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.

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.

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.

Ascent/Descent Software

NASA Technical Reports Server (NTRS)

Brown, Charles; Andrew, Robert; Roe, Scott; Frye, Ronald; Harvey, Michael; Vu, Tuan; Balachandran, Krishnaiyer; Bly, Ben

2012-01-01

The Ascent/Descent Software Suite has been used to support a variety of NASA Shuttle Program mission planning and analysis activities, such as range safety, on the Integrated Planning System (IPS) platform. The Ascent/Descent Software Suite, containing Ascent Flight Design (ASC)/Descent Flight Design (DESC) Configuration items (Cis), lifecycle documents, and data files used for shuttle ascent and entry modeling analysis and mission design, resides on IPS/Linux workstations. A list of tools in Navigation (NAV)/Prop Software Suite represents tool versions established during or after the IPS Equipment Rehost-3 project.

The meaning and experience of stress among supported employment clients with mental health problems.

PubMed

Besse, Christine; Poremski, Daniel; Laliberté, Vincent; Latimer, Eric

2018-05-01

Many clinicians are concerned that competitive work may cause excessive stress for people with severe mental health problems. Individual Placement and Support (IPS) is acknowledged as the most effective model of supported employment for this population. The manner in which IPS clients define and experience employment-related stress is poorly understood. This qualitative study aims to explore how people with mental health problems receiving IPS services define and experience employment-related stress. We purposively sampled and interviewed 16 clients of an IPS programme, who had been competitively employed for more than 1 month. Data were collected between September 2014 and July 2015 in Montreal, Canada. Transcripts of semi-structured interviews were analysed using grounded theory methodology. IPS clients often defined stress similar to its common understanding: the result of experiencing prolonged or/and cumulative strains, or of an incongruence between efforts and rewards, hopes and reality. Stress experienced in this way could exacerbate psychiatric symptoms, especially depression or psychotic symptoms. However, when maintained at a more manageable level, stress stimulated learning and improved planning of tasks. Participants described different coping mechanisms, such as sharing their experiences and difficulties with others, focusing on problem resolution and avoidance. The first two of these helped IPS clients remain at work and bolstered their confidence. Work-related stress has potentially positive as well as negative consequences for IPS clients. In order to maximise the potential beneficial effects of stress, employment specialists can help clients anticipate potential stressors and plan how they might cope with them. Further research on the most effective ways of helping clients cope with stress is needed. © 2017 John Wiley & Sons Ltd.

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).

Randomized Trial of Supported Employment Integrated With Assertive Community Treatment for Rural Adults With Severe Mental Illness

PubMed Central

Gold, Paul B; Meisler, Neil; Santos, Alberto B; Carnemolla, Mark A; Williams, Olivia H; Keleher, Jennie

2006-01-01

Urban-based randomized clinical trials of integrated supported employment (SE) and mental health services in the United States on average have doubled the employment rates of adults with severe mental illness (SMI) compared to traditional vocational rehabilitation. However, studies have not yet explored if the service integrative functions of SE will be effective in coordinating rural-based services that are limited, loosely linked, and geographically dispersed. In addition, SE's ability to replicate the work outcomes of urban programs in rural economies with scarce and less diverse job opportunities remains unknown. In a rural South Carolina county, we designed and implemented a program blending Assertive Community Treatment (ACT) with an SE model, Individual Placement and Support (IPS). The ACT-IPS program operated with ACT and IPS subteams that tightly integrated vocational with mental health services within each self-contained team. In a 24-month randomized clinical trial, we compared ACT-IPS to a traditional program providing parallel vocational and mental health services on competitive work outcomes for adults with SMI (N = 143; 69% schizophrenia, 77% African American). More ACT-IPS participants held competitive jobs (64 versus 26%; p < .001, effect size [ES] = 0.38) and earned more income (median [Mdn] = $549, interquartile range [IQR] = $0–$5,145, versus Mdn = $0, IQR = $0–$40; p < .001, ES = 0.70) than comparison participants. The competitive work outcomes of this rural ACT-IPS program closely resemble those of urban SE programs. However, achieving economic self-sufficiently and developing careers probably require increasing access to higher education and jobs imparting marketable technical skills. PMID:16177278

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.

MHD and Reconnection Activity During Local Helicity Injection

NASA Astrophysics Data System (ADS)

Barr, J. L.; Bongard, M. W.; Burke, M. G.; Fonck, R. J.; Reusch, J. A.; Richner, N. J.

2016-10-01

Scaling local helicity injection (LHI) to larger devices requires a validated, predictive model of its current drive mechanism. NIMROD simulations predict the injected helical current streams persist in the edge and periodically reconnect to form axisymmetric current rings that travel into the bulk plasma to grow Ip and poloidal flux. In simulation, these events result in discrete bursts of Alfvénic-frequency MHD activity and jumps in Ip of order ΔIp Iinj , in qualitative agreement with large n = 1 activity found in experiment. Fast imaging prior to tokamak formation supports the instability of, and apparent reconnection between, adjacent helical streams. The bursts exhibit toroidal amplitude asymmetries consistent with a kink structure singly line-tied to the injectors. Internal measurements localize this activity to the injector radial location. Pairwise correlations of poloidal Mirnov coil amplitude and phase match expectations of an edge-localized current stream carrying Iinj. Prior to tokamak formation, reconnection from both adjacent helical windings and co-injected current streams are shown to strongly heat impurity ions. After tokamak formation, strong anomalous ion heating in the plasma edge is attributed to continuous reconnection between colinear streams. The n = 1 bursts occur less frequently as Ip rises, likely caused by increased stream stability as Bv rises and qedge drops. This evidence supports the general NIMROD model of LHI, confirms the persistence and role of the edge current streams, and motivates experiments at higher Iinj and BT. Supported by US DOE Grants DE-FG02-96ER54375, DE-SC0006928.

Factors affecting annual compensation and professional development support for infection preventionists: Implications for recruitment and retention.

PubMed

Knighton, Shanina C; Gilmartin, Heather M; Reese, Sara M

2018-06-04

Factors affecting annual compensation and professional development support have been studied for various healthcare professions. However, there is little understanding of these factors for infection preventionists (IPs). Using secondary data from the Association for Professionals in Infection Control and Epidemiology 2015 MegaSurvey, we designed a descriptive, correlational study to describe IP annual compensation and professional development support. We tested for associations between demographic variables and annual compensation and investigated for predictors of higher annual compensation. Median salary for IPs was $75,000. IPs who indicated that their compensation was based on industry benchmarks reported a median salary of $85,000 (P < .001). IPs with advanced degrees reported a median salary of $90,000. IPs with bachelor's degrees or lower reported a median salary of $50,000 (P < .001). IPs with CIC® reported a median salary of $85,000. IPs without CIC® reported a median salary of $65,000 (P < .001). This study can be used to develop recruitment and retention guidelines that lead to a well-educated, well-compensated, and competent IP workforce. Published by Elsevier Inc.

Experiences of the individual placement and support approach in persons with severe mental illness.

PubMed

Areberg, Cecilia; Björkman, Tommy; Bejerholm, Ulrika

2013-09-01

Across several research studies comparing the individual placement and support (IPS) approach to traditional vocational services, the approach has achieved employment outcomes superior to comparison conditions. However, to understand the efficacy of IPS, it is equally important to consider what is more or less effective as viewed by the IPS participants. To investigate participants' experiences of IPS participation and their experiences of receiving support from an employment specialist (ES). Interviews were conducted with 17 persons with severe mental illness. The interviews were subjected to qualitative content analysis. The principles of informed consent and the voluntary nature of participation were included as ethical considerations. Participation in IPS was associated with hope, meaning and an individualized support provided by the ES. The skills of the ES facilitated the relationship with the participant and the contact with the labour market. However, to make a change happen, everybody involved in IPS had to contribute. These findings have endorsed the guiding principles of IPS and emphasized the ES's role and skills during IPS as well as the participant's motivation. © 2012 The Authors. Scandinavian Journal of Caring Sciences © 2012 Nordic College of Caring Science.

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

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.

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

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.

Effect on return to work or education of Individual Placement and Support modified for people with mood and anxiety disorders: results of a randomised clinical trial.

PubMed

Hellström, Lone; Bech, Per; Hjorthøj, Carsten; Nordentoft, Merete; Lindschou, Jane; Eplov, Lene Falgaard

2017-10-01

The effect of Individual Placement and Support (IPS) on return to work or education among people with mood or anxiety disorders is unclear, while IPS increases return to work for people with severe mental illness. We examined the effect of IPS modified for people with mood and anxiety disorders (IPS-MA) on return to work and education compared with services as usual (SAU). In a randomised clinical superiority trial, 326 participants with mood and anxiety disorders were centrally randomised to IPS-MA, consisting of individual mentor support and career counselling (n=162) or SAU (n=164). The primary outcome was competitive employment or education at 24 months, while weeks of competitive employment or education, illness symptoms and level of functioning, and well-being were secondary outcomes. After 24 months, 44.4% (72/162) of the participants receiving IPS-MA had returned to work or education compared with 37.8% (62/164) following SAU (OR=1.34, 95% CI: 0.86 to 2.10, p=0.20). We found no difference in mean number of weeks in employment or education (IPS-MA 32.4 weeks vs SAU 26.7 weeks, p=0.14), level of depression (Hamilton Depression 6-Item Scale score IPS-MA 5.7 points vs SAU 5.0 points, p=0.12), level of anxiety (Hamilton Anxiety 6-Item Scale score IPS-MA 5.8 points vs SAU 5.1 points, p=0.17), level of functioning (Global Assessment of Functioning IPS-MA 59.1 points vs SAU 59.5 points, p=0.81) or well-being measured by WHO-Five Well-being Index (IPS-MA 49.6 points vs SAU 48.5 points, p=0.83) at 24 months. The modified version of IPS, IPS-MA, was not superior to SAU in supporting people with mood or anxiety disorders in return to work at 24 months. NCT01721824. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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.

Oral nutritional support can shorten the duration of parenteral hydration in end-of-life cancer patients: a randomized controlled trial.

PubMed

Ishiki, Hiroto; Iwase, Satoru; Gyoda, Yasuaki; Kanai, Yoshiaki; Ariyoshi, Keisuke; Miyaji, Tempei; Tahara, Yukiko; Kawaguchi, Takashi; Chinzei, Mieko; Yamaguchi, Takuhiro

2015-01-01

Tube feeding or hydration is often considered for end-of-life cancer patients despite the negative effects on quality of life. The efficacy of oral nutritional support in this setting is unknown. We conducted a randomized trial to compare the efficacies of an amino acid jelly, Inner Power® (IP), and a liquid enteral product, Ensure Liquid® (EL), in terminally ill cancer patients. We randomly assigned patients to 3 arms: EL, IP, and EL+IP. The primary endpoint was drip infusion in vein (DIV)-free survival, which was defined as the duration from nutritional support initiation to administration of parenteral hydration. Twenty-seven patients were enrolled in the study, of whom 21 were included in the intention-to-treat analysis. The median age of the subjects was 69 yr. There were significant differences between the arms with regard to the median DIV-free survival (0.5, 6.0, and 4.5 days in the EL, IP, and EL + IP arms, respectively; P = 0.05). The median overall survival was 7, 9, and 8 days in the EL, IP, and EL + IP arms, respectively. IP may shorten the duration of parenteral hydration in terminally ill cancer patients and does not affect their survival.

Achieving Better Buying Power through Acquisition of Open Architecture Software Systems: Volume 1

DTIC Science & Technology

2016-01-06

supporting “Bring Your Own Devices” (BYOD)? 22 New business models for OA software components ● Franchising ● Enterprise licensing ● Metered usage...paths IP and cybersecurity requirements will need continuous attention! 35 New business models for OA software components ● Franchising ● Enterprise

47 CFR 10.320 - Provider alert gateway requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... must be identified by a unique IP address or domain name. (b) Authentication and validation. The CMS... alert gateway if a validation fails. (c) Security. The CMS provider gateway must support standardized IP... CMSP Name Unique identification of CMSP. CMSP gateway Address IP address or Domain Name Alternate IP...

Exploring perceptions of occupational competence among participants in Individual Placement and Support (IPS).

PubMed

Nygren, Ulla; Sandlund, Mikael; Bernspång, Birgitta; Fisher, Anne G

2013-11-01

The purpose of this study was to explore perceptions of occupational competence and occupational value among a group of clients engaged in Individual Placement and Support (IPS). The Occupational Self-Assessment (OSA), based on the Model of Human Occupation, was used with 65 men and women with mental illness, and 45 of these completed the study. Rasch analyses showed that the participants perceived "Managing my finances", "Managing my basic needs", and "Doing activities I like" as the most valued occupations. Most competence was perceived in "Taking care of myself". Among the occupations where the participants perceived least competence, "Getting done what I need to do" and "Accomplishing what I set out to do" were the occupations that most stand out. Significant differences were also found between perceived competence and value in most of the occupations. Beyond those occupations valued as most important among the participants, it is essential also to pay attention to those in which they perceived least competence, as they are important for being able to achieve a desired occupation. Support related to perceptions of occupational competence can contribute to enabling clients in IPS to master a desired working life.

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.

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.

A multi-site randomised controlled trial of evidence-based supported employment for adults with severe and persistent mental illness.

PubMed

Waghorn, Geoffrey; Dias, Shannon; Gladman, Beverley; Harris, Meredith; Saha, Sukanta

2014-12-01

The Individual Placement and Support (IPS) approach is an evidence-based form of supported employment for people with severe and persistent mental illness. This approach is not yet widely available in Australia even though there is mounting evidence of its generalisability outside the USA. One previous Australian randomised controlled trial found that IPS is effective for young people with first episode psychosis. The aim of the current trial was to assess the effectiveness of evidence-based supported employment when implemented for Australian adult consumers of public mental health services by utilising existing service systems. A four-site randomised control trial design (n = 208) was conducted in Brisbane (two sites), Townsville and Cairns. The intervention consisted of an IPS supported employment service hosted by a community mental health team. The control condition was delivered at each site by mental health teams referring consumers to other disability employment services in the local area. At 12 months, those in the IPS condition had 2.4 times greater odds of commencing employment than those in the control condition (42.5% vs. 23.5%). The conditions did not differ on secondary employment outcomes including job duration, hours worked, or job diversity. Attrition was higher than expected in both conditions with 28.4% completing the baseline interview but taking no further part in the study. The results support previous international findings that IPS-supported employment is more effective than non-integrated supported employment. IPS can be successfully implemented this way in Australia, but with a loss of effect strength compared to previous USA trials. © 2014 Occupational Therapy Australia.

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.

Additional Interventions to Enhance the Effectiveness of Individual Placement and Support: A Rapid Evidence Assessment

PubMed Central

Boycott, Naomi; Schneider, Justine; McMurran, Mary

2012-01-01

Topic. Additional interventions used to enhance the effectiveness of individual placement and support (IPS). Aim. To establish whether additional interventions improve the vocational outcomes of IPS alone for people with severe mental illness. Method. A rapid evidence assessment of the literature was conducted for studies where behavioural or psychological interventions have been used to supplement standard IPS. Published and unpublished empirical studies of IPS with additional interventions were considered for inclusion. Conclusions. Six published studies were found which compared IPS alone to IPS plus a supplementary intervention. Of these, three used skills training and three used cognitive remediation. The contribution of each discrete intervention is difficult to establish. Some evidence suggests that work-related social skills and cognitive training are effective adjuncts, but this is an area where large RCTs are required to yield conclusive evidence. PMID:22685665

Supported employment: cost-effectiveness across six European sites

PubMed Central

Knapp, Martin; Patel, Anita; Curran, Claire; Latimer, Eric; Catty, Jocelyn; Becker, Thomas; Drake, Robert E; Fioritti, Angelo; Kilian, Reinhold; Lauber, Christoph; Rössler, Wulf; Tomov, Toma; van Busschbach, Jooske; Comas-Herrera, Adelina; White, Sarah; Wiersma, Durk; Burns, Tom

2013-01-01

A high proportion of people with severe mental health problems are unemployed but would like to work. Individual Placement and Support (IPS) offers a promising approach to establishing people in paid employment. In a randomized controlled trial across six European countries, we investigated the economic case for IPS for people with severe mental health problems compared to standard vocational rehabilitation. Individuals (n=312) were randomized to receive either IPS or standard vocational services and followed for 18 months. Service use and outcome data were collected. Cost-effectiveness analysis was conducted with two primary outcomes: additional days worked in competitive settings and additional percentage of individuals who worked at least 1 day. Analyses distinguished country effects. A partial cost-benefit analysis was also conducted. IPS produced better outcomes than alternative vocational services at lower cost overall to the health and social care systems. This pattern also held in disaggregated analyses for five of the six European sites. The inclusion of imputed values for missing cost data supported these findings. IPS would be viewed as more cost-effective than standard vocational services. Further analysis demonstrated cost-benefit arguments for IPS. Compared to standard vocational rehabilitation services, IPS is, therefore, probably cost-saving and almost certainly more cost-effective as a way to help people with severe mental health problems into competitive employment. PMID:23471803

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.

Origin and distribution of desert ants across the Gibraltar Straits.

PubMed

Villalta, Irene; Amor, Fernando; Galarza, Juan A; Dupont, Simon; Ortega, Patrocinio; Hefetz, Abraham; Dahbi, Abdallah; Cerdá, Xim; Boulay, Raphaël

2018-01-01

The creation of geographic barriers has long been suspected to contribute to the formation of new species. We investigated the phylogeography of desert ants in the western Mediterranean basin in order to elucidate their mode of diversification. These insects which have a low dispersal capacity are recently becoming important model systems in evolutionary studies. We conducted an extensive sampling of species belonging to the Cataglyphis albicans group in the Iberian Peninsula (IP) and the northern Morocco (North Africa; NA). We then combined genetic, chemical and morphological analyses. The results suggest the existence of at least three and five clades in the IP and NA, respectively, whose delineation partially encompass current taxonomic classification. The three Iberian clades are monophyletic, but their origin in NA is uncertain (79% and 22% for Bayesian and Maximum Likelihood support, respectively). The estimation of divergence time suggests that a speciation process was initiated after the last reopening of the Gibraltar Straits ≈5.33 Ma. In the IP, the clades are parapatric and their formation may have been triggered by the fragmentation of a large population during the Pleistocene due to extended periods of glaciation. This scenario is supported by demographic analyses pointing at a recent expansion of Iberian populations that contrasts with the progressive contraction of the NA clades. Niche modeling reveals that this area, governed by favorable climatic conditions for desert ants, has recently increased in the IP and decreased in NA. Altogether, our data points at geoclimatic events as major determinants of species formation in desert ants, reinforcing the role of allopatric speciation. Copyright © 2017 Elsevier Inc. All rights reserved.

Delayed early passive motion is harmless to shoulder rotator cuff healing in a rabbit model.

PubMed

Zhang, Shurong; Li, Hong; Tao, Hongyue; Li, Hongyun; Cho, Samson; Hua, Yinghui; Chen, Jiwu; Chen, Shiyi; Li, Yunxia

2013-08-01

Postoperative passive motion is the most widely accepted rehabilitation protocol after rotator cuff repair; however, a rotator cuff retear remains a frequent surgical complication. Clinical outcomes indicate that early passive motion is harmless to rotator cuff healing, but no laboratory evidence supports this proposition. (1) Immediate postoperative immobilization improves rotator cuff healing in rabbits. (2) Early passive motion after short-term immobilization does not harm rotator cuff healing in rabbits. Controlled laboratory study. An injury to the supraspinatus tendon was created and repaired in 90 New Zealand White rabbits, after which they were randomly separated into 3 groups: (1) nonimmobilization (NI; n = 30), (2) continuous immobilization (IM; n = 30), and (3) immobilization with early passive motion (IP; n = 30). At 3, 6, and 12 weeks postoperatively, 5 rabbits from each group were sacrificed for histological evaluation, biomechanical testing, and magnetic resonance imaging. The histological study demonstrated better postoperative healing in the IM and IP groups, with clusters of chondrocytes accumulated at the tendon-bone junction. Magnetic resonance imaging illustrated that the tendon-bone junction was intact in the IM and IP groups. The magnetic resonance quantification analysis showed that the signal-to-noise quotient (SNQ) of the NI group was not significantly higher than that of the immobilization groups at 3 weeks (P = .232) or 6 weeks (P = .117), but it was significantly different at 12 weeks (NI vs IM, P = .006; NI vs IP, P = .009). At 12 weeks, the failure load was significantly higher in the IM and IP groups than in the NI group (NI vs IM, P = .002; NI vs IP, P = .002), but no difference was found between the IM and IP groups (P = .599). Immediate postoperative immobilization led to better tendon-bone healing than immediate postoperative mobilization, and under immobilization, early passive motion was harmless to tendon-bone healing in this study. The results have an implication in supporting the rehabilitation protocol of early passive motion after rotator cuff repair.

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.

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.

Effect of Evidence-Based Supported Employment vs Transitional Work on Achieving Steady Work Among Veterans With Posttraumatic Stress Disorder: A Randomized Clinical Trial.

PubMed

Davis, Lori L; Kyriakides, Tassos C; Suris, Alina M; Ottomanelli, Lisa A; Mueller, Lisa; Parker, Pamela E; Resnick, Sandra G; Toscano, Richard; Scrymgeour, Alexandra A; Drake, Robert E

2018-04-01

Posttraumatic stress disorder (PTSD) often interferes with a person's ability to obtain or sustain employment, which leads to premature exit from the labor force and reduced income. To determine whether individual placement and support (IPS)-supported employment is more effective than stepwise vocational rehabilitation involving transitional work assignments at helping veterans with PTSD attain steady, competitive employment. The Veterans Individual Placement and Support Toward Advancing Recovery (VIP-STAR) study was a prospective, multisite, randomized clinical trial that included 541 unemployed veterans with PTSD at 12 Veterans Affairs medical centers. Data were collected from December 23, 2013, to May 3, 2017. Intent-to-treat analysis was performed. Individual placement and support is a supported employment intervention that rapidly engages people with disabilities in community job development to obtain work based on their individual job preferences. Transitional work is a stepwise vocational rehabilitation intervention that assigns people temporarily to noncompetitive jobs as preparation for competitive employment in the community. A priori hypotheses were that, compared with those in transitional work, more participants in the IPS group would become steady workers (primary) and earn more income from competitive jobs (secondary) over 18 months. Steady worker was defined as holding a competitive job for at least 50% of the 18-month follow-up period. A total of 541 participants (n = 271 IPS; n = 270 transitional work) were randomized. Mean (SD) age was 42.2 (11) years; 99 (18.3%) were women, 274 (50.6%) were white, 225 (41.6%) were African American, and 90 (16.6%) were of Hispanic, Spanish, or Latino ethnicity. More participants in the IPS group achieved steady employment than in the transitional work group (105 [38.7%] vs 63 [23.3%]; odds ratio, 2.14; 95% CI, 1.46-3.14). A higher proportion of IPS participants attained any competitive job (186 [68.6%] vs 154 [57.0%]; P = .005) and had higher cumulative earnings from competitive jobs (median [interquartile range] $7290 [$23 174] in IPS vs $1886 [$17 167] in transitional work; P = .004). This multisite trial demonstrated significantly greater effectiveness of IPS-supported employment over stepwise transitional work vocational rehabilitation for veterans living with chronic PTSD. The results provide supporting evidence for increasing access to IPS for veterans living with PTSD. clinicaltrials.gov Identifier: NCT01817712.

Differentiated optical services: a quality of optical service model for WDM networks

NASA Astrophysics Data System (ADS)

Ndousse, Thomas D.; Golmie, Nada

1999-08-01

This paper addresses the issues of guaranteed and scalable end-to-end QoS in Metropolitan DWDM networks serving as transit networks for IP access networks. DWDM offering few wavelengths have in the past been deployed in backbone networks to upgrade point-to-point transmission where sharing is based on coarse granularity. This type of DWDM backbone networks, offering few lightpaths, provides no support for QoS services traversing the network. As DWDM networks with larger numbers of wavelengths penetrate the data-centric Metro environment, specific IP service requirements such as priority restoration, scalability, dynamic provisioning of capacity and routes, and support for coarse-grain QoS capabilities will have to be addressed in the optical domain in order to support end-to-end Service- Level Agreements. In this paper, we focus on the support of QoS in the optical domain in order to achieve end-to-end QoS over a DWDM network. We propose a QoS service model in the optical domain called Differentiated Optical Services (DOS). Service classification in DOS is based on a set of optical parameters that captures the quality and reliability of the optical lightpath.

Overcoming communication challenges in integrative supportive cancer care: The integrative physician, the psycho-oncologist, and the patient.

PubMed

Ben-Arye, Eran; Shavit, Efrat; Wiental, Haya; Schiff, Elad; Agour, Olga; Samuels, Noah

2016-12-01

Complementary/integrative medicine (CIM) services are increasingly being integrated into conventional supportive cancer care, presenting a number of challenges to communication between healthcare professionals (HCPs). The purpose of the present study was to explore the impact of the communication between integrative physicians (IPs) trained in CIM and social workers (SWs) working as psycho-oncologists in the same oncology setting. We examine whether IP-SW communication correlates with the number of patient-SW sessions, as provided within the oncology department. SW-IP communication, defined as a summary of the IP consultation sent to the patient's SW, was compared to SW-patient communication, defined as the number of psycho-oncology treatment sessions. Of 344 patients referred by their oncology HCP for IP consultation, 91 were referred by an SW and 253 by an oncologist or nurse. IP-to-SW summaries were provided for 150 patients referred by a non-SW HCP (43.6%), and for 91 of SW-referred patients (26.5%). In all, 32 patients referred to the IP had no psycho-oncology interaction with an SW; 58 only one meeting; and 254 with ≥2 interactions, with 119 having >6 sessions. SW-patient interactions were greater with higher rates of IP-SW communication, for both patients referred by an SW (79.1%) and those referred by a non-SW HCP (77.3%) when compared to patients for whom no summary was provided (64.1%; p= 0.02). A greater level of IP-SW communication, measured by the provision of an IP summary to the patient's SW, was found to correlate with a higher rate of SW-patient interactions. The use of a structured two-way referral-summary between IPs and SWs has the potential to advance the SW-patient psycho-oncology interaction, within an integrative supportive cancer care setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

Advanced Simulation and Computing Fiscal Year 2016 Implementation Plan, Version 0

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

McCoy, M.; Archer, B.; Hendrickson, B.

2015-08-27

The Stockpile Stewardship Program (SSP) is an integrated technical program for maintaining the safety, surety, and reliability of the U.S. nuclear stockpile. The SSP uses nuclear test data, computational modeling and simulation, and experimental facilities to advance understanding of nuclear weapons. It includes stockpile surveillance, experimental research, development and engineering programs, and an appropriately scaled production capability to support stockpile requirements. This integrated national program requires the continued use of experimental facilities and programs, and the computational capabilities to support these programs. The purpose of this IP is to outline key work requirements to be performed and to control individualmore » work activities within the scope of work. Contractors may not deviate from this plan without a revised WA or subsequent IP.« less

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.

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

The compensatory dynamic of inter-hemispheric interactions in visuospatial attention revealed using rTMS and fMRI.

PubMed

Plow, Ela B; Cattaneo, Zaira; Carlson, Thomas A; Alvarez, George A; Pascual-Leone, Alvaro; Battelli, Lorella

2014-01-01

A balance of mutual tonic inhibition between bi-hemispheric posterior parietal cortices is believed to play an important role in bilateral visual attention. However, experimental support for this notion has been mainly drawn from clinical models of unilateral damage. We have previously shown that low-frequency repetitive TMS (rTMS) over the intraparietal sulcus (IPS) generates a contralateral attentional deficit in bilateral visual tracking. Here, we used functional magnetic resonance imaging (fMRI) to study whether rTMS temporarily disrupts the inter-hemispheric balance between bilateral IPS in visual attention. Following application of 1 Hz rTMS over the left IPS, subjects performed a bilateral visual tracking task while their brain activity was recorded using fMRI. Behaviorally, tracking accuracy was reduced immediately following rTMS. Areas ventro-lateral to left IPS, including inferior parietal lobule (IPL), lateral IPS (LIPS), and middle occipital gyrus (MoG), showed decreased activity following rTMS, while dorsomedial areas, such as Superior Parietal Lobule (SPL), Superior occipital gyrus (SoG), and lingual gyrus, as well as middle temporal areas (MT+), showed higher activity. The brain activity of the homologues of these regions in the un-stimulated, right hemisphere was reversed. Interestingly, the evolution of network-wide activation related to attentional behavior following rTMS showed that activation of most occipital synergists adaptively compensated for contralateral and ipsilateral decrement after rTMS, while activation of parietal synergists, and SoG remained competing. This pattern of ipsilateral and contralateral activations empirically supports the hypothesized loss of inter-hemispheric balance that underlies clinical manifestation of visual attentional extinction.

Overview of Non-Solenoidal Startup Studies in the Pegasus ST

NASA Astrophysics Data System (ADS)

Bongard, M. W.; Barr, J. L.; Bodner, G. M.; Burke, M. G.; Fonck, R. J.; Pachicano, J. L.; Perry, J. M.; Reusch, J. A.; Richner, N. J.; Rodriguez Sanchez, C.; Schlossberg, D. J.

2016-10-01

Local helicity injection (LHI) is a non-solenoidal startup method pursued on Pegasus utilizing compact, high power current sources (Ainj 2 - 4 cm2, Iinj 10 kA, Vinj 1 kV) at the plasma edge. Outboard injectors (Ninj = 4 , Ainj = 8 cm2) produce Ip 170 kA plasmas compatible with Ohmic drive. A 0-D model that treats the plasma as a resistive element with time-varying inductance and enforces Ip limits from Taylor relaxation is used to interpret experimental Ip(t) in several scenarios. Strong inductive drive arises from the plasma shape evolution, in addition to poloidal field induction. A new injector system has recently been installed in the lower divertor region (Ninj = 2 , Ainj = 8 cm2) to explore the implications of geometric placement of the helicity injectors on LHI startup. This geometry supports tests of reconnection dynamics seen in NIMROD simulations, high-BT effects expected in larger devices, and LHI electron confinement with and without inductive assist. Plasmas with Ip > 130 kA, Vinj 0.5 kV, Δtpulse 8 ms and BT /BT , max <= 50 % are produced with the inboard system to date, consistent with performance expectations. Higher Ip is expected with increased BT, Vinj, and Δtpulse . Thomson scattering data in both geometries indicate high Te >= 100 eV during LHI, suggesting the confinement is not strongly stochastic. Conceptual design work is exploring the feasibility of coaxial helicity injection and ECH heating on Pegasus in addition to LHI. Work supported by US DOE Grant DE-FG02-96ER54375.

Sensor Proxy Mobile IPv6 (SPMIPv6)—A Novel Scheme for Mobility Supported IP-WSNs

PubMed Central

Islam, Md. Motaharul; Huh, Eui-Nam

2011-01-01

IP based Wireless Sensor Networks (IP-WSNs) are gaining importance for their broad range of applications in health-care, home automation, environmental monitoring, industrial control, vehicle telematics and agricultural monitoring. In all these applications, mobility in the sensor network with special attention to energy efficiency is a major issue to be addressed. Host-based mobility management protocols are not suitable for IP-WSNs because of their energy inefficiency, so network based mobility management protocols can be an alternative for the mobility supported IP-WSNs. In this paper we propose a network based mobility supported IP-WSN protocol called Sensor Proxy Mobile IPv6 (SPMIPv6). We present its architecture, message formats and also evaluate its performance considering signaling cost, mobility cost and energy consumption. Our analysis shows that with respect to the number of IP-WSN nodes, the proposed scheme reduces the signaling cost by 60% and 56%, as well as the mobility cost by 62% and 57%, compared to MIPv6 and PMIPv6, respectively. The simulation results also show that in terms of the number of hops, SPMIPv6 decreases the signaling cost by 56% and 53% as well as mobility cost by 60% and 67% as compared to MIPv6 and PMIPv6 respectively. It also indicates that proposed scheme reduces the level of energy consumption significantly. PMID:22319386

Supported employment for people with severe mental illness: systematic review and meta-analysis of the international evidence.

PubMed

Modini, Matthew; Tan, Leona; Brinchmann, Beate; Wang, Min-Jung; Killackey, Eoin; Glozier, Nicholas; Mykletun, Arnstein; Harvey, Samuel B

2016-07-01

Individual placement and support (IPS) is a vocational rehabilitation programme that was developed in the USA to improve employment outcomes for people with severe mental illness. Its ability to be generalised to other countries and its effectiveness in varying economic conditions remains to be ascertained. To investigate whether IPS is effective across international settings and in different economic conditions. A systematic review and meta-analysis of randomised controlled trials comparing IPS with traditional vocational services was undertaken; 17 studies, as well as 2 follow-up studies, were included. Meta-regressions were carried out to examine whether IPS effectiveness varied according to geographic location, unemployment rates or gross domestic product (GDP) growth. The overall pooled risk ratio for competitive employment using IPS compared with traditional vocational rehabilitation was 2.40 (95% CI 1.99-2.90). Meta-regressions indicated that neither geographic area nor unemployment rates affected the overall effectiveness of IPS. Even when a country's GDP growth was less than 2% IPS was significantly more effective than traditional vocational training, and its benefits remained evident over 2 years. Individual placement and support is an effective intervention across a variety of settings and economic conditions and is more than twice as likely to lead to competitive employment when compared with traditional vocational rehabilitation. © The Royal College of Psychiatrists 2016.

Sensor proxy mobile IPv6 (SPMIPv6)--a novel scheme for mobility supported IP-WSNs.

PubMed

Islam, Md Motaharul; Huh, Eui-Nam

2011-01-01

IP based Wireless Sensor Networks (IP-WSNs) are gaining importance for their broad range of applications in health-care, home automation, environmental monitoring, industrial control, vehicle telematics and agricultural monitoring. In all these applications, mobility in the sensor network with special attention to energy efficiency is a major issue to be addressed. Host-based mobility management protocols are not suitable for IP-WSNs because of their energy inefficiency, so network based mobility management protocols can be an alternative for the mobility supported IP-WSNs. In this paper we propose a network based mobility supported IP-WSN protocol called Sensor Proxy Mobile IPv6 (SPMIPv6). We present its architecture, message formats and also evaluate its performance considering signaling cost, mobility cost and energy consumption. Our analysis shows that with respect to the number of IP-WSN nodes, the proposed scheme reduces the signaling cost by 60% and 56%, as well as the mobility cost by 62% and 57%, compared to MIPv6 and PMIPv6, respectively. The simulation results also show that in terms of the number of hops, SPMIPv6 decreases the signaling cost by 56% and 53% as well as mobility cost by 60% and 67% as compared to MIPv6 and PMIPv6 respectively. It also indicates that proposed scheme reduces the level of energy consumption significantly.

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.

Participation of a coordinating center pharmacy in a multicenter international study.

PubMed

Jeon, Jihyun Esther; Mighty, Janet; Lane, Karen; McBee, Nichol; Majkowski, Ryan; Mayo, Steven; Hanley, Daniel

2016-11-15

The activities of a coordinating center pharmacy (CCP) supporting a multicenter, international clinical trial are described. Serving in a research support role comparable to that of a commercial clinical trial supply company, a CCP within the Johns Hopkins Hospital Investigational Drug Service (JHH IDS) uses its management expertise and infrastructure to support multicenter trials, such as the recently completed Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage, Phase III (CLEAR III) trial. The role of the CCP staff in supporting the CLEAR III trial was overall investigational product (IP) management through coordination of IP-related operations to ensure high-quality care for study participants at study sites in the United States and abroad. For the CLEAR III trial, the CCP coordinated IP supply activities; provided education to site pharmacists; developed study-specific documents, including pharmacy manuals; communicated with trial stakeholders, including third-party IP distributors; monitored treatment assignments; and performed quality assurance monitoring to ensure compliance with institutional, state, federal, and international regulations regarding IP procurement and storage. Acting as a CCP for a multicenter international study poses a number of operational challenges while providing opportunities for the CCP to contribute to research of global importance and enrich the skill sets of its personnel. The development and implementation of the CCP at JHH IDS for the CLEAR III trial included several responsibilities, such as IP supply management, communication, and database, regulatory, and finance management. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Tremorolytic effects of safinamide in animal models of drug-induced parkinsonian tremor.

