of unique quality control and analysis challenges. We develop a novel statistical quality control pipeline and accompanying R/Bioconductor package, ChIPexoQual, to enable exploration and analysis of ChIP-exo and related experiments. ChIPexoQual evaluates a number of key issues including strand imbalance, library complexity, and signal enrichment of data. Assessment of these features are facilitated through diagnostic plots and summary statistics computed over regions of the genome with varying levels of coverage. We evaluated our QC pipeline with both large collections of public ChIP-exo/nexus data and multiple, new ChIP-exo datasets from Escherichia coli. ChIPexoQual analysis of these datasets resulted in guidelines for using these QC metrics across a wide range of sequencing depths and provided further insights for modelling ChIP-exo data. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Intestinal ischemic preconditioning reduces liver ischemia reperfusion injury in rats

PubMed Central

XUE, TONG-MIN; TAO, LI-DE; ZHANG, JIE; ZHANG, PEI-JIAN; LIU, XIA; CHEN, GUO-FENG; ZHU, YI-JIA

2016-01-01

The aim of the current study was to investigate whether intestinal ischemic preconditioning (IP) reduces damage to the liver during hepatic ischemia reperfusion (IR). Sprague Dawley rats were used to model liver IR injury, and were divided into the sham operation group (SO), IR group and IP group. The results indicated that IR significantly increased Bax, caspase 3 and NF-κBp65 expression levels, with reduced expression of Bcl-2 compared with the IP group. Compared with the IR group, the levels of AST, ALT, MPO, MDA, TNF-α and IL-1 were significantly reduced in the IP group. Immunohistochemistry for Bcl-2 and Bax indicated that Bcl-2 expression in the IP group was significantly increased compared with the IR group. In addition, IP reduced Bax expression compared with the IR group. The average liver injury was worsened in the IR group and improved in the IP group, as indicated by the morphological evaluation of liver tissues. The present study suggested that IP may alleviates apoptosis, reduce the release of pro-inflammatory cytokines, ameloriate reductions in liver function and reduce liver tissue injury. To conclude, IP provided protection against hepatic IR injury. PMID:26821057

The therapeutic potential of human adipose-derived mesenchymal stem cells producing CXCL10 in a mouse melanoma lung metastasis model.

PubMed

Mirzaei, Hamed; Salehi, Hossein; Oskuee, Reza Kazemi; Mohammadpour, Ali; Mirzaei, Hamid Reza; Sharifi, Mohammad Reza; Salarinia, Reza; Darani, Hossein Yousofi; Mokhtari, Mojgan; Masoudifar, Aria; Sahebkar, Amirhossein; Salehi, Rasoul; Jaafari, Mahmoud Reza

2018-04-10

Interferon γ-induced protein 10 kDa (IP-10) is a potent chemoattractant and has been suggested to enhance antitumor activity and mediate tumor regression through multiple mechanisms of action. Multiple lines of evidence have indicated that genetically-modified adult stem cells represent a potential source for cell-based cancer therapy. In the current study, we assessed therapeutic potential of human adipose derived mesenchymal stem cells (hADSC) genetically-modified to express IP-10 for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma. A Piggybac vector encoding IP-10 was employed to transfect hADSC ex vivo. Expression and bioactivity of the transgenic protein from hADSCs expressing IP-10 were confirmed prior to in vivo studies. Our results indicated that hADSCs expressing IP-10 could inhibit the growth of B16F10 melanoma cells and significantly prolonged survival. Immunohistochemistry analysis, TUNEL assay and western blot analysis indicated that hADSCs expressing IP-10 inhibited tumor cell growth, hindered tumor infiltration of Tregs, restricted angiogenesis and significantly prolonged survival. In conclusion, our results demonstrated that targeting metastatic tumor sites by hADSC expressing IP-10 could reduce melanoma tumor growth and lung metastasis. Copyright © 2018 Elsevier B.V. All rights reserved.

IP-10 protects while MIP-2 promotes experimental anesthetic hapten - induced hepatitis

PubMed Central

Njoku, Dolores B.; Li, Zhaoxia; Mellerson, Jenelle L; Sharma, Rajni; Talor, Monica V.; Barat, Nicole; Rose, Noel R.

2009-01-01

MIP-2 and IFN-γ inducible protein-10 (IP-10) and their respective receptors, CXCR2 and CXCR3, modulate tissue inflammation by recruiting neutrophils or T cells from the spleen or bone marrow. Yet, how these chemokines modulate diseases such as immune-mediated drug-induced liver injury (DILI) is essentially unknown. To investigate how chemokines modulate experimental DILI in our model we used susceptible BALB/c (WT) and IL-4−/− (KO) mice that develop significantly reduced hepatitis and splenic T cell priming to anesthetic haptens and self proteins following TFA-S100 immunizations. We detected CXCR2+ splenic granulocytes in all mice two weeks following immunizations; by 3 weeks, MIP-2 levels (p<0.001) and GR1+ cells were elevated in WT livers, suggesting MIP-2-recruited granulocytes. Elevated splenic CXCR3+ CD4+T cells were identified after 2 weeks in KO mice indicating elevated IP-10 levels which were confirmed during T cell priming. This result suggested that IP-10 reduced T cell priming to critical DILI antigens. Increased T cell proliferation following co-culture of TFA-S100-primed WT splenocytes with anti-IP-10 (p<0.05) confirmed that IP-10 reduced T cell priming to CYP2E1 and TFA. We propose that MIP-2 promotes and IP-10 protects against the development of hepatitis and T cell priming in this murine model. PMID:19131211

New Geophysical Technique for Mineral Exploration and Mineral Discrimination Based on Electromagnetic Methods

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

Michael S. Zhdanov

2005-03-09

The research during the first year of the project was focused on developing the foundations of a new geophysical technique for mineral exploration and mineral discrimination, based on electromagnetic (EM) methods. The proposed new technique is based on examining the spectral induced polarization effects in electromagnetic data using modern distributed acquisition systems and advanced methods of 3-D inversion. The analysis of IP phenomena is usually based on models with frequency dependent complex conductivity distribution. One of the most popular is the Cole-Cole relaxation model. In this progress report we have constructed and analyzed a different physical and mathematical model ofmore » the IP effect based on the effective-medium theory. We have developed a rigorous mathematical model of multi-phase conductive media, which can provide a quantitative tool for evaluation of the type of mineralization, using the conductivity relaxation model parameters. The parameters of the new conductivity relaxation model can be used for discrimination of the different types of rock formations, which is an important goal in mineral exploration. The solution of this problem requires development of an effective numerical method for EM forward modeling in 3-D inhomogeneous media. During the first year of the project we have developed a prototype 3-D IP modeling algorithm using the integral equation (IP) method. Our IE forward modeling code INTEM3DIP is based on the contraction IE method, which improves the convergence rate of the iterative solvers. This code can handle various types of sources and receivers to compute the effect of a complex resistivity model. We have tested the working version of the INTEM3DIP code for computer simulation of the IP data for several models including a southwest US porphyry model and a Kambalda-style nickel sulfide deposit. The numerical modeling study clearly demonstrates how the various complex resistivity models manifest differently in the observed EM data. These modeling studies lay a background for future development of the IP inversion method, directed at determining the electrical conductivity and the intrinsic chargeability distributions, as well as the other parameters of the relaxation model simultaneously. The new technology envisioned in this proposal, will be used for the discrimination of different rocks, and in this way will provide an ability to distinguish between uneconomic mineral deposits and the location of zones of economic mineralization and geothermal resources.« less

Straddling care and education: Developing interprofessional collaboration through a hotspotting service learning project.

PubMed

Jones, Anne C; Li, Trudy; Zomorodi, Meg; Broadhurst, Rob; Weil, Amy B

2018-06-01

Interprofessional (IP) team work has been shown to decrease burnout and improve care and decrease costs. However, institutional barriers have challenged adoption in practice and education. Faculty and students are turning to IP service-learning projects to help students gain experience and provide needed services. This paper highlights a "hotspotting" program where students from different health professions work collaboratively to improve high utilizing patients' health. Benefits, challenges and preliminary results including cost savings and student efficacy are shared. Institutions should surmount barriers that make hotspotting service-learning challenging as IP team-based experiences prepare students for the workplace and can help mitigate burnout. Copyright © 2018 Elsevier Inc. All rights reserved.

Energy star compliant voice over internet protocol (VoIP) telecommunications network including energy star compliant VoIP devices

DOEpatents

Kouchri, Farrokh Mohammadzadeh

2012-11-06

A Voice over Internet Protocol (VoIP) communications system, a method of managing a communications network in such a system and a program product therefore. The system/network includes an ENERGY STAR (E-star) aware softswitch and E-star compliant communications devices at system endpoints. The E-star aware softswitch allows E-star compliant communications devices to enter and remain in power saving mode. The E-star aware softswitch spools messages and forwards only selected messages (e.g., calls) to the devices in power saving mode. When the E-star compliant communications devices exit power saving mode, the E-star aware softswitch forwards spooled messages.

ChIP-nexus: a novel ChIP-exo protocol for improved detection of in vivo transcription factor binding footprints

PubMed Central

He, Qiye; Johnston, Jeff; Zeitlinger, Julia

2014-01-01

Understanding how eukaryotic enhancers are bound and regulated by specific combinations of transcription factors is still a major challenge. To better map transcription factor binding genome-wide at nucleotide resolution in vivo, we have developed a robust ChIP-exo protocol called ChIP experiments with nucleotide resolution through exonuclease, unique barcode and single ligation (ChIP-nexus), which utilizes an efficient DNA self-circularization step during library preparation. Application of ChIP-nexus to four proteins—human TBP and Drosophila NFkB, Twist and Max— demonstrates that it outperforms existing ChIP protocols in resolution and specificity, pinpoints relevant binding sites within enhancers containing multiple binding motifs and allows the analysis of in vivo binding specificities. Notably, we show that Max frequently interacts with DNA sequences next to its motif, and that this binding pattern correlates with local DNA sequence features such as DNA shape. ChIP-nexus will be broadly applicable to studying in vivo transcription factor binding specificity and its relationship to cis-regulatory changes in humans and model organisms. PMID:25751057

Inhibition of P-Glycoprotein Mediated Efflux in Caco-2 Cells by Phytic Acid.

PubMed

Li, Lujia; Fu, Qingxue; Xia, Mengxin; Xin, Lei; Shen, Hongyi; Li, Guowen; Ji, Guang; Meng, Qianchao; Xie, Yan

2018-01-31

Phytic acid (IP6) is a natural phosphorylated inositol, which is abundantly present in most cereal grains and seeds. This study investigated the effects of IP6 regulation on P-glycoprotein (P-gp) and its potential mechanisms using in situ and in vitro models. The effective permeability of the typical P-gp substrate rhodamine 123 (R123) in colon was significantly increased from (1.69 ± 0.22) × 10 -5 cm/s in the control group to (3.39 ± 0.417) × 10 -5 cm/s (p < 0.01) in the 3.5 mM IP6 group. Additionally, IP6 can concentration-dependently decrease the R123 efflux ratio in both Caco-2 and MDCK II-MDR1 cell monolayers and increase intracellular R123 accumulation in Caco-2 cells. Furthermore, IP6 noncompetitively inhibited P-gp by impacting R123 efflux kinetics. The noncompetitive inhibition of P-gp by IP6 was likely due to decreases in P-gp ATPase activity and P-gp molecular conformational changes induced by IP6. In summary, IP6 is a promising P-gp inhibitor candidate.

The frequently used intraperitoneal hyponatraemia model induces hypovolaemic hyponatraemia with possible model-dependent brain sodium loss.

PubMed

Overgaard-Steensen, Christian; Stødkilde-Jørgensen, Hans; Larsson, Anders; Tønnesen, Else; Frøkiaer, Jørgen; Ring, Troels

2016-07-01

What is the central question of this study? The brain response to acute hyponatraemia is usually studied in rodents by intraperitoneal instillation of hypotonic fluids (i.p. model). The i.p. model is described as 'dilutional' and 'syndrome of inappropriate ADH (SIADH)', but the mechanism has not been explored systematically and might affect the brain response. Therefore, in vivo brain and muscle response were studied in pigs. What is the main finding and its importance? The i.p. model induces hypovolaemic hyponatraemia attributable to sodium redistribution, not dilution. A large reduction in brain sodium is observed, probably because of the specific mechanism causing the hyponatraemia. This is not accounted for in current understanding of the brain response to acute hyponatraemia. Hyponatraemia is common clinically, and if it develops rapidly, brain oedema evolves, and severe morbidity and even death may occur. Experimentally, acute hyponatraemia is most frequently studied in small animal models, in which the hyponatraemia is produced by intraperitoneal instillation of hypotonic fluids (i.p. model). This hyponatraemia model is described as 'dilutional' or 'syndrome of inappropriate ADH (SIADH)', but seminal studies contradict this interpretation. To confront this issue, we developed an i.p. model in a large animal (the pig) and studied water and electrolyte responses in brain, muscle, plasma and urine. We hypothesized that hyponatraemia was induced by simple water dilution, with no change in organ sodium content. Moderate hypotonic hyponatraemia was induced by a single i.v. dose of desmopressin and intraperitoneal instillation of 2.5% glucose. All animals were anaesthetized and intensively monitored. In vivo brain and muscle water was determined by magnetic resonance imaging and related to the plasma sodium concentration. Muscle water content increased less than expected as a result of pure dilution, and muscle sodium content decreased significantly (by 28%). Sodium was redistributed to the peritoneal fluid, resulting in a significantly reduced plasma volume. This shows that the i.p. model induces hypovolaemic hyponatraemia and not dilutional/SIADH hyponatraemia. Brain oedema evolved, but brain sodium content decreased significantly (by 21%). To conclude, the i.p. model induces hypovolaemic hyponatraemia attributable to sodium redistribution and not water dilution. The large reduction in brain sodium is probably attributable to the specific mechanism that causes the hyponatraemia. This is not accounted for in the current understanding of the brain response to acute hyponatraemia. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

ANTIPROLIFERATIVE EFFECT OF INOSITOL HEXAPHOSPHATE ON HUMAN SKIN MELANOMA CELLS IN VITRO.

PubMed

Wawszczyk, Joanna; Kapral, Małgorzata; Lodowska, Jolanta; Jesse, Katarzyna; Hollek, Andrzej; Węglarz, Ludmiła

2015-01-01

Human malignant melanoma is a highly metastatic tumor with poor prognosis. The majority of metastatic melanomas are resistant to diverse chemotherapeutic agents. Consequently, the search for novel antimelanoma agents continues. In recent years, the interest in plants and their biologically active constituents as a source of novel potential drugs significantly increased. Inositol hexaphosphate (IP6) is a naturally occurring compound that has been shown to inhibit the growth of a wide variety of tumor cells in multiple experimental model systems. The aim of this study was to evaluate the antiproliferative and cytotoxic influence of IP6 on melanotic melanoma cells in vitro. The A2058 cells used as a model of human skin melanoma malignum were exposed to different concentrations of IP6 (0.1-5 mM) for a various period of time and their growth was determined by sulforhodamine B assay after 24, 48 and 72 h. The cytotoxicity of IP6 was measured at 24 and 72 h by XTT assay. IP6 has been found to cause dose-dependent growth suppression of A2058 melanoma cells. At low concentrations (0.1 and 0.5 mM) it did not exert any influence on the cell proliferation as compared to control cultures. Higher concentrations of IP6 (from 1 to 5 mM) had a statistically significant, suppressive effect on cell proliferation after 24 h incubation. When the experimental time period was increased up to 72 h, statistically significant inhibition of cell proliferation was monitored at all IP6 concentrations used. Data obtained from XTT assay indicated that IP6 had dose- and time-dependent cytotoxic effect on melanoma cells. The results demonstrate the antiproliferative and cytotoxic properties of IP6 in a wide range of concentrations on human A2058 melanoma cells. Hence, it can be suggested that IP6 could have a promising therapeutic significance in treating cancer.

DDN (Defense Data Network) Protocol Implementations and Vendors Guide,

DTIC Science & Technology

1988-02-01

TELNET) TCP/IP on an ethernet network. The program simulates a Hayes modem through the serial port. BWFTP is a thorough implementation of the FTP...25 IMP interface at VV from 19.2 Kbps to 56K bps. The IP, ICMP, TCP, Telnet. FFP and SMTP protocols are implemented along with R-Utxities...WANs. microcomputers, dataswitches. minicomputers. "black boxes" and modems . DOCUMENTATION: Software System Overview, Generic X.25 Porting Guide

Transition to an IP Environment. A Report of the Annual Aspen Institute Conference on Telecommunications Policy (15th, Aspen, Colorado, August 12-16, 2000) with Thoughts on the Implications of Technological Change for Telecommunications Policy.

ERIC Educational Resources Information Center

Entman, Robert M.; Katz, Michael L.

The Aspen Institute's Communications and Society Program convened leaders and experts in the telecommunications and related fields to address telecommunications regulation in an IP (Internet Protocols) environment at the 15th annual Aspen Institute Telecommunications Policy Conference (Aspen, Colorado, August 12-16, 2000). The report from this…

Regulation of myeloid leukemia factor-1 interacting protein (MLF1IP) expression in glioblastoma.

PubMed

Hanissian, Silva H; Teng, Bin; Akbar, Umar; Janjetovic, Zorica; Zhou, Qihong; Duntsch, Christopher; Robertson, Jon H

2005-06-14

The myelodysplasia/myeloid leukemia factor 1-interacting protein MLF1IP is a novel gene which encodes for a putative transcriptional repressor. It is localized to human chromosome 4q35.1 and is expressed in both the nuclei and cytoplasm of cells. Northern and Western blot analyses have revealed MLF1IP to be present at very low amounts in normal brain tissues, whereas a number of human and rat glioblastoma (GBM) cell lines demonstrated a high level expression of the MLF1IP protein. Immunohistochemical analysis of rat F98 and C6 GBM tumor models showed that MLF1IP was highly expressed in the tumor core where it was co-localized with MLF1 and nestin. Moreover, MLF1IP expression was elevated in the contralateral brain where no tumor cells were detected. These observations, together with previous data demonstrating a role for MLF1IP in erythroleukemias, suggest a possible function for this protein in glioma pathogenesis and potentially in other types of malignancies.

Immunopotentiator from Pantoea agglomerans Prevents Atopic Dermatitis Induced by Dermatophagoides farinae Extract in NC/Nga Mouse.

PubMed

Wakame, Koji; Komatsu, Ken-Ichi; Inagawa, Hiroyuki; Nishizawa, Takashi

2015-08-01

Pantoea agglomerans LPS (immunopotentiator from Pantoea agglomerans 1: IP-PA1) has been reported to have anti-inflammatory effects in in vitro and in vivo models. The aim of the present study was to investigate the effects of orally-administered IP-PA1 on atopic dermatitis (AD) symptoms induced by Dermatophagoides farinae body extract (DFE) in NC/Nga mice. Using the NC/Nga AD murine model, mice were orally administered 0.1% (High) or 0.01% (Low) water-containing IP-PA1. Skin lesion assessment and blood collection from the caudal vein was performed on days 0, 7, 21 and 31. On day 31, all mice were sacrificed and blood, skin, spleen, as well as intestine samples, were obtained. Assessment score of the skin lesion and serum immunoglobulin E (IgE) level of both IP-PA1 groups were significantly lower than that of the DFE group on days 14 and 21. The serum periostin and thymus and activation-regulated chemokine (TARC) level of IP-PA1-Low group was significantly lower than that of the DFE group on day 31. On histological examination of the skin, hyperplasia of epidermal and dermal layers and infiltration of inflammatory cells were suppressed by IP-PA1 administration. Deposition of periostin was observed in the DFE group skin tissue. Moreover, the CD4(+)/CD8(+) ratio of splenic T-cells increased by IP-PA1 administration. IP-PA1 administration may have an inhibitory effect on AD skin lesions. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Spectra of High-Ionization Seyfert 1 Galaxies: Implications for the Narrow-Line Region

NASA Technical Reports Server (NTRS)

Moore, David; Cohen, Ross D.; Marcy, Geoffrey W.

1996-01-01

We present line profiles and profile parameters for the Narrow-Line Regions (NLRs) of six Seyfert 1 galaxies with high-ionization lines: MCG 8-11-11, Mrk 79, Mrk 704, Mrk 841, NGC 4151, and NGC 5548. The sample was chosen primarily with the goal of obtaining high-quality [Fe VII] lambda6087 and, when possible, [Fe X] lambda6374 profiles to determine if these lines are more likely formed in a physically distinct 'coronal line region' or are formed throughout the NLR along with lines of lower critical density (n(sub cr)) and/or Ionization Potential (IP). We discuss correlations of velocity shift and width with n(sub cr) and IP. In some objects, lines of high IP and/or n(sub cr) are systematically broader than those of low IP/n(sub cr). Of particular interest, however, are objects that show no correlations of line width with either IP or n(sub cr). In these objects, lines of high and low IP/n(sub cr), are remarkably similar, which is difficult to reconcile with the classical picture of the NLR, in which lines of high and low IP/n(sub cr) are formed in physically distinct regions. We argue for similar spatial extents for the flux in lines with similar profiles. Here, as well as in a modeling-oriented companion paper, we develop further an idea suggested by Moore & Cohen that objects that do and do not show line width correlations with IP/n(sub cr) can both be explained in terms of a single NLR model with only a small difference in the cloud column density distinguishing the two types of object. Overall, our objects do not show correlations between the Full Width at Half-Maximum (FWHM) and IP and/or n(sub cr). The width must be defined by a parameter that is sensitive to extended profile wings in order for the correlations to result. We present models in which FWHM correlations with IP and/or n(sub cr) result only after simulating the lower spectral resolution used in previous observational studies. The models that simulate the higher spectral resolution of our observational study produce line width correlations only if the width is defined by a parameter that is more sensitive to extended profile wings than is the FWHM. Our sample of six objects is in effect augmented by incorporating the larger sample (16 objects) of Veilleux into some of our discussion. This paper focuses on new interpretations of NLR emission-line spectra and line profiles that stem directly from the observations. Paper 2 focuses on modeling and complements this paper by illustrating explicitly the effects that spatial variations in electron density, ionization parameter, and column density have on model profiles. By comparing model profiles with the observed profiles presented here, as well as with those presented by Veilleux, Paper 2 yields insight into how the electron density, ionization parameter, and column density likely vary throughout the NLR.

Team Modelling: Review of Experimental Scenarios and Computational Models

DTIC Science & Technology

2006-09-01

les auteurs ont réuni et examiné des scénarios ayant servi dans le cadre d’études antérieures sur les équipes, ils ont développé d’importants...cognition, perception, sensation, motor action and knowledge, that embody a principled underlying theory or framework for human information...Processing) integrates Qinetiq’s (POP) model with DRDC’s IP/PCT (Perceptual Control Theory ) models. In particular, the POP/IP model includes the

Generation of iPS-derived model cells for analyses of hair shaft differentiation.

PubMed

Kido, Takumi; Horigome, Tomoatsu; Uda, Minori; Adachi, Naoki; Hirai, Yohei

2017-09-01

Biological evaluation of hair growth/differentiation activity in vitro has been a formidable challenge, primarily due to the lack of relevant model cell systems. To solve this problem, we generated a stable model cell line in which successive differentiation via epidermal progenitors to hair components is easily inducible and traceable. Mouse induced pluripotent stem (iPS) cell-derived cells were selected to stably express a tetracycline (Tet)-inducible bone morphogenic protein-4 (BMP4) expression cassette and a luciferase reporter driven by a hair-specific keratin 31 gene (krt31) promoter (Tet-BMP4-KRT31-Luc iPS). While Tet- BMP4-KRT31-Luc iPS cells could be maintained as stable iPS cells, the cells differentiated to produce luciferase luminescence in the presence of all-trans retinoic acid (RA) and doxycycline (Dox), and addition of a hair differentiation factor significantly increased luciferase fluorescence. Thus, this cell line may provide a reliable cell-based screening system to evaluate drug candidates for hair differentiation activity.

Efficacy of bacteriophage therapy in a model of Burkholderia cenocepacia pulmonary infection

PubMed Central

Carmody, Lisa A.; Gill, Jason J.; Summer, Elizabeth J.; Sajjan, Uma S.; Gonzalez, Carlos F.; Young, Ryland F.; LiPuma, John J.

2009-01-01

The therapeutic potential of bacteriophage (phage) in a mouse model of acute B. cenocepacia pulmonary infection was assessed. Phage were administered by either intranasal (i.n.) inhalation or intraperitoneal (i.p.) injection. Bacterial density, macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-α (TNFα) levels were significantly reduced in lungs of mice treated with i.p. phage. No significant differences in lung bacterial density or MIP-2 levels were found between untreated mice and mice treated with i.n. phage, i.p. UV-inactivated phage, or i.p. λ phage controls. Mock-infected mice treated with phage showed no significant increase in lung MIP-2 or TNFα levels compared to mock-infected / mock-treated mice. We have demonstrated the efficacy of phage therapy in an acute B. cenocepacia lung infection model. Systemic administration of phage was more effective than inhalational administration, suggesting that circulating phage have better access to bacteria in lung compared to topical phage. PMID:20001604

Predictive IP controller for robust position control of linear servo system.

PubMed

Lu, Shaowu; Zhou, Fengxing; Ma, Yajie; Tang, Xiaoqi

2016-07-01

Position control is a typical application of linear servo system. In this paper, to reduce the system overshoot, an integral plus proportional (IP) controller is used in the position control implementation. To further improve the control performance, a gain-tuning IP controller based on a generalized predictive control (GPC) law is proposed. Firstly, to represent the dynamics of the position loop, a second-order linear model is used and its model parameters are estimated on-line by using a recursive least squares method. Secondly, based on the GPC law, an optimal control sequence is obtained by using receding horizon, then directly supplies the IP controller with the corresponding control parameters in the real operations. Finally, simulation and experimental results are presented to show the efficiency of proposed scheme. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Mathematical modeling of intraperitoneal drug delivery: simulation of drug distribution in a single tumor nodule.

PubMed

Steuperaert, Margo; Falvo D'Urso Labate, Giuseppe; Debbaut, Charlotte; De Wever, Olivier; Vanhove, Christian; Ceelen, Wim; Segers, Patrick

2017-11-01

The intraperitoneal (IP) administration of chemotherapy is an alternative treatment for peritoneal carcinomatosis, allowing for higher intratumor concentrations of the cytotoxic agent compared to intravenous administration. Nevertheless, drug penetration depths are still limited to a few millimeters. It is thus necessary to better understand the limiting factors behind this poor penetration in order to improve IP chemotherapy delivery. By developing a three-dimensional computational fluid dynamics (CFD) model for drug penetration in a tumor nodule, we investigated the impact of a number of key parameters on the drug transport and penetration depth during IP chemotherapy. Overall, smaller tumors showed better penetration than larger ones, which could be attributed to the lower IFP in smaller tumors. Furthermore, the model demonstrated large improvements in penetration depth by subjecting the tumor nodules to vascular normalization therapy, and illustrated the importance of the drug that is used for therapy. Explicitly modeling the necrotic core had a limited effect on the simulated penetration. Similarly, the penetration depth remained virtually constant when the Darcy permeability of the tissue changed. Our findings illustrate that the developed parametrical CFD model is a powerful tool providing more insight in the drug transport and penetration during IP chemotherapy.

Research into alternative network approaches for space operations

NASA Technical Reports Server (NTRS)

Kusmanoff, Antone L.; Barton, Timothy J.

1990-01-01

The main goal is to resolve the interoperability problem of applications employing DOD TCP/IP (Department of Defence Transmission Control Protocol/Internet Protocol) family of protocols on a CCITT/ISO based network. The objective is to allow them to communicate over the CCITT/ISO protocol GPLAN (General Purpose Local Area Network) network without modification to the user's application programs. There were two primary assumptions associated with the solution that was actually realized. The first is that the solution had to allow for future movement to the exclusive use of the CCITT/ISO standards. The second is that the solution had to be software transparent to the currently installed TCP/IP and CCITT/ISO user application programs.

Scoping review of resources for integrating evidence-based supported employment into spinal cord injury rehabilitation.

PubMed

Cotner, Bridget A; Ottomanelli, Lisa; Keleher, Virginia; Dirk, Lynn

2018-02-27

Individual placement and support (IPS), an evidence-based supported employment (SE) program, has helped Veterans with spinal cord injury (SCI) receiving care in the Veterans Health Administration to obtain work. To facilitate integration of IPS into SCI rehabilitation, resources are needed. A scoping review was conducted to identify tools and resources suitable for providers of SCI care. Applying a modified version of Arksey and O'Malley's framework, a scoping review of literature on SE tools or resources was conducted. The original review focused on resources published between 2002 and 2015 and available in English. Prior to publication an updated review through 2017 was conducted. From 1822 tools and resources identified in the initial review, 24 met criteria for inclusion and were evaluated by an advisory panel of experts, who selected 16 tools that addressed five topics: IPS in SCI (n = 2) orientation to SCI (n = 3); IPS SE (n = 7), job accommodations (n = 2), and benefits planning (n = 2). The updated review yielded no tools or resources that met inclusion criteria. Despite few resources to guide implementation of IPS in SCI, 16 essential resources were identified that, combined into a toolkit, may facilitate translation of IPS in SCI from research to clinical care. Implications for rehabilitation The toolkit consists of 16 essential resources and is currently available online to all persons involved in spinal cord injury rehabilitation to educate them about this effective means of assisting persons with spinal cord injury to find employment and to facilitate translation of individual placement and support in spinal cord injury from research to clinical care. While expert-informed, the toolkit is being field tested with both clinical and vocational providers to facilitate the adoption of individual placement and support by spinal cord injury rehabilitation programs. The revised version will be made available online.

Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain.

PubMed

Potter, Jane A; Randall, Richard E; Taylor, Garry L

2008-02-28

IPS-1/MAVS/VISA/Cardif is an adaptor protein that plays a crucial role in the induction of interferons in response to viral infection. In the initial stage of the intracellular antiviral response two RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-association gene 5 (MDA5), are independently able to bind viral RNA in the cytoplasm. The 62 kDa protein IPS-1/MAVS/VISA/Cardif contains an N-terminal caspase activation and recruitment (CARD) domain that associates with the CARD regions of RIG-I and MDA5, ultimately leading to the induction of type I interferons. As a first step towards understanding the molecular basis of this important adaptor protein we have undertaken structural studies of the IPS-1 MAVS/VISA/Cardif CARD region. The crystal structure of human IPS-1/MAVS/VISA/Cardif CARD has been determined to 2.1A resolution. The protein was expressed and crystallized as a maltose-binding protein (MBP) fusion protein. The MBP and IPS-1 components each form a distinct domain within the structure. IPS-1/MAVS/VISA/Cardif CARD adopts a characteristic six-helix bundle with a Greek-key topology and, in common with a number of other known CARD structures, contains two major polar surfaces on opposite sides of the molecule. One face has a surface-exposed, disordered tryptophan residue that may explain the poor solubility of untagged expression constructs. The IPS-1/MAVS/VISA/Cardif CARD domain adopts the classic CARD fold with an asymmetric surface charge distribution that is typical of CARD domains involved in homotypic protein-protein interactions. The location of the two polar areas on IPS-1/MAVS/VISA/Cardif CARD suggest possible types of associations that this domain makes with the two CARD domains of MDA5 or RIG-I. The N-terminal CARD domains of RIG-I and MDA5 share greatest sequence similarity with IPS-1/MAVS/VISA/Cardif CARD and this has allowed modelling of their structures. These models show a very different charge profile for the equivalent surfaces compared to IPS-1/MAVS/VISA/Cardif CARD.

MOBE-ChIP: Probing Cell Type-Specific Binding Through Large-Scale Chromatin Immunoprecipitation.

PubMed

Wang, Shenqi; Lau, On Sun

2018-01-01

In multicellular organisms, the initiation and maintenance of specific cell types often require the activity of cell type-specific transcriptional regulators. Understanding their roles in gene regulation is crucial but probing their DNA targets in vivo, especially in a genome-wide manner, remains a technical challenge with their limited expression. To improve the sensitivity of chromatin immunoprecipitation (ChIP) for detecting the cell type-specific signals, we have developed the Maximized Objects for Better Enrichment (MOBE)-ChIP, where ChIP is performed at a substantially larger experimental scale and under low background conditions. Here, we describe the procedure in the study of transcription factors in the model plant Arabidopsis. However, with some modifications, the technique should also be implemented in other systems. Besides cell type-specific studies, MOBE-ChIP can also be used as a general strategy to improve ChIP signals.

An RCT Evaluating the Effects of Skills Training and Medication Type on Work Outcomes Among Patients With Schizophrenia.

PubMed

Glynn, Shirley M; Marder, Stephen R; Noordsy, Douglas L; O'Keefe, Christopher; Becker, Deborah R; Drake, Robert E; Sugar, Catherine A

2017-03-01

Although supported employment increases job acquisition for people with serious mental illness, data on participants' job tenure have been variable. This study evaluated the effects of a standardized work skills training program (the Workplace Fundamentals Module [WPFM]) on job tenure and other work outcomes among individuals receiving individual placement and support (IPS). The effects of two atypical antipsychotic medications on side effects were also tested. The primary hypothesis tested was that participants in IPS plus WPFM would have increased job tenure compared with those enrolled in IPS only, and the secondary hypothesis was that different antipsychotic medications would yield unique side effects. A 2×2 randomized controlled trial compared work outcomes, including job tenure, of participants receiving IPS with or without WPFM for up to two years after obtaining a job. Participants were also randomly assigned to olanzapine or risperidone. Measures of work outcomes, clinical status, and medication side effects were collected. Among 107 participants, 63% obtained at least one job. WPFM did not increase job tenure (51.53 and 41.37 total weeks worked for IPS only and IPS plus WPFM, respectively) or affect other work outcomes. Participants on olanzapine experienced increased body mass index, whereas those on risperidone lost weight, but medications did not differentially affect clinical or job outcomes. Clinic-based skills training did not improve work outcomes accruing from IPS. Risperidone, compared with olanzapine, may reduce body mass but has no differential effect on other work or clinical outcomes.

Telemetry and Communication IP Video Player

NASA Technical Reports Server (NTRS)

OFarrell, Zachary L.

2011-01-01

Aegis Video Player is the name of the video over IP system for the Telemetry and Communications group of the Launch Services Program. Aegis' purpose is to display video streamed over a network connection to be viewed during launches. To accomplish this task, a VLC ActiveX plug-in was used in C# to provide the basic capabilities of video streaming. The program was then customized to be used during launches. The VLC plug-in can be configured programmatically to display a single stream, but for this project multiple streams needed to be accessed. To accomplish this, an easy to use, informative menu system was added to the program to enable users to quickly switch between videos. Other features were added to make the player more useful, such as watching multiple videos and watching a video in full screen.

Mechanism of proteasomal degradation of inositol trisphosphate receptors in CHO-K1 cells.

PubMed

Bhanumathy, Cunnigaiper D; Nakao, Steven K; Joseph, Suresh K

2006-02-10

myo-Inositol 1,4,5-trisphosphate receptor (IP3R) degradation occurs in response to carbachol (Cch) stimulation of CHO-K1 cells. The response was mediated by endogenous muscarinic receptors and was blocked by atropine or proteasomal inhibitors. We have used these cells to identify the sites of ubiquitination on IP3Rs and study the role of Ca2+ and substrate recognition properties of the degradation system using exogenously expressed IP3R constructs. Employing caspase-3 for IP3R cleavage, we show that Cch promotes polyubiquitination in the N-terminal domain and monoubiquitination in the C-terminal domain. The addition of extracellular Ca2+ to Ca2+-depleted Chinese hamster ovary (CHO) cells initiates IP3R degradation provided Cch is present. This effect is inhibited by thapsigargin. The data suggest that both a sustained elevation of IP3 and a minimal content of Ca2+ in the endoplasmic reticulum lumen is required to initiate IP3R degradation. Transient transfection of IP3R constructs into CHO cells indicated the selective degradation of only the SI+ splice variant of the type I IP3R. This was also the splice form present endogenously in these cells. A pore-defective, nonfunctional SI+ IP3R mutant (D2550A) was also degraded in Cch-stimulated cells. The Cch-mediated response in CHO cells provides a convenient model system to further analyze the Ca2+ dependence and structural requirements of the IP3R proteasomal degradation pathway.

Perturbation of myo-inositol-1,4,5-trisphosphate levels during agonist-induced Ca2+ oscillations.

PubMed Central

Chatton, J Y; Cao, Y; Stucki, J W

1998-01-01

Agonist-induced Ca2+ oscillations in rat hepatocytes involve the production of myo-inositol-1,4,5-trisphosphate (IP3), which stimulates the release of Ca2+ from intracellular stores. The oscillatory frequency is conditioned by the agonist concentration. This study investigated the role of IP3 concentration in the modulation of oscillatory frequency by using microinjected photolabile IP3 analogs. Photorelease of IP3 during hormone-induced oscillations evoked a Ca2+ spike, after which oscillations resumed with a delay corresponding to the period set by the agonists. IP3 photorelease had no influence on the frequency of oscillations. After photorelease of 1-(alpha-glycerophosphoryl)-D-myo-inositol-4,5-diphosphate (GPIP2), a slowly metabolized IP3 analog, the frequency of oscillations initially increased by 34% and declined to its original level within approximately 6 min. Both IP3 and GPIP2 effects can be explained by their rate of degradation: the half-life of IP3, which is a few seconds, can account for the lack of influence of IP3 photorelease on the frequency, whereas the slower metabolism of GPIP2 allowed a transient acceleration of the oscillations. The phase shift introduced by IP3 is likely the result of the brief elevation of Ca2+ during spiking that resets the IP3 receptor to a state of maximum inactivation. A mathematical model of Ca2+ oscillations is in satisfactory agreement with the observed results. PMID:9449352

European Space Agency /ESA/ pointing systems - Requirements and fulfillment

NASA Astrophysics Data System (ADS)

Nellessen, W.; Wolf, P.

1982-02-01

The Instrument Pointing System (IPS), a three-axes gimballed experimentation facility, is to be first used in the second Spacelab flight, in 1984. In response to crew motions and Space Shuttle thruster disturbances, payload mass and inertia, and IPS positioning in the cargo bay, the IPS will provide a stable pointing capability for payloads of up to 2000 kg whose accuracy is in the 1-10 arcsec range. The IPS is complemented in the up-to-200 kg payload mass range by a small Position and Hold Mount, a functional model of which is now available for performance demonstration tests.

iASeq: integrative analysis of allele-specificity of protein-DNA interactions in multiple ChIP-seq datasets

PubMed Central

2012-01-01

Background ChIP-seq provides new opportunities to study allele-specific protein-DNA binding (ASB). However, detecting allelic imbalance from a single ChIP-seq dataset often has low statistical power since only sequence reads mapped to heterozygote SNPs are informative for discriminating two alleles. Results We develop a new method iASeq to address this issue by jointly analyzing multiple ChIP-seq datasets. iASeq uses a Bayesian hierarchical mixture model to learn correlation patterns of allele-specificity among multiple proteins. Using the discovered correlation patterns, the model allows one to borrow information across datasets to improve detection of allelic imbalance. Application of iASeq to 77 ChIP-seq samples from 40 ENCODE datasets and 1 genomic DNA sample in GM12878 cells reveals that allele-specificity of multiple proteins are highly correlated, and demonstrates the ability of iASeq to improve allelic inference compared to analyzing each individual dataset separately. Conclusions iASeq illustrates the value of integrating multiple datasets in the allele-specificity inference and offers a new tool to better analyze ASB. PMID:23194258

An fMRI Investigation of Preparatory Set in the Human Cerebral Cortex and Superior Colliculus for Pro- and Anti-Saccades

PubMed Central

Furlan, Michele; Smith, Andrew T.; Walker, Robin

2016-01-01

Previous studies have identified several cortical regions that show larger BOLD responses during preparation and execution of anti-saccades than pro-saccades. We confirmed this finding with a greater BOLD response for anti-saccades than pro-saccades during the preparation phase in the FEF, IPS and DLPFC and in the FEF and IPS in the execution phase. We then applied multi-voxel pattern analysis (MVPA) to establish whether different neural populations are involved in the two types of saccade. Pro-saccades and anti-saccades were reliably decoded during saccade execution in all three cortical regions (FEF, DLPFC and IPS) and in IPS during saccade preparation. This indicates neural specialization, for programming the desired response depending on the task rule, in these regions. In a further study tailored for imaging the superior colliculus in the midbrain a similar magnitude BOLD response was observed for pro-saccades and anti-saccades and the two saccade types could not be decoded with MVPA. This was the case both for activity related to the preparation phase and also for that elicited during the execution phase. We conclude that separate cortical neural populations are involved in the task-specific programming of a saccade while in contrast, the SC has a role in response preparation but may be less involved in high-level, task-specific aspects of the control of saccades. PMID:27391390

78 FR 39619 - Closed Captioning of Internet Protocol-Delivered Video Programming: Implementation of the Twenty...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-02

... covered apparatus may convey from the source device to the consumer equipment the information necessary to... using Internet protocol (``IP'') and apparatus used by consumers to view video programming. The action...-delivered video programming and rules governing the closed captioning capabilities of certain apparatus on...

NICA project at JINR: status and prospects

NASA Astrophysics Data System (ADS)

Kekelidze, V. D.

2017-06-01

The project NICA (Nuclotron-based Ion Collider fAcility) is aimed to study hot and dense baryonic matter in heavy-ion collisions in the energy range up to 11.0 AGeV . The plan of NICA accelerator block development includes an upgrade of the existing superconducting (SC) synchrotron Nuclotron and construction of the new injection complex, SC Booster, and SC Collider with two interaction points (IP). The heavy-ion collision program will be performed with the fixed target experiment Baryonic Matter at Nuclotron (BM@N) at the beam extracted from the Nuclotron, and with Multi-Purpose Detector (MPD) at the first IP of NICA Collider. Investigation of nucleon spin structure and polarization phenomena is foreseen with the Spin Physics Detector (SPC) at the second IP of the Collider.

Stochastic fire-diffuse-fire model with realistic cluster dynamics.

PubMed

Calabrese, Ana; Fraiman, Daniel; Zysman, Daniel; Ponce Dawson, Silvina

2010-09-01

Living organisms use waves that propagate through excitable media to transport information. Ca2+ waves are a paradigmatic example of this type of processes. A large hierarchy of Ca2+ signals that range from localized release events to global waves has been observed in Xenopus laevis oocytes. In these cells, Ca2+ release occurs trough inositol 1,4,5-trisphosphate receptors (IP3Rs) which are organized in clusters of channels located on the membrane of the endoplasmic reticulum. In this article we construct a stochastic model for a cluster of IP3R 's that replicates the experimental observations reported in [D. Fraiman, Biophys. J. 90, 3897 (2006)]. We then couple this phenomenological cluster model with a reaction-diffusion equation, so as to have a discrete stochastic model for calcium dynamics. The model we propose describes the transition regimes between isolated release and steadily propagating waves as the IP3 concentration is increased.

Evolution of interprofessional learning: Dalhousie University's "From Family Violence to Health" module.

PubMed

Johnston, Grace M; Ryding, Helen A; Campbell, Lindsay M

2003-11-01

At Dalhousie University, interprofessional (IP) learning modules are used to help future health care professionals learn to work together in resolving complex problems. One module, "From Family Violence to Health," features the role of dental professionals. This paper describes the evolution of this module from the year 2000. By February 2003, 1,182 students from 15 health care professions had completed the module. Qualitative evaluation in years 1 and 2 of the program (2000 and 2001) revealed that, before participating in the IP module, many students were able to identify a role for themselves in the recognition of family violence and knew their responsibility to report incidents. However, after participating in the module, they had a greater understanding of the reporting of family violence, a more comprehensive and supportive perspective, increased recognition of how health care professionals could work together and improved awareness of the roles of other professions. In a quantitative evaluation in year 3 (2002), mean student ratings on a scale of 1 to 5 indicated that the IP module was relevant (4.2), increased their understanding of family violence (4.0), and had some impact in promoting IP learning (3.8). As health care delivery becomes more focused on care teams and system thinking, the provision of IP training is expected to increase. The Dalhousie University IP modules (available at http://www.dal.ca/~fhp/ipl/index.html) address health and social problems for which it is critical that health care and other professionals work together. Feedback from practitioners on the development of IP education is welcomed, particularly with regard to the IP module addressing family violence.

Imaging Coronal Mass Ejections and Large-Scale Solar Wind Structure Using IPS and Thomson-Scattered Sunlight (Invited)

NASA Astrophysics Data System (ADS)

Clover, J. M.; Jackson, B. V.; Buffington, A.; Hick, P. P.; Bisi, M. M.; Tokumaru, M.; Fujiki, K.

2010-12-01

The Solar Mass Ejection Imager (SMEI) observes Thomson-scattered white light from heliospheric electrons across almost all of the sky nearly all of the time since early 2003. Interplanetary scintillation (IPS) observations of velocity and g-level provide similar structure information but with a less-complete sky-and-time coverage. The Solar TErrestrial RElations Observatory (STEREO) twin spacecraft outer Heliospheric Imagers (HI-2) currently image the heliosphere in Thomson-scattered light near the ecliptic plane far from Earth. The Solar-Terrestrial Environment Laboratory (STELab) IPS observations provide IPS velocity and g-level values, which in conjunction with our tomographic reconstruction program, yield velocities and densities of the inner heliosphere in three dimensions. The same tomographic program substitutes SMEI Thomson-scattering brightness information for the g-level values to derive heliospheric densities from these data alone. We look at the global structure of the heliosphere concentrating mainly on three events from 2007 through the rise phase of Solar Cycle 24. The first event, observed in both the IPS and SMEI defines the three-dimensional velocity and density structure around the time of the shock observed at Earth on 02:02 UT 17 December 2007. The second event, seen only by SMEI, is that of the 23-26 April 2008 coronal mass ejection (CME) and its interplanetary counterpart. The third event is the CME (and its interplanetary counterpart) that took place 17 January 2010 and arrived at STEREO-B about four days later. For each event, we isolate the particular portion of the heliosphere attributed to the transient density structure using our tomographic technique, and then estimate its extent.

Multi-wavelength Observations of the Enduring Type IIn Supernovae 2005ip and 2006jd

NASA Astrophysics Data System (ADS)

Stritzinger, Maximilian; Taddia, Francesco; Fransson, Claes; Fox, Ori D.; Morrell, Nidia; Phillips, M. M.; Sollerman, Jesper; Anderson, J. P.; Boldt, Luis; Brown, Peter J.; Campillay, Abdo; Castellon, Sergio; Contreras, Carlos; Folatelli, Gastón; Habergham, S. M.; Hamuy, Mario; Hjorth, Jens; James, Phil A.; Krzeminski, Wojtek; Mattila, Seppo; Persson, Sven E.; Roth, Miguel

2012-09-01

We present an observational study of the Type IIn supernovae (SNe IIn) 2005ip and 2006jd. Broadband UV, optical, and near-IR photometry, and visual-wavelength spectroscopy of SN 2005ip complement and extend upon published observations to 6.5 years past discovery. Our observations of SN 2006jd extend from UV to mid-infrared wavelengths, and like SN 2005ip, are compared to reported X-ray measurements to understand the nature of the progenitor. Both objects display a number of similarities with the 1988Z-like subclass of SN IIn including (1) remarkably similar early- and late-phase optical spectra, (2) a variety of high-ionization coronal lines, (3) long-duration optical and near-IR emission, and (4) evidence of cold and warm dust components. However, diversity is apparent, including an unprecedented late-time r-band excess in SN 2006jd. The observed differences are attributed to differences between the mass-loss history of the progenitor stars. We conclude that the progenitor of SN 2006jd likely experienced a significant mass-loss event during its pre-SN evolution akin to the great 19th century eruption of η Carinae. Contrarily, as advocated by Smith et al., the circumstellar environment of SN 2005ip is found to be more consistent with a clumpy wind progenitor. This paper includes data gathered with the 6.5 m Magellan Telescopes, located at Las Campanas Observatory, Chile; the Gemini-North Telescope, Mauna Kea, USA (Gemini Program GN-2010B-Q-67, PI: Stritzinger); the ESO NTT, La Silla, Chile (Program 076.A-0156 and 078.D-0048, PI: Hamuy); and the INT and the NOT (Proposal number 45 - 004, PI: Taddia), La Palma, Spain.