PubMed

Podurgiel, Samantha; Collins-Praino, Lyndsey E; Yohn, Samantha; Randall, Patrick A; Roach, Arthur; Lobianco, Christophe; Salamone, John D

2013-04-01

Safinamide is an α-aminoamide derivative that is currently in Phase III clinical trial development as an add-on therapy to levodopa or dopamine agonists for patients with Parkinson's disease. Safinamide is a monoamine oxidase B inhibitor with additional non-dopaminergic actions. The present experiments were performed to evaluate the ability of safinamide to attenuate parkinsonian motor impairments using the tremulous jaw movement model, an animal model of parkinsonian tremor. In rats, tremulous jaw movements can be induced with dopamine (DA) antagonists, DA depletion, and cholinomimetics, and can be reversed by various antiparkinsonian drugs, including L-DOPA, DA agonists, anticholinergics and adenosine A2A antagonists. In these present experiments, tremulous jaw movements were induced with the anticholinesterase galantamine (3.0mg/kg IP), the muscarinic agonist pilocarpine (0.5mg/kg IP), and the dopamine D2 antagonist pimozide (1.0mg/kg IP). Safinamide significantly reduced the number of tremulous jaw movements induced by galantamine, pilocarpine, and pimozide, with consistent effects across all three drugs at a dose range of 5.0-10.0mg/kg. The results of this study support the use of safinamide as a treatment for parkinsonian tremor. Copyright © 2013 Elsevier Inc. All rights reserved.

Protocol for the effect evaluation of Individual Placement and Support (IPS): a randomized controlled multicenter trial of IPS versus treatment as usual for patients with moderate to severe mental illness in Norway.

PubMed

Sveinsdottir, Vigdis; Løvvik, Camilla; Fyhn, Tonje; Monstad, Karin; Ludvigsen, Kari; Øverland, Simon; Reme, Silje Endresen

2014-11-18

Roughly one third of disability pensions in Norway are issued for mental and behavioral disorders, and vocational rehabilitation offered to this group has traditionally been dominated by train-and-place approaches with assisted or sheltered employment. Based on a more innovative place-and-train approach, Individual Placement and Support (IPS) involves supported employment in real-life competitive work settings, and has shown great promise for patients with severe mental illness. The study is a multicenter Randomized Controlled Trial (RCT) of IPS in a Norwegian context, involving an effect evaluation, a process evaluation, and a cost/benefit analysis. IPS will be compared to high quality treatment as usual (TAU), with labor market participation and educational activity at 12 months post inclusion as the primary outcome. The primary outcome will be measured using register data, and the project will also include complete follow-up up to 4 years after inclusion for long-term outcome data. Secondary outcomes include mental health status, disability and quality of life, collected through survey questionnaires at baseline, and after 6 and 12 months. Participants will include patients undergoing treatment for moderate to severe mental illness who are either unemployed or on sickness or social benefits. The estimated total sample size of 400-500 will be randomly assigned to the interventions. To be eligible, participants must have an expressed desire to work, and sufficient Norwegian reading and writing skills to fill out the questionnaires. The Effect Evaluation of Individual Placement and Support (IPS) will be one of the largest randomized controlled trials to date investigating the effectiveness of IPS on competitive employment, and the first study to evaluate the effectiveness of IPS for patients with moderate to severe mental illness within a Norwegian context. Clinicaltrials.gov: NCT01964092 . Registered October 16th, 2013.

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.

Exploiting unsupervised and supervised classification for segmentation of the pathological lung in CT

NASA Astrophysics Data System (ADS)

Korfiatis, P.; Kalogeropoulou, C.; Daoussis, D.; Petsas, T.; Adonopoulos, A.; Costaridou, L.

2009-07-01

Delineation of lung fields in presence of diffuse lung diseases (DLPDs), such as interstitial pneumonias (IP), challenges segmentation algorithms. To deal with IP patterns affecting the lung border an automated image texture classification scheme is proposed. The proposed segmentation scheme is based on supervised texture classification between lung tissue (normal and abnormal) and surrounding tissue (pleura and thoracic wall) in the lung border region. This region is coarsely defined around an initial estimate of lung border, provided by means of Markov Radom Field modeling and morphological operations. Subsequently, a support vector machine classifier was trained to distinguish between the above two classes of tissue, using textural feature of gray scale and wavelet domains. 17 patients diagnosed with IP, secondary to connective tissue diseases were examined. Segmentation performance in terms of overlap was 0.924±0.021, and for shape differentiation mean, rms and maximum distance were 1.663±0.816, 2.334±1.574 and 8.0515±6.549 mm, respectively. An accurate, automated scheme is proposed for segmenting abnormal lung fields in HRC affected by IP

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.

Development and Evaluation of a Computerized Engagement Intervention for IPS Supported Employment

ERIC Educational Resources Information Center

Haslett, William R.

2013-01-01

Background: Current information technology offers the promise of innovative approaches to engagement for mental health. Specific psychosocial services may also benefit from technology-based engagement interventions. Individual Placement and Support (IPS) is an evidence-based service that helps people who have a severe mental illness to gain…

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.

Application of graph-based semi-supervised learning for development of cyber COP and network intrusion detection

NASA Astrophysics Data System (ADS)

Levchuk, Georgiy; Colonna-Romano, John; Eslami, Mohammed

2017-05-01

The United States increasingly relies on cyber-physical systems to conduct military and commercial operations. Attacks on these systems have increased dramatically around the globe. The attackers constantly change their methods, making state-of-the-art commercial and military intrusion detection systems ineffective. In this paper, we present a model to identify functional behavior of network devices from netflow traces. Our model includes two innovations. First, we define novel features for a host IP using detection of application graph patterns in IP's host graph constructed from 5-min aggregated packet flows. Second, we present the first application, to the best of our knowledge, of Graph Semi-Supervised Learning (GSSL) to the space of IP behavior classification. Using a cyber-attack dataset collected from NetFlow packet traces, we show that GSSL trained with only 20% of the data achieves higher attack detection rates than Support Vector Machines (SVM) and Naïve Bayes (NB) classifiers trained with 80% of data points. We also show how to improve detection quality by filtering out web browsing data, and conclude with discussion of future research directions.

The compensatory dynamic of inter-hemispheric interactions in visuospatial attention revealed using rTMS and fMRI

PubMed Central

Plow, Ela B.; Cattaneo, Zaira; Carlson, Thomas A.; Alvarez, George A.; Pascual-Leone, Alvaro; Battelli, Lorella

2014-01-01

A balance of mutual tonic inhibition between bi-hemispheric posterior parietal cortices is believed to play an important role in bilateral visual attention. However, experimental support for this notion has been mainly drawn from clinical models of unilateral damage. We have previously shown that low-frequency repetitive TMS (rTMS) over the intraparietal sulcus (IPS) generates a contralateral attentional deficit in bilateral visual tracking. Here, we used functional magnetic resonance imaging (fMRI) to study whether rTMS temporarily disrupts the inter-hemispheric balance between bilateral IPS in visual attention. Following application of 1 Hz rTMS over the left IPS, subjects performed a bilateral visual tracking task while their brain activity was recorded using fMRI. Behaviorally, tracking accuracy was reduced immediately following rTMS. Areas ventro-lateral to left IPS, including inferior parietal lobule (IPL), lateral IPS (LIPS), and middle occipital gyrus (MoG), showed decreased activity following rTMS, while dorsomedial areas, such as Superior Parietal Lobule (SPL), Superior occipital gyrus (SoG), and lingual gyrus, as well as middle temporal areas (MT+), showed higher activity. The brain activity of the homologues of these regions in the un-stimulated, right hemisphere was reversed. Interestingly, the evolution of network-wide activation related to attentional behavior following rTMS showed that activation of most occipital synergists adaptively compensated for contralateral and ipsilateral decrement after rTMS, while activation of parietal synergists, and SoG remained competing. This pattern of ipsilateral and contralateral activations empirically supports the hypothesized loss of inter-hemispheric balance that underlies clinical manifestation of visual attentional extinction. PMID:24860462

CCSDS Advanced Orbiting Systems Virtual Channel Access Service for QoS MACHETE Model

NASA Technical Reports Server (NTRS)

Jennings, Esther H.; Segui, John S.

2011-01-01

To support various communications requirements imposed by different missions, interplanetary communication protocols need to be designed, validated, and evaluated carefully. Multimission Advanced Communications Hybrid Environment for Test and Evaluation (MACHETE), described in "Simulator of Space Communication Networks" (NPO-41373), NASA Tech Briefs, Vol. 29, No. 8 (August 2005), p. 44, combines various tools for simulation and performance analysis of space networks. The MACHETE environment supports orbital analysis, link budget analysis, communications network simulations, and hardware-in-the-loop testing. By building abstract behavioral models of network protocols, one can validate performance after identifying the appropriate metrics of interest. The innovators have extended the MACHETE model library to include a generic link-layer Virtual Channel (VC) model supporting quality-of-service (QoS) controls based on IP streams. The main purpose of this generic Virtual Channel model addition was to interface fine-grain flow-based QoS (quality of service) between the network and MAC layers of the QualNet simulator, a commercial component of MACHETE. This software model adds the capability of mapping IP streams, based on header fields, to virtual channel numbers, allowing extended QoS handling at link layer. This feature further refines the QoS v existing at the network layer. QoS at the network layer (e.g. diffserv) supports few QoS classes, so data from one class will be aggregated together; differentiating between flows internal to a class/priority is not supported. By adding QoS classification capability between network and MAC layers through VC, one maps multiple VCs onto the same physical link. Users then specify different VC weights, and different queuing and scheduling policies at the link layer. This VC model supports system performance analysis of various virtual channel link-layer QoS queuing schemes independent of the network-layer QoS systems.

Using OPC technology to support the study of advanced process control.

PubMed

Mahmoud, Magdi S; Sabih, Muhammad; Elshafei, Moustafa

2015-03-01

OPC, originally the Object Linking and Embedding (OLE) for Process Control, brings a broad communication opportunity between different kinds of control systems. This paper investigates the use of OPC technology for the study of distributed control systems (DCS) as a cost effective and flexible research tool for the development and testing of advanced process control (APC) techniques in university research centers. Co-Simulation environment based on Matlab, LabVIEW and TCP/IP network is presented here. Several implementation issues and OPC based client/server control application have been addressed for TCP/IP network. A nonlinear boiler model is simulated as OPC server and OPC client is used for closed loop model identification, and to design a Model Predictive Controller. The MPC is able to control the NOx emissions in addition to drum water level and steam pressure. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

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.

Universal Verification Methodology Based Register Test Automation Flow.

PubMed

Woo, Jae Hun; Cho, Yong Kwan; Park, Sun Kyu

2016-05-01

In today's SoC design, the number of registers has been increased along with complexity of hardware blocks. Register validation is a time-consuming and error-pron task. Therefore, we need an efficient way to perform verification with less effort in shorter time. In this work, we suggest register test automation flow based UVM (Universal Verification Methodology). UVM provides a standard methodology, called a register model, to facilitate stimulus generation and functional checking of registers. However, it is not easy for designers to create register models for their functional blocks or integrate models in test-bench environment because it requires knowledge of SystemVerilog and UVM libraries. For the creation of register models, many commercial tools support a register model generation from register specification described in IP-XACT, but it is time-consuming to describe register specification in IP-XACT format. For easy creation of register model, we propose spreadsheet-based register template which is translated to IP-XACT description, from which register models can be easily generated using commercial tools. On the other hand, we also automate all the steps involved integrating test-bench and generating test-cases, so that designers may use register model without detailed knowledge of UVM or SystemVerilog. This automation flow involves generating and connecting test-bench components (e.g., driver, checker, bus adaptor, etc.) and writing test sequence for each type of register test-case. With the proposed flow, designers can save considerable amount of time to verify functionality of registers.

The effectiveness of individual placement and support for people with mental illness new on social benefits: a study protocol

PubMed Central

2013-01-01

Background In Switzerland, people with a severe mental illness and unable to work receive disability benefits (‘IV-pension’). Once they are granted these benefits, the chances to regain competitive employment are usually small. However, previous studies have shown that individual placement and support (IPS) supports a successful reintegration into competitive employment. This study focuses on the integration of newly appointed IV-pensioners, who have received an IV-pension for less than a year. Method/design The present pilot project ZHEPP (Zürcher Eingliederungs-Pilot Projekt; engl.: Zurich integration pilot project) is a randomized controlled trial (RCT). The 250 participants will be randomized to either the intervention or the control group. The intervention group receives support of a job coach according to the approach of IPS. Participants in the control group do not receive IPS support. Participation takes a total of two years for each participant. Each group is interviewed every six months (T0-T4). A two-factor analysis of variance will be conducted with the two factors group (intervention versus control group) and outcome (employment yes/no). The main criterion of the two-factor analysis will be the number of competitive employment contracts in each group. Discussion This study will focus on the impact of IPS on new IV-pensioners and aims to identify predictors for a successful integration. Furthermore, we will examine the effect of IPS on stigma variables and recovery orientation. Trial registration ISRCTN54951166 PMID:23883137

Non-solenoidal Startup via Local Helicity Injection on Pegasus: Progress and Plans

NASA Astrophysics Data System (ADS)

Reusch, J. A.; Barr, J. L.; Bodner, G. M.; Bongard, M. W.; Burke, M. G.; Fonck, R. J.; Hinson, E. T.; Lewicki, B. T.; Perry, J. M.; Schlossberg, D. J.

2015-11-01

Non-solenoidal plasma startup via local helicity injection (LHI) at the Pegasus toroidal experiment now provides routine operation at Ip ~ 0.17MA with Iinj ~ 5kA and Vinj ~ 1kV from four active arc injectors. Experiments in the past year have advanced the understanding of the governing physics of LHI and its supporting technology. Injector impedance scales as Vinj3/ 2 and is governed by two effects: a quasineutrality constraint on electron beam propagation, related to the tokamak edge density, and double-layer sheath expansion, related to narc. Injector design improvements permit operation at Vinj >= 1 kV without deleterious PMI or impurity generation. Discharges with varied shape, Ip(t), and helicity input test a predictive 0D power-balance model for LHI startup. Anomalous, reconnection-driven Ti >800 eV and strong MHD activity localized near the injectors are observed during LHI. Preliminary core Thomson scattering measurements indicate surprisingly high Te >300 eV, which if verified may indicate the dominance of high-energy electron fueling from the injector current streams. A new divertor injector system has been designed to substantially increase the available helicity input rate and support critical studies of confinement during LHI and reconnection activity at high Ip. A proposed upgrade to the Pegasus experiment will extend these studies to NSTX-U relevant parameters. Support: US DOE grants DE-FG02-96ER54375; and DE-SC0006928.

Vaccines and IP Rights: A Multifaceted Relationship.

PubMed

Durell, Karen

2016-01-01

Just as there are many forms of vaccines and components to vaccines-particular compositions, delivery systems, components, and distribution networks-there are a variety of intellectual property (IP) protections applicable for vaccines. IP rights such as patent, copyright, trademarks, plant breeders' rights, and trade secrets may all be applicable to vaccines. Thus, discussion of IP rights and vaccines should not begin and end with the application of one IP right to a vaccine. The discussion should engage considerations of multiple IP rights applicable to a vaccine and how these can be utilized in an integrated manner in a strategy aimed at supporting the development and distribution of the vaccine. Such an approach to IP rights to vaccines allows for the integrated rights to be considered in light of the justifications for protecting vaccines with IP rights, as well as the issues relating to specific IP rights for vaccines, such as compulsory license regimes, available humanitarian purpose IP credits, etc. To view vaccines as the subject of multiple IP protections involves a refocusing, but the outcome can provide significant benefits for vaccine development and distribution.

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.

Integrative physicians and an herbal cancer "cure".

PubMed

Ben-Arye, Eran; Rosenberg, Shoshana Keren; Samuels, Noah

2016-08-01

Oncologists are frequently asked about herbal remedies claiming to "cure" cancer, or at least delay its progression. While complementary and integrative medicine (CIM) should be aimed primarily at improving quality-of-life (QOL) related concerns, "wonder cures" are part of an alternative health belief model providing hope for a "miracle" where conventional treatment has failed. We describe a physician with extensive small-cell lung cancer (SCLC) undergoing chemotherapy, with significant toxicities and impaired daily function. He had come for an integrative physician (IP) consultation, provided by a medical doctor dually trained in CIM and supportive cancer care, taking place in a conventional supportive cancer care service. We describe the IP consultation in general and regarding an herbal remedy which was being promoted as a "cure" for cancer. The subsequent patient-tailored CIM treatment process, in which patients receive evidence-based guidance on treatments which address QOL-related concerns, are presented.

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.

Clinical evidence for individual animal therapy for papillomatous digital dermatitis (hairy heel wart) and infectious bovine pododermatitis (foot rot).

PubMed

Apley, Michael D

2015-03-01

Data supporting individual animal therapy for papillomatous digital dermatitis (PDD) and infectious pododermatitis (IP) in cattle are available for treatment with multiple drugs in the form of randomized, prospective clinical trials conducted in naturally occurring disease with negative controls and masked subjective evaluators. In the case of PDD, these trials support the use of topical tetracycline and oxytetracycline, lincomycin, a copper-containing preparation, and a nonantimicrobial cream. In individual therapy for IP, trial evidence is available to support systemic treatment with ceftiofur, florfenicol, tulathromycin, and oxytetracycline. However, it was not available for IP standards such as penicillin G, sulfadimethoxine, and tylosin. Copyright © 2015 Elsevier Inc. All rights reserved.

On the implementation of IP protection using biometrics based information hiding and firewall

NASA Astrophysics Data System (ADS)

Basu, Abhishek; Nandy, Kingshuk; Banerjee, Avishek; Giri, Supratick; Sarkar, Souvik; Sarkar, Subir Kumar

2016-02-01

System-on-chip-based design style creates a revolution in very large scale integration industry with design efficiency, operating speed and development time. To support this process, reuse and exchange of components are essential in electronic form called intellectual property (IP). This, however, increases the possibility of encroachment of IP of the design. So copyright protection of IP against piracy is the most important concern for IP vendors. The existing solutions for IP protection are still not secure enough with flexibility, cost, etc. This paper proposes an information-hiding-based solution for IP protection by embedding a biometric copyright information and firewall inside an IP in the form of a finite state machine with unique configuration. The scheme first introduces biometric signature-based copyright as ownership proof. Second, firewall interrupts the normal functionality of IP at the end of the user time period. The experimental outcomes of field-programmable-gate-array implementation illustrate the efficiency of the proposed method.

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…

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

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

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

Supported Employment for the Reintegration of Disability Pensioners with Mental Illnesses: A Randomized Controlled Trial.

PubMed

Viering, Sandra; Jäger, Matthias; Bärtsch, Bettina; Nordt, Carlos; Rössler, Wulf; Warnke, Ingeborg; Kawohl, Wolfram

2015-01-01

Work is beneficial for the recovery from mental illness. Although the approach of individual placement and support (IPS) has been shown to be effective in Europe, it has not yet been widely implemented in European health care systems. The aim of this randomized controlled trial was to assess the effectiveness of IPS for disability pensioners with mental illnesses new on disability benefits in Switzerland. In the study at hand, 250 participants were randomly assigned to either the control or the intervention group. The participants in the intervention group received job coaching according to IPS during 2 years. The control group received no structured support. Both groups were interviewed at baseline and followed up every 6 months (baseline, 6, 12, 16, 18, 24 months) for 2 years. Primary outcome was to obtain a job in the competitive employment. IPS was more effective for the reintegration into the competitive employment market for disability pensioners than the control condition. Thirty-two percent of the participants of the intervention group and 12% of the control group obtained new jobs in the competitive employment. IPS is also effective for the reintegration into competitive employment of people with mental illness receiving disability pensions.

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.

Fracture Resistance and Mode of Failure of Ceramic versus Titanium Implant Abutments and Single Implant-Supported Restorations.

PubMed

Sghaireen, Mohd G

2015-06-01

The material of choice for implant-supported restorations is affected by esthetic requirements and type of abutment. This study compares the fracture resistance of different types of implant abutments and implant-supported restorations and their mode of failure. Forty-five Oraltronics Pitt-Easy implants (Oraltronics Dental Implant Technology GmbH, Bremen, Germany) (4 mm diameter, 10 mm length) were embedded in clear autopolymerizing acrylic resin. The implants were randomly divided into three groups, A, B and C, of 15 implants each. In group A, titanium abutments and metal-ceramic crowns were used. In group B, zirconia ceramic abutments and In-Ceram Alumina crowns were used. In group C, zirconia ceramic abutments and IPS Empress Esthetic crowns were used. Specimens were tested to failure by applying load at 130° from horizontal plane using an Instron Universal Testing Machine. Subsequently, the mode of failure of each specimen was identified. Fracture resistance was significantly different between groups (p < .05). The highest fracture loads were associated with metal-ceramic crowns supported by titanium abutments (p = .000). IPS Empress crowns supported by zirconia abutments had the lowest fracture loads (p = .000). Fracture modes of metal-ceramic crowns supported by titanium abutments included screw fracture and screw bending. Fracture of both crown and abutment was the dominant mode of failure of In-Ceram/IPS Empress crowns supported by zirconia abutments. Metal-ceramic crowns supported by titanium abutments were more resistant to fracture than In-Ceram crowns supported by zirconia abutments, which in turn were more resistant to fracture than IPS Empress crowns supported by zirconia abutments. In addition, failure modes of restorations supported by zirconia abutments were more catastrophic than those for restorations supported by titanium abutments. © 2013 Wiley Periodicals, Inc.

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.

Characterization of the hollow fiber assay for the determination of microtubule disruption in vivo.

PubMed

Suggitt, Marie; Swaine, David J; Pettit, George R; Bibby, Michael C

2004-10-01

The hollow fiber assay is used successfully as a routine in vivo screening model to quantitatively define anticancer activity by the National Cancer Institute. This study investigates whether the hollow fiber assay can be used as a short-term in vivo model to demonstrate specific pharmacodynamic end points, namely microtubule and cell cycle disruption. The growth of A549 cells was characterized within hollow fibers over 5 days in vivo at both subcutaneous (s.c.) and intraperitoneal (i.p.) sites. Drugs were administered on day 4 (i.p.). At 24 hours, cells were retrieved from fibers at both i.p. and s.c. sites of paclitaxel-treated (20 mg/kg) and combretastatin A1 phosphate-treated (150 mg/kg) mice. Cell cycle analysis after paclitaxel treatment revealed a mean G(2)-M phase population of 48.04% (i.p.) and 25.76% (s.c.) compared with vehicle group mice (6.78 and 5.56%, respectively; P = <0.001 and 0.005, respectively). Tumor cells retrieved from combretastatin A1 phosphate-treated mice had a mean G2-M phase population of 36.3% (i.p.) and 29.36% (s.c.) compared with cells retrieved from vehicle group mice (5.58 and 5.49%, respectively; P = <0.001). Using fluorescence and laser-confocal microscopy, paclitaxel was revealed to induce the formation of spindle asters and tubulin polymerization. Combretastatin A1 phosphate was shown to hold cells in mitosis. Changes in nuclear morphology were also observed. These data demonstrate that the hollow fiber assay can be used as a short-term in vivo model for studying the pharmacodynamic effects of both standard and novel compounds on microtubules. Evidence has also been provided to support the routine use of the in vivo hollow fiber assay for demonstrating the mechanism of action of a drug.

Validation of a Brief Structured Interview: The Children's Interview for Psychiatric Syndromes (ChIPS).

PubMed

Young, Matthew E; Bell, Ziv E; Fristad, Mary A

2016-12-01

Evidence-based assessment is important in the treatment of childhood psychopathology. While researchers and clinicians frequently use structured diagnostic interviews to ensure reliability, the most commonly used instrument, the Schedule for Affective Disorders and Schizophrenia for School Aged Children (K-SADS) is too long for most clinical applications. The Children's Interview for Psychiatric Syndromes (ChIPS/P-ChIPS) is a highly-structured brief diagnostic interview. The present study compared K-SADS and ChIPS/P-ChIPS diagnoses in an outpatient clinical sample of 50 parent-child pairs aged 7-14. Agreement between most diagnoses was moderate to high between the instruments and with consensus clinical diagnoses. ChIPS was significantly briefer to administer than the K-SADS. Interviewer experience level and participant demographics did not appear to affect agreement. Results provide further evidence for the validity of the ChIPS and support its use in clinical and research settings.

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.

Initiatives in Non-Solenoidal Startup and H-mode Physics at Near-Unity A

NASA Astrophysics Data System (ADS)

Bongard, M. W.; Barr, J. L.; Burke, M. G.; Fonck, R. J.; Hinson, E. T.; Lewicki, B. T.; Perry, J. M.; Redd, A. J.; Schlossberg, D. J.; Thome, K. E.; Winz, G. R.

2014-10-01

Research on the A ~ 1 Pegasus ST is advancing the physics of non-solenoidal tokamak startup and the H-mode confinement regime. Local helicity injection (LHI) uses current sources in the plasma edge to initiate and drive Ip via DC helicity injection, subject to constraints from helicity conservation and Taylor relaxation. To date, Ip ~ 0 . 18 MA has been initiated with Iinj ~ 6 kA. A predictive 0-D power balance model of LHI Ip (t) evolution matches present discharges with strong PF induction. It projects Ip ~ 0 . 3 MA operation in Pegasus will achieve the LHI-dominated physics regime expected for 1 MA NSTX-U startup. Ohmic H-mode plasmas are routinely attained, due to the low Pth at the low BT of A --> 1 plasmas. However, both limited and favorable ∇B SN plasmas have Pth ~ 11 times higher than expected from high- A scalings. They have improved τe (H98 ~ 1) and a quiescent Jedge pedestal between edge localized modes (ELMs). Unique Jedge (t) measurements through a single Type I ELM show a complex, multimodal pedestal collapse and filament ejection. A proposed Pegasus-U initiative will upgrade the centerstack assembly and LHI injector systems, increasing BT to 1 T, Ohmic V-s by × 6 , and pulse length to 100 ms at A = 1 . 2 . This allows the physics and technology of LHI to be validated at NSTX-U relevant parameters, supports studies of nonlinear ELM dynamics, and will test high-βT tokamak stability. Work supported by US DOE Grant DE-FG02-96ER54375.

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.

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.

Towards a Predictive Capability for Local Helicity Injection Startup

NASA Astrophysics Data System (ADS)

Barr, J. L.; Bongard, M. W.; Burke, M. G.; Fonck, R. J.; Hinson, E. T.; Lewicki, B. T.; Perry, J. M.; Redd, A. J.; Schlossberg, D. J.

2014-10-01

Local helicity injection (LHI) is a non-solenoidal tokamak startup technique under development on the Pegasus ST. New designs of the injector cathode geometry and plasma-facing shield rings support high-voltage operation up to 1.5 kV. This leads to reduced requirements in injector area for a given helicity input rate. Near-term experiments in Pegasus are testing the gain in Ip obtained with a 1 . 5 × increase in the helicity input rate and the efficacy of helicity injection in the lower divertor region. A predictive model for LHI is needed to project scalable scenarios for larger devices. A lumped-parameter circuit model using power and helicity balance is being developed for LHI on Pegasus-U and NSTX-U. The model indicates that MA-class startup on NSTX-U will require operating in a regime where the drive from LHI dominates the inductive effects arising from dynamically evolving plasma geometry. The physics of this new regime can be tested in Pegasus-U at Ip ~ 0 . 3 MA. The LHI systems on the proposed Pegasus-U will be expanded to provide 3 - 4 × helicity injection rate and the toroidal field doubled to reach this regime. Predictive models to be validated on Pegasus-U include the 0-D power balance model, NIMROD, and TSC. Work supported by US DOE Grants DE-FG02-96ER54375 and DE-SC0006928.

Introduction to the Evaluation of the Intensive Partnerships for Effective Teaching (IP). Working Paper WR-1034-BMGF

ERIC Educational Resources Information Center

Stecher, Brian M.; Garet, Michael

2014-01-01

On November 19, 2009, the Bill & Melinda Gates Foundation announced that it would invest $290 million to support effective teaching as a means to ensure all students receive the education they need to succeed in high school and beyond. The foundation made six-year grants to support four Intensive Partnership for Effective Teaching (IP) sites…

The development of the Australian Space Forecast Centre (ASFC)

NASA Astrophysics Data System (ADS)

Wilkinson, Phil; Kennewell, John A.; Cole, David

2018-05-01

The Ionospheric Prediction Service (IPS) was formed in 1947 to provide monthly prediction services for high frequency (HF) radio, in particular to support HF communications with the United Kingdom. It was quickly recognized that to be effective such a service also had to provide advice when ionospheric storms prevented HF communications from taking place. With the advent of the International Geophysical Year (IGY), short-term forecasts were also required for research programmes and the task of supplying the Australian input to these was given to Frank Cook, of the IPS, while Jack Turner, also of the IPS, supervised the generation of ionospheric maps to support high latitude HF communications. These two important IGY activities formed the platform on which all future IPS services would be built. This paper reviews the development of the Australian Space Forecast Centre (ASFC), which arose from these early origins.

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

Economic, Labor, and Regulatory Moderators of the Effect of Individual Placement and Support Among People With Severe Mental Illness: A Systematic Review and Meta-analysis.

PubMed

Metcalfe, Justin D; Drake, Robert E; Bond, Gary R

2018-01-13

As Individual Placement and Support (IPS) has become the international standard for vocational rehabilitation of adults with serious mental illness, researchers must consider the relationship between IPS and local environments. This meta-analysis used mixed-effects meta-regressions to assess the impact of site-level moderators on the likelihood that IPS recipients, compared with recipients of alternative vocational services, achieved competitive employment. Potential moderators included change in gross domestic product (GDP), local unemployment and unionization rates, and indices describing employment protection regulations, level of disability benefits compensation, and efforts to integrate people with disabilities into the workforce. Regulatory moderators represent facilitators and barriers to employment that may reinforce or detract from the effectiveness of IPS. Across 30 sites drawn from 21 randomized controlled trials in 12 countries (33% in the United States), IPS recipients were 2.31 (95% CI 1.99-2.69) times more likely to find competitive employment than recipients of alternative vocational rehabilitation services. The significant competitive-employment rate advantage of IPS over control services increased in the presence of weaker employment protection legislation and integration efforts, and less generous disability benefits. Policy makers should recognize and account for the fact that labor and disability regulations can create an arrangement of incentives that reduces the relative efficacy of supported employment. © The Author(s) 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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.

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.

The extended TRIP supporting VoIP routing reservation with distributed QoS

NASA Astrophysics Data System (ADS)

Wang, Furong; Wu, Ye

2004-04-01

In this paper, an existing protocol, i.e. TRIP (Telephony Routing over IP) is developed to provide distributed QoS when making resource reservations for VoIP services such as H.323, SIP. Enhanced LSs (location servers) are deployed in ITADs (IP Telephony Administrative Domains) to take in charge of intra-domain routing policy because of small propagation price. It is an easy way to find an IP telephone route for intra-domain VoIP media association and simultaneously possess intra-domain load balancing features. For those routing reservations bridging domains, inter-domain routing policy is responsible for finding the shortest inter-domain route with enough resources. I propose the routing preference policy based on QoS price when the session traffic is shaped by a token bucket, related QoS messages, and message cooperation.

[Stem cell research and science and technology policy in Japan].

PubMed

Yashiro, Yoshimi

2011-12-01

In this paper I review the present condition of the regeneration medicine research using pluripotency and a somatic stem cell, and I describe the subject of the science and technology policy in Japan towards realization of regeneration medicine. The Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) supported research promotion by the prompt action in 2007 when establishment of the iPS cell was reported by Shinya Yamanaka. Although the hospitable support of the Japanese government to an iPS cell is continued still now, there are some problems in respect of the support to other stem cell researches, and industrialization of regeneration medicine. In order to win a place in highly competitive area of investigation, MEXT needs to change policy so that funds may be widely supplied also to stem cell researches other than iPS cell research.

Fostering interprofessional learning in a rehabilitation setting: development of an interprofessional clinical learning unit.

PubMed

Vanderzalm, Jeanne; Hall, Mark D; McFarlane, Lu-Anne; Rutherford, Laurie; Patterson, Steven K

2013-01-01

The development and implementation of interprofessional (IP) clinical learning units as a method to enhance IP clinical education and improve patient care in a rehabilitation setting are described. Using a community-based participatory research approach, academia and healthcare delivery agencies formed a partnership to create an IP clinical learning unit in a rehabilitation setting. Preimplementation data from surveys and focus group data identified areas for improvement to enhance IP understanding and collaboration. A working group developed and implemented initiatives to enhance IP practice. Preimplementation, eight themes emerged from which the working group identified goals and implemented strategies to strengthen IP learning. Goals included Creation of an IP Learning Environment, Increased Awareness of IP Practice, Role Clarification, Enhanced IP Communication, and Reflection and Evaluation. Postimplementation data revealed six themes: Communication, Informal IP Learning, Role Awareness, Positive Learning Environment, Logistics, and Challenges. The development of the IP clinical learning unit was successful and rewarding, but not without its challenges. Formal IP education was necessary to enhance collaborative practice, even in a multidisciplinary environment. Commitment and support from all participants, particularly managers and administrators from the healthcare agency, were critical to success. The focus of this unit was on a stroke rehabilitation unit; however, the development and implementation principles identified may be applicable to any team-based clinical setting. © 2013 Association of Rehabilitation Nurses.

Space-Based Telemetry and Range Safety (STARS) Study

NASA Technical Reports Server (NTRS)

Hogie, Keith; Crisuolo, Ed; Parise, Ron

2004-01-01

This presentation will describe the design, development, and testing of a system to collect telemetry, format it into UDP/IP packets, and deliver it to a ground test range using standard IP technologies over a TDRSS link. This presentation will discuss the goal of the STARS IP Formatter along with the overall design. It will also present performance results of the current version of the IP formatter. Finally, it will discuss key issues for supporting constant rate telemetry data delivery when using standard components such as PCI/104 processors, the Linux operating system, Internet Protocols, and synchronous serial interfaces.

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.

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.

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.

Integrating QoS and security functions in an IP-VPN gateway

NASA Astrophysics Data System (ADS)

Fan, Kuo-Pao; Chang, Shu-Hsin; Lin, Kuan-Ming; Pen, Mau-Jy

2001-10-01

IP-based Virtual Private Network becomes more and more popular. It can not only reduce the enterprise communication cost but also increase the revenue of the service provider. The common IP-VPN application types include Intranet VPN, Extranet VPN, and remote access VPN. For the large IP-VPN market, some vendors develop dedicated IP-VPN devices; while some vendors add the VPN functions into their existing network equipment such as router, access gateway, etc. The functions in the IP-VPN device include security, QoS, and management. The common security functions supported are IPSec (IP Security), IKE (Internet Key Exchange), and Firewall. The QoS functions include bandwidth control and packet scheduling. In the management component, policy-based network management is under standardization in IETF. In this paper, we discuss issues on how to integrate the QoS and security functions in an IP-VPN Gateway. We propose three approaches to do this. They are (1) perform Qos first (2) perform IPSec first and (3) reserve fixed bandwidth for IPSec. We also compare the advantages and disadvantages of the three proposed approaches.