An in vitro and in silico study on the flavonoid-mediated modulation of the transport of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through Caco-2 monolayers

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

Schutte, Maaike E.; Freidig, Andreas P.; Sandt, Johannes J.M. van de

The present study describes the effect of different flavonoids on the absorption of the pro-carcinogen PhIP through Caco-2 monolayers and the development of an in silico model describing this process taking into account passive diffusion and active transport of PhIP. Various flavonoids stimulated the apical to basolateral PhIP transport. Using the in silico model for flavone, kaempferol and chrysoeriol, the apparent Ki value for inhibition of the active transport to the apical side was estimated to be below 53 {mu}M and for morin, robinetin and taxifolin between 164 and 268 {mu}M. For myricetin, luteolin, naringenin and quercetin, the apparent Kimore » values were determined more accurately and amounted to 37.3, 12.2, 11.7 and 5.6 {mu}M respectively. Additional experiments revealed that the apical to basolateral PhIP transport was also increased in the presence of a typical BCRP or MRP inhibitor with apparent Ki values in the same range as those of the flavonoids. This observation together with the fact that flavonoids are known to be inhibitors of MRPs and BCRP, corroborates that inhibition of these apical membrane transporters is involved in the flavonoid-mediated increased apical to basolateral PhIP transport. Based on the apparent Ki values obtained, it is concluded that the flavonols, at the levels present in the regular Western diet, are capable of stimulating the transport of PhIP through Caco-2 monolayers from the apical to the basolateral compartment. This points to flavonoid-mediated stimulation of the bioavailability of PhIP and, thus, a possible adverse effect of these supposed beneficial food ingredients.« less

TECHNICAL AND REGULATORY CONSIDERATIONS IN USING FREIGHT CONTAINERS AS INDUSTRIAL PACKAGES

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

Opperman, E; Mark Hawk, M; Ron Natali, R

2007-10-16

The United States (US) Department of Energy (DOE), Office of Environmental Management (EM), is actively pursuing activities to reduce the radiological risk and clean up the environmental legacy of the nation's nuclear weapons programs. EM has made significant progress in recent years in the clean-up and closure of sites and is also focusing on longer-term activities necessary for the completion of the clean-up program. The packaging and transportation of contaminated demolition debris and low-level waste (LLW) materials in a safe and cost-effective manner are essential in completing this mission. Toward this end, the US Department of Transportation's (DOT) Final Rulemore » on Hazardous Materials Regulation Final Rule issued January 26, 2004, included a new provision authorizing the use of Freight Containers (e.g., 20 and 40-foot ISO Containers) as Industrial Packages Type 1, 2, or 3 (IP-1, IP-2, and IP-3). This paper will discuss the technical and regulatory considerations in using these newly authorized and large packages for the packaging and transportation of LLW materials.« less

IP-Based Video Modem Extender Requirements

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

Pierson, L G; Boorman, T M; Howe, R E

2003-12-16

Visualization is one of the keys to understanding large complex data sets such as those generated by the large computing resources purchased and developed by the Advanced Simulation and Computing program (aka ASCI). In order to be convenient to researchers, visualization data must be distributed to offices and large complex visualization theaters. Currently, local distribution of the visual data is accomplished by distance limited modems and RGB switches that simply do not scale to hundreds of users across the local, metropolitan, and WAN distances without incurring large costs in fiber plant installation and maintenance. Wide Area application over the DOEmore » Complex is infeasible using these limited distance RGB extenders. On the other hand, Internet Protocols (IP) over Ethernet is a scalable well-proven technology that can distribute large volumes of data over these distances. Visual data has been distributed at lower resolutions over IP in industrial applications. This document describes requirements of the ASCI program in visual signal distribution for the purpose of identifying industrial partners willing to develop products to meet ASCI's needs.« less

Intellectual property rights and detached human body parts.

PubMed

Pila, Justine

2014-01-01

This paper responds to an invitation by the editors to consider whether the intellectual property (IP) regime suggests an appropriate model for protecting interests in detached human body parts. It begins by outlining the extent of existing IP protection for body parts in Europe, and the relevant strengths and weaknesses of the patent system in that regard. It then considers two further species of IP right of less obvious relevance. The first are the statutory rights of ownership conferred by domestic UK law in respect of employee inventions, and the second are the economic and moral rights recognised by European and international law in respect of authorial works. In the argument made, both of these species of IP right may suggest more appropriate models of sui generis protection for detached human body parts than patent rights because of their capacity better to accommodate the relevant public and private interests in respect of the same.

Generation of an ICF syndrome model by efficient genome editing of human induced pluripotent stem cells using the CRISPR system.

PubMed

Horii, Takuro; Tamura, Daiki; Morita, Sumiyo; Kimura, Mika; Hatada, Izuho

2013-09-30

Genome manipulation of human induced pluripotent stem (iPS) cells is essential to achieve their full potential as tools for regenerative medicine. To date, however, gene targeting in human pluripotent stem cells (hPSCs) has proven to be extremely difficult. Recently, an efficient genome manipulation technology using the RNA-guided DNase Cas9, the clustered regularly interspaced short palindromic repeats (CRISPR) system, has been developed. Here we report the efficient generation of an iPS cell model for immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF) syndrome using the CRISPR system. We obtained iPS cells with mutations in both alleles of DNA methyltransferase 3B (DNMT3B) in 63% of transfected clones. Our data suggest that the CRISPR system is highly efficient and useful for genome engineering of human iPS cells.

Sequential computation of elementary modes and minimal cut sets in genome-scale metabolic networks using alternate integer linear programming

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

Song, Hyun-Seob; Goldberg, Noam; Mahajan, Ashutosh

Elementary (flux) modes (EMs) have served as a valuable tool for investigating structural and functional properties of metabolic networks. Identification of the full set of EMs in genome-scale networks remains challenging due to combinatorial explosion of EMs in complex networks. It is often, however, that only a small subset of relevant EMs needs to be known, for which optimization-based sequential computation is a useful alternative. Most of the currently available methods along this line are based on the iterative use of mixed integer linear programming (MILP), the effectiveness of which significantly deteriorates as the number of iterations builds up. Tomore » alleviate the computational burden associated with the MILP implementation, we here present a novel optimization algorithm termed alternate integer linear programming (AILP). Results: Our algorithm was designed to iteratively solve a pair of integer programming (IP) and linear programming (LP) to compute EMs in a sequential manner. In each step, the IP identifies a minimal subset of reactions, the deletion of which disables all previously identified EMs. Thus, a subsequent LP solution subject to this reaction deletion constraint becomes a distinct EM. In cases where no feasible LP solution is available, IP-derived reaction deletion sets represent minimal cut sets (MCSs). Despite the additional computation of MCSs, AILP achieved significant time reduction in computing EMs by orders of magnitude. The proposed AILP algorithm not only offers a computational advantage in the EM analysis of genome-scale networks, but also improves the understanding of the linkage between EMs and MCSs.« less

Astronaut Medical Selection and Flight Medicine Care During the Shuttle ERA 1981 to 2011

NASA Technical Reports Server (NTRS)

Johnston, S.; Jennings, R.; Stepaniak, P.; Schmid, J.; Rouse, B.; Gray, G.; Tarver, B.

2011-01-01

The NASA Shuttle Program began with congressional budget approval in January 5, 1972 and the launch of STS-1 on April 12, 1981 and recently concluded with the landing of STS-135 on July 21, 2011. The evolution of the medical standards and care of the Shuttle Era Astronauts began in 1959 with the first Astronaut selection. The first set of NASA minimal medical standards were documented in 1977 and based on Air Force, Navy, Department of Defense, and the Federal Aviation Administration standards. Many milestones were achieved over the 30 years from 1977 to 2007 and the subsequent 13 Astronaut selections and 4 major expert panel reviews performed by the NASA Flight Medicine Clinic, Aerospace Medicine Board, and Medical Policy Board. These milestones of aerospace medicine standards, evaluations, and clinical care encompassed the disciplines of preventive, occupational, and primary care medicine and will be presented. The screening and retention standards, testing, and specialist evaluations evolved through periodic expert reviews, evidence based medicine, and Astronaut medical care experience. The last decade of the Shuttle Program saw the development of the International Space Station (ISS) with further Space medicine collaboration and knowledge gained from our International Partners (IP) from Russia, Canada, Japan, and the European Space Agencies. The Shuttle Program contribution to the development and implementation of NASA and IP standards and waiver guide documents, longitudinal data collection, and occupational surveillance models will be presented along with lessons learned and recommendations for future vehicles and missions.

Chronic exposure to combined carcinogens enhances breast cell carcinogenesis with mesenchymal and stem-like cell properties.

PubMed

Pluchino, Lenora Ann; Wang, Hwa-Chain Robert

2014-01-01

Breast cancer is the most common type of cancer affecting women in North America and Europe. More than 85% of breast cancers are sporadic and attributable to long-term exposure to small quantities of multiple carcinogens. To understand how multiple carcinogens act together to induce cellular carcinogenesis, we studied the activity of environmental carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P), and dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using our breast cell carcinogenesis model. Our study revealed, for the first time, that combined NNK and B[a]P enhanced breast cell carcinogenesis chronically induced by PhIP in both non-cancerous and cancerous breast cells. Co-exposure was more potent than sequential exposure to combined NNK and B[a]P followed by PhIP in inducing carcinogenesis. Initiation of carcinogenesis was measured by transient endpoints induced in a single exposure, while progression of carcinogenesis was measured by acquisition of constitutive endpoints in cumulative exposures. Transient endpoints included DNA damage, Ras-Erk-Nox pathway activation, reactive oxygen species elevation, and increased cellular proliferation. Constitutive endpoints included various cancer-associated properties and signaling modulators, as well as enrichment of cancer stem-like cell population and activation of the epithelial-to-mesenchymal transition program. Using transient and constitutive endpoints as targets, we detected that a combination of the green tea catechins ECG and EGCG, at non-cytotoxic levels, was more effective than individual agents in intervention of cellular carcinogenesis induced by combined NNK, B[a]P, and PhIP. Thus, use of combined ECG and EGCG should be seriously considered for early intervention of breast cell carcinogenesis associated with long-term exposure to environmental and dietary carcinogens.

Chronic Exposure to Combined Carcinogens Enhances Breast Cell Carcinogenesis with Mesenchymal and Stem-Like Cell Properties

PubMed Central

Pluchino, Lenora Ann; Wang, Hwa-Chain Robert

2014-01-01

Breast cancer is the most common type of cancer affecting women in North America and Europe. More than 85% of breast cancers are sporadic and attributable to long-term exposure to small quantities of multiple carcinogens. To understand how multiple carcinogens act together to induce cellular carcinogenesis, we studied the activity of environmental carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P), and dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) using our breast cell carcinogenesis model. Our study revealed, for the first time, that combined NNK and B[a]P enhanced breast cell carcinogenesis chronically induced by PhIP in both non-cancerous and cancerous breast cells. Co-exposure was more potent than sequential exposure to combined NNK and B[a]P followed by PhIP in inducing carcinogenesis. Initiation of carcinogenesis was measured by transient endpoints induced in a single exposure, while progression of carcinogenesis was measured by acquisition of constitutive endpoints in cumulative exposures. Transient endpoints included DNA damage, Ras-Erk-Nox pathway activation, reactive oxygen species elevation, and increased cellular proliferation. Constitutive endpoints included various cancer-associated properties and signaling modulators, as well as enrichment of cancer stem-like cell population and activation of the epithelial-to-mesenchymal transition program. Using transient and constitutive endpoints as targets, we detected that a combination of the green tea catechins ECG and EGCG, at non-cytotoxic levels, was more effective than individual agents in intervention of cellular carcinogenesis induced by combined NNK, B[a]P, and PhIP. Thus, use of combined ECG and EGCG should be seriously considered for early intervention of breast cell carcinogenesis associated with long-term exposure to environmental and dietary carcinogens. PMID:25372613

Quantification of histone modification ChIP-seq enrichment for data mining and machine learning applications

PubMed Central

2011-01-01

Background The advent of ChIP-seq technology has made the investigation of epigenetic regulatory networks a computationally tractable problem. Several groups have applied statistical computing methods to ChIP-seq datasets to gain insight into the epigenetic regulation of transcription. However, methods for estimating enrichment levels in ChIP-seq data for these computational studies are understudied and variable. Since the conclusions drawn from these data mining and machine learning applications strongly depend on the enrichment level inputs, a comparison of estimation methods with respect to the performance of statistical models should be made. Results Various methods were used to estimate the gene-wise ChIP-seq enrichment levels for 20 histone methylations and the histone variant H2A.Z. The Multivariate Adaptive Regression Splines (MARS) algorithm was applied for each estimation method using the estimation of enrichment levels as predictors and gene expression levels as responses. The methods used to estimate enrichment levels included tag counting and model-based methods that were applied to whole genes and specific gene regions. These methods were also applied to various sizes of estimation windows. The MARS model performance was assessed with the Generalized Cross-Validation Score (GCV). We determined that model-based methods of enrichment estimation that spatially weight enrichment based on average patterns provided an improvement over tag counting methods. Also, methods that included information across the entire gene body provided improvement over methods that focus on a specific sub-region of the gene (e.g., the 5' or 3' region). Conclusion The performance of data mining and machine learning methods when applied to histone modification ChIP-seq data can be improved by using data across the entire gene body, and incorporating the spatial distribution of enrichment. Refinement of enrichment estimation ultimately improved accuracy of model predictions. PMID:21834981

Efficient genomic correction methods in human iPS cells using CRISPR-Cas9 system.

PubMed

Li, Hongmei Lisa; Gee, Peter; Ishida, Kentaro; Hotta, Akitsu

2016-05-15

Precise gene correction using the CRISPR-Cas9 system in human iPS cells holds great promise for various applications, such as the study of gene functions, disease modeling, and gene therapy. In this review article, we summarize methods for effective editing of genomic sequences of iPS cells based on our experiences correcting dystrophin gene mutations with the CRISPR-Cas9 system. Designing specific sgRNAs as well as having efficient transfection methods and proper detection assays to assess genomic cleavage activities are critical for successful genome editing in iPS cells. In addition, because iPS cells are fragile by nature when dissociated into single cells, a step-by-step confirmation during the cell recovery process is recommended to obtain an adequate number of genome-edited iPS cell clones. We hope that the techniques described here will be useful for researchers from diverse backgrounds who would like to perform genome editing in iPS cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Single and combined effects of Δ9 -tetrahydrocannabinol and cannabidiol in a mouse model of chemotherapy-induced neuropathic pain.

PubMed

King, Kirsten M; Myers, Alyssa M; Soroka-Monzo, Ariele J; Tuma, Ronald F; Tallarida, Ronald J; Walker, Ellen A; Ward, Sara Jane

2017-09-01

The non-psychoactive phytocannabinoid cannabidiol (CBD) can affect the pharmacological effects of Δ 9 -tetrahydrocannabinol (THC). We tested the possible synergy between CBD and THC in decreasing mechanical sensitivity in a mouse model of paclitaxel-induced neuropathic pain. We also tested the effects of CBD on oxaliplatin- and vincristine-induced mechanical sensitivity. Paclitaxel-treated mice (8.0 mg·kg -1 i.p., days 1, 3, 5 and 7) were pretreated with CBD (0.625-20.0 mg·kg -1 i.p.), THC (0.625-20.0 mg·kg -1 i.p.) or CBD + THC (0.04 + 0.04-20.0 + 20.0 mg·kg -1 i.p.), and mechanical sensitivity was assessed on days 9, 14 and 21. Oxaliplatin-treated (6.0 mg·kg -1 i.p., day 1) or vincristine-treated mice (0.1 mg·kg -1 i.p. days 1-7) were pretreated with CBD (1.25-10.0 mg·kg -1 i.p.), THC (10.0 mg·kg -1 i.p.) or THC + CBD (0.16 mg·kg -1 THC + 0.16 mg·kg -1 CBD i.p.). Both CBD and THC alone attenuated mechanical allodynia in mice treated with paclitaxel. Very low ineffective doses of CBD and THC were synergistic when given in combination. CBD also attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity, while THC significantly attenuated vincristine- but not oxaliplatin-induced mechanical sensitivity. The low dose combination significantly attenuated oxaliplatin- but not vincristine-induced mechanical sensitivity. CBD may be potent and effective at preventing the development of chemotherapy-induced peripheral neuropathy, and its clinical use may be enhanced by co-administration of low doses of THC. These treatment strategies would increase the therapeutic window of cannabis-based pharmacotherapies. © 2017 The British Pharmacological Society.

GenoGAM: genome-wide generalized additive models for ChIP-Seq analysis.

PubMed

Stricker, Georg; Engelhardt, Alexander; Schulz, Daniel; Schmid, Matthias; Tresch, Achim; Gagneur, Julien

2017-08-01

Chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) is a widely used approach to study protein-DNA interactions. Often, the quantities of interest are the differential occupancies relative to controls, between genetic backgrounds, treatments, or combinations thereof. Current methods for differential occupancy of ChIP-Seq data rely however on binning or sliding window techniques, for which the choice of the window and bin sizes are subjective. Here, we present GenoGAM (Genome-wide Generalized Additive Model), which brings the well-established and flexible generalized additive models framework to genomic applications using a data parallelism strategy. We model ChIP-Seq read count frequencies as products of smooth functions along chromosomes. Smoothing parameters are objectively estimated from the data by cross-validation, eliminating ad hoc binning and windowing needed by current approaches. GenoGAM provides base-level and region-level significance testing for full factorial designs. Application to a ChIP-Seq dataset in yeast showed increased sensitivity over existing differential occupancy methods while controlling for type I error rate. By analyzing a set of DNA methylation data and illustrating an extension to a peak caller, we further demonstrate the potential of GenoGAM as a generic statistical modeling tool for genome-wide assays. Software is available from Bioconductor: https://www.bioconductor.org/packages/release/bioc/html/GenoGAM.html . gagneur@in.tum.de. Supplementary information is available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Order Without Intellectual Property Law: Open Science in Influenza.

PubMed

Kapczynski, Amy

Today, intellectual property (IP) scholars accept that IP as an approach to information production has serious limits. But what lies beyond IP? A new literature on "intellectual production without IP" (or "IP without IP") has emerged to explore this question, but its examples and explanations have yet to convince skeptics. This Article reorients this new literature via a study of a hard case: a global influenza virus-sharing network that has for decades produced critically important information goods, at significant expense, and in a loose-knit group--all without recourse to IP. I analyze the Network as an example of "open science," a mode of information production that differs strikingly from conventional IP, and yet that successfully produces important scientific goods in response to social need. The theory and example developed here refute the most powerful criticisms of the emerging "IP without IP" literature, and provide a stronger foundation for this important new field. Even where capital costs are high, creation without IP can be reasonably effective in social terms, if it can link sources of funding to reputational and evaluative feedback loops like those that characterize open science. It can also be sustained over time, even by loose-knit groups and where the stakes are high, because organizations and other forms of law can help to stabilize cooperation. I also show that contract law is well suited to modes of information production that rely upon a "supply side" rather than "demand side" model. In its most important instances, "order without IP" is not order without governance, nor order without law. Recognizing this can help us better ground this new field, and better study and support forms of knowledge production that deserve our attention, and that sometimes sustain our very lives.

Protection against cancer by dietary IP6 and inositol.

PubMed

Vucenik, Ivana; Shamsuddin, AbulKalam M

2006-01-01

Inositol hexaphosphate (IP(6)) is a naturally occurring polyphosphorylated carbohydrate, abundantly present in many plant sources and in certain high-fiber diets, such as cereals and legumes. In addition to being found in plants, IP(6) is contained in almost all mammalian cells, although in much smaller amounts, where it is important in regulating vital cellular functions such as signal transduction, cell proliferation, and differentiation. For a long time IP(6) has been recognized as a natural antioxidant. Recently IP(6) has received much attention for its role in cancer prevention and control of experimental tumor growth, progression, and metastasis. In addition, IP(6) possesses other significant benefits for human health, such as the ability to enhance immune system, prevent pathological calcification and kidney stone formation, lower elevated serum cholesterol, and reduce pathological platelet activity. In this review we show the efficacy and discuss some of the molecular mechanisms that govern the action of this dietary agent. Exogenously administered IP(6) is rapidly taken up into cells and dephosphorylated to lower inositol phosphates, which further affect signal transduction pathways resulting in cell cycle arrest. A striking anticancer action of IP(6) was demonstrated in different experimental models. In addition to reducing cell proliferation, IP(6) also induces differentiation of malignant cells. Enhanced immunity and antioxidant properties also contribute to tumor cell destruction. Preliminary studies in humans show that IP(6) and inositol, the precursor molecule of IP(6), appear to enhance the anticancer effect of conventional chemotherapy, control cancer metastases, and improve quality of life. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP(6) + inositol holds great promise in our strategies for cancer prevention and therapy. There is clearly enough evidence to justify the initiation of full-scale clinical trials in humans.

Are Current Insulin Pumps Accessible to Blind and Visually Impaired People?

PubMed Central

Burton, Darren M.; Uslan, Mark M.; Blubaugh, Morgan V.; Clements, Charles W.

2009-01-01

Background In 2004, Uslan and colleagues determined that insulin pumps (IPs) on the market were largely inaccessible to blind and visually impaired persons. The objective of this study is to determine if accessibility status changed in the ensuing 4 years. Methods Five IPs on the market in 2008 were acquired and analyzed for key accessibility traits such as speech and other audio output, tactual nature of control buttons, and the quality of visual displays. It was also determined whether or not a blind or visually impaired person could independently complete tasks such as programming the IP for insulin delivery, replacing batteries, and reading manuals and other documentation. Results It was found that IPs have not improved in accessibility since 2004. None have speech output, and with the exception of the Animas IR 2020, no significantly improved visual display characteristics were found. Documentation is still not completely accessible. Conclusion Insulin pumps are relatively complex devices, with serious health consequences resulting from improper use. For IPs to be used safely and independently by blind and visually impaired patients, they must include voice output to communicate all the information presented on their display screens. Enhancing display contrast and the size of the displayed information would also improve accessibility for visually impaired users. The IPs must also come with accessible user documentation in alternate formats. PMID:20144301

Intraperitoneal chemotherapy for advanced ovarian and peritoneal cancers in patients following interval debulking surgery or primary cytoreductive surgery: Tom Baker Cancer Centre experience from 2006 to 2009.

PubMed

Nelson, Gregory; Lucero, Carlos Aspe; Chu, Pamela; Nation, Jill; Ghatage, Prafull

2010-03-01

To describe our experience with cisplatin- and paclitaxel-based IP chemotherapy in patients treated initially with either neoadjuvant chemotherapy and interval debulking surgery (IDS) or primary cytoreductive surgery (PCRS). We performed a retrospective review of the records of 67 patients (38 IDS, 29 PCRS) enrolled in the intraperitoneal (IP) chemotherapy program at the Tom Baker Cancer Centre between 2006 and 2009. Information pertaining to patient demographics, IP chemotherapy toxicity, and catheter complications was extracted, and the median time to recurrence was calculated. Most patients in the study were aged 50 to 70 years and had a diagnosis of stage III serous ovarian cancer. Overall, 295/393 IP cycles (75%) were successfully administered. The proportion of patients completing six cycles of chemotherapy in the IDS and PCRS groups was 53% and 59%, respectively. Frequent (> 25%) Grade 1 to 2 chemotherapy toxicities included fatigue, peripheral neuropathy, and nausea. Catheter complications were observed in 34% of patients (23/67). The recurrence rates for patients completing four or more cycles of IP chemotherapy in the IDS and PCRS groups were 58% and 35%, respectively, with the median time to recurrence approximately one year. Although IP chemotherapy is well tolerated in both IDS and PCRS patients, the median time to recurrence is shorter than expected.

Are current insulin pumps accessible to blind and visually impaired people?

PubMed

Burton, Darren M; Uslan, Mark M; Blubaugh, Morgan V; Clements, Charles W

2009-05-01

In 2004, Uslan and colleagues determined that insulin pumps (IPs) on the market were largely inaccessible to blind and visually impaired persons. The objective of this study is to determine if accessibility status changed in the ensuing 4 years. Five IPs on the market in 2008 were acquired and analyzed for key accessibility traits such as speech and other audio output, tactual nature of control buttons, and the quality of visual displays. It was also determined whether or not a blind or visually impaired person could independently complete tasks such as programming the IP for insulin delivery, replacing batteries, and reading manuals and other documentation. It was found that IPs have not improved in accessibility since 2004. None have speech output, and with the exception of the Animas IR 2020, no significantly improved visual display characteristics were found. Documentation is still not completely accessible. Insulin pumps are relatively complex devices, with serious health consequences resulting from improper use. For IPs to be used safely and independently by blind and visually impaired patients, they must include voice output to communicate all the information presented on their display screens. Enhancing display contrast and the size of the displayed information would also improve accessibility for visually impaired users. The IPs must also come with accessible user documentation in alternate formats. 2009 Diabetes Technology Society.

Crossover from isotropic to directed percolation

NASA Astrophysics Data System (ADS)

Zhou, Zongzheng; Yang, Ji; Ziff, Robert M.; Deng, Youjin

2012-08-01

We generalize the directed percolation (DP) model by relaxing the strict directionality of DP such that propagation can occur in either direction but with anisotropic probabilities. We denote the probabilities as p↓=ppd and p↑=p(1-pd), with p representing the average occupation probability and pd controlling the anisotropy. The Leath-Alexandrowicz method is used to grow a cluster from an active seed site. We call this model with two main growth directions biased directed percolation (BDP). Standard isotropic percolation (IP) and DP are the two limiting cases of the BDP model, corresponding to pd=1/2 and pd=0,1 respectively. In this work, besides IP and DP, we also consider the 1/2

The effects of high intensity short rest resistance exercise on muscle damage markers in men and women.

PubMed

Heavens, Kristen R; Szivak, Tunde K; Hooper, David R; Dunn-Lewis, Courtenay; Comstock, Brett A; Flanagan, Shawn D; Looney, David P; Kupchak, Brian R; Maresh, Carl M; Volek, Jeff S; Kraemer, William J

2014-04-01

Within and between sexes, universal load prescription (as assigned in extreme conditioning programs) creates extreme ranges in individual training intensities. Exercise intensity has been proposed to be the main factor determining the degree of muscle damage. Thus, the purpose of this study was to examine markers of muscle damage in resistance-trained men (n = 9) and women (n = 9) from a high intensity (HI) short rest (SR) (HI/SR) resistance exercise protocol. The HI/SR consisted of a descending pyramid scheme starting at 10 repetitions, decreasing 1 repetition per set for the back squat, bench press, and deadlift, as fast as possible. Blood was drawn pre-exercise (pre), immediately postexercise (IP), 15 minutes postexercise (+15), 60 minutes postexercise (+60), and 24 hours postexercise (+24). Women demonstrated significant increases in interleukin 6 (IL-6; IP), creatine kinase (CK; +24), myoglobin (IP, +15, +60), and a greater relative increase when compared with men (+15, +60). Men demonstrated significant increases in myoglobin (IP, +15, +60, +24), IL-6 (IP, +15), CK (IP, +60, +24), and testosterone (IP, +15). There were significant sex interactions observed in CK (IP, +60, +24) and testosterone (IP, +15, +60, +24). Women completed the protocol faster (women: 34:04 ± 9:40 minutes, men: 39:22 ± 14:43 minutes), and at a slightly higher intensity (women: 70.1 ± 3.5%, men 68.8 ± 3.1%); however, men performed significantly more work (men: 14384.6 ± 1854.5 kg, women: 8774.7 ± 1612.7 kg). Overall, women demonstrated a faster inflammatory response with increased acute damage, whereas men demonstrated a greater prolonged damage response. Therefore, strength and conditioning professionals need to be aware of the level of stress imposed on individuals when creating such volitional high intensity metabolic type workouts and allow for adequate progression and recovery from such workouts.

Investigation of the pathogenesis of autoimmune diseases by iPS cells.

PubMed

Natsumoto, Bunki; Shoda, Hirofumi; Fujio, Keishi; Otsu, Makoto; Yamamoto, Kazuhiko

2017-01-01

The pluripotent stem cells have a self-renewal ability and can be differentiated into theoretically all of cell types. The induced pluripotent stem (iPS) cells overcame the ethical problems of the human embryonic stem (ES) cell, and enable pathologic analysis of intractable diseases and drug discovery. The in vitro disease model using disease-specific iPS cells enables repeated analyses of human cells without influence of environment factors. Even though autoimmune diseases are polygenic diseases, autoimmune disease-specific iPS cells are thought to be a promising tool for analyzing the pathogenesis of the diseases and drug discovery in future.

Advances in simulation of wave interactions with extended MHD phenomena

NASA Astrophysics Data System (ADS)

Batchelor, D.; Abla, G.; D'Azevedo, E.; Bateman, G.; Bernholdt, D. E.; Berry, L.; Bonoli, P.; Bramley, R.; Breslau, J.; Chance, M.; Chen, J.; Choi, M.; Elwasif, W.; Foley, S.; Fu, G.; Harvey, R.; Jaeger, E.; Jardin, S.; Jenkins, T.; Keyes, D.; Klasky, S.; Kruger, S.; Ku, L.; Lynch, V.; McCune, D.; Ramos, J.; Schissel, D.; Schnack, D.; Wright, J.

2009-07-01

The Integrated Plasma Simulator (IPS) provides a framework within which some of the most advanced, massively-parallel fusion modeling codes can be interoperated to provide a detailed picture of the multi-physics processes involved in fusion experiments. The presentation will cover four topics: 1) recent improvements to the IPS, 2) application of the IPS for very high resolution simulations of ITER scenarios, 3) studies of resistive and ideal MHD stability in tokamk discharges using IPS facilities, and 4) the application of RF power in the electron cyclotron range of frequencies to control slowly growing MHD modes in tokamaks and initial evaluations of optimized location for RF power deposition.

Stem/progenitor cells from inflamed human dental pulp retain tissue regeneration potential

PubMed Central

Alongi, Dominick J; Yamaza, Takayoshi; Song, Yingjie; Fouad, Ashraf F; Romberg, Elaine E; Shi, Songtao; Tuan, Rocky S; Huang, George T-J

2011-01-01

Background Potent stem/progenitor cells have been isolated from normal human dental pulps termed dental pulp stem cells (DPSCs). However, it is unknown whether these cells exist in inflamed pulps (IPs). Aims To determine whether DPSCs can be identified and isolated from IPs; and if they can be successfully cultured, whether they retain tissue regeneration potential in vivo. Materials & methods DPSCs from freshly collected normal pulps (NPs) and IPs were characterized in vitro and their tissue regeneration potential tested using an in vivo study model. Results The immunohistochemical analysis showed that IPs expressed higher levels of mesenchymal stem cell markers STRO-1, CD90, CD105 and CD146 compared with NPs (p < 0.05). Flow cytometry analysis showed that DPSCs from both NPs and IPs expressed moderate to high levels of CD146, stage-specific embryonic antigen-4, CD73 and CD166. Total population doubling of DPSCs-IPs (44.6 ± 2.9) was lower than that of DPSCs-NPs (58.9 ± 2.5) (p < 0.05), and DPSCs-IPs appeared to have a decreased osteo/dentinogenic potential compared with DPSCs-NPs based on the mineral deposition in cultures. Nonetheless, DPSCs-IPs formed pulp/dentin complexes similar to DPSCs-NPs when transplanted into immunocompromised mice. Conclusion DPSCs-IPs can be isolated and their mesenchymal stem cell marker profiles are similar to those from NPs. Although some stem cell properties of DPSCs-IPs were altered, cells from some samples remained potent in tissue regeneration in vivo. PMID:20465527

Recommendations for the Interagency Ship Structure Committee’s Fiscal 1985 Research Program.

DTIC Science & Technology

1984-01-01

Houston, TX Mr. D. Price , (84), National Ocean and Atmospheric Administration, Rockville, MD Mr. D. A. Sarno, (84), ARMCO Inc., Middletown, OH Mr. R. W...A. B. Stevovy Dr. V. R. Porter AMERICAN BUREAU Of SKIPPING U.S. COAST GUARD ACADEMY Dr. D. Liu* Lt. John Tuttle - Liaison Mr. 1. L. Stern T-TU.S...which defines the combination of fastest running crack length and stress level that must be exceeded for a crack to 4 % % k ipS penetrate a structural

Mobile Vehicle Teleoperated Over Wireless IP

DTIC Science & Technology

2007-06-13

VideoLAN software suite. The VLC media player portion of this suite handles net- work streaming of video, as well as the receipt and display of the video...is found in appendix C.7. Video Display The video feed is displayed for the operator using VLC opened independently from the control sending program...This gives the operator the most choice in how to configure the display. To connect VLC to the feed all you need is the IP address from the Java

Lactocepin secreted by Lactobacillus exerts anti-inflammatory effects by selectively degrading proinflammatory chemokines.

PubMed

von Schillde, Marie-Anne; Hörmannsperger, Gabriele; Weiher, Monika; Alpert, Carl-Alfred; Hahne, Hannes; Bäuerl, Christine; van Huynegem, Karolien; Steidler, Lothar; Hrncir, Tomas; Pérez-Martínez, Gaspar; Kuster, Bernhard; Haller, Dirk

2012-04-19

The intestinal microbiota has been linked to inflammatory bowel diseases (IBD), and oral treatment with specific bacteria can ameliorate IBD. One bacterial mixture, VSL#3, containing Lactobacillus, Bifidobacterium, and Streptococcus, was clinically shown to reduce inflammation in IBD patients and normalize intestinal levels of IP-10, a lymphocyte-recruiting chemokine, in a murine colitis model. We identified Lactobacillus paracasei prtP-encoded lactocepin as a protease that selectively degrades secreted, cell-associated, and tissue-distributed IP-10, resulting in significantly reduced lymphocyte recruitment after intraperitoneal injection in an ileitis model. A human Lactobacillus casei isolate was also found to encode lactocepin and degrade IP-10. L. casei feeding studies in a murine colitis model (T cell transferred Rag2(-/-) mice) revealed that a prtP-disruption mutant was significantly less potent in reducing IP-10 levels, T cell infiltration and inflammation in cecal tissue compared to the isogenic wild-type strain. Thus, lactocepin-based therapies may be effective treatments for chemokine-mediated diseases like IBD. Copyright © 2012 Elsevier Inc. All rights reserved.

Using Human Induced Pluripotent Stem Cells to Model Skeletal Diseases.

PubMed

Barruet, Emilie; Hsiao, Edward C

2016-01-01

Musculoskeletal disorders affecting the bones and joints are major health problems among children and adults. Major challenges such as the genetic origins or poor diagnostics of severe skeletal disease hinder our understanding of human skeletal diseases. The recent advent of human induced pluripotent stem cells (human iPS cells) provides an unparalleled opportunity to create human-specific models of human skeletal diseases. iPS cells have the ability to self-renew, allowing us to obtain large amounts of starting material, and have the potential to differentiate into any cell types in the body. In addition, they can carry one or more mutations responsible for the disease of interest or be genetically corrected to create isogenic controls. Our work has focused on modeling rare musculoskeletal disorders including fibrodysplasia ossificans progressive (FOP), a congenital disease of increased heterotopic ossification. In this review, we will discuss our experiences and protocols differentiating human iPS cells toward the osteogenic lineage and their application to model skeletal diseases. A number of critical challenges and exciting new approaches are also discussed, which will allow the skeletal biology field to harness the potential of human iPS cells as a critical model system for understanding diseases of abnormal skeletal formation and bone regeneration.

Informing the Design and Evaluation of Superuser Care Management Initiatives: Accounting for Regression-to-the-Mean.

PubMed

Chakravarty, Sujoy; Cantor, Joel C

2016-09-01

Health care spending is concentrated among a small number of high-cost patients, and the popularity of initiatives to improve care and reduce cost among such "superusers" (SUs) is growing. However, SU costs decline naturally over time, even without intervention, a statistical phenomenon known as regression-to-the-mean (RTM). We assess the magnitude of RTM in hospital costs for cohorts of hospital SUs identified on the basis of high inpatient (IP) or emergency department (ED) utilization. We further examine how cost and RTM are associated with patient characteristics including behavioral health (BH) problems, multiple chronic conditions, and indicators of vulnerability. Using longitudinally linked all-payer hospital billing data, we selected patient cohorts with ≥2 IP stays (IP SUs) or ≥6 ED visits (ED SUs) during a 6-month baseline period, and additional subgroups defined by combinations of IP and ED superuse. A total of 289,060 NJ hospital IP and treat-and-release ED patients over 2009-2011. Hospital costs among IP and ED SUs declined 70% and 38%, respectively, over 8 quarters following the baseline period. The decrease occurs more quickly for IP SUs compared with ED SUs. Presence of BH problems was positively associated with costs among patients overall, but the relationship varied by SU cohort. Understanding patterns of RTM among SU populations is important for designing intervention strategies, as there is greater potential for savings among patients with more persistent costs (less RTM). Further, as many SU initiatives lack resources for rigorous evaluation, quantifying the extent of RTM is vital for interpreting program outcomes.

Ethernet direct display: a new dimension for in-vehicle video connectivity solutions

NASA Astrophysics Data System (ADS)

Rowley, Vincent

2009-05-01

To improve the local situational awareness (LSA) of personnel in light or heavily armored vehicles, most military organizations recognize the need to equip their fleets with high-resolution digital video systems. Several related upgrade programs are already in progress and, almost invariably, COTS IP/Ethernet is specified as the underlying transport mechanism. The high bandwidths, long reach, networking flexibility, scalability, and affordability of IP/Ethernet make it an attractive choice. There are significant technical challenges, however, in achieving high-performance, real-time video connectivity over the IP/Ethernet platform. As an early pioneer in performance-oriented video systems based on IP/Ethernet, Pleora Technologies has developed core expertise in meeting these challenges and applied a singular focus to innovating within the required framework. The company's field-proven iPORTTM Video Connectivity Solution is deployed successfully in thousands of real-world applications for medical, military, and manufacturing operations. Pleora's latest innovation is eDisplayTM, a smallfootprint, low-power, highly efficient IP engine that acquires video from an Ethernet connection and sends it directly to a standard HDMI/DVI monitor for real-time viewing. More costly PCs are not required. This paper describes Pleora's eDisplay IP Engine in more detail. It demonstrates how - in concert with other elements of the end-to-end iPORT Video Connectivity Solution - the engine can be used to build standards-based, in-vehicle video systems that increase the safety and effectiveness of military personnel while fully leveraging the advantages of the lowcost COTS IP/Ethernet platform.

Protective effects of tempol in an experimental ovarian ischemia-reperfusion injury model in female Wistar albino rats.

PubMed

Pınar, Neslihan; Soylu Karapınar, Oya; Özcan, Oğuzhan; Atik Doğan, Esin; Bayraktar, Suphi

2017-07-01

The aim of this study was to investigate the antioxidant effects of tempol on ovarian ischemia-reperfusion (I/R) injury in rats. Forty female Wistar albino rats were randomly divided into 5 groups: Group I, sham; Group II, ischemia (I); Group III, I/R; Group IV, I/R + tempol 30 mg/kg i.p; Group V, I/R + tempol 50 mg/kg i.p. Oxidative stress index (OSI) was significantly higher in the ischemia group and the I/R group than in the sham group. Catalase levels were significantly lower in the I/R group than in the I/R + tempol 30 mg/kg i.p. and the I/R + tempol 50 mg/kg i.p. groups. Glutathione peroxidase levels were lower in the I/R group than in the I/R + tempol 30 mg/kg i.p. and the I/R + tempol 50 mg/kg i.p. groups. MDA levels were significantly lower in the I/R + tempol 30 mg/kg i.p. group and the I/R + tempol 50 mg/kg i.p. group than in the I/R group. The levels of the histopathological parameters were significantly decreased in the I/R + tempol 50 mg/kg i.p. group compared with the I/R group. Tempol can be used for reducing ovarian I/R injury.

Imaging probe for breast cancer localization

NASA Astrophysics Data System (ADS)

Soluri, A.; Scafè, R.; Capoccetti, F.; Burgio, N.; Schiaratura, A.; Pani, R.; Pellegrini, R.; Cinti, M. N.; Mechella, M.; Amanti, A.; David, V.; Scopinaro, F.

2003-01-01

High spatial resolution, small Field Of View (FOV), fully portable scintillation cameras are lower cost and obviously lower weight than large FOV, not transportable Anger gamma cameras. Portable cameras allow easy transfer of the detector, thus of radioisotope imaging, where the bioptical procedure takes place. In this paper we describe a preliminary experience on radionuclide Breast Cancer (BC) imaging with a 22.8×22.8 mm 2 FOV minicamera, already used by our group for sentinel node detection with the name of Imaging Probe (IP). In this work IP BC detection was performed with the aim of guiding biopsy, in particular open biopsy, or to help or modify fine needle or needle addressing when main driving method was echography or digital radiography. The IP prototype weight was about 1 kg. This small scintillation camera is based on the compact Position Sensitive Photomultiplier Tube Hamamatsu R7600-00-C8, coupled to a CsI(Tl) scintillation array 2.6×2.6×5.0 mm 3 crystal-pixel size. Spatial resolution of the IP was 2.5 mm Full-Width at Half-Maximum at laboratory tests. IP was provided with acquisition software allowing quick change of pixels number on the computer acquisition frame and an on-line image-smoothing program. Both these programs were developed in order to allow nuclear physicians to quickly get target source when the patient was anesthetized in the operator room, with sterile conditions. 99mTc Sestamibi (MIBI) was injected at the dose of 740 MBq 1 h before imaging and biopsy to 14 patients with suspicious or known BC. Scintigraphic images were acquired before and after biopsy in each patient. Operator was allowed to take into account scintigraphic images as well as previously performed X-ray mammograms and echographies. High-resolution IP images were able to guide biopsy toward cancer or washout zones of the cancer, that are thought to be chemoresistant in 7 patients out of 10. Four patients, in whom IP and MIBI were not able to guide biopsy, did not show cancer. Two patients in whom biopsy was performed in the high washout zone, did show Multi Drug Resistance (MDR) gene product at immunohistochemistry on bioptical samples. Specific radioactivity was measured on biopsy specimens and measurement confirmed the etherogeneous distribution of MIBI within cancers. Our study confirms the ability of IP to guide breast biopsy even when our mini-camera has to be manually handled by trained physicians during operation.

On recovering distributed IP information from inductive source time domain electromagnetic data

NASA Astrophysics Data System (ADS)

Kang, Seogi; Oldenburg, Douglas W.

2016-10-01

We develop a procedure to invert time domain induced polarization (IP) data for inductive sources. Our approach is based upon the inversion methodology in conventional electrical IP (EIP), which uses a sensitivity function that is independent of time. However, significant modifications are required for inductive source IP (ISIP) because electric fields in the ground do not achieve a steady state. The time-history for these fields needs to be evaluated and then used to define approximate IP currents. The resultant data, either a magnetic field or its derivative, are evaluated through the Biot-Savart law. This forms the desired linear relationship between data and pseudo-chargeability. Our inversion procedure has three steps: (1) Obtain a 3-D background conductivity model. We advocate, where possible, that this be obtained by inverting early-time data that do not suffer significantly from IP effects. (2) Decouple IP responses embedded in the observations by forward modelling the TEM data due to a background conductivity and subtracting these from the observations. (3) Use the linearized sensitivity function to invert data at each time channel and recover pseudo-chargeability. Post-interpretation of the recovered pseudo-chargeabilities at multiple times allows recovery of intrinsic Cole-Cole parameters such as time constant and chargeability. The procedure is applicable to all inductive source survey geometries but we focus upon airborne time domain EM (ATEM) data with a coincident-loop configuration because of the distinctive negative IP signal that is observed over a chargeable body. Several assumptions are adopted to generate our linearized modelling but we systematically test the capability and accuracy of the linearization for ISIP responses arising from different conductivity structures. On test examples we show: (1) our decoupling procedure enhances the ability to extract information about existence and location of chargeable targets directly from the data maps; (2) the horizontal location of a target body can be well recovered through inversion; (3) the overall geometry of a target body might be recovered but for ATEM data a depth weighting is required in the inversion; (4) we can recover estimates of intrinsic τ and η that may be useful for distinguishing between two chargeable targets.

The effect of internal possession laws on underage drinking among high school students: a 12-state analysis.

PubMed

Disney, Lynn D; LaVallee, Robin A; Yi, Hsiao-Ye

2013-06-01

We assessed the effect of internal possession (IP) laws, which allow law enforcement to charge underage drinkers with alcohol possession if they have ingested alcohol, on underage drinking behaviors. We examined Youth Risk Behavior Survey (YRBS) data from 12 states with IP laws and with YRBS data before and after each law's implementation. We used logistic regression models with fixed effects for state to assess the effects of IP laws on drinking and binge drinking among high school students. Implementation of IP laws is associated with reductions in the odds of past-month drinking. This reduction was bigger among male than among female adolescents (27% vs 15%) and only significant among younger students aged 14 and 15 years (15% and 11%, respectively). Male adolescents also reported a significant reduction (24%) in the odds of past-month binge drinking under IP laws. These findings suggest that IP laws are effective in reducing underage drinking, particularly among younger adolescents.

The Effect of Internal Possession Laws on Underage Drinking Among High School Students: A 12-State Analysis

PubMed Central

Disney, Lynn D.; Yi, Hsiao-ye

2013-01-01

Objectives. We assessed the effect of internal possession (IP) laws, which allow law enforcement to charge underage drinkers with alcohol possession if they have ingested alcohol, on underage drinking behaviors. Methods. We examined Youth Risk Behavior Survey (YRBS) data from 12 states with IP laws and with YRBS data before and after each law’s implementation. We used logistic regression models with fixed effects for state to assess the effects of IP laws on drinking and binge drinking among high school students. Results. Implementation of IP laws is associated with reductions in the odds of past-month drinking. This reduction was bigger among male than among female adolescents (27% vs 15%) and only significant among younger students aged 14 and 15 years (15% and 11%, respectively). Male adolescents also reported a significant reduction (24%) in the odds of past-month binge drinking under IP laws. Conclusions. These findings suggest that IP laws are effective in reducing underage drinking, particularly among younger adolescents. PMID:23597385

The UCSD Time-dependent Tomography and IPS use for Exploring Space Weather Events

NASA Astrophysics Data System (ADS)

Yu, H. S.; Jackson, B. V.; Buffington, A.; Hick, P. P.; Tokumaru, M.; Odstrcil, D.; Kim, J.; Yun, J.

2016-12-01

The University of California, San Diego (UCSD) time-dependent, iterative, kinematic reconstruction technique has been used and expanded upon for over two decades. It provides some of the most-accurate predictions and three-dimensional (3D) analyses of heliospheric solar-wind parameters now available using interplanetary scintillation (IPS) data. The parameters provided include reconstructions of velocity, density, and three-component magnetic fields. Precise time-dependent results are now obtained at any solar distance in the inner heliosphere using ISEE (formerly STELab), Japan, IPS data sets, and can be used to drive 3D-MHD models including ENLIL. Using IPS data, these reconstructions provide a real-time prediction of the global solar wind parameters across the whole heliosphere with a time cadence of about one day (see http://ips.ucsd.edu). Here we compare the results (such as density, velocity, and magnetic fields) from the IPS tomography with different in-situ measurements and discuss several specific space weather events that demonstrate the issues resulting from these analyses.

Systemic synergism between codeine and morphine in three pain models in mice.

PubMed

Miranda, Hugo F; Noriega, Viviana; Zepeda, Ramiro J; Sierralta, Fernando; Prieto, Juan C

2013-01-01

The combination of two analgesic agents offers advantages in pain treatment. Codeine and morphine analgesia is due to activation of opioid receptor subtypes. This study, performed in mice using isobolographic analysis, evaluated the type of interaction in intraperitoneal (ip) or intrathecal (it) coadministration of codeine and morphine, in three nociceptive behavioral models. Intrathecal morphine resulted to be 7.5 times more potent than ip morphine in the writhing test, 55.6 times in the tail flick test and 1.7 times in phase II of the orofacial formalin test; however, in phase I of the same test ip was 1.2 times more potent than it morphine. Intrathecal codeine resulted being 3.4 times more potent than ip codeine in the writhing test, 1.6 times in the tail flick test, 2.5 times in phase I and 6.7 times in phase II of the orofacial formalin test. Opioid coadministration had a synergistic effect in the acute tonic pain (acetic acid writhing test), acute phasic pain (tail flick test) and inflammatory pain (orofacial formalin test). The interaction index ranged between 0.284 (writhing ip) and 0.440 (orofacial formalin phase II ip). This synergy may relate to the different pathways of pain transmission and to the different intracellular signal transduction. The present findings also raise the possibility of potential clinical advantages in combining opioids in pain management.

A spatial econometric panel data examination of endogenous versus exogenous interaction in Chinese province-level patenting

NASA Astrophysics Data System (ADS)

LeSage, James P.; Sheng, Yuxue

2014-07-01

We examine the provincial-level relationship between domestic Chinese intellectual property (IP) and knowledge stocks using a space-time panel model and data set covering monthly patent activity over the period 2002-2010. The goal of the modeling exercise is to explore the elasticity response of IP to knowledge stocks classified by type of creator (universities and research institutes, enterprises, and individuals). A focus is on spatial and time dependence in the relationship between knowledge stocks and IP, which implies spatial spillovers and diffusion over time. Many past studies of regional knowledge production have focused on patent applications as a proxy for regional output from the knowledge production process. However, this ignores the distinction between patent applications and patents granted, with the latter reflecting a decision and ability to convert knowledge produced into IP. This study differs in its focus on the regional relation between IP and knowledge stocks and the space-time dynamics of these. Using patents granted as a proxy for IP, and past patent applications as a proxy for regional knowledge stocks, allows us to explore the implied quality of knowledge production by various types of creators. Because Chinese patent applications have grown by 22 %, questions have been raised about the quantity versus quality of these applications. Our findings shed light on this issue.

Vocational Counselors in France: Comparison to Competencies of Employment Specialists Working in Canadian IPS Programs.

PubMed

de Pierrefeu, Inès; Corbière, Marc; Pachoud, Bernard

2017-10-01

Supported employment programs are evidence-based practices to help people with severe mental illness to obtain competitive employment. The competencies of employment specialists working in these programs are key elements related to work integration. In France, the Messidor Association, a prevocational organisation, has developed a practice with similarities to supported employment and is beginning to develop supported employment programs in their context. The objective of this quantitative study was to evaluate the Messidor vocational counselors' competencies using the Behaviors, Attitudes and Knowledge in Employment Specialists' scale by comparing their results to those of employment specialists working in IPS programs in Canada. Descriptive analyses and a MANOVA highlighted similarities between French and Canadian counselors such as the same importance given to the working alliance with clients and the development of relationships with different stakeholders (e.g., employers). Skills that should be developed in vocational counselors in France include those related to rapid job search and dealing with stigma. In addition, clinical implications are suggested to ensure the development of vocational counselors' competencies in France.

Tools for Administration of a UNIX-Based Network

NASA Technical Reports Server (NTRS)

LeClaire, Stephen; Farrar, Edward

2004-01-01

Several computer programs have been developed to enable efficient administration of a large, heterogeneous, UNIX-based computing and communication network that includes a variety of computers connected to a variety of subnetworks. One program provides secure software tools for administrators to create, modify, lock, and delete accounts of specific users. This program also provides tools for users to change their UNIX passwords and log-in shells. These tools check for errors. Another program comprises a client and a server component that, together, provide a secure mechanism to create, modify, and query quota levels on a network file system (NFS) mounted by use of the VERITAS File SystemJ software. The client software resides on an internal secure computer with a secure Web interface; one can gain access to the client software from any authorized computer capable of running web-browser software. The server software resides on a UNIX computer configured with the VERITAS software system. Directories where VERITAS quotas are applied are NFS-mounted. Another program is a Web-based, client/server Internet Protocol (IP) address tool that facilitates maintenance lookup of information about IP addresses for a network of computers.