Reducing Manpower for a Technologically Advanced Ship

DTIC Science & Technology

2010-01-27

Watchstations by 84% (119 to 34) “ Autonomic ” Fire Suppression System AFSS is designed to automatically: (1) Isolate damage to firemain piping... System (IPS) Advanced VLS Autonomic Fire Suppression Hull Form Scale Models Total Ship Computing Environment (TSCE) Integrated Undersea...Warfare (IUSW) System ( AFSS ) 8 Total Ship Organization Ship C3I Engage Support Technical Director TSCEI Sense Integrated Product Teams TSSE Director

Visualization of Air Particle Dynamics in an Engine Inertial Particle Separator

NASA Astrophysics Data System (ADS)

Wolf, Jason; Zhang, Wei

2015-11-01

Unmanned Aerial Vehicles (UAVs) are regularly deployed around the world in support of military, civilian and humanitarian efforts. Due to their unique mission profiles, these advanced UAVs utilize various internal combustion engines, which consume large quantities of air. Operating these UAVs in areas with high concentrations of sand and dust can be hazardous to the engines, especially during takeoff and landing. In such events, engine intake filters quickly become saturated and clogged with dust particles, causing a substantial decrease in the UAVs' engine performance and service life. Development of an Engine Air Particle Separator (EAPS) with high particle separation efficiency is necessary for maintaining satisfactory performance of the UAVs. Inertial Particle Separators (IPS) have been one common effective method but they experience complex internal particle-laden flows that are challenging to understand and model. This research employs an IPS test rig to simulate dust particle separation under different flow conditions. Soda lime glass spheres with a mean diameter of 35-45 microns are used in experiments as a surrogate for airborne particulates encountered during flight. We will present measurements of turbulent flow and particle dynamics using flow visualization techniques to understand the multiphase fluid dynamics in the IPS device. This knowledge can contribute to design better performing IPS systems for UAVs. Cleveland State University, Cleveland, Ohio, 44115.

Improving the delineation of hydrocarbon-impacted soils and water through induced polarization (IP) tomographies: a field study at an industrial waste land.

PubMed

Deceuster, John; Kaufmann, Olivier

2012-08-01

Without a good estimation of samples representativeness, the delineation of the contaminated plume extent and the evaluation of volumes of hydrocarbon-impacted soils may remain difficult. To contribute to this question, a time domain induced polarization (IP) field experiment was conducted on an industrial waste land. Boreholes were drilled to specify the local geological context. Cross-hole seismic tomographies were performed to extend borehole logs and to draw an interpreted geological cross-section. Soil samples taken during drillings were analysed in laboratory. A preliminary survey was conducted to locate the IP profile. The polarization signatures linked to the presence of clayey sediments were filtered out from the data set. Chargeability and resistivity depth soundings were computed and compared to mean concentrations of total organic products to overcome the data support issue between the geophysical models and the spot samples of soils. A logarithmic relation between chargeabilities and smoothed hydrocarbon concentrations in soils was found. Taking into account contaminant's concentration thresholds defined in local codes and regulations allows defining chargeability classes to delineate hotspots on this site. This showed that IP tomography can be an accurate screening methodology. A statistical methodology is proposed to assess the efficiency of the investigation strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

The prevalence of gastric heterotopia of the proximal esophagus is underestimated, but preneoplasia is rare - correlation with Barrett's esophagus.

PubMed

Peitz, Ulrich; Vieth, Michael; Evert, Matthias; Arand, Jovana; Roessner, Albert; Malfertheiner, Peter

2017-07-12

The previously reported prevalence of gastric heterotopia in the cervical esophagus, also termed inlet patch (IP), varies substantially, ranging from 0.18 to 14%. Regarding cases with adenocarcinoma within IP, some experts recommend to routinely obtain biopsies from IP for histopathology. Another concern is the reported relation to Barrett's esophagus. The objectives of the study were to prospectively determine the prevalence of IP and of preneoplasia within IP, and to investigate the association between IP and Barrett's esophagus. 372 consecutive patients undergoing esophagogastroduodenoscopy were carefully searched for the presence of IP. Biopsies for histopathology were targeted to the IP, columnar metaplasia of the lower esophagus, gastric corpus and antrum. Different definitions of Barrett's esophagus were tested for an association with IP. At least one IP was endoscopically identified in 53 patients (14.5%). Histopathology, performed in 46 patients, confirmed columnar epithelium in 87% of cases, which essentially presented corpus and/or cardia-type mucosa. Intestinal metaplasia was detected in two cases, but no neoplasia. A previously reported association of IP with Barrett's esophagus was weak, statistically significant only when short segments of cardia-type mucosa of the lower esophagus were included in the definition of Barrett's esophagus. The prevalence of IP seems to be underestimated, but preneoplasia within IP is rare, which does not support the recommendation to regularly obtain biopsies for histopathology. Biopsies should be targeted to any irregularities within the heterotopic mucosa. The correlation of IP with Barrett's esophagus hints to a partly common pathogenesis.

Effects of methotrexate upon inflammatory parameters induced by carrageenan in the mouse model of pleurisy.

PubMed Central

Dalmarco, Eduardo Monguilhott; Fröde, Tânia Silvia; Medeiros, Yara Santos

2002-01-01

BACKGROUND: The model of pleurisy induced by carrageenan exhibits a biphasic response (4 and 48 h) and permits the quantification of exudate, cell migration and certain enzymes such as myeloperoxidase (MPO) and adenosine-deaminase (ADA) that are markers of activated leukocytes. AIMS: The present study evaluates whether there exists, in the pleurisy model, a significant inhibition of ADA and MPO enzymes, leukocyte kinetics and other markers of inflammation [nitric oxide (NO) levels, exudation] caused by methotrexate treatment by the intraperitoneal (i.p.) route. METHODS: The pleurisy was induced by carrageenan (1%) in mice, and the parameters were analyzed 4 and 48 h after. RESULTS: After the induction of inflammation (4 h), methotrexate (20 mg/kg, i.p., 24 h before pleurisy induction) inhibited the leukocyte infiltration (p < 0.05), NO levels and MPO activity (p < 0.01), but not ADA activity and fluid leakage (p > 0.05). Regarding the second phase of pleurisy (48 h), methotrexate (40 mg/kg, i.p., 0.5 h before pleurisy induction) inhibited the leukocyte infiltration (p < 0.05), fluid leakage, NO levels (p < 0.01), and ADA and MPO activity (p < 0.05). CONCLUSIONS: These findings support the evidence that the acute administration of methotrexate has an important systemic anti-inflammatory activity in the studied inflammatory model. This effect was due to a significant inhibition on both neutrophil and mononuclear cells, being less marked in relation to exudation 48 h after. In relation to the enzymes studied and to NO levels, the findings support the evidence that methotrexate inhibits both enzymes (MPO and ADA) from leukocytes at the site of injury, thus reflecting the activation of both neutrophils and lymphocytes, respectively. Furthermore, the inhibiting effect on NO in both phases of pleurisy induced by carrageenan (4 and 48 h) indicates that methotrexate acts on constitutive and/or inducible NO synthases by means of different cells of the pleural cavity. PMID:12467522

Tumor Penetrating Theranostic Nanoparticles for Enhancement of Targeted and Image-guided Drug Delivery into Peritoneal Tumors following Intraperitoneal Delivery.

PubMed

Gao, Ning; Bozeman, Erica N; Qian, Weiping; Wang, Liya; Chen, Hongyu; Lipowska, Malgorzata; Staley, Charles A; Wang, Y Andrew; Mao, Hui; Yang, Lily

2017-01-01

The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery. Targeted delivery of near infrared dye labeled IONPs into orthotopic tumors could be detected by non-invasive optical and magnetic resonance imaging. Histological analysis revealed that a high level of uPAR targeted, PEGylated IONPs efficiently penetrated into both the peripheral and central tumor areas in the primary tumor as well as peritoneal metastatic tumor. Improved theranostic IONP delivery into the tumor center was not mediated by nonspecific macrophage uptake and was independent from tumor blood vessel locations. Importantly, i.p. delivery of uPAR targeted theranostic IONPs carrying chemotherapeutics, cisplatin or doxorubicin, significantly inhibited the growth of pancreatic tumors without apparent systemic toxicity. The levels of proliferating tumor cells and tumor vessels in tumors treated with the above theranostic IONPs were also markedly decreased. The detection of strong optical signals in residual tumors following i.p. therapy suggested the feasibility of image-guided surgery to remove drug-resistant tumors. Therefore, our results support the translational development of i.p. delivery of uPAR-targeted theranostic IONPs for image-guided treatment of peritoneal tumors.

Interprofessional mentoring: enhancing students' clinical learning.

PubMed

Lait, Jana; Suter, Esther; Arthur, Nancy; Deutschlander, Siegrid

2011-05-01

Interprofessional (IP) collaboration is recognized as critical for patient-centred care. The clinical setting is an ideal environment for students to learn the competencies required to effectively work with providers from other professions. To enhance traditional clinical placements, we propose an IP mentoring approach, defined as learning that takes place between providers and students who are from different disciplines or health professions. In IP mentoring, students have primary relationships with their preceptors, but also have interactions with providers from other professions. We implemented IP mentoring with the support of two faculties of nursing in Alberta, Canada who provided an IP clinical focus for interested fourth year students. We emphasized to providers and students that there are no prescribed interactions that comprise IP mentoring; experiences between providers and students are context-specific and often informal. Through our evaluation we demonstrated that in IP mentoring, provider commitment was important, students engaged in IP activities of varying complexity, and students learned about roles of other professions and how to work together to provide patient-centred care. IP mentoring is an effective learning strategy to enhance students' knowledge and skills in IP collaboration without radical changes to the structure of the placements or to the educational curricula. Copyright © 2010 Elsevier Ltd. All rights reserved.

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®.

DNA damage response curtails detrimental replication stress and chromosomal instability induced by the dietary carcinogen PhIP

PubMed Central

Mimmler, Maximilian; Peter, Simon; Kraus, Alexander; Stroh, Svenja; Nikolova, Teodora; Seiwert, Nina; Hasselwander, Solveig; Neitzel, Carina; Haub, Jessica; Monien, Bernhard H.; Nicken, Petra; Steinberg, Pablo; Shay, Jerry W.; Kaina, Bernd; Fahrer, Jörg

2016-01-01

PhIP is an abundant heterocyclic aromatic amine (HCA) and important dietary carcinogen. Following metabolic activation, PhIP causes bulky DNA lesions at the C8-position of guanine. Although C8-PhIP-dG adducts are mutagenic, their interference with the DNA replication machinery and the elicited DNA damage response (DDR) have not yet been studied. Here, we analyzed PhIP-triggered replicative stress and elucidated the role of the apical DDR kinases ATR, ATM and DNA-PKcs in the cellular defense response. First, we demonstrate that PhIP induced C8-PhIP-dG adducts and DNA strand breaks. This stimulated ATR-CHK1 signaling, phosphorylation of histone 2AX and the formation of RPA foci. In proliferating cells, PhIP treatment increased the frequency of stalled replication forks and reduced fork speed. Inhibition of ATR in the presence of PhIP-induced DNA damage strongly promoted the formation of DNA double-strand breaks, activation of the ATM-CHK2 pathway and hyperphosphorylation of RPA. The abrogation of ATR signaling potentiated the cell death response and enhanced chromosomal aberrations after PhIP treatment, while ATM and DNA-PK inhibition had only marginal effects. These results strongly support the notion that ATR plays a key role in the defense against cancer formation induced by PhIP and related HCAs. PMID:27599846

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

Orellana, S.A.; Trilivas, I.; Brown, J.H.

Carbachol and guanine nucleotides stimulate formation of the (/sup 3/H)inositol phosphates IP, IP2, and IP3 in saponin-permeabilized monolayers labelled with (/sup 3/H) inositol. Carbachol alone has little effect on formation of the (/sup 3/H) inositol phosphates (IPs), but GTP..gamma..S causes synergistic accumulation of (/sup 3/H)IPs to levels similar to those seen in intact cells. GTP, GppNHp, and GTP..gamma..S all support formation of the (/sup 3/H)IPs, with or without hormone, but GTP..gamma..S is the most effective. In the presence of GTP..gamma..S, the effect of carbachol is dose-dependent. Half-maximal and maximal accumulation of the (/sup 3/H)IPs occur at approx. 5 ..mu..M andmore » approx. 100 ..mu..M carbachol, respectively; values close to those seen in intact cells. GTP..gamma..S alone stimulates formation of the (/sup 3/H)IPs after a brief lag time. The combination of GTP..gamma..S and carbachol both increases the rate of, and decreases the lag in, formation of the (/sup 3/H)IPs. LiCl increases (/sup 3/H)IP and IP2, but not IP3, accumulation; while 2,3-diphosphoglycerate substantially increases that of (/sup 3/H)IP3. GTP..gamma..S and carbachol cause formation of (/sup 3/H)IPs in the absence of Ca/sup + +/, but formation induced by GTP..gamma..S with or without carbachol is Ca/sup + +/-sensitive over a range of physiological concentrations. Although carbachol, Ca/sup + +/, and GTP..gamma..S all have effects on formation of (/sup 3/H)IPs, GTP..gamma..S appears to be a primary and obligatory regulator of phosphoinositide hydrolysis in the permeabilized 1321N1 astrocytoma cell.« less

[PSI+] prion propagation is controlled by inositol polyphosphates

PubMed Central

Wickner, Reed B.; Kelly, Amy C.; Bezsonov, Evgeny E.; Edskes, Herman K.

2017-01-01

The yeast prions [PSI+] and [URE3] are folded in-register parallel β-sheet amyloids of Sup35p and Ure2p, respectively. In a screen for antiprion systems curing [PSI+] without protein overproduction, we detected Siw14p as an antiprion element. An array of genetic tests confirmed that many variants of [PSI+] arising in the absence of Siw14p are cured by restoring normal levels of the protein. Siw14p is a pyrophosphatase specifically cleaving the β phosphate from 5-diphosphoinositol pentakisphosphate (5PP-IP5), suggesting that increased levels of this or some other inositol polyphosphate favors [PSI+] propagation. In support of this notion, we found that nearly all variants of [PSI+] isolated in a WT strain were lost upon loss of ARG82, which encodes inositol polyphosphate multikinase. Inactivation of the Arg82p kinase by D131A and K133A mutations (preserving Arg82p’s nonkinase transcription regulation functions) resulted the loss of its ability to support [PSI+] propagation. The loss of [PSI+] in arg82Δ is independent of Hsp104’s antiprion activity. [PSI+] variants requiring Arg82p could propagate in ipk1Δ (IP5 kinase), kcs1Δ (IP6 5-kinase), vip1Δ (IP6 1-kinase), ddp1Δ (inositol pyrophosphatase), or kcs1Δ vip1Δ mutants but not in ipk1Δ kcs1Δ or ddp1Δ kcs1Δ double mutants. Thus, nearly all [PSI+] prion variants require inositol poly-/pyrophosphates for their propagation, and at least IP6 or 5PP-IP4 can support [PSI+] propagation. PMID:28923943

Antinociceptive effects of the extracts of Xylopia parviflora bark and its alkaloidal components in experimental animals.

PubMed

Nishiyama, Yumi; Moriyasu, Masataka; Ichimaru, Momoyo; Iwasa, Kinuko; Kato, Atsushi; Mathenge, Simon G; Chalo Mutiso, Patrick B; Juma, Francis D

2010-01-01

In the present study, we attempted to elucidate the antinociceptive activity of Xylopia parviflora bark using the acetic acid-induced writhing test, hot plate test, and formalin test in mice. The MeOH extract (100 and 200 mg/kg, administered intraperitoneally (i.p.)) had an antinociceptive effect demonstrated by its inhibitory effects on writhing number induced by acetic acid. Three alkaloidal fractions exhibited significant antinociceptive effects in three animal models; the chloroform-soluble fraction, including secondary and tertiary alkaloids, exhibited the strongest effect. This result supported its use in folk medicine as an analgesic agent. We tested the main alkaloids of these fractions for their antinociceptive effects to clarify the active components. (+)-Corytuberine (6.3 and 12.5 mg/kg, i.p.) showed very strong activity, had a significant antinociceptive effect in the acetic acid-induced writhing test (with 49.4 and 98.9% reduction of writhes), in the hot plate test, and in the formalin test (with 55.4 and 90.6% inhibition during the first phase, and 73.9 and 99.9% during the second phase, respectively). (+)-Glaucine (12.5 and 25 mg/kg, i.p.) showed strong activity in three animal models, too. The activity of these compounds was also observed following oral administration in the acetic acid-induced writhing test.

The Worldwide Interplanetary Scintillation (IPS) Stations (WIPSS) Network in support of Space-Weather Science and Forecasting

NASA Astrophysics Data System (ADS)

Bisi, M. M.; Gonzalez-Esparza, A.; Jackson, B. V.; Aguilar-Rodriguez, E.; Tokumaru, M.; Chashei, I. V.; Tyul'bashev, S. A.; Manoharan, P. K.; Fallows, R. A.; Chang, O.; Mejia-Ambriz, J. C.; Yu, H. S.; Fujiki, K.; Shishov, V.

2016-12-01

The phenomenon of space weather - analogous to terrestrial weather which describes the changing low-altitude atmospheric conditions on Earth - is essentially a description of the changes in the plasma environment at and near the Earth. Some key parameters for space-weather purposes driving space weather at the Earth include velocity, density, magnetic field, high-energy particles, and radiation coming into and within the near-Earth space environment. Interplanetary scintillation (IPS) can be used to provide a global measure of velocity and density as well as indications of changes in the plasma and magnetic-field rotations along each observational line of sight. If the observations are formally inverted into a three-dimensional (3-D) tomographic reconstruction (such as using the University of California, San Diego - UCSD - kinematic model and reconstruction technique), then source-surface magnetic fields can also be propagated out to the Earth (and beyond) as well as in-situ data also being incorporated into the reconstruction. Currently, this has been done using IPS data only from the Institute for Space-Earth Environmental (ISEE) and has been scientifically since the 1990s, and in a forecast mode since around 2000. There is now a defined IPS Common Data Format (IPSCDFv1.0) which is being implemented by the majority of the IPS community (this also feeds into the tomography). The Worldwide IPS Stations (WIPSS) Network aims to bring together, using IPSCDFv1.0, the worldwide real-time capable IPS observatories with well-developed and tested analyses techniques being unified across all single-site systems (such as MEXART, Pushchino, and Ooty) and cross-calibrated to the multi-site ISEE system (as well as learning from the scientific-based systems such as EISCAT, LOFAR, and the MWA), into the UCSD 3-D tomography to improve the accuracy, spatial and temporal data coverage, and both the spatial and temporal resolution for improved space-weather science and forecast capabilities.

The Worldwide Interplanetary Scintillation (IPS) Stations (WIPSS) Network in support of Space-Weather Science and Forecasting

NASA Astrophysics Data System (ADS)

Bisi, Mario Mark; Americo Gonzalez-Esparza, J.; Jackson, Bernard; Aguilar-Rodriguez, Ernesto; Tokumaru, Munetoshi; Chashei, Igor; Tyul'bashev, Sergey; Manoharan, Periasamy; Fallows, Richard; Chang, Oyuki; Yu, Hsiu-Shan; Fujiki, Ken'ichi; Shishov, Vladimir; Barnes, David

2017-04-01

The phenomenon of space weather - analogous to terrestrial weather which describes the changing low-altitude atmospheric conditions on Earth - is essentially a description of the changes in the plasma environment at and near the Earth. Some key parameters for space-weather purposes driving space weather at the Earth include velocity, density, magnetic field, high-energy particles, and radiation coming into and within the near-Earth space environment. Interplanetary scintillation (IPS) can be used to provide a global measure of velocity and density as well as indications of changes in the plasma and magnetic-field rotations along each observational line of sight. If the observations are formally inverted into a three-dimensional (3-D) tomographic reconstruction (such as using the University of California, San Diego - UCSD - kinematic model and reconstruction technique), then source-surface magnetic fields can also be propagated out to the Earth (and beyond) as well as in-situ data also being incorporated into the reconstruction. Currently, this has been done using IPS data only from the Institute for Space-Earth Environmental (ISEE) and has been scientifically since the 1990s, and in a forecast mode since around 2000. There is now a defined (and updated) IPS Common Data Format (IPSCDFv1.1) which is being implemented by the majority of the IPS community (this also feeds into the UCSD tomography). The Worldwide IPS Stations (WIPSS) Network aims to bring together, using IPSCDFv1.1, the worldwide real-time capable IPS observatories with well-developed and tested analyses techniques being unified across all single-site systems (such as MEXART, Pushchino, and Ooty) and cross-calibrated to the multi-site ISEE system (as well as learning from the scientific-based systems such as EISCAT, LOFAR, and the MWA), into the UCSD 3-D tomography to improve the accuracy, spatial and temporal data coverage, and both the spatial and temporal resolution for improved space-weather science and forecast capabilities.

Involvement of N-methyl-d-aspartate receptors in the antidepressant-like effect of 5-hydroxytryptamine 3 antagonists in mouse forced swimming test and tail suspension test.

PubMed

Kordjazy, Nastaran; Haj-Mirzaian, Arya; Amiri, Shayan; Ostadhadi, Sattar; Amini-Khoei, Hossein; Dehpour, Ahmad Reza

2016-02-01

Recent evidence indicates that 5-hydroxytryptamine 3 (5-HT3) antagonists such as ondansetron and tropisetron exert positive behavioral effects in animal models of depression. Due to the ionotropic nature of 5-HT3 and N-methyl-d-aspartate (NMDA) receptors, plus their contribution to the pathophysiology of depression, we investigated the possible role of NMDA receptors in the antidepressant-like effect of 5-HT3 receptor antagonists in male mice. In order to evaluate the animals' behavior in response to different treatments, we performed open-field test (OFT), forced swimming test (FST), and tail-suspension test (TST), which are considered as valid tasks for measuring locomotor activity and depressive-like behaviors in mice. Our data revealed that intraperitoneal (i.p.) administration of tropisetron (5, 10, and 30mg/kg) and ondansetron (0.01, and 0.1μg/kg) significantly decreased the immobility time in FST and TST. Also, co-administration of subeffective doses of tropisetron (1mg/kg, i.p.) or ondansetron (0.001μg/kg, i.p.) with subeffective doses of NMDA receptor antagonists, ketamine (1mg/kg, i.p.), MK-801 (0.05mg/kg, i.p.) and magnesium sulfate (10mg/kg, i.p.) resulted in a reduced immobility time both in FST and TST. The subeffective dose of NMDA (NMDA receptor agonist, 75mg/kg, i.p.) abolished the effects of 5-HT3 antagonists in FST and TST, further supporting the presumed interaction between 5-HT3 and NMDA receptors. These treatments did not affect the locomotor behavior of animals in OFT. Finally, the results of our study suggest that the positive effects of 5-HT3 antagonists on the coping behavior of mice in FST and TST are at least partly mediated through NMDA receptors participation. Copyright © 2015 Elsevier Inc. All rights reserved.

Nutrition -- a key issue for Africa. PANFRICO IV notes importance of strengthening nutrition activities to assist FP promotion.

PubMed

1993-12-01

Malnutrition is a major concern in African countries. The incorporation of nutrition education into maternal-child health services has a direct effect on child survival and the promotion of family planning (FP). The 4th Regional Workshop on the integrated Project (PANFRICO IV) was held in Banjul, The Gambia, from September 27 through October 1, 1993, and focused on the role of nutrition in promoting the integrated project on FP, nutrition, and parasite control (IP). PANFRICO was supported by UNFPA and IPPF, and was attended by 50 participants from 15 countries, some of them IP-implementing countries such as Ethiopia, The Gambia, Ghana, Tanzania, and Zambia. Officials of UNFPA, IPPF, and JOICFP also attended the meeting, as well as two representatives of the Japan International Cooperation Agency. IPPF has supported IP since 1974 because of IP's commitment to community participation. This forum allowed participants to discuss how nutrition could be incorporated into the IP for increased acceptance of FP. Recommendations called for a stronger nutritional component in IP without losing sight of FP promotion as the main focus. The participants stressed that the improvement of the nutrition component requires government commitment, policy, analysis of the nutritional situation in planning for action, community participation (of men in particular) in implementation, intersectoral coordination of nutrition and FP strategies, and nutrition education.

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.

Predictive Power-balance Modeling of PEGASUS and NSTX-U Local Helicity Injection Discharges

NASA Astrophysics Data System (ADS)

Barr, J. L.; Bongard, M. W.; Burke, M. G.; Fonck, R. J.; Hinson, E. T.; Perry, J. M.; Redd, A. J.; Schlossberg, D. J.

2013-10-01

Local helicity injection (LHI) with outer poloidal-field (PF) induction for solenoid-free startup is being studied on PEGASUS, reaching Ip <= 0 . 175 MA with 6 kA of injected current. A lumped-parameter circuit model for predicting the performance of LHI initiated plasmas is under development. The model employs energy and helicity balance, and includes applied PF ramping and the inductive effects of shape evolution. Low- A formulations for both the plasma external inductance and a uniform equilibrium-field are used to estimate inductive voltages. PEGASUS LHI plasmas are created near the outboard injectors with aspect ratio (A) ~ 5-6.5 and grow inward to fill the confinement region at A <= 1 . 3 . Initial results match experimental Ip (t) trajectories within 15 kA with a prescribed geometry evolution. Helicity injection is the largest driving term in the initial phase, but in the later phase is reduced to 20-45% of the total drive as PF induction and decreasing plasma inductance become dominant. In contrast, attaining ~1 MA non-solenoidal startup via LHI on NSTX-U will require operation in the regime where helicity injection drive exceeds inductive and geometric changes at full size. A large-area multi-injector array will increase available helicity injection by 3-4 times and allow exploration of this helicity-dominated regime at Ip ~ 0 . 3 MA in PEGASUS. Comparison of model predictions with time-evolving magnetic equilibria is in progress for model validation. Work supported by US DOE Grant DE-FG02-96ER54375.

Two Sides of the Same Coin: ERP and Wavelet Analyses of Visual Potentials Evoked and Induced by Task-Relevant Faces.

PubMed

Van der Lubbe, Rob H J; Szumska, Izabela; Fajkowska, Małgorzata

2016-01-01

New analysis techniques of the electroencephalogram (EEG) such as wavelet analysis open the possibility to address questions that may largely improve our understanding of the EEG and clarify its relation with related potentials (ER Ps). Three issues were addressed. 1) To what extent can early ERERP components be described as transient evoked oscillations in specific frequency bands? 2) Total EEG power (TP) after a stimulus consists of pre-stimulus baseline power (BP), evoked power (EP), and induced power (IP), but what are their respective contributions? 3) The Phase Reset model proposes that BP predicts EP, while the evoked model holds that BP is unrelated to EP; which model is the most valid one? EEG results on NoGo trials for 123 individuals that took part in an experiment with emotional facial expressions were examined by computing ERPs and by performing wavelet analyses on the raw EEG and on ER Ps. After performing several multiple regression analyses, we obtained the following answers. First, the P1, N1, and P2 components can by and large be described as transient oscillations in the α and θ bands. Secondly, it appears possible to estimate the separate contributions of EP, BP, and IP to TP, and importantly, the contribution of IP is mostly larger than that of EP. Finally, no strong support was obtained for either the Phase Reset or the Evoked model. Recent models are discussed that may better explain the relation between raw EEG and ERPs.

Two Sides of the Same Coin: ERP and Wavelet Analyses of Visual Potentials Evoked and Induced by Task-Relevant Faces

PubMed Central

Van der Lubbe, Rob H. J.; Szumska, Izabela; Fajkowska, Małgorzata

2016-01-01

New analysis techniques of the electroencephalogram (EEG) such as wavelet analysis open the possibility to address questions that may largely improve our understanding of the EEG and clarify its relation with related potentials (ER Ps). Three issues were addressed. 1) To what extent can early ERERP components be described as transient evoked oscillations in specific frequency bands? 2) Total EEG power (TP) after a stimulus consists of pre-stimulus baseline power (BP), evoked power (EP), and induced power (IP), but what are their respective contributions? 3) The Phase Reset model proposes that BP predicts EP, while the evoked model holds that BP is unrelated to EP; which model is the most valid one? EEG results on NoGo trials for 123 individuals that took part in an experiment with emotional facial expressions were examined by computing ERPs and by performing wavelet analyses on the raw EEG and on ER Ps. After performing several multiple regression analyses, we obtained the following answers. First, the P1, N1, and P2 components can by and large be described as transient oscillations in the α and θ bands. Secondly, it appears possible to estimate the separate contributions of EP, BP, and IP to TP, and importantly, the contribution of IP is mostly larger than that of EP. Finally, no strong support was obtained for either the Phase Reset or the Evoked model. Recent models are discussed that may better explain the relation between raw EEG and ERPs. PMID:28154612

Overview of Initial NSTX-U Experimental Operations

NASA Astrophysics Data System (ADS)

Battaglia, Devon; the NSTX-U Team

2016-10-01

Initial operation of the National Spherical Torus Experiment Upgrade (NSTX-U) has satisfied a number of commissioning milestones, including demonstration of discharges that exceed the field and pulse length of NSTX. ELMy H-mode operation at the no-wall βN limit is obtained with Boronized wall conditioning. Peak H-mode parameters include: Ip = 1 MA, BT0 = 0.63 T, WMHD = 330 kJ, βN = 4, βN/li = 6, κ = 2.3, τE , tot >50 ms. Access to high-performance H-mode scenarios with long MHD-quiescent periods is enabled by the resilient timing of the L-H transition via feedback control of the diverting time and shape, and correction of the dominant n =1 error fields during the Ip ramp. Stationary L-mode discharges have been realized up to 1 MA with 2 s discharges achieved at Ip = 650 kA. The long-pulse L-mode discharges enabled by the new central solenoid supported initial experiments on error field measurements and correction, plasma shape control, controlled discharge ramp-down, L-mode transport and fast ion physics. Increased off-axis current drive and reduction of fast ion instabilities has been observed with the new, more tangential neutral beamline. The initial results support that access to increased field, current and heating at low-aspect-ratio expands the regimes available to develop scenarios, diagnostics and predictive models that inform the design and optimization of future burning plasma tokamak devices, including ITER. Work Supported by U.S. DOE Contract No. DE-AC02-09CH11466.

A decentralized software bus based on IP multicas ting

NASA Technical Reports Server (NTRS)

Callahan, John R.; Montgomery, Todd

1995-01-01

We describe decentralized reconfigurable implementation of a conference management system based on the low-level Internet Protocol (IP) multicasting protocol. IP multicasting allows low-cost, world-wide, two-way transmission of data between large numbers of conferencing participants through the Multicasting Backbone (MBone). Each conference is structured as a software bus -- a messaging system that provides a run-time interconnection model that acts as a separate agent (i.e., the bus) for routing, queuing, and delivering messages between distributed programs. Unlike the client-server interconnection model, the software bus model provides a level of indirection that enhances the flexibility and reconfigurability of a distributed system. Current software bus implementations like POLYLITH, however, rely on a centralized bus process and point-to-point protocols (i.e., TCP/IP) to route, queue, and deliver messages. We implement a software bus called the MULTIBUS that relies on a separate process only for routing and uses a reliable IP multicasting protocol for delivery of messages. The use of multicasting means that interconnections are independent of IP machine addresses. This approach allows reconfiguration of bus participants during system execution without notifying other participants of new IP addresses. The use of IP multicasting also permits an economy of scale in the number of participants. We describe the MULITIBUS protocol elements and show how our implementation performs better than centralized bus implementations.

Creation of a competency-based professional development program for infection preventionists guided by the APIC Competency Model: steps in the process.

PubMed

Bernard, Heather; Hackbarth, Diana; Olmsted, Russell N; Murphy, Denise

2018-06-07

Infection Preventionists have varying levels of educational preparation. Many have no prior experience in IP. The diversity makes design of professional development programs challenging. Recent surveys suggest that only about half of practicing IPs are board certified. There is an urgent need to employ competent IP's to drive improvement in patient outcomes. This is a project that utilized the APIC Competency Model to create a professional development program characterizing three career stages. Methods included a review of literature on professional development; a survey of IP competence; an assessment of job descriptions and performance evaluations; and a crosswalk of IP competencies. The professional development program includes competency - based IP job descriptions and performance evaluations for each career stage; a professional portfolio; and a toolkit for supervisors. Participants agreed that application of the model resulted in tools which are more closely aligned with current roles for IPs; and increased satisfaction and motivation with the new program. Competent and knowledgeable IP's are crucial to optimizing efficacy of IPC programs. A professional development program has the potential to guide staff orientation, improve satisfaction and retention, improve patient outcomes and promote a positive trajectory in advancing practice. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

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.

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

A rapid assessment method to estimate the distribution of juvenile Chinook Salmon in tributary habitats using eDNA and occupancy estimation

USGS Publications Warehouse

Matter, A.; Falke, Jeffrey A.; López, J. Andres; Savereide, James W.

2018-01-01

Identification and protection of water bodies used by anadromous species are critical in light of increasing threats to fish populations, yet often challenging given budgetary and logistical limitations. Noninvasive, rapid‐assessment, sampling techniques may reduce costs and effort while increasing species detection efficiencies. We used an intrinsic potential (IP) habitat model to identify high‐quality rearing habitats for Chinook Salmon Oncorhynchus tshawytscha and select sites to sample throughout the Chena River basin, Alaska, for juvenile occupancy using an environmental DNA (eDNA) approach. Water samples were collected from 75 tributary sites in 2014 and 2015. The presence of Chinook Salmon DNA in water samples was assessed using a species‐specific quantitative PCR (qPCR) assay. The IP model predicted over 900 stream kilometers in the basin to support high‐quality (IP ≥ 0.75) rearing habitat. Occupancy estimation based on eDNA samples indicated that 80% and 56% of previously unsampled sites classified as high or low IP (IP < 0.75), respectively, were occupied. The probability of detection (p) of Chinook Salmon DNA from three replicate water samples was high (p = 0.76) but varied with drainage area (km2). A power analysis indicated high power to detect proportional changes in occupancy based on parameter values estimated from eDNA occupancy models, although power curves were not symmetrical around zero, indicating greater power to detect positive than negative proportional changes in occupancy. Overall, the combination of IP habitat modeling and occupancy estimation provided a useful, rapid‐assessment method to predict and subsequently quantify the distribution of juvenile salmon in previously unsampled tributary habitats. Additionally, these methods are flexible and can be modified for application to other species and in other locations, which may contribute towards improved population monitoring and management.

Data Services and Transnational Access for European Geosciences Multi-Scale Laboratories

NASA Astrophysics Data System (ADS)

Funiciello, Francesca; Rosenau, Matthias; Sagnotti, Leonardo; Scarlato, Piergiorgio; Tesei, Telemaco; Trippanera, Daniele; Spires, Chris; Drury, Martyn; Kan-Parker, Mirjam; Lange, Otto; Willingshofer, Ernst

2016-04-01

The EC policy for research in the new millennium supports the development of european-scale research infrastructures. In this perspective, the existing research infrastructures are going to be integrated with the objective to increase their accessibility and to enhance the usability of their multidisciplinary data. Building up integrating Earth Sciences infrastructures in Europe is the mission of the Implementation Phase (IP) of the European Plate Observing System (EPOS) project (2015-2019). The integration of european multiscale laboratories - analytical, experimental petrology and volcanology, magnetic and analogue laboratories - plays a key role in this context and represents a specific task of EPOS IP. In the frame of the WP16 of EPOS IP working package 16, European geosciences multiscale laboratories aims to be linked, merging local infrastructures into a coherent and collaborative network. In particular, the EPOS IP WP16-task 4 "Data services" aims at standardize data and data products, already existing and newly produced by the participating laboratories, and made them available through a new digital platform. The following data and repositories have been selected for the purpose: 1) analytical and properties data a) on volcanic ash from explosive eruptions, of interest to the aviation industry, meteorological and government institutes, b) on magmas in the context of eruption and lava flow hazard evaluation, and c) on rock systems of key importance in mineral exploration and mining operations; 2) experimental data describing: a) rock and fault properties of importance for modelling and forecasting natural and induced subsidence, seismicity and associated hazards, b) rock and fault properties relevant for modelling the containment capacity of rock systems for CO2, energy sources and wastes, c) crustal and upper mantle rheology as needed for modelling sedimentary basin formation and crustal stress distributions, d) the composition, porosity, permeability, and frackability of reservoir rocks of interest in relation to unconventional resources and geothermal energy; 3) repository of analogue models on tectonic processes, from the plate to the reservoir scale, relevant to the understanding of Earth dynamics, geo-hazards and geo-energy; 4) paleomagnetic data, that are crucial a) for understanding the evolution of sedimentary basins and associated resources, and b) for charting geo-hazard frequency. EPOS IP WP16 - task 5 aims to create mechanisms and procedures for easy trans-national access to multiscale laboratory facilities. Moreover, the same task will coordinate all the activities in a pilot phase to test, validate and consolidate the over mentioned services and to provide a proof of concept for what will be offered beyond the completion of the EPOS IP.