Effects of the brain-penetrant and selective 5-HT6 receptor antagonist SB-399885 in animal models of anxiety and depression.

PubMed

Wesołowska, Anna; Nikiforuk, Agnieszka

2007-04-01

The effects of a selective 5-HT(6) receptor antagonist, SB-399885 (N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide), were evaluated in behavioural tests sensitive to clinically effective anxiolytic- and antidepressant-compounds using diazepam and imipramine as reference drugs. In the Vogel conflict drinking test in rats, SB-399885 (1-3mg/kg i.p.) caused an anxiolytic-like activity comparable to that of diazepam (2.5-5mg/kg i.p.). An anxiolytic-like effect was also seen in the elevated plus-maze test in rats, where SB-399885 (0.3-3mg/kg i.p.) was slightly weaker than diazepam (2.5-5mg/kg i.p.). In the four-plate test in mice, SB-399885 (3-20mg/kg i.p.) showed an anxiolytic-like effect which was weaker than that produced by diazepam (2.5-5mg/kg i.p.). In the forced swim test in rats, SB-399885 (10mg/kg i.p.) significantly shortened the immobility time and the effect was stronger than that of imipramine (30mg/kg i.p.). In the forced swim test in mice, SB-399885 (20-30mg/kg i.p.) had an anti-immobility action, comparable to imipramine (30mg/kg i.p.) and also in the tail suspension test in mice, SB-399885 (10-30mg/kg i.p.) had an antidepressant-like effect, though was weaker than imipramine (10-20mg/kg i.p.). The tested 5-HT(6) antagonist (3-20mg/kg i.p.) shortened the walking time of rats in the open field test and, at a dose of 30mg/kg i.p. reduced the locomotor activity of mice. SB-399885 (in doses up to 30mg/kg i.p.) did not affect motor coordination in mice and rats tested in the rota-rod test. Such data indicate that the selective 5-HT(6) receptor antagonist SB-399885had specific effects, indicative of this compound's anxiolytic and antidepressant potential.

Normalization, bias correction, and peak calling for ChIP-seq

PubMed Central

Diaz, Aaron; Park, Kiyoub; Lim, Daniel A.; Song, Jun S.

2012-01-01

Next-generation sequencing is rapidly transforming our ability to profile the transcriptional, genetic, and epigenetic states of a cell. In particular, sequencing DNA from the immunoprecipitation of protein-DNA complexes (ChIP-seq) and methylated DNA (MeDIP-seq) can reveal the locations of protein binding sites and epigenetic modifications. These approaches contain numerous biases which may significantly influence the interpretation of the resulting data. Rigorous computational methods for detecting and removing such biases are still lacking. Also, multi-sample normalization still remains an important open problem. This theoretical paper systematically characterizes the biases and properties of ChIP-seq data by comparing 62 separate publicly available datasets, using rigorous statistical models and signal processing techniques. Statistical methods for separating ChIP-seq signal from background noise, as well as correcting enrichment test statistics for sequence-dependent and sonication biases, are presented. Our method effectively separates reads into signal and background components prior to normalization, improving the signal-to-noise ratio. Moreover, most peak callers currently use a generic null model which suffers from low specificity at the sensitivity level requisite for detecting subtle, but true, ChIP enrichment. The proposed method of determining a cell type-specific null model, which accounts for cell type-specific biases, is shown to be capable of achieving a lower false discovery rate at a given significance threshold than current methods. PMID:22499706

Functional myogenic engraftment from mouse iPS cells.

PubMed

Darabi, Radbod; Pan, Weihong; Bosnakovski, Darko; Baik, June; Kyba, Michael; Perlingeiro, Rita C R

2011-11-01

Direct reprogramming of adult fibroblasts to a pluripotent state has opened new possibilities for the generation of patient- and disease-specific stem cells. However the ability of induced pluripotent stem (iPS) cells to generate tissue that mediates functional repair has been demonstrated in very few animal models of disease to date. Here we present the proof of principle that iPS cells may be used effectively for the treatment of muscle disorders. We combine the generation of iPS cells with conditional expression of Pax7, a robust approach to derive myogenic progenitors. Transplantation of Pax7-induced iPS-derived myogenic progenitors into dystrophic mice results in extensive engraftment, which is accompanied by improved contractility of treated muscles. These findings demonstrate the myogenic regenerative potential of iPS cells and provide rationale for their future therapeutic application for muscular dystrophies.

Inter-alpha inhibitor protein administration improves survival from neonatal sepsis in mice.

PubMed

Singh, Kultar; Zhang, Ling Xiu; Bendelja, Kreso; Heath, Ryan; Murphy, Shaun; Sharma, Surendra; Padbury, James F; Lim, Yow-Pin

2010-09-01

Inter-alpha inhibitor proteins (IaIp) are serine proteases inhibitors that modulate endogenous protease activity and have been shown to improve survival in adult models of sepsis. We evaluated the effect of IaIp on survival and systemic responses to sepsis in neonatal mice. Sepsis was induced in 2-d-old mice with lipopolysaccharide (LPS), Escherichia coli, and group B Streptococci. Sepsis was associated with 75% mortality. IaIp, given by i.p. administration at doses between 15 and 45 mg/kg from 1 to 6 h after the onset of sepsis, improved survival to approximately 90% (p = 0.0159) in both LPS-induced sepsis and with live bacterial infections. The greatest effect was on reversal of hemorrhagic pneumonitis. The effects were dose and time dependent. Systemic cytokine profile and tissue histology were examined. Survival was compared in IL-10 knock out animals. Systemic cytokine levels including TNF-[alpha] and IL-10 were increased after induction of sepsis and modulated significantly after IaIp administration. Because the effect of IaIp was still demonstrable in IL-10 deficient mice, we conclude the beneficial effects of IaIp is because of suppression of proinflammatory cytokines such as TNF-[alpha] rather than augmentation of IL-10. IaIp may offer significant benefits as a therapeutic

Pharmacological profile of dexketoprofen in orofacial pain.

PubMed

Miranda, Hugo F; Sierralta, Fernando; Aranda, Nicolás; Noriega, Viviana; Prieto, Juan Carlos

2016-12-01

Non-steroidal anti-inflammatory drugs (NSAIDs) may act through others mechanisms, in addition to inhibition of prostaglandin synthesis. These includes cholinergic, NO, serotonergic and opioids pathways. The aim of this work was to evaluate the effect of systemic action of (S)-+-ketoprofen (dexketoprofen, DEX) on pain behaviors using the orofacial formalin test in mice and the potential involvement of cholinergic, NO, serotonergic and opioids pathways. The pretreatment of the mice with 1mg/kg ip of atropine or opoid antagonists: 1mg/kg, ip of NTX or 1mg/kg ip of NTI or 1mg/kg of NOR-BNI ip, did not produce significant change in the ED 50 values of the antinociception to orofacial test induced by DEX. The pretreatment of the mice with 0.5mg/kg ip tropisetron, increased in a significant fashion the values of ED 50 of DEX. When the mice were treated with 5mg/kg ip of L-NAME or 25mg/kg ip of aminoguanidine or 50mg/kg ip of 7-nitroindazole reversed the antinociception of DEX. The findings of this study demonstrate activation of NO and 5-HTpathways play important roles in the systemic antinociceptive effect of DEX in a murine model of inflammatory pain. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Recognition and prevention of computed radiography image artifacts.

PubMed

Hammerstrom, Kevin; Aldrich, John; Alves, Len; Ho, Andrew

2006-09-01

Initiated by complaints of image artifacts, a thorough visual and radiographic investigation of 197 Fuji, 35 Agfa, and 37 Kodak computed radiography (CR) cassettes with imaging plates (IPs) in clinical use at four radiology departments was performed. The investigation revealed that the physical deterioration of the cassettes and IPs was more extensive than previously believed. It appeared that many of the image artifacts were the direct result of premature wear of the cassettes and imaging plates. The results indicate that a quality control program for CR cassettes and IPs is essential and should include not only cleaning of the cassettes and imaging plates on a regular basis, but also visual and radiographic image inspection to limit the occurrence of image artifacts and to prolong the life cycle of the CR equipment.

The strengths and weaknesses of inverted pendulum models of human walking.

PubMed

McGrath, Michael; Howard, David; Baker, Richard

2015-02-01

An investigation into the kinematic and kinetic predictions of two "inverted pendulum" (IP) models of gait was undertaken. The first model consisted of a single leg, with anthropometrically correct mass and moment of inertia, and a point mass at the hip representing the rest of the body. A second model incorporating the physiological extension of a head-arms-trunk (HAT) segment, held upright by an actuated hip moment, was developed for comparison. Simulations were performed, using both models, and quantitatively compared with empirical gait data. There was little difference between the two models' predictions of kinematics and ground reaction force (GRF). The models agreed well with empirical data through mid-stance (20-40% of the gait cycle) suggesting that IP models adequately simulate this phase (mean error less than one standard deviation). IP models are not cyclic, however, and cannot adequately simulate double support and step-to-step transition. This is because the forces under both legs augment each other during double support to increase the vertical GRF. The incorporation of an actuated hip joint was the most novel change and added a new dimension to the classic IP model. The hip moment curve produced was similar to those measured during experimental walking trials. As a result, it was interpreted that the primary role of the hip musculature in stance is to keep the HAT upright. Careful consideration of the differences between the models throws light on what the different terms within the GRF equation truly represent. Copyright © 2014 Elsevier B.V. All rights reserved.

Modeling hypertrophic IP3 transients in the cardiac myocyte.

PubMed

Cooling, Michael; Hunter, Peter; Crampin, Edmund J

2007-11-15

Cardiac hypertrophy is a known risk factor for heart disease, and at the cellular level is caused by a complex interaction of signal transduction pathways. The IP3-calcineurin pathway plays an important role in stimulating the transcription factor NFAT which binds to DNA cooperatively with other hypertrophic transcription factors. Using available kinetic data, we construct a mathematical model of the IP3 signal production system after stimulation by a hypertrophic alpha-adrenergic agonist (endothelin-1) in the mouse atrial cardiac myocyte. We use a global sensitivity analysis to identify key controlling parameters with respect to the resultant IP3 transient, including the phosphorylation of cell-membrane receptors, the ligand strength and binding kinetics to precoupled (with G(alpha)GDP) receptor, and the kinetics associated with precoupling the receptors. We show that the kinetics associated with the receptor system contribute to the behavior of the system to a great extent, with precoupled receptors driving the response to extracellular ligand. Finally, by reparameterizing for a second hypertrophic alpha-adrenergic agonist, angiotensin-II, we show that differences in key receptor kinetic and membrane density parameters are sufficient to explain different observed IP3 transients in essentially the same pathway.

Point-source helicity injection for ST plasma startup in Pegasus

NASA Astrophysics Data System (ADS)

Redd, A. J.; Battaglia, D. J.; Bongard, M. W.; Fonck, R. J.; Schlossberg, D. J.

2009-11-01

Plasma current guns are used as point-source DC helicity injectors for forming non-solenoidal tokamak plasmas in the Pegasus Toroidal Experiment. Discharges driven by this injection scheme have achieved Ip>= 100 kA using Iinj<= 4 kA. They form at the outboard midplane, transition to a tokamak-like equilibrium, and continue to grow inward as Ip increases due to helicity injection and outer- PF induction. The maximum Ip is determined by helicity balance (injection rate vs resistive dissipation) and a Taylor relaxation limit, in which Ip√ITF Iinj/w, where w is the radial thickness of the gun-driven edge. Preliminary experiments tentatively confirm these scalings with ITF, Iinj, and w, increasing confidence in this simple relaxation model. Adding solenoidal inductive drive during helicity injection can push Ip up to, but not beyond, the predicted relaxation limit, demonstrating that this is a hard performance limit. Present experiments are focused on increasing the injection voltage (i.e., helicity injection rate) and reducing w. Near-term goals are to further test scalings predicted by the simple relaxation model and to study in detail the observed bursty n=1 activity correlated with rapid increases in Ip.

Validation of modelled imaging plates sensitivity to 1-100 keV x-rays and spatial resolution characterisation for diagnostics for the "PETawatt Aquitaine Laser".

PubMed

Boutoux, G; Batani, D; Burgy, F; Ducret, J-E; Forestier-Colleoni, P; Hulin, S; Rabhi, N; Duval, A; Lecherbourg, L; Reverdin, C; Jakubowska, K; Szabo, C I; Bastiani-Ceccotti, S; Consoli, F; Curcio, A; De Angelis, R; Ingenito, F; Baggio, J; Raffestin, D

2016-04-01

Thanks to their high dynamic range and ability to withstand electromagnetic pulse, imaging plates (IPs) are commonly used as passive detectors in laser-plasma experiments. In the framework of the development of the diagnostics for the Petawatt Aquitaine Laser facility, we present an absolute calibration and spatial resolution study of five different available types of IP (namely, MS-SR-TR-MP-ND) performed by using laser-induced K-shell X-rays emitted by a solid silver target irradiated by the laser ECLIPSE at CEntre Lasers Intenses et Applications. In addition, IP sensitivity measurements were performed with a 160 kV X-ray generator at CEA DAM DIF, where the absolute response of IP SR and TR has been calibrated to X-rays in the energy range 8-75 keV with uncertainties of about 15%. Finally, the response functions have been modeled in Monte Carlo GEANT4 simulations in order to reproduce experimental data. Simulations enable extrapolation of the IP response functions to photon energies from 1 keV to 1 GeV, of interest, e.g., for laser-driven radiography.

Ajinomoto joins GO and NGO in promoting RH / nutrition in the Philippines.

PubMed

2000-01-01

The Integrated Project (IP) on Reproductive Health/Nutrition (RH/N) in Batangas Province in the Philippines was launched on December 2, 1999. This project is a new form of collaboration, joining government agencies, nongovernmental organizations, and corporate forces to promote a RH/N project in six municipalities in Batangas. The Ajinomoto Company, one of the largest food companies in Japan, decided to support the project because of its emphasis on training of trainers such as local leaders, community health workers, and volunteers, which is the key to self-sustainability. Another reason for support was that nutrition education is considered an integral part of the IP in the Philippines, which in some way is in line with the company's mission to contribute to the improvement of the people's quality of life. The IP on RH/N is designed to expand the successful IP model achieved in villages in the municipalities of Malvar and Balayan during the past 6 years, while reinforcing the capacities of these model areas to lead in transferring their lessons and experience with successful IP to four other municipalities in Batangas. Attention will also be given to promoting the use of integrated information, education, and communication materials for RH/N.

Validation of modelled imaging plates sensitivity to 1-100 keV x-rays and spatial resolution characterisation for diagnostics for the "PETawatt Aquitaine Laser"

NASA Astrophysics Data System (ADS)

Boutoux, G.; Batani, D.; Burgy, F.; Ducret, J.-E.; Forestier-Colleoni, P.; Hulin, S.; Rabhi, N.; Duval, A.; Lecherbourg, L.; Reverdin, C.; Jakubowska, K.; Szabo, C. I.; Bastiani-Ceccotti, S.; Consoli, F.; Curcio, A.; De Angelis, R.; Ingenito, F.; Baggio, J.; Raffestin, D.

2016-04-01

Thanks to their high dynamic range and ability to withstand electromagnetic pulse, imaging plates (IPs) are commonly used as passive detectors in laser-plasma experiments. In the framework of the development of the diagnostics for the Petawatt Aquitaine Laser facility, we present an absolute calibration and spatial resolution study of five different available types of IP (namely, MS-SR-TR-MP-ND) performed by using laser-induced K-shell X-rays emitted by a solid silver target irradiated by the laser ECLIPSE at CEntre Lasers Intenses et Applications. In addition, IP sensitivity measurements were performed with a 160 kV X-ray generator at CEA DAM DIF, where the absolute response of IP SR and TR has been calibrated to X-rays in the energy range 8-75 keV with uncertainties of about 15%. Finally, the response functions have been modeled in Monte Carlo GEANT4 simulations in order to reproduce experimental data. Simulations enable extrapolation of the IP response functions to photon energies from 1 keV to 1 GeV, of interest, e.g., for laser-driven radiography.

Validation of modelled imaging plates sensitivity to 1-100 keV x-rays and spatial resolution characterisation for diagnostics for the “PETawatt Aquitaine Laser”

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

Boutoux, G., E-mail: boutoux@celia.u-bordeaux1.fr; Batani, D.; Burgy, F.

2016-04-15

Thanks to their high dynamic range and ability to withstand electromagnetic pulse, imaging plates (IPs) are commonly used as passive detectors in laser-plasma experiments. In the framework of the development of the diagnostics for the Petawatt Aquitaine Laser facility, we present an absolute calibration and spatial resolution study of five different available types of IP (namely, MS-SR-TR-MP-ND) performed by using laser-induced K-shell X-rays emitted by a solid silver target irradiated by the laser ECLIPSE at CEntre Lasers Intenses et Applications. In addition, IP sensitivity measurements were performed with a 160 kV X-ray generator at CEA DAM DIF, where the absolutemore » response of IP SR and TR has been calibrated to X-rays in the energy range 8-75 keV with uncertainties of about 15%. Finally, the response functions have been modeled in Monte Carlo GEANT4 simulations in order to reproduce experimental data. Simulations enable extrapolation of the IP response functions to photon energies from 1 keV to 1 GeV, of interest, e.g., for laser-driven radiography.« less

Testing Brain Overgrowth and Synaptic Models of Autism Using NPC’s and Neurons from Patient-Derived IPS Cells

DTIC Science & Technology

2014-10-01

Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Autism and autism spectrum disorders (ASD) are complex neurodevelopmental ...1. INTRODUCTION: Autism and autism spectrum disorders (ASD) are complex neurodevelopmental diseases that affect about 1% of children in the...and neurons. 2. KEYWORDS: Autism spectrum disorder, ASD, neurodevelopmental disease, disease modeling, induced pluripotent stem cell, iPS

Simultaneously learning DNA motif along with its position and sequence rank preferences through expectation maximization algorithm.

PubMed

Zhang, ZhiZhuo; Chang, Cheng Wei; Hugo, Willy; Cheung, Edwin; Sung, Wing-Kin

2013-03-01

Although de novo motifs can be discovered through mining over-represented sequence patterns, this approach misses some real motifs and generates many false positives. To improve accuracy, one solution is to consider some additional binding features (i.e., position preference and sequence rank preference). This information is usually required from the user. This article presents a de novo motif discovery algorithm called SEME (sampling with expectation maximization for motif elicitation), which uses pure probabilistic mixture model to model the motif's binding features and uses expectation maximization (EM) algorithms to simultaneously learn the sequence motif, position, and sequence rank preferences without asking for any prior knowledge from the user. SEME is both efficient and accurate thanks to two important techniques: the variable motif length extension and importance sampling. Using 75 large-scale synthetic datasets, 32 metazoan compendium benchmark datasets, and 164 chromatin immunoprecipitation sequencing (ChIP-Seq) libraries, we demonstrated the superior performance of SEME over existing programs in finding transcription factor (TF) binding sites. SEME is further applied to a more difficult problem of finding the co-regulated TF (coTF) motifs in 15 ChIP-Seq libraries. It identified significantly more correct coTF motifs and, at the same time, predicted coTF motifs with better matching to the known motifs. Finally, we show that the learned position and sequence rank preferences of each coTF reveals potential interaction mechanisms between the primary TF and the coTF within these sites. Some of these findings were further validated by the ChIP-Seq experiments of the coTFs. The application is available online.

Improved Discovery of Molecular Interactions in Genome-Scale Data with Adaptive Model-Based Normalization

PubMed Central

Brown, Patrick O.

2013-01-01

Background High throughput molecular-interaction studies using immunoprecipitations (IP) or affinity purifications are powerful and widely used in biology research. One of many important applications of this method is to identify the set of RNAs that interact with a particular RNA-binding protein (RBP). Here, the unique statistical challenge presented is to delineate a specific set of RNAs that are enriched in one sample relative to another, typically a specific IP compared to a non-specific control to model background. The choice of normalization procedure critically impacts the number of RNAs that will be identified as interacting with an RBP at a given significance threshold – yet existing normalization methods make assumptions that are often fundamentally inaccurate when applied to IP enrichment data. Methods In this paper, we present a new normalization methodology that is specifically designed for identifying enriched RNA or DNA sequences in an IP. The normalization (called adaptive or AD normalization) uses a basic model of the IP experiment and is not a variant of mean, quantile, or other methodology previously proposed. The approach is evaluated statistically and tested with simulated and empirical data. Results and Conclusions The adaptive (AD) normalization method results in a greatly increased range in the number of enriched RNAs identified, fewer false positives, and overall better concordance with independent biological evidence, for the RBPs we analyzed, compared to median normalization. The approach is also applicable to the study of pairwise RNA, DNA and protein interactions such as the analysis of transcription factors via chromatin immunoprecipitation (ChIP) or any other experiments where samples from two conditions, one of which contains an enriched subset of the other, are studied. PMID:23349766

Stably Fluorescent Cell Line of Human Ovarian Epithelial Cancer Cells SK-OV-3ip-red.

PubMed

Konovalova, E V; Shulga, A A; Chumakov, S P; Khodarovich, Yu M; Woo, Eui-Jeon; Deev, S M

2017-11-01

Stable red fluorescing line of human ovarian epithelial cancer cells SK-OV-3ip-red was generated expressing gene coding for protein TurboFP635 (Katushka) fluorescing in the far-red spectrum region with excitation and emission peaks at 588 and 635 nm, respectively. Fluorescence of SK-OV-3ip-red line remained high during long-term cell culturing and after cryogenic freezing. The obtained cell line SK-OV-3ip-red can serve a basis for a model of a scattered tumor with numerous/extended metastases and used both for testing anticancer drugs inhibiting metastasis growth and for non-invasive monitoring of the growth dynamics with high precision.

An Impact Assessment Model for Distributed Adaptive Security Situation Assessment

DTIC Science & Technology

2005-01-01

the cargo manifest can be either a 56K modem-based TCP/IP connection (the oval labeled internet) or a 40K wireless modem connection ( cell phone ) that...via a UDP connection on the 40K wireless modem ( cell phone ). For each resource, either alternative may be used to achieve the same goal, but some...Manifests Comm-in Comp- power Comm- out JTF Internet (TCP-IP) Cell phone (TCP-IP) Internet (UDP) Cell phone (UDP) Manual Computer 4

Obesity prevention for Mexican American children: for whom is it most effective?

USDA-ARS?s Scientific Manuscript database

The objective of the current study was to determine which Mexican American children benefited most from an obesity prevention program. Data used were taken from a larger randomized clinical trial in which participants received either an intensive (IP) or a self-help (SH) program for preventing the ...

Bayesian reconstruction of transmission within outbreaks using genomic variants.

PubMed

De Maio, Nicola; Worby, Colin J; Wilson, Daniel J; Stoesser, Nicole

2018-04-01

Pathogen genome sequencing can reveal details of transmission histories and is a powerful tool in the fight against infectious disease. In particular, within-host pathogen genomic variants identified through heterozygous nucleotide base calls are a potential source of information to identify linked cases and infer direction and time of transmission. However, using such data effectively to model disease transmission presents a number of challenges, including differentiating genuine variants from those observed due to sequencing error, as well as the specification of a realistic model for within-host pathogen population dynamics. Here we propose a new Bayesian approach to transmission inference, BadTrIP (BAyesian epiDemiological TRansmission Inference from Polymorphisms), that explicitly models evolution of pathogen populations in an outbreak, transmission (including transmission bottlenecks), and sequencing error. BadTrIP enables the inference of host-to-host transmission from pathogen sequencing data and epidemiological data. By assuming that genomic variants are unlinked, our method does not require the computationally intensive and unreliable reconstruction of individual haplotypes. Using simulations we show that BadTrIP is robust in most scenarios and can accurately infer transmission events by efficiently combining information from genetic and epidemiological sources; thanks to its realistic model of pathogen evolution and the inclusion of epidemiological data, BadTrIP is also more accurate than existing approaches. BadTrIP is distributed as an open source package (https://bitbucket.org/nicofmay/badtrip) for the phylogenetic software BEAST2. We apply our method to reconstruct transmission history at the early stages of the 2014 Ebola outbreak, showcasing the power of within-host genomic variants to reconstruct transmission events.

An adenosine kinase inhibitor attenuates tactile allodynia in a rat model of diabetic neuropathic pain.

PubMed

Lynch, J J; Jarvis, M F; Kowaluk, E A

1999-01-08

The present study was conducted to characterize the development of tactile allodynia in the streptozotocin-induced rat model of diabetes, and to evaluate the antinociceptive effects of systemically administered morphine and the adenosine kinase inhibitor, 5'-deoxy-5-iodotubercidin (5'd-5IT) in this model. Rats were injected with 75 mg/kg streptozotocin (i.p.), and blood glucose levels were determined 3-4 weeks later. Diabetic (blood glucose levels > or = 250 mg/dl) and vehicle-injected rats were examined weekly for the development of tactile allodynia by measuring the threshold for hind paw withdrawal using von Frey hairs. Withdrawal thresholds were reduced to 6.8+/-0.6 g (mean+/-S.E.M.) in approximately one-third of streptozotocin-treated rats 7 weeks after streptozotocin treatment as compared to control thresholds (13.2+/-0.1 g), and this allodynia persisted for at least an additional 7 weeks. In additional experiments, morphine sulfate (5-21 micromol/kg, i.p.) produced dose-dependent antinociceptive effects on tactile allodynia for up to 2 h post-dosing. The adenosine kinase inhibitor, 5'd-5IT (2.5 and 5 micromol/kg, i.p.) also dose-dependently attenuated tactile allodynia. Pretreatment with the opioid receptor antagonist, naloxone (27 micromol/kg, i.p.) or the non-selective adenosine receptor antagonist, theophylline (111 micromol/kg, i.p.) significantly diminished the anti-allodynic effects of morphine and 5'd-5IT, respectively. The present study demonstrates that the potent and selective adenosine kinase inhibitor, 5'd-5IT, is equally effective as morphine in blocking tactile allodynia in this model.

Employee and family assistance video counseling program: a post launch retrospective comparison with in-person counseling outcomes.

PubMed

Veder, Barbara; Pope, Stan; Mani, Michèle; Beaudoin, Kelly; Ritchie, Janice

2014-01-01

Access to technologically mediated information and services under the umbrella of mental and physical health has become increasingly available to clients via Internet modalities, according to a recent study. In May 2010, video counseling was added to the counseling services offered through the Employee and Family Assistance Program at Shepell·fgi as a pilot project with a full operational launch in September 2011. The objective of this study was to conduct a retrospective post launch examination of the video counseling service through an analysis of the reported clinical outcomes of video and in-person counseling modalities. A chronological sample of 68 video counseling (VC) cases and 68 in-person (IP) cases were collected from a pool of client clinical files closed in 2012. To minimize the variables impacting the study and maintain as much clinical continuity as possible, the IP and the VC clients must have attended clinical sessions with any one of six counselors who provided both the VC and the IP services. The study compared the two counseling modalities along the following data points (see glossary of terms): (1) client demographic profiles (eg, age, gender, whether the sessions involved individuals or conjoint sessions with couples or families, etc), (2) presenting issue, (3) average session hours, (4) client rating of session helpfulness, (5) rates of goal completion, (6) client withdrawal rates, (7) no show and late cancellation rates, and (8) pre/post client self-assessment. Specific to VC, we examined client geographic location. Data analysis demonstrates that the VC and the IP showed a similar representation of presenting issues with nearly identical outcomes for client ratings of session helpfulness, rates of goal completion, pre/post client self-assessment, average session duration, and client geographic location. There were no statistically significant differences in the rates of withdrawal from counseling, no shows, and late cancellations between the VC and the IP counseling. The statistical analysis of the data was done on SPSS statistical software using 2-sample and pairwise comparison t tests at a 95% level of significance. Based on the study, VC and IP show similar outcomes in terms of client rating of session and goal attainment.

Testing Brain Overgrowth and Synaptic Models of Autism Using NPCs and Neurons From Patient Derived iPS Cells

DTIC Science & Technology

2015-12-01

AWARD NUMBER: W81XWH-13-1-0414 TITLE: Testing Brain Overgrowth and Synaptic Models of Autism Using NPCs and Neurons From Patient-Derived iPS...3. DATES COVERED 15 Sep 2013 - 14 Sep 2015 4. TITLE AND SUBTITLE Testing Brain Overgrowth and Synaptic Models of Autism Using NPCs and Neurons From...AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Autism and autism spectrum disorders (ASD

Coupled Cluster Studies of Ionization Potentials and Electron Affinities of Single-Walled Carbon Nanotubes

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

Peng, Bo; Govind, Niranjan; Aprà, Edoardo

In this paper we apply equation-of-motion coupled cluster (EOMCC) methods in studies of vertical ionization potentials (IP) and electron affinities (EA) for sin- gled walled carbon nanotubes. EOMCC formulations for ionization potentials and electron affinities employing excitation manifolds spanned by single and double ex- citations (IP/EA-EOMCCSD) are used to study IPs and EAs of nanotubes as a function of nanotube length. Several armchair nanotubes corresponding to C20nH20 models with n = 2 - 6 have been used in benchmark calculations. In agreement with previous studies, we demonstrate that the electronegativity of C20nH20 systems remains, to a large extent, independent ofmore » nanotube length. We also compare IP/EA- EOMCCSD results with those obtained with the coupled cluster models with single and double excitations corrected by perturbative triples, CCSD(T), and density func- tional theory (DFT) using global and range-separated hybrid exchange-correlation functionals.« less

Traffic-engineering-aware shortest-path routing and its application in IP-over-WDM networks [Invited

NASA Astrophysics Data System (ADS)

Lee, Youngseok; Mukherjee, Biswanath

2004-03-01

Single shortest-path routing is known to perform poorly for Internet traffic engineering (TE) where the typical optimization objective is to minimize the maximum link load. Splitting traffic uniformly over equal-cost multiple shortest paths in open shortest path first and intermediate system-intermediate system protocols does not always minimize the maximum link load when multiple paths are not carefully selected for the global traffic demand matrix. However, a TE-aware shortest path among all the equal-cost multiple shortest paths between each ingress-egress pair can be selected such that the maximum link load is significantly reduced. IP routers can use the globally optimal TE-aware shortest path without any change to existing routing protocols and without any serious configuration overhead. While calculating TE-aware shortest paths, the destination-based forwarding constraint at a node should be satisfied, because an IP router will forward a packet to the next hop toward the destination by looking up the destination prefix. We present a mathematical problem formulation for finding a set of TE-aware shortest paths for the given network as an integer linear program, and we propose a simple heuristic for solving large instances of the problem. Then we explore the usage of our proposed algorithm for the integrated TE method in IP-over-WDM networks. The proposed algorithm is evaluated through simulations in IP networks as well as in IP-over-WDM networks.

Effects of the Voice over Internet Protocol on Perturbation Analysis of Normal and Pathological Phonation

PubMed Central

Zhu, Yanmei; Witt, Rachel E.; MacCallum, Julia K.; Jiang, Jack J.

2010-01-01

Objective In this study, a Voice over Internet Protocol (VoIP) communication based on G.729 protocol was simulated to determine the effects of this system on acoustic perturbation parameters of normal and pathological voice signals. Patients and Methods: Fifty recordings of normal voice and 48 recordings of pathological voice affected by laryngeal paralysis were transmitted through a VoIP communication system. The acoustic analysis programs of CSpeech and MDVP were used to determine the percent jitter and percent shimmer from the voice samples before and after VoIP transmission. The effects of three frequently used audio compression protocols (MP3, WMA, and FLAC) on the perturbation measures were also studied. Results It was found that VoIP transmission disrupts the waveform and increases the percent jitter and percent shimmer of voice samples. However, after VoIP transmission, significant discrimination between normal and pathological voices affected by laryngeal paralysis was still possible. It was found that the lossless compression method FLAC does not exert any influence on the perturbation measures. The lossy compression methods MP3 and WMA increase percent jitter and percent shimmer values. Conclusion This study validates the feasibility of these transmission and compression protocols in developing remote voice signal data collection and assessment systems. PMID:20588051

Photometric studies of δ Scuti stars. I. IP Virginis

USGS Publications Warehouse

Joner, Michael D.; Hintz, Eric G.; Collier, Matthew W.

1998-01-01

We report 15 new times of maximum light for the δ Scuti star IP Virginis (formerly known as SA 106‐1024). An analysis of all times of maximum light indicates that IP Vir has been decreasing in period at a constant rate of − days day−1. Evidence is also presented that IP Vir is a double‐mode variable with a period ratio of . This period ratio predicts a [Fe/H] value of −0.3. From photometric (uvbyβ) observations, we find a foreground reddening of .008 mag and a metallicity of [Fe/H] = +0.05. It is shown that [Fe/H] = −0.3 is most likely the correct value. Intrinsic ‐ and c1‐values, plotted in a model atmosphere grid, indicate a mean effective temperature, K, and a mean surface gravity, . All of these physical parameters support Landolt's initial conclusion that IP Vir is an ordinary δ Sct star.

MHC-matched induced pluripotent stem cells can attenuate cellular and humoral immune responses but are still susceptible to innate immunity in pigs.

PubMed

Mizukami, Yoshihisa; Abe, Tomoyuki; Shibata, Hiroaki; Makimura, Yukitoshi; Fujishiro, Shuh-hei; Yanase, Kimihide; Hishikawa, Shuji; Kobayashi, Eiji; Hanazono, Yutaka

2014-01-01

Recent studies have revealed negligible immunogenicity of induced pluripotent stem (iPS) cells in syngeneic mice and in autologous monkeys. Therefore, human iPS cells would not elicit immune responses in the autologous setting. However, given that human leukocyte antigen (HLA)-matched allogeneic iPS cells would likely be used for medical applications, a more faithful model system is needed to reflect HLA-matched allogeneic settings. Here we examined whether iPS cells induce immune responses in the swine leukocyte antigen (SLA)-matched setting. iPS cells were generated from the SLA-defined C1 strain of Clawn miniature swine, which were confirmed to develop teratomas in mice, and transplanted into the testes (n = 4) and ovary (n = 1) of C1 pigs. No teratomas were found in pigs on 47 to 125 days after transplantation. A Mixed lymphocyte reaction revealed that T-cell responses to the transplanted MHC-matched (C1) iPS cells were significantly lower compared to allogeneic cells. The humoral immune responses were also attenuated in the C1-to-C1 setting. More importantly, even MHC-matched iPS cells were susceptible to innate immunity, NK cells and serum complement. iPS cells lacked the expression of SLA class I and sialic acids. The in vitro cytotoxic assay showed that C1 iPS cells were targeted by NK cells and serum complement of C1. In vivo, the C1 iPS cells developed larger teratomas in NK-deficient NOG (T-B-NK-) mice (n = 10) than in NK-competent NOD/SCID (T-B-NK+) mice (n = 8) (p<0.01). In addition, C1 iPS cell failed to form teratomas after incubation with the porcine complement-active serum. Taken together, MHC-matched iPS cells can attenuate cellular and humoral immune responses, but still susceptible to innate immunity in pigs.

A geometric analysis of hallux valgus: correlation with clinical assessment of severity

PubMed Central

Piqué-Vidal, Carlos; Vila, Joan

2009-01-01

Background Application of plane geometry to the study of bunion deformity may represent an interesting and novel approach in the research field of hallux valgus. For the purpose of contributing to development of a different perspective in the assessment of hallux valgus, this study was conducted with three objectives: a) to determine the position on the intersection point of the perpendicular bisectors of the longitudinal axes of the first metatarsal and proximal phalanx (IP), b) to correlate the location of this point with hallux valgus deformity according to angular measurements and according to visual assessment of the severity carried out by three independent observers, and c) to assess whether this IP correlated with the radius of the first metatarsophalangeal arc circumference. Methods Measurements evaluated were intermetatarsal angle (IMA), hallux valgus angle (HVA), and proximal phalangeal articular angle (PPAA). The Autocad® program computed the location of the IP inside or outside of the foot. Three independent observers rated the severity of hallux valgus in photographs using a 100-mm visual analogue scale (VAS). Results Measurements of all angles except PPAA showed significantly lower values when the IP was located out of the foot more distantly and vice versa, significantly higher values for severe deformities in which the IP was found inside the foot (p < 0.001). The IP correlated significantly with VAS scores and with the length of the radius of the circle that included the first metatarsophalangeal arc circumference (p < 0.001) Conclusion The IP is a useful indicator of hallux valgus deformity because correlated significantly with IMA and HVA measurements, VAS scores obtained by visual inspection of the degree of deformity, and location of the center of the first metatarsophalangeal arc circumference. PMID:19442286

In vivo programming of tumor antigen-specific T lymphocytes from pluripotent stem cells to promote cancer immunosurveillance.

PubMed

Lei, Fengyang; Zhao, Baohua; Haque, Rizwanul; Xiong, Xiaofang; Budgeon, Lynn; Christensen, Neil D; Wu, Yuzhang; Song, Jianxun

2011-07-15

Adoptive T-cell immunotherapy has garnered wide attention, but its effective use is limited by the need of multiple ex vivo manipulations and infusions that are complex and expensive. In this study, we show how highly reactive antigen (Ag)-specific CTLs can be generated from induced pluripotent stem (iPS) cells to provide an unlimited source of functional CTLs for adoptive immunotherapy. iPS cell-derived T cells can offer the advantages of avoiding possible immune rejection and circumventing ethical and practical issues associated with other stem cell types. iPS cells can be differentiated into progenitor T cells in vitro by stimulation with the Notch ligand Delta-like 1 (DL1) overexpressed on bone marrow stromal cells, with complete maturation occurring upon adoptive transfer into Rag1-deficient mice. Here, we report that these iPS cells can be differentiated in vivo into functional CTLs after overexpression of MHC I-restricted Ag-specific T-cell receptors (TCR). In this study, we generated murine iPS cells genetically modified with ovalbumin (OVA)-specific and MHC-I restricted TCR (OT-I) by retrovirus-mediated transduction. After their adoptive transfer into recipient mice, the majority of OT-I/iPS cells underwent differentiation into CD8+ CTLs. TCR-transduced iPS cells developed in vivo responded in vitro to peptide stimulation by secreting interleukin 2 and IFN-γ. Most importantly, adoptive transfer of TCR-transduced iPS cells triggered infiltration of OVA-reactive CTLs into tumor tissues and protected animals from tumor challenge. Taken together, our findings offer proof of concept for a potentially more efficient approach to generate Ag-specific T lymphocytes for adoptive immunotherapy. ©2011 AACR.

Microdistribution of fluorescently-labeled monoclonal antibody in a peritoneal dissemination model of ovarian cancer

NASA Astrophysics Data System (ADS)

Kosaka, Nobuyuki; Ogawa, Mikako; Paik, David S.; Paik, Chang H.; Choyke, Peter L.; Kobayashi, Hisataka

2010-02-01

The microdistribution of therapeutic monoclonal antibodies within a tumor is important for determining clinical response. Nonuniform microdistribution predicts therapy failure. Herein, we developed a semiquantitative method for measuring microdistribution of an antibody within a tumor using in situ fluorescence microscopy and sought to modulate the microdistribution by altering the route and timing of antibody dosing. The microdistribution of a fluorescently-labeled antibody, trastuzumab (50-μg and 150-μg intraperitoneal injection (i.p.), and 100-μg intravenous injection (i.v.)) was evaluated in a peritoneal dissemination mouse model of ovarian cancer. In addition, we evaluated the microdistribution of concurrently-injected (30-μg i.p. and 100-μg i.v.) or serial (two doses of 30-μg i.p.) trastuzumab using in situ multicolor fluorescence microscopy. After the administration of 50-μg i.p. and 100-μg i.v. trastuzumab fluorescence imaging showed no significant difference in the central to peripheral signal ratio (C/P ratio) and demonstrated a peripheral-dominant accumulation, whereas administration of 150-μg i.p. trastuzumab showed relatively uniform, central dominant accumulation. With concurrent-i.p.-i.v. injections trastuzumab showed slightly higher C/P ratio than concurrently-injected i.p. trastuzumab. Moreover, in the serial injection study, the second injection of trastuzumab distributed more centrally than the first injection, while no difference was observed in the control group. Our results suggest that injection routes do not affect the microdistribution pattern of antibody in small peritoneal disseminations. However, increasing the dose results in a more uniform antibody distribution within peritoneal nodules. Furthermore, the serial i.p. injection of antibody can modify the microdistribution within tumor nodules. This work has implications for the optimal delivery of antibody based cancer therapies.

Mobility management techniques for the next-generation wireless networks

NASA Astrophysics Data System (ADS)

Sun, Junzhao; Howie, Douglas P.; Sauvola, Jaakko J.

2001-10-01

The tremendous demands from social market are pushing the booming development of mobile communications faster than ever before, leading to plenty of new advanced techniques emerging. With the converging of mobile and wireless communications with Internet services, the boundary between mobile personal telecommunications and wireless computer networks is disappearing. Wireless networks of the next generation need the support of all the advances on new architectures, standards, and protocols. Mobility management is an important issue in the area of mobile communications, which can be best solved at the network layer. One of the key features of the next generation wireless networks is all-IP infrastructure. This paper discusses the mobility management schemes for the next generation mobile networks through extending IP's functions with mobility support. A global hierarchical framework model for the mobility management of wireless networks is presented, in which the mobility management is divided into two complementary tasks: macro mobility and micro mobility. As the macro mobility solution, a basic principle of Mobile IP is introduced, together with the optimal schemes and the advances in IPv6. The disadvantages of the Mobile IP on solving the micro mobility problem are analyzed, on the basis of which three main proposals are discussed as the micro mobility solutions for mobile communications, including Hierarchical Mobile IP (HMIP), Cellular IP, and Handoff-Aware Wireless Access Internet Infrastructure (HAWAII). A unified model is also described in which the different micro mobility solutions can coexist simultaneously in mobile networks.

Inflammation and Atrophy Precede Prostate Neoplasia in PhIP Induced Rat Model

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

Borowsky, A D; Dingley, K; Ubick, E

2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) has been implicated as a major mutagenic heterocyclic amine in the human diet and is carcinogenic in the rat prostate. In order to validate PhIP induced rat prostate neoplasia as a model of human prostate cancer progression, we sought to study the earliest histologic and morphologic changes in the prostate and to follow the progressive changes over time. We fed 67 male Fischer F344 5 week old rats with PhIP (400 PPM) or control diets for 20 weeks, and then sacrificed animals for histomorphologic examination at age 25 weeks, 45 weeks, and 65 weeks. Animals treated with PhIPmore » showed significantly more inflammation (P=.002 (25wk), >.001(45wk), .016(65wk)) and atrophy (P=.003(25wk), >.001(45wk), .006 (65wk)) in their prostate glands relative to controls. Prostatic intraepithelial neoplasia (PIN) occurred only in PhIP treated rats. PIN lesions arose in areas of glandular atrophy, most often in the ventral prostate. Atypical cells in areas of atrophy show loss of glutathione S-transferase pi immunostaining preceding development of PIN. None of the animals in this study developed invasive carcinomas differing from previous reports. Overall, these findings suggest that the pathogenesis of prostatic neoplasia in the PhIP treated rat prostate proceeds from inflammation to post-inflammatory proliferative atrophy to PIN.« less

A novel statistical method for quantitative comparison of multiple ChIP-seq datasets.

PubMed

Chen, Li; Wang, Chi; Qin, Zhaohui S; Wu, Hao

2015-06-15

ChIP-seq is a powerful technology to measure the protein binding or histone modification strength in the whole genome scale. Although there are a number of methods available for single ChIP-seq data analysis (e.g. 'peak detection'), rigorous statistical method for quantitative comparison of multiple ChIP-seq datasets with the considerations of data from control experiment, signal to noise ratios, biological variations and multiple-factor experimental designs is under-developed. In this work, we develop a statistical method to perform quantitative comparison of multiple ChIP-seq datasets and detect genomic regions showing differential protein binding or histone modification. We first detect peaks from all datasets and then union them to form a single set of candidate regions. The read counts from IP experiment at the candidate regions are assumed to follow Poisson distribution. The underlying Poisson rates are modeled as an experiment-specific function of artifacts and biological signals. We then obtain the estimated biological signals and compare them through the hypothesis testing procedure in a linear model framework. Simulations and real data analyses demonstrate that the proposed method provides more accurate and robust results compared with existing ones. An R software package ChIPComp is freely available at http://web1.sph.emory.edu/users/hwu30/software/ChIPComp.html. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Ureaplasma parvum causes hyperammonemia in a pharmacologically immunocompromised murine model.

PubMed

Wang, X; Greenwood-Quaintance, K E; Karau, M J; Block, D R; Mandrekar, J N; Cunningham, S A; Mallea, J M; Patel, R

2017-03-01

A relationship between hyperammonemia and Ureaplasma infection has been shown in lung transplant recipients. We have demonstrated that Ureaplasma urealyticum causes hyperammonemia in a novel immunocompromised murine model. Herein, we determined whether Ureaplasma parvum can do the same. Male C3H mice were given mycophenolate mofetil, tacrolimus, and prednisone for 7 days, and then challenged with U. parvum intratracheally (IT) and/or intraperitoneally (IP), while continuing immunosuppression over 6 days. Plasma ammonia concentrations were determined and compared using Wilcoxon rank-sum tests. Plasma ammonia concentrations of immunosuppressed mice challenged IT/IP with spent broth (median, 188 μmol/L; range, 102-340 μmol/L) were similar to those of normal (median, 226 μmol/L; range, 154-284 μmol/L, p > 0.05), uninfected immunosuppressed (median, 231 μmol/L; range, 122-340 μmol/L, p > 0.05), and U. parvum IT/IP challenged immunocompetent (median, 226 μmol/L; range, 130-330 μmol/L, p > 0.05) mice. Immunosuppressed mice challenged with U. parvum IT/IP (median 343 μmol/L; range 136-1,000 μmol/L) or IP (median 307 μmol/L; range 132-692 μmol/L) had higher plasma ammonia concentrations than those challenged IT/IP with spent broth (p < 0.001). U. parvum can cause hyperammonemia in pharmacologically immunocompromised mice.

The Expanding Marketplace for Applied Geophysics

NASA Astrophysics Data System (ADS)

Carlson, N.; Sirles, P.

2012-12-01

While the image of geophysics for the proverbial "layman" often seems limited to volcanoes and earthquakes, and to the geoscientist this image enlarges to include oil or minerals exploration and whole earth studies, there has been a steady increase in the application of geophysics into the realm of "daily life", such as real estate deals, highway infrastructure, and flood protection. This expansion of applications can be attributed to the improved economics from advances in equipment and interpretation. Traditional geophysical methods that at one time often only fit within the budgets of oil, gas, and minerals exploration programs can now be economically applied to much smaller scale needs like contaminant mapping, landfill delineation, and levee investigations. A real-world, economic example of this expanding marketplace is our company, which began very small and was aimed almost exclusively at the minerals exploration market. Most of our growth has been in the last 10 years, when we have expanded to five offices and a staff with almost 40 geoscientist degrees (21 in geophysics); much of this growth has been in the non-oil, non-minerals arenas. While much of our work still includes minerals exploration, other projects this year include wind-farm foundation studies, cavity detection above underground nuclear tests, landfill studies, acid mine drainage problems, and leaks in evaporation ponds. A methodology example of this expanding market is the induced polarization (IP) survey, once primarily used for minerals exploration, particularly large porphyry copper deposits, but now efficient enough to also use in environmental studies. The IP method has been particularly useful in delineating and characterizing old, poorly documented landfills, and recent research suggests it may also be useful in monitoring the accelerated biodegradation processes used in some cases to rehabilitate the sites. Compared to temperature monitoring systems, IP may be more useful in providing a better image of the subsurface to locate areas that are not being properly decomposed due to poor fluid flow or inefficient air circulation.Raw IP data in traditional pseudosection format, prior to modeling, showing the change in IP effects after four years of accelerated biodegradation of an old, buried, municipal solid waste landfill. Posted values are chargeability in milliseconds.

Interplanetary scintillation at large elongation angles: Response to solar wind density structure

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

Erskine, F.T.; Cronyn, W.M.; Shawhan, S.D.

1978-09-01

Synoptic interplanetary scintillation (IPS) index measurements were taken at 34.3 MHz during May-December 1974 using the University of Iowa Coca Cross radiotelescope on a 'grid' of 150 selected radio sources covering solar elongation angles up to 180/sup 0/. Over 80 of these sources displayed definite IPS. The solar elongation dependence of the 34.3-MHz IPS index is consistent with the elongation angle dependence measured at higher frequencies. Large enhancements (factors of> or approx. =2) of the IPS index are found to coincide with the solar wind (proton density increases greater than 10 cm/sup -3/ as measured by Imp 7 and 8more » for nearly all observed IPS sources throughout the sky. These 'all-sky' IPS enhancements appear to be caused by incresed contributions to the scintillation power by turbulent plasma in regions close to the earth (< or approx. =0.3AU) in all directions. Correlation analysis confirms the IPS response to solar wind density and indicates that the events are due primarily to the corotating solar wind turbulent plasma structures which dominated the interplanetary medium during 1974. The expected IPS space-time signature for a simple model of an approaching corotating turbulent structure is not apparent in our observations. In some cases, the enhancement variatons can be attributed to structural differences in the solar wind density turbulence in and out of the ecliptic.« less

Selection of intracellular calcium patterns in a model with clustered Ca2+ release channels

NASA Astrophysics Data System (ADS)

Shuai, J. W.; Jung, P.

2003-03-01

A two-dimensional model is proposed for intracellular Ca2+ waves, which incorporates both the discrete nature of Ca2+ release sites in the endoplasmic reticulum membrane and the stochastic dynamics of the clustered inositol 1,4,5-triphosphate (IP3) receptors. Depending on the Ca2+ diffusion coefficient and concentration of IP3, various spontaneous Ca2+ patterns, such as calcium puffs, local waves, abortive waves, global oscillation, and tide waves, can be observed. We further investigate the speed of the global waves as a function of the IP3 concentration and the Ca2+ diffusion coefficient and under what conditions the spatially averaged Ca2+ response can be described by a simple set of ordinary differential equations.

The quantitative transperitoneal absorption of a fat emulsion: implications for intraperitoneal nutrition.

PubMed

Klein, M D; Coran, A G; Drongowski, R A; Wesley, J R

1983-12-01

Intraperitoneal (IP) administration of nutrients would be an attractive alternative to intravenous nutrition since it eliminates intravascular complications. If glucose alone were used as the nonprotein calorie source, associated fluid shifts might not be well tolerated by the patient. A fat emulsion does not have osmotic properties and thus might be incorporated into a program of IP nutrition as a calorie source. Transperitoneal absorption of a commercial fat emulsion (Liposyn 10%, Abbott Laboratories, N Chicago, IL) was studied in 12 beagle puppies divided into two groups. One group received 2.5 gm/kg of fat and the other group received a similar volume of 3.5% crystalline amino acids and 5% glucose in one IP dose. In the first group, the serum triglyceride (TG) increased three fold from 61 +/- 25 mg% to 185 +/- 61 mg% at 15 minutes and then decreased slowly while remaining significantly elevated (p less than 0.05) at 4 hours. 1.94 +/- 0.20 gm/kg of TG were absorbed from the peritoneal cavity over 4 hours. Concommitant IP administration of amino acids and glucose did not affect that absorption. Radiolabeled amino acids and glucose instilled IP were demonstrated in the blood immediately after administration and their absorption was not affected by the presence of a fat emulsion. Plasma free fatty acids showed a small increase at 4 hours (from 0.32 +/- 0.09 mEq/L to 0.59 +/- 0.22 mEq/L). Animals receiving no IP fat showed no change in serum TG. Serum glucose rose in both groups and serum cholesterol showed no changes in either group. Peritoneal fluid accumulation 4 hours after IP fat administration was minimal at 12.7 +/- 6.4 mL/kg. This study shows that a fat emulsion can be quantitatively absorbed from the peritoneal cavity over four hours and that IP nutrition may be feasible.

Using lifestyle factors to identify individuals at higher risk of inflammatory polyarthritis (results from the European Prospective Investigation of Cancer-Norfolk and the Norfolk Arthritis Register—the EPIC-2-NOAR Study)

PubMed Central

Lahiri, Manjari; Luben, Robert N; Morgan, Catharine; Bunn, Diane K; Marshall, Tarnya; Lunt, Mark; Verstappen, Suzanne M M; Symmons, Deborah P M; Khaw, Kay-Tee; Wareham, Nick; Bruce, Ian N

2014-01-01

Objectives To investigate the association of lifestyle factors with risk of inflammatory polyarthritis (IP) and rheumatoid arthritis (RA). Methods The European Prospective Investigation of Cancer, Norfolk, UK (EPIC-Norfolk) gathered lifestyle data from participants aged 40–79 years from 1993 to 1997. Individuals who subsequently developed IP were identified by linkage with the Norfolk Arthritis Register. A Cox proportional hazard model was developed, and a score assigned to each risk factor to calculate the odds of developing IP. Results 25 455 EPIC participants were followed for a median (IQR) of 14.2 (12.9, 15.3) years; 184 developed incident IP (138 cumulatively fulfilled criteria for RA; 107 were seropositive). Pack-years of smoking were associated with increased risk of IP and RA in men (HR 1.21 (95% CI 1.08 to 1.37) per 10-pack-years) and seropositive IP (HR 1.24 (95% CI 1.10 to 1.41)) for all. Diabetes mellitus was associated with increased risk of IP (HR 2.54 (95% CI 1.26 to 5.09)), while alcohol (HR 0.86 (95% CI 0.74 to 0.99) per unit/day) and higher social class (HR 0.36 (95% CI 0.15 to 0.89) for professionals vs manual workers) were associated with reduced risk. Body mass index was associated with seronegative IP (HR 2.75 (95% CI 1.39 to 5.46) for obese vs normal-weight participants). In women, parity (HR 2.81 (95% CI 1.37 to 5.76) for ≥2 vs no children) was associated with increased risk, and breast feeding (HR 0.66 (95% CI 0.46 to 0.94) for every 52 weeks of breast feeding) was inversely associated with risk. Risk factors from the model were used to generate a ‘risk score’. A total of 1159 (8.4%) women had scores reflecting a >3-fold increased risk of IP over those with a score of 0. Conclusions Several easily ascertained clinical and lifestyle factors can be used to stratify populations for risk of IP. PMID:23505230

Medical homes versus individual practice in primary care: impact on health care expenditures.

PubMed

Perelman, Julian; Roch, Isabelle; Heymans, Isabelle; Moureaux, Catherine; Lagasse, Raphael; Annemans, Lieven; Closon, Marie-Christine

2013-08-01

The medical home (MH) model has prompted increasing attention given its potential to improve quality of care while reducing health expenditures. We compare overall and specific health care expenditures in Belgium, from the third-party payer perspective (compulsory social insurance), between patients treated at individual practices (IP) and at MHs. We compare the sociodemographic profile of MH and IP users. This is a retrospective study using public insurance claims data. Generalized linear models estimate the impact on health expenditures of being treated at a MH versus IP, controlling for individual, and area-based sociodemographic characteristics. The choice of primary care setting is modeled using logistic regressions. A random sample of 43,678 persons followed during the year 2004. Third-party payer expenditures for primary care, secondary care consultations, pharmaceuticals, laboratory tests, acute and long-term inpatient care. Overall third-party payer expenditures do not differ significantly between MH and IP users (€+27). Third-party payer primary care expenditures are higher for MH than for IP users (€+129), but this difference is offset by lower expenditures for secondary care consultations (€-11), drugs (€-40), laboratory tests (€-5) and acute and long-term inpatient care (€-53). MHs attract younger and more underprivileged populations. MHs induce a shift in expenditures from secondary care, drugs, and laboratory tests to primary care, while treating a less economically favored population. Combined with positive results regarding quality, MH structures are a promising way to tackle the challenges of primary care.

Generation and characterization of induced pluripotent stem cells from guinea pig fetal fibroblasts.

PubMed

Wu, Yuehong; Li, Ouyang; He, Chengwen; Li, Yong; Li, Min; Liu, Xiaoming Liu; Wang, Yujiong; He, Yulong

2017-06-01

Induced pluripotent stem cells (iPS) represent an important tool to develop disease‑modeling assays, drug testing assays and cell‑based replacement therapies. The application of iPS in these fields requires the development of suitable animal models. Of the suitable species, guinea pigs are particularly important and offer significant advantages. Successful iPS generation has been accomplished in a number of species; however, it has not been reported in the guinea pig. The present study successfully generated iPS from guinea pigs (giPS) using single polycistronic virus transduction with mouse octamer‑binding transcription factor 4 (Oct4), sex determining region Y‑box 2 (Sox2), Kruppel‑like factor 4 and c‑Myc. The giPS cell lines were cultured in media containing leukemia inhibitory factor and guinea pig fibroblast cells were used as feeder cells. These cultures were expanded under feeder‑free culture conditions using ESGRO Complete Plus Clonal Grade medium containing 15% fetal bovine serum on gelatin‑coated dishes. The resultant cells had a normal karyotype, exhibited alkaline phosphatase activity and expressed the pluripotency markers Oct4, Sox2 and Nanog. The cells differentiated in vivo to form teratomas that contained all three germ layers of the tissue cells. The generation of giPS may facilitate future studies investigating the mechanisms underlying innate immunity, particularly for tuberculosis. These experiments provide proof of principle that iPS technology may be adapted to use the guinea pig as a model of human diseases.

Effect of caffeic acid phenethyl ester on oxidant and anti-oxidant status of liver and serum in a rat model with acute methanol intoxication.

PubMed

Yazgan, Ü C; Elbey, B; Kuş, S; Baykal, B; Keskin, I; Yılmaz, A; Şahin, A

2017-05-01

Methanol toxicity is one of the major public health problems because it can cause severe morbidity and mortality. Methanol intoxication causes changes in the balance between the production of free radicals and antioxidant capacity. We aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on the total oxidant status, total antioxidant status (TAS), and oxidative stress index (OSI) parameters of the liver and the serum in a rat model of acute methanol intoxication. Rats were treated with intraperitoneal (i.p.) Methotrexate (MTX) for 7 days. On the 8th day, i.p. Methanol was administered in the methanol, ethanol and CAPE groups. Four hours after methanol treatment, ethanol was injected i.p. in the ethanol group; CAPE (i.p.) in the CAPE group; serum physiologic i.p. in other groups. After 8 hours, rats were killed and the serum and the liver samples were obtained for biochemical analyses. The OSI value was significantly higher in the methanol group compared to the ethanol and CAPE groups. Serum TAS levels of the methanol group were significantly different compared to the control group, but not compared to the MTX group. The amelioration of oxidative stress was greater in the CAPE group compared to the ethanol group but was not statistically significant. This study demonstrates that CAPE treatment ameliorates oxidative stress in the serum and liver in a rat model of acute methanol intoxication.

Generation and characterization of induced pluripotent stem cells from guinea pig fetal fibroblasts

PubMed Central

Wu, Yuehong; Li, Ouyang; He, Chengwen; Li, Yong; Li, Min; Liu, Xiaoming; Wang, Yujiong; He, Yulong

2017-01-01

Induced pluripotent stem cells (iPS) represent an important tool to develop disease-modeling assays, drug testing assays and cell-based replacement therapies. The application of iPS in these fields requires the development of suitable animal models. Of the suitable species, guinea pigs are particularly important and offer significant advantages. Successful iPS generation has been accomplished in a number of species; however, it has not been reported in the guinea pig. The present study successfully generated iPS from guinea pigs (giPS) using single polycistronic virus transduction with mouse octamer-binding transcription factor 4 (Oct4), sex determining region Y-box 2 (Sox2), Kruppel-like factor 4 and c-Myc. The giPS cell lines were cultured in media containing leukemia inhibitory factor and guinea pig fibroblast cells were used as feeder cells. These cultures were expanded under feeder-free culture conditions using ESGRO Complete Plus Clonal Grade medium containing 15% fetal bovine serum on gelatin-coated dishes. The resultant cells had a normal karyotype, exhibited alkaline phosphatase activity and expressed the pluripotency markers Oct4, Sox2 and Nanog. The cells differentiated in vivo to form teratomas that contained all three germ layers of the tissue cells. The generation of giPS may facilitate future studies investigating the mechanisms underlying innate immunity, particularly for tuberculosis. These experiments provide proof of principle that iPS technology may be adapted to use the guinea pig as a model of human diseases. PMID:28393187

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

Thoma, Clemens, E-mail: c.thoma@oxfordalumni.org; Bachy, Veronique; Seaton, Patricia

In a phase II/III clinical trial intraperitoneal (i.p.) administration of a group C adenovirus vector (Ad5) caused bowel adhesion formation, perforation and obstruction. However, we had found that i.p. group B, in contrast to group C adenoviruses, did not cause adhesions in nude BALB/c ovarian cancer models, prompting further investigation. Ex vivo, group B Ad11 caused lower inflammatory responses than Ad5 on BALB/c peritoneal macrophages. In vivo, i.p. Ad11 triggered short-term cytokine and cellular responses equal to Ad5 in both human CD46-positive and -negative mice. In contrast, in a long-term study of repeated i.p. administration, Ad11 caused no/mild, whereas Ad5more » induced moderate/severe adhesions and substantial liver toxicity accompanied by elevated levels of IFNγ and VEGF and loss of i.p. macrophages, regardless of CD46 expression. It appears that, although i.p. Ad11 evokes immediate inflammation similar to Ad5, repeated administration of Ad11 is better tolerated and long-term fibrotic tissue remodelling is reduced. - Highlights: • i.p. Ad11 causes less long-term intraperitoneal inflammation than Ad5 in CD46-transgenic mice. • Ex vivo BALB/c peritoneal macrophages express less RANTES after Ad11 than Ad3 or Ad5 treatment. • In vivo, cytokine and cellular responses 6 h after i.p. Ad11 are equal to Ad5. • In contrast, after repeated i.p. application, Ad5, but not Ad11, causes severe i.p. toxicity. • The use of Ad11 instead of Ad5 might increase patient safety in future virotherapy of ovarian cancer.« less

Finite-element time-domain modeling of electromagnetic data in general dispersive medium using adaptive Padé series

NASA Astrophysics Data System (ADS)

Cai, Hongzhu; Hu, Xiangyun; Xiong, Bin; Zhdanov, Michael S.

2017-12-01

The induced polarization (IP) method has been widely used in geophysical exploration to identify the chargeable targets such as mineral deposits. The inversion of the IP data requires modeling the IP response of 3D dispersive conductive structures. We have developed an edge-based finite-element time-domain (FETD) modeling method to simulate the electromagnetic (EM) fields in 3D dispersive medium. We solve the vector Helmholtz equation for total electric field using the edge-based finite-element method with an unstructured tetrahedral mesh. We adopt the backward propagation Euler method, which is unconditionally stable, with semi-adaptive time stepping for the time domain discretization. We use the direct solver based on a sparse LU decomposition to solve the system of equations. We consider the Cole-Cole model in order to take into account the frequency-dependent conductivity dispersion. The Cole-Cole conductivity model in frequency domain is expanded using a truncated Padé series with adaptive selection of the center frequency of the series for early and late time. This approach can significantly increase the accuracy of FETD modeling.

Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation[S

PubMed Central

Allende, Maria L.; Cook, Emily K.; Larman, Bridget C.; Nugent, Adrienne; Brady, Jacqueline M.; Golebiowski, Diane; Sena-Esteves, Miguel; Tifft, Cynthia J.

2018-01-01

Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of β-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells using CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB-corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids, but not the HEXB-corrected organoids, accumulated GM2 ganglioside and exhibited increased size and cellular proliferation compared with the HEXB-corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses. PMID:29358305

Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation.

PubMed

Allende, Maria L; Cook, Emily K; Larman, Bridget C; Nugent, Adrienne; Brady, Jacqueline M; Golebiowski, Diane; Sena-Esteves, Miguel; Tifft, Cynthia J; Proia, Richard L

2018-03-01

Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of β-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells using CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB -corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids, but not the HEXB -corrected organoids, accumulated GM2 ganglioside and exhibited increased size and cellular proliferation compared with the HEXB -corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses.

Testing Brain Overgrowth and Synaptic Models of Autism Using NPCs and Neurons from Patient-Derived IPS Cells

DTIC Science & Technology

2015-12-01

Award Number: W81XWH-13-1-0415 TITLE: Testing Brain Overgrowth and Synaptic Models of Autism Using NPC’s and Neurons from Patient-Derived IPS...Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Autism and autism spectrum disorders (ASD) are complex...impaired social interaction, and limited and repetitive interests and behavior. Recent studies have led to two major hypotheses for autism

Accountability and Accreditation for Special Libraries: It Can Be Done!

ERIC Educational Resources Information Center

Glockner, Brigitte

2004-01-01

Health librarians are very familiar with the accreditation process in hospitals. In 2000 the first ALIA National Policy Congress recommended that accreditation of special libraries should be implemented. The proposed guidelines have been roughly based on the EQuIP Program of the Australian Council on Healthcare Standards. This program is…

78 FR 40581 - Structure and Practices of the Video Relay Service Program; Telecommunications Relay Services and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-05

... Relay Service (IP Relay) providers; Adopts rules to protect the privacy of customer information relating... Structure and Practices of the Video Relay Service Program; Telecommunications Relay Services and Speech-to-Speech Services for Individuals With Hearing and Speech Disabilities; Final Rule #0;#0;Federal Register...

ABCG2/BCRP decreases the transfer of a food-born chemical carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in perfused term human placenta.

PubMed

Myllynen, Päivi; Kummu, Maria; Kangas, Tiina; Ilves, Mika; Immonen, Elina; Rysä, Jaana; Pirilä, Rauna; Lastumäki, Anni; Vähäkangas, Kirsi H

2008-10-15

We have studied the role of ATP binding cassette (ABC) transporters in fetal exposure to carcinogens using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) a known substrate for ABC transporters as a model compound. In perfusion of human term placenta, transfer of (14)C-PhIP (2 microM) through the placenta resulted in fetal-to-maternal concentration ratio (FM ratio) of 0.72+/-0.09 at 6 h. The specific ABCG2 inhibitor KO143 increased the transfer of (14)C-PhIP from maternal to fetal circulation (FM ratio 0.90+/-0.08 at 6 h, p<0.05) while the ABCC1/ABCC2 inhibitor probenecid had no effect (FM ratio at 6 h 0.75+/-0.10, p=0.84). There was a negative correlation between the expression of ABCG2 protein in perfused tissue and the FM ratio of (14)C-PhIP (R=-0.81, p<0.01) at the end of the perfusion. The expression of ABCC2 protein did not correlate with FM ratio of PhIP (R: -0.11, p=0.76). In addition, PhIP induced the expression of ABC transporters in BeWo cells at mRNA level. In conclusion, our data indicates that ABCG2 decreases placental transfer of (14)C-PhIP in perfused human placenta. Also, PhIP may modify ABC transporter expression in choriocarcinoma cells.

Efficient Generation of β-Globin-Expressing Erythroid Cells Using Stromal Cell-Derived Induced Pluripotent Stem Cells from Patients with Sickle Cell Disease.

PubMed

Uchida, Naoya; Haro-Mora, Juan J; Fujita, Atsushi; Lee, Duck-Yeon; Winkler, Thomas; Hsieh, Matthew M; Tisdale, John F

2017-03-01

Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent an ideal source for in vitro modeling of erythropoiesis and a potential alternative source for red blood cell transfusions. However, iPS cell-derived erythroid cells predominantly produce ε- and γ-globin without β-globin production. We recently demonstrated that ES cell-derived sacs (ES sacs), known to express hemangioblast markers, allow for efficient erythroid cell generation with β-globin production. In this study, we generated several iPS cell lines derived from bone marrow stromal cells (MSCs) and peripheral blood erythroid progenitors (EPs) from sickle cell disease patients, and evaluated hematopoietic stem/progenitor cell (HSPC) generation after iPS sac induction as well as subsequent erythroid differentiation. MSC-derived iPS sacs yielded greater amounts of immature hematopoietic progenitors (VEGFR2 + GPA-), definitive HSPCs (CD34 + CD45+), and megakaryoerythroid progenitors (GPA + CD41a+), as compared to EP-derived iPS sacs. Erythroid differentiation from MSC-derived iPS sacs resulted in greater amounts of erythroid cells (GPA+) and higher β-globin (and βS-globin) expression, comparable to ES sac-derived cells. These data demonstrate that human MSC-derived iPS sacs allow for more efficient erythroid cell generation with higher β-globin production, likely due to heightened emergence of immature progenitors. Our findings should be important for iPS cell-derived erythroid cell generation. Stem Cells 2017;35:586-596. © 2016 AlphaMed Press.

ABCG2/BCRP decreases the transfer of a food-born chemical carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in perfused term human placenta

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

Myllynen, Paeivi; Kummu, Maria; Kangas, Tiina

2008-10-15

We have studied the role of ATP binding cassette (ABC) transporters in fetal exposure to carcinogens using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) a known substrate for ABC transporters as a model compound. In perfusion of human term placenta, transfer of {sup 14}C-PhIP (2 {mu}M) through the placenta resulted in fetal-to-maternal concentration ratio (FM ratio) of 0.72 {+-} 0.09 at 6 h. The specific ABCG2 inhibitor KO143 increased the transfer of {sup 14}C-PhIP from maternal to fetal circulation (FM ratio 0.90 {+-} 0.08 at 6 h, p < 0.05) while the ABCC1/ABCC2 inhibitor probenecid had no effect (FM ratio at 6 h 0.75 {+-}more » 0.10, p = 0.84). There was a negative correlation between the expression of ABCG2 protein in perfused tissue and the FM ratio of {sup 14}C-PhIP (R = - 0.81, p < 0.01) at the end of the perfusion. The expression of ABCC2 protein did not correlate with FM ratio of PhIP (R: - 0.11, p = 0.76). In addition, PhIP induced the expression of ABC transporters in BeWo cells at mRNA level. In conclusion, our data indicates that ABCG2 decreases placental transfer of {sup 14}C-PhIP in perfused human placenta. Also, PhIP may modify ABC transporter expression in choriocarinoma cells.« less

A Real-time Spectrum Handoff Algorithm for VoIP based Cognitive Radio Networks: Design and Performance Analysis

NASA Astrophysics Data System (ADS)

Chakraborty, Tamal; Saha Misra, Iti

2016-03-01

Secondary Users (SUs) in a Cognitive Radio Network (CRN) face unpredictable interruptions in transmission due to the random arrival of Primary Users (PUs), leading to spectrum handoff or dropping instances. An efficient spectrum handoff algorithm, thus, becomes one of the indispensable components in CRN, especially for real-time communication like Voice over IP (VoIP). In this regard, this paper investigates the effects of spectrum handoff on the Quality of Service (QoS) for VoIP traffic in CRN, and proposes a real-time spectrum handoff algorithm in two phases. The first phase (VAST-VoIP based Adaptive Sensing and Transmission) adaptively varies the channel sensing and transmission durations to perform intelligent dropping decisions. The second phase (ProReact-Proactive and Reactive Handoff) deploys efficient channel selection mechanisms during spectrum handoff for resuming communication. Extensive performance analysis in analytical and simulation models confirms a decrease in spectrum handoff delay for VoIP SUs by more than 40% and 60%, compared to existing proactive and reactive algorithms, respectively and ensures a minimum 10% reduction in call-dropping probability with respect to the previous works in this domain. The effective SU transmission duration is also maximized under the proposed algorithm, thereby making it suitable for successful VoIP communication.

Glial cells isolated from dorsal root ganglia express prostaglandin E(2) (EP(4)) and prostacyclin (IP) receptors.

PubMed

Ng, Kai Yu; Wong, Yung Hou; Wise, Helen

2011-07-01

Isolated cells from adult rat dorsal root ganglia (DRG) are frequently used as a model system to study responses of primary sensory neurons to nociceptor sensitizing agents such as prostaglandin E(2) and prostacyclin, which are presumed to act only on the neurons in typical mixed cell cultures. In the present study, we evaluated the expression of prostaglandin E(2) (EP(4)) and prostacyclin (IP) receptors in cultures of mixed DRG cells and in purified DRG glia. We show here that EP(4) and IP receptor agonists stimulated adenylyl cyclase activity in both mixed DRG cells and in purified DRG glia, and that these responses were specifically inhibited by EP(4) and IP receptor antagonists, respectively. The presence of EP(4) and IP receptors in DRG glia was further confirmed by the expression of EP(4) and IP receptor immunoreactivity and mRNA. With the increasing awareness of neuron-glial interactions within intact DRG and the use of isolated DRG cells in the study of mechanisms underlying nociception, it will be essential to consider the role played by EP(4) and IP receptor-expressing glial cells when evaluating prostanoid-induced sensitization of DRG neurons. Copyright © 2011 Elsevier B.V. All rights reserved.

Human induced pluripotent stem cells labeled with fluorescent magnetic nanoparticles for targeted imaging and hyperthermia therapy for gastric cancer.

PubMed

Li, Chao; Ruan, Jing; Yang, Meng; Pan, Fei; Gao, Guo; Qu, Su; Shen, You-Lan; Dang, Yong-Jun; Wang, Kan; Jin, Wei-Lin; Cui, Da-Xiang

2015-09-01

Human induced pluripotent stem (iPS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human iPS cells labeled with fluorescent magnetic nanoparticles (FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Human iPS cells were prepared and cultured for 72 h. The culture medium was collected, and then was co-incubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human iPS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. iPS cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iPS cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. FMNP-labeled human iPS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer.

ChIP-PaM: an algorithm to identify protein-DNA interaction using ChIP-Seq data.

PubMed

Wu, Song; Wang, Jianmin; Zhao, Wei; Pounds, Stanley; Cheng, Cheng

2010-06-03

ChIP-Seq is a powerful tool for identifying the interaction between genomic regulators and their bound DNAs, especially for locating transcription factor binding sites. However, high cost and high rate of false discovery of transcription factor binding sites identified from ChIP-Seq data significantly limit its application. Here we report a new algorithm, ChIP-PaM, for identifying transcription factor target regions in ChIP-Seq datasets. This algorithm makes full use of a protein-DNA binding pattern by capitalizing on three lines of evidence: 1) the tag count modelling at the peak position, 2) pattern matching of a specific tag count distribution, and 3) motif searching along the genome. A novel data-based two-step eFDR procedure is proposed to integrate the three lines of evidence to determine significantly enriched regions. Our algorithm requires no technical controls and efficiently discriminates falsely enriched regions from regions enriched by true transcription factor (TF) binding on the basis of ChIP-Seq data only. An analysis of real genomic data is presented to demonstrate our method. In a comparison with other existing methods, we found that our algorithm provides more accurate binding site discovery while maintaining comparable statistical power.

Comparative calibration of IP scanning equipment

NASA Astrophysics Data System (ADS)

Ingenito, F.; Andreoli, P.; Batani, D.; Boutoux, G.; Cipriani, M.; Consoli, F.; Cristofari, G.; Curcio, A.; De Angelis, R.; Di Giorgio, G.; Ducret, J.; Forestier-Colleoni, P.; Hulin, S.; Jakubowska, K.; Rabhi, N.

2016-05-01

Imaging Plates (IP) are diagnostic devices which contain a photostimulable phosphor layer that stores the incident radiation dose as a latent image. The image is read with a scanner which stimulates the decay of electrons, previously excited by the incident radiation, by exposition to a laser beam. This results in emitted light, which is detected by photomultiplier tubes; so the latent image is reconstructed. IPs have the interesting feature that can be reused many times, after erasing stored information. Algorithms to convert signals stored in the detector to Photostimulated luminescence (PSL) counts depend on the scanner and are not available on every model. A comparative cross-calibration of the IP scanner Dürr CR35 BIO, used in ABC laboratory, was performed, using the Fujifilm FLA 7000 scanner as a reference, to find the equivalence between grey-scale values given by the Dürr scanner to PSL counts. Using an IP and a 55Fe β-source, we produced pairs of samples with the same exposition times, which were analysed by both scanners, placing particular attention to fading times of the image stored on IPs. Data analysis led us to the determine a conversion formula which can be used to compare data of experiments obtained in different laboratories and to use IP calibrations available, till now, only for Fujifilm scanners.

Paradoxical ventilator associated pneumonia incidences among selective digestive decontamination studies versus other studies of mechanically ventilated patients: benchmarking the evidence base

PubMed Central

2011-01-01

Introduction Selective digestive decontamination (SDD) appears to have a more compelling evidence base than non-antimicrobial methods for the prevention of ventilator associated pneumonia (VAP). However, the striking variability in ventilator associated pneumonia-incidence proportion (VAP-IP) among the SDD studies remains unexplained and a postulated contextual effect remains untested for. Methods Nine reviews were used to source 45 observational (benchmark) groups and 137 component (control and intervention) groups of studies of SDD and studies of three non-antimicrobial methods of VAP prevention. The logit VAP-IP data were summarized by meta-analysis using random effects methods and the associated heterogeneity (tau2) was measured. As group level predictors of logit VAP-IP, the mode of VAP diagnosis, proportion of trauma admissions, the proportion receiving prolonged ventilation and the intervention method under study were examined in meta-regression models containing the benchmark groups together with either the control (models 1 to 3) or intervention (models 4 to 6) groups of the prevention studies. Results The VAP-IP benchmark derived here is 22.1% (95% confidence interval; 95% CI; 19.2 to 25.5; tau2 0.34) whereas the mean VAP-IP of control groups from studies of SDD and of non-antimicrobial methods, is 35.7 (29.7 to 41.8; tau2 0.63) versus 20.4 (17.2 to 24.0; tau2 0.41), respectively (P < 0.001). The disparity between the benchmark groups and the control groups of the SDD studies, which was most apparent for the highest quality studies, could not be explained in the meta-regression models after adjusting for various group level factors. The mean VAP-IP (95% CI) of intervention groups is 16.0 (12.6 to 20.3; tau2 0.59) and 17.1 (14.2 to 20.3; tau2 0.35) for SDD studies versus studies of non-antimicrobial methods, respectively. Conclusions The VAP-IP among the intervention groups within the SDD evidence base is less variable and more similar to the benchmark than among the control groups. These paradoxical observations cannot readily be explained. The interpretation of the SDD evidence base cannot proceed without further consideration of this contextual effect. PMID:21214897

An assessment of ten ocean reanalyses in the polar regions

NASA Astrophysics Data System (ADS)

Uotila, Petteri

2017-04-01

Ocean reanalysis (ORA) combines observations either statistically or with a hydrodynamical model, to reconstruct historical changes in the ocean. Global and regional ORA products are increasingly used in polar research, but their quality remains to be systematically assessed. To address this, the Polar ORA Intercomparison Project (PORA-IP) has been established following on from the ORA-IP project (Balmaseda et al. 2015, with other papers in a special issue of Climate Dynamics). The PORA-IP is constituted under the COST EOS initiative with plans to review reanalyses products in both the Arctic and Antarctic, and is endorsed by YOPP - the Year of Polar Prediction project. Currently, the PORA-IP team consists of 21 researchers from 15 institutes and universities. The ORA-IP products with polar physics, such as sea ice, have been updated where necessary and collected in a public database. In addition to model output, available observational polar climatologies are collected and used in the assessments. Due to the extensive variety of products, this database should become a valuable resource outside the PORA-IP community. For a comprehensive evaluation of the ten ORA products (CGLORSv5, ECDA3.1, GECCO2, Glorys2v4, GloSea5_GO5, MOVEG2i, ORAP5, SODA3.3.1, TOPAZ4 and UR025.4) in the Arctic and Southern Oceans several specific diagnostics are assessed. The PORA-IP diagnostics target the following topics: hydrography; heat, salinity and freshwater content; ocean transports and surface currents; mixed layer depth; sea-ice concentration and thickness; and snow thickness over sea ice. Based on these diagnostics, ORA product biases against observed data and their mutual spread are quantified, and possible reasons for discrepancies discussed. So far, we have identified product outliers and evaluated the multi-model mean. We have identified the importance of the atmospheric forcing, air-ocean coupling protocol and sea-ice data assimilation for the product performance. Moreover, we are investigating co-variability between the Arctic Ocean heat content and the North Atlantic heat transport, and between the mixed layer depth, oceanic convection, the upper ocean hydrography and sea ice. We will also present other diagnostic results which provide closely related information for those interested in enhancing model predictive skill over a range of time scales, including seasonal to decadal.

Building sustainable organizational capacity to deliver HIV programs in resource-constrained settings: stakeholder perspectives.

PubMed

Sharma, Anjali; Chiliade, Philippe; Michael Reyes, E; Thomas, Kate K; Collens, Stephen R; Rafael Morales, José

2013-12-13

In 2008, the US government mandated that HIV/AIDS care and treatment programs funded by the US President's Emergency Plan for AIDS Relief (PEPFAR) should shift from US-based international partners (IPs) to registered locally owned organizations (local partners, or LPs). The US Health Resources and Services Administration (HRSA) developed the Clinical Assessment for Systems Strengthening (ClASS) framework for technical assistance in resource-constrained settings. The ClASS framework involves all stakeholders in the identification of LPs' strengths and needs for technical assistance. This article examines the role of ClASS in building capacity of LPs that can endure and adapt to changing financial and policy environments. All stakeholders (n=68) in Kenya, Zambia, and Nigeria who had participated in the ClASS from LPs and IPs, the US Centers for Disease Control and Prevention (CDC), and, in Nigeria, HIV/AIDS treatment facilities (TFs) were interviewed individually or in groups (n=42) using an open-ended interview guide. Thematic analysis revealed stakeholder perspectives on ClASS-initiated changes and their sustainability. Local organizations were motivated to make changes in internal operations with the ClASS approach, PEPFAR's competitive funding climate, organizational goals, and desired patient health outcomes. Local organizations drew on internal resources and, if needed, technical assistance from IPs. Reportedly, ClASS-initiated changes and remedial action plans made LPs more competitive for PEPFAR funding. LPs also attributed their successful funding applications to their preexisting systems and reputation. Bureaucracy, complex and competing tasks, and staff attrition impeded progress toward the desired changes. Although CDC continues to provide technical assistance through IPs, declining PEPFAR funds threaten the consolidation of gains, smooth program transition, and continuity of treatment services. The well-timed adaptation and implementation of ClASS successfully engaged stakeholders who committed their own resources toward strengthening organizational capacity. The sustainability of built capacity depends on continued investment in leadership, staff retention, and quality improvement.

Building sustainable organizational capacity to deliver HIV programs in resource-constrained settings: stakeholder perspectives

PubMed Central

Sharma, Anjali; Chiliade, Philippe; Reyes, E. Michael; Thomas, Kate K.; Collens, Stephen R.; Morales, José Rafael

2013-01-01

Background In 2008, the US government mandated that HIV/AIDS care and treatment programs funded by the US President's Emergency Plan for AIDS Relief (PEPFAR) should shift from US-based international partners (IPs) to registered locally owned organizations (local partners, or LPs). The US Health Resources and Services Administration (HRSA) developed the Clinical Assessment for Systems Strengthening (ClASS) framework for technical assistance in resource-constrained settings. The ClASS framework involves all stakeholders in the identification of LPs’ strengths and needs for technical assistance. Objective This article examines the role of ClASS in building capacity of LPs that can endure and adapt to changing financial and policy environments. Design All stakeholders (n=68) in Kenya, Zambia, and Nigeria who had participated in the ClASS from LPs and IPs, the US Centers for Disease Control and Prevention (CDC), and, in Nigeria, HIV/AIDS treatment facilities (TFs) were interviewed individually or in groups (n=42) using an open-ended interview guide. Thematic analysis revealed stakeholder perspectives on ClASS-initiated changes and their sustainability. Results Local organizations were motivated to make changes in internal operations with the ClASS approach, PEPFAR's competitive funding climate, organizational goals, and desired patient health outcomes. Local organizations drew on internal resources and, if needed, technical assistance from IPs. Reportedly, ClASS-initiated changes and remedial action plans made LPs more competitive for PEPFAR funding. LPs also attributed their successful funding applications to their preexisting systems and reputation. Bureaucracy, complex and competing tasks, and staff attrition impeded progress toward the desired changes. Although CDC continues to provide technical assistance through IPs, declining PEPFAR funds threaten the consolidation of gains, smooth program transition, and continuity of treatment services. Conclusions The well-timed adaptation and implementation of ClASS successfully engaged stakeholders who committed their own resources toward strengthening organizational capacity. The sustainability of built capacity depends on continued investment in leadership, staff retention, and quality improvement. PMID:24331715

Dietary Chemoprevention of PhIP Induced Carcinogenesis in Male Fischer 344 Rats with Tomato and Broccoli

PubMed Central

Canene-Adams, Kirstie; Sfanos, Karen S.; Liang, Chung-Tiang; Yegnasubramanian, Srinivasan; Nelson, William G.; Brayton, Cory; De Marzo, Angelo M.

2013-01-01

The heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-B]pyridine (PhIP), found in meats cooked at high temperatures, has been implicated in epidemiological and rodent studies for causing breast, prostate, and colorectal cancers. A previous animal study using a xenograft model has shown that whole tomato and broccoli, when eaten in combination, exhibit a marked effect on tumor reduction compared to when eaten alone. Our aim was to determine if PhIP-induced carcinogenesis can be prevented by dietary consumption of whole tomato + broccoli powders. Male Fischer 344 rats (n = 45) were randomized into the following treatment groups: control (AIN93G diet), PhIP (200 ppm in AIN93G diet for the first 20 weeks of the study), or tomato + broccoli + PhIP (mixed in AIN93G diet at 10% each and fed with PhIP for 20 weeks, and then without PhIP for 32 weeks). Study animals were monitored for 52 weeks and were euthanized as necessary based on a set of criteria for health status and tumor burden. Although there appeared to be some hepatic and intestinal toxicity due to the combination of PhIP and tomato + broccoli, these rodents had improved survival and reduced incidence and/or severity of PhIP-induced neoplastic lesions compared to the PhIP-alone treated group. Rats eating tomato + broccoli exhibited a marked decrease in the number and size of cribiform prostatic intraepitheilial neoplasia/carcinoma in situ (cribiform PIN/CIS) lesions and in the incidence of invasive intestinal adenocarcinomas and skin carcinomas. Although the apparent toxic effects of combined PhIP and tomato + broccoli need additional study, the results of this study support the hypothesis that a diet rich in tomato and broccoli can reduce or prevent dietary carcinogen-induced cancers. PMID:24312188

Advanced Models and Algorithms for Self-Similar IP Network Traffic Simulation and Performance Analysis

NASA Astrophysics Data System (ADS)

Radev, Dimitar; Lokshina, Izabella

2010-11-01

The paper examines self-similar (or fractal) properties of real communication network traffic data over a wide range of time scales. These self-similar properties are very different from the properties of traditional models based on Poisson and Markov-modulated Poisson processes. Advanced fractal models of sequentional generators and fixed-length sequence generators, and efficient algorithms that are used to simulate self-similar behavior of IP network traffic data are developed and applied. Numerical examples are provided; and simulation results are obtained and analyzed.

Transient Analysis of Pressurization and Pneumatic Subsystems of the X-34 Main Propulsion System

NASA Technical Reports Server (NTRS)

Hedayat, A.; Knight, K. C.; Chamption, R. H., Jr.; Kennedy, Jim W. (Technical Monitor)

2000-01-01

Transient models for the pressurization, vent/relief, and pneumatic subsystems of the X-34 Main Propulsion System are presented and simulation of their operation within prescribed requirements are provided. First, using ROCket Engine Transient Simulation (ROCETS) program, pressurization subsystem operation was simulated and helium requirements and the ullage thermodynamic condition within each propellant tank were calculated. Then, Overpressurization scenarios of propellant tanks and the response of vent/relief valves were evaluated using ROCETS simulation of simultaneous operation of the pressurization and vent/relief subsystems by incorporating the valves data into the model. Finally, the ROCETS simulation of in-flight operation of pneumatic subsystem predicted the overall helium consumption, Inter-Propellant Seal (IPS) purge flowrate and thermodynamic conditions, and Spin Start power.

The cooked meat-derived mammary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine promotes invasive behaviour of breast cancer cells.

PubMed

Lauber, Sandra N; Gooderham, Nigel J

2011-01-11

The cooked meat derived genotoxic carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces cancer of the colon, prostate and mammary gland when fed to rats. Epidemiology studies link these tumours to a Western diet and exposure to heterocyclic amines such as PhIP. We have shown that PhIP is also potently estrogenic and have proposed that this hormonal activity contributes to its target site carcinogenicity. We now postulate that the estrogenic properties of PhIP influence metastatic potential. We have used an in vitro assay for cell invasion based upon digestion and migration through a reconstituted basement membrane model. Zymography and immunoblotting were used to confirm PhIP-mediated changes associated with induction of the invasive phenotype. Treatment of the mammary cancer cell lines MCF-7 and T47D with PhIP induces cells to digest and migrate through a reconstituted basement membrane. The response was dose dependent, observed at sub-nanomolar concentrations of PhIP and was inhibited by the antiestrogen ICI 182,780. The PhIP-induced invasive phenotype was associated with expression of cathepsin D, cyclooxygenase-2 and matrix metalloproteinase activity. These findings emphasise the range and potency of the biological activities associated with this cooked meat product and mechanistically support the tissue-specific carcinogenicity of the chemical. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

High resolution reconstruction of monthly precipitation of Iberian Peninsula using circulation weather types

NASA Astrophysics Data System (ADS)

Cortesi, N.; Trigo, R.; Gonzalez-Hidalgo, J. C.; Ramos, A. M.

2012-06-01

Precipitation over the Iberian Peninsula (IP) is highly variable and shows large spatial contrasts between wet mountainous regions, to the north, and dry regions in the inland plains and southern areas. In this work, a high-density monthly precipitation dataset for the IP was coupled with a set of 26 atmospheric circulation weather types (Trigo and DaCamara, 2000) to reconstruct Iberian monthly precipitation from October to May with a very high resolution of 3030 precipitation series (overall mean density one station each 200 km2). A stepwise linear regression model with forward selection was used to develop monthly reconstructed precipitation series calibrated and validated over 1948-2003 period. Validation was conducted by means of a leave-one-out cross-validation over the calibration period. The results show a good model performance for selected months, with a mean coefficient of variation (CV) around 0.6 for validation period, being particularly robust over the western and central sectors of IP, while the predicted values in the Mediterranean and northern coastal areas are less acute. We show for three long stations (Lisbon, Madrid and Valencia) the comparison between model and original data as an example to how these models can be used in order to obtain monthly precipitation fields since the 1850s over most of IP for this very high density network.

Systems view on spatial planning and perception based on invariants in agent-environment dynamics

PubMed Central

Mettler, Bérénice; Kong, Zhaodan; Li, Bin; Andersh, Jonathan

2015-01-01

Modeling agile and versatile spatial behavior remains a challenging task, due to the intricate coupling of planning, control, and perceptual processes. Previous results have shown that humans plan and organize their guidance behavior by exploiting patterns in the interactions between agent or organism and the environment. These patterns, described under the concept of Interaction Patterns (IPs), capture invariants arising from equivalences and symmetries in the interaction with the environment, as well as effects arising from intrinsic properties of human control and guidance processes, such as perceptual guidance mechanisms. The paper takes a systems' perspective, considering the IP as a unit of organization, and builds on its properties to present a hierarchical model that delineates the planning, control, and perceptual processes and their integration. The model's planning process is further elaborated by showing that the IP can be abstracted, using spatial time-to-go functions. The perceptual processes are elaborated from the hierarchical model. The paper provides experimental support for the model's ability to predict the spatial organization of behavior and the perceptual processes. PMID:25628524

Attentional priorities and access to short-term memory: parietal interactions.

PubMed

Gillebert, Céline R; Dyrholm, Mads; Vangkilde, Signe; Kyllingsbæk, Søren; Peeters, Ronald; Vandenberghe, Rik

2012-09-01

The intraparietal sulcus (IPS) has been implicated in selective attention as well as visual short-term memory (VSTM). To contrast mechanisms of target selection, distracter filtering, and access to VSTM, we combined behavioral testing, computational modeling and functional magnetic resonance imaging. Sixteen healthy subjects participated in a change detection task in which we manipulated both target and distracter set sizes. We directly compared the IPS response as a function of the number of targets and distracters in the display and in VSTM. When distracters were not present, the posterior and middle segments of IPS showed the predicted asymptotic activity increase with an increasing target set size. When distracters were added to a single target, activity also increased as predicted. However, the addition of distracters to multiple targets suppressed both middle and posterior IPS activities, thereby displaying a significant interaction between the two factors. The interaction between target and distracter set size in IPS could not be accounted for by a simple explanation in terms of number of items accessing VSTM. Instead, it led us to a model where items accessing VSTM receive differential weights depending on their behavioral relevance, and secondly, a suppressive effect originates during the selection phase when multiple targets and multiple distracters are simultaneously present. The reverse interaction between target and distracter set size was significant in the right temporoparietal junction (TPJ), where activity was highest for a single target compared to any other condition. Our study reconciles the role of middle IPS in attentional selection and biased competition with its role in VSTM access. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of intra-abdominal pressure increase on intestinal ischemia and bacterial translocation in experimental sepsis model.

PubMed

Kesici, Ugur; Kesici, Sevgi; Polat, Erdal; Agca, Birol; Turkmen, Ulku A; Ozcan, Deniz; Sari, Musa K

2011-08-01

To investigate the safety of laparoscopic intervention for diagnosis and treatment at 8 mm Hg pressure in one-hour period on acute peritonitis related intra-abdominal sepsis model. In this study, we included 32 female Wistar-Albino rats, weighing 250 +/- 20 g, and divided them into 4 groups. This study was conducted in Istanbul University Experimental Medical Research Institution (DETAE) laboratory from April to May 2009. Intra-abdominal sepsis was created with intraperitoneal (i.p.) one mL (109 CFU/mL) Escherichia coli (E. coli) injection, and pneumoperitoneum was formed with CO2 insufflation at 8 mm Hg pressure for one hour i.p. The rats were administered with: Group 1 - one mL i.p. isotonic saline; Group 2 - one mL i.p. isotonic saline + pneumoperitoneum; Group 3 - i.p E. coli; and Group 4 - i.p. E.coli + pneumoperitoneum. Data were analyzed using the Statistical Package for Social Sciences version 15 for Windows (SPSS Inc, Chicago, IL, USA). Fever and leukocyte values were considered high in Groups 3 and 4 compared with Groups 1 and 2 (p=0.001). The administered reproduction ratio of the E. coli strain was determined as 0% in Groups 1 and 2, and 100% in Groups 3 and 4. In this study, as pneumoperitoneum was formed for one hour at 8 mm Hg pressure, in case of intra-abdominal derived sepsis where emergency intervention is needed, we consider that laparoscopic approaches with low pressure may be used safely for diagnosis and treatment.

The Effect of Water or Wax-based Binders on the Chemical and Morphological Characteristics of the Margin Ceramic-Framework Interface.

PubMed

Güler, Umut; de Queiroz, José Renato Cavalcanti; de Oliveira, Luiz Fernando Cappa; Canay, Senay; Ozcan, Mutlu

2015-09-01

This study evaluated the effect of binder choice in mixing ceramic powder on the chemical and morphological features between the margin ceramic-framework interfaces. Titanium and zirconia frameworks (15 x 5 x 0.5 mm3) were veneered with margin ceramics prepared with two different binders, namely a) water/conventional or b) wax-based. For each zirconia framework material, four different margin ceramics were used: a- Creation Zi (Creation Willi Geller International); b- GC Initial Zr (GC America); Triceram (Dentaurum); and d- IPS emax (voclar Vivadent). For the titanium framework, three different margin ceramics were used: a- Creation Ti (Creation Willi Geller International); b- Triceram (Dentaurum); and c- VITA Titaniumkeramik (Vita Zahnfabrik). The chemical composition of the framework-margin ceramic interface was analyzed using Energy Dispersive X-ray Spectroscopy (EDS) and porosity level was quantified within the margin ceramic using an image program (ImageJ) from four random areas (100 x 100 pixels) on each SEM image. EDS analysis showed the presence of Carbon at the margin ceramic-framework interface in the groups where wax-based binder technique was used with the concentration being the highest for the IPS emax ZirCAD group. While IPS system (IPS ZirCAD and IPS Emax) presented higher porosity concentration using wax binder, in the other groups wax-based binder reduced the porosity of margin ceramic, except for Titanium - Triceram combination.

Monitoring and risk assessment of the spruce bark beetle, Ips typographus

Treesearch

S. Netherer; J. Pennerstorfer; P. Baier; E. Fuhrer; A. Schopf

2003-01-01

A model describing development of the spruce bark beetle, Ips typographus, combines topo-climatic aspects of the terrain with eco-physiological aspects of the bark beetle. By correlating air temperature and solar irradiation measured at a reference station, along with topographic data and microclimatic conditions of terrain plots, topo-climatic...

Temperamental, Parental, and Contextual Contributors to Early-Emerging Internalizing Problems: A New Integrative Analysis Approach

ERIC Educational Resources Information Center

Mills, Rosemary S. L.; Hastings, Paul D.; Helm, Jonathan; Serbin, Lisa A.; Etezadi, Jamshid; Stack, Dale M.; Schwartzman, Alex E.; Li, Hai Hong

2012-01-01

This study evaluated a comprehensive model of factors associated with internalizing problems (IP) in early childhood, hypothesizing direct, mediated, and moderated pathways linking child temperamental inhibition, maternal overcontrol and rejection, and contextual stressors to IP. In a novel approach, three samples were integrated to form a large…

Caffeine, Adenosine Receptors and Estrogen in Toxin Models of Parkinson’s Disease

DTIC Science & Technology

2007-10-01

KW-6002 (3 mg/kg, ip; in the presence of a sub-threshold dose of the dopamine D2 antagonist haloperidol ) induced ipsilateral turning, and amphetamine... haloperidol ) induced ipsilateral turning, and amphetamine (2.5 mg/kg i.p. on its own) induced contralateral turning relative to that in the control

Gene therapy decreases seizures in a model of Incontinentia pigmenti.

PubMed

Dogbevia, Godwin K; Töllner, Kathrin; Körbelin, Jakob; Bröer, Sonja; Ridder, Dirk A; Grasshoff, Hanna; Brandt, Claudia; Wenzel, Jan; Straub, Beate K; Trepel, Martin; Löscher, Wolfgang; Schwaninger, Markus

2017-07-01

Incontinentia pigmenti (IP) is a genetic disease leading to severe neurological symptoms, such as epileptic seizures, but no specific treatment is available. IP is caused by pathogenic variants that inactivate the Nemo gene. Replacing Nemo through gene therapy might provide therapeutic benefits. In a mouse model of IP, we administered a single intravenous dose of the adeno-associated virus (AAV) vector, AAV-BR1-CAG-NEMO, delivering the Nemo gene to the brain endothelium. Spontaneous epileptic seizures and the integrity of the blood-brain barrier (BBB) were monitored. The endothelium-targeted gene therapy improved the integrity of the BBB. In parallel, it reduced the incidence of seizures and delayed their occurrence. Neonate mice intravenously injected with the AAV-BR1-CAG-NEMO vector developed no hepatocellular carcinoma or other major adverse effects 11 months after vector injection, demonstrating that the vector has a favorable safety profile. The data show that the BBB is a target of antiepileptic treatment and, more specifically, provide evidence for the therapeutic benefit of a brain endothelial-targeted gene therapy in IP. Ann Neurol 2017;82:93-104. © 2017 American Neurological Association.

Enhancing interacting residue prediction with integrated contact matrix prediction in protein-protein interaction.