A back translation of pregabalin and carbamazepine against evoked and non-evoked endpoints in the rat spared nerve injury model of neuropathic pain.

PubMed

Lau, W; Dykstra, C; Thevarkunnel, S; Silenieks, L B; de Lannoy, I A M; Lee, D K H; Higgins, G A

2013-10-01

The purpose of the present study was twofold. First to characterize endpoints distinct to the reflexive responses to sensory stimuli typically used in neuropathic pain models. A second aim was to evaluate two clinically approved drugs carbamazepine (Tegretol) and pregabalin (Lyrica) against these endpoints with the purpose to backtranslate from the clinical to preclinical setting. The selected neuropathic pain model was the spared nerve injury (SNI) model and the endpoints were burrowing and measures of paw posture in Sprague Dawley rats. As previously described, SNI surgery produced a robust heightened sensitivity to tactile and thermal (cold) stimuli. SNI surgery also produced robust decreases in burrowing and affected multiple measures of paw position. There was no correlation between magnitude of change in burrowing and sensory allodynia within SNI operated rats. Pregabalin (10-30 mg/kg IP) produced a reliable reversal of both tactile and cold allodynia and also the burrowing deficit, with minimal effect on neurological function evaluated using rotorod, beam walking and open field activity. Pregabalin did not affect any measure of paw position. Pharmacokinetic studies conducted in satellite animals identified plasma levels of pregabalin at the 10 mg/kg IP dose to be equivalent to clinically efficacious levels recorded in neuropathic patients (3-6 μg/ml). In contrast carbamazepine (10-60 mg/kg IP) had only a very modest effect against a reflexive (tactile) measure, and no effect against the burrowing deficit. Carbamazepine also affected various measures of neurological function, complicating interpretation of the reflexive measure. Measurement of burrowing appears to detect a behavioural deficit associated with the SNI model, that may be attenuated by pregabalin but not carbamazepine. Overall the present findings support an advantage of pregabalin over carbamazepine in terms of both efficacy and tolerability which is consistent with clinical experience. The inclusion of additional endpoints beyond traditional reflexive behaviours further supports the value of rodent neuropathic pain models, such as the SNI, as behavioural assays to detect new chemical entities to treat this pain condition. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

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.

Machine Learning Approach to Automated Quality Identification of Human Induced Pluripotent Stem Cell Colony Images.

PubMed

Joutsijoki, Henry; Haponen, Markus; Rasku, Jyrki; Aalto-Setälä, Katriina; Juhola, Martti

2016-01-01

The focus of this research is on automated identification of the quality of human induced pluripotent stem cell (iPSC) colony images. iPS cell technology is a contemporary method by which the patient's cells are reprogrammed back to stem cells and are differentiated to any cell type wanted. iPS cell technology will be used in future to patient specific drug screening, disease modeling, and tissue repairing, for instance. However, there are technical challenges before iPS cell technology can be used in practice and one of them is quality control of growing iPSC colonies which is currently done manually but is unfeasible solution in large-scale cultures. The monitoring problem returns to image analysis and classification problem. In this paper, we tackle this problem using machine learning methods such as multiclass Support Vector Machines and several baseline methods together with Scaled Invariant Feature Transformation based features. We perform over 80 test arrangements and do a thorough parameter value search. The best accuracy (62.4%) for classification was obtained by using a k-NN classifier showing improved accuracy compared to earlier studies.

Tensions inherent in the evolving role of the infection preventionist.

PubMed

Conway, Laurie J; Raveis, Victoria H; Pogorzelska-Maziarz, Monika; Uchida, May; Stone, Patricia W; Larson, Elaine L

2013-11-01

The role of infection preventionists (IPs) is expanding in response to demands for quality and transparency in health care. Practice analyses and survey research have demonstrated that IPs spend a majority of their time on surveillance and are increasingly responsible for prevention activities and management; however, deeper qualitative aspects of the IP role have rarely been explored. We conducted a qualitative content analysis of in-depth interviews with 19 IPs at hospitals throughout the United States to describe the current IP role, specifically the ways that IPs effect improvements and the facilitators and barriers they face. The narratives document that the IP role is evolving in response to recent changes in the health care landscape and reveal that this progression is associated with friction and uncertainty. Tensions inherent in the evolving role of the IP emerged from the interviews as 4 broad themes: (1) expanding responsibilities outstrip resources, (2) shifting role boundaries create uncertainty, (3) evolving mechanisms of influence involve trade-offs, and (4) the stress of constant change is compounded by chronic recurring challenges. Advances in implementation science, data standardization, and training in leadership skills are needed to support IPs in their evolving role. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Validation of the Spanish version of the Irrational Procrastination Scale (IPS).

PubMed

Guilera, Georgina; Barrios, Maite; Penelo, Eva; Morin, Christopher; Steel, Piers; Gómez-Benito, Juana

2018-01-01

The present study is centered in adapting and validating a Spanish version of the Irrational Procrastination Scale (IPS). The sample consists of 365 adults aged 18-77 years (M = 37.70, SD = 12.64). Participants were administered two measures of procrastination, the IPS and the Decisional Procrastination Questionnaire, as well as the Big Five Inventory, and the Satisfaction With Life Scale. First, the factor and replication analysis revealed that the internal structure of the scale is clearly one-dimensional, supporting the idea that IPS seems to measure general procrastination as a single trait. Second, the internal consistency is satisfactory as is the temporal stability of the IPS scores. Third, the correlations encountered between the IPS scores and other measures of procrastination, personality traits and satisfaction with life are all in the expected direction and magnitude. Finally, consistent with previous research, procrastination is related to age, with the youngest being the most procrastinating group. This study represents the first attempt in adapting and validating the IPS measure of procrastination into Spanish. Results suggest that the Spanish version of the IPS offers valid and reliable scores when applied to adult population.

Validation of the Spanish version of the Irrational Procrastination Scale (IPS)

PubMed Central

Guilera, Georgina; Penelo, Eva; Morin, Christopher; Steel, Piers; Gómez-Benito, Juana

2018-01-01

The present study is centered in adapting and validating a Spanish version of the Irrational Procrastination Scale (IPS). The sample consists of 365 adults aged 18–77 years (M = 37.70, SD = 12.64). Participants were administered two measures of procrastination, the IPS and the Decisional Procrastination Questionnaire, as well as the Big Five Inventory, and the Satisfaction With Life Scale. First, the factor and replication analysis revealed that the internal structure of the scale is clearly one-dimensional, supporting the idea that IPS seems to measure general procrastination as a single trait. Second, the internal consistency is satisfactory as is the temporal stability of the IPS scores. Third, the correlations encountered between the IPS scores and other measures of procrastination, personality traits and satisfaction with life are all in the expected direction and magnitude. Finally, consistent with previous research, procrastination is related to age, with the youngest being the most procrastinating group. This study represents the first attempt in adapting and validating the IPS measure of procrastination into Spanish. Results suggest that the Spanish version of the IPS offers valid and reliable scores when applied to adult population. PMID:29304119

Phosphatidylcholine-specific phospholipase C inhibition reduces HER2-overexpression, cell proliferation and in vivo tumor growth in a highly tumorigenic ovarian cancer model

PubMed Central

Spadaro, Francesca; Abalsamo, Laura; Pisanu, Maria Elena; Ricci, Alessandro; Cecchetti, Serena; Altabella, Luisa; Buoncervello, Maria; Lozneanu, Ludmila; Bagnoli, Marina; Ramoni, Carlo; Canevari, Silvana; Mezzanzanica, Delia

2017-01-01

Antagonizing the oncogenic effects of human epidermal growth factor receptor 2 (HER2) with current anti-HER2 agents has not yet yielded major progress in the treatment of advanced HER2-positive epithelial ovarian cancer (EOC). Using preclinical models to explore alternative molecular mechanisms affecting HER2 overexpression and oncogenicity may lead to new strategies for EOC patient treatment. We previously reported that phosphatidylcholine-specific phospholipase C (PC-PLC) exerts a pivotal role in regulating HER2 overexpression in breast cancer cells. The present study, conducted on two human HER2-overexpressing EOC cell lines - SKOV3 and its in vivo-passaged SKOV3.ip cell variant characterized by enhanced in vivo tumorigenicity - and on SKOV3.ip xenografts implanted in SCID mice, showed: a) about 2-fold higher PC-PLC and HER2 protein expression levels in SKOV3.ip compared to SKOV3 cells; b) physical association of PC-PLC with HER2 in non-raft domains; c) HER2 internalization and ca. 50% reduction of HER2 mRNA and protein expression levels in SKOV3.ip cells exposed to the PC-PLC inhibitor tricyclodecan-9-yl-potassium xanthate (D609); d) differential effects of D609 and trastuzumab on HER2 protein expression and cell proliferation; e) decreased in vivo tumor growth in SKOV3.ip xenografts during in vivo treatment with D609; f) potential use of in vivo magnetic resonance spectroscopy (MRS) and imaging (MRI) parameters as biomarkers of EOC response to PC-PLC inhibition. Overall, these findings support the view that PC-PLC inhibition may represent an effective means to target the tumorigenic effects of HER2 overexpression in EOC and that in vivo MR approaches can efficiently monitor its effects. PMID:28903399

Validation of a Brief Structured Interview: The Children’s Interview for Psychiatric Syndromes (ChIPS)

PubMed Central

Young, Matthew E.; Bell, Ziv E.; Fristad, Mary A.

2016-01-01

Evidence-based assessment is important in the treatment of childhood psychopathology (Jensen-Doss, 2011). While researchers and clinicians frequently use structured diagnostic interviews to ensure reliability, the most commonly used instrument, the Schedule for Affective Disorders and Schizophrenia for School Aged Children (K-SADS; Kaufman et al., 1997), is too long for most clinical applications. The Children’s Interview for Psychiatric Syndromes, (ChIPS/P-ChIPS; Weller, Weller, Rooney, & Fristad, 1999a; 1999b) is a highly-structured brief diagnostic interview. The present study compared K-SADS and ChIPS/P-ChIPS diagnoses in an outpatient clinical sample of 50 parent-child pairs aged 7–14. Agreement between most diagnoses was moderate to high between instruments and with consensus clinical diagnoses. ChIPS was significantly briefer to administer than the K-SADS. Interviewer experience level and participant demographics did not appear to affect agreement. Results provide further evidence for the validity of the ChIPS and support its use in clinical and research settings. PMID:27761777

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.

A mathematical model for maximizing the value of phase 3 drug development portfolios incorporating budget constraints and risk.

PubMed

Patel, Nitin R; Ankolekar, Suresh; Antonijevic, Zoran; Rajicic, Natasa

2013-05-10

We describe a value-driven approach to optimizing pharmaceutical portfolios. Our approach incorporates inputs from research and development and commercial functions by simultaneously addressing internal and external factors. This approach differentiates itself from current practices in that it recognizes the impact of study design parameters, sample size in particular, on the portfolio value. We develop an integer programming (IP) model as the basis for Bayesian decision analysis to optimize phase 3 development portfolios using expected net present value as the criterion. We show how this framework can be used to determine optimal sample sizes and trial schedules to maximize the value of a portfolio under budget constraints. We then illustrate the remarkable flexibility of the IP model to answer a variety of 'what-if' questions that reflect situations that arise in practice. We extend the IP model to a stochastic IP model to incorporate uncertainty in the availability of drugs from earlier development phases for phase 3 development in the future. We show how to use stochastic IP to re-optimize the portfolio development strategy over time as new information accumulates and budget changes occur. Copyright © 2013 John Wiley & Sons, Ltd.

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

Immunohistochemical localization of DPP10 in rat brain supports the existence of a Kv4/KChIP/DPPL ternary complex in neurons.

PubMed

Wang, Wan-Chen; Cheng, Chau-Fu; Tsaur, Meei-Ling

2015-03-01

Subthreshold A-type K(+) currents (ISA s) have been recorded from the cell bodies of hippocampal and neocortical interneurons as well as neocortical pyramidal neurons. Kv4 channels are responsible for the somatodendritic ISA s. It has been proposed that neuronal Kv4 channels are ternary complexes including pore-forming Kv4 subunits, K(+) channel-interacting proteins (KChIPs), and dipeptidyl peptidase-like proteins (DPPLs). However, colocalization evidence was still lacking. The distribution of DPP10 mRNA in rodent brain has been reported but its protein localization remains unknown. In this study, we generated a DPP10 antibody to label DPP10 protein in adult rat brain by immunohistochemistry. Absent from glia, DPP10 proteins appear mainly in the cell bodies of DPP10(+) neurons, not only at the plasma membrane but also in the cytoplasm. At least 6.4% of inhibitory interneurons in the hippocampus coexpressed Kv4.3, KChIP1, and DPP10, with the highest density in the CA1 strata alveus/oriens/pyramidale and the dentate hilus. Colocalization of Kv4.3/KChIP1/DPP10 was also detected in at least 6.9% of inhibitory interneurons scattered throughout the neocortex. Both hippocampal and neocortical Kv4.3/KChIP1/DPP10(+) inhibitory interneurons expressed parvalbumin or somatostatin, but not calbindin or calretinin. Furthermore, we found colocalization of Kv4.2/Kv4.3/KChIP3/DPP10 in neocortical layer 5 pyramidal neurons and olfactory bulb mitral cells. Together, although DPP10 is also expressed in some brain neurons lacking Kv4 (such as parvalbumin- and somatostatin-positive Golgi cells in the cerebellum), colocalization of DPP10 with Kv4 and KChIP at the plasma membrane of ISA -expressing neuron somata supports the existence of Kv4/KChIP/DPPL ternary complex in vivo. © 2014 Wiley Periodicals, Inc.

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.

Distinct Representations of Magnitude and Spatial Position within Parietal Cortex during Number-Space Mapping.

PubMed

Kanayet, Frank J; Mattarella-Micke, Andrew; Kohler, Peter J; Norcia, Anthony M; McCandliss, Bruce D; McClelland, James L

2018-02-01

Mapping numbers onto space is foundational to mathematical cognition. These cognitive operations are often conceptualized in the context of a "mental number line" and involve multiple brain regions in or near the intraparietal sulcus (IPS) that have been implicated both in numeral and spatial cognition. Here we examine possible differentiation of function within these brain areas in relating numbers to spatial positions. By isolating the planning phase of a number line task and introducing spatiotopic mapping tools from fMRI into mental number line task research, we are able to focus our analysis on the neural activity of areas in anterior IPS (aIPS) previously associated with number processing and on spatiotopically organized areas in and around posterior IPS (pIPS), while participants prepare to place a number on a number line. Our results support the view that the nonpositional magnitude of a numerical symbol is coded in aIPS, whereas the position of a number in space is coded in posterior areas of IPS. By focusing on the planning phase, we are able to isolate activation related to the cognitive, rather than the sensory-motor, aspects of the task. Also, to allow the separation of spatial position from magnitude, we tested both a standard positive number line (0 to 100) and a zero-centered mixed number line (-100 to 100). We found evidence of a functional dissociation between aIPS and pIPS: Activity in aIPS was associated with a landmark distance effect not modulated by spatial position, whereas activity in pIPS revealed a contralateral preference effect.

Architectures and Design for Next-Generation Hybrid Circuit/Packet Networks

NASA Astrophysics Data System (ADS)

Vadrevu, Sree Krishna Chaitanya

Internet traffic is increasing rapidly at an annual growth rate of 35% with aggregate traffic exceeding several Exabyte's per month. The traffic is also becoming heterogeneous in bandwidth and quality-of-service (QoS) requirements with growing popularity of cloud computing, video-on-demand (VoD), e-science, etc. Hybrid circuit/packet networks which can jointly support circuit and packet services along with the adoption of high-bit-rate transmission systems form an attractive solution to address the traffic growth. 10 Gbps and 40 Gbps transmission systems are widely deployed in telecom backbone networks such as Comcast, AT&T, etc., and network operators are considering migration to 100 Gbps and beyond. This dissertation proposes robust architectures, capacity migration strategies, and novel service frameworks for next-generation hybrid circuit/packet architectures. In this dissertation, we study two types of hybrid circuit/packet networks: a) IP-over-WDM networks, in which the packet (IP) network is overlaid on top of the circuit (optical WDM) network and b) Hybrid networks in which the circuit and packet networks are deployed side by side such as US DoE's ESnet. We investigate techniques to dynamically migrate capacity between the circuit and packet sections by exploiting traffic variations over a day, and our methods show that significant bandwidth savings can be obtained with improved reliability of services. Specifically, we investigate how idle backup circuit capacity can be used to support packet services in IP-over-WDM networks, and similarly, excess capacity in packet network to support circuit services in ESnet. Control schemes that enable our mechanisms are also discussed. In IP-over-WDM networks, with upcoming 100 Gbps and beyond, dedicated protection will induce significant under-utilization of backup resources. We investigate design strategies to loan idle circuit backup capacity to support IP/packet services. However, failure of backup circuits will preempt IP services routed over them, and thus it is important to ensure IP topology survivability to successfully re-route preempted IP services. Integer-linear-program (ILP) and heuristic solutions have been developed and network cost reduction up to 60% has been observed. In ESnet, we study loaning packet links to support circuit services. Mixed-line-rate (MLR) networks supporting 10/40/100 Gbps on the same fiber are becoming increasingly popular. Services that accept degradation in bandwidth, latency, jitter, etc. under failure scenarios for lower cost are known as degraded services. We study degradation in bandwidth for lower cost under failure scenarios, a concept called partial protection, in the context of MLR networks. We notice partial protection enables significant cost savings compared to full protection. To cope with traffic growth, network operators need to deploy equipment at periodic time intervals, and this is known as the multi-period planning and upgrade problem. We study three important multi-period planning approaches, namely incremental planning, all-period planning, and two-period planning with mixed line rates. Our approaches predict the network equipment that needs to be deployed optimally at which nodes and at which time periods in the network to meet QoS requirements.

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.

Unanticipated region- and cell-specific downregulation of individual KChIP auxiliary subunit isotypes in Kv4.2 knock-out mouse brain.

PubMed

Menegola, Milena; Trimmer, James S

2006-11-22

Kv4 family voltage-gated potassium channel alpha subunits and Kv channel-interacting protein (KChIP) and dipeptidyl aminopeptidase-like protein subunits comprise somatodendritic A-type channels in mammalian neurons. Recently, a mouse was generated with a targeted deletion of Kv4.2, a Kv4 alpha subunit expressed in many but not all mammalian brain neurons. Kv4.2-/- mice are grossly indistinguishable from wild-type (WT) littermates. Here we used immunohistochemistry to analyze expression of component Kv4 and KChIP subunits of A-type channels in WT and Kv4.2-/- brains. We found that the expression level, and cellular and subcellular distribution of the other prominent brain Kv4 family member Kv4.3, was indistinguishable between WT and Kv4.2-/- samples. However, we found unanticipated regional and cell-specific decreases in expression of KChIPs. The degree of altered expression of individual KChIP isoforms in different regions and neurons precisely follows the level of Kv4.2 normally found at those sites and presumably their extent of association of these KChIPs with Kv4.2. The dramatic effects of Kv4.2 deletion on KChIP expression suggest that, in addition to previously characterized effects of KChIPs on the functional properties, trafficking, and turnover rate of Kv4 channels, Kv4:KChIP association may confer reciprocal Kv4.2-dependent effects on KChIPs. The impact of Kv4.2 deletion on KChIP expression also supports the major role of KChIPs as auxiliary subunits of Kv4 channels.

Teaching Note--Asserting Social Work's Role in Developing an Interprofessional Education Project

ERIC Educational Resources Information Center

Kobayashi, Rie; Fitzgerald, Cindy

2017-01-01

Interprofessional (IP) education is an essential component of today's health care education. IP education has been recognized and supported for its potential to educate workforce-ready health care clinicians with the knowledge and skills, necessary to collaboratively deliver high-quality, client-centered care. While social work's reflective,…

MSFC institutional area network and ATM technology

NASA Technical Reports Server (NTRS)

Amin, Ashok T.

1994-01-01

The New Institutional Area Network (NEWIAN) at Marshall supports over 5000 end users with access to 26 file servers providing work presentation services. It is comprised of some 150 Ethernet LAN's interconnected by bridges/routers which are in turn connected to servers over two dual FDDI rings. The network supports various higher level protocols such as IP, IPX, AppleTalk (AT), and DECNet. At present IPX and AT protocols packets are routed, and IP protocol packets are bridged; however, work is in progress to route all IP packets. The impact of routing IP packets on network operation is examined. Broadband Integrated Services Data Network (BISDN), presently at various stages of development, is intended to provide voice, video, and data transfer services over a single network. BISDN will use asynchronous transfer mode (ATM) as a data transfer technique which provides for transmission, multiplexing, switching, and relaying of small size data units called cells. Limited ATM Wide Area Network (WAN) services are offered by Wiltel, AT&T, Sprint, and others. NASA is testing a pilot ATM WAN with a view to provide Program Support Communication Network services using ATM. ATM supports wide range of data rates and quality of service requirements. It is expected that ATM switches will penetrate campus networks as well. However, presently products in these areas are at various stages of development and standards are not yet complete. We examine development of ATM to help assess its role in the evolution of NEWIAN.

Design of real-time voice over internet protocol system under bandwidth network

NASA Astrophysics Data System (ADS)

Zhang, Li; Gong, Lina

2017-04-01

With the increasing bandwidth of the network and network convergence accelerating, VoIP means of communication across the network is becoming increasingly popular phenomenon. The real-time identification and analysis for VOIP flow over backbone network become the urgent needs and research hotspot of network operations management. Based on this, the paper proposes a VoIP business management system over backbone network. The system first filters VoIP data stream over backbone network and further resolves the call signaling information and media voice. The system can also be able to design appropriate rules to complete real-time reduction and presentation of specific categories of calls. Experimental results show that the system can parse and process real-time backbone of the VoIP call, and the results are presented accurately in the management interface, VoIP-based network traffic management and maintenance provide the necessary technical support.

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

Research on an IP disaster recovery storage system

NASA Astrophysics Data System (ADS)

Zeng, Dong; Wang, Yusheng; Zhu, Jianfeng

2008-12-01

According to both the Fibre Channel (FC) Storage Area Network (SAN) switch and Fabric Application Interface Standard (FAIS) mechanism, an iSCSI storage controller is put forward and based upon it, an internet Small Computer System Interface (iSCSI) SAN construction strategy for disaster recovery (DR) is proposed and some multiple sites replication models and a closed queue performance analysis method are also discussed in this paper. The iSCSI storage controller lies in the fabric level of the networked storage infrastructure, and it can be used to connect to both the hybrid storage applications and storage subsystems, besides, it can provide virtualized storage environment and support logical volume access control, and by cooperating with the remote peerparts, a disaster recovery storage system can be built on the basis of the data replication, block-level snapshot and Internet Protocol (IP) take-over functions.

Vented versus unvented chest seals for treatment of pneumothorax and prevention of tension pneumothorax in a swine model.

PubMed

Kheirabadi, Bijan S; Terrazas, Irasema B; Koller, Alexandra; Allen, Paul B; Klemcke, Harold G; Convertino, Victor A; Dubick, Michael A; Gerhardt, Robert T; Blackbourne, Lorne H

2013-07-01

Unvented chest seals (CSs) are currently recommended for the management of penetrating thoracic injuries in the battlefield. Since no supporting data exist, we compared the efficacy of a preferred unvented with that of a vented CS in a novel swine model of pneumothorax (PTx). An open chest wound was created in the left thorax of spontaneously air-breathing anesthetized pigs (n = 8). A CS was applied over the injury, then tension PTx was induced by incremental air injections (0.2 L) into the pleural cavity via a cannula that was also used to measure intrapleural pressure (IP). Both CS were tested on each pig in series. Tidal volume (V(T)), respiratory rate, IP, heart rate, mean arterial pressure, cardiac output, central venous pressure, pulmonary arterial pressure, venous and peripheral oxygen saturations (SvO2, SpO2) were recorded. Tension PTx was defined as a mean IP equal to or greater than +1 mm Hg plus significant (20-30%) deviation in baseline levels of the previously mentioned parameters and confirmed by chest x-ray study. PaO2 and PaCo2 were also measured. PTx produced immediate breathing difficulty and significant rises in IP and pulmonary arterial pressure and falls in V(T), SpO2, and SvO2. Both CSs returned these parameters to near baseline within 5 minutes of application. After vented CS was applied, serial air injections up to 2 L resulted in no significant change in the previously mentioned parameters. After unvented CS application, progressive deterioration of all respiratory parameters and onset of tension PTx were observed in all subjects after approximately 1.4-L air injection. Both vented and unvented CSs provided immediate improvements in breathing and blood oxygenation in our model of penetrating thoracic trauma. However, in the presence of ongoing intrapleural air accumulation, the unvented CS led to tension PTx, hypoxemia, and possible respiratory arrest, while the vented CS prevented these outcomes.

Administration of a co-crystal of tramadol and celecoxib in a 1:1 molecular ratio produces synergistic antinociceptive effects in a postoperative pain model in rats.

PubMed

Merlos, Manuel; Portillo-Salido, Enrique; Brenchat, Alex; Aubel, Bertrand; Buxens, Jordi; Fisas, Angels; Codony, Xavier; Romero, Luz; Zamanillo, Daniel; Vela, José Miguel

2018-06-19

Drug combination for the treatment of pain is common clinical practice. Co-crystal of Tramadol-Celecoxib (CTC) consists of two active pharmaceutical ingredients (APIs), namely the atypical opioid tramadol and the preferential cyclooxygenase-2 inhibitor celecoxib, at a 1:1 molecular ratio. In this study, a non-formulated 'raw' form of CTC administered in suspension (referred to as ctc susp ) was compared with both tramadol and celecoxib alone in a rat plantar incision postoperative pain model. For comparison, the strong opioids morphine and oxycodone, and a tramadol plus acetaminophen combination at a molecular ratio of 1:17 were also tested. Isobolographic analyses showed that ctc susp exerted synergistic mechanical antiallodynic (experimental ED 50 =2.0±0.5mg/kg, i.p.; theoretical ED 50 =3.8±0.4mg/kg, i.p.) and thermal (experimental ED 50 =2.3±0.5mg/kg, i.p.; theoretical ED 50 =9.8±0.8mg/kg, i.p.) antihyperalgesic effects in the postoperative pain model. In contrast, the tramadol and acetaminophen combination showed antagonistic effects on both mechanical allodynia and thermal hyperalgesia. No synergies between tramadol and celecoxib on locomotor activity, motor coordination, ulceration potential and gastrointestinal transit were observed after the administration of ctc susp . Overall, rat efficacy and safety data revealed that ctc susp provided synergistic analgesic effects compared with each API alone, without enhancing adverse effects. Moreover, ctc susp showed similar efficacy but improved safety ratio (80, measured as gastrointestinal transit vs postoperative pain ED 50 ratios) compared with the strong opioids morphine (2.5) and oxycodone (5.8). The overall in vivo profile of ctc susp supports the further investigation of CTC in the clinical management of moderate-to-severe acute pain as an alternative to strong opioids. Copyright © 2018. Published by Elsevier B.V.

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

IP-10 measured by Dry Plasma Spots as biomarker for therapy responses in Mycobacterium Tuberculosis infection.

PubMed

Tonby, Kristian; Ruhwald, Morten; Kvale, Dag; Dyrhol-Riise, Anne Ma

2015-03-18

Tuberculosis (TB) has huge impact on human morbidity and mortality and biomarkers to support rapid TB diagnosis and ensure treatment initiation and cure are needed, especially in regions with high prevalence of multi-drug resistant TB. Soluble interferon gamma inducible protein 10 (IP-10) analyzed from dry plasma spots (DPS) has potential as an immunodiagnostic marker in TB infection. We analyzed IP-10 levels in plasma directly and extracted from DPS in parallel by ELISA from 34 clinically well characterized patients with TB disease before and throughout 24 weeks of effective anti-TB chemotherapy. We detected a significant decline of IP-10 levels in both plasma and DPS already after two weeks of therapy with good correlation between the tests. This was observed both in pulmonary and extrapulmonary TB. In conclusion, plasma IP-10 may serve as an early biomarker for anti-TB chemotherapy responses and the IP-10 DPS method has potential to be developed into a point-of care test for use in resource-limited settings. Further studies must be performed to validate the use of IP-10 DPS in TB high endemic countries.

Role of Caspase-3 Cleaved IP3R1 on Ca2+ Homeostasis and Developmental Competence of Mouse Oocytes and Eggs

PubMed Central

Zhang, Nan; Fissore, Rafael. A.

2014-01-01

Apoptosis in most cell types is accompanied by altered Ca2+ homeostasis. During apoptosis, caspase-3 mediated cleavage of the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) generates a 95-kDa C-terminal fragment (C-IP3R1), which represents the channel domain of the receptor. Aged mouse eggs display abnormal Ca2+ homeostasis and express C-IP3R1, although whether or not C-IP3R1 expression contributes to Ca2+ misregulation or a decrease in developmental competency is unknown. We sought to answer these questions by injecting in mouse oocytes and eggs cRNAs encoding CIP3R1. We found that: 1) expression of C-IP3R1 in eggs lowered the Ca2+ content of the endoplasmic reticulum (ER), although, as C-IP3R1 is quickly degraded at this stage, its expression did not impair pre-implantation embryo development; 2) expression of CIP3R1 in eggs enhanced fragmentation associated with aging; 3) endogenous IP3R1 is required for aging associated apoptosis, as its down-regulation prevented fragmentation, and expression of C-IP3R1 in eggs with downregulated IP3R1 partly restored fragmentation; 4) C-IP3R1 expression in GV oocytes resulted in persistent levels of protein, which abolished the increase in the ER releasable Ca2+ pool that occurs during maturation, undermined the Ca2+ oscillatory ability of matured eggs and their activation potential. Collectively, this study supports a role for IP3R1 and C-IP3R1 in regulating Ca2+ homeostasis and the ER Ca2+ content during oocyte maturation. Nevertheless, the role of C-IP3R1 on Ca2+ homeostasis in aged eggs seems minor, as in MII eggs the majority of endogenous IP3R1 remains intact and C-IP3R1 undergoes rapid turnover. PMID:24692207

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

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.

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.

Pindolol potentiates the panicolytic effect of paroxetine in the elevated T-maze.

PubMed

Sela, Vânia R; Roncon, Camila M; Zangrossi, Hélio; Graeff, Frederico G; Audi, Elisabeth A

2010-09-25

the β-adrenergic and 5-HT(1A) receptor antagonist pindolol has been used in combination with antidepressant drugs, to shorten the time of onset of clinical efficacy and/or increase the proportion of responders in depressive and anxiety disorders. The aim of this study was to examine the interaction between pindolol and the selective serotonin reuptake inhibitor (SSRI), paroxetine in rats submitted to the elevated T-maze (ETM). for assessing the drug combination effect, rats were administered with pindolol before paroxetine, using oral or intraperitoneal (i.p.) routes of acute administration, and were submitted to the ETM model. the highest dose of pindolol used (15.0mg/kg, i.p.) increased both inhibitory avoidance and escape latencies in the ETM, probably due to nonspecific motor deficit, since locomotion in a circular arena was also significantly decreased. The highest dose of paroxetine (3.0mg/kg, i.p.) selectively impaired escape, considered a panicolytic effect. Combination of pindolol (5.0mg/kg, i.p.) with an ineffective dose of paroxetine (1.5mg/kg, i.p.) impaired escape, indicating a potentiation of the panicolytic effect of paroxetine. By the oral route, neither paroxetine (3.0mg/kg) nor pindolol (5.0mg/kg) alone were effective, but the combination treatment had a marked panicolytic effect, again indicating drug potentiation. the present results show that the combination of the ineffective doses of pindolol and paroxetine significantly increased escape latency, indicating a selective panicolytic effect. These findings give preclinical support for the use of this drug combination in the treatment of panic disorder (PD). 2010 Elsevier Inc. All rights reserved.

Role of inositol 1,4,5-trisphosphate receptors in pathogenesis of Huntington's disease and spinocerebellar ataxias.

PubMed

Bezprozvanny, Ilya

2011-07-01

Huntington's disease (HD) and spinocerebellar ataxias (SCAs) are autosomal-dominant neurodegenerative disorders. HD is caused by polyglutamine (polyQ) expansion in the amino-terminal region of a protein huntingtin (Htt) and primarily affects medium spiny striatal neurons (MSN). Many SCAs are caused by polyQ-expansion in ataxin proteins and primarily affect cerebellar Purkinje cells. The reasons for neuronal dysfunction and death in HD and SCAs remain poorly understood and no cure is available for the patients. Our laboratory discovered that mutant huntingtin, ataxin-2 and ataxin-3 proteins specifically bind to the carboxy-terminal region of the type 1 inositol 1,4,5-trisphosphate receptor (IP(3)R1), an intracellular Ca(2+) release channel. Moreover, we found that association of mutant huntingtin or ataxins with IP(3)R1 causes sensitization of IP(3)R1 to activation by IP(3) in planar lipid bilayers and in neuronal cells. These results suggested that deranged neuronal Ca(2+) signaling might play an important role in pathogenesis of HD, SCA2 and SCA3. In support of this idea, we demonstrated a connection between abnormal Ca(2+) signaling and neuronal cell death in experiments with HD, SCA2 and SCA3 transgenic mouse models. Additional data in the literature indicate that abnormal neuronal Ca(2+) signaling may also play an important role in pathogenesis of SCAl, SCA5, SCA6, SCA14 and SCA15/16. Based on these results I propose that IP(3)R and other Ca(2+) signaling proteins should be considered as potential therapeutic targets for treatment of HD and SCAs.

Pharmacokinetics and brain uptake of an IgG-TNF decoy receptor fusion protein following intravenous, intraperitoneal, and subcutaneous administration in mice.

PubMed

Sumbria, Rachita K; Zhou, Qing-Hui; Hui, Eric Ka-Wai; Lu, Jeff Zhiqiang; Boado, Ruben J; Pardridge, William M

2013-04-01

Tumor necrosis factor (TNF)-α is a proinflammatory cytokine active in the brain. Etanercept, the TNF decoy receptor (TNFR), does not cross the blood-brain barrier (BBB). The TNFR was re-engineered for BBB penetration as a fusion protein with a chimeric monoclonal antibody (mAb) against the mouse transferrin receptor (TfR), and this fusion protein is designated cTfRMAb-TNFR. The cTfRMAb domain of the fusion protein acts as a molecular Trojan horse and mediates transport via the endogenous BBB TfR. To support future chronic treatment of mouse models of neural disease with daily administration of the cTfRMAb-TNFR fusion protein, a series of pharmacokinetics and brain uptake studies in the mouse was performed. The cTfRMAb-TNFR fusion protein was radiolabeled and injected into mice via the intravenous, intraperitoneal (IP), or subcutaneous (SQ) routes of administration at doses ranging from 0.35 to 10 mg/kg. The distribution of the fusion protein into plasma following the IP or SQ routes was enhanced by increasing the injection dose from 3 to 10 mg/kg. The fusion protein demonstrated long circulation times with high metabolic stability following the IP or SQ routes of injection. The IP or SQ routes produced concentrations of the cTfRMAb-TNFR fusion protein in the brain that exceed by 20- to 50-fold the concentration of TNFα in pathologic conditions of the brain. The SQ injection is the preferred route of administration, as the level of cTfRMAb fusion protein produced in the brain is comparable to that generated with intravenous injection, and at a much lower plasma area under the concentration curve of the fusion protein as compared to IP administration.