PubMed

Du, Tianchuan; Liao, Li; Wu, Cathy H

2016-12-01

Identifying the residues in a protein that are involved in protein-protein interaction and identifying the contact matrix for a pair of interacting proteins are two computational tasks at different levels of an in-depth analysis of protein-protein interaction. Various methods for solving these two problems have been reported in the literature. However, the interacting residue prediction and contact matrix prediction were handled by and large independently in those existing methods, though intuitively good prediction of interacting residues will help with predicting the contact matrix. In this work, we developed a novel protein interacting residue prediction system, contact matrix-interaction profile hidden Markov model (CM-ipHMM), with the integration of contact matrix prediction and the ipHMM interaction residue prediction. We propose to leverage what is learned from the contact matrix prediction and utilize the predicted contact matrix as "feedback" to enhance the interaction residue prediction. The CM-ipHMM model showed significant improvement over the previous method that uses the ipHMM for predicting interaction residues only. It indicates that the downstream contact matrix prediction could help the interaction site prediction.

Research of x-ray nondestructive detector for high-speed running conveyor belt with steel wire ropes

NASA Astrophysics Data System (ADS)

Wang, Junfeng; Miao, Changyun; Wang, Wei; Lu, Xiaocui

2008-03-01

An X-ray nondestructive detector for high-speed running conveyor belt with steel wire ropes is researched in the paper. The principle of X-ray nondestructive testing (NDT) is analyzed, the general scheme of the X-ray nondestructive testing system is proposed, and the nondestructive detector for high-speed running conveyor belt with steel wire ropes is developed. The hardware of system is designed with Xilinx's VIRTEX-4 FPGA that embeds PowerPC and MAC IP core, and its network communication software based on TCP/IP protocol is programmed by loading LwIP to PowerPC. The nondestructive testing of high-speed conveyor belt with steel wire ropes and network transfer function are implemented. It is a strong real-time system with rapid scanning speed, high reliability and remotely nondestructive testing function. The nondestructive detector can be applied to the detection of product line in industry.

Motif-based analysis of large nucleotide data sets using MEME-ChIP

PubMed Central

Ma, Wenxiu; Noble, William S; Bailey, Timothy L

2014-01-01

MEME-ChIP is a web-based tool for analyzing motifs in large DNA or RNA data sets. It can analyze peak regions identified by ChIP-seq, cross-linking sites identified by cLIP-seq and related assays, as well as sets of genomic regions selected using other criteria. MEME-ChIP performs de novo motif discovery, motif enrichment analysis, motif location analysis and motif clustering, providing a comprehensive picture of the DNA or RNA motifs that are enriched in the input sequences. MEME-ChIP performs two complementary types of de novo motif discovery: weight matrix–based discovery for high accuracy; and word-based discovery for high sensitivity. Motif enrichment analysis using DNA or RNA motifs from human, mouse, worm, fly and other model organisms provides even greater sensitivity. MEME-ChIP’s interactive HTML output groups and aligns significant motifs to ease interpretation. this protocol takes less than 3 h, and it provides motif discovery approaches that are distinct and complementary to other online methods. PMID:24853928

iTAR: a web server for identifying target genes of transcription factors using ChIP-seq or ChIP-chip data.

PubMed

Yang, Chia-Chun; Andrews, Erik H; Chen, Min-Hsuan; Wang, Wan-Yu; Chen, Jeremy J W; Gerstein, Mark; Liu, Chun-Chi; Cheng, Chao

2016-08-12

Chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) or microarray hybridization (ChIP-chip) has been widely used to determine the genomic occupation of transcription factors (TFs). We have previously developed a probabilistic method, called TIP (Target Identification from Profiles), to identify TF target genes using ChIP-seq/ChIP-chip data. To achieve high specificity, TIP applies a conservative method to estimate significance of target genes, with the trade-off being a relatively low sensitivity of target gene identification compared to other methods. Additionally, TIP's output does not render binding-peak locations or intensity, information highly useful for visualization and general experimental biological use, while the variability of ChIP-seq/ChIP-chip file formats has made input into TIP more difficult than desired. To improve upon these facets, here we present are fined TIP with key extensions. First, it implements a Gaussian mixture model for p-value estimation, increasing target gene identification sensitivity and more accurately capturing the shape of TF binding profile distributions. Second, it enables the incorporation of TF binding-peak data by identifying their locations in significant target gene promoter regions and quantifies their strengths. Finally, for full ease of implementation we have incorporated it into a web server ( http://syslab3.nchu.edu.tw/iTAR/ ) that enables flexibility of input file format, can be used across multiple species and genome assembly versions, and is freely available for public use. The web server additionally performs GO enrichment analysis for the identified target genes to reveal the potential function of the corresponding TF. The iTAR web server provides a user-friendly interface and supports target gene identification in seven species, ranging from yeast to human. To facilitate investigating the quality of ChIP-seq/ChIP-chip data, the web server generates the chart of the characteristic binding profiles and the density plot of normalized regulatory scores. The iTAR web server is a useful tool in identifying TF target genes from ChIP-seq/ChIP-chip data and discovering biological insights.

Power Balance Modeling and Validation for ST Startup Using Local Helicity Injection

NASA Astrophysics Data System (ADS)

Barr, J. L.; Bodner, G. M.; Bongard, M. W.; Burke, M. G.; Fonck, R. J.; Hinson, E. T.; Perry, J. M.; Reusch, J. A.; Schlossberg, D. J.

2015-11-01

Local Helicity Injection (LHI) uses localized current injectors for routine Ip<0.18 MA non-solenoidal startup on the Pegasus ST. A power-balance model is under development for predictive Ip t using helicity-balance to quantify LHI's effective current drive, Veff. Analytic formulas for low-A plasma inductance and vertical field are used to account for the inductive effects of dynamic shape evolution. These formulas are being validated against magnetic reconstructions of LHI discharges with varied shape evolutions. Initial results match experimental Ip t within 20 kA with assumed shaping and average resistivity (Spitzer, Te = 60 eV). Geometric effects and inductive drive provide 2.0 V along with Veff = 0.3 V to balance 1.1 V of resistive losses and 1.2 V inductive reactance to ramping Ip. The model is especially sensitive to resistivity when Te<150 eV. Initial Thomson Scattering results give core Te = 72 +/-22 eV, and at times suggest higher central electron energies. Spatial and temporal scans are underway to quantify LHI plasma resistivity and transport. MA-class startup in NSTX-U will require increased area (Ainj >= 40 cm2) LHI systems that play a larger role in current drive than geometric effects, with Veff dropping from >10 V to on-par with inductive effects. This regime is accessed in Pegasus at Ip ≅ 300 kA. Work supported by US DOE grants DE-FG02-96ER54375 and DE-SC0006928.

Inhibitory effect of fruit extracts on the formation of heterocyclic amines.

PubMed

Cheng, Ka-Wing; Wu, Qingli; Zheng, Zong Ping; Peng, Xiaofang; Simon, James E; Chen, Feng; Wang, Mingfu

2007-12-12

Natural extracts have attracted considerable attention for development into effective inhibitors against the formation of genotoxic heterocyclic amines (HAs) in processed foods. In this study, four fruit extracts (apple, elderberry, grape seed, and pineapple) were evaluated for their effects on HA formation in fried beef patties. Apple and grape seed extracts were found to be the most effective in both the degree of inhibition in the formation of individual HAs (2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), and 2-amino-1-methyl-6-henylimidazo [4,5-b]pyridine (PhIP)) and in the reduction of total HA content (approximately 70% relative to the control). Activity-guided analysis of apple extract using model systems (PhIP- and MeIQx-producing models) showed that the proanthocyanidins, phloridzin and chlorogenic acid were responsible for reducing the amount of HAs formed. Proanthocyanidins were identified as the dominant inhibitors because they were strongly active against HA formation in both the PhIP and MeIQx model systems. For phloridzin, the inhibitory effect was observed only on the formation of PhIP. In contrast, chlorogenic acid, although effective against the formation of MeIQx, significantly enhanced the formation of PhIP. This is the first report showing the inhibitory activities of apple phenolics on the formation of heterocyclic amines. The findings provide valuable information for the development of effective strategies to minimize HA content of cooked meats and to identify several new natural products that may have new applications in the food industry.

Effect of Ozone on Intestinal Epithelial Homeostasis in a Rat Model

PubMed Central

Sukhotnik, Igor; Starikov, Alona; Coran, Arnold G.; Pollak, Yulia; Sohotnik, Rima; Shaoul, Ron

2015-01-01

Background: The positive effects of ozone therapy have been described in many gastrointestinal disorders. The mechanisms of this positive effect of ozone therapy are poorly understood. The purpose of the present study was to investigate whether the use of ozone may potentiate the gut intestinal mucosal homeostasis in a rat model. Methods: Adult rats weighing 250–280 g were randomly assigned to one of three experimental groups of 8 rats each: 1) Control rats were given 2 mL of water by gavage and intraperitoneally (IP) for 5 days; 2) O3-PO rats were treated with 2 mL of ozone/oxygen mixture by gavage and 2 mL of water IP for 5 days; 3) O3-IP rats were treated with 2 mL of water by gavage and 2 mL of ozone/oxygen mixture IP for 5 days. Rats were sacrificed on day 6. Bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, and cell proliferation and apoptosis were evaluated following sacrifice. Results: The group of O3-IP rats demonstrated a greater jejunal and ileal villus height and crypt depth, a greater enterocyte proliferation index in jejunum, and lower enterocyte apoptosis in ileum compared to control animals. Oral administration of the ozone/oxygen mixture resulted in a less significant effect on cell turnover. Conclusions: Treatment with an ozone/oxygen mixture stimulates intestinal cell turnover in a rat model. Intraperitoneal administration of ozone resulted in a more significant intestinal trophic effect than oral administration. PMID:25717388

Sundstrand’s Precision Metal Forming Cell. Industrial Modernization Incentive Program (IMIP). Phase 2

DTIC Science & Technology

1991-03-01

1-2 1.4 CONCLUSIONS AND RECOMMENDATIONS ....................... 1-2 20. PHASE II MANAGEMENT PLAN...2-1 2.1 PROGRAM MANAGEMENT ................................... 2-1 2.2 IM IP TEAM...Barbier, reference Section 2.0 (Phase II Management Plan), is complete and this report provides the results of the Phase II study. 1.2 OBJECTIVES The

Tseunis Transformative Teacher Induction Plan, T3IP: TTTIPing the Scale in Favor of Reform

ERIC Educational Resources Information Center

Tseunis, Paula

2011-01-01

Facing a teacher shortage in math, science, and language arts secondary courses, a suburban, unified, K-12 district partnered with a university in the southwest to create a program for alternatively certified teachers. This specialized program permitted candidates to teach with an intern certificate while completing university coursework leading…

Parent-Adolescent Relationship Education (PARE): Program Delivery to Reduce Risks for Adolescent Pregnancy and STDs

ERIC Educational Resources Information Center

Lederman, Regina P.; Chan, Wenyaw; Roberts-Gray, Cynthia

2008-01-01

The first author recruited parent-adolescent dyads (N = 192) into after-school prevention education groups at middle schools in southeast Texas. This author placed participants in either (1) an Interactive Program (IP) in which they role-played, practiced resistance skills, and held parent-child discussions or (2) an Attention Control Program…

Power Balance Modeling of Local Helicity Injection for Non-Solenoidal ST Startup

NASA Astrophysics Data System (ADS)

Weberski, J. D.; Barr, J. L.; Bongard, M. W.; Fonck, R. J.; Perry, J. M.; Reusch, J. A.

2017-10-01

A zero-dimensional power balance model for predicting Ip(t) for Local Helicity Injection (LHI) discharges has been used to interpret experimental results from recent experimental campaigns using high-field-side (HFS) helicity injection. This model quantifies LHI's effective drive (Veff) through helicity balance while enforcing the Taylor relaxation current limit and tracking inductive effects to determine Ip(t) . Recent analysis of HFS LHI discharges indicate LHI is the dominant source of drive and provides Veff up to 1.3 V while geometric effects and inductive drive provide < 0.1 V throughout much of the discharge. In contrast to previous analysis of low-field-side (LFS) LHI discharges, which were driven by Veff = 0.3 V and 2.0 V from geometric effects and inductive drive. A significant remaining uncertainty in the model is the resistive dissipation of LHI discharges. This requires greater understanding of LHI confinement scaling and impurity content, which are currently under investigation. However, the model and experimental Ip(t) exhibit good agreement for parameters consistent with previous experimental findings. Extrapolation of plasma parameters and shaping from recent experiments allow for the model to project the performance of LHI systems. These projections indicate Ip 0.3 MA can be accessed on Pegasus via HFS LHI through changes to injector geometry to provide more Veff. This regime can be accessed via a LFS system by increasing the Taylor relaxation current limit early in the discharge. Work supported by US DOE Grants DE-FG02-96ER54375 and DE-SC0006928.

A Three-Pool Model Dissecting Readily Releasable Pool Replenishment at the Calyx of Held

PubMed Central

Guo, Jun; Ge, Jian-long; Hao, Mei; Sun, Zhi-cheng; Wu, Xin-sheng; Zhu, Jian-bing; Wang, Wei; Yao, Pan-tong; Lin, Wei; Xue, Lei

2015-01-01

Although vesicle replenishment is critical in maintaining exo-endocytosis recycling, the underlying mechanisms are not well understood. Previous studies have shown that both rapid and slow endocytosis recycle into a very large recycling pool instead of within the readily releasable pool (RRP), and the time course of RRP replenishment is slowed down by more intense stimulation. This finding contradicts the calcium/calmodulin-dependence of RRP replenishment. Here we address this issue and report a three-pool model for RRP replenishment at a central synapse. Both rapid and slow endocytosis provide vesicles to a large reserve pool (RP) ~42.3 times the RRP size. When moving from the RP to the RRP, vesicles entered an intermediate pool (IP) ~2.7 times the RRP size with slow RP-IP kinetics and fast IP-RRP kinetics, which was responsible for the well-established slow and rapid components of RRP replenishment. Depletion of the IP caused the slower RRP replenishment observed after intense stimulation. These results establish, for the first time, a realistic cycling model with all parameters measured, revealing the contribution of each cycling step in synaptic transmission. The results call for modification of the current view of the vesicle recycling steps and their roles. PMID:25825223

[Progress and application prospect of pig induced pluripotent stem cells].

PubMed

Yan, Yi-Bo; Zhang, Yan-Li; Qi, Wei-Wei; Wan, Yong-Jie; Fan, Yi-Xuan; Wang, Feng

2011-04-01

Pig has always been the focus of establishing a big ungulate animal ES cell lines because of its convenient source, genetic similarity with humans, and their importance in animal husbandry, but little development is achieved. Induced pluripotent stem cells technology creates a new method of reprogramming somatic cells to pluripotent state. As the pig iPS cells is established and perfected, pig ES cells will be established in the coming years. The pig iPS cells will give a hint on other livestock ES cells. On the other hand, pig iPS cells can be used to improve the efficiency of transgenic cloning pigs to conduct effective breeding and conservation of breeds. It is particularly important that the pig iPS cells can provide new model for human medical research, a new donor cells for human tissue and organ engineering, and have extensive and far-reaching impact on the biomedical field. Here, we briefly review the major progress of iPS cells, and emphasize current state of pig iPS cells and its application prospect in biomedicine and animal husbandry in order to provide a useful reference for researchers working in this area.

Fluorescence Fluctuations and Equivalence Classes of Ca 2+ Imaging Experiments

PubMed Central

Piegari, Estefanía; Lopez, Lucía; Perez Ipiña, Emiliano; Ponce Dawson, Silvina

2014-01-01

release into the cytosol through inositol 1,4,5-trisphosphate receptors (IP3Rs) plays a relevant role in numerous physiological processes. IP3R-mediated signals involve -induced -release (CICR) whereby release through one open IP3R induces the opening of other channels. IP3Rs are apparently organized in clusters. The signals can remain localized (i.e., puffs) if CICR is limited to one cluster or become waves that propagate between clusters. puffs are the building blocks of waves. Thus, there is great interest in determining puff properties, especially in view of the current controversy on the spatial distribution of activatable IP3Rs. puffs have been observed in intact cells with optical techniques proving that they are intrinsically stochastic. Obtaining a correct picture of their dynamics then entails being able to detect the whole range of puff sizes. puffs are observed using visible single-wavelength dyes, slow exogenous buffers (e.g., EGTA) to disrupt inter-cluster CICR and UV-photolyzable caged IP3. Single-wavelength dyes increase their fluorescence upon calcium binding producing images that are strongly dependent on their kinetic, transport and photophysical properties. Determining the artifacts that the imaging setting introduces is particularly relevant when trying to analyze the smallest signals. In this paper we introduce a method to estimate the expected signal-to-noise ratio of imaging experiments that use single-wavelength dyes. The method is based on the Number and Brightness technique. It involves the performance of a series of experiments and their subsequent analysis in terms of a fluorescence fluctuation model with which the model parameters are quantified. Using the model, the expected signal-to-noise ratio is then computed. Equivalence classes between different experimental conditions that produce images with similar signal-to-noise ratios can then be established. The method may also be used to estimate the smallest signals that can reliably be observed with each setting. PMID:24776736

Assessing the role of metabotropic glutamate receptor 5 in multiple nociceptive modalities.

PubMed

Zhu, Chang Z; Wilson, Sonya G; Mikusa, Joseph P; Wismer, Carol T; Gauvin, Donna M; Lynch, James J; Wade, Carrie L; Decker, Michael W; Honore, Prisca

2004-12-15

Preclinical data, performed in a limited number of pain models, suggest that functional blockade of metabotropic glutamate (mGlu) receptors may be beneficial for pain management. In the present study, effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective mGlu5 receptor antagonist, were examined in a wide variety of rodent nociceptive and hypersensitivity models in order to fully characterize the potential analgesic profile of mGlu5 receptor blockade. Effects of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP), as potent and selective as MPEP at mGlu5/mGlu1 receptors but more selective than MPEP at N-methyl-aspartate (NMDA) receptors, were also evaluated in selected nociceptive and side effect models. MPEP (3-30 mg/kg, i.p.) produced a dose-dependent reversal of thermal and mechanical hyperalgesia following complete Freund's adjuvant (CFA)-induced inflammatory hypersensitivity. Additionally, MPEP (3-30 mg/kg, i.p.) decreased thermal hyperalgesia observed in carrageenan-induced inflammatory hypersensitivity without affecting paw edema, abolished acetic acid-induced writhing activity in mice, and was shown to reduce mechanical allodynia and thermal hyperalgesia observed in a model of post-operative hypersensitivity and formalin-induced spontaneous pain. Furthermore, at 30 mg/kg, i.p., MPEP significantly attenuated mechanical allodynia observed in three neuropathic pain models, i.e. spinal nerve ligation, sciatic nerve constriction and vincristine-induced neuropathic pain. MTEP (3-30 mg/kg, i.p.) also potently reduced CFA-induced thermal hyperalgesia. However, at 100 mg/kg, i.p., MPEP and MTEP produced central nerve system (CNS) side effects as measured by rotarod performance and exploratory locomotor activity. These results suggest a role for mGlu5 receptors in multiple nociceptive modalities, though CNS side effects may be a limiting factor in developing mGlu5 receptor analgesic compounds.

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

Chen, Ying, E-mail: ying.chen@hc.msu.edu; Wang, Kai; Chandramouli, Gadisetti V.R.

Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomesmore » a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro.« less

Drive Innovation Faster.

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

Lemon, Douglas K.

2005-08-01

Authored article by Doug Lemon. An expert opinion/thought piece on how PNNL approaches R&D projects, incorporating IP protection earlier in the process of innovation to shorten the development timeline. Article cites example of SMART program to illustrate point.

MS PHD'S: A successful model for reaching underrepresented minorities (URM) students through virtual platforms

NASA Astrophysics Data System (ADS)

Scott, O.; Johnson, A.; Williamson, V.; Ricciardi, L.; Jearld, A., Jr.; Guzman, W. I.

2014-12-01

To successfully recruit and retain underrepresented minority (URM) students and early career scientists, many programs supplement traditional curricular activities with multiple online platforms, establishing "virtual communities" that are free and easily accessible. These virtual communities offer readily sustainable opportunities to facilitate communication across a wide range of cultural lines and socioeconomic levels thereby broadening participation and inclusivity in STEM. Established in 2003, the Minorities Striving and Pursuing Higher Degrees of Success (MS PHD'S) in Earth System Science Professional Development Program has successfully used virtual community tools such as a listserv, community forum, social media, and VoIP technologies, to extend the face-to-face activities of the program and support the advancement of URM students and early career scientists in STEM. The use of multiple facets of virtual community by MS PHD'S participants supports and encourages "real life" interactions and mentorship, facilitates networking and professional development, and maintains continuity of shared networks. The program is now in its ninth cohort and supports 213 participants. To date, 54 participants have completed their PhD and another 61 are currently enrolled in doctoral programs.

Argo_CUDA: Exhaustive GPU based approach for motif discovery in large DNA datasets.

PubMed

Vishnevsky, Oleg V; Bocharnikov, Andrey V; Kolchanov, Nikolay A

2018-02-01

The development of chromatin immunoprecipitation sequencing (ChIP-seq) technology has revolutionized the genetic analysis of the basic mechanisms underlying transcription regulation and led to accumulation of information about a huge amount of DNA sequences. There are a lot of web services which are currently available for de novo motif discovery in datasets containing information about DNA/protein binding. An enormous motif diversity makes their finding challenging. In order to avoid the difficulties, researchers use different stochastic approaches. Unfortunately, the efficiency of the motif discovery programs dramatically declines with the query set size increase. This leads to the fact that only a fraction of top "peak" ChIP-Seq segments can be analyzed or the area of analysis should be narrowed. Thus, the motif discovery in massive datasets remains a challenging issue. Argo_Compute Unified Device Architecture (CUDA) web service is designed to process the massive DNA data. It is a program for the detection of degenerate oligonucleotide motifs of fixed length written in 15-letter IUPAC code. Argo_CUDA is a full-exhaustive approach based on the high-performance GPU technologies. Compared with the existing motif discovery web services, Argo_CUDA shows good prediction quality on simulated sets. The analysis of ChIP-Seq sequences revealed the motifs which correspond to known transcription factor binding sites.

Inter-Alpha Inhibitor Protein (IAIP) Administration Improves Survival From Neonatal Sepsis In Mice

PubMed Central

Singh, Kultar; Zhang, Ling Xiu; Bendelja, Kreso; Heath, Ryan; Murphy, Shaun; Sharma, Surendra; Padbury, James F.; Lim, Yow-Pin

2010-01-01

Inter-alpha Inhibitor proteins (IaIp) are serine proteases inhibitors which modulate endogenous protease activity and have been shown to improve survival in adult models of sepsis. We evaluated the effect of IaIp on survival and systemic responses to sepsis in neonatal mice. Sepsis was induced in 2-day-old mice with LPS, E. coli and Group B Streptococci. Sepsis was associated with 75% mortality. IaIp, given by intraperitoneal administration at doses between 15–45 mg/kg from 1–6 hours following the onset of sepsis improved survival to nearly 90% (p = 0.0159) in both LPS induced sepsis and with live bacterial infections. The greatest effect was on reversal of hemorrhagic pneumonitis. The effects were dose and time dependent. Systemic cytokine profile and tissue histology were examined. Survival was compared in interleukin 10 knock out animals. Systemic cytokine levels, including TNF-α and IL-10 were increased following induction of sepsis and modulated significantly following IaIp administration. Because the effect of IaIp was still demonstrable in IL-10 deficient mice, we conclude the beneficial effect(s) of IaIp is due to suppression of pro-inflammatory cytokines like TNF-α rather than augmentation of IL-10. IaIp may offer significant benefits as a therapeutic adjunct to treatment of sepsis in neonates and adults. PMID:20520583

Effectiveness of Individual Placement and Support Supported Employment for Young Adults

PubMed Central

Bond, Gary R.; Drake, Robert E.; Campbell, Kikuko

2015-01-01

Objective The Individual Placement and Support (IPS) model of supported employment was first developed in community mental health centers for adults with severe mental illness. While IPS is an established evidence-based practice in this broad population, evidence on its effectiveness focused specifically on young adults has been limited. The current study aimed to address this gap. Methods To investigate the effects of IPS on young adults, the authors conducted a secondary analysis on a pooled sample of 109 unemployed young adults (under age 30) from four randomized controlled trials employing a common research protocol that included a standardized measurement battery and rigorous fidelity monitoring. Researchers assessed these participants over 18 months on nine competitive employment outcome measures. Results On all measures the IPS group had significantly better employment outcomes. Overall, 40 (82%) of IPS participants obtained employment during follow-up compared to 25 (42%) of control participants, Χ2 =17.9, p < .001. IPS participants averaged 25.0 weeks of employment, compared to 7.0 weeks for control participants, t = 4.50, p < .001. Conclusions The current analysis supports a small number of previous studies in showing that IPS is highly effective in helping young adults to attain competitive employment. When young adults acquire competitive jobs and initiate a path toward normal adult roles, they may avoid the cycle of disability and psychiatric patient roles that are demeaning and demoralizing. PMID:25138195

A native IP satellite communications system

NASA Astrophysics Data System (ADS)

Koudelka, O.; Schmidt, M.; Ebert, J.; Schlemmer, H.; Kastner-Puschl, S.; Riedler, W.

2004-08-01

≪ In the framework of ESA's ARTES-5 program the Institute of Applied Systems Technology (Joanneum Research) in cooperation with the Department of Communications and Wave Propagation has developed a novel meshed satellite communications system which is optimised for Internet traffic and applications (L*IP—Local Network Interconnection via Satellite Systems Using the IP Protocol Suite). Both symmetrical and asymmetrical connections are supported. Bandwidth on demand and guaranteed quality of service are key features of the system. A novel multi-frequency TDMA access scheme utilises efficient methods of IP encapsulation. In contrast to other solutions it avoids legacy transport network techniques. While the DVB-RCS standard is based on ATM or MPEG transport cells, the solution of the L*IP system uses variable-length cells which reduces the overhead significantly. A flexible and programmable platform based on Linux machines was chosen to allow the easy implementation and adaptation to different standards. This offers the possibility to apply the system not only to satellite communications, but provides seamless integration with terrestrial fixed broadcast wireless access systems. The platform is also an ideal test-bed for a variety of interactive broadband communications systems. The paper describes the system architecture and the key features of the system.

Generation of Healthy Mice from Gene-Corrected Disease-Specific Induced Pluripotent Stem Cells

PubMed Central

Rittelmeyer, Ina; Sharma, Amar Deep; Sgodda, Malte; Zaehres, Holm; Bleidißel, Martina; Greber, Boris; Gentile, Luca; Han, Dong Wook; Rudolph, Cornelia; Steinemann, Doris; Schambach, Axel; Ott, Michael; Schöler, Hans R.; Cantz, Tobias

2011-01-01

Using the murine model of tyrosinemia type 1 (fumarylacetoacetate hydrolase [FAH] deficiency; FAH −/− mice) as a paradigm for orphan disorders, such as hereditary metabolic liver diseases, we evaluated fibroblast-derived FAH −/−-induced pluripotent stem cells (iPS cells) as targets for gene correction in combination with the tetraploid embryo complementation method. First, after characterizing the FAH −/− iPS cell lines, we aggregated FAH −/−-iPS cells with tetraploid embryos and obtained entirely FAH −/−-iPS cell–derived mice that were viable and exhibited the phenotype of the founding FAH −/− mice. Then, we transduced FAH cDNA into the FAH −/−-iPS cells using a third-generation lentiviral vector to generate gene-corrected iPS cells. We could not detect any chromosomal alterations in these cells by high-resolution array CGH analysis, and after their aggregation with tetraploid embryos, we obtained fully iPS cell–derived healthy mice with an astonishing high efficiency for full-term development of up to 63.3%. The gene correction was validated functionally by the long-term survival and expansion of FAH-positive cells of these mice after withdrawal of the rescuing drug NTBC (2-(2-nitro-4-fluoromethylbenzoyl)-1,3-cyclohexanedione). Furthermore, our results demonstrate that both a liver-specific promoter (transthyretin, TTR)-driven FAH transgene and a strong viral promoter (from spleen focus-forming virus, SFFV)-driven FAH transgene rescued the FAH-deficiency phenotypes in the mice derived from the respective gene-corrected iPS cells. In conclusion, our data demonstrate that a lentiviral gene repair strategy does not abrogate the full pluripotent potential of fibroblast-derived iPS cells, and genetic manipulation of iPS cells in combination with tetraploid embryo aggregation provides a practical and rapid approach to evaluate the efficacy of gene correction of human diseases in mouse models. PMID:21765802

LAN attack detection using Discrete Event Systems.

PubMed

Hubballi, Neminath; Biswas, Santosh; Roopa, S; Ratti, Ritesh; Nandi, Sukumar

2011-01-01

Address Resolution Protocol (ARP) is used for determining the link layer or Medium Access Control (MAC) address of a network host, given its Internet Layer (IP) or Network Layer address. ARP is a stateless protocol and any IP-MAC pairing sent by a host is accepted without verification. This weakness in the ARP may be exploited by malicious hosts in a Local Area Network (LAN) by spoofing IP-MAC pairs. Several schemes have been proposed in the literature to circumvent these attacks; however, these techniques either make IP-MAC pairing static, modify the existing ARP, patch operating systems of all the hosts etc. In this paper we propose a Discrete Event System (DES) approach for Intrusion Detection System (IDS) for LAN specific attacks which do not require any extra constraint like static IP-MAC, changing the ARP etc. A DES model is built for the LAN under both a normal and compromised (i.e., spoofed request/response) situation based on the sequences of ARP related packets. Sequences of ARP events in normal and spoofed scenarios are similar thereby rendering the same DES models for both the cases. To create different ARP events under normal and spoofed conditions the proposed technique uses active ARP probing. However, this probing adds extra ARP traffic in the LAN. Following that a DES detector is built to determine from observed ARP related events, whether the LAN is operating under a normal or compromised situation. The scheme also minimizes extra ARP traffic by probing the source IP-MAC pair of only those ARP packets which are yet to be determined as genuine/spoofed by the detector. Also, spoofed IP-MAC pairs determined by the detector are stored in tables to detect other LAN attacks triggered by spoofing namely, man-in-the-middle (MiTM), denial of service etc. The scheme is successfully validated in a test bed. Copyright © 2010 ISA. Published by Elsevier Ltd. All rights reserved.

Red Wine Consumption is inversely associated with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA Adduct Levels in Prostate

PubMed Central

Rybicki, Benjamin A.; Neslund-Dudas, Christine; Bock, Cathryn H.; Nock, Nora L.; Rundle, Andrew; Jankowski, Michelle; Levin, Albert M.; Beebe-Dimmer, Jennifer; Savera, Adnan T.; Takahashi, Satoru; Shirai, Tomoyuki; Tang, Deliang

2011-01-01

In humans, genetic variation and dietary factors may alter the biologic effects of exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), one of the major heterocyclic amines generated from cooking meats at high temperatures that has carcinogenic potential through the formation of DNA adducts. Previously, we reported grilled red meat consumption associated with PhIP-DNA adduct levels in human prostate. In the present study, we expanded our investigation to estimate the associations between beverage consumption and PhIP-DNA adduct levels in prostate for 391 prostate cancer cases. Of the 15 beverages analyzed, red wine consumption had the strongest association with PhIP-DNA adduct levels showing an inverse correlation in both tumor (p=0.006) and non-tumor (p=0.002) prostate cells. Red wine consumption differed significantly between African-American and white cases, but PhIP-DNA adduct levels in prostate did not vary by race. In African Americans compared with whites, however, associations between red wine consumption and PhIP-DNA adduct levels were not as strong as associations with specific (e.g., SULT1A1 and UGT1A10 genotypes) and non-specific (e.g., African ancestry) genetic variation. In a multivariable model, the covariate for red wine consumption explained a comparable percentage (13-16%) of the variation in PhIP-DNA adduct levels in prostate across the two racial groups, but the aforementioned genetic factors explained 33% of the PhIP-DNA adduct variation in African-American cases, while only 19% of the PhIPDNA adduct variation in whites. We conclude that red wine consumption may counteract biologic effects of PhIP exposure in human prostate, but genetic factors may play an even larger role, particularly in African Americans. PMID:21846795

Cardiac-restricted Overexpression of TRAF3 Interacting Protein 2 (TRAF3IP2) Results in Spontaneous Development of Myocardial Hypertrophy, Fibrosis, and Dysfunction *

PubMed Central

Sakamuri, Siva S. V. P.; Siddesha, Jalahalli M.; Saifudeen, Zubaida; Ma, Lixin; Siebenlist, Ulrich; Gardner, Jason D.; Chandrasekar, Bysani

2016-01-01

TRAF3IP2 (TRAF3 interacting protein 2; previously known as CIKS or Act1) is a key intermediate in the normal inflammatory response and the pathogenesis of various autoimmune and inflammatory diseases. Induction of TRAF3IP2 activates IκB kinase (IKK)/NF-κB, JNK/AP-1, and c/EBPβ and stimulates the expression of various inflammatory mediators with negative myocardial inotropic effects. To investigate the role of TRAF3IP2 in heart disease, we generated a transgenic mouse model with cardiomyocyte-specific TRAF3IP2 overexpression (TRAF3IP2-Tg). Echocardiography, magnetic resonance imaging, and pressure-volume conductance catheterization revealed impaired cardiac function in 2-month-old male transgenic (Tg) mice as evidenced by decreased ejection fraction, stroke volume, cardiac output, and peak ejection rate. Moreover, the male Tg mice spontaneously developed myocardial hypertrophy (increased heart/body weight ratio, cardiomyocyte cross-sectional area, GATA4 induction, and fetal gene re-expression). Furthermore, TRAF3IP2 overexpression resulted in the activation of IKK/NF-κB, JNK/AP-1, c/EBPβ, and p38 MAPK and induction of proinflammatory cytokines, chemokines, and extracellular matrix proteins in the heart. Although myocardial hypertrophy decreased with age, cardiac fibrosis (increased number of myofibroblasts and enhanced expression and deposition of fibrillar collagens) increased progressively. Despite these adverse changes, TRAF3IP2 overexpression did not result in cell death at any time period. Interestingly, despite increased mRNA expression, TRAF3IP2 protein levels and activation of its downstream signaling intermediates remained unchanged in the hearts of female Tg mice. The female Tg mice also failed to develop myocardial hypertrophy. In summary, these results demonstrate that overexpression of TRAF3IP2 in male mice is sufficient to induce myocardial hypertrophy, cardiac fibrosis, and contractile dysfunction. PMID:27466370

Involvement of NMDA receptors and L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effects of topiramate in mice forced swimming test.

PubMed

Ostadhadi, Sattar; Khan, Muhammad Imran; Norouzi-Javidan, Abbas; Chamanara, Mohsen; Jazaeri, Farahnaz; Zolfaghari, Samira; Dehpour, Ahmad-Reza

2016-04-01

Topiramate (TPM) is an agent primarily used in the treatment of epilepsy. Using mice model of forced swimming test (FST) the current study was basically aimed to investigate the influence of TPM on depression by inhibiting NMDA receptor and nitric oxide-cGMP production. When TPM was administered in a dose of 20 and 30 mg/kg by i.p. route it reduced the immobility time during FST. However this effect of TPM (30 mg/kg, i.p.) in the FST was abolished when the mice were pretreated either with NMDA (75 mg/kg, i.p.), or l-arginine (750 mg/kg, i.p. NO precursor), or sildenafil (5mg/kg, i.p. Phosphodiesterase 5 inhibitor). The immobility time in the FST was reduced after administration of L-NAME (10mg/kg, i.p, a non-specific NOS inhibitor), 7-nitoinidazol (30 mg/kg, i.p. a nNOS inhibitor) or MK-801 (0.05 mg/kg, i.p, a NMDA receptor antagonist) in combination with a subeffective dose of TPM (10mg/kg, i.p.) as compared with single use of either drug. Co-administrated of lower doses of MK-801 (0.01 mg/kg) or L-NAME (1mg/kg) failed to effect immobility time. However, simultaneous administration of these two agents in the same doses with subeffective dose of TPM (10mg/kg, i.p.), reduced the immobility time during FST. None of these drugs were found to have a profound effect on the locomotor activity per se during the open field test. Taken together, our data demonstrates that TPM exhibit antidepressant-like effect which is accomplished either due to inhibition of NMDA receptors or NO-cGMP production. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of Optimal Jitter Buffer Size for VoIP QoS under WiMAX Power-Saving Mode

NASA Astrophysics Data System (ADS)

Kim, Hyungsuk; Kim, Taehyoun

VoIP service is expected as one of the key applications of Mobile WiMAX, but the speech quality of VoIP service often suffers deterioration due to the fluctuating transmission delay called jitter. This is commonly ameliorated by a de-jitter buffer, and we aim to find the optimal size of de-jitter buffer to achieve speech quality comparable to PSTN. We developed a new model of the packet drops at the de-jitter buffer and the end-to-end packet delay which takes account of the additional delay introduced by the WiMAX power-saving mode. Using our model, we analyzed the optimal size of the de-jitter buffer for various network parameters, and showed that the results obtained by analysis accord with simulation results.

A model for the implementation of a two-shift municipal solid waste and recyclable material collection plan that offers greater convenience to residents.

PubMed

Lin, Hung-Yueh; Tsai, Zong-Pei; Chen, Guan-Hwa; Kao, Jehng-Jung

2011-01-01

Separating recyclables from municipal solid waste (MSW) before collection reduces not only the quantity of MSW that needs to be treated but also the depletion of resources. However, the participation of residents is essential for a successful recycling program, and the level of participation usually depends on the degree of convenience associated with accessing recycling collection points. The residential accessing convenience (RAC) of a collection plan is determined by the proximity of its collection points to all residents and its temporal flexibility in response to resident requirements. The degree of proximity to all residents is determined by using a coverage radius that represents the maximum distance residents need to travel to access a recycling point. The temporal flexibility is assessed by the availability of proximal recycling points at times suitable to the lifestyles of all residents concerned. In Taiwan, the MSW collection is implemented at fixed locations and at fixed times. Residents must deposit their garbage directly into the collection vehicle. To facilitate the assignment of collection vehicles and to encourage residents to thoroughly separate their recyclables, in Taiwan MSW and recyclable materials are usually collected at the same time by different vehicles. A heuristic procedure including an integer programming (IP) model and ant colony optimization (ACO) is explored in this study to determine an efficient two-shift collection plan that takes into account RAC factors. The IP model has been developed to determine convenient collection points in each shift on the basis of proximity, and then the ACO algorithm is applied to determine the most effective routing plan of each shift. With the use of a case study involving a city in Taiwan, this study has demonstrated that collection plans generated using the above procedure are superior to current collection plans on the basis of proximity and total collection distance.

Unmonitored use of herbal medicine by patients with breast cancer: reframing expectations.

PubMed

Samuels, Noah; Ben-Arye, Eran; Maimon, Yair; Berger, Raanan

2017-11-01

To identify the unmonitored use of herbal medicine by female patients with breast cancer, examining the impact of an integrative physician (IP) consultation on this practice. The files of 269 female patients with breast cancer following an IP consultation were surveyed retrospectively for use of herbal medicine for cancer-related goals. Expectations from the IP consultation and adherence to the IP-guided treatments were examined as well. Among the cohort, 111 (41.3%) reported using herbal medicine for cancer-related goals, unmonitored by their oncology healthcare professional. Factors predicting herbal medicine use were the adoption of dietary changes (odds ratio = 13.6, p < 0.001, CI 7.16-26.0) and the expectation that the IP consultation and treatments would address cancer-related goals (odds ratio = 3.29, p = 0.001, CI 1.64-6.6). Patients with metastatic disease were more likely to be using herbal medicine than non-users (34.5 vs. 22.8%; p = 0.088), as were those who had consulted with a complementary/alternative medicine practitioner (54.9 vs. 20.8%; p = 0.005). The IP advised 17 patients (15.3%) to stop taking specific herbal products due to safety-related concerns; and 10 patients to take dietary supplements for relief of specific symptoms. Herbal medicine users were less likely than non-users to adhere to the IP-recommended treatment program (34.7 vs. 48.3%; p = 0.037). Unmonitored use of herbal medicine by patients with breast cancer is more frequent among those adopting dietary changes for cancer-related goals. Integrative physicians provide evidence-based guidance on the safe and effective use of herbal products, and reframe patient expectations from cancer-related goals to reducing symptoms and improving quality of life.

Antidepressant Imipramine Protects Bupivacaine-Induced Neurotoxicity in Dorsal Root Ganglion Neurons Through Coactivation of TrkA and TrkB.

PubMed

Guo, Jianrong; Wang, Huan; Tao, Qiang; Sun, Shiyu; Liu, Li; Zhang, Jianping; Yang, Dawei

2017-11-01

In our work, we used an in vitro culture model to investigate whether antidepressant imipramine (Ip) may protect bupivacaine (Bv)-induced neurotoxicity in mouse dorsal root ganglion (DRG). Adult mouse DRG was treated with 5 mM Bv in vitro to induce neurotoxicity. DRG was then pre-treated with Ip, prior to Bv, to examine its effects on protecting Bv-induced DRG apoptosis and neurite degeneration. Ip-induced dynamic changes in Trk receptors, including TrkA/B/C and phosphor (p-)TrkA/B/C, were examined by qPCR and Western blot. TrkA and TrkB were inhibited by siRNAs to further investigate their functional role in Ip- and Bv-treated DRG. Ip protected Bv-induced apoptosis and neurite loss in DRG. Ip did not alter TrkA/B/C expressions, whereas significantly augmented protein productions of p-TrkA and p-TrkB, but not p-TrkC. SiRNA-mediated TrkA or TrkB downregulation inhibited Trk receptors, and reduced p-TrkA and p-TrkB in DRG. TrkA or TrkB downregulation alone had no effect on Ip-induced protection in Bv-injured DRG. However, co-inhibition of TrkA and TrkB significantly ameliorated the protective effect of Ip on Bv-induced apoptosis and neurite loss in DRG. Imipramine protected bupivacaine-induced neurotoxicity in DRG, likely via the co-activation of TrkA and TrkB signaling pathways. J. Cell. Biochem. 118: 3960-3967, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Refinement of the Interprofessional Socialization and Valuing Scale (ISVS-21) and Development of 9-Item Equivalent Versions.

PubMed

King, Gillian; Orchard, Carole; Khalili, Hossein; Avery, Lisa

2016-01-01

Measures of interprofessional (IP) socialization are needed to capture the role of interprofessional education in preparing students and health practitioners to function as part of IP health care teams. The aims of this study were to refine a previously published version of the Interprofessional Socialization and Valuing Scale (the ISVS-24) and create two shorter equivalent forms to be used in pre-post studies. A graded response model was used to identify ISVS items in a practitioner data set (n = 345), with validation (measure invariance) conducted using a separate student sample (n = 341). Analyses indicated a unidimensional 21-item version with excellent measurement properties, Cronbach alpha of 0.988, 95% confidence interval (CI) 0.985-0.991. There was evidence of measure invariance, as there was excellent agreement of the factor scores for the practitioner and student data, intraclass correlation coefficient = 0.993, 95% CI 0.991-0.994. This indicates that the ISVS-21 measures IP socialization consistently across groups. Two 9-item equivalent versions for pre-post use were developed, with excellent agreement between the two forms. The student score agreement for the two item sets was excellent: intraclass correlation coefficient = 0.970, 95% CI 0.963-0.976. The ISVS-21 is a refined measure to assess existing levels of IP socialization in practitioners and students, and relate IP socialization to other important constructs such as IP collaboration and the development of an IP identity. The equivalent versions can be used to assess change in IP socialization as a result of interprofessional education.

Design, Realization, and First Validation of an Immersive Web-Based Virtual Patient Simulator for Training Clinical Decisions in Surgery.

PubMed

Kleinert, Robert; Heiermann, Nadine; Wahba, Roger; Chang, De-Huan; Hölscher, Arnulf H; Stippel, Dirk L

2015-01-01

Immersive patient simulators (IPS) allow an illusionary immersion into a synthetic world where the user can freely navigate through a 3-dimensional environment similar to computer games. Playful learning with IPS allows internalization of medical workflows without harming real patients. Ideally, IPS show high student acceptance and can have positive effect on knowledge gain. Development of IPS with high technical quality is resource intensive. Therefore most of the "high-fidelity" IPS are commercially driven. Usage of IPS in the daily curriculum is still rare. There is no academic-driven simulator that is freely accessible to every student and combines high immersion grade with a profound amount of medical content. Therefore it was our aim to develop an academic-driven IPS prototype that is free to use and combines a high immersion grade with profound medical content. In addition, a first validation of the prototype was conducted. The conceptual design included definition of the following parameters: amount of curricular content, grade of technical quality, availability, and level of validation. A preliminary validation was done with 25 students. Students' opinion about acceptance was evaluated by a Likert-scale questionnaire. Effect on knowledge gain was determined by testing concordance and predictive validity. A custom-made simulator prototype (Artificial learning interface for clinical education [ALICE]) displays a virtual clinic environment that can be explored from a first-person view similar to a video game. By controlling an avatar, the user navigates through the environment, is able to treat virtual patients, and faces the consequence of different decisions. ALICE showed high students' acceptance. There was positive correlation for concordance validity and predictive validity. Simulator usage had positive effect on reproduction of trained content and declarative knowledge. We successfully developed a university-based, IPS prototype (ALICE) with profound medical content. ALICE is a nonprofit simulator, easy to use, and showed high students' acceptance; thus it potentially provides an additional tool for supporting student teaching in the daily clinical curriculum. Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Analyzing multiple data sets by interconnecting RSAT programs via SOAP Web services: an example with ChIP-chip data.

PubMed

Sand, Olivier; Thomas-Chollier, Morgane; Vervisch, Eric; van Helden, Jacques

2008-01-01

This protocol shows how to access the Regulatory Sequence Analysis Tools (RSAT) via a programmatic interface in order to automate the analysis of multiple data sets. We describe the steps for writing a Perl client that connects to the RSAT Web services and implements a workflow to discover putative cis-acting elements in promoters of gene clusters. In the presented example, we apply this workflow to lists of transcription factor target genes resulting from ChIP-chip experiments. For each factor, the protocol predicts the binding motifs by detecting significantly overrepresented hexanucleotides in the target promoters and generates a feature map that displays the positions of putative binding sites along the promoter sequences. This protocol is addressed to bioinformaticians and biologists with programming skills (notions of Perl). Running time is approximately 6 min on the example data set.

Interprofessional Education and Practice Guide No. 7: Development, implementation, and evaluation of a large-scale required interprofessional education foundational programme.

PubMed

Shrader, Sarah; Hodgkins, Renee; Laverentz, Delois; Zaudke, Jana; Waxman, Michael; Johnston, Kristy; Jernigan, Stephen

2016-09-01

Health profession educators and administrators are interested in how to develop an effective and sustainable interprofessional education (IPE) programme. We describe the approach used at the University of Kansas Medical Centre, Kansas City, United States. This approach is a foundational programme with multiple large-scale, half-day events each year. The programme is threaded with common curricular components that build in complexity over time and assures that each learner is exposed to IPE. In this guide, lessons learned and general principles related to the development of IPE programming are discussed. Important areas that educators should consider include curriculum development, engaging leadership, overcoming scheduling barriers, providing faculty development, piloting the programming, planning for logistical coordination, intentionally pairing IP facilitators, anticipating IP conflict, setting clear expectations for learners, publicising the programme, debriefing with faculty, planning for programme evaluation, and developing a scholarship and dissemination plan.

Using digital multimedia to improve parents' and children's understanding of clinical trials.

PubMed

Tait, Alan R; Voepel-Lewis, Terri; Levine, Robert

2015-06-01

Data show that many research subjects have difficulty understanding study information using traditional paper consent documents. This study, therefore, was designed to evaluate the effect of an interactive multimedia program on improving parents' and children's understanding of clinical trial concepts and participation. Parents (n=148) and children (n=135) were each randomised to receive information regarding clinical trials using either a traditional paper format (TF) or an interactive iPad program (IP) with inline exercises. Participants' understanding of the information was assessed using semistructured interviews prior to (pretest) and after (post-test) receiving the information. Participants also completed a short survey to assess their perceptions of information delivery and satisfaction with the process. Regardless of the mode of information delivery, all participants demonstrated improved pretest to post-test understanding. While there were no statistical differences in parents' post-test understanding between the TF and IP groups, children in the IP group had significantly greater post-test understanding compared with children in the TF group (11.65 (4.1) vs 8.85 (4.1) (2.8, 1.4, 4.2) 0-18 scale where 18=complete understanding). Furthermore, the IP was found to be significantly 'easier to follow' and 'more effective' in presenting information compared with the TF. Results demonstrated the importance of providing information regarding clinical trial concepts to parents and children. Importantly, the ability of interactive multimedia to improve understanding of clinical trial concepts and satisfaction with information delivery, particularly among children, supports this approach as a novel and effective vehicle for enhancing the informed consent process. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Switching performance of OBS network model under prefetched real traffic

NASA Astrophysics Data System (ADS)

Huang, Zhenhua; Xu, Du; Lei, Wen

2005-11-01

Optical Burst Switching (OBS) [1] is now widely considered as an efficient switching technique in building the next generation optical Internet .So it's very important to precisely evaluate the performance of the OBS network model. The performance of the OBS network model is variable in different condition, but the most important thing is that how it works under real traffic load. In the traditional simulation models, uniform traffics are usually generated by simulation software to imitate the data source of the edge node in the OBS network model, and through which the performance of the OBS network is evaluated. Unfortunately, without being simulated by real traffic, the traditional simulation models have several problems and their results are doubtable. To deal with this problem, we present a new simulation model for analysis and performance evaluation of the OBS network, which uses prefetched IP traffic to be data source of the OBS network model. The prefetched IP traffic can be considered as real IP source of the OBS edge node and the OBS network model has the same clock rate with a real OBS system. So it's easy to conclude that this model is closer to the real OBS system than the traditional ones. The simulation results also indicate that this model is more accurate to evaluate the performance of the OBS network system and the results of this model are closer to the actual situation.

49 CFR 173.427 - Transport requirements for low specific activity (LSA) Class 7 (radioactive) materials and...

Code of Federal Regulations, 2010 CFR

2010-10-01

... package (IP-1, IP-2 or IP-3; § 173.411), subject to the limitations of Table 6; (2) In a DOT Specification... use shipment 1. LSA-I: Solid IP-1 IP-1 Liquid IP-1 IP-2 2. LSA-II: Solid IP-2 IP-2 Liquid and gas IP-2 IP-3 3. LSA-III IP-2 IP-3 4. SCO-I IP-1 IP-1 5. SCO-II IP-2 IP-2 [69 FR 3676, Jan. 26, 2004; 69 FR...

49 CFR 173.427 - Transport requirements for low specific activity (LSA) Class 7 (radioactive) materials and...

Code of Federal Regulations, 2011 CFR

2011-10-01

... package (IP-1, IP-2 or IP-3; § 173.411), subject to the limitations of Table 6; (2) In a DOT Specification... use shipment 1. LSA-I: Solid IP-1 IP-1 Liquid IP-1 IP-2 2. LSA-II: Solid IP-2 IP-2 Liquid and gas IP-2 IP-3 3. LSA-III IP-2 IP-3 4. SCO-I IP-1 IP-1 5. SCO-II IP-2 IP-2 [69 FR 3676, Jan. 26, 2004; 69 FR...

Sequential computation of elementary modes and minimal cut sets in genome-scale metabolic networks using alternate integer linear programming.

PubMed

Song, Hyun-Seob; Goldberg, Noam; Mahajan, Ashutosh; Ramkrishna, Doraiswami

2017-08-01

Elementary (flux) modes (EMs) have served as a valuable tool for investigating structural and functional properties of metabolic networks. Identification of the full set of EMs in genome-scale networks remains challenging due to combinatorial explosion of EMs in complex networks. It is often, however, that only a small subset of relevant EMs needs to be known, for which optimization-based sequential computation is a useful alternative. Most of the currently available methods along this line are based on the iterative use of mixed integer linear programming (MILP), the effectiveness of which significantly deteriorates as the number of iterations builds up. To alleviate the computational burden associated with the MILP implementation, we here present a novel optimization algorithm termed alternate integer linear programming (AILP). Our algorithm was designed to iteratively solve a pair of integer programming (IP) and linear programming (LP) to compute EMs in a sequential manner. In each step, the IP identifies a minimal subset of reactions, the deletion of which disables all previously identified EMs. Thus, a subsequent LP solution subject to this reaction deletion constraint becomes a distinct EM. In cases where no feasible LP solution is available, IP-derived reaction deletion sets represent minimal cut sets (MCSs). Despite the additional computation of MCSs, AILP achieved significant time reduction in computing EMs by orders of magnitude. The proposed AILP algorithm not only offers a computational advantage in the EM analysis of genome-scale networks, but also improves the understanding of the linkage between EMs and MCSs. The software is implemented in Matlab, and is provided as supplementary information . hyunseob.song@pnnl.gov. Supplementary data are available at Bioinformatics online. Published by Oxford University Press 2017. This work is written by US Government employees and are in the public domain in the US.

Survey of perceived influence of the conceptual design model of interactive television advertising towards impulse purchase tendency

NASA Astrophysics Data System (ADS)

Sarif, Siti Mahfuzah; Omar, Azizah Che; Shiratuddin, Norshuhada

2016-08-01

With the proliferation of technology assisted shopping, there is growing evidence that impulse buying is an emerging phenomenon, which has been the focus of this study. Literatures indicate that studies related to impulse purchase for interactive television (iTV) advertising are highly scarce. It was found that most of the existing impulse purchase elements are mainly focusing on traditional retail store, website advertising, and traditional TV advertising, but not on iTV advertising. Due to that, through a systematic process, a design model for developing iTV advertising with influence towards impulse purchase tendency was developed and tested in this study. The design model is named as iTVAdIP and comprises of three main components; technology, impulse purchase components, and development process. This paper describes the survey, which measures the influence of iTVAdIP design model towards impulse purchase tendency. 37 potential advertising designers were involved in the survey. The results indicate that the iTVAdIP is practical and workable in developing iTV advertisement that could influence consumer to buy the advertised product.

Effects of generation time on spray aerosol transport and deposition in models of the mouth-throat geometry.

PubMed

Worth Longest, P; Hindle, Michael; Das Choudhuri, Suparna

2009-06-01

For most newly developed spray aerosol inhalers, the generation time is a potentially important variable that can be fully controlled. The objective of this study was to determine the effects of spray aerosol generation time on transport and deposition in a standard induction port (IP) and more realistic mouth-throat (MT) geometry. Capillary aerosol generation (CAG) was selected as a representative system in which spray momentum was expected to significantly impact deposition. Sectional and total depositions in the IP and MT geometries were assessed at a constant CAG flow rate of 25 mg/sec for aerosol generation times of 1, 2, and 4 sec using both in vitro experiments and a previously developed computational fluid dynamics (CFD) model. Both the in vitro and numerical results indicated that extending the generation time of the spray aerosol, delivered at a constant mass flow rate, significantly reduced deposition in the IP and more realistic MT geometry. Specifically, increasing the generation time of the CAG system from 1 to 4 sec reduced the deposition fraction in the IP and MT geometries by approximately 60 and 33%, respectively. Furthermore, the CFD predictions of deposition fraction were found to be in good agreement with the in vitro results for all times considered in both the IP and MT geometries. The numerical results indicated that the reduction in deposition fraction over time was associated with temporal dissipation of what was termed the spray aerosol "burst effect." Based on these results, increasing the spray aerosol generation time, at a constant mass flow rate, may be an effective strategy for reducing deposition in the standard IP and in more realistic MT geometries.

The anaemia control model: Does it help nephrologists in therapeutic decision-making in the management of anaemia?

PubMed

Bucalo, María Laura; Barbieri, Carlo; Roca, Susana; Ion Titapiccolo, Jasmine; Ros Romero, Maria Soledad; Ramos, Rosa; Albaladejo, Mercedes; Manzano, Diana; Mari, Flavio; Molina, Manuel

2018-06-03

Anaemia is common in haemodialysis patients and treating it with erythropoiesis-stimulating agents (ESAs) is complex due to many factors. To assess the usefulness of the Anaemia Control Model (ACM) in the treatment of anaemia in haemodialysis. ACM is a software that predicts the optimal dose of darbepoetin and iron sucrose to achieve target haemoglobin (Hb) and ferritin levels, and makes prescription suggestions. Study conducted in dialysis clinics lasting 18months with two intervention phases (IPs) with ACM (IP1, n:213; IP2, n:218) separated by a control phase (CP, n:219). The primary outcome was the percentage of Hb in range and the median dose of ESAs, and the secondary outcomes were transfusion, hospitalisation and cardiovascular events. Clinical and patient analyses were performed. Hb variability was assessed by the standard deviation (SD) of the Hb. We also analysed the patients with most of the suggestions confirmed (ACM compliant group). ACM increased the percentage of Hb in range: 80.9% in IP2, compared with 72.7% in the CP and reduced the intake of darbepoetin (IP1: 20 [70]; CP 30 [80] μg P=0.032) with less Hb fluctuation (0.91±0.49 in the CP to 0.82±0.37g/dl in IP2, P<0.05), improving in the ACM compliant group. The secondary outcomes decreased with the use of ACM. ACM helps to obtain better anaemia results in haemodialysis patients, minimising the risks of treatment with ESAs and reducing costs. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Modelling IRF8 Deficient Human Hematopoiesis and Dendritic Cell Development with Engineered iPS Cells.

PubMed

Sontag, Stephanie; Förster, Malrun; Qin, Jie; Wanek, Paul; Mitzka, Saskia; Schüler, Herdit M; Koschmieder, Steffen; Rose-John, Stefan; Seré, Kristin; Zenke, Martin

2017-04-01

Human induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers, including hematopoietic stem cells and their progeny. Interferon regulatory factor 8 (IRF8) is a transcription factor, which acts in hematopoiesis as lineage determining factor for myeloid cells, including dendritic cells (DC). Autosomal recessive or dominant IRF8 mutations occurring in patients cause severe monocytic and DC immunodeficiency. To study IRF8 in human hematopoiesis we generated human IRF8-/- iPS cells and IRF8-/- embryonic stem (ES) cells using RNA guided CRISPR/Cas9n genome editing. Upon induction of hematopoietic differentiation, we demonstrate that IRF8 is dispensable for iPS cell and ES cell differentiation into hemogenic endothelium and for endothelial-to-hematopoietic transition, and thus development of hematopoietic progenitors. We differentiated iPS cell and ES cell derived progenitors into CD141+ cross-presenting cDC1 and CD1c+ classical cDC2 and CD303+ plasmacytoid DC (pDC). We found that IRF8 deficiency compromised cDC1 and pDC development, while cDC2 development was largely unaffected. Additionally, in an unrestricted differentiation regimen, IRF8-/- iPS cells and ES cells exhibited a clear bias toward granulocytes at the expense of monocytes. IRF8-/- DC showed reduced MHC class II expression and were impaired in cytokine responses, migration, and antigen presentation. Taken together, we engineered a human IRF8 knockout model that allows studying molecular mechanisms of human immunodeficiencies in vitro, including the pathophysiology of IRF8 deficient DC. Stem Cells 2017;35:898-908. © 2017 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Report of Interest in an Intramural Program. Volume XX, No. 7.

ERIC Educational Resources Information Center

Ryan, J.; Lucas, J.

In fall 1991, a study was conducted at William Rainey Harper College (WRHC), in Palatine, Illinois, to determine the level of interest in a new sports intramural program (IP). Surveys were mailed to a random sample of 600 degree credit students, out of a total population of 15,418 such students. After two mailings and a prompting follow-up, a…

IP and Data Access | Division of Cancer Prevention

Cancer.gov

The following outlines the different patent and licensing mechanisms applicable to studies of third-party agents in the PREVENT Program. Please note that the NCI has a variety of agreement mechanisms by which these terms may be applied and will work with the NCI Technology Transfer Center to determine the appropriate agreement for the studies approved by the PREVENT Program. |

Interactive Profiler: An Intuitive, Web-Based Statistical Application in Visualizing Educational and Marketing Databases

ERIC Educational Resources Information Center

Ip, Edward H.; Leung, Phillip; Johnson, Joseph

2004-01-01

We describe the design and implementation of a web-based statistical program--the Interactive Profiler (IP). The prototypical program, developed in Java, was motivated by the need for the general public to query against data collected from the National Assessment of Educational Progress (NAEP), a large-scale US survey of the academic state of…

Preventive dental management of osteonecrosis of the jaws related to zoledronic acid treatment.

PubMed

Coello-Suanzes, J A; Rollon-Ugalde, V; Castaño-Seiquer, A; Lledo-Villar, E; Herce-Lopez, J; Infante-Cossio, P; Rollon-Mayordomo, A

2018-02-07

To evaluate the effect of preventive dental management on reducing the incidence and delaying the onset of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients treated with intravenous zoledronic acid (ZA). This single-center clinical study included 255 cancer patients monitored over a 6-year period. Patients received dental treatment prior (Group A) or after (Group B) the initiation of ZA therapy. Dental treatments performed, incidence proportion (IP) and incidence rate (IR) in both groups were analyzed using significance tests. BRONJ onset were estimated using the Kaplan-Meier estimator and log-rank test. Independent risk factors to develop BRONJ were evaluated using Cox regression analysis models. 37 patients suffered from BRONJ (IP=14.5%), 7.3% in group A and 36.5% in group B (p=0.000). The IR was 0.007 patients/month in group B and 0.004 in group A. BRONJ free survival at 3 years were 97% in group A and 66% in group B. Survival curves were significant (p=0.056) according to log-rank test. Multivariate Cox models showed that dental extractions (p=0.000) were significant. BRONJ occurred significantly in patients who underwent dental extractions after the initiation of ZA and did not accomplish a preventive dental program. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Telemedicine in the management of chronic pain: a cost analysis study.

PubMed

Pronovost, Antoine; Peng, Philip; Kern, Ralph

2009-08-01

Telemedicine provides patients with easy and remote access to consultant expertise irrespective of geographic location. In a randomized controlled trial, this study has applied a rigorous costing methodology to the use of telemedicine in chronic pain management. We performed a randomized two-period crossover trial comparing in-person (IP) consultation with telemedicine (TM) consultation in the management of chronic pain. Over an 18-month period, 26 patients each completed two diaries capturing their direct and indirect travel costs, daily pain scores, and satisfaction with physician consultation. Costing models were developed to account for direct, indirect, fixed, and variable costs in order to perform break-even analyses. Sensitivity analysis was performed over a broad range of assumptions. Direct patient costs were significantly lower in the TM group than in the IP group, with median cost and interquartile range 133 dollars (28-377) vs 443 dollars (292-1075), respectively (P = 0.001). More patients were highly satisfied with the TM consultation than with the IP consultation (56 and 24%, respectively; P < 0.05). Break-even annual patient volume was estimated at 57 patients. A two-way sensitivity analysis controlling for annual patient volume and round-trip distance indicated that TM remains cost-effective at volumes >50 patients/year or at round-trip distances >200 km. Telemedicine is cost-effective over a broad range of assumptions, including annual patient volumes, travel distance, fuel costs, amortization, and discount rates. This study provides data from a real-world setting to determine relevant thresholds and targets for establishing a TM program for patients who are undergoing chronic pain therapy.

Animal model of methylphenidate's long-term memory-enhancing effects.

PubMed

Carmack, Stephanie A; Howell, Kristin K; Rasaei, Kleou; Reas, Emilie T; Anagnostaras, Stephan G

2014-01-16

Methylphenidate (MPH), introduced more than 60 years ago, accounts for two-thirds of current prescriptions for attention deficit hyperactivity disorder (ADHD). Although many studies have modeled MPH's effect on executive function, almost none have directly modeled its effect on long-term memory (LTM), even though improvement in LTM is a critical target of therapeutic intervention in ADHD. We examined the effects of a wide range of doses of MPH (0.01-10 mg/kg, i.p.) on Pavlovian fear learning, a leading model of memory. MPH's effects were then compared to those of atomoxetine (0.1-10 mg/kg, i.p.), bupropion (0.5-20 mg/kg, i.p.), and citalopram (0.01-10 mg/kg, i.p.). At low, clinically relevant doses, MPH enhanced fear memory; at high doses it impaired memory. MPH's memory-enhancing effects were not confounded by its effects on locomotion or anxiety. Further, MPH-induced memory enhancement seemed to require both dopamine and norepinephrine transporter inhibition. Finally, the addictive potential of MPH (1 mg/kg and 10 mg/kg) was compared to those of two other psychostimulants, amphetamine (0.005 mg/kg and 1.5 mg/kg) and cocaine (0.15 mg/kg and 15 mg/kg), using a conditioned place preference and behavioral sensitization paradigm. We found that memory-enhancing effects of psychostimulants observed at low doses are readily dissociable from their reinforcing and locomotor activating effects at high doses. Together, our data suggest that fear conditioning will be an especially fruitful platform for modeling the effects of psychostimulants on LTM in drug development.

Animal model of methylphenidate's long-term memory-enhancing effects

PubMed Central

Carmack, Stephanie A.; Howell, Kristin K.; Rasaei, Kleou; Reas, Emilie T.; Anagnostaras, Stephan G.

2014-01-01

Methylphenidate (MPH), introduced more than 60 years ago, accounts for two-thirds of current prescriptions for attention deficit hyperactivity disorder (ADHD). Although many studies have modeled MPH's effect on executive function, almost none have directly modeled its effect on long-term memory (LTM), even though improvement in LTM is a critical target of therapeutic intervention in ADHD. We examined the effects of a wide range of doses of MPH (0.01–10 mg/kg, i.p.) on Pavlovian fear learning, a leading model of memory. MPH's effects were then compared to those of atomoxetine (0.1–10 mg/kg, i.p.), bupropion (0.5–20 mg/kg, i.p.), and citalopram (0.01–10 mg/kg, i.p.). At low, clinically relevant doses, MPH enhanced fear memory; at high doses it impaired memory. MPH's memory-enhancing effects were not confounded by its effects on locomotion or anxiety. Further, MPH-induced memory enhancement seemed to require both dopamine and norepinephrine transporter inhibition. Finally, the addictive potential of MPH (1 mg/kg and 10 mg/kg) was compared to those of two other psychostimulants, amphetamine (0.005 mg/kg and 1.5 mg/kg) and cocaine (0.15 mg/kg and 15 mg/kg), using a conditioned place preference and behavioral sensitization paradigm. We found that memory-enhancing effects of psychostimulants observed at low doses are readily dissociable from their reinforcing and locomotor activating effects at high doses. Together, our data suggest that fear conditioning will be an especially fruitful platform for modeling the effects of psychostimulants on LTM in drug development. PMID:24434869

Recapitulating muscle disease phenotypes with myotonic dystrophy 1 iPS cells: a tool for disease modeling and drug discovery.

PubMed

Mondragon-Gonzalez, Ricardo; Perlingeiro, Rita C R

2018-06-13

Myotonic Dystrophy 1 (DM1) is a multi-system disorder primarily affecting the central nervous system, heart and skeletal muscle. It is caused by an expansion of the CTG trinucleotide repeats in the 3' untranslated region of the DMPK gene. Although patient myoblasts have been used for studying the disease in vitro , the invasiveness as well as the low accessibility to muscle biopsies motivate the development of alternative reliable myogenic models. Here, we established two DM1 iPS cell lines from patient-derived fibroblasts, and using the PAX7 conditional expression system, differentiated these into myogenic progenitors, and subsequently, terminally differentiated myotubes. Both DM1 myogenic progenitors and myotubes were found to express the intranuclear RNA foci exhibiting sequestration of MBNL1. Moreover, we found the DM1-related mis-splicing, namely BIN1 exon 11 in DM1 myotubes. We use this model to test a specific therapy, antisense oligonucleotide treatment, and find that this efficiently abolished RNA foci and rescued BIN1 mis-splicing in DM1 iPS cell-derived myotubes. Together, our results demonstrate that myotubes derived from DM1 iPS cells recapitulate the critical molecular features of DM1 and are sensitive to ASO treatment, confirming that these cells can be used for in vitro disease modeling and candidate drug testing or screening. © 2018. Published by The Company of Biologists Ltd.

The role of the human papillomavirus in the pathogenesis of Schneiderian inverted papillomas: an analytic overview of the evidence.

PubMed

Lawson, William; Schlecht, Nicolas F; Brandwein-Gensler, Margaret

2008-06-01

Evidence of an etiological role for human papillomavirus (HPV) in Schneiderian inverted papillomas IP arose in the late 1980's; yet almost three decades later, the association between HPV and IP has yet to be universally accepted. This is probably due to the disparate HPV detection rates in IP reported in the literature. We analyzed the weight of published data in order to address the following questions: why do the HPV detection rates in IP vary so greatly? What is the relationship between low-risk (LR) and high-risk (HR) HPV types and HPV detection rates in IP? Is there a relationship between the presence and type of HPV in IP and recurrence and malignant progression? A search using the Pubmed search engine was performed to identify studies published in English from 01/87 through 12/06 using the MeSH terms ''HPV'' and ''Inverted", "Exophytic", "Oncocytic Schneiderian" or "Fungiform papilloma''. Data was abstracted from publications including histology, HPV target, HPV type, method of detection, etc. HPV results were stratified by histology and other variables. Tests for heterogeneity (between-study variability) were conducted, and weighted prevalence (WP) estimates and 95% confidence intervals (CI) were calculated using a random-effects inverse-variance model stratified on study. The association between HPV IP recurrence was estimated by random-effects inverse-variance weighted odds ratio (OR). Weighted estimates revealed similar detection rates across detection methods, 26.8% (95%CI 16.4-37.2%) by ISH, 25.2% (95%CI 14.7-35.6%) by consensus PCR, and 23.6% (95%CI 12.2-35.0%) by type-specific PCR. A preponderance of HPV 6/11 is found in IP as compared to HPV 16/18; the overall unadjusted ratio of LR to high-risk HR HPV types is 2.8:1 The HPV detection rates significantly increase (Wald t-test P < 0.02) in IPs with high-grade dysplasia (WP 55.8%, 95%CI 30.5-81.0%) and carcinoma (WP 55.1%, 95%CI 37.0-73.2%) as compared to IPs with no dysplasia or mild dysplasia (WP 22.3%, 95%CI 15.9-28.6%). Furthermore, the preponderance of LR HPV in benign IP (ratio LR/HR = 4.8:1) shifts in dysplastic and malignant IP. The LR/HR ratio is 1.1:1 for IPs with high-grade dysplasias, this ratio is inverted to favor HR HPV (1:2.4) for malignant IP. Recurrences developed in 44 of 236 patients; HPV was detected in 27 of 44 IPs (WP 57.9%, 95%CI 31.6-84.2%) that developed recurrences and in 24 of 192 IPs (WP 9.7%, 95%CI 4.4-15.0%) that did not develop recurrence. The presence of HPV was significantly associated with the likelihood of developing recurrence (weighted OR of 10.2, 95%CI 3.2-32.8). We hypothesize that LR HPV may induce IP formation, and then are lost as infected cells are shed, as a "hit and run" phenomenon. HPV detection rates increase in dysplastic IP and SCC-ex-IP with increasing ratio of HR to LR HPV types, compared to nondysplastic IP. We believe that one explanation for the variation in HPV detection rates between different studies may be the actual histologic composition of the cohort. That is, if one series contains a higher frequency of dysplastic and malignant IP, it may have a higher detection rate than another series which contains only nondysplastic IP. We hypothesize that the higher rates of HPV detection in dysplastic and malignant IP may be related to HPV integration. The implication of this is that HPV sub-type testing may identify patients at risk for recurrence, or progression to dysplasia and malignancy, and thus may impact surveillance protocols.

BCX4430, a novel nucleoside analog, effectively treats yellow fever in a Hamster model.

PubMed

Julander, Justin G; Bantia, Shanta; Taubenheim, Brian R; Minning, Dena M; Kotian, Pravin; Morrey, John D; Smee, Donald F; Sheridan, William P; Babu, Yarlagadda S

2014-11-01

No effective antiviral therapies are currently available to treat disease after infection with yellow fever virus (YFV). A Syrian golden hamster model of yellow fever (YF) was used to characterize the effect of treatment with BCX4430, a novel adenosine nucleoside analog. Significant improvement in survival was observed after treatment with BCX4430 at 4 mg/kg of body weight per day dosed intraperitoneally (i.p.) twice daily (BID). Treatment with BCX4430 at 12.5 mg/kg/day administered i.p. BID for 7 days offered complete protection from mortality and also resulted in significant improvement of other YF disease parameters, including weight loss, serum alanine aminotransferase levels (6 days postinfection [dpi]), and viremia (4 dpi). In uninfected hamsters, BCX4430 at 200 mg/kg/day administered i.p. BID for 7 days was well tolerated and did not result in mortality or weight loss, suggesting a potentially wide therapeutic index. Treatment with BCX4430 at 12 mg/kg/day i.p. remained effective when administered once daily and for only 4 days. Moreover, BCX4430 dosed at 200 mg/kg/day i.p. BID for 7 days effectively treated YF, even when treatment was delayed up to 4 days after virus challenge, corresponding with peak viral titers in the liver and serum. BCX4430 treatment did not preclude a protective antibody response, as higher neutralizing antibody (nAb) concentrations corresponded with increasing delays of treatment initiation, and greater nAb responses resulted in the protection of animals from a secondary challenge with YFV. In summary, BCX4430 is highly active in a hamster model of YF, even when treatment is initiated at the peak of viral replication. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Comparison of the WSA-ENLIL model with three CME cone types

NASA Astrophysics Data System (ADS)

Jang, Soojeong; Moon, Y.; Na, H.

2013-07-01

We have made a comparison of the CME-associated shock propagation based on the WSA-ENLIL model with three cone types using 29 halo CMEs from 2001 to 2002. These halo CMEs have cone model parameters as well as their associated interplanetary (IP) shocks. For this study we consider three different cone types (an asymmetric cone model, an ice-cream cone model and an elliptical cone model) to determine 3-D CME parameters (radial velocity, angular width and source location), which are the input values of the WSA-ENLIL model. The mean absolute error (MAE) of the arrival times for the asymmetric cone model is 10.6 hours, which is about 1 hour smaller than those of the other models. Their ensemble average of MAE is 9.5 hours. However, this value is still larger than that (8.7 hours) of the empirical model of Kim et al. (2007). We will compare their IP shock velocities and densities with those from ACE in-situ measurements and discuss them in terms of the prediction of geomagnetic storms.Abstract (2,250 Maximum Characters): We have made a comparison of the CME-associated shock propagation based on the WSA-ENLIL model with three cone types using 29 halo CMEs from 2001 to 2002. These halo CMEs have cone model parameters as well as their associated interplanetary (IP) shocks. For this study we consider three different cone types (an asymmetric cone model, an ice-cream cone model and an elliptical cone model) to determine 3-D CME parameters (radial velocity, angular width and source location), which are the input values of the WSA-ENLIL model. The mean absolute error (MAE) of the arrival times for the asymmetric cone model is 10.6 hours, which is about 1 hour smaller than those of the other models. Their ensemble average of MAE is 9.5 hours. However, this value is still larger than that (8.7 hours) of the empirical model of Kim et al. (2007). We will compare their IP shock velocities and densities with those from ACE in-situ measurements and discuss them in terms of the prediction of geomagnetic storms.

Infection Control Link Nurse Program: An interdisciplinary approach n targeting health care-acquired infection

PubMed Central

Sopirala, Madhuri M.; Yahle-Dunbar, Lisa; Smyer, Justin; Wellington, Linda; Dickman, Jeanne; Zikri, Nancy; Martin, Jennifer; Kulich, Pat; Taylor, David; Mekhjian, Hagop; Nash, Mary; Mansfield, Jerry; Pancholi, Preeti; Howard, Mary; Chase, Linda; Brown, Susan; Kipp, Kristopher; Lefeld, Kristen; Myers, Amber; Pan, Xueliang; Mangino, Julie E.

2014-01-01

Background We describe a successful interdisciplinary liaison program that effectively reduced health care-acquired (HCA), methicillin-resistant Staphylococcus aureus (MRSA) in a university hospital setting. Methods Baseline was from January 2006 to March 2008, and intervention period was April 2008 to September 2009. Staff nurses were trained to be liaisons (link nurses) to infection prevention (IP) personnel with clearly defined goals assigned and with ongoing monthly education. HCA-MRSA incidence per 1,000 patient-days (PD) was compared between baseline and intervention period along with total and non-HCA-MRSA, HCA and non-HCA-MRSA bacteremia, and hand soap/sanitizer usage. Hand hygiene compliance was assessed. Results A reduction in MRSA rates was as follows in intervention period compared with baseline: HCA-MRSA decreased by 28% from 0.92 to 0.67 cases per 1,000 PD (incidence rate ratio, 0.72; 95% confidence interval: 0.62–0.83, P < .001), and HCA-MRSA bacteremia rate was reduced by 41% from 0.18 to 0.10 per 1,000 PD (incidence rate ratio, 0.59; 95% confidence interval: 0.42–0.84, P = .003). Total MRSA rate and MRSA bacteremia rate also showed significant reduction with nonsignificant reductions in overall non-HCA-MRSA and non-HCA-MRSA bacteremia. Hand soap/sanitizer usage and compliance with hand hygiene also increased significantly during IP. Conclusion Link nurse program effectively reduced HCA-MRSA. Goal-defined metrics with ongoing reeducation for the nurses by IP personnel helped drive these results. PMID:24548456

Prediction of oxidation parameters of purified Kilka fish oil including gallic acid and methyl gallate by adaptive neuro-fuzzy inference system (ANFIS) and artificial neural network.

PubMed

Asnaashari, Maryam; Farhoosh, Reza; Farahmandfar, Reza

2016-10-01

As a result of concerns regarding possible health hazards of synthetic antioxidants, gallic acid and methyl gallate may be introduced as natural antioxidants to improve oxidative stability of marine oil. Since conventional modelling could not predict the oxidative parameters precisely, artificial neural network (ANN) and neuro-fuzzy inference system (ANFIS) modelling with three inputs, including type of antioxidant (gallic acid and methyl gallate), temperature (35, 45 and 55 °C) and concentration (0, 200, 400, 800 and 1600 mg L(-1) ) and four outputs containing induction period (IP), slope of initial stage of oxidation curve (k1 ) and slope of propagation stage of oxidation curve (k2 ) and peroxide value at the IP (PVIP ) were performed to predict the oxidation parameters of Kilka oil triacylglycerols and were compared to multiple linear regression (MLR). The results showed ANFIS was the best model with high coefficient of determination (R(2)  = 0.99, 0.99, 0.92 and 0.77 for IP, k1 , k2 and PVIP , respectively). So, the RMSE and MAE values for IP were 7.49 and 4.92 in ANFIS model. However, they were to be 15.95 and 10.88 and 34.14 and 3.60 for the best MLP structure and MLR, respectively. So, MLR showed the minimum accuracy among the constructed models. Sensitivity analysis based on the ANFIS model suggested a high sensitivity of oxidation parameters, particularly the induction period on concentrations of gallic acid and methyl gallate due to their high antioxidant activity to retard oil oxidation and enhanced Kilka oil shelf life. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

The Incredibly Long-Lived SN 2005ip

NASA Astrophysics Data System (ADS)

Fox, Ori

2016-10-01

Type IIn supernovae (SNe IIn) are defined by their relatively narrow spectral line features associated with a dense circumstellar medium (CSM) formed by the progenitor star. The nature of the progenitor and mass loss remains relatively unknown. Shock interaction with the dense CSM can often result in significant UV emission for several years post-explosion, thereby probing the CSM characteristics, progenitor mass loss history and, ultimately, the progenitor itself. The Type IIn SN 2005ip proves to be one of the most interesting and well-studied targets within this subclass. Compared to all other supernovae, SN 2005ip is the most luminous for its age. Now more than 11 years post-explosion, the SN has released >10^51 erg throughout its lifetime as the forward shock continues to collide with a dense CSM. Here we propose HST/STIS-MAMA UV observations of SN 2005ip to investigate the massive CSM. When accounting for the shock travel time, these observations will probe material lost from the progenitor more than 1000 years prior to the explosion. We already have a single HST/STIS spectrum of SN 2005ip from 2014, which was obtained while the shock was still within a higher mass regime. With just 5 orbits, a second spectrum will allow us to directly trace the evolution of the CSM and produce new constraints on the pre-SN mass-loss history. Coinciding with Cycle 24's UV Initiative, this program offers new insight regarding both the progenitor and explosion characteristics of the SN IIn subclass.

The Characteristic Response of Whistler Mode Waves to Interplanetary Shocks

DOE PAGES

Yue, Chao; Chen, Lunjin; Bortnik, Jacob; ...

2017-09-29

Magnetospheric whistler mode waves play a key role in regulating the dynamics of the electron radiation belts. Recent satellite observations indicate a significant influence of interplanetary (IP) shocks on whistler mode wave power in the inner magnetosphere. In this study, we statistically investigate the response of whistler mode chorus and plasmaspheric hiss to IP shocks based on Van Allen Probes and THEMIS satellite observations. Immediately after the IP shock arrival, chorus wave power is usually intensified, often at postmidnight to prenoon sector, while plasmaspheric hiss wave power predominantly decreases near the dayside but intensifies near the nightside. We conclude thatmore » chorus wave intensification outside the plasmasphere is probably associated with the suprathermal electron flux enhancement caused by the IP shock. Through a simple ray tracing modeling assuming the scenario that plasmaspheric hiss is originated from chorus, we find that the solar wind dynamic pressure increase changes the magnetic field configuration to favor ray penetration in the nightside and promote ray refraction away from the dayside, potentially explaining the magnetic local time–dependent responses of plasmaspheric hiss waves following IP shock arrivals.« less

Predictors of intestinal pseudo-obstruction in systemic lupus erythematosus complicated by digestive manifestations: data from a Southern China lupus cohort.

PubMed

Huang, Q; Lai, W; Yuan, C; Shen, S; Cui, D; Zhao, J; Lin, J; Ren, H; Yang, M

2016-03-01

To determine factors that may predict intestinal pseudo-obstruction (IpsO) in systemic lupus erythematosus (SLE) patients complicated by digestive manifestations. SLE patients with digestive manifestations (n = 135) were followed at Southern Medical University affiliated Nanfang Hospital from 2000 until 2013. Demographic variables, clinical features, and laboratory data were compared between the two groups. Univariate and multivariate logistic regression models were used to establish factors that predispose to IpsO in these patients. At the end of the study period, 32 (23.7%) patients had developed IpsO. Mortality (9 patients) was infrequent and the cause of death was unrelated to IpsO. Independent predictors of IpsO in SLE were ureterectasia, anti-U1 RNP(+), peritonitis, and low C3 levels. Regular abdominal X-ray examinations are recommended in SLE patients with ureterectasia, anti-U1 RNP(+), peritonitis, or low C3 levels, as early diagnosis and therapy may prevent unnecessary surgical intervention and improve the disease course. © The Author(s) 2015.

The Characteristic Response of Whistler Mode Waves to Interplanetary Shocks

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

Yue, Chao; Chen, Lunjin; Bortnik, Jacob

Magnetospheric whistler mode waves play a key role in regulating the dynamics of the electron radiation belts. Recent satellite observations indicate a significant influence of interplanetary (IP) shocks on whistler mode wave power in the inner magnetosphere. In this study, we statistically investigate the response of whistler mode chorus and plasmaspheric hiss to IP shocks based on Van Allen Probes and THEMIS satellite observations. Immediately after the IP shock arrival, chorus wave power is usually intensified, often at postmidnight to prenoon sector, while plasmaspheric hiss wave power predominantly decreases near the dayside but intensifies near the nightside. We conclude thatmore » chorus wave intensification outside the plasmasphere is probably associated with the suprathermal electron flux enhancement caused by the IP shock. Through a simple ray tracing modeling assuming the scenario that plasmaspheric hiss is originated from chorus, we find that the solar wind dynamic pressure increase changes the magnetic field configuration to favor ray penetration in the nightside and promote ray refraction away from the dayside, potentially explaining the magnetic local time–dependent responses of plasmaspheric hiss waves following IP shock arrivals.« less

Bandwidth Management in Resource Constrained Networks

DTIC Science & Technology

2012-03-01

Postgraduate School OSI Open Systems Interconnection QoS Quality of Service TCP Transmission Control Protocol/Internet Protocol TCP/IP Transmission...filtering. B. NORMAL TCP/IP COMMUNICATIONS The Internet is a “complex network WAN that connects LANs and clients around the globe” (Dean, 2009...of the Open Systems Interconnection ( OSI ) model allowing them to route traffic based on MAC address (Kurose & Ross, 2009). While switching

INDUCTION OF DNA ADDUCTS, TUMORS, AND KI-RAS ONCOGENE MUTATIONS IN STRAIN A/J MOUSE LUNG BY IP. ADMINISTRATION OF DIBENZ[A,H]ANTHRACENE

EPA Science Inventory

Induction of DNA adducts, tumors, and Ki-ras oncogene mutations in strain AlJ mouse lung by ip. administration of dibenz[a,h]anthracene

Previous studies of polycyclic aromatic hydrocarbon (P AH) induced lung tumors in the strain NJ mouse model system have demonstrated qua...

Adaptation technology between IP layer and optical layer in optical Internet

NASA Astrophysics Data System (ADS)

Ji, Yuefeng; Li, Hua; Sun, Yongmei

2001-10-01

Wavelength division multiplexing (WDM) optical network provides a platform with high bandwidth capacity and is supposed to be the backbone infrastructure supporting the next-generation high-speed multi-service networks (ATM, IP, etc.). In the foreseeable future, IP will be the predominant data traffic, to make fully use of the bandwidth of the WDM optical network, many attentions have been focused on IP over WDM, which has been proposed as the most promising technology for new kind of network, so-called Optical Internet. According to OSI model, IP is in the 3rd layer (network layer) and optical network is in the 1st layer (physical layer), so the key issue is what adaptation technology should be used in the 2nd layer (data link layer). In this paper, firstly, we analyze and compare the current adaptation technologies used in backbone network nowadays. Secondly, aiming at the drawbacks of above technologies, we present a novel adaptation protocol (DONA) between IP layer and optical layer in Optical Internet and describe it in details. Thirdly, the gigabit transmission adapter (GTA) we accomplished based on the novel protocol is described. Finally, we set up an experiment platform to apply and verify the DONA and GTA, the results and conclusions of the experiment are given.

Intellectual property rights, moral imagination, and access to life-enhancing drugs.

PubMed

Werhane, Patricia H; Gorman, Michael

2005-10-01

Although the idea of intellectual property (IP) rights--proprietary rights to what one invents, writes, paints, composes or creates--is firmly embedded in Western thinking, these rights are now being challenged across the globe in a number of areas. This paper will focus on one of those challenges: government-sanctioned copying of patented drugs without permission or license of the patent owner in the name of national security, in health emergencies, or life-threatening epidemics. After discussing standard rights-based and utilitarian arguments defending intellectual property we will present another model. IP is almost always a result of a long history of of scientific or technological development and numbers of networks of creativity, not the act of a single person or a group of people at one moment in time. Thus thinking about and evaluating IP requires a traditional model of IP. It follows that the owner of those rights has some obligations to share that information or its outcomes. If that conclusion is applied to the distribution of antiretroviral drugs, what pharmaceutical companies are ethically required to do to increase access to these medicines in the developing world will have to be reanalyzed from a more systemic perspective.

Scrape-off-layer currents during MHD activity and disruptions in HBT-EP

NASA Astrophysics Data System (ADS)

Levesque, J. P.; Desanto, S.; Battey, A.; Bialek, J.; Brooks, J. W.; Mauel, M. E.; Navratil, G. A.

2017-10-01

We report scrape-off layer (SOL) current measurements during MHD mode activity and disruptions in the HBT-EP tokamak. Currents are measured via Rogowski coils mounted on tiles in the low-field-side SOL, toroidal jumpers between otherwise-isolated vessel sections, and segmented plasma current Rogowski coils. These currents strongly depend on the plasma's major radius, mode amplitude, and mode phase. Plasma current asymmetries and SOL currents during disruptions reach 4% of the plasma current. Asymmetric toroidal currents between vessel sections rotate at tens of kHz through most of the current quench, then symmetrize once Ip reaches 30% of its pre-disruptive value. Toroidal jumper currents oscillate between co- and counter-Ip, with co-Ip being dominant on average during disruptions. Increases in local plasma current correlate with counter-Ip current in the nearest toroidal jumper. Measurements are interpreted in the context of two models that produce contrary predictions for the toroidal vessel current polarity during disruptions. Plasma current asymmetries are consistent with both models, and scale with plasma displacement toward the wall. Progress of ongoing SOL current diagnostic upgrades is also presented. Supported by U.S. DOE Grant DE-FG02-86ER53222.

Service-Oriented Architecture Afloat: A Capabilities-Based Prioritization Scheme

DTIC Science & Technology

2013-04-01

to “information superiority,” ultimately enhancing warfighting capability. Introduction The Program Executive Office for Command, Control...gateway architecture for IP satellite networks with dynamic resource mangement and DiffServ QoS provision. International Journal of Satellite

Photonic Network R&D Activities in Japan-Current Activities and Future Perspectives

NASA Astrophysics Data System (ADS)

Kitayama, Ken-Ichi; Miki, Tetsuya; Morioka, Toshio; Tsushima, Hideaki; Koga, Masafumi; Mori, Kazuyuki; Araki, Soichiro; Sato, Ken-Ichi; Onaka, Hiroshi; Namiki, Shu; Aoyama, Tomonori

2005-10-01

R&D activities on photonic networks in Japan are presented. First, milestones in current ongoing R&D programs supported by Japanese government agencies are introduced, including long-distance and wavelength division multiplexing (WDM) fiber transmission, wavelength routing, optical burst switching (OBS), and control-plane technology for IP backbone networks. Their goal was set to evolve a legacy telecommunications network to IP-over-WDM networks by introducing technologies for WDM and wavelength routing. We then discuss the perspectives of so-called PHASE II R&D programs for photonic networks over the next 5 years until 2010, by focusing on the report that has been recently issued by the Photonic Internet Forum (PIF), a consortium that has major carriers, telecom vendors, and Japanese academics as members. The PHASE II R&D programs should serve to establish a photonic platform to provide abundant bandwidth on demand, at any time on a real-time basis, through the customer's initiative to promote bandwidth-rich applications, such as grid computing, real-time digital-cinema streaming, medical and educational applications, and network storage in e-commerce.

Photonic network R and D activities in Japan

NASA Astrophysics Data System (ADS)

Kitayama, Ken-ichi; Miki, Tetsuya; Morioka, Toshio; Tsushima, Hideaki; Koga, Masafumi; Mori, Kazuyuki; Araki, Soichiro; Sato, Ken-ichi; Onaka, Hiroshi; Namiki, Shu; Aovama, Tomonori

2005-11-01

R and D activities on photonic networks in Japan are presented. First, milestones in current, ongoing R and D programs supported by Japanese government agencies are introduced, including long-distance and WDM fiber transmission, wavelength routing, optical burst switching, and control plane technology for IP backbone networks. Their goal was set to evolve a legacy telecommunications network to IP over WDM networks by introducing technologies for WDM and wavelength routing. We then discuss the perspectives of so-called PHASE II R and D programs for photonic networks over the next five years until 2010, by focusing on the report which has been recently issued by the Photonic Internet Forum (PIF), a consortium that has major carriers, telecom vendors, and Japanese academics as members. The PHASE II R and D programs should serve to establish a photonic platform to provide abundant bandwidth on demand, at any time on a real-time basis through the customer's initiative, to promote bandwidth-rich applications, such as grid computing, real-time digital-cinema streaming, medical and educational applications, and network storage in e-commerce.

The solar ionisation rate deduced from Ulysses measurements and its implications to interplanetary Lyman alpha-intensity

NASA Technical Reports Server (NTRS)

Summanen, T.; Kyroelae, E.

1995-01-01

We have developed a computer code which can be used to study 3-dimensional and time-dependent effects of the solar cycle on the interplanetary (IP) hydrogen distribution. The code is based on the inverted Monte Carlo simulation. In this work we have modelled the temporal behaviour of the solar ionisation rate. We have assumed that during the most of the time of the solar cycle there is an anisotopic latitudinal structure but right at the solar maximum the anisotropy disappears. The effects of this behaviour will be discussed both in regard to the IP hydrogen distribution and IP Lyman a a-intensity.

Induced pluripotent stem cells for regenerative medicine.

PubMed

Hirschi, Karen K; Li, Song; Roy, Krishnendu

2014-07-11

With the discovery of induced pluripotent stem (iPS) cells, it is now possible to convert differentiated somatic cells into multipotent stem cells that have the capacity to generate all cell types of adult tissues. Thus, there is a wide variety of applications for this technology, including regenerative medicine, in vitro disease modeling, and drug screening/discovery. Although biological and biochemical techniques have been well established for cell reprogramming, bioengineering technologies offer novel tools for the reprogramming, expansion, isolation, and differentiation of iPS cells. In this article, we review these bioengineering approaches for the derivation and manipulation of iPS cells and focus on their relevance to regenerative medicine.

Comparison of 74-MHz interplanetary scintillation and IMP 7 observations of the solar wind during 1973

NASA Technical Reports Server (NTRS)

Coles, W. A.; Harmon, J. K.; Lazarus, A. J.; Sullivan, J. D.

1978-01-01

Solar wind velocities measured by earth-orbiting spacecraft are compared with velocities determined from interplanetary scintillation (IPS) observations for 1973, a period when high-velocity streams were prevalent. The spacecraft and IPS velocities agree well in the mean and are highly correlated. No simple model for the distribution of enhanced turbulence within streams is sufficient to explain the velocity comparison results for the entire year. Although a simple proportionality between density fluctuation level and bulk density is consistent with IPS velocities for some periods, some streams appear to have enhanced turbulence in the high-velocity region, where the density is low.

Determining the Roles of Inositol Trisphosphate Receptors in Neurodegeneration: Interdisciplinary Perspectives on a Complex Topic.

PubMed

Takada, Silvia Honda; Ikebara, Juliane Midori; de Sousa, Erica; Cardoso, Débora Sterzeck; Resende, Rodrigo Ribeiro; Ulrich, Henning; Rückl, Martin; Rüdiger, Sten; Kihara, Alexandre Hiroaki

2017-11-01

It is well known that calcium (Ca 2+ ) is involved in the triggering of neuronal death. Ca 2+ cytosolic levels are regulated by Ca 2+ release from internal stores located in organelles, such as the endoplasmic reticulum. Indeed, Ca 2+ transit from distinct cell compartments follows complex dynamics that are mediated by specific receptors, notably inositol trisphosphate receptors (IP3Rs). Ca 2+ release by IP3Rs plays essential roles in several neurological disorders; however, details of these processes are poorly understood. Moreover, recent studies have shown that subcellular location, molecular identity, and density of IP3Rs profoundly affect Ca 2+ transit in neurons. Therefore, regulation of IP3R gene products in specific cellular vicinities seems to be crucial in a wide range of cellular processes from neuroprotection to neurodegeneration. In this regard, microRNAs seem to govern not only IP3Rs translation levels but also subcellular accumulation. Combining new data from molecular cell biology with mathematical modelling, we were able to summarize the state of the art on this topic. In addition to presenting how Ca 2+ dynamics mediated by IP3R activation follow a stochastic regimen, we integrated a theoretical approach in an easy-to-apply, cell biology-coherent fashion. Following the presented premises and in contrast to previously tested hypotheses, Ca 2+ released by IP3Rs may play different roles in specific neurological diseases, including Alzheimer's disease and Parkinson's disease.

Effectiveness of individual placement and support supported employment for young adults.

PubMed

Bond, Gary R; Drake, Robert E; Campbell, Kikuko

2016-08-01

The individual placement and support (IPS) model of supported employment was first developed in community mental health centres for adults with severe mental illness. While IPS is an established evidence-based practice in this broad population, evidence on its effectiveness focused specifically on young adults has been limited. The current study aimed to address this gap. To investigate the effects of IPS on young adults, the authors conducted a secondary analysis on a pooled sample of 109 unemployed young adults (under age 30) from four randomized controlled trials employing a common research protocol that included a standardized measurement battery and rigorous fidelity monitoring. Researchers assessed these participants over 18 months on nine competitive employment outcome measures. On all measures, the IPS group had significantly better employment outcomes. Overall, 40 (82%) of IPS participants obtained employment during follow-up compared with 25 (42%) of control participants, χ(2) = 17.9, P < .001. IPS participants averaged 25.0 weeks of employment, compared with 7.0 weeks for control participants, t = 4.50, P < .001. The current analysis supports a small number of previous studies in showing that IPS is highly effective in helping young adults with severe mental illness to attain competitive employment. When young adults acquire competitive jobs and initiate a path towards normal adult roles, they may avoid the cycle of disability and psychiatric patient roles that are demeaning and demoralizing. © 2014 Wiley Publishing Asia Pty Ltd.

Modeling and inversion Matlab algorithms for resistivity, induced polarization and seismic data

NASA Astrophysics Data System (ADS)

Karaoulis, M.; Revil, A.; Minsley, B. J.; Werkema, D. D.

2011-12-01

M. Karaoulis (1), D.D. Werkema (3), A. Revil (1,2), A., B. Minsley (4), (1) Colorado School of Mines, Dept. of Geophysics, Golden, CO, USA. (2) ISTerre, CNRS, UMR 5559, Université de Savoie, Equipe Volcan, Le Bourget du Lac, France. (3) U.S. EPA, ORD, NERL, ESD, CMB, Las Vegas, Nevada, USA . (4) USGS, Federal Center, Lakewood, 10, 80225-0046, CO. Abstract We propose 2D and 3D forward modeling and inversion package for DC resistivity, time domain induced polarization (IP), frequency-domain IP, and seismic refraction data. For the resistivity and IP case, discretization is based on rectangular cells, where each cell has as unknown resistivity in the case of DC modelling, resistivity and chargeability in the time domain IP modelling, and complex resistivity in the spectral IP modelling. The governing partial-differential equations are solved with the finite element method, which can be applied to both real and complex variables that are solved for. For the seismic case, forward modeling is based on solving the eikonal equation using a second-order fast marching method. The wavepaths are materialized by Fresnel volumes rather than by conventional rays. This approach accounts for complicated velocity models and is advantageous because it considers frequency effects on the velocity resolution. The inversion can accommodate data at a single time step, or as a time-lapse dataset if the geophysical data are gathered for monitoring purposes. The aim of time-lapse inversion is to find the change in the velocities or resistivities of each model cell as a function of time. Different time-lapse algorithms can be applied such as independent inversion, difference inversion, 4D inversion, and 4D active time constraint inversion. The forward algorithms are benchmarked against analytical solutions and inversion results are compared with existing ones. The algorithms are packaged as Matlab codes with a simple Graphical User Interface. Although the code is parallelized for multi-core cpus, it is not as fast as machine code. In the case of large datasets, someone should consider transferring parts of the code to C or Fortran through mex files. This code is available through EPA's website on the following link http://www.epa.gov/esd/cmb/GeophysicsWebsite/index.html Although this work was reviewed by EPA and approved for publication, it may not necessarily reflect official Agency policy.