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.

Enhanced International Space Station Ku-Band Telemetry Service

NASA Technical Reports Server (NTRS)

Cecil, Andrew; Pitts, Lee; Welch, Steven; Bryan, Jason

2014-01-01

(1) The ISS is diligently working to increase utilization of the resources this unique laboratory provides; (2) Recent upgrades enabled the use of Internet Protocol communication using the CCSDS IP Encapsulation protocol; and (3) The Huntsville Operations Support Center has extended the onboard LAN to payload teams enabling the use of standard IP protocols for payload operations.

Enantiospecific Pheromone Production and Response Profiles for Populations of Pine Engraver, Ips pini (SAY) (Coleoptera: Scolytidae), in British Columbia

Treesearch

D.R. Miller; J.H. Borden; K.N. Slessor

1996-01-01

Analyses of the enantiomeric composition of ipsdienol produced by individual male pine engravers, Ips pini (Say), from six populations in British Columbia, support the hypothesis that New York and Idaho races of this species hybridize in southeastern British Columbia. Production profiles, expressed as frequency distributions of (+):(-) ipsdienol...

Client predictors of employment outcomes in high-fidelity supported employment: a regression analysis.

PubMed

Campbell, Kikuko; Bond, Gary R; Drake, Robert E; McHugo, Gregory J; Xie, Haiyi

2010-08-01

Research on vocational rehabilitation for clients with severe mental illness over the past 2 decades has yielded inconsistent findings regarding client factors statistically related to employment. The present study aimed to elucidate the relationship between baseline client characteristics and competitive employment outcomes-job acquisition and total weeks worked during an 18-month follow-up-in Individual Placement and Support (IPS). Data from 4 recent randomized controlled trials of IPS were aggregated for within-group regression analyses. In the IPS sample (N = 307), work history was the only significant predictor for job acquisition, but receiving Supplemental Security Income-with or without Social Security Disability Insurance-was associated with fewer total weeks worked (2.0%-2.8% of the variance). In the comparison sample (N = 374), clients with a diagnosis of mood disorder or with less severe thought disorder symptoms were more likely to obtain competitive employment. The findings confirm that clients with severe mental illness interested in competitive work best benefit from high-fidelity supported employment regardless of their work history and sociodemographic and clinical background, and highlight the needs for changes in federal policies for disability income support and insurance regulations.

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

IP access networks with QoS support

NASA Astrophysics Data System (ADS)

Sargento, Susana; Valadas, Rui J. M. T.; Goncalves, Jorge; Sousa, Henrique

2001-07-01

The increasing demand of new services and applications is pushing for drastic changes on the design of access networks targeted mainly for residential and SOHO users. Future access networks will provide full service integration (including multimedia), resource sharing at the packet level and QoS support. It is expected that using IP as the base technology, the ideal plug-and-play scenario, where the management actions of the access network operator are kept to a minimum, will be achieved easily. This paper proposes an architecture for access networks based on layer 2 or layer 3 multiplexers that allows a number of simplifications in the network elements and protocols (e.g. in the routing and addressing functions). We discuss two possible steps in the evolution of access networks towards a more efficient support of IP based services. The first one still provides no QoS support and was designed with the goal of reusing as much as possible current technologies; it is based on tunneling to transport PPP sessions. The second one introduces QoS support through the use of emerging technologies and protocols. We illustrate the different phases of a multimedia Internet access session, when using SIP for session initiation, COPS for the management of QoS policies including the AAA functions and RSVP for resource reservation.

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.

The CANopen Controller IP Core: Implementation, Synthesis and Test Results

NASA Astrophysics Data System (ADS)

Caramia, Maurizio; Bolognino, Luca; Montagna, Mario; Tosi, Pietro; Errico, Walter; Bigongiari, Franco; Furano, Gianluca

2011-08-01

This paper will describe the implementation and test results of the CANopen Controller IP Core (CCIPC) implemented by Thales Alenia Space and SITAEL Aerospace with the support of ESA in the frame of the EXOMARS Project. The CCIPC is a configurable VHDL implementation of the CANOPEN protocol [1]; it is foreseen to be used as CAN bus slave controller within the EXOMARS Entry Descending and Landing Demonstrato Module (EDM) and Rover Module. The CCIPC features, configuration capability, synthesis and test results will be described and the evidence of the state of maturity of this innovative IP core will be demonstrated.

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.

Display Sharing: An Alternative Paradigm

NASA Technical Reports Server (NTRS)

Brown, Michael A.

2010-01-01

The current Johnson Space Center (JSC) Mission Control Center (MCC) Video Transport System (VTS) provides flight controllers and management the ability to meld raw video from various sources with telemetry to improve situational awareness. However, maintaining a separate infrastructure for video delivery and integration of video content with data adds significant complexity and cost to the system. When considering alternative architectures for a VTS, the current system's ability to share specific computer displays in their entirety to other locations, such as large projector systems, flight control rooms, and back supporting rooms throughout the facilities and centers must be incorporated into any new architecture. Internet Protocol (IP)-based systems also support video delivery and integration. IP-based systems generally have an advantage in terms of cost and maintainability. Although IP-based systems are versatile, the task of sharing a computer display from one workstation to another can be time consuming for an end-user and inconvenient to administer at a system level. The objective of this paper is to present a prototype display sharing enterprise solution. Display sharing is a system which delivers image sharing across the LAN while simultaneously managing bandwidth, supporting encryption, enabling recovery and resynchronization following a loss of signal, and, minimizing latency. Additional critical elements will include image scaling support, multi -sharing, ease of initial integration and configuration, integration with desktop window managers, collaboration tools, host and recipient controls. This goal of this paper is to summarize the various elements of an IP-based display sharing system that can be used in today's control center environment.

Aqueous root extracts from Mimosa albida Humb. & Bonpl. ex Willd display antinociceptive activity in mice.

PubMed

Rejón-Orantes, J C; Suaréz, D P Perdomo; Rejón-Rodríguez, A; Hernández, S Hernández; Liévano, O E García; Rodríguez, D López; de la Mora, M Pérez

2013-09-16

In this work, we study whether aqueous extracts from the roots of Mimosa albida Humb. & Bonpl. ex Willd, a plant known in the Highlands of Chiapas, Mexico as "Lotóm chíx" are endowed with both antinociceptive and anxiolytic effects. ICR mice were systemically treated with aqueous extracts from Mimosa albida and the reference compounds (diazepam, dipyrone and/or fentanyl) and their behavior was evaluated in several behavioral tests. Administration of aqueous extracts from the roots of Mimosa albida resulted in a reduction of the nociception elicited in mice by both the hot plate (12.5, 25 and 50 mg/kg; i.p.) and the acetic acid-induced writhing (25 and 50 mg/kg; i.p.) tests. No effects were however observed both in the elevated plus-maze and hole board test (3.2, 12.5 and 25 mg/kg; i.p.). In contrast, both locomotion (open field test) and motor coordination (rotarod test) were affected at doses (50, 100 y 200 mg/kg; i.p.) higher than those having antinociceptive effects. These data suggest that in mice the systemic administration of low doses of aqueous extracts from the roots of Mimosa albida results in antinociceptive effects in several models of pain through mechanisms that do not involve the opioid system pathway. These results support the ethnopharmacological use of Mimosa albida in popular medicine. © 2013 Elsevier Ireland Ltd. All rights reserved.

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.

Multi-service terminal adapter based on IP technology applications in rural area

NASA Astrophysics Data System (ADS)

Gao, Li; Li, Xiaobo; Yan, Juntao; Ren, Xupeng

Take advantage of ample modern existing telecom network resources to rural areas may achieve it's information society gradually. This includes the establishment of integrated rural information service platform, modern remote education center and electronic administration management platform for rural areas. The geographical and economic constraints must be overcome for structuring the rural service support system, in order to provide technical support, information products and information services to modern rural information service system. It is important that development an access platform based IP technology, which supports multi-service access in order to implement a variety of types of mobile terminal equipment adapter access and to reduce restrictions on mobile terminal equipment.

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

Impact of social challenges on gaining employment for veterans with posttraumatic stress disorder: an exploratory moderator analysis.

PubMed

Davis, Lori L; Pilkinton, Patricia; Poddar, Swati; Blansett, Catherine; Toscano, Richard; Parker, Pamela E

2014-06-01

To explore whether psychosocial challenges impact effects of vocational rehabilitation in Veterans with Posttraumatic Stress Disorder (PTSD). A post hoc exploratory analysis of possible moderators of treatment was conducted on outcomes from a randomized, controlled trial of Individual Placement and Support in Veterans with PTSD. When examining groups within each moderator, there was a greater IPS supportive employment benefit in gaining competitive employment for those with inadequate transportation (number needed to treat [NNT] = 1.5) and inadequate housing (NNT = 1.5) compared with the main finding of the pilot study (NNT = 2.07). Compared with the main finding of the pilot study, there was no greater advantage of IPS for those with adequate transportation (NNT = 2.4) or adequate housing (NNT = 2.4). Compared with the main finding in the pilot study, those without a family care burden had a greater benefit from IPS (NNT = 1.4) and those with family care burden had a reduced treatment effect (NNT = 3.3). These results are exploratory and are not intended to guide clinical decision-making, but rather offer a potentially useful strategy in the design of larger trials of IPS.

Melanopsin-based brightness discrimination in mice and humans.

PubMed

Brown, Timothy M; Tsujimura, Sei-Ichi; Allen, Annette E; Wynne, Jonathan; Bedford, Robert; Vickery, Graham; Vugler, Anthony; Lucas, Robert J

2012-06-19

Photoreception in the mammalian retina is not restricted to rods and cones but extends to a small number of intrinsically photoreceptive retinal ganglion cells (ipRGCs), expressing the photopigment melanopsin. ipRGCs are known to support various accessory visual functions including circadian photoentrainment and pupillary reflexes. However, despite anatomical and physiological evidence that they contribute to the thalamocortical visual projection, no aspect of visual discrimination has been shown to rely upon ipRGCs. Based on their currently known roles, we hypothesized that ipRGCs may contribute to distinguishing brightness. This percept is related to an object's luminance-a photometric measure of light intensity relevant for cone photoreceptors. However, the perceived brightness of different sources is not always predicted by their respective luminance. Here, we used parallel behavioral and electrophysiological experiments to first show that melanopsin contributes to brightness discrimination in both retinally degenerate and fully sighted mice. We continued to use comparable paradigms in psychophysical experiments to provide evidence for a similar role in healthy human subjects. These data represent the first direct evidence that an aspect of visual discrimination in normally sighted subjects can be supported by inner retinal photoreceptors. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cell surface expression of channel catfish leukocyte immune-type receptors (IpLITRs) and recruitment of both Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1 and SHP-2.

PubMed

Montgomery, Benjamin C S; Mewes, Jacqueline; Davidson, Chelsea; Burshtyn, Deborah N; Stafford, James L

2009-04-01

Channel catfish leukocyte immune-type receptors (IpLITRs) are immunoglobulin superfamily (IgSF) members believed to play a role in the control and coordination of cellular immune responses in teleost. Putative stimulatory and inhibitory IpLITRs are co-expressed by different types of catfish immune cells (e.g. NK cells, T cells, B cells, and macrophages) but their signaling potential has not been determined. Following cationic polymer-mediated transfections into human cell lines we examined the surface expression, tyrosine phosphorylation, and phosphatase recruitment potential of two types of putative inhibitory IpLITRs using 'chimeric' expression constructs and an epitope-tagged 'native' IpLITR. We also cloned and expressed the teleost Src homology 2 domain-containing protein tyrosine phosphatases (SHP)-1 and SHP-2 and examined their expression in adult tissues and developing zebrafish embryos. Co-immunoprecipitation experiments support the inhibitory signaling potential of distinct IpLITR-types that bound both SHP-1 and SHP-2 following the phosphorylation of tyrosine residues within their cytoplasmic tail (CYT) regions. Phosphatase recruitment by IpLITRs represents an important first step in understanding their influence on immune cell effector functions and suggests that certain inhibitory signaling pathways are conserved among vertebrates.

Compact Modbus TCP/IP protocol for data acquisition systems based on limited hardware resources

NASA Astrophysics Data System (ADS)

Bai, Q.; Jin, B.; Wang, D.; Wang, Y.; Liu, X.

2018-04-01

The Modbus TCP/IP has been a standard industry communication protocol and widely utilized for establishing sensor-cloud platforms on the Internet. However, numerous existing data acquisition systems built on traditional single-chip microcontrollers without sufficient resources cannot support it, because the complete Modbus TCP/IP protocol always works dependent on a full operating system which occupies abundant hardware resources. Hence, a compact Modbus TCP/IP protocol is proposed in this work to make it run efficiently and stably even on a resource-limited hardware platform. Firstly, the Modbus TCP/IP protocol stack is analyzed and the refined protocol suite is rebuilt by streamlining the typical TCP/IP suite. Then, specific implementation of every hierarchical layer is respectively presented in detail according to the protocol structure. Besides, the compact protocol is implemented in a traditional microprocessor to validate the feasibility of the scheme. Finally, the performance of the proposed scenario is assessed. The experimental results demonstrate that message packets match the frame format of Modbus TCP/IP protocol and the average bandwidth reaches to 1.15 Mbps. The compact protocol operates stably even based on a traditional microcontroller with only 4-kB RAM and 12-MHz system clock, and no communication congestion or frequent packet loss occurs.

A Systematic Review of Root Canal Filling Materials for Deciduous Teeth: Is There an Alternative for Zinc Oxide-Eugenol?

PubMed Central

Barja-Fidalgo, Fernanda; Moutinho-Ribeiro, Michele; Oliveira, Maria Angelina Amorim; de Oliveira, Branca Heloísa

2011-01-01

The aim of this systematic review was to determine whether there is a root canal filling for deciduous teeth equally or more effective than zinc oxide-eugenol cement (ZOE). Six clinical trials selected for inclusion were independently reviewed by two researchers. Only two showed statistically significant different success rates between the test and the control groups. One found that an iodoform paste with calcium hydroxide (IP + Ca) performed better than ZOE, and the other found that ZOE performed similarly to IP + Ca. The other four studies compared ZOE with an iodoform paste (IP), a calcium hydroxide cement (Ca(OH)2), or IP + Ca. In these trials, the success rates in the ZOE groups were slightly lower than in the other groups. There seems to be no convincing evidence to support the superiority of any material over ZOE, and both ZOE and IP + Ca appear to be suitable as root canal fillings for deciduous teeth. PMID:21991471

Operational Space Weather Products at IPS

NASA Astrophysics Data System (ADS)

Neudegg, D.; Steward, G.; Marshall, R.; Terkildsen, M.; Kennewell, J.; Patterson, G.; Panwar, R.

2008-12-01

IPS Radio and Space Services operates an extensive network (IPSNET) of monitoring stations and observatories within the Australasian and Antarctic regions to gather information on the space environment. This includes ionosondes, magnetometers, GPS-ISM, oblique HF sounding, riometers, and solar radio and optical telescopes. IPS exchanges this information with similar organisations world-wide. The Regional Warning Centre (RWC) is the Australian Space Forecast Centre (ASFC) and it utilizes this data to provide products and services to support customer operations. A wide range of customers use IPS services including; defence force and emergency services using HF radio communications and surveillance systems, organisations involved in geophysical exploration and pipeline cathodic protection, GPS users in aviation. Subscriptions to the alerts, warnings, forecasts and reports regarding the solar, geophysical and ionospheric conditions are distributed by email and Special Message Service (SMS). IPS also develops and markets widely used PC software prediction tools for HF radio skywave and surface wave (ASAPS/GWPS) and provides consultancy services for system planning.

Melanopsin tristability for sustained and broadband phototransduction.

PubMed

Emanuel, Alan Joseph; Do, Michael Tri Hoang

2015-03-04

Mammals rely upon three ocular photoreceptors to sense light: rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). Rods and cones resolve details in the visual scene. Conversely, ipRGCs integrate over time and space, primarily to support "non-image" vision. The integrative mechanisms of ipRGCs are enigmatic, particularly since these cells use a phototransduction motif that allows invertebrates like Drosophila to parse light with exceptional temporal resolution. Here, we provide evidence for a single mechanism that allows ipRGCs to integrate over both time and wavelength. Light distributes the visual pigment, melanopsin, across three states, two silent and one signaling. Photoequilibration among states maintains pigment availability for sustained signaling, stability of the signaling state permits minutes-long temporal summation, and modest spectral separation of the silent states promotes uniform activation across wavelengths. By broadening the tuning of ipRGCs in both temporal and chromatic domains, melanopsin tristability produces signal integration for physiology and behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Trade Secret Law and Information Systems: Can Your Students Keep a Secret?

ERIC Educational Resources Information Center

Willey, Lorrie; Ford, Janet C.; White, Barbara Jo; Clapper, Danial L.

2011-01-01

The impact of intellectual property (IP) law on information systems (IS) professionals in business cannot be overstated. The IS 2010 model curriculum guidelines for undergraduate IS programs stress the importance of information security and knowledge about IP. While copyright and patents are the most well-known types of IP, another, trade secrets,…

Feasibility of a modified outpatient regimen of intravenous/intraperitoneal chemotherapy in optimally debulked stage III ovarian cancer patients: a GEICO study.

PubMed

Oaknin, Ana; Roda, Desamparado; González-Martín, Antonio; Chiva, Luis; García-Donas, Jesús; de Juan, Ana; Redondo, Andrés; Martínez, Sergio; García, Yolanda; Catot, Sílvia; Ponce, Jordi; Del Campo, J M; Cervantes, Andrés; Poveda, Andrés

2011-08-01

The objective of the study was to assess the feasibility, toxicity, and reasons for early discontinuation of a modified outpatient intraperitoneal/intravenous (IP/IV) chemotherapy regimen for the treatment of patients with optimally debulked stage III ovarian cancer. Between February 2006 and November 2008, 51 consecutive patients from Institutions of the Spanish Ovarian Cancer Group (GEICO) were treated with a modified outpatient IP chemotherapy regimen. Patients received IV paclitaxel 175 mg/m over 3 hours on day 1, followed by IP cisplatin 100 mg/m (or 75 mg/m according to the principal investigator's criteria) on day 2. On day 8, patients received IP paclitaxel 60 mg/m. To homogenize the IP administration and supportive measures, a GEICO guideline for IP chemotherapy was established. Patients were treated with the intention to receive 6 courses of chemotherapy every 21 days. The median age of the patients was 49 years (range, 36-75 years), and most of them had papillary serous ovarian cancer (78%), International Federation of Gynecology and Obstetrics stage IIIC (76%). Thirty-nine patients completed 4 or more IP cycles, and 28 (61%) completed all 6 IP cycles. Twenty-two patients discontinued the IP/IV treatment, mainly because of chemotherapy toxicity (10 patients) and catheter-related complications (5 patients). The most prevalent grade 3/4 toxicities were neutropenia (14 patients; 30%) and gastrointestinal events (12 patients; 26%). The GEICO outpatient modified regimen resulted in a lesser toxicity and a greater rate of treatment completion than previously reported. The accurate selection of patients and the administration following well-defined guidelines can increase the feasibility of IP chemotherapy administration.

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.

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.

The relative contribution of neurocognition and social cognition to 6-month vocational outcomes following Individual Placement and Support in first-episode psychosis.

PubMed

Allott, Kelly A; Cotton, Susan M; Chinnery, Gina L; Baksheev, Gennady N; Massey, Jessica; Sun, Pamela; Collins, Zoe; Barlow, Emma; Broussard, Christina; Wahid, Tasha; Proffitt, Tina-Marie; Jackson, Henry J; Killackey, Eoin

2013-10-01

To examine whether baseline neurocognition and social cognition predict vocational outcomes over 6 months in patients with first-episode psychosis (FEP) enrolled in a randomised controlled trial of Individual Placement and Support (IPS) versus treatment as usual (TAU). 135 FEP participants (IPS n=69; TAU n=66) completed a comprehensive neurocognitive and social cognitive battery. Principal axis factor analysis using PROMAX rotation was used to determine the underlying cognitive structure of the battery. Setwise (hierarchical) logistic and multivariate linear regressions were used to examine predictors of: (a) enrolment in education and employment; and (b) hours of employment over 6 months. Neurocognition and social cognition factors were entered into the models after accounting for premorbid IQ, baseline functioning and treatment group. Six cognitive factors were extracted: (i) social cognition; (ii) information processing speed; (iii) verbal learning and memory; (iv) attention and working memory; (v) visual organisation and memory; and (vi) verbal comprehension. Enrolment in education over 6 months was predicted by enrolment in education at baseline (p=.002) and poorer visual organisation and memory (p=.024). Employment over 6 months was predicted by employment at baseline (p=.041) and receiving IPS (p=.020). Better visual organisation and memory predicted total hours of paid work over 6 months (p<.001). Visual organisation and memory predicted the enrolment in education and duration of employment, after accounting for premorbid IQ, baseline functioning and treatment. Social cognition did not contribute to the prediction of vocational outcomes. Neurocognitive interventions may enhance employment duration in FEP. © 2013 Elsevier B.V. All rights reserved.

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.

Morphological Analysis of Live Undifferentiated Cells Derived from Induced Pluripotent Stem Cells.

PubMed

Osawa, Yukihiko; Miyamoto, Tomoyuki; Ohno, Setsuyo; Ohno, Eiji

2018-01-01

Induced pluripotent stem (iPS) cells possess pluripotency and self-renewal ability. Therefore, iPS cells are expected to be useful in regenerative medicine. However, iPS cells form malignant immature teratomas after transplantation into animals, even after differentiation induction. It has been suggested that undifferentiated cells expressing Nanog that remain after differentiation induction are responsible for teratoma formation. Various methods of removing these undifferentiated cells have therefore been investigated, but few methods involve morphological approaches, which may induce less cell damage. In addition, for cells derived from iPS cells to be applied in regenerative medicine, they must be alive. However, detailed morphological analysis of live undifferentiated cells has not been performed. For the above reasons, we assessed the morphological features of live undifferentiated cells remaining after differentiation induction as a basic investigation into the clinical application of iPS cells. As a result, live undifferentiated cells remaining after differentiation induction exhibited a round or oval cytoplasm about 12 μm in diameter and a nucleus. They exhibited nucleo-cytoplasmic (N/C) ratio of about 60% and eccentric nuclei, and they possessed partially granule-like structures in the cytoplasm and prominent nucleoli. Although they were similar to iPS cells, they were smaller than live iPS cells. Furthermore, very small cells were present among undifferentiated cells after differentiation induction. These results suggest that the removal of undifferentiated cells may be possible using the morphological features of live iPS cells and undifferentiated cells after differentiation induction. In addition, this study supports safe regenerative medicine using iPS cells.

Somatodendritic surface expression of epitope-tagged and KChIP binding-deficient Kv4.2 channels in hippocampal neurons.

PubMed

Prechtel, Helena; Hartmann, Sven; Minge, Daniel; Bähring, Robert

2018-01-01

Kv4.2 channels mediate a subthreshold-activating somatodendritic A-type current (ISA) in hippocampal neurons. We examined the role of accessory Kv channel interacting protein (KChIP) binding in somatodendritic surface expression and activity-dependent decrease in the availability of Kv4.2 channels. For this purpose we transfected cultured hippocampal neurons with cDNA coding for Kv4.2 wild-type (wt) or KChIP binding-deficient Kv4.2 mutants. All channels were equipped with an externally accessible hemagglutinin (HA)-tag and an EGFP-tag, which was attached to the C-terminal end. Combined analyses of EGFP self-fluorescence, surface HA immunostaining and patch-clamp recordings demonstrated similar dendritic trafficking and functional surface expression for Kv4.2[wt]HA,EGFP and the KChIP binding-deficient Kv4.2[A14K]HA,EGFP. Coexpression of exogenous KChIP2 augmented the surface expression of Kv4.2[wt]HA,EGFP but not Kv4.2[A14K]HA,EGFP. Notably, activity-dependent decrease in availability was more pronounced in Kv4.2[wt]HA,EGFP + KChIP2 coexpressing than in Kv4.2[A14K]HA,EGFP + KChIP2 coexpressing neurons. Our results do not support the notion that accessory KChIP binding is a prerequisite for dendritic trafficking and functional surface expression of Kv4.2 channels, however, accessory KChIP binding may play a potential role in Kv4.2 modulation during intrinsic plasticity processes.

Performance analysis of signaling protocols on OBS switches

NASA Astrophysics Data System (ADS)

Kirci, Pinar; Zaim, A. Halim

2005-10-01

In this paper, Just-In-Time (JIT), Just-Enough-Time (JET) and Horizon signalling schemes for Optical Burst Switched Networks (OBS) are presented. These signaling schemes run over a core dWDM network and a network architecture based on Optical Burst Switches (OBS) is proposed to support IP, ATM and Burst traffic. In IP and ATM traffic several packets are assembled in a single packet called burst and the burst contention is handled by burst dropping. The burst length distribution in IP traffic is arbitrary between 0 and 1, and is fixed in ATM traffic at 0,5. Burst traffic on the other hand is arbitrary between 1 and 5. The Setup and Setup ack length distributions are arbitrary. We apply the Poisson model with rate λ and Self-Similar model with pareto distribution rate α to identify inter-arrival times in these protocols. We consider a communication between a source client node and a destination client node over an ingress and one or more multiple intermediate switches.We use buffering only in the ingress node. The communication is based on single burst connections in which, the connection is set up just before sending a burst and then closed as soon as the burst is sent. Our analysis accounts for several important parameters, including the burst setup, burst setup ack, keepalive messages and the optical switching protocol. We compare the performance of the three signalling schemes on the network under as burst dropping probability under a range of network scenarios.

'Placement budgets' for supported employment--improving competitive employment for people with mental illness: study protocol of a multicentre randomized controlled trial.

PubMed

Nordt, Carlos; Brantschen, Elisabeth; Kawohl, Wolfram; Bärtsch, Bettina; Haker, Helene; Rüsch, Nicolas; Rössler, Wulf

2012-10-04

Vocational integration of people with mental illness is poor despite their willingness to work. The 'Individual Placement and Support' (IPS) model which emphasises rapid and direct job placement and continuing support to patient and employer has proven to be the most effective vocational intervention programme. Various studies have shown that every second patient with severe mental illness was able to find competitive employment within 18 months. However, the goal of taking up employment within two months was rarely achieved. Thus, we aim to test whether the new concept of limited placement budgets increases the effectiveness of IPS. Six job coaches in six out-patients psychiatric clinics in the Canton of Zurich support unemployed patients of their clinic who seek competitive employment. Between June 2010 and May 2011 patients (N=100) are randomly assigned to three different placement budgets of 25h, 40h, or 55h working hours of job coaches. Support lasts two years for those who find a job. The intervention ends for those who fail to find competitive employment when the respective placement budgets run out. The primary outcome measure is the time between study inclusion and first competitive employment that lasted three months or longer. Over a period of three years interviews are carried out every six months to measure changes in motivation, stigmatization, social network and social support, quality of life, job satisfaction, financial situation, and health conditions. Cognitive and social-cognitive tests are conducted at baseline to control for confounding variables. This study will show whether the effectiveness of IPS can be increased by the new concept of limited placement budgets. It will also be examined whether competitive employment leads in the long term to an improvement of mental illness, to a transfer of the psychiatric support system to private and vocational networks, to an increase in financial independence, to a reduction of perceived and internalized stigma, and to an increase in quality of life and job satisfaction of the patient. In addition, factors connected with fast competitive employment and holding that job down in the long term are being examined (motivation, stigmatization, social and financial situation). ISRCTN89670872.

Linking seasonal climate forecasts with crop models in Iberian Peninsula

NASA Astrophysics Data System (ADS)

Capa, Mirian; Ines, Amor; Baethgen, Walter; Rodriguez-Fonseca, Belen; Han, Eunjin; Ruiz-Ramos, Margarita

2015-04-01

Translating seasonal climate forecasts into agricultural production forecasts could help to establish early warning systems and to design crop management adaptation strategies that take advantage of favorable conditions or reduce the effect of adverse conditions. In this study, we use seasonal rainfall forecasts and crop models to improve predictability of wheat yield in the Iberian Peninsula (IP). Additionally, we estimate economic margins and production risks associated with extreme scenarios of seasonal rainfall forecast. This study evaluates two methods for disaggregating seasonal climate forecasts into daily weather data: 1) a stochastic weather generator (CondWG), and 2) a forecast tercile resampler (FResampler). Both methods were used to generate 100 (with FResampler) and 110 (with CondWG) weather series/sequences for three scenarios of seasonal rainfall forecasts. Simulated wheat yield is computed with the crop model CERES-wheat (Ritchie and Otter, 1985), which is included in Decision Support System for Agrotechnology Transfer (DSSAT v.4.5, Hoogenboom et al., 2010). Simulations were run at two locations in northeastern Spain where the crop model was calibrated and validated with independent field data. Once simulated yields were obtained, an assessment of farmer's gross margin for different seasonal climate forecasts was accomplished to estimate production risks under different climate scenarios. This methodology allows farmers to assess the benefits and risks of a seasonal weather forecast in IP prior to the crop growing season. The results of this study may have important implications on both, public (agricultural planning) and private (decision support to farmers, insurance companies) sectors. Acknowledgements Research by M. Capa-Morocho has been partly supported by a PICATA predoctoral fellowship of the Moncloa Campus of International Excellence (UCM-UPM) and MULCLIVAR project (CGL2012-38923-C02-02) References Hoogenboom, G. et al., 2010. The Decision Support System for Agrotechnology Transfer (DSSAT).Version 4.5 [CD-ROM].University of Hawaii, Honolulu, Hawaii. Ritchie, J.T., Otter, S., 1985. Description and performanceof CERES-Wheat: a user-oriented wheat yield model. In: ARS Wheat Yield Project. ARS-38.Natl Tech Info Serv, Springfield, Missouri, pp. 159-175.

Study of imaging plate detector sensitivity to 5-18 MeV electrons

NASA Astrophysics Data System (ADS)

Boutoux, G.; Rabhi, N.; Batani, D.; Binet, A.; Ducret, J.-E.; Jakubowska, K.; Nègre, J.-P.; Reverdin, C.; Thfoin, I.

2015-11-01

Imaging plates (IPs) are commonly used as passive detectors in laser-plasma experiments. We calibrated at the ELSA electron beam facility (CEA DIF) the five different available types of IPs (namely, MS-SR-TR-MP-ND) to electrons from 5 to 18 MeV. In the context of diagnostic development for the PETawatt Aquitaine Laser (PETAL), we investigated the use of stacks of IP in order to increase the detection efficiency and get detection response independent from the neighboring materials such as X-ray shielding and detector supports. We also measured fading functions in the time range from a few minutes up to a few days. Finally, our results are systematically compared to GEANT4 simulations in order to provide a complete study of the IP response to electrons over the energy range relevant for PETAL experiments.

A TMS Investigation on the Role of Lateral Occipital Complex and Caudal Intraparietal Sulcus in the Perception of Object Form and Orientation.

PubMed

Chouinard, Philippe A; Meena, Deiter K; Whitwell, Robert L; Hilchey, Matthew D; Goodale, Melvyn A

2017-05-01

We used TMS to assess the causal roles of the lateral occipital (LO) and caudal intraparietal sulcus (cIPS) areas in the perceptual discrimination of object features. All participants underwent fMRI to localize these areas using a protocol in which they passively viewed images of objects that varied in both form and orientation. fMRI identified six significant brain regions: LO, cIPS, and the fusiform gyrus, bilaterally. In a separate experimental session, we applied TMS to LO or cIPS while the same participants performed match-to-sample form or orientation discrimination tasks. Compared with sham stimulation, TMS to either the left or right LO increased RTs for form but not orientation discrimination, supporting a critical role for LO in form processing for perception- and judgment-based tasks. In contrast, we did not observe any effects when we applied TMS to cIPS. Thus, despite the clear functional evidence of engagement for both LO and cIPS during the passive viewing of objects in the fMRI experiment, the TMS experiment revealed that cIPS is not critical for making perceptual judgments about their form or orientation.

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.

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.

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.

65nm RadSafe™ Technology for RC64 and Advanced SOCs

NASA Astrophysics Data System (ADS)

Liran, Tuvia; Ginosar, Ran; Lange, Fredy; Mandler, Alberto; Aviely, Peleg; Meirov, Henri; Goldberg, Michael; Meister, Zeev; Oliel, Mickey

2015-09-01

The trend of scaling of microelectronic provides certain advantages for space components, as well as some challenges. It enables implementing highly integrated and high performance ASICs, reducing power, area and weight. Scaling also improves the immunity to TID and SEL in most cases, but increases soft error rate significantly. Ramon Chips adopted the 65nm technology for implementing RC64 [1,2], a 64 core DSP for space applications, and for making other future products. The 65nm process node is widely used, very mature, and supported by wide range of IP providers. Thus the need for full custom design of cores and IPs is minimized, and radiation hardening is achievable by mitigating the radiation effects on the available IPs, and developing proprietary IPs only for complementing the available IPs. The RadSafe_65TM technology includes hardened standard cells and I/O libraries, methods for mitigation of radiation effects in COTS IP cores (SRAM, PLL, SERDES, DDR2/3 interface) and adding unique cores for monitoring radiation effects and junction temperature. We had developed RADIC6, a technology development vehicle, for verification of all hard cores and verification of the methodologies and design flow required for RC64. RADIC6 includes the test structures for characterizing the IP cores for immunity to all radiation effects. This paper describes the main elements and IP cores of RadSafe_65TM, as well as the contents of RADIC6 test chip.

Infection prevention staffing and resources in U.S. acute care hospitals: Results from the APIC MegaSurvey.

PubMed

Pogorzelska-Maziarz, Monika; Gilmartin, Heather; Reese, Sara

2018-06-01

Given the changing nature of infection prevention and control (IPC), appropriate infection preventionist (IP) staffing needs to be established. In this study, we aimed to describe current IP staffing levels and IPC department resources in U.S. acute care hospitals. These data came from the 2015 MegaSurvey conducted by the Association of Professionals in Infection Prevention and Epidemiology. Descriptive statistics and bivariate analyses were conducted to examine differences in respondent, facility, and department characteristics by facility size (average inpatient census ≤100 vs >100). Data from 1623 respondents were included. Most (72%) had single-site responsibilities and dedicated 76%-100% of their job to IPC (68%). The overall median IP staffing was 1.25 IPs per 100 inpatient census (interquartile range = 1.81). Almost half (46%) represented facilities with daily inpatient census ≤100; the average number of IPs in these facilities was 1.1 (standard deviation = 0.7). The reported number of IPs increased steadily with higher patient census. Significant differences were observed in IP staffing, responsibilities, and support to the IPC department between smaller and larger hospitals. This study represents the current snapshot of IP staffing and IPC resources in acute care hospitals. Findings indicate important differences between large and small facilities in staffing and IPC resources. The field of infection prevention would benefit from a comprehensive assessment of IPC department staffing and resource needs. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

Alternative Fuels Compatibility with Army Equipment Testing-Effects of JP-8+100 on Military Filtration Equipment

DTIC Science & Technology

2012-02-21

Summary of Proposed Additive Packages for API /IP 1581 4th Edition ...................................... 4 Table 2. Summary of DoD Test Results...15 Table 8. ISO 4406 Cleanliness Codes for the API /IP 1581 5th Edition...Improver WSIM Water Separation Index Measure NSN National Stock Number API American Petroleum Institute DESC Defense Energy Support Center DOE Design of

A novel TFC forward osmosis (FO) membrane supported by polyimide (PI) microporous nanofiber membrane

NASA Astrophysics Data System (ADS)

Chi, Xiang-Yu; Zhang, Ping-Yun; Guo, Xue-Jiao; Xu, Zhen-Liang

2018-01-01

A novel interfacial polymerization (IP) procedure on polyimide (PI) microporous nanofiber membrane support with mean pore size 1.27 μm was reported. Using m-phenylenediamine (MPD) as aqueous phase monomer, trimesoyl chloride (TMC) as organic phase monomer, ethanol as aqueous phase co-solvent, thin-film composite (TFC) forward osmosis (FO) membrane was fabricated by two IP procedures. The first IP procedure with the unconventional order (ie, the membrane was immersed in the TMC organic phase first, then in the co-solvent ethanol-water MPD aqueous phase) was used to diminish the pore size of PI microporous nanofiber membrane support for the formation of the polyamide layer. The secondary IP procedure was employed to form the relatively dense polyamide layer with conventional order (ie, the membrane was immersed in the co-solvent ethanol-water MPD aqueous phase first, then in the TMC organic phase). The experimental results showed that higher ethanol concentration led to the relatively higher pure water permeability in RO process and osmotic water flux in FO process, whereas NaCl rejection in RO process decreased and reverse salt flux increased. The specific salt flux (Js/Jv) of TFC FO PI nanofiber membrane (PIN-2-4) could be as low as 0.095 g/L in FO mode. These results could be attributed to influence of the addition of ethanol into aqueous phase on the surface morphology, hydrophilicity and polyamide layer structure.