A Thriving and Innovative Undergraduate Experiential Physics Program

NASA Astrophysics Data System (ADS)

Roughani, Bahram

2013-03-01

The thriving physics program at Kettering University has experienced a three-fold increase in the number of physics majors since 2002. Our unique physics program requires students alternate between on-campus academic terms and off-campus co-op work terms on a three months rotation format to complete their degree in 4.5 years that includes summer as either school or co-op term. Students complete a minimum of five terms (~15 months) of cooperative work terms, and two terms (~6 months) of senior thesis work. The IP of the thesis work done at a co-op site belongs to the company. This has attracted co-op sponsors for our program by removing the IP concerns. The cooperative and experiential education part of our program is required for graduation, without any credits assigned to it. At the end of every co-op term students' work performance is evaluated by their co-op supervisor, which should match expected performance standards. In addition to co-op and thesis, our programs include a senior capstone design project course, concentrations within physics (Acoustics, Optics, and Materials), a required technical sequence outside physics, as well as entrepreneurship across curriculum. The success of our student securing the highest paid jobs for undergraduate physics majors in the nation plus their success in graduate studies are the main ``Pull Factors'' that has lead to three fold increase the physics majors since 2002.

Multi-views storage model and access methods of conversation history in converged IP messaging system

NASA Astrophysics Data System (ADS)

Lu, Meilian; Yang, Dong; Zhou, Xing

2013-03-01

Based on the analysis of the requirements of conversation history storage in CPM (Converged IP Messaging) system, a Multi-views storage model and access methods of conversation history are proposed. The storage model separates logical views from physical storage and divides the storage into system managed region and user managed region. It simultaneously supports conversation view, system pre-defined view and user-defined view of storage. The rationality and feasibility of multi-view presentation, the physical storage model and access methods are validated through the implemented prototype. It proves that, this proposal has good scalability, which will help to optimize the physical data storage structure and improve storage performance.

Antidiarrhoeal activity of seed extract of Albizzia lebbeck Benth.

PubMed

Besra, S E; Gomes, A; Chaudhury, L; Vedasiromoni, J R; Ganguly, D K

2002-09-01

The antidiarrhoeal activity of the seed extract of Albizzia lebbeck (Benth.) was investigated employing conventional rodent models of diarrhoea, i.e. castor oil-induced diarrhoea, upper gastrointestinal transit (u.g.t.) and fluid secretion. It was found that the aqueous methanol extract of Albizzia lebbeck seeds (2.5-5 mg/kg i.p.) possessed antidiarrhoeal activity which strengthens the earlier use of the seeds in the treatment of diarrhoea and dysentery. The antidiarrhoeal dose of the extract was at least 10-30 times less than the LD(50) dose. The extract (2.5-5 mg/kg i.p.) potentiated the antidiarrhoeal activity of loperamide (1 mg/kg i.p.). Nalaxone (0.5 mg/kg i.p.) significantly inhibited the antidiarrhoeal activity of the extract as well as loperamide, thus indicating a role of the opioid system in the antidiarrhoeal activity of the extract. Copyright 2002 John Wiley & Sons, Ltd.

Assessing the role of Hartree-Fock exchange, correlation energy and long range corrections in evaluating ionization potential, and electron affinity in density functional theory.

PubMed

Vikramaditya, Talapunur; Lin, Shiang-Tai

2017-06-05

Accurate determination of ionization potentials (IPs), electron affinities (EAs), fundamental gaps (FGs), and HOMO, LUMO energy levels of organic molecules play an important role in modeling and predicting the efficiencies of organic photovoltaics, OLEDs etc. In this work, we investigate the effects of Hartree Fock (HF) Exchange, correlation energy, and long range corrections in predicting IP and EA in Hybrid Functionals. We observe increase in percentage of HF exchange results in increase of IPs and decrease in EAs. Contrary to the general expectations inclusion of both HF exchange and correlation energy (from the second order perturbation theory MP2) leads to poor prediction. Range separated Hybrid Functionals are found to be more reliable among various DFT Functionals investigated. DFT Functionals predict accurate IPs whereas post HF methods predict accurate EAs. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Time Series Model Identification and Prediction Variance Horizon.

DTIC Science & Technology

1980-06-01

stationary time series Y(t). -6- In terms of p(v), the definition of the three time series memory types is: No Memory Short Memory Long Memory X IP (v)I 0 0...X lp(v)l < - I IP (v) = v=1 v=l v=l Within short memory time series there are three types whose classification in terms of correlation functions is...1974) "Some Recent Advances in Time Series Modeling", TEEE Transactions on Automatic ControZ, VoZ . AC-19, No. 6, December, 723-730. Parzen, E. (1976) "An

HIGH-TIME-RESOLUTION MEASUREMENTS OF THE POLARIZATION OF THE CRAB PULSAR AT 1.38 GHz

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

Słowikowska, Agnieszka; Stappers, Benjamin W.; Harding, Alice K.

2015-01-20

Using the Westerbork Synthesis Radio Telescope, we obtained high-time-resolution measurements of the full polarization of the Crab pulsar. At a resolution of 1/8192 of the 34 ms pulse period (i.e., 4.1 μs), the 1.38 GHz linear-polarization measurements are in general agreement with previous lower-time-resolution 1.4 GHz measurements of linear polarization in the main pulse (MP), in the interpulse (IP), and in the low-frequency component (LFC). We find the MP and IP to be linearly polarized at about 24% and 21% with no discernible difference in polarization position angle. However, contrary to theoretical expectations and measurements in the visible, we find nomore » evidence for significant variation (sweep) in the polarization position angle over the MP, the IP, or the LFC. We discuss the implications, which appear to be in contradiction to theoretical expectations. We also detect weak circular polarization in the MP and IP, and strong (≈20%) circular polarization in the LFC, which also exhibits very strong (≈98%) linear polarization at a position angle of 40° from that of the MP or IP. The properties are consistent with the LFC, which is a low-altitude component, and the MP and IP, which are high-altitude caustic components. Current models for the MP and IP emission do not readily account for the absence of pronounced polarization changes across the pulse. We measure IP and LFC pulse phases relative to the MP consistent with recent measurements, which have shown that the phases of these pulse components are evolving with time.« less

Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2.

PubMed

Grubb, Søren; Aistrup, Gary L; Koivumäki, Jussi T; Speerschneider, Tobias; Gottlieb, Lisa A; Mutsaers, Nancy A M; Olesen, Søren-Peter; Calloe, Kirstine; Thomsen, Morten B

2015-08-01

Inherited ion channelopathies and electrical remodeling in heart disease alter the cardiac action potential with important consequences for excitation-contraction coupling. Potassium channel-interacting protein 2 (KChIP2) is reduced in heart failure and interacts under physiological conditions with both Kv4 to conduct the fast-recovering transient outward K(+) current (Ito,f) and with CaV1.2 to mediate the inward L-type Ca(2+) current (ICa,L). Anesthetized KChIP2(-/-) mice have normal cardiac contraction despite the lower ICa,L, and we hypothesized that the delayed repolarization could contribute to the preservation of contractile function. Detailed analysis of current kinetics shows that only ICa,L density is reduced, and immunoblots demonstrate unaltered CaV1.2 and CaVβ₂ protein levels. Computer modeling suggests that delayed repolarization would prolong the period of Ca(2+) entry into the cell, thereby augmenting Ca(2+)-induced Ca(2+) release. Ca(2+) transients in disaggregated KChIP2(-/-) cardiomyocytes are indeed comparable to wild-type transients, corroborating the preserved contractile function and suggesting that the compensatory mechanism lies in the Ca(2+)-induced Ca(2+) release event. We next functionally probed dyad structure, ryanodine receptor Ca(2+) sensitivity, and sarcoplasmic reticulum Ca(2+) load and found that increased temporal synchronicity of the Ca(2+) release in KChIP2(-/-) cardiomyocytes may reflect improved dyad structure aiding the compensatory mechanisms in preserving cardiac contractile force. Thus the bimodal effect of KChIP2 on Ito,f and ICa,L constitutes an important regulatory effect of KChIP2 on cardiac contractility, and we conclude that delayed repolarization and improved dyad structure function together to preserve cardiac contraction in KChIP2(-/-) mice. Copyright © 2015 the American Physiological Society.

Uncertain translation, uncertain benefit and uncertain risk: ethical challenges facing first-in-human trials of induced pluripotent stem (ips) cells.

PubMed

Fung, Ronald K F; Kerridge, Ian H

2013-02-01

The discovery of induced pluripotent stem (iPS) cells in 2006 was heralded as a major breakthrough in stem cell research. Since then, progress in iPS cell technology has paved the way towards clinical application, particularly cell replacement therapy, which has refueled debate on the ethics of stem cell research. However, much of the discourse has focused on questions of moral status and potentiality, overlooking the ethical issues which are introduced by the clinical testing of iPS cell replacement therapy. First-in-human trials, in particular, raise a number of ethical concerns including informed consent, subject recruitment and harm minimisation as well as the inherent uncertainty and risks which are involved in testing medical procedures on humans for the first time. These issues, while a feature of any human research, become more complex in the case of iPS cell therapy, given the seriousness of the potential risks, the unreliability of available animal models, the vulnerability of the target patient group, and the high stakes of such an intensely public area of science. Our paper will present a detailed case study of iPS cell replacement therapy for Parkinson's disease to highlight these broader ethical and epistemological concerns. If we accept that iPS cell technology is fraught with challenges which go far beyond merely refuting the potentiality of the stem cell line, we conclude that iPS cell research should not replace, but proceed alongside embryonic and adult somatic stem cell research to promote cross-fertilisation of knowledge and better clinical outcomes. © 2011 Blackwell Publishing Ltd.

The involvement of NMDA receptor/NO/cGMP pathway in the antidepressant like effects of baclofen in mouse force swimming test.

PubMed

Khan, Muhammad Imran; Ostadhadi, Sattar; Zolfaghari, Samira; Ejtemaei Mehr, Shahram; Hassanzadeh, Gholamreza; Dehpour, Ahmad-Reza

2016-01-26

In the current study, the involvement of N-methyl-d-aspartate receptor (NMDAR) and nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system in the antidepressant-like effects of baclofen was evaluated by using animal model in forced swimming test. Followed by an open field test for the evaluation of locomotor activity, the immobility time for mice in force swimming test was recorded. Only the last four min was analyzed. Administration of Baclofen (0.5 and 1mg/kg, i.p.) reduced the immobility interval in the FST. Prior administration of l-arginine (750mg/kg, i.p.,) a nitric oxide synthase substrate or sildenafil (5mg/kg, i.p.) a phosphodiesterase 5 into mice suppressed the antidepressant-like activity of baclofen (1mg/kg, i.p.).Co-treatment of 7-nitroindazole (50mg/kg, i.p.,) an inhibitor of neuronal nitric oxide synthase, L-NAME (10mg/kg, i.p.,) a non-specific inhibitor of nitric oxide synthase or MK-801 (0.05mg/kg, i.p.) an NMDA receptor antagonist with subeffective dose of baclofen (0.1mg/kg, i.p.), reduced the immobility time in the FST as compared to the drugs when used alone. Co-administrated of lower doses of MK-801 (0.01mg/kg) or l-NAME (1mg/kg) failed to effect immobility time however, simultaneous administration of these two agents in same dose with subeffective dose of baclofen (0.1mg/kg, i.p.), minimized the immobility time in the FST. Thus, our results support the role of NMDA receptors and l-arginine-NO-GMP pathway in the antidepressant-like action of baclofen. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cord Blood 8-Isoprostane in the Preterm Infant

PubMed Central

Mestan, Karen; Matoba, Nana; Arguelles, Lester; Harvey, Candace; Ernst, Linda M.; Farrow, Kathryn; Wang, Xiaobin

2012-01-01

Background Cord blood 8-isoprostane (8-IP) is a marker of lipid peroxidation in the peripartum period. The independent association with degree of prematurity is not well-described. Objective To identify patterns of lipid peroxidation among early, moderate and late preterm infants, and to understand how cord blood 8-IP varies with gestational age (GA) and related covariates. Study Design Mother-infant pairs from 237 preterm births were studied as part of a longitudinal birth cohort study. GA subgroups were defined as extremely (≤28w), moderately (29-33w), and late (34-36w) preterm. Cord blood 8-IP was measured using EIA. Elevated 8-IP (4th quartile) was the primary outcome for multivariate logistic regression models, which were adjusted for maternal age/race, multiple gestation and infant gender, as well as other relevant covariates. Results Elevated 8-IP was associated with extremely preterm birth (OR=4.31; 95% CI=1.90, 9.76), and was inversely associated with increasing GA (OR=0.88; 95% CI=0.80, 0.97). Elevated 8-IP was also associated with decreasing birth weight (BW), clinical chorioamnionitis, fetal inflammatory response of the placenta (FIR), and signs of perinatal depression. The GA on 8-IP association appeared to be modified by several maternal disease and fetal-infant factors. Lastly, the indirect associations between log-transformed 8-IP, GA and BW appeared to be most prominent for GA<30w and for BW<2000 grams. Conclusion Lipid peroxidation in preterm birth, and the relative influence of accompanying peripartum factors, varies according to degree of prematurity. These findings have important implications for the developmental regulation of antioxidant defense and its impact on neonatal outcomes. PMID:22425039

Neuropharmacology of light-induced locomotor activation.

PubMed

Amato, Davide; Pum, Martin E; Groos, Dominik; Lauber, Andrea C; Huston, Joseph P; Carey, Robert J; de Souza Silva, Maria A; Müller, Christian P

2015-08-01

Presentation of non-aversive light stimuli for several seconds was found to reliably induce locomotor activation and exploratory-like activity. Light-induced locomotor activity (LIA) can be considered a convenient simple model to study sensory-motor activation. LIA was previously shown to coincide with serotonergic and dopaminergic activation in specific cortical areas in freely moving and anesthetized animals. In the present study we explore the neuropharmacology of LIA using a receptor antagonist/agonist approach in rats. The non-selective 5-HT2-receptor antagonist ritanserin (1.5-6 mg/kg, i.p.) dose-dependently reduced LIA. Selective antagonism of either the 5-HT2A-receptor by MDL 11,939 (0.1-0.4 mg/kg, i.p.), or the 5-HT2C-receptor by SDZ SER 082 (0.125-0.5 mg/kg, i.p.), alone or in combination, had no significant influence on LIA. Also the selective 5-HT1A-receptor antagonist, WAY 100635 (0.4 mg/kg, i.p.) did not affect LIA. Neither did the preferential dopamine D2-receptor antagonist, haloperidol (0.025-0.1 mg/kg, i.p.) nor the D2/D3-receptor agonist, quinpirole (0.025-0.5 mg/kg, i.p.) affect the expression of LIA. However, blocking the glutamatergic NMDA-receptor with phencyclidine (PCP, 1.5-6 mg/kg, i.p.) dose-dependently reduced LIA. This effect was also observed with ketamine (10 mg/kg, i.p.). These findings suggest that serotonin and dopamine receptors abundantly expressed in the cortex do not mediate light-stimulus triggered locomotor activity. PCP and ketamine effects, however, suggest an important role of NMDA receptors in LIA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human IP10-scFv and DC-induced CTL synergistically inhibit the growth of glioma in a xenograft model.

PubMed

Wang, Xuan; Zhang, Fang-Cheng; Zhao, Hong-Yang; Lu, Xiao-Ling; Sun, Yun; Xiong, Zhi-Yong; Jiang, Xiao-Bing

2014-08-01

The epidermal growth factor receptor (EGFR) mutant of EGFRvIII is highly expressed in glioma cells, and the EGFRvIII-specific dendritic cell (DC)-induced tumor antigen-specific CD8(+) cytotoxic T lymphocytes (CTLs) may hold promise in cancer immunotherapy. Interferon (IFN)-γ-inducible protein (IP)-10 (IP-10) is a potent inhibitor of angiogenesis and can recruit CXCR3(+) T cells, including CD8(+) T cells, which are important for the control of tumor growth. In this study, we assessed if the combination of IP10-EGFRvIIIscFv with DC-induced CTLs would improve the therapeutic antitumor efficacy. IP10-scFv was generated by linking the human IP-10 gene with the DNA fragment for anti-EGFRvIIIscFv with a (Gly4Ser)3 flexible linker, purified by affinity chromatography, and characterized for its anti-EGFRvIII immunoreactivity and chemotactic activity. DCs were isolated from human peripheral blood monocyte cells and pulsed with EGFRvIII-peptide, then co-cultured with autologous CD8(+) T cells. BALB/c-nu mice were inoculated with human glioma U87-EGFRvIII cells in the brain and treated intracranially with IP10-scFv and/or intravenously with DC-induced CTLs for evaluating the therapeutic effect. Treatment with both IP10-scFv and EGFRvIII peptide-pulsed, DC-induced CTL synergistically inhibited the growth of glioma and prolonged the survival of tumor-bearing mice, which was accompanied by the inhibition of tumor angiogenesis and enhancement of cytotoxicity, thereby increasing the numbers of brain-infiltrating lymphocytes (BILs) and prolonging the residence time of CTLs in the tumor.

Functional Cooperation between the IP3 Receptor and Phospholipase C Secures the High Sensitivity to Light of Drosophila Photoreceptors In Vivo

PubMed Central

Kohn, Elkana; Katz, Ben; Yasin, Bushra; Peters, Maximilian; Rhodes, Elisheva; Zaguri, Rachel; Weiss, Shirley

2015-01-01

Drosophila phototransduction is a model system for the ubiquitous phosphoinositide signaling. In complete darkness, spontaneous unitary current events (dark bumps) are produced by spontaneous single Gqα activation, while single-photon responses (quantum bumps) arise from synchronous activation of several Gqα molecules. We have recently shown that most of the spontaneous single Gqα activations do not produce dark bumps, because of a critical phospholipase Cβ (PLCβ) activity level required for bump generation. Surpassing the threshold of channel activation depends on both PLCβ activity and cellular [Ca2+], which participates in light excitation via a still unclear mechanism. We show here that in IP3 receptor (IP3R)-deficient photoreceptors, both light-activated Ca2+ release from internal stores and light sensitivity were strongly attenuated. This was further verified by Ca2+ store depletion, linking Ca2+ release to light excitation. In IP3R-deficient photoreceptors, dark bumps were virtually absent and the quantum-bump rate was reduced, indicating that Ca2+ release from internal stores is necessary to reach the critical level of PLCβ catalytic activity and the cellular [Ca2+] required for excitation. Combination of IP3R knockdown with reduced PLCβ catalytic activity resulted in highly suppressed light responses that were partially rescued by cellular Ca2+ elevation, showing a functional cooperation between IP3R and PLCβ via released Ca2+. These findings suggest that in contrast to the current dogma that Ca2+ release via IP3R does not participate in light excitation, we show that released Ca2+ plays a critical role in light excitation. The positive feedback between PLCβ and IP3R found here may represent a common feature of the inositol-lipid signaling. PMID:25673847

[Effects of propranolol on oxygen-induced retinal neovascularization in mouse].

PubMed

Huang, Xuerong; Wang, Yajuan; Yang, Guangran; Yang, Zixin; Zhang, Jingshang

2016-02-01

To investigate whether propranolol application as collyrium or intraperitoneal (IP) injection can promote the recovery of oxygen-induced retinopathy (OIR). Thirty-six 7-day-old mice were divided into the following 6 groups: normal control, propranolol eye drops, propranolol IP injection, eye drops negative control, IP injection negative control, and pathological model with 6 mice in each. In a typical model of OIR, litters of mice pups with their nursing mothers were exposed to an infant incubator to high oxygen concentration (75 ± 5)% between postnatal day (PD) 7 and PD12, prior to returning to room air. Two routes of propranolol treatment were assessed from PD12 to PD17: IP injection and eye drop, with doses 2 mg/(kg·time), three times a day. Another three groups were given citric acid buffer eye drops, IP injection of citric acid buffer, and negative control were not treated with any drug. Neonatal mice fed in normal conditions served as normal control. Mice were sacrificed at PD17 to evaluate the morphological changes of retinal vessels by fluorescein isothiocyanate-dextran perfusion and retinal whole mount. The retinal neovascularization was evaluated by counting the number of nuclei of the endothelial cell breaking through the internal limiting membrane (ILM). Compared with the oxygen-exposed group, the branches of retinal vessels went normal with a less un-perfused area in the propranolol eye drops and propranolol IP injection groups [(38.9 ± 9.9)% and (5.6 ± 2.3)% vs. (16.2 ± 10.0)% and (2.2 ± 0.8)%, (25.9 ± 5.0)% and (2.1 ± 2.7)%, F=36.12 and 14.55, P both<0.001]. The number of nuclei of endothelial cells breaking through the ILM on the retinal cross-section in the propranolol eye drops group decreased (14.2 ± 5.1) per slide, which was less than that in the oxygen-exposed group (49.1 ± 8.9) per slide and the propranolol IP injection group (18.0 ± 5.9) per slide; it was also less than that in the eye drops negative control group (47.4 ± 8.1) per slide (F=187.60, P<0.05). Moreover, the number of nuclei of endothelial cells breaking through the ILM on the retinal cross-section in the propranolol IP injection group was less than that in the IP injection negative control group (49.9 ± 7.1) per slide (P<0.05). Propranolol could effectively inhibit the formation of retinal neovascularization in mice; the eye drops was more effective than the IP injection.

Ergosteryl 2-naphthoate, An Ergosterol Derivative, Exhibits Antidepressant Effects Mediated by the Modification of GABAergic and Glutamatergic Systems.

PubMed

Lin, Mingzhu; Li, Haijun; Zhao, Yan; Cai, Enbo; Zhu, Hongyan; Gao, Yugang; Liu, Shuangli; Yang, He; Zhang, Lianxue; Tang, Guosheng; Wang, Ruiqing

2017-03-31

Phytosterols are a kind of natural component including sitosterol, campesterol, avenasterol, ergosterol (Er) and others. Their main natural sources are vegetable oils and their processed products, followed by grains, by-products of cereals and nuts, and small amounts of fruits, vegetables and mushrooms. In this study, three new Er monoester derivatives were obtained from the reflux reaction with Er: organic acids (furoic acid, salicylic acid and 2-naphthoic acid), 1-Ethylethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP) in dichloromethane. Their chemical structures were defined by IR and NMR. The present study was also undertaken to investigate the antidepressant-like effects of Er and its derivatives in male adult mice models of depression, and their probable involvement of GABAergic and glutamatergic systems by the forced swim test (FST). The results indicated that Er and its derivatives display antidepressant effects. Moreover, one derivative of Er, ergosteryl 2-naphthoate (ErN), exhibited stronger antidepressant activity in vivo compared to Er. Acute administration of ErN (5 mg/kg, i.p.) and a combination of ErN (0.5 mg/kg, i.p.), reboxetine (2.5 mg/kg, i.p.), and tianeptine (15 mg/kg, i.p.) reduced the immobility time in the FST. Pretreatment with bicuculline (a competitive γ-aminobutyric acid (GABA) antagonist, 4 mg/kg, i.p.) and N -methyl-d-aspartic acid (NMDA, an agonist at the glutamate site, 75 mg/kg, i.p.) effectively reversed the antidepressant-like effect of ErN (5 mg/kg, i.p.). However, prazosin (a α1-adrenoceptor antagonist, 1 mg/kg, i.p.) and haloperidol (a non-selective D2 receptor antagonist, 0.2 mg/kg, i.p.) did not eliminate the reduced immobility time. Altogether, these results indicated that ErN produced antidepressant-like activity, which might be mediated by GABAergic and glutamatergic systems.

Superior reductions in hepatic steatosis and fibrosis with co-administration of a glucagon-like peptide-1 receptor agonist and obeticholic acid in mice.

PubMed

Jouihan, Hani; Will, Sarah; Guionaud, Silvia; Boland, Michelle L; Oldham, Stephanie; Ravn, Peter; Celeste, Anthony; Trevaskis, James L

2017-11-01

Nonalcoholic steatohepatitis (NASH) is an unmet need associated with metabolic syndrome. There are no approved therapies for NASH; however, glucagon-like peptide-1 receptor (GLP-1R) and farnesoid-X receptor (FXR) agonists are promising drug targets. We investigated the therapeutic effects of co-administration of a GLP-1R agonist, IP118, with FXR agonist obeticholic acid (OCA) in mice. OCA and IP118 alone and in combination were sub-chronically administered to Lep ob /Lep ob mice with diet-induced NASH or diet-induced obese (DIO) mice. Metabolic (body weight and glucose) and liver (biochemical and histological) endpoints were assessed. NASH severity in Lep ob /Lep ob mice was graded using a customized integrated scoring system. OCA reduced liver weight and lipid in NASH mice (both by -17%) but had no effect on plasma ALT or AST levels. In contrast, IP118 significantly reduced liver weight (-21%), liver lipid (-15%), ALT (-29%), and AST (-27%). The combination of OCA + IP118 further reduced liver weight (-29%), liver lipid (-22%), ALT (-39%), and AST (-36%). Combination therapy was superior to monotherapies in reducing hepatic steatosis, inflammation, and fibrosis. Hepatic improvements with IP118 and OCA + IP118 were associated with reduced body weight (-4.3% and -3.5% respectively) and improved glycemic control in OCA + IP118-treated mice. In DIO mice, OCA + IP118 co-administration reduced body weight (-25.3%) to a greater degree than IP118 alone (-12.5%) and further improved glucose tolerance and reduced hepatic lipid. Our data suggest a complementary or synergistic therapeutic effect of GLP-1R and FXR agonism in mouse models of metabolic disease and NASH. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Non-Viral Generation of Marmoset Monkey iPS Cells by a Six-Factor-in-One-Vector Approach

PubMed Central

Debowski, Katharina; Warthemann, Rita; Lentes, Jana; Salinas-Riester, Gabriela; Dressel, Ralf; Langenstroth, Daniel; Gromoll, Jörg; Sasaki, Erika; Behr, Rüdiger

2015-01-01

Groundbreaking studies showed that differentiated somatic cells of mouse and human origin could be reverted to a stable pluripotent state by the ectopic expression of only four proteins. The resulting pluripotent cells, called induced pluripotent stem (iPS) cells, could be an alternative to embryonic stem cells, which are under continuous ethical debate. Hence, iPS cell-derived functional cells such as neurons may become the key for an effective treatment of currently incurable degenerative diseases. However, besides the requirement of efficacy testing of the therapy also its long-term safety needs to be carefully evaluated in settings mirroring the clinical situation in an optimal way. In this context, we chose the long-lived common marmoset monkey (Callithrix jacchus) as a non-human primate species to generate iPS cells. The marmoset monkey is frequently used in biomedical research and is gaining more and more preclinical relevance due to the increasing number of disease models. Here, we describe, to our knowledge, the first-time generation of marmoset monkey iPS cells from postnatal skin fibroblasts by non-viral means. We used the transposon-based, fully reversible piggyback system. We cloned the marmoset monkey reprogramming factors and established robust and reproducible reprogramming protocols with a six-factor-in-one-construct approach. We generated six individual iPS cell lines and characterized them in comparison with marmoset monkey embryonic stem cells. The generated iPS cells are morphologically indistinguishable from marmoset ES cells. The iPS cells are fully reprogrammed as demonstrated by differentiation assays, pluripotency marker expression and transcriptome analysis. They are stable for numerous passages (more than 80) and exhibit euploidy. In summary, we have established efficient non-viral reprogramming protocols for the derivation of stable marmoset monkey iPS cells, which can be used to develop and test cell replacement therapies in preclinical settings. PMID:25785453

Non-viral generation of marmoset monkey iPS cells by a six-factor-in-one-vector approach.

PubMed

Debowski, Katharina; Warthemann, Rita; Lentes, Jana; Salinas-Riester, Gabriela; Dressel, Ralf; Langenstroth, Daniel; Gromoll, Jörg; Sasaki, Erika; Behr, Rüdiger

2015-01-01

Groundbreaking studies showed that differentiated somatic cells of mouse and human origin could be reverted to a stable pluripotent state by the ectopic expression of only four proteins. The resulting pluripotent cells, called induced pluripotent stem (iPS) cells, could be an alternative to embryonic stem cells, which are under continuous ethical debate. Hence, iPS cell-derived functional cells such as neurons may become the key for an effective treatment of currently incurable degenerative diseases. However, besides the requirement of efficacy testing of the therapy also its long-term safety needs to be carefully evaluated in settings mirroring the clinical situation in an optimal way. In this context, we chose the long-lived common marmoset monkey (Callithrix jacchus) as a non-human primate species to generate iPS cells. The marmoset monkey is frequently used in biomedical research and is gaining more and more preclinical relevance due to the increasing number of disease models. Here, we describe, to our knowledge, the first-time generation of marmoset monkey iPS cells from postnatal skin fibroblasts by non-viral means. We used the transposon-based, fully reversible piggyback system. We cloned the marmoset monkey reprogramming factors and established robust and reproducible reprogramming protocols with a six-factor-in-one-construct approach. We generated six individual iPS cell lines and characterized them in comparison with marmoset monkey embryonic stem cells. The generated iPS cells are morphologically indistinguishable from marmoset ES cells. The iPS cells are fully reprogrammed as demonstrated by differentiation assays, pluripotency marker expression and transcriptome analysis. They are stable for numerous passages (more than 80) and exhibit euploidy. In summary, we have established efficient non-viral reprogramming protocols for the derivation of stable marmoset monkey iPS cells, which can be used to develop and test cell replacement therapies in preclinical settings.

State of Infection Prevention in US Hospitals Enrolled in NHSN

PubMed Central

Pogorzelska-Maziarz, Monika; Herzig, Carolyn T. A.; Weiner, Lindsey M.; Furuya, E. Yoko; Dick, Andrew; Larson, Elaine

2014-01-01

Background This report provides a national cross-sectional snapshot of infection prevention and control programs and clinician compliance with the implementation of processes to prevent healthcare associated infections (HAI) in intensive care units (ICUs). Methods All hospitals, except for Veterans Affairs hospitals, enrolled in the National Healthcare Safety Network (NHSN) were eligible to participate. Participation included: 1) completion of a survey that assessed presence of evidence-based prevention policies and clinician adherence, and 2) joining our NHSN research group. Descriptive statistics were computed. Facility characteristics and HAI rates by ICU type were compared between respondents and non-respondents. Results Of the 3,374 eligible hospitals, 975 hospitals provided data (29% response rate) on 1,653 ICUs; and, there were complete data on the presence of policies in 1,534 ICUs. The average number of infection preventionists (IPs) per 100 beds was 1.2. Certification of IP staff varied across institutions and the average hours per week of data management and secretarial support were generally low. There was variation in the presence of policies and clinician adherence to these policies. There were no differences in HAI rates between respondents and non-respondents. Conclusions Guidelines around IP staffing in acute care hospitals should be updated. In future publications we will analyze the associations between HAI rates and infection prevention and control program characteristics, presence of and clinician adherence to evidence-based policies. PMID:24485365

Altitude Scaling of Thermal Ice Protection Systems in Running Wet Operation

NASA Technical Reports Server (NTRS)

Orchard, D. M.; Addy, H. E.; Wright, W. B.; Tsao, J.

2017-01-01

A study into the effects of altitude on an aircraft thermal Ice Protection System (IPS) performance has been conducted by the National Research Council Canada (NRC) in collaboration with the NASA Glenn Icing Branch. The study included tests of an airfoil model, with a heated-air IPS, installed in the NRCs Altitude Icing Wind Tunnel (AIWT) at altitude and ground level conditions.

R5 clade C SHIV strains with tier 1 or 2 neutralization sensitivity: tools to dissect env evolution and to develop AIDS vaccines in primate models.

PubMed

Siddappa, Nagadenahalli B; Watkins, Jennifer D; Wassermann, Klemens J; Song, Ruijiang; Wang, Wendy; Kramer, Victor G; Lakhashe, Samir; Santosuosso, Michael; Poznansky, Mark C; Novembre, Francis J; Villinger, François; Else, James G; Montefiori, David C; Rasmussen, Robert A; Ruprecht, Ruth M

2010-07-21

HIV-1 clade C (HIV-C) predominates worldwide, and anti-HIV-C vaccines are urgently needed. Neutralizing antibody (nAb) responses are considered important but have proved difficult to elicit. Although some current immunogens elicit antibodies that neutralize highly neutralization-sensitive (tier 1) HIV strains, most circulating HIVs exhibiting a less sensitive (tier 2) phenotype are not neutralized. Thus, both tier 1 and 2 viruses are needed for vaccine discovery in nonhuman primate models. We constructed a tier 1 simian-human immunodeficiency virus, SHIV-1157ipEL, by inserting an "early," recently transmitted HIV-C env into the SHIV-1157ipd3N4 backbone [1] encoding a "late" form of the same env, which had evolved in a SHIV-infected rhesus monkey (RM) with AIDS. SHIV-1157ipEL was rapidly passaged to yield SHIV-1157ipEL-p, which remained exclusively R5-tropic and had a tier 1 phenotype, in contrast to "late" SHIV-1157ipd3N4 (tier 2). After 5 weekly low-dose intrarectal exposures, SHIV-1157ipEL-p systemically infected 16 out of 17 RM with high peak viral RNA loads and depleted gut CD4+ T cells. SHIV-1157ipEL-p and SHIV-1157ipd3N4 env genes diverge mostly in V1/V2. Molecular modeling revealed a possible mechanism for the increased neutralization resistance of SHIV-1157ipd3N4 Env: V2 loops hindering access to the CD4 binding site, shown experimentally with nAb b12. Similar mutations have been linked to decreased neutralization sensitivity in HIV-C strains isolated from humans over time, indicating parallel HIV-C Env evolution in humans and RM. SHIV-1157ipEL-p, the first tier 1 R5 clade C SHIV, and SHIV-1157ipd3N4, its tier 2 counterpart, represent biologically relevant tools for anti-HIV-C vaccine development in primates.

Sampling and data handling methods for inhalable particulate sampling. Final report nov 78-dec 80

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

Smith, W.B.; Cushing, K.M.; Johnson, J.W.

1982-05-01

The report reviews the objectives of a research program on sampling and measuring particles in the inhalable particulate (IP) size range in emissions from stationary sources, and describes methods and equipment required. A computer technique was developed to analyze data on particle-size distributions of samples taken with cascade impactors from industrial process streams. Research in sampling systems for IP matter included concepts for maintaining isokinetic sampling conditions, necessary for representative sampling of the larger particles, while flowrates in the particle-sizing device were constant. Laboratory studies were conducted to develop suitable IP sampling systems with overall cut diameters of 15 micrometersmore » and conforming to a specified collection efficiency curve. Collection efficiencies were similarly measured for a horizontal elutriator. Design parameters were calculated for horizontal elutriators to be used with impactors, the EPA SASS train, and the EPA FAS train. Two cyclone systems were designed and evaluated. Tests on an Andersen Size Selective Inlet, a 15-micrometer precollector for high-volume samplers, showed its performance to be with the proposed limits for IP samplers. A stack sampling system was designed in which the aerosol is diluted in flow patterns and with mixing times simulating those in stack plumes.« less

Effects of cannabidiol on amphetamine-induced oxidative stress generation in an animal model of mania.

PubMed

Valvassori, Samira S; Elias, Guilherme; de Souza, Bruna; Petronilho, Fabrícia; Dal-Pizzol, Felipe; Kapczinski, Flávio; Trzesniak, Clarissa; Tumas, Vitor; Dursun, Serdar; Chagas, Marcos Hortes Nisihara; Hallak, Jaime E C; Zuardi, Antonio W; Quevedo, João; Crippa, José A S

2011-02-01

Cannabidiol (CBD), a Cannabis sativa constituent, may present a pharmacological profile similar to mood stabilizing drugs, in addition to anti-oxidative and neuroprotective properties. The present study aims to directly investigate the effects of CBD in an animal model of mania induced by D-amphetamine (D-AMPH). In the first model (reversal treatment), rats received saline or D-AMPH (2 mg/kg) once daily intraperitoneal (i.p.) for 14 days, and from the 8th to the 14th day, they were treated with saline or CBD (15, 30 or 60 mg/kg) i.p. twice a day. In the second model (prevention treatment), rats were pretreated with saline or CBD (15, 30, or 60 mg/kg) regime i.p. twice a day, and from the 8th to the 14th day, they also received saline or D-AMPH i.p. once daily. In the hippocampus CBD (15 mg/kg) reversed the d-AMPH-induced damage and increased (30 mg/kg) brain-derived neurotrophic factor (BDNF) expression. In the second experiment, CBD (30 or 60 mg/kg) prevented the D-AMPH-induced formation of carbonyl group in the prefrontal cortex. In the hippocampus and striatum the D-AMPH-induced damage was prevented by CBD (15, 30 or 60 mg/kg). At both treatments CBD did not present any effect against d-AMPH-induced hyperactivity. In conclusion, we could not observe effects on locomotion, but CBD protect against d-AMPH-induced oxidative protein damage and increased BDNF levels in the reversal model and these effects vary depending on the brain regions evaluated and doses of CBD administered.

Targeting Src in Mucinous Ovarian Carcinoma

PubMed Central

Matsuo, Koji; Nishimura, Masato; Bottsford-Miller, Justin N.; Huang1, Jie; Komurov, Kakajan; Armaiz-Pena, Guillermo N.; Shahzad, Mian M. K.; Stone, Rebecca L.; Roh, Ju Won; Sanguino, Angela M.; Lu, Chunhua; Im, Dwight D.; Rosenshien, Neil B.; Sakakibara, Atsuko; Nagano, Tadayoshi; Yamasaki, Masato; Enomoto, Takayuki; Kimura, Tadashi; Ram, Prahlad T.; Schmeler, Kathleen M.; Gallick, Gary E.; Wong, Kwong K.; Frumovitz, Michael; Sood, Anil K.

2014-01-01

PURPOSE Mucinous ovarian carcinomas have a distinct clinical pattern compared to other subtypes of ovarian carcinoma. Here, we evaluated (i) stage-specific clinical significance of mucinous ovarian carcinomas in a large cohort and (ii) the functional role of src kinase in pre-clinical models of mucinous ovarian carcinoma. EXPERIMENTAL DESIGN 1302 ovarian cancer patients including 122 (9.4%) cases of mucinous carcinoma were evaluated for survival analyses. Biological effects of src kinase inhibition were tested in a novel orthotopic mucinous ovarian cancer model (RMUG-S-ip2) using dasatinib-based therapy. RESULTS Patients with advanced-stage mucinous ovarian cancer had significantly worse survival compared to those with serous histology: median overall survival, 1.67 versus 3.41 years, p=0.002; and median survival time after recurrence of 0.53 versus 1.66 years, p<0.0001. Among multiple ovarian cancer cell lines, RMUG-S-ip2 mucinous ovarian cancer cells showed the highest src kinase activity. Moreover, oxaliplatin treatment induced phosphorylation of src kinase. This induced activity by oxaliplatin therapy was inhibited by concurrent administration of dasatinib. Targeting src with dasatinib in vivo showed significant anti-tumor effects in the RMUG-S-ip2 model, but not in the serous ovarian carcinoma (SKOV3-TR) model. Combination therapy of oxaliplatin with dasatinib further demonstrated significant effects on reducing cell viability, increasing apoptosis, and in vivo anti-tumor effects in the RMUG-S-ip2 model. CONCLUSIONS Our results suggest that poor survival of women with mucinous ovarian carcinoma is associated with resistance to cytotoxic therapy. Targeting src kinase with combination of dasatinib and oxaliplatin may be an attractive approach in this disease. PMID:21737505

Implementation fidelity of Multidimensional Family Therapy in an international trial.

PubMed

Rowe, Cynthia; Rigter, Henk; Henderson, Craig; Gantner, Andreas; Mos, Kees; Nielsen, Philip; Phan, Olivier

2013-04-01

Implementation fidelity, a critical aspect of clinical trials research that establishes adequate delivery of the treatment as prescribed in treatment manuals and protocols, is also essential to the successful implementation of effective programs into new practice settings. Although infrequently studied in the drug abuse field, stronger implementation fidelity has been linked to better outcomes in practice but appears to be more difficult to achieve with greater distance from model developers. In the INternational CAnnabis Need for Treatment (INCANT) multi-national randomized clinical trial, investigators tested the effectiveness of Multidimensional Family Therapy (MDFT) in comparison to individual psychotherapy (IP) in Brussels, Berlin, Paris, The Hague, and Geneva with 450 adolescents with a cannabis use disorder and their parents. This study reports on the implementation fidelity of MDFT across these five Western European sites in terms of treatment adherence, dose and program differentiation, and discusses possible implications for international implementation efforts. Copyright © 2013 Elsevier Inc. All rights reserved.

The ability of GAP1IP4BP to function as a Rap1 GTPase-activating protein (GAP) requires its Ras GAP-related domain and an arginine finger rather than an asparagine thumb.

PubMed

Kupzig, Sabine; Bouyoucef-Cherchalli, Dalila; Yarwood, Sam; Sessions, Richard; Cullen, Peter J

2009-07-01

GAP1(IP4BP) is a member of the GAP1 family of Ras GTPase-activating proteins (GAPs) that includes GAP1(m), CAPRI, and RASAL. Composed of a central Ras GAP-related domain (RasGRD), surrounded by amino-terminal C2 domains and a carboxy-terminal PH/Btk domain, these proteins, with the notable exception of GAP1(m), possess an unexpected arginine finger-dependent GAP activity on the Ras-related protein Rap1 (S. Kupzig, D. Deaconescu, D. Bouyoucef, S. A. Walker, Q. Liu, C. L. Polte, O. Daumke, T. Ishizaki, P. J. Lockyer, A. Wittinghofer, and P. J. Cullen, J. Biol. Chem. 281:9891-9900, 2006). Here, we have examined the mechanism through which GAP1(IP4BP) can function as a Rap1 GAP. We show that deletion of domains on either side of the RasGRD, while not affecting Ras GAP activity, do dramatically perturb Rap1 GAP activity. By utilizing GAP1(IP4BP)/GAP1(m) chimeras, we establish that although the C2 and PH/Btk domains are required to stabilize the RasGRD, it is this domain which contains the catalytic machinery required for Rap1 GAP activity. Finally, a key residue in Rap1-specific GAPs is a catalytic asparagine, the so-called asparagine thumb. By generating a molecular model describing the predicted Rap1-binding site in the RasGRD of GAP1(IP4BP), we show that mutagenesis of individual asparagine or glutamine residues that lie in close proximity to the predicted binding site has no detectable effect on the in vivo Rap1 GAP activity of GAP1(IP4BP). In contrast, we present evidence consistent with a model in which the RasGRD of GAP1(IP4BP) functions to stabilize the switch II region of Rap1, allowing stabilization of the transition state during GTP hydrolysis initiated by the arginine finger.

Performance improvement and implementation science: infection prevention competencies for current and future role development.

PubMed

Hanchett, Marilyn

2012-05-01

The Association for Professionals in Infection Control and Epidemiology, Inc, developed its first model of infection preventionist (IP) competency in 2011. The model is based on the principles of patient safety, professional and practice standards, and core competencies identified through research conducted by the Certification Board of Infection Control and Epidemiology, Inc. In addition, the model highlights 4 domains that are predicted to be key areas for future competency development. Performance improvement (PI) and implementation represent 1 of the 4 forward-focused domains. Concurrently, the inclusion of implementation science (IS) in the competency model is consistent with the research goals established by the Association for Professionals in Infection Control and Epidemiology, Inc, in its 2020 strategic plan. This article explains the importance of PI and IS and describes their relevance to the current and future IP role development. Significant challenges such as role delineation and compression are discussed. The need for the IP to acquire new competencies at integrating, as well as differentiating, PI and IS are explored in terms of emerging issues and trends. Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Integrative Analysis of PRKAG2 Cardiomyopathy iPS and Microtissue Models Identifies AMPK as a Regulator of Metabolism, Survival, and Fibrosis.

PubMed

Hinson, J Travis; Chopra, Anant; Lowe, Andre; Sheng, Calvin C; Gupta, Rajat M; Kuppusamy, Rajarajan; O'Sullivan, John; Rowe, Glenn; Wakimoto, Hiroko; Gorham, Joshua; Burke, Michael A; Zhang, Kehan; Musunuru, Kiran; Gerszten, Robert E; Wu, Sean M; Chen, Christopher S; Seidman, Jonathan G; Seidman, Christine E

2016-12-20

AMP-activated protein kinase (AMPK) is a metabolic enzyme that can be activated by nutrient stress or genetic mutations. Missense mutations in the regulatory subunit, PRKAG2, activate AMPK and cause left ventricular hypertrophy, glycogen accumulation, and ventricular pre-excitation. Using human iPS cell models combined with three-dimensional cardiac microtissues, we show that activating PRKAG2 mutations increase microtissue twitch force by enhancing myocyte survival. Integrating RNA sequencing with metabolomics, PRKAG2 mutations that activate AMPK remodeled global metabolism by regulating RNA transcripts to favor glycogen storage and oxidative metabolism instead of glycolysis. As in patients with PRKAG2 cardiomyopathy, iPS cell and mouse models are protected from cardiac fibrosis, and we define a crosstalk between AMPK and post-transcriptional regulation of TGFβ isoform signaling that has implications in fibrotic forms of cardiomyopathy. Our results establish critical connections among metabolic sensing, myocyte survival, and TGFβ signaling. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Iconographic Professional Interests Inventory (3IP): A New Validation Study

PubMed Central

Boerchi, Diego; Magnano, Paola

2015-01-01

Interests have been a central focus of counselling psychology (and vocational psychology in particular) for over 100 years. The awareness of professional interests increases self-knowledge and provides occupational information. In career counselling, vocational interests are assessed more frequently than any other vocational construct, though early evaluations (before 13 years old) of professional interests are very rare. The aim of this research is to examine the 3IP construct (Iconographic Professional Interests Inventory; an inventory composed of 65 stylised pictures that represent people in the act of performing a job) in depth, testing more models in addition to the 19 vocational areas proposed in the 3IP manual. Results show that most of the vocational areas can be grouped into 4 second-level areas (“things”, “people”, “leisure”, and “culture”). Moreover, Holland’s RIASEC model is tested; an accurate selection of items reveals that this model works well using 24 specific jobs. The research concludes that the inventory has good psychometric qualities which can grow further by mean of the increasing, in a targeted way, of the number of jobs. PMID:27247679

Unraveling the biology of bipolar disorder using induced pluripotent stem-derived neurons.

PubMed

Miller, Nathaniel D; Kelsoe, John R

2017-11-01

Bipolar disorder has been studied from numerous angles, from pathological studies to large-scale genomic studies, overall making moderate gains toward an understanding of the disorder. With the advancement of induced pluripotent stem (iPS) cell technology, in vitro models based on patient samples are now available that inherently incorporate the complex genetic variants that largely are the basis for this disorder. A number of groups are starting to apply iPS technology to the study of bipolar disorder. We selectively reviewed the literature related to understanding bipolar disorder based on using neurons derived from iPS cells. So far, most work has used the prototypical iPS cells. However, others have been able to transdifferentiate fibroblasts directly to neurons. Others still have utilized olfactory epithelium tissue as a source of neural-like cells that do not need reprogramming. In general, iPS and related cells can be used for studies of disease pathology, drug discovery, or stem cell therapy. Published studies have primarily focused on understanding bipolar disorder pathology, but initial work is also being done to use iPS technology for drug discovery. In terms of disease pathology, some evidence is pointing toward a differentiation defect with more ventral cell types being prominent. Additionally, there is evidence for a calcium signaling defect, a finding that builds on the genome-wide association study results. Continued work with iPS cells will certainly help us understand bipolar disorder and provide a way forward for improved treatments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Avoidance of accelerated aging in schizophrenia?: Clinical and biological characterization of an exceptionally high functioning individual.

PubMed

Palmer, Barton W; Moore, Raeanne C; Eyler, Lisa T; Pinto, Luz L; Saks, Elyn R; Jeste, Dilip V

2018-06-01

To determine the clinical and biological characteristics of an exceptionally high functioning index person (IP) with schizophrenia in her mid-50s, which may represent compensatory mechanisms, and potentially, avoidance of the accelerated aging typically associated with schizophrenia. IP, 11 other women with schizophrenia, and 11 non-psychiatric comparison (NC) women were assessed with standard ratings of psychopathology, neurocognitive function, decisional capacity, and functional brain imaging. IP was also compared to a sample of demographically similar NCs (N=45) and persons with schizophrenia (N=42) on a set of blood-based biomarkers of aging related to metabolic function, oxidative stress, and inflammation. IP's scores on working memory, and levels of brain activation during an affective face matching task in the left fusiform, right lingual, and left precentral gyri, exceeded NCs. IP was similar to NCs in severity of negative symptoms, most neurocognitive functions, decisional capacity, and brain activation in the left inferior occipital gyrus during a selective stopping task. IP's levels on 11 of 14 metabolic and inflammatory biomarkers of aging were better than NCs and the schizophrenia group. Although speculative, results suggest a possible model in which superior working memory permits a person to be aware of the potentially psychotic nature of a thought or perception, and adjust response accordingly. Compensatory overactivity of brain regions during affective processing may also reflect heightened meta-awareness in emotional situations. Biomarker levels raise the possibility that IP partially avoided the accelerated biological aging associated with schizophrenia. Published by Elsevier B.V.

Updated estimate of trans fat intake by the US population.

PubMed

Doell, D; Folmer, D; Lee, H; Honigfort, M; Carberry, S

2012-01-01

The dietary intake of industrially-produced trans fatty acids (IP-TFA) was estimated for the US population (aged 2 years or more), children (aged 2-5 years) and teenage boys (aged 13-18 years) using the 2003-2006 National Health and Nutrition Examination Survey (NHANES) food consumption database, market share information and trans fat levels based on label survey data and analytical data for packaged and in-store purchased foods. For fast foods, a Monte Carlo model was used to estimate IP-TFA intake. Further, the intake of trans fat was also estimated using trans fat levels reported in the US Department of Agriculture (USDA) National Nutrient Database for Standard Reference, Release 22 (SR 22, 2009) and the 2003-2006 NHANES food consumption database. The cumulative intake of IP-TFA was estimated to be 1.3 g per person per day (g/p/d) at the mean for the US population. Based on this estimate, the mean dietary intake of IP-TFA has decreased significantly from that cited in the 2003 US Food and Drug Administration (FDA) final rule that established labelling requirements for trans fat (4.6 g/p/d for adults). Although the overall intake of IP-TFA has decreased as a result of the implementation of labelling requirements, individuals with certain dietary habits may still consume high levels of IP-TFA if certain brands or types of food products are frequently chosen.