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.

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.

Twelve tips for delivering successful interprofessional case conferences.

PubMed

O'Brien, Bridget C; Patel, Shalini R; Pearson, Meg; Eastburn, Abigail P; Earnest, Gillian E; Strewler, Anna; Gager, Krista; Manuel, Jennifer K; Dulay, Maya; Bachhuber, Melissa R; Shunk, Rebecca

2017-12-01

Interprofessional case conferences (ICCs) offer an interactive, practical way to engage members of two or more health professions in discussions that involve learning and working together to improve patient care. Well-orchestrated ICCs provide opportunities to integrate interprofessional (IP) education into routine clinical practice. The authors provide 12 tips to support the conceptualization, planning, implementation, facilitation, evaluation, and sustainability of ICCs. They draw from extensive experience as IP educators and facilitators of ICCs and from literature on IP education, case-based learning, small-group facilitation, peer-assisted learning, and learner engagement - all of which offer insights into ICCs but have not been integrated and applied to this context.

The IPS supported employment learning collaborative.

PubMed

Becker, Deborah R; Drake, Robert E; Bond, Gary R

2014-06-01

Learning collaboratives aim to improve the quality and outcomes of health care. This paper updates the Johnson & Johnson-Dartmouth Community Mental Health Program, a 12-year learning collaborative on supported employment for people with mental illness. We gathered data from quarterly employment reports, monthly Individual Placement and Support (IPS) meetings, and presentations at the 2013 annual meeting of the learning collaborative. The number of participant states or regions (and sites within these jurisdictions) was expanded to 16 jurisdictions in the United States and 3 in European countries. The quarterly rate of competitive employment has averaged 43% over 11 years in the U.S. sites. The collaborative has spawned numerous interactions, trainings, innovations, and research projects. Long-term learning collaboratives can produce high quality services, good outcomes, sustainability, and innovation.

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

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.

Chromatin immunoprecipitation in microfluidic droplets: towards fast and cheap analyses.

PubMed

Teste, Bruno; Champ, Jerome; Londono-Vallejo, Arturo; Descroix, Stéphanie; Malaquin, Laurent; Viovy, Jean-Louis; Draskovic, Irena; Mottet, Guillaume

2017-01-31

Genetic organization is governed by the interaction of DNA with histone proteins, and differential modifications of these proteins is a fundamental mechanism of gene regulation. Histone modifications are primarily studied through chromatin immunoprecipitation (ChIP) assays, however conventional ChIP procedures are time consuming, laborious and require a large number of cells. Here we report for the first time the development of ChIP in droplets based on a microfluidic platform combining nanoliter droplets, magnetic beads (MB) and magnetic tweezers (MT). The droplet approach enabled compartmentalization and improved mixing, while reducing the consumption of samples and reagents in an integrated workflow. Anti-histone antibodies grafted to MB were used as a solid support to capture and transfer the target chromatin from droplets to droplets in order to perform chromatin immunoprecipitation, washing, elution and purification of DNA. We designed a new ChIP protocol to investigate four different types of modified histones with known roles in gene activation or repression. We evaluated the performances of this new ChIP in droplet assay in comparison with conventional methods. The proposed technology dramatically reduces analytical time from a few days to 7 hours, simplifies the ChIP protocol and decreases the number of cells required by 100 fold while maintaining a high degree of sensitivity and specificity. Therefore this droplet-based ChIP assay represents a new, highly advantageous and convenient approach to epigenetic analyses.

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.

De novo prediction of human chromosome structures: Epigenetic marking patterns encode genome architecture.

PubMed

Di Pierro, Michele; Cheng, Ryan R; Lieberman Aiden, Erez; Wolynes, Peter G; Onuchic, José N

2017-11-14

Inside the cell nucleus, genomes fold into organized structures that are characteristic of cell type. Here, we show that this chromatin architecture can be predicted de novo using epigenetic data derived from chromatin immunoprecipitation-sequencing (ChIP-Seq). We exploit the idea that chromosomes encode a 1D sequence of chromatin structural types. Interactions between these chromatin types determine the 3D structural ensemble of chromosomes through a process similar to phase separation. First, a neural network is used to infer the relation between the epigenetic marks present at a locus, as assayed by ChIP-Seq, and the genomic compartment in which those loci reside, as measured by DNA-DNA proximity ligation (Hi-C). Next, types inferred from this neural network are used as an input to an energy landscape model for chromatin organization [Minimal Chromatin Model (MiChroM)] to generate an ensemble of 3D chromosome conformations at a resolution of 50 kilobases (kb). After training the model, dubbed Maximum Entropy Genomic Annotation from Biomarkers Associated to Structural Ensembles (MEGABASE), on odd-numbered chromosomes, we predict the sequences of chromatin types and the subsequent 3D conformational ensembles for the even chromosomes. We validate these structural ensembles by using ChIP-Seq tracks alone to predict Hi-C maps, as well as distances measured using 3D fluorescence in situ hybridization (FISH) experiments. Both sets of experiments support the hypothesis of phase separation being the driving process behind compartmentalization. These findings strongly suggest that epigenetic marking patterns encode sufficient information to determine the global architecture of chromosomes and that de novo structure prediction for whole genomes may be increasingly possible. Copyright © 2017 the Author(s). Published by PNAS.

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.

Gigabit Network Communications Research

DTIC Science & Technology

1992-12-31

additional BPF channels, raw bytesync support for video codecs, and others. All source file modifications were logged with RCS. Source and object trees were...34 (RFCs). 20 RFCs were published this quarter: RFC 1366: Gerich, E., " Guidelines for Management of IP Address Space", Merit, October 1992. RFC 1367...Topolcic, C., "Schedule for IP Address Space Management Guidelines ", CNRI, October 1992. RFC 1368: McMaster, D. (Synoptics Communications, Inc.), K

[Effectiveness of individual supported employment for people with severe mental disorders].

PubMed

Rodríguez Pulido, Francisco; Caballero Estebaranz, Nayra; Tallo Aldana, Elena; Méndez Abad, Manuel E; Hernández Álvarez-Sotomayor, M Carmen; López Reig, Susana; Vílchez de León, Patricia Inés; González-Dávila, Enrique

2017-07-13

To assess the effectiveness of an individual placement and support (IPS) strategy in people with severe mental disorders in Tenerife Island (Spain). Patients of Community Mental Health Services with severe mental disorders were randomly assigned to two groups. One of them received IPS (n=124), and the control group (n=75) was advised in the usual job search. Patients were followed up for an average of 3.4 years and an analysis was made of how many patients worked at least one day, working hours, wages, the number of contracts and the number of hospital admissions. Non-parametric methods were used to compare the results (Mann-Whitney U test). The percentage of patients who worked at least one day was 99% in the IPS group compared with 75% in the control group; they worked on average 30.1 weeks per year vs 7.4; the monthly salary was € 777.9 vs € 599.9; the number of contracts per person was 3.89 vs 4.85, and hospital admissions were 0.19 vs 2.1. The IPS strategy is effective for the labour integration of people with severe mental illness getting them to work longer, have higher wages and fewer hospital admissions. Copyright © 2017 SESPAS. 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.

Presumptive intraperitoneal envenomation resulting in hemoperitoneum and acute abdominal pain in a dog.

PubMed

Istvan, Stephanie A; Walker, Julie M; Hansen, Bernard D; Hanel, Rita M; Marks, Steven L

2015-01-01

To describe the clinical features, diagnostic findings, treatment, and outcome of a dog with acute abdominal pain and hemoperitoneum secondary to a presumptive intraperitoneal (IP) snakebite. A 10-month-old castrated male mixed-breed dog was evaluated for suspected snake envenomation. The dog presented recumbent and tachycardic with signs of severe abdominal pain. Two cutaneous puncture wounds and hemoperitoneum were discovered during evaluation. Ultrasonographic examination revealed communication of the wounds with the peritoneal cavity. The dog was treated with supportive care, parenteral analgesia, packed red blood cell and fresh frozen plasma transfusions, crotalid antivenom, and placement of an IP catheter to provide local analgesia. The dog recovered fully and was discharged 5 days after initial presentation. To our knowledge, this is the first report of IP envenomation accompanied by hemorrhage treated with continuous IP analgesia in the veterinary literature. © Veterinary Emergency and Critical Care Society 2015.

Melanopsin-expressing retinal ganglion-cell photoreceptors: cellular diversity and role in pattern vision

PubMed Central

Ecker, Jennifer L.; Dumitrescu, Olivia N.; Wong, Kwoon Y.; Alam, Nazia M.; Chen, Shih-Kuo; LeGates, Tara; Renna, Jordan M.; Prusky, Glen T.; Berson, David M.; Hattar, Samer

2010-01-01

Using the photopigment melanopsin, intrinsically photosensitive retinal ganglion cells (ipRGCs) respond directly to light to drive circadian clock resetting and pupillary constriction. We now report that ipRGCs are more abundant and diverse than previously appreciated, project more widely within the brain, and can support spatial visual perception. A Cre-based melanopsin reporter mouse line revealed at least five subtypes of ipRGCs with distinct morphological and physiological characteristics. Collectively, these cells project beyond the known brain targets of ipRGCs to heavily innervate the superior colliculus and dorsal lateral geniculate nucleus, retinotopically-organized nuclei mediating object localization and discrimination. Mice lacking classical rod-cone photoreception, and thus entirely dependent on melanopsin for light detection, were able to discriminate grating stimuli from equiluminant gray, and had measurable visual acuity. Thus, non-classical retinal photoreception occurs within diverse cell types, and influences circuits and functions encompassing luminance as well as spatial information. PMID:20624591

Psychometric Evaluation of an Instrument for Measuring Organizational Climate for Quality: Evidence From a National Sample of Infection Preventionists.

PubMed

Pogorzelska-Maziarz, Monika; Nembhard, Ingrid M; Schnall, Rebecca; Nelson, Shanelle; Stone, Patricia W

2016-09-01

In recent years, there has been increased interest in measuring the climate for infection prevention; however, reliable and valid instruments are lacking. This study tested the psychometric properties of the Leading a Culture of Quality for Infection Prevention (LCQ-IP) instrument measuring the infection prevention climate in a sample of 972 infection preventionists from acute care hospitals. An exploratory principal component analysis showed that the instrument had structural validity and captured 4 factors related to the climate for infection prevention: Psychological Safety, Prioritization of Quality, Supportive Work Environment, and Improvement Orientation. LCQ-IP exhibited excellent internal consistency, with a Cronbach α of .926. Criterion validity was supported with overall LCQ-IP scores, increasing with the number of evidence-based prevention policies in place (P = .047). This psychometrically sound instrument may be helpful to researchers and providers in assessing climate for quality related to infection prevention. © The Author(s) 2015.

Midgut tissue of male pine engraver , Ips pini, synthesizes monoterpenoid pheromone component ipsdienol de novo

NASA Astrophysics Data System (ADS)

Hall, Gregory M.; Tittiger, Claus; Andrews, Gracie L.; Mastick, Grant S.; Kuenzli, Marilyn; Luo, Xin; Seybold, Steven J.; Blomquist, Gary J.

2002-02-01

For over three decades the site and pathways of bark beetle aggregation pheromone production have remained elusive. Studies on pheromone production in Ips spp. bark beetles have recently shown de novo biosynthesis of pheromone components via the mevalonate pathway. The gene encoding a key regulated enzyme in this pathway, 3-hydroxy-3-methylglutaryl-CoA reductase ( HMG-R), showed high transcript levels in the anterior midgut of male pine engravers, Ips pini (Say) (Coleoptera:Scolytidae). HMG-R expression in the midgut was sex, juvenile hormone, and feeding dependent, providing strong evidence that this is the site of acyclic monoterpenoid (ipsdienol) pheromone production in male beetles. Additionally, isolated midgut tissue from fed or juvenile hormone III (JH III)-treated males converted radiolabeled acetate to ipsdienol, as assayed by radio-HPLC. These data support the de novo production of this frass-associated aggregation pheromone component by the mevalonate pathway. The induction of a metazoan HMG-R in this process does not support the postulated role of microorganisms in ipsdienol production.

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.

‘Placement budgets’ for supported employment – improving competitive employment for people with mental illness: study protocol of a multicentre randomized controlled trial

PubMed Central

2012-01-01

Background Vocational integration of people with mental illness is poor despite their willingness to work. The ‘Individual Placement and Support’ (IPS) model which emphasises rapid and direct job placement and continuing support to patient and employer has proven to be the most effective vocational intervention programme. Various studies have shown that every second patient with severe mental illness was able to find competitive employment within 18 months. However, the goal of taking up employment within two months was rarely achieved. Thus, we aim to test whether the new concept of limited placement budgets increases the effectiveness of IPS. Methods/Design Six job coaches in six out-patients psychiatric clinics in the Canton of Zurich support unemployed patients of their clinic who seek competitive employment. Between June 2010 and May 2011 patients (N=100) are randomly assigned to three different placement budgets of 25h, 40h, or 55h working hours of job coaches. Support lasts two years for those who find a job. The intervention ends for those who fail to find competitive employment when the respective placement budgets run out. The primary outcome measure is the time between study inclusion and first competitive employment that lasted three months or longer. Over a period of three years interviews are carried out every six months to measure changes in motivation, stigmatization, social network and social support, quality of life, job satisfaction, financial situation, and health conditions. Cognitive and social-cognitive tests are conducted at baseline to control for confounding variables. Discussion This study will show whether the effectiveness of IPS can be increased by the new concept of limited placement budgets. It will also be examined whether competitive employment leads in the long term to an improvement of mental illness, to a transfer of the psychiatric support system to private and vocational networks, to an increase in financial independence, to a reduction of perceived and internalized stigma, and to an increase in quality of life and job satisfaction of the patient. In addition, factors connected with fast competitive employment and holding that job down in the long term are being examined (motivation, stigmatization, social and financial situation). Trial register ISRCTN89670872 PMID:23034095

A Randomized Clinical Trial Comparing Family-Focused Treatment and Individual Supportive Therapy for Depression in Childhood and Early Adolescence.

PubMed

Tompson, Martha C; Sugar, Catherine A; Langer, David A; Asarnow, Joan R

2017-06-01

Despite the morbidity and negative outcomes associated with early-onset depression, few studies have examined the efficacy of psychosocial treatment for depressive disorders during childhood. Integrating family in treatment could have particularly salutary effects during this developmental period. This trial compared immediate posttreatment effects of family-focused treatment for childhood depression (FFT-CD) with those of individual supportive psychotherapy (IP) for children 7 to 14 years old with depressive disorders. Children were randomized to 15 sessions of FFT-CD (n = 67) or IP (n = 67) over 4 months. The primary treatment outcome was adequate clinical depression response, defined as at least a 50% decrease in score on the Children's Depression Rating Scale-Revised (CDRS-R). Additional outcomes included patient-centered outcomes (parent- and child-reported treatment satisfaction), remission (defined as CDRS-R score ≤28), change in continuous CDRS-R score, and change in child and parent reports of depressive and non-depressive symptoms and social adjustment. Significant improvement was evident across groups for depressive and non-depressive symptoms, global response, and functioning and social adjustment. Compared with children randomized to IP, children randomized to FFT-CD showed higher rates of adequate clinical depression response (77.7% versus 59.9%; number needed to treat = 5.72; odds ratio 2.29; 95% CI 1.001-5.247; t = 1.97, p = .0498). Across treatments, families reported high satisfaction; compared with IP families, FFT-CD families reported greater knowledge and skills for managing depression. There were no significant differences between treatment arms on secondary outcomes. Results support the value of psychosocial intervention, emphasize the important role that families play, and highlight the potential for FFT-CD for supporting recovery in children with depression. Clinical trial registration information-Systems of Support Study for Childhood Depression; http://clinicaltrials.gov; NCT01159041. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Predicting domain-domain interaction based on domain profiles with feature selection and support vector machines

PubMed Central

2010-01-01

Background Protein-protein interaction (PPI) plays essential roles in cellular functions. The cost, time and other limitations associated with the current experimental methods have motivated the development of computational methods for predicting PPIs. As protein interactions generally occur via domains instead of the whole molecules, predicting domain-domain interaction (DDI) is an important step toward PPI prediction. Computational methods developed so far have utilized information from various sources at different levels, from primary sequences, to molecular structures, to evolutionary profiles. Results In this paper, we propose a computational method to predict DDI using support vector machines (SVMs), based on domains represented as interaction profile hidden Markov models (ipHMM) where interacting residues in domains are explicitly modeled according to the three dimensional structural information available at the Protein Data Bank (PDB). Features about the domains are extracted first as the Fisher scores derived from the ipHMM and then selected using singular value decomposition (SVD). Domain pairs are represented by concatenating their selected feature vectors, and classified by a support vector machine trained on these feature vectors. The method is tested by leave-one-out cross validation experiments with a set of interacting protein pairs adopted from the 3DID database. The prediction accuracy has shown significant improvement as compared to InterPreTS (Interaction Prediction through Tertiary Structure), an existing method for PPI prediction that also uses the sequences and complexes of known 3D structure. Conclusions We show that domain-domain interaction prediction can be significantly enhanced by exploiting information inherent in the domain profiles via feature selection based on Fisher scores, singular value decomposition and supervised learning based on support vector machines. Datasets and source code are freely available on the web at http://liao.cis.udel.edu/pub/svdsvm. Implemented in Matlab and supported on Linux and MS Windows. PMID:21034480

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.

Structural basis of arrestin-3 activation and signaling

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

Chen, Qiuyan; Perry, Nicole A.; Vishnivetskiy, Sergey A.

A unique aspect of arrestin-3 is its ability to support both receptor-dependent and receptor-independent signaling. Here, we show that inositol hexakisphosphate (IP6) is a non-receptor activator of arrestin-3 and report the structure of IP6-activated arrestin-3 at 2.4-Å resolution. IP6-activated arrestin-3 exhibits an inter-domain twist and a displaced C-tail, hallmarks of active arrestin. IP6 binds to the arrestin phosphate sensor, and is stabilized by trimerization. Analysis of the trimerization surface, which is also the receptor-binding surface, suggests a feature called the finger loop as a key region of the activation sensor. We show that finger loop helicity and flexibility may underliemore » coupling to hundreds of diverse receptors and also promote arrestin-3 activation by IP6. Importantly, we show that effector-binding sites on arrestins have distinct conformations in the basal and activated states, acting as switch regions. These switch regions may work with the inter-domain twist to initiate and direct arrestin-mediated signaling.« less

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

Network Upgrade for the SLC: PEP II Network

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

Crane, M.; Call, M.; Clark, S.

2011-09-09

The PEP-II control system required a new network to support the system functions. This network, called CTLnet, is an FDDI/Ethernet based network using only TCP/IP protocols. An upgrade of the SLC Control System micro communications to use TCP/IP and SLCNET would allow all PEP-II control system nodes to use TCP/IP. CTLnet is private and separate from the SLAC public network. Access to nodes and control system functions is provided by multi-homed application servers with connections to both the private CTLnet and the SLAC public network. Monitoring and diagnostics are provided using a dedicated system. Future plans and current status informationmore » is included.« less

Standard Spacecraft Interfaces and IP Network Architectures: Prototyping Activities at the GSFC

NASA Technical Reports Server (NTRS)

Schnurr, Richard; Marquart, Jane; Lin, Michael

2003-01-01

Advancements in fright semiconductor technology have opened the door for IP-based networking in spacecraft architectures. The GSFC believes the same signlJicant cost savings gained using MIL-STD-1553/1773 as a standard low rate interface for spacecraft busses cun be realized for highspeed network interfaces. To that end, GSFC is developing hardware and software to support a seamless, space mission IP network based on Ethernet and MIL-STD-1553. The Ethernet network shall connect all fright computers and communications systems using interface standards defined by the CCSDS Standard Onboard InterFace (SOIF) Panel. This paper shall discuss the prototyping effort underway at GSFC and expected results.

In Vitro Comparison of Marginal and Internal Fit of Press-on-Metal Ceramic (PoM) Restorations with Zirconium-Supported and Conventional Metal Ceramic Fixed Partial Dentures Before and After Veneering.

PubMed

Varol, Seda; Kulak-Özkan, Yasemin

2015-07-01

To compare marginal and internal fit between 3- and 4-unit press-on-metal (PoM) ceramic, zirconia-supported, and conventional metal ceramic fixed partial dentures (FPDs) before and after veneering. Ten pieces for each 3- and 4-unit MC, IPS InLine PoM, and IPS e.max ZirCAD/Zir Press FPDs were produced. Cross-sections from silicone replicas were examined and measured with a light microscope. Occlusal, axial, intermarginal, and marginal mean adaptation scores of cross-sectioned replicas and means of measurements obtained from 4 sites were calculated independently. Mean values for molars were 78.44 ± 32.01 μm (MC), 89.84 ± 29.20 μm (PoM), and 85.17 ± 28.49 μm (Zir). Premolar values were 76.08 ± 27.92 μm (MC), 89.94 ± 23.49 μm (PoM), and 87.18 ± 28.25 μm (Zir). No difference existed between the means of 3- and 4-unit FPDs except the molar-intermarginal region. The mean value of 4-unit FPDs (93.88 ± 25.41 μm) was less than the 3-unit FPDs (103.68 ± 24.55 μm) at the molar-inter marginal region. A gap increase was observed in all sites except the molar-axio-occlusal region after veneering. According to the mean difference, gap increases at the molar-marginal, molar-intermarginal, and premolar-intermarginal regions were statistically significant. A statistical difference was found at the molar-marginal region for 4-unit MCR (p = 0.041) and 4-unit PoM FPDs (p = 0.042) before and after veneering. Gap increase after veneering of 4-unit metal ceramics at molar-intermarginal, premolar-marginal, and premolar-intermarginal regions (p = 0.020; p = 0.015; p = 0.004) was significant. The gap measurements of the IPS InLine PoM and IPS e.max ZirCAD/Zir Press groups were all clinically acceptable. No studies on marginal and internal fit in the IPS InLine PoM system have been published to date. This study should be supported with future studies. No significant increase was observed after press-veneering the IPS e.max ZirCAD frameworks with an IPS e.max ZirPress material; therefore, we recommend the use of this combination. © 2014 by the American College of Prosthodontists.

Long-term Culture of Human iPS Cell-derived Telencephalic Neuron Aggregates on Collagen Gel.

PubMed

Oyama, Hiroshi; Takahashi, Koji; Tanaka, Yoshikazu; Takemoto, Hiroshi; Haga, Hisashi

2018-01-01

It takes several months to form the 3-dimensional morphology of the human embryonic brain. Therefore, establishing a long-term culture method for neuronal tissues derived from human induced pluripotent stem (iPS) cells is very important for studying human brain development. However, it is difficult to keep primary neurons alive for more than 3 weeks in culture. Moreover, long-term adherent culture to maintain the morphology of telencephalic neuron aggregates induced from human iPS cells is also difficult. Although collagen gel has been widely used to support long-term culture of cells, it is not clear whether human iPS cell-derived neuron aggregates can be cultured for long periods on this substrate. In the present study, we differentiated human iPS cells to telencephalic neuron aggregates and examined long-term culture of these aggregates on collagen gel. The results indicated that these aggregates could be cultured for over 3 months by adhering tightly onto collagen gel. Furthermore, telencephalic neuronal precursors within these aggregates matured over time and formed layered structures. Thus, long-term culture of telencephalic neuron aggregates derived from human iPS cells on collagen gel would be useful for studying human cerebral cortex development.Key words: Induced pluripotent stem cell, forebrain neuron, collagen gel, long-term culture.

Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1

PubMed Central

Moon, Jai-Hee; Heo, June Seok; Kim, Jun Sung; Jun, Eun Kyoung; Lee, Jung Han; Kim, Aeree; Kim, Jonggun; Whang, Kwang Youn; Kang, Yong-Kook; Yeo, Seungeun; Lim, Hee-Joung; Han, Dong Wook; Kim, Dong-Wook; Oh, Sejong; Yoon, Byung Sun; Schöler, Hans R; You, Seungkwon

2011-01-01

Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by the transcription factors Oct4, Sox2, and Klf4 in combination with c-Myc. Recently, Sox2 plus Oct4 was shown to reprogram fibroblasts and Oct4 alone was able to reprogram mouse and human neural stem cells (NSCs) into iPS cells. Here, we report that Bmi1 leads to the transdifferentiation of mouse fibroblasts into NSC-like cells, and, in combination with Oct4, can replace Sox2, Klf4 and c-Myc during the reprogramming of fibroblasts into iPS cells. Furthermore, activation of sonic hedgehog signaling (by Shh, purmorphamine, or oxysterol) compensates for the effects of Bmi1, and, in combination with Oct4, reprograms mouse embryonic and adult fibroblasts into iPS cells. One- and two-factor iPS cells are similar to mouse embryonic stem cells in their global gene expression profile, epigenetic status, and in vitro and in vivo differentiation into all three germ layers, as well as teratoma formation and germline transmission in vivo. These data support that converting fibroblasts with Bmi1 or activation of the sonic hedgehog pathway to an intermediate cell type that expresses Sox2, Klf4, and N-Myc allows iPS generation via the addition of Oct4. PMID:21709693

Protective versus promotional effects of white tea and caffeine on PhIP-induced tumorigenesis and β-catenin expression in the rat

PubMed Central

Wang, Rong; Dashwood, W. Mohaiza; Löhr, Christiane V.; Fischer, Kay A.; Pereira, Clifford B.; Louderback, Mandy; Nakagama, Hitoshi; Bailey, George S.; Williams, David E.; Dashwood, Roderick H.

2009-01-01

A 1 year carcinogenicity bioassay was conducted in rats treated with three short cycles of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)/high-fat (HF) diet, followed by 2% white tea (wt/vol), 0.05% epigallocatechin-3-gallate (EGCG) or 0.065% caffeine as sole source of fluid intake. Thirty-two percent of the PhIP/HF controls survived to 1 year, compared with 50, 48.7 and 18.2% in groups given white tea, EGCG and caffeine, respectively. After 1 year, PhIP/HF controls had tumors in the colon, skin, small intestine, Zymbal’s gland, salivary gland and pancreas. For all sites combined, excluding the colon, tumor incidence data were as follows: PhIP/HF 69.5%, PhIP/HF + EGCG 48.7%, PhIP/HF + white tea 46.9% and PhIP/HF + caffeine 13.3%. Unexpectedly, a higher incidence of colon tumors was detected in rats post-treated with white tea (69%) and caffeine (73%) compared with the 42% incidence in PhIP/HF controls. In the colon tumors, β-catenin mutations were detected at a higher frequency after caffeine posttreatment, and there was a shift toward more tumors harboring substitutions of Gly34 with correspondingly high protein and messenger RNA expression seen for both β-catenin and c-Myc. c-Myc expression exhibited concordance with tumor promotion, and there was a concomitant increase in cell proliferation versus apoptosis in colonic crypts. A prior report described suppression of PhIP-induced colonic aberrant crypts by the same test agents, but did not incorporate a HF diet. These findings are discussed in the context of epidemiological data which do not support an adverse effect of tea and coffee on colon tumor outcome—indeed, some such studies suggest a protective role for caffeinated beverages. PMID:18283038

Ternary Kv4.2 channels recapitulate voltage-dependent inactivation kinetics of A-type K+ channels in cerebellar granule neurons.

PubMed

Amarillo, Yimy; De Santiago-Castillo, Jose A; Dougherty, Kevin; Maffie, Jonathon; Kwon, Elaine; Covarrubias, Manuel; Rudy, Bernardo

2008-04-15

Kv4 channels mediate most of the somatodendritic subthreshold operating A-type current (I(SA)) in neurons. This current plays essential roles in the regulation of spike timing, repetitive firing, dendritic integration and plasticity. Neuronal Kv4 channels are thought to be ternary complexes of Kv4 pore-forming subunits and two types of accessory proteins, Kv channel interacting proteins (KChIPs) and the dipeptidyl-peptidase-like proteins (DPPLs) DPPX (DPP6) and DPP10. In heterologous cells, ternary Kv4 channels exhibit inactivation that slows down with increasing depolarization. Here, we compared the voltage dependence of the inactivation rate of channels expressed in heterologous mammalian cells by Kv4.2 proteins with that of channels containing Kv4.2 and KChIP1, Kv4.2 and DPPX-S, or Kv4.2, KChIP1 and DPPX-S, and found that the relation between inactivation rate and membrane potential is distinct for these four conditions. Moreover, recordings from native neurons showed that the inactivation kinetics of the I(SA) in cerebellar granule neurons has voltage dependence that is remarkably similar to that of ternary Kv4 channels containing KChIP1 and DPPX-S proteins in heterologous cells. The fact that this complex and unique behaviour (among A-type K(+) currents) is observed in both the native current and the current expressed in heterologous cells by the ternary complex containing Kv4, DPPX and KChIP proteins supports the hypothesis that somatically recorded native Kv4 channels in neurons include both types of accessory protein. Furthermore, quantitative global kinetic modelling showed that preferential closed-state inactivation and a weakly voltage-dependent opening step can explain the slowing of the inactivation rate with increasing depolarization. Therefore, it is likely that preferential closed-state inactivation is the physiological mechanism that regulates the activity of both ternary Kv4 channel complexes and native I(SA)-mediating channels.

Modelling crop yield in Iberia under drought conditions

NASA Astrophysics Data System (ADS)

Ribeiro, Andreia; Páscoa, Patrícia; Russo, Ana; Gouveia, Célia

2017-04-01

The improved assessment of the cereal yield and crop loss under drought conditions are essential to meet the increasing economy demands. The growing frequency and severity of the extreme drought conditions in the Iberian Peninsula (IP) has been likely responsible for negative impacts on agriculture, namely on crop yield losses. Therefore, a continuous monitoring of vegetation activity and a reliable estimation of drought impacts is crucial to contribute for the agricultural drought management and development of suitable information tools. This works aims to assess the influence of drought conditions in agricultural yields over the IP, considering cereal yields from mainly rainfed agriculture for the provinces with higher productivity. The main target is to develop a strategy to model drought risk on agriculture for wheat yield at a province level. In order to achieve this goal a combined assessment was made using a drought indicator (Standardized Precipitation Evapotranspiration Index, SPEI) to evaluate drought conditions together with a widely used vegetation index (Normalized Difference Vegetation Index, NDVI) to monitor vegetation activity. A correlation analysis between detrended wheat yield and SPEI was performed in order to assess the vegetation response to each time scale of drought occurrence and also identify the moment of the vegetative cycle when the crop yields are more vulnerable to drought conditions. The time scales and months of SPEI, together with the months of NDVI, better related with wheat yield were chosen to perform a multivariate regression analysis to simulate crop yield. Model results are satisfactory and highlighted the usefulness of such analysis in the framework of developing a drought risk model for crop yields. In terms of an operational point of view, the results aim to contribute to an improved understanding of crop yield management under dry conditions, particularly adding substantial information on the advantages of combining vegetation and hydro-meteorological drought indices for the assessment of cereal yield. Moreover, the present study will provide some guidance on user's decision making process in agricultural practices in the IP, assisting farmers in deciding whether to purchase crop insurance. Acknowledgements: This work was partially supported by national funds through FCT (Fundação para a Ciência e a Tecnologia, Portugal) under project IMDROFLOOD (WaterJPI/0004/2014). Ana Russo thanks FCT for granted support (SFRH/BPD/99757/2014). Andreia Ribeiro also thanks FCT for grant PD/BD/114481/2016.

Building of communication system for nuclear accident emergency disposal based on IP multimedia subsystem

NASA Astrophysics Data System (ADS)

Wang, Kang; Gao, Guiqing; Qin, Yuanli; He, Xiangyong

2018-05-01

The nuclear accident emergency disposal must be supported by an efficient, real-time modularization and standardization communication system. Based on the analysis of communication system for nuclear accident emergency disposal which included many functions such as the internal and external communication, multiply access supporting and command center. Some difficult problems of the communication system were discussed such as variety access device type, complex composition, high mobility, set up quickly, multiply business support, and so on. Taking full advantages of the IP Multimedia Subsystem (IMS), a nuclear accident emergency communication system was build based on the IMS. It was studied and implemented that some key unit and module functions of communication system were included the system framework implementation, satellite access, short-wave access, load/vehicle-mounted communication units. The application tests showed that the system could provide effective communication support for the nuclear accident emergency disposal, which was of great practical value.

Antidepressant activity of nociceptin/orphanin FQ receptor antagonists in the mouse learned helplessness.

PubMed

Holanda, Victor A D; Medeiros, Iris U; Asth, Laila; Guerrini, Remo; Calo', Girolamo; Gavioli, Elaine C

2016-07-01

Pharmacological and genetic evidence support antidepressant-like effects elicited by the blockade of the NOP receptor. The learned helplessness (LH) model employs uncontrollable and unpredictable electric footshocks as a stressor stimulus to induce a depressive-like phenotype that can be reversed by classical antidepressants. The present study aimed to evaluate the action of NOP receptor antagonists in helpless mice. Male Swiss mice were subjected to the three steps of the LH paradigm (i.e., (1) induction, (2) screening, and (3) test). Only helpless animals were subjected to the test session. During the test session, animals were placed in the electrified chamber and the latency to escape after the footshock and the frequency of escape failures were recorded. The effect of the following treatments administered before the test session were evaluated: nortriptyline (30 mg/kg, ip, 60 min), fluoxetine (30 mg/kg, ip, four consecutive days of treatment), and NOP antagonists SB-612111 (1-10 mg/kg, ip, 30 min) and UFP-101 (1-10 nmol, icv, 5 min). To rule out possible biases, the effects of treatments on controllable stressful and non stressful situations were assessed. In helpless mice, nortriptyline, fluoxetine, UFP-101 (3-10 nmol), and SB-612111 (3-10 mg/kg) significantly reduced escape latencies and escape failures. No effects of drug treatments were observed in mice subjected to the controllable electric footshocks and non stressful situations. Acute treatment with NOP antagonists reversed helplessness similarly to the classical antidepressants. These findings support the proposal that NOP receptor antagonists are worthy of development as innovative antidepressant drugs.

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.

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

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.

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.

Nonlinear Gap Junctions Enable Long-Distance Propagation of Pulsating Calcium Waves in Astrocyte Networks

PubMed Central

Goldberg, Mati; De Pittà, Maurizio; Volman, Vladislav; Berry, Hugues; Ben-Jacob, Eshel

2010-01-01

A new paradigm has recently emerged in brain science whereby communications between glial cells and neuron-glia interactions should be considered together with neurons and their networks to understand higher brain functions. In particular, astrocytes, the main type of glial cells in the cortex, have been shown to communicate with neurons and with each other. They are thought to form a gap-junction-coupled syncytium supporting cell-cell communication via propagating Ca2+ waves. An identified mode of propagation is based on cytoplasm-to-cytoplasm transport of inositol trisphosphate (IP3) through gap junctions that locally trigger Ca2+ pulses via IP3-dependent Ca2+-induced Ca2+ release. It is, however, currently unknown whether this intracellular route is able to support the propagation of long-distance regenerative Ca2+ waves or is restricted to short-distance signaling. Furthermore, the influence of the intracellular signaling dynamics on intercellular propagation remains to be understood. In this work, we propose a model of the gap-junctional route for intercellular Ca2+ wave propagation in astrocytes. Our model yields two major predictions. First, we show that long-distance regenerative signaling requires nonlinear coupling in the gap junctions. Second, we show that even with nonlinear gap junctions, long-distance regenerative signaling is favored when the internal Ca2+ dynamics implements frequency modulation-encoding oscillations with pulsating dynamics, while amplitude modulation-encoding dynamics tends to restrict the propagation range. As a result, spatially heterogeneous molecular properties and/or weak couplings are shown to give rise to rich spatiotemporal dynamics that support complex propagation behaviors. These results shed new light on the mechanisms implicated in the propagation of Ca2+ waves across astrocytes and the precise conditions under which glial cells may participate in information processing in the brain. PMID:20865153

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

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.

Evaluation of the filter paper IP-10 tests in school children after exposure to tuberculosis: a prospective cohort study with a 4-year follow-up

PubMed Central

Tuuminen, Tamara; Salo, Eeva; Kotilainen, Hannele; Ruhwald, Morten

2012-01-01

Objectives The prevalence of active tuberculosis (TB) is low in Finland, but outbreaks do occur. Following exposure national guidelines recommend either tuberculosis skin test or interferon-γ-release assay-testing of asymptomatic children. The aim of this study was to compare QuantiFERON-TB Gold In-Tube test (QFT) and interferon-γ-inducible protein (IP-10) release assay for detection of Mycobacterium tuberculosis infection following exposure to TB in a primary school. Design A prospective cohort study. Setting School children in Helsinki, Finland. Participants Two siblings of the index case and 58 classmates exposed to M tuberculosis. Intervention All the children were screened using the QFT, which was used to guide preventive treatment. All those exposed were followed up through the national TB registry. Outcome measures IP-10 was measured in plasma supernatants from the QFT test supernatants and in plasma dried and stored for 1 year on filter paper. IP-10 test results were calculated using preset algorithms for positive and indeterminate tests. The negative predictive values of the tests were assessed. Results At an initial screening 2 months after the debut of symptoms in the index case, QFT was positive in two children; 56 tests were negative; one was indeterminate and one was borderline. IP-10 showed a perfect concordance between the dried plasma spot and plasma method; two children were IP-10 positive and two were IP-10 indeterminate. There were two (3%) discordant results between the QFT and IP-10 tests. Four children converted to positive QFT at a 1–3 month follow-up. None of the QFT negative/borderline children developed TB in the 4-year period since exposure. Conclusions We demonstrated that IP-10 and QFT perform comparably as screening tools for infection with M tuberculosis in a contact investigation. IP-10 determined in dried plasma spots was at par with IP-10 determined in plasma, which further supports the usefulness of this alternative approach. PMID:23212994

Ethanol potentiates the genotoxicity of the food-derived mammary carcinogen PhIP in human estrogen receptor-positive mammary cells: mechanistic support for lifestyle factors (cooked red meat and ethanol) associated with mammary cancer.

PubMed

Malik, Durr-E-Shahwar; David, Rhiannon M; Gooderham, Nigel J

2018-04-01

Consumption of cooked/processed meat and ethanol are lifestyle risk factors in the aetiology of breast cancer. Cooking meat generates heterocyclic amines such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Epidemiology, mechanistic and animal studies indicate that PhIP is a mammary carcinogen that could be causally linked to breast cancer incidence; PhIP is DNA damaging, mutagenic and oestrogenic. PhIP toxicity involves cytochrome P450 (CYP1 family)-mediated metabolic activation to DNA-damaging species, and transcriptional responses through Aryl hydrocarbon receptor (AhR) and estrogen-receptor-α (ER-α). Ethanol consumption is a modifiable lifestyle factor strongly associated with breast cancer risk. Ethanol toxicity involves alcohol dehydrogenase metabolism to reactive acetaldehyde, and is also a substrate for CYP2E1, which when uncoupled generates reactive oxygen species (ROS) and DNA damage. Here, using human mammary cells that differ in estrogen-receptor status, we explore genotoxicity of PhIP and ethanol and mechanisms behind this toxicity. Treatment with PhIP (10 -7 -10 -4 M) significantly induced genotoxicity (micronuclei formation) preferentially in ER-α positive human mammary cell lines (MCF-7, ER-α+) compared to MDA-MB-231 (ER-α-) cells. PhIP-induced CYP1A2 in both cell lines but CYP1B1 was selectively induced in ER-α(+) cells. ER-α inhibition in MCF-7 cells attenuated PhIP-mediated micronuclei formation and CYP1B1 induction. PhIP-induced CYP2E1 and ROS via ER-α-STAT-3 pathway, but only in ER-α (+) MCF-7 cells. Importantly, simultaneous treatments of physiological concentrations ethanol (10 -3 -10 -1 M) with PhIP (10 -7 -10 -4 M) increased oxidative stress and genotoxicity in MCF-7 cells, compared to the individual chemicals. Collectively, these data offer a mechanistic basis for the increased risk of breast cancer associated with dietary cooked meat and ethanol lifestyle choices.

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

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

Assessing methods for developing crop forecasting in the Iberian Peninsula

NASA Astrophysics Data System (ADS)

Ines, A. V. M.; Capa Morocho, M. I.; Baethgen, W.; Rodriguez-Fonseca, B.; Han, E.; Ruiz Ramos, M.

2015-12-01

Seasonal climate prediction may allow predicting crop yield to reduce the vulnerability of agricultural production to climate variability and its extremes. It has been already demonstrated that seasonal climate predictions at European (or Iberian) scale from ensembles of global coupled climate models have some skill (Palmer et al., 2004). The limited predictability that exhibits the atmosphere in mid-latitudes, and therefore de Iberian Peninsula (PI), can be managed by a probabilistic approach based in terciles. This study presents an application for the IP of two methods for linking tercile-based seasonal climate forecasts with crop models to improve crop predictability. Two methods were evaluated and applied for disaggregating seasonal rainfall forecasts into daily weather realizations: 1) a stochastic weather generator and 2) a forecast tercile resampler. Both methods were evaluated in a case study where the impacts of two seasonal rainfall forecasts (wet and dry forecast for 1998 and 2015 respectively) on rainfed wheat yield and irrigation requirements of maize in IP were analyzed. Simulated wheat yield and irrigation requirements of maize were computed with the crop models CERES-wheat and CERES-maize which are included in Decision Support System for Agrotechnology Transfer (DSSAT v.4.5, Hoogenboom et al., 2010). Simulations were run at several locations in Spain where the crop model was calibrated and validated with independent field data. These methodologies would allow quantifying the benefits and risks of a seasonal climate forecast to potential users as farmers, agroindustry and insurance companies in the IP. Therefore, we would be able to establish early warning systems and to design crop management adaptation strategies that take advantage of favorable conditions or reduce the effect of adverse ones. ReferencesPalmer, T. et al., 2004. Development of a European multimodel ensemble system for seasonal-to-interannual prediction (DEMETER). Bulletin of the American Meteorological Society, 85(6): 853-872.

The value of DCIP geophysical surveys for contaminated site investigations

NASA Astrophysics Data System (ADS)

Balbarini, N.; Rønde, V.; Maurya, P. K.; Møller, I.; McKnight, U. S.; Christiansen, A. V.; Binning, P. J.; Bjerg, P. L.

2017-12-01

Geophysical methods are increasingly being used in contaminant hydrogeology to map lithology, hydraulic properties, and contaminant plumes with a high ionic strength. Advances in the Direct Current resistivity and Induced Polarization (DCIP) method allow the collection of high resolution three dimensional (3D) data sets. The DC resistivity can describe both soil properties and the water electrical conductivity, while the IP can describe the lithology and give information on hydrogeological properties. The aim of the study was to investigate a large contaminant plume discharging to a stream from an old factory site by combining traditional geological, hydrological, and contaminant concentration data with DCIP surveys. The plume consisted of xenobiotic organic compounds and inorganics. The study assesses benefits and limitations of DCIP geophysics for contaminated site investigations. A 3D geological model was developed from borehole logs and DCIP data as framework for the complex transport pathways near the meandering stream. IP data were useful in indicating the continuity and the changes in thickness of local clay layers between the borehole logs. The geological model was employed to develop a groundwater flow model describing groundwater flows to the stream. The hydraulic conductivity distribution was based on IP data, slug tests and grain size analysis. The distribution of contaminant concentrations revealed two chemically distinct plumes, separated by a clay layer, with different transport paths to the stream. The DC resistivity was useful in mapping ionic compounds, but also organic compounds whose spatial distribution coincided with the ionic compounds. A conceptual model describing the contaminant plume was developed, and it matched well with contaminant concentrations in stream water and below the streambed. Surface DCIP surveys supported the characterization of the spatial variability in geology, hydraulic conductivity and contaminant concentration. Though DCIP data interpretation required additional borehole data, the DCIP survey reduced the number of boreholes required and helped design field campaigns. The results suggest DCIP surveys are useful and inexpensive tools, which has potential as an integrated part of contaminated site investigations.

International Space Station Aeromedical Support in Star City, Russia

NASA Technical Reports Server (NTRS)

Cole, Richard; Chamberlin, Blake; Dowell, Gene; Castleberry, Tarah; Savage, Scott

2010-01-01

The Space Medicine Division at Johnson Space Center works with the International Space Station s international partners (IP) to accomplish assigned health care tasks. Each IP may assign a flight surgeon to support their assigned crewmembers during all phases of training, in-flight operations, and postflight activities. Because of the extensive amount of astronaut training conducted in Star City; NASA, in collaboration with its IPs, has elected to keep a flight surgeon assigned to NASA s Star City office to provide support to the U.S., Canadian, Japanese, and European astronauts during hazardous training activities and provide support for any contingency landings of Soyuz spacecraft in Kazakhstan. The physician also provides support as necessary to the Mission Control Center in Moscow for non-Russian crew-related activities. In addition, the physician in Star City provides ambulatory medical care to the non-Russian-assigned personnel in Star City and visiting dependents. Additional work involves all medical supplies, administration, and inventory. The Star City physician assists in medical evacuation and/or in obtaining support from western clinics in Moscow when required care exceeds local resources. Overall, the Russians are responsible for operations and the medical care of the entire crew when training in Star City and during launch/landing operations. However, they allow international partner flight surgeons to care for their crewmembers as agreed to in the ISS Medical Operations Requirements Document. Medical support focuses on pressurized, monitored, and other hazardous training activities. One of the most important jobs is to act as a medical advocate for the astronauts and to reduce the threat that these hazardous activities pose. Although the Russians have a robust medical system, evacuation may be needed to facilitate ongoing medical care. There are several international medical evacuation companies that provide this care.

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.

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.

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.

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.

Orbit Software Suite

NASA Technical Reports Server (NTRS)

Osgood, Cathy; Williams, Kevin; Gentry, Philip; Brownfield, Dana; Hallstrom, John; Stuit, Tim

2012-01-01

Orbit Software Suite is used to support a variety of NASA/DM (Dependable Multiprocessor) mission planning and analysis activities on the IPS (Intrusion Prevention System) platform. The suite of Orbit software tools (Orbit Design and Orbit Dynamics) resides on IPS/Linux workstations, and is used to perform mission design and analysis tasks corresponding to trajectory/ launch window, rendezvous, and proximity operations flight segments. A list of tools in Orbit Software Suite represents tool versions established during/after the Equipment Rehost-3 Project.

Navigation/Prop Software Suite

NASA Technical Reports Server (NTRS)

Bruchmiller, Tomas; Tran, Sanh; Lee, Mathew; Bucker, Scott; Bupane, Catherine; Bennett, Charles; Cantu, Sergio; Kwong, Ping; Propst, Carolyn

2012-01-01

Navigation (Nav)/Prop software is used to support shuttle mission analysis, production, and some operations tasks. The Nav/Prop suite containing configuration items (CIs) resides on IPS/Linux workstations. It features lifecycle documents, and data files used for shuttle navigation and propellant analysis for all flight segments. This suite also includes trajectory server, archive server, and RAT software residing on MCC/Linux workstations. Navigation/Prop represents tool versions established during or after IPS Equipment Rehost-3 or after the MCC Rehost.

Barriers and strategies for improving communication between inpatient and outpatient mental health clinicians.

PubMed

Stockdale, Susan E; Sherin, Jonathan E; Chan, Jeffrey A; Hermann, Richard C

2011-11-01

To explore hospital leaders' perceptions of organisational factors as barriers and/or facilitators in improving inpatient-outpatient (IP-OP) communication. Semistructured in-person interviews. Constant comparative method of qualitative data. Inpatient psychiatry units in 33 general medical/surgical and specialty psychiatric hospitals in California and Massachusetts (USA). Psychiatry chair/chief, service director or medical director. Importance to leadership, resources, organisational structure and culture. A majority of hospital leaders rated the IP-OP communication objective as highly or moderately important. Hospitals with good IP-OP communication had structures in place to support communication or had changed/implemented new procedures to enhance communication, and anticipated clinicians would 'buy in' to the goal of improved communication. Hospitals reporting no improvement efforts were less likely to have structures supporting IP-OP communication, anticipated resistance among clinicians and reported a need for technological resources such as electronic health records, integrated IT and secure online communication. Most leaders reported a need for additional staff time and information, knowledge or data. For many hospitals, successfully improving communication will require overcoming organisational barriers such as cultures not conducive to change and lack of resources and infrastructure. Creating a culture that values communication at discharge may help improve outcomes following hospitalisation, but changes in healthcare delivery in the past few decades may necessitate new strategies or changes at the systems level to address barriers to effective communication.

Methicillin-resistant Staphylococcus aureus prevention practices in hospitals throughout a rural state.

PubMed

McDanel, Jennifer S; Ward, Melissa A; Leder, Laurie; Schweizer, Marin L; Dawson, Jeffrey D; Diekema, Daniel J; Smith, Tara C; Chrischilles, Elizabeth A; Perencevich, Eli N; Herwaldt, Loreen A

2014-08-01

The Institute for Healthcare Improvement (IHI) created an evidence-based bundle to help reduce methicillin-resistant Staphylococcus aureus (MRSA) health care-associated infections. The study aim was to identify which components of the IHI's MRSA bundle that rural hospitals have implemented and to identify barriers that hindered implementation of bundle components. Four surveys about the IHI's MRSA bundle were administered at the Iowa Statewide Infection Prevention Seminar between 2007 and 2011. Surveys were mailed to infection preventionists (IPs) who did not attend the meetings. The percentage of IPs reporting that their hospital implemented a hand hygiene program (range by year, 87%-94%) and used contact precautions for patients infected (range by year, 97%-100%) or colonized (range by year, 77%-92%) with MRSA did not change significantly. The number of hospitals that monitored the effectiveness of environmental cleaning significantly increased from 23%-71% (P < .01). Few hospitals assessed daily if central lines were necessary (range by year, 22%-26%). IPs perceived lack of support to be a major barrier to implementing bundle components. Most IPs reported that their hospitals had implemented most components of the MRSA bundle. Support within the health care system is essential for implementing each component of an evidence-based bundle. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Design of SIP transformation server for efficient media negotiation

NASA Astrophysics Data System (ADS)

Pack, Sangheon; Paik, Eun Kyoung; Choi, Yanghee

2001-07-01

Voice over IP (VoIP) is one of the advanced services supported by the next generation mobile communication. VoIP should support various media formats and terminals existing together. This heterogeneous environment may prevent diverse users from establishing VoIP sessions among them. To solve the problem an efficient media negotiation mechanism is required. In this paper, we propose the efficient media negotiation architecture using the transformation server and the Intelligent Location Server (ILS). The transformation server is an extended Session Initiation Protocol (SIP) proxy server. It can modify an unacceptable session INVITE message into an acceptable one using the ILS. The ILS is a directory server based on the Lightweight Directory Access Protocol (LDAP) that keeps userí*s location information and available media information. The proposed architecture can eliminate an unnecessary response and re-INVITE messages of the standard SIP architecture. It takes only 1.5 round trip times to negotiate two different media types while the standard media negotiation mechanism takes 2.5 round trip times. The extra processing time in message handling is negligible in comparison to the reduced round trip time. The experimental results show that the session setup time in the proposed architecture is less than the setup time in the standard SIP. These results verify that the proposed media negotiation mechanism is more efficient in solving diversity problems.

Approaches in highly parameterized inversion - GENIE, a general model-independent TCP/IP run manager

USGS Publications Warehouse

Muffels, Christopher T.; Schreuder, Willem A.; Doherty, John E.; Karanovic, Marinko; Tonkin, Matthew J.; Hunt, Randall J.; Welter, David E.

2012-01-01

GENIE is a model-independent suite of programs that can be used to generally distribute, manage, and execute multiple model runs via the TCP/IP infrastructure. The suite consists of a file distribution interface, a run manage, a run executer, and a routine that can be compiled as part of a program and used to exchange model runs with the run manager. Because communication is via a standard protocol (TCP/IP), any computer connected to the Internet can serve in any of the capacities offered by this suite. Model independence is consistent with the existing template and instruction file protocols of the widely used PEST parameter estimation program. This report describes (1) the problem addressed; (2) the approach used by GENIE to queue, distribute, and retrieve model runs; and (3) user instructions, classes, and functions developed. It also includes (4) an example to illustrate the linking of GENIE with Parallel PEST using the interface routine.

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.

ERalpha and AP-1 interact in vivo with a specific sequence of the F promoter of the human ERalpha gene in osteoblasts.

PubMed

Lambertini, Elisabetta; Tavanti, Elisa; Torreggiani, Elena; Penolazzi, Letizia; Gambari, Roberto; Piva, Roberta

2008-07-01

Estrogen-responsive genes often have an estrogen response element (ERE) positioned next to activator protein-1 (AP-1) binding sites. Considering that the interaction between ERE and AP-1 elements has been described for the modulation of bone-specific genes, we investigated the 17-beta-estradiol responsiveness and the role of these cis-elements present in the F promoter of the human estrogen receptor alpha (ERalpha) gene. The F promoter, containing the sequence analyzed here, is one of the multiple promoters of the human ERalpha gene and is the only active promoter in bone tissue. Through electrophoretic mobility shift (EMSA), chromatin immunoprecipitation (ChIP), and re-ChIP assays, we investigated the binding of ERalpha and four members of the AP-1 family (c-Jun, c-fos, Fra-2, and ATF2) to a region located approximately 800 bp upstream of the transcriptional start site of exon F of the human ERalpha gene in SaOS-2 osteoblast-like cells. Reporter gene assay experiments in combination with DNA binding assays demonstrated that F promoter activity is under the control of upstream cis-acting elements which are recognized by specific combinations of ERalpha, c-Jun, c-fos, and ATF2 homo- and heterodimers. Moreover, ChIP and re-ChIP experiments showed that these nuclear factors bind the F promoter in vivo with a simultaneous occupancy stimulated by 17-beta-estradiol. Taken together, our findings support a model in which ERalpha/AP-1 complexes modulate F promoter activity under conditions of 17-beta-estradiol stimulation. (c) 2008 Wiley-Liss, Inc.

Distribution of finger nodes and their association with underlying radiographic features of osteoarthritis.

PubMed

Rees, Frances; Doherty, Sally; Hui, Michelle; Maciewicz, Rose; Muir, Kenneth; Zhang, Weiya; Doherty, Michael

2012-04-01

To determine the distribution of clinically palpable hand interphalangeal (IP) nodes at each finger and thumb joint in a population with nodes, the influence of left or right hand dominance and sex on the development of nodes, and the association between nodes and underlying radiographic features of osteoarthritis (OA). We performed a cross-sectional analysis of participants in the Genetics of Osteoarthritis and Lifestyle (GOAL) study who had ≥1 Heberden's nodes or Bouchard's nodes on clinical examination. Frequencies (%) of nodes were described for each IP joint in the hand. Associations between nodes and underlying radiographic OA were shown with odds ratios (ORs) and 95% confidence intervals. A logistic regression model was used to adjust for the following confounding factors: age, sex, body mass index, left or right hand dominance, hand trauma, occupation with heavy manual activity, and participation in sports. Of the 3,170 GOAL participants, 1,939 had ≥1 nodes (mean age 68 years, 54% women). The distal IP joints of the index finger were the most frequently affected, followed by the thumb IP joint. Nodes were more common in dominant hands and women. There was a significant association between nodes and underlying radiographic OA (OR range 2.26-21.23). This association was stronger for joint space narrowing than for osteophytes. A dose-response relationship was found between clinical severity of Heberden's nodes and underlying radiographic change. Our study supports the positive association between nodes and radiographic OA, especially narrowing, and the influence of sex and left or right hand dominance on development of nodes. In this age group, presence of nodes may be taken as an indication of underlying small joint OA. Copyright © 2012 by the American College of Rheumatology.

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

An interprofessional approach to shared decision making: an exploratory case study with family caregivers of one IP home care team.

PubMed

Légaré, France; Stacey, Dawn; Brière, Nathalie; Robitaille, Hubert; Lord, Marie-Claude; Desroches, Sophie; Drolet, Renée

2014-07-02

Within the context of an exploratory case study, the authors assessed the perceptions of family caregivers about the decision-making process regarding relocating their relative and about the applicability of an interprofessional approach to shared decision making (IP-SDM). They also assessed perceptions of health professionals and health managers about IP-SDM. From November 2010 to October 2011, we worked with one IP home care team dedicated to older adults (the case) from a large primary health care organization in Quebec City, Canada. We identified six of their clients who had faced a decision about whether to stay at home or move to a long-term care facility in the past year and interviewed their family caregivers. We explored the decision-making process they had experienced regarding relocating their relative and their perceptions about the applicability of IP-SDM in this context. Attitudes towards IP-SDM and potential barriers to this approach were explored using a focus group with the participating IP home care team, individual interviews with 8 managers and a survey of 272 health professionals from the primary care organization. A hybrid process of inductive and deductive thematic analysis was used and data were triangulated across all sources. Family caregivers reported lack of agreement on the nature of the decision to be made, a disconnection between home care services and relatives' needs, and high cost of long-term care alternatives. Factors influencing their decision included their ability to provide care for their relative. While they felt somewhat supported by the IP home care team, they also felt pressured in the decision. Overall, they did not perceive they had been exposed to IP-SDM but agreed that it was applicable in this context. Results from the survey, focus group and interviews with health professionals and managers indicated they all had a favourable attitude towards IP-SDM but many barriers hampered its implementation in their practice. The family caregivers in this study did not experience IP-SDM when relocating their relative. Added to results obtained with health professionals and managers, this highlights the need for an effective intervention targeting identified barriers to implementing IP-SDM in this context.

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.

Rottlerin impairs the formation and maintenance of psychostimulant-supported memory.

PubMed

Liao, Tien You; Tzeng, Wen-Yu; Wu, Hsin-Hua; Cherng, Chianfang G; Wang, Ching-Yi; Hu, Sherry S-J; Yu, Lung

2016-04-01

Since brain proteins such as protein kinase C (PKC), brain-derived neurotrophic factor (BDNF), and mammalian target of rapamycin (mTOR) are involved in the establishment and maintenance of psychostimulant memory, we sought to determine if systemic treatment with rottlerin, a natural compound affecting all these proteins, may modulate stimulant-supported memory. Stimulant-induced conditioned place preference (CPP) was used in modeling stimulant-supported memory. Three cocaine (10 mg/kg; COC) or three methamphetamine (1 mg/kg; MA) conditioning trials reliably established the drug-induced CPP in male C57BL/6 mice. An intra-peritoneal rottlerin injection (5 mg/kg) at least 24 h prior to the first COC or first MA conditioning trial prevented the establishment of CPP. Following the establishment of the COC- or MA-induced CPP, saline conditioning trial was used to extinguish the CPP. Rottlerin (5 mg/kg, intra-peritoneal (i.p.)) administered 20 h prior to the first saline conditioning trial diminished subsequent drug- and stressor-primed reinstatement of the extinguished CPP. Rottlerin (5 mg/kg, i.p.) produced a fast-onset and long-lasting increase in hippocampal BDNF levels. However, treatment with a BDNF tropomyosin receptor kinase B (TrkB) receptor antagonist, K252a (5 μg/kg), did not affect rottlerin's suppressing effect on COC-induced CPP and treatment with 7,8-dihydroxyflavone (10 mg/kg x 6, 7,8-DHF), a selective TrkB agonist, prior to each conditioning trial did not affect COC-induced CPP. These results suggest that systemic rottlerin treatment may impair the formation of COC- and MA-supported memory. Importantly, such a treatment may advance our understanding of the underlying mechanism through which extinction training resulted in the "forgetting" of the COC- and MA-supported memory.

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.

Forward Tracking with the JLab/MEIC Detector Concept

NASA Astrophysics Data System (ADS)

Hyde, Charles; JLab/MEIC Design Team

2015-10-01

At a future electron ion collider (EIC), the quark-gluon structure of the NN force can be probed in e . g . deeply virtual exclusive scattering on a tensor polarized Deuteron and diffractive DIS on the deuteron with tagging of the NN final state. The MEIC design includes two Interaction Points (IPs), each of which can operate simultaneously at full luminosity. The detector and beam-line optics for IP1 are designed to be nearly hermetic for all particles outside the presumed 10-sigma admittance (longitudinal and transverse) of the figure-8 accelerator lattice. The integration of the IP1 detector with the lattice extends 40 m downstream of the IP in both the electron and ion directions. The central region of the detector is a new 4 m long 3 m diameter 3 Tesla solenoid. Analysis in the forward ion direction is enhanced by the 50 mrad crossing angle at the IP, and a two-stage spectrometer integrated into the first 36 m of the accelerator lattice. In this talk I will present the optics and resolution of the forward ion spectrometer, including resolution effects of an initial beam pipe design. Supported by U.S. Department of Energy.

NMDA receptor antagonists inhibit catalepsy induced by either dopamine D1 or D2 receptor antagonists.

PubMed

Moore, N A; Blackman, A; Awere, S; Leander, J D

1993-06-11

In the present study, we investigated the ability of NMDA receptor antagonists to inhibit catalepsy induced by haloperidol, or SCH23390 and clebopride, selective dopamine D1 and D2 receptor antagonists respectively. Catalepsy was measured by recording the time the animal remained with its forepaws placed over a rod 6 cm above the bench. Pretreatment with either the non-competitive NMDA receptor antagonist, MK-801 (0.25-0.5 mg/kg i.p.) or the competitive antagonist, LY274614 (10-20 mg/kg i.p.) reduced the cataleptic response produced by haloperidol (10 mg/kg), SCH23390 (2.5-10 mg/kp i.p.) or clebopride (5-20 mg/kg i.p.). This demonstrates that NMDA receptor antagonists will reduce both dopamine D1 and D2 receptor antagonist-induced catalepsy. Muscle relaxant doses of chlordiazepoxide (10 mg/kg i.p.) failed to reduce the catalepsy induced by haloperidol, suggesting that the anticataleptic effect of the NMDA receptor antagonists was not due to a non-specific action. These results support the hypothesis that NMDA receptor antagonists may have beneficial effects in disorders involving reduced dopaminergic function, such as Parkinson's disease.

Efficient Generation of iPS Cells from Skeletal Muscle Stem Cells

PubMed Central

Tan, Kah Yong; Eminli, Sarah; Hettmer, Simone; Hochedlinger, Konrad; Wagers, Amy J.

2011-01-01

Reprogramming of somatic cells into inducible pluripotent stem cells generally occurs at low efficiency, although what limits reprogramming of particular cell types is poorly understood. Recent data suggest that the differentiation status of the cell targeted for reprogramming may influence its susceptibility to reprogramming as well as the differentiation potential of the induced pluripotent stem (iPS) cells that are derived from it. To assess directly the influence of lineage commitment on iPS cell derivation and differentiation, we evaluated reprogramming in adult stem cell and mature cell populations residing in skeletal muscle. Our data using clonal assays and a second-generation inducible reprogramming system indicate that stem cells found in mouse muscle, including resident satellite cells and mesenchymal progenitors, reprogram with significantly greater efficiency than their more differentiated daughters (myoblasts and fibroblasts). However, in contrast to previous reports, we find no evidence of biased differentiation potential among iPS cells derived from myogenically committed cells. These data support the notion that adult stem cells reprogram more efficiently than terminally differentiated cells, and argue against the suggestion that “epigenetic memory” significantly influences the differentiation potential of iPS cells derived from distinct somatic cell lineages in skeletal muscle. PMID:22028872

Management of ATM-based networks supporting multimedia medical information systems

NASA Astrophysics Data System (ADS)

Whitman, Robert A.; Blaine, G. James; Fritz, Kevin; Goodgold, Ken; Heisinger, Patrick

1997-05-01

Medical information systems are acquiring the ability to collect and deliver many different types of medical information. In support of the increased network demands necessitated by these expanded capabilities, asynchronous transfer mode (ATM) based networks are being deployed in medical care systems. While ATM supplies a much greater line rate than currently deployed networks, the management and standards surrounding ATM are yet to mature. This paper explores the management and control issues surrounding an ATM network supporting medical information systems, and examines how management impacts network performance and robustness. A multivendor ATM network at the BJC Health System/Washington University and the applications using the network are discussed. Performance information for specific applications is presented and analyzed. Network management's influence on application reliability is outlined. The information collected is used to show how ATM network standards and management tools influence network reliability and performance. Performance of current applications using the ATM network is discussed. Special attention is given to issues encountered in implementation of hypertext transfer protocol over ATM internet protocol (IP) communications. A classical IP ATM implementation yields greater than twenty percent higher network performance over LANE. Maximum performance for a host's suite of applications can be obtained by establishing multiple individually engineered IP links through its ATM network connection.

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.

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

Parallel factor ChIP provides essential internal control for quantitative differential ChIP-seq.

PubMed

Guertin, Michael J; Cullen, Amy E; Markowetz, Florian; Holding, Andrew N

2018-04-17

A key challenge in quantitative ChIP combined with high-throughput sequencing (ChIP-seq) is the normalization of data in the presence of genome-wide changes in occupancy. Analysis-based normalization methods were developed for transcriptomic data and these are dependent on the underlying assumption that total transcription does not change between conditions. For genome-wide changes in transcription factor (TF) binding, these assumptions do not hold true. The challenges in normalization are confounded by experimental variability during sample preparation, processing and recovery. We present a novel normalization strategy utilizing an internal standard of unchanged peaks for reference. Our method can be readily applied to monitor genome-wide changes by ChIP-seq that are otherwise lost or misrepresented through analytical normalization. We compare our approach to normalization by total read depth and two alternative methods that utilize external experimental controls to study TF binding. We successfully resolve the key challenges in quantitative ChIP-seq analysis and demonstrate its application by monitoring the loss of Estrogen Receptor-alpha (ER) binding upon fulvestrant treatment, ER binding in response to estrodiol, ER mediated change in H4K12 acetylation and profiling ER binding in patient-derived xenographs. This is supported by an adaptable pipeline to normalize and quantify differential TF binding genome-wide and generate metrics for differential binding at individual sites.

Three-dimensional printing and deformation behavior of low-density target structures by two-photon polymerization

NASA Astrophysics Data System (ADS)

Liu, Ying; Stein, Ori; Campbell, John H.; Jiang, Lijia; Petta, Nicole; Lu, Yongfeng

2017-08-01

Two-photon polymerization (2PP), a 3D nano to microscale additive manufacturing process, is being used for the first time to fabricate small custom experimental packages ("targets") to support laser-driven high-energy-density (HED) physics research. Of particular interest is the use of 2PP to deterministically print low-density, low atomic-number (CHO) polymer matrices ("foams") at millimeter scale with sub-micrometer resolution. Deformation during development and drying of the foam structures remains a challenge when using certain commercial photo-resins; here we compare use of acrylic resins IP-S and IP-Dip. The mechanical strength of polymeric beam and foam structures is examined particularly the degree of deformation that occurs during the development and drying processes. The magnitude of the shrinkage in the two resins in quantified by printing sample structures and by use of FEA to simulate the deformation. Capillary drying forces are shown to be small and likely below the elastic limit of the core foam structure. In contrast the substantial shrinkage in IP-Dip ( 5-10%) cause large shear stresses and associated plastic deformation particularly near constrained boundaries such as the substrate and locations with sharp density variation. The inherent weakness of stitching boundaries is also evident and in certain cases can lead to delamination. Use of IP-S shows marked reduction in deformation with a minor loss of print resolution

Workable solutions to FP in Africa.

PubMed

1991-12-01

The 3rd Pan African Conference on the Integrated Family Planning, Nutrition and Parasite Control Project (PANFRICO III) was held in October 1991 and organized by JOICFP, UNFPA and IPPF. The Ghana IP Steering Committee implemented it. In addition to the 5 IP implementing countries--Ethiopia, the Gambia, Ghana, Tanzania, and Zambia--other countries attending were: Kenya, Lesotho, Madagascar, Mali, Nigeria, Senegal, Sierra Leone, Swaziland, Togo, and Uganda. Governmental and nongovernmental organizations (NGOs) and international groups such as UNFPA, IPPF, FAO, and USAID also attended. The theme was seeking a strategic approach to family planning through primary health care. Participants resolved to increase the support and involvement of African governments in IP implementation. It was recognized that self-reliance, cost effectiveness, and efficient use of resources were important to sustainability. It was also agreed that IP should integrate family planning (FP) with Maternal and Child Health (MCH) and Primary Health Care (PHC) in order to overcome traditional and cultural obstacles to FP and to gain full participation of men in the communities. Horizontal integration was the primary thrust. there was agreement that there should be collaboration between UNFPA, IPPF, and JOICFP, and relevant governments and NGOs. Country-specific attention needs to be paid to expanding IP functions within the 5 IP countries. In Ghana, IP pilot areas have been successful in increasing the FP acceptance rate from 17.4% in 1988 to 51.9% in 1991. IP experiences in Indonesia were presented, including the concept of fee-charged PHC services in order to achieve self-reliance in FP/MCH projects. The response was the request for further technical cooperation between developing countries. The workshop activities were particularly beneficial, and requests were made for discussion of IEC, management, service delivery, nutrition, environmental sanitation, self-reliance, community participation, and evaluation. To further regional IP development within the country, it was suggested that national workshops be held. It was emphasized that FP and population are basic elements of socioeconomic development.

Host responses to interspecific brood parasitism: a by-product of adaptations to conspecific parasitism?