Patterns of tobacco-use behavior among Chinese smokers with medical conditions.

PubMed

Wong, Candice C; Tong, Elisa K; Tsoh, Janice Y; Chen, Meng-Jinn; Hom, Fred B

2009-12-01

Understanding the characteristics of Chinese American smokers with medical conditions and factors associated with their tobacco-use behaviors will guide effective cessation programs. In 2008, the authors described socio-demographic profiles of Chinese smokers with medical conditions treated during the period 2002-2006, documented their tobacco-use behaviors (i.e., average daily cigarette use, nicotine dependence, and number of past-year quit attempts), and drew comparisons between subjects recruited from hospitals (IP) and ambulatory settings (OP). Compared to OP, IP were significantly older, less educated, less acculturated, and more likely to be retired. Of the two groups, IP had poorer disease profiles, smoked less (4.4 vs. 11.9 cigarettes per day), and had lower nicotine-addiction scores (5.5 vs. 6.7). There was no difference between groups in past-year quit attempts. After adjustments, the data revealed that being employed and OP was associated with higher average daily cigarette use; IP were less nicotine dependent than OP; and for both groups, years of smoking was negatively associated with past-year quit attempts. Our study suggests that, more than acculturation level, health status influences the Chinese smoker's level of cigarette use and nicotine addiction. Given the severity of their disease profiles, IP should be aggressively targeted for intervention, as they are more likely to be light smokers and to be less nicotine dependent than OP. Future tobacco treatment studies should pay attention to health status among smokers in health-care settings in order to provide a more accurate assessment of treatment needs and of barriers to successful smoking cessation.

How Interplanetary Scintillation Data Can Improve Modeling of Coronal Mass Ejection Propagation

NASA Astrophysics Data System (ADS)

Taktakishvili, A.; Mays, M. L.; Manoharan, P. K.; Rastaetter, L.; Kuznetsova, M. M.

2017-12-01

Coronal mass ejections (CMEs) can have a significant impact on the Earth's magnetosphere-ionosphere system and cause widespread anomalies for satellites from geosynchronous to low-Earth orbit and produce effects such as geomagnetically induced currents. At the NASA/GSFC Community Coordinated Modeling Center we have been using ensemble modeling of CMEs since 2012. In this presnetation we demonstrate that using of interplanetary scintillation (IPS) observations from the Ooty Radio Telescope facility in India can help to track CME propagaion and improve ensemble forecasting of CMEs. The observations of the solar wind density and velocity using IPS from hundreds of distant sources in ensemble modeling of CMEs can be a game-changing improvement of the current state of the art in CME forecasting.

Non-Singular Modeling of Rigid Manipulators.

DTIC Science & Technology

1986-12-01

SOJQCE 09 FONDING NoMBERS PROG-RAM PRO,ECT -ASK v1 W K .. Ni ELEMEFNT NO NO NO I ACCES;C)1 NO N ON:-zlVTLvIP ’"fPFILINC OFPTRCI1) TAIT rT( Q ; E RSO...AUTHORIS r eamrred. khavvq’_ .33 " t0 QFOQ 13t)’ E COIRED TO4 DATE OF REPORT lYcir MonfhP Day) S P.%t~r (,),%T S I ; . - A T 0 N& (C)SAI. CODES I i...tr he po--,nt of singul -ar-ity. One solution is to s:e:-, a --,mmamu: t me at r oosit:ocn or to avoid t>i:c’ . alt :- e ::.: n t-.te r *solution is to

Modular data acquisition system and its use in gas-filled detector readout at ESRF

NASA Astrophysics Data System (ADS)

Sever, F.; Epaud, F.; Poncet, F.; Grave, M.; Rey-Bakaikoa, V.

1996-09-01

Since 1992, 18 ESRF beamlines are open to users. Although the data acquisition requirements vary a lot from one beamline to another, we are trying to implement a modular data acquisition system architecture that would fit with the maximum number of acquisition projects at ESRF. Common to all of these systems are large acquisition memories and the requirement to visualize the data during an acquisition run and to transfer them quickly after the run to safe storage. We developed a general memory API handling the acquisition memory and its organization and another library that provides calls for transferring the data over TCP/IP sockets. Interesting utility programs using these libraries are the `online display' program and the `data transfer' program. The data transfer program as well as an acquisition control program rely on our well-established `device server model', which was originally designed for the machine control system and then successfully reused in beamline control systems. In the second half of this paper, the acquisition system for a 2D gas-filled detector is presented, which is one of the first concrete examples using the proposed modular data acquisition architecture.

A Kinetic Model for Calcium Dynamics in RAW 264.7 Cells: 1. Mechanisms, Parameters, and Subpopulational Variability

PubMed Central

Maurya, Mano Ram; Subramaniam, Shankar

2007-01-01

Calcium (Ca2+) is an important second messenger and has been the subject of numerous experimental measurements and mechanistic studies in intracellular signaling. Calcium profile can also serve as a useful cellular phenotype. Kinetic models of calcium dynamics provide quantitative insights into the calcium signaling networks. We report here the development of a complex kinetic model for calcium dynamics in RAW 264.7 cells stimulated by the C5a ligand. The model is developed using the vast number of measurements of in vivo calcium dynamics carried out in the Alliance for Cellular Signaling (AfCS) Laboratories. Ligand binding, phospholipase C-β (PLC-β) activation, inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) dynamics, and calcium exchange with mitochondria and extracellular matrix have all been incorporated into the model. The experimental data include data from both native and knockdown cell lines. Subpopulational variability in measurements is addressed by allowing nonkinetic parameters to vary across datasets. The model predicts temporal response of Ca2+ concentration for various doses of C5a under different initial conditions. The optimized parameters for IP3R dynamics are in agreement with the legacy data. Further, the half-maximal effect concentration of C5a and the predicted dose response are comparable to those seen in AfCS measurements. Sensitivity analysis shows that the model is robust to parametric perturbations. PMID:17483174

Immunoendocrine alterations following Marine Corps Martial Arts training are associated with changes in moral cognitive processes.

PubMed

Siedlik, Jacob A; Deckert, Jake A; Clopton, Aaron W; Gigliotti, Nicole; Chan, Marcia A; Benedict, Stephen H; Herda, Trent J; Gallagher, Philip M; Vardiman, John P

2016-02-01

Combined physical and psychological stress events have been associated with exacerbated endocrine responses and increased alterations in immune cell trafficking when compared to exercise stress alone. Military training programs are rigorous in nature and often purposefully delivered in environments combining high levels of both physical and mental stress. The objective of this study was to assess physiological and cognitive changes following U.S. Marine Corps Martial Arts training. Seven active-duty, male Marines were observed during a typical Marine Corps Martial Arts training session. Immune parameters, including immunomodulatory cytokines, and hormone concentrations were determined from blood samples obtained at baseline, immediately post training (IP) and at 15min intervals post-training to 1h (R15, R30, R45, R60). Assessments of cognitive moral functioning (moral judgment and intent) were recorded at intervals during recovery. There were significant fluctuations in immunoendocrine parameters. Peak endocrine measures were observed within the IP-R15 time interval. Distributions of circulating immune cells were significantly altered with neutrophils and all lymphocyte subsets elevated at IP. IFN-γ and IL-17a exhibited small, non-significant, parallel increases over the recovery period. Moral functioning was informed by different social identities during the recovery resulting in changes in moral decision-making. These data demonstrate that the Marine Corps Martial Arts Program induces significant alterations in lymphocyte and leukocyte distributions, but does not shift the balance of Th1/Th2 cytokines or induce a systemic inflammatory response. The program does, however, induce alterations in moral decision-making ability associated with the observed endocrine responses, even suggesting a potential interaction between one's social identities and endocrine responses upon moral decision-making. Copyright © 2015. Published by Elsevier Inc.

Characterization of Burkholderia pseudomallei Strains Using a Murine Intraperitoneal Infection Model and In Vitro Macrophage Assays.

PubMed

Welkos, Susan L; Klimko, Christopher P; Kern, Steven J; Bearss, Jeremy J; Bozue, Joel A; Bernhards, Robert C; Trevino, Sylvia R; Waag, David M; Amemiya, Kei; Worsham, Patricia L; Cote, Christopher K

2015-01-01

Burkholderia pseudomallei, the etiologic agent of melioidosis, is a gram-negative facultative intracellular bacterium. This bacterium is endemic in Southeast Asia and Northern Australia and can infect humans and animals by several routes. It has also been estimated to present a considerable risk as a potential biothreat agent. There are currently no effective vaccines for B. pseudomallei, and antibiotic treatment can be hampered by nonspecific symptomology, the high incidence of naturally occurring antibiotic resistant strains, and disease chronicity. Accordingly, there is a concerted effort to better characterize B. pseudomallei and its associated disease. Before novel vaccines and therapeutics can be tested in vivo, a well characterized animal model is essential. Previous work has indicated that mice may be a useful animal model. In order to develop standardized animal models of melioidosis, different strains of bacteria must be isolated, propagated, and characterized. Using a murine intraperitoneal (IP) infection model, we tested the virulence of 11 B. pseudomallei strains. The IP route offers a reproducible way to rank virulence that can be readily reproduced by other laboratories. This infection route is also useful in distinguishing significant differences in strain virulence that may be masked by the exquisite susceptibility associated with other routes of infection (e.g., inhalational). Additionally, there were several pathologic lesions observed in mice following IP infection. These included varisized abscesses in the spleen, liver, and haired skin. This model indicated that commonly used laboratory strains of B. pseudomallei (i.e., K96243 and 1026b) were significantly less virulent as compared to more recently acquired clinical isolates. Additionally, we characterized in vitro strain-associated differences in virulence for macrophages and described a potential inverse relationship between virulence in the IP mouse model of some strains and in the macrophage phagocytosis assay. Strains which were more virulent for mice (e.g., HBPU10304a) were often less virulent in the macrophage assays, as determined by several parameters such as intracellular bacterial replication and host cell cytotoxicity.

IPS analysis on relationship among velocity, density and temperature of the solar wind

NASA Astrophysics Data System (ADS)

Hayashi, K.; Tokumaru, M.; Fujiki, K.

2015-12-01

The IPS(Interplanetary Scintillation)-MHD(magnetohydrodynamics) tomography is a method we have developed to determine three-dimensional MHD solution of the solar wind that best matches the line-of-sight IPS solar-wind speed data (Hayashi et al., 2003). The tomographic approach is an iteration method in which IPS observations are simulated in MHD steady-state solution, then differences between the simulated observation and the actual IPS observation is reduced by modifying solar-wind boundary map at 50 solar radii. This forward model needs to assume solar wind density and temperature as function of speed. We use empirical functions, N(V) and T(V), derived from Helios in-situ measurement data within 0.5 AU in 1970s. For recent years, especially after 2006, these functions yield higher densities and lower temperatures than in-situ measurements indicate. To characterize the differences between the simulated and actual solar wind plasma, we tune parameters in the functions so that agreements with in-situ data (near the Earth and at Ulysses) will be optimized. This optimization approach can help better simulations of the solar corona and heliosphere, and will help our understandings on roles of magnetic field in solar wind heating and acceleration.

[Unresolved issues in the evaluation of research projects involving induced pluripotent stem cells (iPS)].

PubMed

Casado, María; de Lecuona, Itziar

2013-01-01

This paper identifies problems and analyzes those conflicts posed by the evaluation of research projects involving the collection and use of human induced pluripotent stem cells (iPS) in Spain. Current legislation is causing problems of interpretation, circular and unnecessary referrals, legal uncertainty and undue delays. Actually, this situation may cause a lack of control and monitoring, and even some paralysis in regenerative medicine and cell therapy research, that is a priority nowadays. The analysis of the current legislation and its bioethical implications, led us to conclude that the review of iPS research projects cannot be assimilated to the evaluation of research projects that involve human embryonic stem cell (hESC). In this context, our proposal is based on the review by the Research Ethics Committees and the checkout by the Spanish Comission of Guarantees for Donation and Use of Human Cells and Tissues (CGDUCTH) of human iPS cells research projects. Moreover, this article claims for a more transparent research system, by effectively articulating the Registry on Research Projects. Finally, a model of verification protocol (checklist) for checking out biomedical research projects involving human iPS cells is suggested.

ASN reputation system model

NASA Astrophysics Data System (ADS)

Hutchinson, Steve; Erbacher, Robert F.

2015-05-01

Network security monitoring is currently challenged by its reliance on human analysts and the inability for tools to generate indications and warnings for previously unknown attacks. We propose a reputation system based on IP address set membership within the Autonomous System Number (ASN) system. Essentially, a metric generated based on the historic behavior, or misbehavior, of nodes within a given ASN can be used to predict future behavior and provide a mechanism to locate network activity requiring inspection. This will provide reinforcement of notifications and warnings and lead to inspection for ASNs known to be problematic even if initial inspection leads to interpretation of the event as innocuous. We developed proof of concept capabilities to generate the IP address to ASN set membership and analyze the impact of the results. These results clearly show that while some ASNs are one-offs with individual or small numbers of misbehaving IP addresses, there are definitive ASNs with a history of long term and wide spread misbehaving IP addresses. These ASNs with long histories are what we are especially interested in and will provide an additional correlation metric for the human analyst and lead to new tools to aid remediation of these IP address blocks.

Chromatin Immunoprecipitation in Early Mouse Embryos.

PubMed

García-González, Estela G; Roque-Ramirez, Bladimir; Palma-Flores, Carlos; Hernández-Hernández, J Manuel

2018-01-01

Epigenetic regulation is achieved at many levels by different factors such as tissue-specific transcription factors, members of the basal transcriptional apparatus, chromatin-binding proteins, and noncoding RNAs. Importantly, chromatin structure dictates the availability of a specific genomic locus for transcriptional activation as well as the efficiency with which transcription can occur. Chromatin immunoprecipitation (ChIP) is a method that allows elucidating gene regulation at the molecular level by assessing if chromatin modifications or proteins are present at a specific locus. Initially, the majority of ChIP experiments were performed on cultured cell lines and more recently this technique has been adapted to a variety of tissues in different model organisms. Using ChIP on mouse embryos, it is possible to document the presence or absence of specific proteins and chromatin modifications at genomic loci in vivo during mammalian development and to get biological meaning from observations made on tissue culture analyses. We describe here a ChIP protocol on freshly isolated mouse embryonic somites for in vivo analysis of muscle specific transcription factor binding on chromatin. This protocol has been easily adapted to other mouse embryonic tissues and has also been successfully scaled up to perform ChIP-Seq.

Antidepressant-like effect of harmane and other beta-carbolines in the mouse forced swim test.

PubMed

Farzin, Davood; Mansouri, Nazanin

2006-07-01

The purpose of the present study was to determine the effects of harmane, norharmane and harmine on the immobility time in the mouse forced swim test (FST) - an animal model of depression. After 30 min of the beta-carbolines injections, mice were placed individually in a vertical glass cylinder (height, 25 cm; diameter, 12 cm) containing water about 15 cm deep at 22+/-1 degrees C and forced to swim. Treatment of animals with harmane (5-15 mg/kg, i.p.), norharmane (2.5-10 mg/kg, i.p.) and harmine (5-15 mg/kg, i.p.) reduced dose-dependently the time of immobility. Their antidepressant-like effects were not affected by pretreatment with reserpine at the dose of 5 mg/kg, i.p., 18 h before the test, which did not modify the immobility time. Conversely, when flumazenil (5 mg/kg, i.p.) was administered 30 min before the test, it was able to antagonize completely the antidepressant-like effects of harmane, norharmane and harmine. It was concluded that harmane, norharmane and harmine reduce the immobility time in this test, suggesting an antidepressant-like effect, via an inverse-agonistic mechanism located in the benzodiazepine receptors.

IP3R deficit underlies loss of salivary fluid secretion in Sjögren’s Syndrome

PubMed Central

Teos, Leyla Y.; Zhang, Yu; Cotrim, Ana P.; Swaim, William; Won, Jon H.; Ambrus, Julian; Shen, Long; Bebris, Lolita; Grisius, Margaret; Jang, Shyh-Ing; Yule, David I.; Ambudkar, Indu S.; Alevizos, Ilias

2015-01-01

The autoimmune exocrinopathy, Sjögren’s syndrome (SS), is associated with secretory defects in patients, including individuals with mild lymphocytic infiltration and minimal glandular damage. The mechanism(s) underlying the secretory dysfunction is not known. We have used minor salivary gland biopsies from SS patients and healthy individuals to assess acinar cell function in morphologically intact glandular areas. We report that agonist-regulated intracellular Ca2+ release, critically required for Ca2+ entry and fluid secretion, is defective in acini from SS patients. Importantly, these acini displayed reduction in IP3R2 and IP3R3, but not AQP5 or STIM1. Similar decreases in IP3R and carbachol (CCh)-stimulated [Ca2+]i elevation were detected in acinar cells from lymphotoxin-alpha (LTα) transgenic (TG) mice, a model for (SS). Treatment of salivary glands from healthy individuals with LT α, a cytokine linked to disease progression in SS and IL14α mice, reduced Ca2+ signaling. Together, our findings reveal novel IP3R deficits in acinar cells that underlie secretory dysfunction in SS patients. PMID:26365984

Protective Effects of Extracellular and Intracellular Polysaccharides on Hepatotoxicity by Hericium erinaceus SG-02.

PubMed

Cui, Fangyuan; Gao, Xia; Zhang, Jianjun; Liu, Min; Zhang, Chen; Xu, Nuo; Zhao, Huajie; Lin, Lin; Zhou, Meng; Jia, Le

2016-09-01

The protective effects of extracellular and intracellular polysaccharides from Hericium erinaceus SG-02 on the CCl4-induced hepatic injury of mice were investigated in this work. By the analysis of GC, the extracellular polysaccharides (EPS) were composed of arabinose, mannose, galactose, and glucose with a ratio of 1:7:14:52, and the composition of intracellular polysaccharides (IPS) was rhamnose, xylose, mannose, galactose, and glucose with a ratio of 3:4:7:14:137. The model of hepatic injury of mice was induced by CCl4 and three tested levels (200, 400, and 800 mg/kg) of EPS and IPS were set as the experimental group. Results showed that the aspartate aminotransferase and glutamic pyruvic transaminase activities in serum were reduced by the supplement of EPS and IPS, while the blood lipid levels including cholesterol, triglyceride, and albumin were improved. In liver tissue, the lipid peroxidation and malondialdehyde were largely decreased, and the superoxide dismutase and catalase activities were significantly increased. The evidence demonstrated that the EPS and IPS of H. erinaceus SG-02 were protective for liver injury. The histopathological observations of mice liver slices indicated that EPS and IPS had obvious effects on liver protection.

A Metacognitive model of procrastination.

PubMed

Fernie, Bruce A; Bharucha, Zinnia; Nikčević, Ana V; Marino, Claudia; Spada, Marcantonio M

2017-03-01

procrastination refers to the delay or postponement of task or decision-making initiation or completion and is often conceptualised as a failure of self-regulation. Recent research has suggested that metacognitions play a role in procrastination and that unintentional procrastination (UP), as opposed to intentional procrastination (IP), may be the most problematic form of this behaviour. We aimed to test a metacognitive model of procrastination that was grounded in the Self-Regulatory Executive Function model. a convenience sample of 400 participants were recruited and completed (at least partially) a battery of online questionnaires that measured IP and UP, metacognitions about procrastination, depression, and Cognitive Attentional Syndrome (CAS) configurations. Initially, we tested series of hypotheses to establish the relationships between the experimental variables and to test whether CAS configurations would independently predict UP when controlling for age, depression, IP, metacognitions about procrastination, and whether an individual reported that they had been diagnosed with a psychiatric disorder. CAS configurations, depression, and metacognitions independently predicted UP. Additionally, path analysis revealed that the study data was an excellent fit to the proposed metacognitive model of procrastination. the study is cross-sectional. the metacognitive model of procrastination presented in this paper can be used to generate novel interventions to treat this problematic behaviour. Copyright © 2016 Elsevier B.V. All rights reserved.

Chicken Induced Pluripotent Stem Cells: Establishment and Characterization.

PubMed

Fuet, Aurelie; Pain, Bertrand

2017-01-01

In mammals, the introduction of the OSKM (Oct4, Sox2, Klf4, and c-Myc) genes into somatic cells has allowed generating induced pluripotent stem (iPS) cells. So far, this process has been only clearly demonstrated in mammals. Here, using chicken as an avian model, we describe a set of protocols allowing the establishment, characterization, maintenance, differentiation, and injection of putative reprogrammed chicken Induced Pluripotent Stem (iPS) cells.

Induced pluripotent stem cells in hematology: current and future applications

PubMed Central

Focosi, D; Amabile, G; Di Ruscio, A; Quaranta, P; Tenen, D G; Pistello, M

2014-01-01

Reprogramming somatic cells into induced pluripotent stem (iPS) cells is nowadays approaching effectiveness and clinical grade. Potential uses of this technology include predictive toxicology, drug screening, pathogenetic studies and transplantation. Here, we review the basis of current iPS cell technology and potential applications in hematology, ranging from disease modeling of congenital and acquired hemopathies to hematopoietic stem and other blood cell transplantation. PMID:24813079

Targeting the Mevalonate Pathway to Reduce Mortality from Ovarian Cancer

DTIC Science & Technology

2015-10-01

intraperitoneal (i.p.) injection twice weekly; atorvastatin (10 mg/kg per injection) was i.p. administered daily (19). Tumor Translational Relevance Recent...other lipophilic statins exerted an anti- tumor phenotype, we assessed another inhibitor of HMG-CoA reductase, atorvastatin (Brand name: Lipitor), in an...OVCAR5 tumor xenograft model. Daily injections of atorvastatin (10 mg/kg) led to significantly reduced tumor sizes as compared with vehicle control

Real-time services in IP network architectures

NASA Astrophysics Data System (ADS)

Gilardi, Antonella

1996-12-01

The worldwide internet system seems to be the success key for the provision of real time multimedia services to both residential and business users and someone says that in such a way broadband networks will have a reason to exist. This new class of applications that use multiple media (voice, video and data) impose constraints to the global network nowadays consisting of subnets with various data links. The attention will be focused on the interconnection of IP non ATM and ATM networks. IETF and ATM forum are currently involved in the developing specifications suited to adapt the connectionless IP protocol to the connection oriented ATM protocol. First of all the link between the ATM and the IP service model has to be set in order to match the QoS and traffic requirements defined in the relative environment. A further significant topic is represented by the mapping of IP resource reservation model onto the ATM signalling and in the end it is necessary to define how the routing works when there are QoS parameters associated. This paper, considering only unicast applications, will examine the above issues taking as a starting point the situation where an host launches as call set up request with the relevant QoS and traffic descriptor and at some point a router at the edge of the ATM network has to decide how forwarding and request in order to establish an end to end link with the right capabilities. The aim is to compare the proposals emerging from different standard bodies to point out convergency or incompatibility.

River Protection Project (RPP) Dangerous Waste Training Plan

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

POHTO, R.E.

2000-03-09

This supporting document contains the training plan for dangerous waste management at River Protection Project TSD Units. This document outlines the dangerous waste training program developed and implemented for all Treatment, Storage, and Disposal (TSD) Units operated by River Protection Project (RPP) in the Hanford 200 East, 200 West and 600 Areas and the <90 Day Accumulation Area at 209E. Operating TSD Units managed by RPP are: the Double-Shell Tank (DST) System, 204-AR Waste Unloading Facility, Grout, and the Single-Shell Tank (SST) System. The program is designed in compliance with the requirements of Washington Administrative Code (WAC) 173-303-330 and Titlemore » 40 Code of Federal Regulations (CFR) 265.16 for the development of a written dangerous waste training program and the Hanford Facility Permit. Training requirements were determined by an assessment of employee duties and responsibilities. The RPP training program is designed to prepare employees to operate and maintain the Tank Farms in a safe, effective, efficient, and environmentally sound manner. In addition to preparing employees to operate and maintain the Tank Farms under normal conditions, the training program ensures that employees are prepared to respond in a prompt and effective manner should abnormal or emergency conditions occur. Emergency response training is consistent with emergency responses outlined in the following Building Emergency Plans: HNF-IP-0263-TF and HNF-=IP-0263-209E.« less

Conference Scene: Induced pluripotent cells: a new path for regenerative medicine. 7 October 2010, BioPark, Welwyn Garden City, Hertfordshire, UK.

PubMed

Crutzen, Hélène S G

2011-01-01

Embryonic stem cells and induced pluripotent stem (iPS) cells, which are embryonic stem-like cells derived from adult tissues, have the broadest differentiation potential. These cells are unique in their ability to self-renew, to be maintained in an undifferentiated state for long periods of culturing and to give rise to many different cell lineages including germ-line cells. They therefore represent an invaluable tool for facilitating research towards the realization of regenerative medicine. The recent developments in embryonic stem cell and iPS cell technology have allowed human cell models to be developed that will hopefully provide novel platforms for disease analysis not only at the basic science level, but also for drug discovery and screening, and other clinical applications. This 1-day conference, chaired by Professor Peter Andrews from the University of Sheffield, UK, and Dr Chris Denning from the University of Nottingham, UK, focused on generation of iPS cells, their differentiation into specific fates and applications to disease modeling. It consisted of 11 talks by UK-based and international researchers, and three posters; Ms Azra Fatima from Cologne University, Germany, won the competition for her poster on the derivation of iPS cells from a patient with arrhythmogenic right ventricular cardiomyopathy.

Robust experimental design for optimizing the microbial inhibitor test for penicillin detection in milk.

PubMed

Nagel, O G; Molina, M P; Basílico, J C; Zapata, M L; Althaus, R L

2009-06-01

To use experimental design techniques and a multiple logistic regression model to optimize a microbiological inhibition test with dichotomous response for the detection of Penicillin G in milk. A 2(3) x 2(2) robust experimental design with two replications was used. The effects of three control factors (V: culture medium volume, S: spore concentration of Geobacillus stearothermophilus, I: indicator concentration), two noise factors (Dt: diffusion time, Ip: incubation period) and their interactions were studied. The V, S, Dt, Ip factors and V x S, V x Ip, S x Ip interactions showed significant effects. The use of 100 microl culture medium volume, 2 x 10(5) spores ml(-1), 60 min diffusion time and 3 h incubation period is recommended. In these elaboration conditions, the penicillin detection limit was of 3.9 microg l(-1), similar to the maximum residue limit (MRL). Of the two noise factors studied, the incubation period can be controlled by means of the culture medium volume and spore concentration. We were able to optimize bioassays of dichotomous response using an experimental design and logistic regression model for the detection of residues at the level of MRL, aiding in the avoidance of health problems in the consumer.

Functional mechanisms of probabilistic inference in feature- and space-based attentional systems.

PubMed

Dombert, Pascasie L; Kuhns, Anna; Mengotti, Paola; Fink, Gereon R; Vossel, Simone

2016-11-15

Humans flexibly attend to features or locations and these processes are influenced by the probability of sensory events. We combined computational modeling of response times with fMRI to compare the functional correlates of (re-)orienting, and the modulation by probabilistic inference in spatial and feature-based attention systems. Twenty-four volunteers performed two task versions with spatial or color cues. Percentage of cue validity changed unpredictably. A hierarchical Bayesian model was used to derive trial-wise estimates of probability-dependent attention, entering the fMRI analysis as parametric regressors. Attentional orienting activated a dorsal frontoparietal network in both tasks, without significant parametric modulation. Spatially invalid trials activated a bilateral frontoparietal network and the precuneus, while invalid feature trials activated the left intraparietal sulcus (IPS). Probability-dependent attention modulated activity in the precuneus, left posterior IPS, middle occipital gyrus, and right temporoparietal junction for spatial attention, and in the left anterior IPS for feature-based and spatial attention. These findings provide novel insights into the generality and specificity of the functional basis of attentional control. They suggest that probabilistic inference can distinctively affect each attentional subsystem, but that there is an overlap in the left IPS, which responds to both spatial and feature-based expectancy violations. Copyright © 2016 Elsevier Inc. All rights reserved.

Computational biology analysis of platelet signaling reveals roles of feedbacks through phospholipase C and inositol 1,4,5-trisphosphate 3-kinase in controlling amplitude and duration of calcium oscillations.

PubMed

Balabin, Fedor A; Sveshnikova, Anastasia N

2016-06-01

Blood platelet activation is required to allow their participation in hemostasis and thrombosis. It is regulated by a complicated signaling network, whose functioning has been recently attracting attention for basic research and pharmacological purposes. Phospholipase С (PLC) is an enzyme playing an important role in platelet calcium signaling and responsible for release of inositol triphosphate (IP3) into platelet cytoplasm thus controlling intracellular calcium concentration. Using a comprehensive computational model of platelet calcium signaling, we studied the influence of the positive feedback executed by cytosolic calcium on the PLC isoform β2 during platelet activation. With the positive feedback, the model predicted hyperintensive response to platelet activation by thrombin, where non-physiologically high calcium concentrations arose. However, if one took into account a negative feedback determined by IP3 3-kinase (IP3K), combination of the feedback resulted in the formation of a stepped response (with a stable oscillation amplitude and activation-dependent duration). Stochastic simulations confirmed that PLC and IP3K should act in pair to ensure platelet's "all-or-none" response to activation, when the activation level sets the probability of platelet activation, but not its intensity. Copyright © 2016 Elsevier Inc. All rights reserved.

The biology of human cytomegalovirus infection after bone marrow transplantation.

PubMed

Zaia, J A

1986-01-01

Human cytomegalovirus (HCMV) infection remains the most common infectious cause of morbidity after bone marrow transplantation (BMT). In a prospective study of 127 BMT recipients who received blood cultures for HCMV between days 28 to 105 after marrow grafting, HCMV viremia occurred in 68 patients (53.4%). Twenty patients (15.7%) had one or two positive cultures, and 48 (37.7%) had greater than or equal to three positive cultures. Fifty-nine patients (46.4%) had no viremia. HCMV-associated interstitial pneumonia (HCMV-IP) occurred in one-third of the viremic patients. Quantitative measurements of infectious HCMV or of HCMV DNA in lung tissue were made to determine whether HCMV replication correlated with clinical disease. Using DNA probes, viral DNA was measured by dot-blot hybridization, and this correlated with infectious HCMV. However, neither HCMV DNA nor HCMV viral titer correlated with time from the onset of pneumonia to death. The hypothesis is presented that HCMV-IP is caused by immunologic events induced after HCMV infection. In this model HCMV alterations in recipient cell surfaces induce donor alloreactivity to minor histocompatibility differences and lead to the subsequent pneumonitis which we term HCMV-IP. This model suggests that prevention of HCMV-IP will require early use of antiviral therapy or late use of immune response modification.

D-peaks: a visual tool to display ChIP-seq peaks along the genome.

PubMed

Brohée, Sylvain; Bontempi, Gianluca

2012-01-01

ChIP-sequencing is a method of choice to localize the positions of protein binding sites on DNA on a whole genomic scale. The deciphering of the sequencing data produced by this novel technique is challenging and it is achieved by their rigorous interpretation using dedicated tools and adapted visualization programs. Here, we present a bioinformatics tool (D-peaks) that adds several possibilities (including, user-friendliness, high-quality, relative position with respect to the genomic features) to the well-known visualization browsers or databases already existing. D-peaks is directly available through its web interface http://rsat.ulb.ac.be/dpeaks/ as well as a command line tool.

Use of Cumulative Degradation Factor Prediction and Life Test Result of the Thruster Gimbal Assembly Actuator for the Dawn Flight Project

NASA Technical Reports Server (NTRS)

Lo, C. John; Brophy, John R.; Etters, M. Andy; Ramesham, Rajeshuni; Jones, William R., Jr.; Jansen, Mark J.

2009-01-01

The Dawn Ion Propulsion System is the ninth project in NASA s Discovery Program. The Dawn spacecraft is being developed to enable the scientific investigation of the two heaviest main-belt asteroids, Vesta and Ceres. Dawn is the first mission to orbit two extraterrestrial bodies, and the first to orbit a main-belt asteroid. The mission is enabled by the onboard Ion Propulsion System (IPS) to provide the post-launch delta-V. The three Ion Engines of the IPS are mounted on Thruster Gimbal Assembly (TGA), with only one engine operating at a time for this 10-year mission. The three TGAs weigh 14.6 kg.

Pinhole occulter experiment

NASA Technical Reports Server (NTRS)

Ring, Jeff; Pflug, John

1987-01-01

Viewgraphs and charts from a briefing summarize the accomplishments, results, conclusions, and recommendations of a feasibility study using the Pinhole Occulter Facility (POF). Accomplishments for 1986 include: (1) improved IPS Gimbal Model; (2) improved Crew Motion Disturbance Model; (3) use of existing shuttle on-orbit simulation to study the effects of orbiter attitude deadband size on POF performance; (4) increased understanding of maximum performance expected from current actuator/sensor set; (5) use of TREETOPS nonlinear time domain program to obtain system dynamics describing the complex multibody flexible structures; (6) use of HONEY-X design tool to design and evaluate multivariable compensator for stability, robustness, and performance; (7) application of state-of-the-art compensator design methodology Linear Quadratic Gaussian/Loop Transfer Recovery (LQG/LTR); and (8) examination of tolerance required on knowledge of the POF boom flexible mode frequencies to insure stability, using structure uncertainty analysis.

A behavioural study of the effect of pentadecapeptide BPC 157 in Parkinson's disease models in mice and gastric lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydrophyridine.

PubMed

Sikiric, P; Marovic, A; Matoz, W; Anic, T; Buljat, G; Mikus, D; Stancic-Rokotov, D; Separovic, J; Seiwerth, S; Grabarevic, Z; Rucman, R; Petek, M; Ziger, T; Sebecic, B; Zoricic, I; Turkovic, B; Aralica, G; Perovic, D; Duplancic, B; Lovric-Bencic, M; Rotkvic, I; Mise, S; Jagic, V; Hahn, V

1999-12-01

The effect of a stomach pentadecapeptide, BPC 157, on Parkinson's disease in mice was investigated, along with its salutary activity on stomach lesions induced by parkinsongenic agents. Parkinsongenic agents, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30.0 mg x kg(-1)b.w. i.p. once daily for 6d, and after 4d once 50.0 mg x kg(-1)b.w. i.p.) or reserpine (5.0 mg x kg(-1)b.w. i.p.) were applied i.p. BPC 157 (1.50 microg or 15.0 ng x kg(-1)b.w. i.p.) was applied 15 min before or alternatively 15 min after each MPTP administration. In reserpine studies, BPC 157 (10.0 microg or 10.0 ng x kg(-1)b.w. i.p.) was given either 15 min before reserpine or in the already established complete catalepsy 24 h thereafter. BPC 157 strongly improved the MPTP-impaired somatosensory orientation and reduced the MPTP-induced hyperactivity, and most importantly, MPTP-motor abnormalities (tremor, akinesia, catalepsy -otherwise very prominent in saline control), leading to almost complete abolition of otherwise regularly lethal course of MPTP treatment in controls. Likewise, in reserpine experiments, BPC 157 strongly prevented the development of otherwise very prominent catalepsy and when applied 24 h thereafter reversed the established catalepsy. In addition, a reduction of reserpine-hypothermy (BPC 157 pre-treatment) and reversal of further prominent temperature fall (BPC 157 post-treatment) have been consistently observed. Taking together these data, as the two most suitable animal models were consistently used and since the high effectiveness was demonstrated in pre- and post-treatment, microg and ng regimens, BPC 157 as an organoprotector should be further therapeutically investigated. Additionally, given in either regimen, pentadecapeptide BPC 157 strongly attenuated the stomach lesions in mice that otherwise consistently appeared in mice treated with the parkinsogenic neurotoxin MPTP.

Peripheral antinociceptive effects of the cyclic endomorphin-1 analog c[YpwFG] in a mouse visceral pain model.

PubMed

Bedini, Andrea; Baiula, Monica; Gentilucci, Luca; Tolomelli, Alessandra; De Marco, Rossella; Spampinato, Santi

2010-11-01

We previously described a novel cyclic endomorphin-1 analog c[Tyr-D-Pro-D-Trp-Phe-Gly] (c[YpwFG]), acting as a mu-opioid receptor (MOR) agonist. This study reports that c[YpwFG] is more lipophilic and resistant to enzymatic hydrolysis than endomorphin-1 and produces preemptive antinociception in a mouse visceral pain model when injected intraperitoneally (i.p.) or subcutaneously (s.c.) before 0.6% acetic acid, employed to evoke abdominal writhing (i.p. ED(50)=1.24 mg/kg; s.c. ED(50)=2.13 mg/kg). This effect is reversed by the selective MOR antagonist β-funaltrexamine and by a high dose of the mu(1)-opioid receptor-selective antagonist naloxonazine. Conversely, the kappa-opioid receptor antagonist nor-binaltorphimine and the delta-opioid receptor antagonist naltrindole are ineffective. c[YpwFG] produces antinociception when injected i.p. after acetic acid (ED(50)=4.80 mg/kg), and only at a dose of 20mg/kg did it elicit a moderate antinociceptive response in the mouse, evaluated by the tail flick assay. Administration of a lower dose of c[YpwFG] (10mg/kg i.p.) apparently produces a considerable part of antinociception on acetic acid-induced writhes through peripheral opioid receptors as this action is fully prevented by i.p. naloxone methiodide, which does not readily cross the blood-brain barrier; whereas this opioid antagonist injected intracerebroventricularly (i.c.v.) is not effective. Antinociception produced by a higher dose of c[YpwFG] (20mg/kg i.p.) is partially reversed by naloxone methiodide i.c.v. administered. Thus, only at the dose of 20mg/kg c[YpwFG] can produce antinociception through both peripheral and central opioid receptors. In conclusion, c[YpwFG] displays sufficient metabolic stability to be effective after peripheral administration and demonstrates the therapeutic potential of endomorphin derivatives as novel analgesic agents to control visceral pain. Copyright © 2010 Elsevier Inc. All rights reserved.

Fan Blade Development

DTIC Science & Technology

1982-09-01

Reviewed by: IP. A. Saigh, P.E. L. B. Hoyl , Ph.D. Director, Government Programs Manageri Mechanical Engineering Department I I GARD, INC. r I...D.C. 20301 Mr. C. Wilton 2 Scientific Service Inc. 517 East Bayshore Drive Redwood City, California 94060 Mr. Fred Sauer 1 Physics International

Subtype-selective regulation of IP(3) receptors by thimerosal via cysteine residues within the IP(3)-binding core and suppressor domain.

PubMed

Khan, Samir A; Rossi, Ana M; Riley, Andrew M; Potter, Barry V L; Taylor, Colin W

2013-04-15

IP(3)R (IP(3) [inositol 1,4,5-trisphosphate] receptors) and ryanodine receptors are the most widely expressed intracellular Ca(2+) channels and both are regulated by thiol reagents. In DT40 cells stably expressing single subtypes of mammalian IP(3)R, low concentrations of thimerosal (also known as thiomersal), which oxidizes thiols to form a thiomercurylethyl complex, increased the sensitivity of IP(3)-evoked Ca(2+) release via IP(3)R1 and IP(3)R2, but inhibited IP(3)R3. Activation of IP(3)R is initiated by IP(3) binding to the IBC (IP(3)-binding core; residues 224-604) and proceeds via re-arrangement of an interface between the IBC and SD (suppressor domain; residues 1-223). Thimerosal (100 μM) stimulated IP(3) binding to the isolated NT (N-terminal; residues 1-604) of IP(3)R1 and IP(3)R2, but not to that of IP(3)R3. Binding of a competitive antagonist (heparin) or partial agonist (dimeric-IP(3)) to NT1 was unaffected by thiomersal, suggesting that the effect of thimerosal is specifically related to IP(3)R activation. IP(3) binding to NT1 in which all cysteine residues were replaced by alanine was insensitive to thimerosal, so too were NT1 in which cysteine residues were replaced in either the SD or IBC. This demonstrates that thimerosal interacts directly with cysteine in both the SD and IBC. Chimaeric proteins in which the SD of the IP(3)R was replaced by the structurally related A domain of a ryanodine receptor were functional, but thimerosal inhibited both IP(3) binding to the chimaeric NT and IP(3)-evoked Ca(2+) release from the chimaeric IP(3)R. This is the first systematic analysis of the effects of a thiol reagent on each IP(3)R subtype. We conclude that thimerosal selectively sensitizes IP(3)R1 and IP(3)R2 to IP(3) by modifying cysteine residues within both the SD and IBC and thereby stabilizing an active conformation of the receptor.

Analysis of Induced Polarization effects in airborne TEM data - a case study from central East Greenland

NASA Astrophysics Data System (ADS)

Maack Rasmussen, Thorkild; Brethes, Anaïs; Pierpaolo Guarnieri, Pierpaolo; Bauer, Tobias

2017-04-01

Data from a high-resolution airborne SkyTEM time-domain electromagnetic survey conducted in central East Greenland were analysed. An analysis based on utilization of a Self Organizing Map procedure for response curve characterization and analyses based on data inversion and modelling are presented. The survey was flown in 2013 along the eastern margin of the Jameson Land basin with the purpose of base metal exploration and with sulphide mineralization as target. The survey area comprises crystalline basement to the East and layered Early Triassic to Jurassic sediments to the West. The layers are dipping a few degrees towards West. The Triassic sequence is 1 to 2 km thick and mostly of continental origin. The fluviatile Early Triassic arkoses and conglomerates, the Upper Triassic grey limestone and black shale beds and overlying gypsiferous sandstones and mudstones are known to host disseminated sulphides. E-W oriented lines were flown with an average terrain clearance of 30m and a separation of 300m. The data were initially processed and inverted by SkyTEM Aps. The conductivity models showed some conductive layers as well as induced polarization (IP) effects in the data. IP effects in TEM data reflect the relaxation of polarized charges in the ground which can be good indicators of the presence of metallic particles. Some of these locations were drilled during the following field season but unfortunately did not reveal the presence of mineralization. The aim of this study is therefore to understand the possible causes of these IP effects. Electrical charge accumulation in the ground can be related to the presence of sulphides, oxides or graphite or to the presence of clays or fibrous minerals. Permafrost may also cause IP effects and is then expected to be associated with a highly resistive subsurface. Several characteristics of the transient curves (IP indicators) of the SkyTEM survey were extracted and analysed by using the Kohonen Self-Organizing Map (SOM) technique. SOM is a type of neural network algorithm developed for analysis of non-linear relationships in multivariate data. The basic idea of SOM is to provide a method for easy visualizing of multi-dimensional data. The SOM may be viewed as a two-dimensional grid onto which multi-dimensional input data are projected or mapped from a multi-dimensional space. The space dimension is equal to the number of analysed variables containing the geo-referenced IP indicators that characterise the transient curves. Input data that are similar or close to each other, irrespectively of their geographic location, are mapped to the same or adjacent position in the SOM. Data that belongs to a particular cluster in the SOM space are afterwards mapped into a geographical space. Characteristics of the IP effects can therefore be mapped and spatially compared with the geology of the area. Once IP were identified and located, Cole-Cole parameters were recovered from the airborne TEM data in specific locations by inversion of the TEM data. An interpretation of the derived models is discussed in relation to possible causes of the observed IP effects.

Analysis of sea ice and phytoplankton biomarkers in marine sediments from the Nordic Seas - a calibration study

NASA Astrophysics Data System (ADS)

Navarro Rodriguez, A.; Cabedo Sanz, P.; Belt, S.; Brown, T.; Knies, J.; Husum, K.; Giraudeau, J.

2012-04-01

The work presented here is part of the Changing Arctic and SubArctic Environment program (EU CASE) which is an Initial Training Network (ITN) on climate change and marine environment and is an interdisciplinary project focussing on biological proxies. One of these proxies is the sea ice diatom biomarker IP25 which is a highly branched isoprenoid (HBI) alkene synthesised by some Arctic sea-ice diatoms and has been shown to be a specific, stable and sensitive proxy measure of Arctic sea ice when detected in underlying sediments (Belt et al., 2007). The current study focuses on two key elements: (1) An analytical calibration of IP25 isolated from marine sediments and purified using a range of chromatographic methods was conducted in order to improve the quantification of this biomarker in sediment extracts. (2) Analysis of >30 near-surface sediments from the Nordic Seas was carried out to quantify biomarkers previously suggested as indicators of open-water phytoplankton (brassicasterol) (Müller et al., 2011) and sea-ice (IP25) conditions (Belt et al., 2010). The outcomes of the biomarker analyses were used to make comparisons between proxy data and known sea ice conditions in the study area derived from satellite record over the last 20 years. The results of this study should inform longer timescale reconstructions of sea ice conditions in the Nordic sea in the future. Belt, S.T., Massé, G., Rowland. S.J., Poulin. M., Michel. C., LeBlanc. B., (2007). A novel chemical fossil of palaeo sea ice : IP25 . Organic Geochemistry 38 (16-27). Belt, S. T., Vare, L. L., Massé, G., Manners, H. R., Price, J. C., MacLachlan, S. E., Andrews, J. T. & Schmidt, S. (2010) 'Striking similarities in temporal changes to spring sea ice occurrence across the central Canadian Arctic Archipelago over the last 7000 years', Quaternary Science Reviews, 29 (25-26), pp. 3489-3504. Müller, J., Wagner, A., Fahl, K., Stein, R., Prange, M., & Lohmann, G. (2011). Towards quantitative sea ice reconstructions in the northern North Atlantic: A combined biomarker and numerical modelling approach. Earth and Planetary Science Letters, 306, 137-148.

An End-to-End Loss Discrimination Scheme for Multimedia Transmission over Wireless IP Networks

NASA Astrophysics Data System (ADS)

Zhao, Hai-Tao; Dong, Yu-Ning; Li, Yang

As the rapid growth of wireless IP networks, wireless IP access networks have a lot of potential applications in a variety of fields in civilian and military environments. Many of these applications, such as realtime audio/video streaming, will require some form of end-to-end QoS assurance. In this paper, an algorithm WMPLD (Wireless Multimedia Packet Loss Discrimination) is proposed for multimedia transmission control over wired-wireless hybrid IP networks. The relationship between packet length and packet loss rate in the Gilbert wireless error model is investigated. Furthermore, the algorithm can detect the nature of packet losses by sending large and small packets alternately, and control the sending rate of nodes. In addition, by means of updating factor K, this algorithm can adapt to the changes of network states quickly. Simulation results show that, compared to previous algorithms, WMPLD algorithm can improve the networks throughput as well as reduce the congestion loss rate in various situations.

Biosphere Reserve for All: Potentials for Involving Underrepresented Age Groups in the Development of a Biosphere Reserve through Intergenerational Practice.

PubMed

Mitrofanenko, Tamara; Snajdr, Julia; Muhar, Andreas; Penker, Marianne; Schauppenlehner-Kloyber, Elisabeth

2018-05-22

Stakeholder participation is of high importance in UNESCO biosphere reserves as model regions for sustainable development; however, certain groups remain underrepresented. The paper proposes Intergenerational Practice (IP) as a means of involving youth and elderly women and explores its options and barriers, using the example of the Salzburger Lungau and Kärntner Nockberge Biosphere Reserve in Austria. Case study analysis is used involving mixed methods. The results reveal obstacles and motivations to participating in biosphere reserve implementation and intergenerational activities for the youth and the elderly women and imply that much potential for IP exists in the biosphere reserve region. The authors propose suitable solutions from the intergenerational field to overcome identified participation obstacles and suggest benefits of incorporating IP as a management tool into biosphere reserve activities. Suggestions for future research include evaluating applications of IP in the context of protected areas, testing of methods used in other contexts, and contribution to theory development.

[An investigation of the effect of gamma rays emitted by patients undergoing radionuclide bone scintigraphy in computed radiography during X-ray mammography examination].

PubMed

Kamigiri, Akira; Nagasawa, Naoki; Yamaji, Masami; Nakamura, Mikako; Ito, Morihiro; Nakanishi, Satoshi; Kitano, Tokio

2010-03-20

For convenience of outpatients, mammographies of outpatients are often taken after the injection of a radionuclide. In this study, we investigated the effects of gamma rays emitted by a patient onto imaging plates (IPs). We used a flat container filled with (99m)Tc solution as a planar source to irradiate gamma rays onto IPs. We changed irradiation times on each IP, and took radiographies of an ACR-specified 156 model phantom and AGH-D210F phantom. We evaluated radiography images, using visual evaluation, and profile curves, histograms, and CNR and RMS granularities analyses. The results indicated that the depiction ability of a fibrous part began to fall when the irradiation time exceeded 3 minutes. With an increase in irradiation time, an increase in pixel value and RMS granularity value and a decrease in CNR value were observed. In conclusion, IP exposed by gamma rays influenced the evaluation of phantom images.

Calibration of imaging plate detectors to mono-energetic protons in the range 1-200 MeV

NASA Astrophysics Data System (ADS)

Rabhi, N.; Batani, D.; Boutoux, G.; Ducret, J.-E.; Jakubowska, K.; Lantuejoul-Thfoin, I.; Nauraye, C.; Patriarca, A.; Saïd, A.; Semsoum, A.; Serani, L.; Thomas, B.; Vauzour, B.

2017-11-01

Responses of Fuji Imaging Plates (IPs) to proton have been measured in the range 1-200 MeV. Mono-energetic protons were produced with the 15 MV ALTO-Tandem accelerator of the Institute of Nuclear Physics (Orsay, France) and, at higher energies, with the 200-MeV isochronous cyclotron of the Institut Curie—Centre de Protonthérapie d'Orsay (Orsay, France). The experimental setups are described and the measured photo-stimulated luminescence responses for MS, SR, and TR IPs are presented and compared to existing data. For the interpretation of the results, a sensitivity model based on the Monte Carlo GEANT4 code has been developed. It enables the calculation of the response functions in a large energy range, from 0.1 to 200 MeV. Finally, we show that our model reproduces accurately the response of more complex detectors, i.e., stack of high-Z filters and IPs, which could be of great interest for diagnostics of Petawatt laser accelerated particles.