PubMed Central

2014-01-01

Background Why have birds evolved the ability to reject eggs? Typically, foreign egg discrimination is interpreted as evidence that interspecific brood parasitism (IP) has selected for the host’s ability to recognize and eliminate foreign eggs. Fewer studies explore the alternative hypothesis that rejection of interspecific eggs is a by-product of host defenses, evolved against conspecific parasitism (CP). We performed a large scale study with replication across taxa (two congeneric Turdus thrushes), space (populations), time (breeding seasons), and treatments (three types of experimental eggs), using a consistent design of egg rejection experiments (n = 1057 nests; including controls), in areas with potential IP either present (Europe; native populations) or absent (New Zealand; introduced populations). These comparisons benefited from the known length of allopatry (one and a half centuries), with no gene flow between native and introduced populations, which is rarely available in host-parasite systems. Results Hosts rejected CP at unusually high rates for passerines (up to 60%). CP rejection rates were higher in populations with higher conspecific breeding densities and no risks of IP, supporting the CP hypothesis. IP rejection rates did not covary geographically with IP risk, contradicting the IP hypothesis. High egg rejection rates were maintained in the relatively long-term isolation from IP despite non-trivial rejection costs and errors. Conclusions These egg rejection patterns, combined with recent findings that these thrushes are currently unsuitable hosts of the obligate parasitic common cuckoo (Cuculus canorus), are in agreement with the hypothesis that the rejection of IP is a by-product of fine-tuned egg discrimination evolved due to CP. Our study highlights the importance of considering both IP and CP simultaneously as potential drivers in the evolution of egg discrimination, and illustrates how populations introduced to novel ecological contexts can provide critical insights into brood parasite-host coevolution. PMID:24834103

Host responses to interspecific brood parasitism: a by-product of adaptations to conspecific parasitism?

PubMed

Samas, Peter; Hauber, Mark E; Cassey, Phillip; Grim, Tomas

2014-01-01

Why have birds evolved the ability to reject eggs? Typically, foreign egg discrimination is interpreted as evidence that interspecific brood parasitism (IP) has selected for the host's ability to recognize and eliminate foreign eggs. Fewer studies explore the alternative hypothesis that rejection of interspecific eggs is a by-product of host defenses, evolved against conspecific parasitism (CP). We performed a large scale study with replication across taxa (two congeneric Turdus thrushes), space (populations), time (breeding seasons), and treatments (three types of experimental eggs), using a consistent design of egg rejection experiments (n = 1057 nests; including controls), in areas with potential IP either present (Europe; native populations) or absent (New Zealand; introduced populations). These comparisons benefited from the known length of allopatry (one and a half centuries), with no gene flow between native and introduced populations, which is rarely available in host-parasite systems. Hosts rejected CP at unusually high rates for passerines (up to 60%). CP rejection rates were higher in populations with higher conspecific breeding densities and no risks of IP, supporting the CP hypothesis. IP rejection rates did not covary geographically with IP risk, contradicting the IP hypothesis. High egg rejection rates were maintained in the relatively long-term isolation from IP despite non-trivial rejection costs and errors. These egg rejection patterns, combined with recent findings that these thrushes are currently unsuitable hosts of the obligate parasitic common cuckoo (Cuculus canorus), are in agreement with the hypothesis that the rejection of IP is a by-product of fine-tuned egg discrimination evolved due to CP. Our study highlights the importance of considering both IP and CP simultaneously as potential drivers in the evolution of egg discrimination, and illustrates how populations introduced to novel ecological contexts can provide critical insights into brood parasite-host coevolution.

Xeno-free culture of human pluripotent stem cells on oligopeptide-grafted hydrogels with various molecular designs

PubMed Central

Chen, Yen-Ming; Chen, Li-Hua; Li, Meng-Pei; Li, Hsing-Fen; Higuchi, Akon; Kumar, S. Suresh; Ling, Qing-Dong; Alarfaj, Abdullah A.; Munusamy, Murugan A.; Chang, Yung; Benelli, Giovanni; Murugan, Kadarkarai; Umezawa, Akihiro

2017-01-01

Establishing cultures of human embryonic (ES) and induced pluripotent (iPS) stem cells in xeno-free conditions is essential for producing clinical-grade cells. Development of cell culture biomaterials for human ES and iPS cells is critical for this purpose. We designed several structures of oligopeptide-grafted poly (vinyl alcohol-co-itaconic acid) hydrogels with optimal elasticity, and prepared them in formations of single chain, single chain with joint segment, dual chain with joint segment, and branched-type chain. Oligopeptide sequences were selected from integrin- and glycosaminoglycan-binding domains of the extracellular matrix. The hydrogels grafted with vitronectin-derived oligopeptides having a joint segment or a dual chain, which has a storage modulus of 25 kPa, supported the long-term culture of human ES and iPS cells for over 10 passages. The dual chain and/or joint segment with cell adhesion molecules on the hydrogels facilitated the proliferation and pluripotency of human ES and iPS cells. PMID:28332572

Xeno-free culture of human pluripotent stem cells on oligopeptide-grafted hydrogels with various molecular designs.

PubMed

Chen, Yen-Ming; Chen, Li-Hua; Li, Meng-Pei; Li, Hsing-Fen; Higuchi, Akon; Kumar, S Suresh; Ling, Qing-Dong; Alarfaj, Abdullah A; Munusamy, Murugan A; Chang, Yung; Benelli, Giovanni; Murugan, Kadarkarai; Umezawa, Akihiro

2017-03-23

Establishing cultures of human embryonic (ES) and induced pluripotent (iPS) stem cells in xeno-free conditions is essential for producing clinical-grade cells. Development of cell culture biomaterials for human ES and iPS cells is critical for this purpose. We designed several structures of oligopeptide-grafted poly (vinyl alcohol-co-itaconic acid) hydrogels with optimal elasticity, and prepared them in formations of single chain, single chain with joint segment, dual chain with joint segment, and branched-type chain. Oligopeptide sequences were selected from integrin- and glycosaminoglycan-binding domains of the extracellular matrix. The hydrogels grafted with vitronectin-derived oligopeptides having a joint segment or a dual chain, which has a storage modulus of 25 kPa, supported the long-term culture of human ES and iPS cells for over 10 passages. The dual chain and/or joint segment with cell adhesion molecules on the hydrogels facilitated the proliferation and pluripotency of human ES and iPS cells.

Advancing High Current Startup via Localized Helicity Injection in the PEGASUS Toroidal Experiment

NASA Astrophysics Data System (ADS)

Hinson, E. T.; Barr, J. L.; Bongard, M. W.; Burke, M. G.; Fonck, R. J.; Perry, J. M.; Redd, A. J.; Schlossberg, D. J.

2013-10-01

Non-solenoidal startup via local helicity injection (LHI) and poloidal field induction is used to produce Ip = 0 . 17 MA tokamak discharges. Impurity contamination has been reduced to negligible levels by use of conical frustum cathode geometry and local scraper limiters. Attainable currents are governed by global limits of helicity and energy balance, and Taylor relaxation. A simple lumped parameter model based on these limits is used to project discharge evolution, and indicates that attaining 1 MA in NSTX-U will require LHI-driven effective loop voltages to dominate contributions from dLp / dt . This regime contrasts with results to date and will be tested at 0.3 MA in PEGASUS with a new integrated multi-injector array. Injector impedance characteristics are consistent with magnetically-limited regimes observed in higher-power foilless diodes. Bursts of MHD are measured on time scales of order ~ 100 μ s, and correlate with rapid equilibrium changes, discrete rises in Ip, redistribution of the toroidal current, ion heating (Ti ~ 1 keV), transient drops in injector voltage, and apparent n = 1 line-tied kink activity at the injector. NIMROD simulations of high-field-side HI discharges in PEGASUS are in qualitative agreement, suggesting Ip buildup results from inward propagating toroidal current loops created by intermittent reconnection of injected current streams. Work supported by US DOE Grant DE-FG02-96ER54375.

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

Crystal structure of a trapped catalytic intermediate suggests that forced atomic proximity drives the catalysis of mIPS.

PubMed

Neelon, Kelly; Roberts, Mary F; Stec, Boguslaw

2011-12-07

1-L-myo-inositol-phosphate synthase (mIPS) catalyzes the first step of the unique, de novo pathway of inositol biosynthesis. However, details about the complex mIPS catalytic mechanism, which requires oxidation, enolization, intramolecular aldol cyclization, and reduction, are not fully known. To gain further insight into this mechanism, we determined the crystal structure of the wild-type mIPS from Archaeoglobus fulgidus at 1.7 Å, as well as the crystal structures of three active-site mutants. Additionally, we obtained the structure of mIPS with a trapped 5-keto-glucose-6-phosphate intermediate at 2 Å resolution by a novel (to our knowledge) process of activating the crystal at high temperature. A comparison of all of the crystal structures of mIPS described in this work suggests a novel type of catalytic mechanism that relies on the forced atomic proximity of functional groups. The lysine cluster is contained in a small volume in the active site, where random motions of these side chains are responsible for the progress of the complex multistep reaction as well as for the low rate of catalysis. The mechanism requires that functional groups of Lys-274, Lys-278, Lys-306, and Lys-367 assume differential roles in the protonation/deprotonation steps that must occur during the mIPS reaction. This mechanism is supported by the complete loss of activity of the enzyme caused by the Leu-257 mutation to Ala that releases the lysine containment. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

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

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.

Spacewire Routers Implemented with FPGA Technology

NASA Astrophysics Data System (ADS)

Habinc, Sandi; Isomaki, Marko

2011-08-01

Routers are an integral part of SpaceWire networks. Aeroflex Gaisler has developed a highly configurable SpaceWire router VHDL IP core to meet the needs for technology independent router designs. The main design goals have been configurability, technology independence, support of the standard and expandability. The IP core being technologically independent allows it to be used in both ASIC and FPGA technology. The latter is now being used to produce versatile standard products that can reach the market faster than for example an ASIC based product.

Developing an Interface to Order and Document Health Education Videos in the Electronic Health Record.

PubMed

Wojcik, Lauren

2015-01-01

Transitioning to electronic health records (EHRs) provides an opportunity for health care systems to integrate educational content available on interactive patient systems (IPS) with the medical documentation system. This column discusses how one hospital simplified providers' workflow by making it easier to order educational videos and ensure that completed education is documented within the medical record. Integrating the EHR and IPS streamlined the provision of patient education, improved documentation, and supported the organization in meeting core requirements for Meaningful Use.

Eielson Air Force Base Infrastructure Development in Support of RED FLAG-Alaska Environmental Assessment

DTIC Science & Technology

2007-08-01

areas includes Labrador tea, lowbush cranberry, and blueberry . Red squirrels use the spruce cones for food and mosses for nests. Marten use the spruce...in g M at er ia ls h an dl in g St at io na ry E qu ip m en t p ow er ed b y in te rn al c om bu st io n en gi ne s Im pa ct e qu ip m en t O

People are satisfied with it.

PubMed

Hata, K

1992-08-01

The success of the integrated Family Planning (FP) and Parasite Control Project (IP) of Indonesia is discussed in terms of the government's view, the major characteristics of IP, the major problem, future funding sources, the purposes of community participation, obstacles encountered, and impact. Ministry policymakers consider IP effective and desirable, and suggest IP in remote areas with poor infrastructure such as Lombok in West Nusa Tenggara Province. Health is improved for parents and children initially. The project is self-reliant with small, affordable fees. Support has come from the Indonesian Planned Parenthood Association and Kusuma Buana Foundation; although external financial assistance has ceased, expansion is possible with the income generated. The Jakarta Municipal government may pick up the cost of implementing it through the public health center Pukesmas, either with existing project staff or local staff in collaboration with IP staff. The government is not ready to implement it because control of intestinal parasites is of low priority. Major problems are the uneven performance particularly in IP bases in Jakarta, which is attributed to lack of concern by managers for community health conditions. Community participation is important because people are eager to learn how to prevent the parasitic invasions after being successfully treated. When success in cleaning houses and toilets and lower incidence of infection is accomplished, then people trust and use the health services more. Obstacles have been the cost of building hygienic latrines and access to safe and potable water, particularly in slum areas of Jakarta, and changing institutional representation on the IP project National Coordinating Forum, the IP policy making group, and officials from government FP and Health and Education Departments. Government officials need to understand the intricacies of how IP operates. Evaluation is difficult with measures such as the fertility rate or infant mortality rate. Project staff are satisfied with the increase in health consciousness of clients, and the use of paid services. A study by the Forum found that FP participation among the target community increased compared with baseline data, but FP information is available from multiple sources in Jakarta and it would be presumptuous to believe that community participation was solely due to IP.

Production of photons in relativistic heavy-ion collisions

DOE PAGES

Jean -Francois Paquet; Denicol, Gabriel S.; Shen, Chun; ...

2016-04-18

In this work it is shown that the use of a hydrodynamical model of heavy-ion collisions which incorporates recent developments, together with updated photon emission rates, greatly improves agreement with both ALICE and PHENIX measurements of direct photons, supporting the idea that thermal photons are the dominant source of direct photon momentum anisotropy. The event-by-event hydrodynamical model uses the impact parameter dependent Glasma model (IP-Glasma) initial states and includes, for the first time, both shear and bulk viscosities, along with second-order couplings between the two viscosities. Furthermore, the effect of both shear and bulk viscosities on the photon rates ismore » studied, and those transport coefficients are shown to have measurable consequences on the photon momentum anisotropy.« less

Improving access to competitive employment for service users in forensic psychiatric units

PubMed Central

Beck, Charlotte; Wernham, Connie

2014-01-01

Employment has been proven to be an effective recovery tool and therapeutic intervention for those with severe and enduring mental health conditions. Aside from monetary reward, employment is a means of structuring time and provides a sense of worth and achievement, which enhances self-esteem and confidence. A social identity is developed through employment, encouraging social support and increasing social networks. Securing employment can bring about improved quality of life and positive change in one's social circumstances; therefore it can reduce symptoms associated with mental illness and potentially prevent re-offending, as the individual develops a sense of independence, self-efficacy, and value. Barriers to employment exist for forensic mental health service users and therefore it is imperative that employment needs are addressed at the earliest possible stage in recovery. An evaluation of employment activities across two forensic mental health units revealed a lack of appropriate employment opportunities for service users, and those roles available were not implemented in line with recommended best practice. In response to this issue several enterprises were established to offer opportunities for service users to engage in meaningful employment and develop skills that a future employer would value. Each enterprise responds to a business need within the units to ensure sustainability of services. The enterprises are essentially micro-businesses with social objectives whose surpluses are reinvested for the purpose of increasing opportunities for service users. The enterprises are underpinned by the philosophy of the Individual Placement and Support (IPS) model; empirical evidence suggests that the IPS model is the most effective intervention, based on the ‘place then train’ philosophy. The model recommends a focus upon rapid job search to achieve competitive employment for those who want to work; opportunities sourced should be consistent with individual preference and benefits counselling offered. Support should be time unlimited and integrated with mental health treatment. A person-centred and strengths-based approach is also adopted to support people to build on their strengths, establish goals, and encourage motivation. PMID:26734271

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

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.

Calcium bioavailability of vegetarian diets in rats: potential application in a bioregenerative life-support system.

PubMed

Nickel, K P; Nielsen, S S; Smart, D J; Mitchell, C A; Belury, M A

1997-01-01

Calcium bioavailability of vegetarian diets containing various proportions of candidate crops for a controlled ecological life-support system (CELSS) was determined by femur 45Ca uptake. Three vegetarian diets and a control diet were labeled extrinsically with 45Ca and fed to 5-wk old male rats. A fifth group of rats fed an unlabeled control diet received an intraperitoneal (IP) injection of 45Ca. There was no significant difference in mean calcium absorption of vegetarian diets (90.80 +/- 5.23%) and control diet (87.85 +/- 5.25%) when calculated as the percent of an IP dose. The amounts of phytate, oxalate, and dietary fiber in the diets did not affect calcium absorption.

Calcium bioavailability of vegetarian diets in rats: potential application in a bioregenerative life-support system

NASA Technical Reports Server (NTRS)

Nickel, K. P.; Nielsen, S. S.; Smart, D. J.; Mitchell, C. A.; Belury, M. A.

1997-01-01

Calcium bioavailability of vegetarian diets containing various proportions of candidate crops for a controlled ecological life-support system (CELSS) was determined by femur 45Ca uptake. Three vegetarian diets and a control diet were labeled extrinsically with 45Ca and fed to 5-wk old male rats. A fifth group of rats fed an unlabeled control diet received an intraperitoneal (IP) injection of 45Ca. There was no significant difference in mean calcium absorption of vegetarian diets (90.80 +/- 5.23%) and control diet (87.85 +/- 5.25%) when calculated as the percent of an IP dose. The amounts of phytate, oxalate, and dietary fiber in the diets did not affect calcium absorption.

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.

Direct renin inhibition modulates insulin resistance in caveolin-1-deficient mice

PubMed Central

Chuengsamarn, Somlak; Garza, Amanda E.; Krug, Alexander W.; Romero, Jose R.; Adler, Gail K.; Williams, Gordon H.; Pojoga, Luminita H.

2012-01-01

Objective To test the hypothesis that aliskiren improves the metabolic phenotype in a genetic mouse model of the metabolic syndrome (the caveolin-1 knock out (KO) mouse). Materials/Methods Eleven-week-old cav-1 KO and genetically matched wild-type (WT) mice were randomized to three treatment groups: placebo (n = 8/group), amlodipine (6 mg/kg/day, n = 18/ group), and aliskiren (50 mg/kg/day, n = 18/ group). After three weeks of treatment, all treatment groups were assessed for several measures of insulin resistance (fasting insulin and glucose, HOMA-IR, and the response to an intraperitoneal glucose tolerance test (ipGTT)) as well as for triglyceride levels and the blood pressure response to treatment. Results Treatment with aliskiren did not affect the ipGTT response but significantly lowered the HOMA-IR and insulin levels in cav-1 KO mice. However, treatment with amlodipine significantly degraded the ipGTT response, as well as the HOMA-IR and insulin levels in the cav-1 KO mice. Aliskiren also significantly lowered triglyceride levels in the cav-1 KO but not in the WT mice. Moreover, aliskiren treatment had a significantly greater effect on blood pressure readings in the cav-1 KO vs. WT mice, and marginally more effective than amlodipine. Conclusions Our results support the hypothesis that aliskiren reduces insulin resistance as indicated by improved HOMA-IR in cav-1 KO mice whereas amlodipine treatment resulted in changes consistent with increased insulin resistance. In addition, aliskiren was substantially more effective in lowering blood pressure in the cav-1 KO mouse model than in WT mice and marginally more effective than amlodipine. PMID:22954672

Attenuating illusory binding with TMS of the right parietal cortex

PubMed Central

Esterman, Michael; Verstynen, Timothy; Robertson, Lynn C.

2007-01-01

A number of neuroimaging and neuropsychology studies have implicated various regions of parietal cortex as playing a critical role in the binding of color and form into conjunctions. The current study investigates the role of two such regions by examining how parietal transcranial magnetic stimulation (TMS) influences binding errors known as ‘illusory conjunctions.’ Participants made fewer binding errors after 1 Hz rTMS of the right intraparietal sulcus (IPS), while basic perception of features (colors and shape) was unaffected. No perceptual effects were found following left IPS stimulation, or stimulation of the right angular gyrus at the junction of the transverse occipital sulcus (IPS/TOS). These results support a role for the parietal cortex in feature binding but in ways that may require rethinking. PMID:17336097

Modifications of the ionosphere prior to large earthquakes: report from the Ionosphere Precursor Study Group

NASA Astrophysics Data System (ADS)

Oyama, K.-I.; Devi, M.; Ryu, K.; Chen, C. H.; Liu, J. Y.; Liu, H.; Bankov, L.; Kodama, T.

2016-12-01

The current status of ionospheric precursor studies associated with large earthquakes (EQ) is summarized in this report. It is a joint endeavor of the "Ionosphere Precursor Study Task Group," which was formed with the support of the Mitsubishi Foundation in 2014-2015. The group promotes the study of ionosphere precursors (IP) to EQs and aims to prepare for a future EQ dedicated satellite constellation, which is essential to obtain the global morphology of IPs and hence demonstrate whether the ionosphere can be used for short-term EQ predictions. Following a review of the recent IP studies, the problems and specific research areas that emerged from the one-year project are described. Planned or launched satellite missions dedicated (or suitable) for EQ studies are also mentioned.

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.

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.

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

Neuropharmacological effects of essential oil from the leaves of Croton conduplicatus Kunth and possible mechanisms of action involved.

PubMed

Oliveira Júnior, Raimundo Gonçalves de; Ferraz, Christiane Adrielly Alves; Silva, Juliane Cabral; de Andrade Teles, Roxana Braga; Silva, Mariana Gama; Diniz, Tâmara Coimbra; Dos Santos, Uiliane Soares; de Souza, Ana Valéria Vieira; Nunes, Carlos Eduardo Pereira; Salvador, Marcos José; Lorenzo, Vitor Prates; Quintans Júnior, Lucindo José; Almeida, Jackson Roberto Guedes da Silva

2018-07-15

Croton conduplicatus Kunth (Euphorbiaceae) is a Brazilian aromatic medicinal plant, widely known as "quebra-faca". In folk medicine, its leaves and stem-barks are used as a natural analgesic for the treatment of headaches. In this study, we describe for the first time the neuropharmacological potential of the essential oil obtained from the leaves of Croton conduplicatus (EO) in experimental models of pain, anxiety and insomnia. The mechanisms of action involved in these activities were also investigated. Different experimental models were used to evaluate the antinociceptive (acetic acid, formalin-induced nociception and hot plate tests), anxiolytic (elevated plus maze and hole board tests) and sedative (thiopental-induced sleeping time) effects of EO in mice. EO was evaluated in three different doses (25, 50 and 100 mg/kg, i.p.) and compared with positive and negative controls in all experimental protocols. When appropriate, animals were pretreated with pharmacological antagonists (naloxone, atropine and flumazenil) in order to evaluate the mechanisms of action involved. A docking study also was performed to identify possible targets involved. EO (25, 50 and 100 mg/kg, i.p.) demonstrated a significant antinociceptive activity in all experimental models. Pretreatment with naloxone or atropine reversed the antinociceptive response (p < 0.05), suggesting the involvement of opioid and muscarinic receptors, respectively. A docking study was performed with the major components identified in EO (1,8 cineole - 21.42%, spathulenol - 15.47%, p-cymene - 12.41% and caryophyllene oxide - 12.15%), demonstrating favorable interaction profile with different subtypes of muscarinic (M2, M3 and M4) and opioids (delta and mu) receptors. EO also showed anxiolytic (mainly at doses of 25 and 50 mg/kg, i.p.) and sedative (only at the dose of 100 mg/kg, i.p.) effects in mice. These pharmacological responses were reversed by flumazenil (p < 0.05), indicating possible involvement of GABA A receptors. Our findings support the traditional use of this plant as a natural analgesic and suggest that EO is a multi-target natural product, presenting not only antinociceptive effect but also anxiolytic and sedative activities depending on the dose used. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Using the Social Enterprise Intervention (SEI) and Individual Placement and Support (IPS) models to improve employment and clinical outcomes of homeless youth with mental illness1

PubMed Central

Ferguson, Kristin M.

2013-01-01

Prior research reveals high unemployment rates among homeless youth. The literature offers many examples of using evidence-informed and evidence-based supported employment models with vulnerable populations to assist them in obtaining and maintaining employment and concurrently addressing mental health challenges. However, there are few examples to date of these models with homeless youth with mental illness. The purpose of this article was thus to describe a methodology for establishing a university-agency research partnership to design, implement, evaluate, and replicate evidence-informed and evidence-based interventions with homeless youth with mental illness to enhance their employment, mental health, and functional outcomes. Data from two studies are used to illustrate the relationship between vocational skill-building/employment and mental health among homeless youth. The article concludes with a discussion of the implications of conducting community-based participatory employment and clinical intervention research. The author highlights the opportunities and tensions associated with this approach. PMID:24294127

Using the Social Enterprise Intervention (SEI) and Individual Placement and Support (IPS) models to improve employment and clinical outcomes of homeless youth with mental illness.

PubMed

Ferguson, Kristin M

2013-09-01

Prior research reveals high unemployment rates among homeless youth. The literature offers many examples of using evidence-informed and evidence-based supported employment models with vulnerable populations to assist them in obtaining and maintaining employment and concurrently addressing mental health challenges. However, there are few examples to date of these models with homeless youth with mental illness. The purpose of this article was thus to describe a methodology for establishing a university-agency research partnership to design, implement, evaluate, and replicate evidence-informed and evidence-based interventions with homeless youth with mental illness to enhance their employment, mental health, and functional outcomes. Data from two studies are used to illustrate the relationship between vocational skill-building/employment and mental health among homeless youth. The article concludes with a discussion of the implications of conducting community-based participatory employment and clinical intervention research. The author highlights the opportunities and tensions associated with this approach.

Intensive-phase treatment outcomes among hospitalized multidrug-resistant tuberculosis patients: results from a nationwide cohort in Nigeria.

PubMed

Oladimeji, Olanrewaju; Isaakidis, Petros; Obasanya, Olusegun J; Eltayeb, Osman; Khogali, Mohammed; Van den Bergh, Rafael; Kumar, Ajay M V; Hinderaker, Sven Gudmund; Abdurrahman, Saddiq T; Lawson, Lovett; Cuevas, Luis E

2014-01-01

Nigeria is faced with a high burden of Human Immunodeficiency Virus (HIV) infection and multidrug-resistant tuberculosis (MDR-TB). Treatment outcomes among MDR-TB patients registered across the globe have been poor, partly due to high loss-to-follow-up. To address this challenge, MDR-TB patients in Nigeria are hospitalized during the intensive-phase(IP) of treatment (first 6-8 months) and are provided with a package of care including standardized MDR-TB treatment regimen, antiretroviral therapy (ART) and cotrimoxazole prophylaxis (CPT) for HIV-infected patients, nutritional and psychosocial support. In this study, we report the end-IP treatment outcomes among them. In this retrospective cohort study, we reviewed the patient records of all bacteriologically-confirmed MDR-TB patients admitted for treatment between July 2010 and October 2012. Of 162 patients, 105(65%) were male, median age was 34 years and 28(17%) were HIV-infected; all 28 received ART and CPT. Overall, 138(85%) were alive and culture negative at the end of IP, 24(15%) died and there was no loss-to-follow-up. Mortality was related to low CD4-counts at baseline among HIV-positive patients. The median increase in body mass index among those documented to be underweight was 2.6 kg/m2 (p<0.01) and CD4-counts improved by a median of 52 cells/microL among the HIV-infected patients (p<0.01). End-IP treatment outcomes were exceptional compared to previously published data from international cohorts, thus confirming the usefulness of a hospitalized model of care. However, less than five percent of all estimated 3600 MDR-TB patients in Nigeria were initiated on treatment during the study period. Given the expected scale-up of MDR-TB care, the hospitalized model is challenging to sustain and the national TB programme is contemplating to move to ambulatory care. Hence, we recommend using both ambulatory and hospitalized approaches, with the latter being reserved for selected high-risk groups.

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

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.

Psychoses in epilepsy: A comparison of postictal and interictal psychoses.

PubMed

Hilger, Eva; Zimprich, Friedrich; Pataraia, Ekaterina; Aull-Watschinger, Susanne; Jung, Rebekka; Baumgartner, Christoph; Bonelli, Silvia

2016-07-01

We retrospectively analyzed data of patients with epilepsy (n=1434) evaluated with prolonged EEG monitoring in order to estimate the prevalence of postictal psychosis (PP) and interictal psychosis (IP), to investigate a potential association of psychosis subtype with epilepsy type, and to assess differences between PP and IP. The overall prevalence of psychosis was 5.9% (N=85); prevalence of PP (N=53) and IP (N=32) was 3.7% and 2.2%, respectively. Of patients with psychosis, 97.6% had localization-related epilepsy (LRE). Prevalence of psychosis was highest (9.3%) in patients with temporal lobe epilepsy (TLE). When comparing PP with IP groups on demographic, clinical, and psychopathological variables, patients with IP were younger at occurrence of first psychosis (P=0.048), had a shorter interval between epilepsy onset and first psychosis (P=0.002), and more frequently exhibited schizophreniform traits (conceptual disorganization: P=0.008; negative symptoms: P=0.017) than those with PP. Postictal psychosis was significantly associated with a temporal seizure onset on ictal EEG (P=0.000) and a higher incidence of violent behavior during psychosis (P=0.047). To conclude, our results support the presumption of a preponderance of LRE in patients with psychosis and that of a specific association of TLE with psychosis, in particular with PP. Given the significant differences between groups, PP and IP may represent distinct clinical entities potentially with a different neurobiological background. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of Gated Audiovisual Speech Identification in Elderly Hearing Aid Users and Elderly Normal-Hearing Individuals

PubMed Central

Lidestam, Björn; Rönnberg, Jerker

2016-01-01

The present study compared elderly hearing aid (EHA) users (n = 20) with elderly normal-hearing (ENH) listeners (n = 20) in terms of isolation points (IPs, the shortest time required for correct identification of a speech stimulus) and accuracy of audiovisual gated speech stimuli (consonants, words, and final words in highly and less predictable sentences) presented in silence. In addition, we compared the IPs of audiovisual speech stimuli from the present study with auditory ones extracted from a previous study, to determine the impact of the addition of visual cues. Both participant groups achieved ceiling levels in terms of accuracy in the audiovisual identification of gated speech stimuli; however, the EHA group needed longer IPs for the audiovisual identification of consonants and words. The benefit of adding visual cues to auditory speech stimuli was more evident in the EHA group, as audiovisual presentation significantly shortened the IPs for consonants, words, and final words in less predictable sentences; in the ENH group, audiovisual presentation only shortened the IPs for consonants and words. In conclusion, although the audiovisual benefit was greater for EHA group, this group had inferior performance compared with the ENH group in terms of IPs when supportive semantic context was lacking. Consequently, EHA users needed the initial part of the audiovisual speech signal to be longer than did their counterparts with normal hearing to reach the same level of accuracy in the absence of a semantic context. PMID:27317667

Phosphoinositide and Inositol Phosphate Analysis in Lymphocyte Activation

PubMed Central

Sauer, Karsten; Huang, Yina Hsing; Lin, Hongying; Sandberg, Mark; Mayr, Georg W.

2015-01-01

Lymphocyte antigen receptor engagement profoundly changes the cellular content of phosphoinositide lipids and soluble inositol phosphates. Among these, the phosphoinositides phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) play key signaling roles by acting as pleckstrin homology (PH) domain ligands that recruit signaling proteins to the plasma membrane. Moreover, PIP2 acts as a precursor for the second messenger molecules diacylglycerol and soluble inositol 1,4,5-trisphosphate (IP3), essential mediators of PKC, Ras/Erk, and Ca2+ signaling in lymphocytes. IP3 phosphorylation by IP3 3-kinases generates inositol 1,3,4,5-tetrakisphosphate (IP4), an essential soluble regulator of PH domain binding to PIP3 in developing T cells. Besides PIP2, PIP3, IP3, and IP4, lymphocytes produce multiple other phosphoinositides and soluble inositol phosphates that could have important physiological functions. To aid their analysis, detailed protocols that allow one to simultaneously measure the levels of multiple different phosphoinositide or inositol phosphate isomers in lymphocytes are provided here. They are based on thin layer, conventional and high-performance liquid chromatographic separation methods followed by radiolabeling or non-radioactive metal-dye detection. Finally, less broadly applicable nonchromatographic methods for detection of specific phosphoinositide or inositol phosphate isomers are discussed. Support protocols describe how to obtain pure unstimulated CD4+CD8+ thymocyte populations for analyses of inositol phosphate turnover during positive and negative selection, key steps in T cell development. PMID:19918943

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.

Preclinical evidence of the anxiolytic and sedative-like activities of Tagetes erecta L. reinforces its ethnobotanical approach.

PubMed

Pérez-Ortega, Gimena; Angeles-López, Guadalupe Esther; Argueta-Villamar, Arturo; González-Trujano, María Eva

2017-09-01

Morelos State is one of the regions of Mexico where several plant species are used in traditional medicine. Species from Tagetes genus (Asteraceae) are reported as useful in infusion to treat stomachache and intestinal diseases, but also as tranquilizers. In this study, medicinal uses of T. erecta including its depressant effect on the central nervous system (CNS) were explored by interviewing healers and merchants of local markets of Morelos State, and by investigation of the phytochemical and pharmacological tranquilizing properties. Specific anxiolytic and/or sedative-like responses of different doses of T. erecta (10, 30 and 100 or 300mg/kg, i.p.) were investigated using experimental models in mice such as: open-field, exploration cylinder, hole-board, and the barbituric-induced hypnosis potentiation. The possible anxiolytic mechanism of action was assessed in the presence of WAY100635 (0.32mg/kg, i.p.) and flumazenil (10mg/kg, i.p.), antagonists of 5-HT 1A and GABA/BDZs receptors, respectively. Individual flavonoids reported in this species were also evaluated in these experimental models. As a result of this study, healers and merchants from ten local regions of Morelos State recommended T. erecta flowers as an infusion or as a tincture for several culture-bound syndromes associated with CNS, among others. Anxiolytic and sedative-like activities of the T. erecta aqueous and organic polar extracts were corroborated in these models associated to a participation of rutin, kaempferol, quercetin, kaempferitrin, and β-sitosterol constituents; where 5-HT 1A , but not BDZs, receptors were involved as anxiolytic mechanism of action. These data support the anxiolytic and sedative-like properties of T. erecta in traditional medicine by involving mainly serotonergic neurotransmission because of the presence in part of flavonoids and the terpenoid β-sitosterol. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Observation of Image Potential State in Oxygen Intercalated Graphene on Iridium by Two-Photon-Photoemission Spectroscopy

NASA Astrophysics Data System (ADS)

Lin, Yi; Li, Yunzhe; Sadowski, Jerzy; Dadap, Jerry; Jin, Wencan; Osgood, Richard

In this talk, we report our experimental results on the first direct observation of image potential state (IPS) in oxygen-intercalated graphene on iridium by two-photo-photoemission spectroscopy. We demonstrate how oxygen intercalation influences the IPS in Gr/Ir and decouples the interlayer interaction. We present measurements of the electronic dispersion and work function in pristine Gr/Ir, oxygen-intercalated Gr/O/Ir, and deintercalated Gr/Ir. LEED patterns are measured during the pristine, oxygen-intercalated, and deintercalated phases of the Gr/Ir sample. Based on these measurements, relative to the pristine case, the work function and the energy location of n =1 IPS relative to the Fermi level increases by 0.39 eV and 0.3 eV, respectively, due to oxygen intercalation, whereas the effective mass of n =1 IPS is hardly influenced by the intercalation process. Moreover, we achieve the quenching and restoration of the resonance from Ir Rashba states to n =1 IPS in Gr/Ir by oxygen intercalation and deintercalation. This work was supported by the DOE, Office of Basic Energy Sciences, Division of MSE under Contract No. DE-FG 02-04-ER-46157. This research used resources of the CFN, which is the U.S. DOE Office of Science User Facility, under Contract No. DE-SC0012704.

The Physics of Local Helicity Injection Non-Solenoidal Tokamak Startup

NASA Astrophysics Data System (ADS)

Redd, A. J.; Barr, J. L.; Bongard, M. W.; Fonck, R. J.; Hinson, E. T.; Jardin, S.

2013-10-01

Non-solenoidal startup via Local Helicity Injection (LHI) uses compact current injectors to produce toroidal plasma current Ip up to 170 kA in the PEGASUS Toroidal Experiment, driven by 4-8 kA injector current on timescales of 5-20 milliseconds. Increasing the Ip buildup duration enables experimental demonstration of plasma position control on timescales relevant for high-current startup. LHI-driven discharges exhibit bursty MHD activity, apparently line-tied kinking of LHI-driven field lines, with the bursts correlating with rapid equilibrium changes, sharp Ip rises, and sharp drops in the injector impedance. Preliminary NIMROD results suggest that helical LHI-driven current channels remain coherent, with Ip increases due to reconnection between adjacent helical turns forming axisymmetric plasmoids, and corresponding sharp drops in the bias circuit impedance. The DC injector impedance is consistent with a space charge limit at low bias current and a magnetic limit at high bias current. Internal measurements show the current density profile starts strongly hollow and rapidly fills in during Ip buildup. Simulations of LHI discharges using the Tokamak Simulation Code (TSC) will provide insight into the detailed current drive mechanism and guide experiments on PEFASUS and NSTX-U. Work supported by US DOE Grants DE-FG02-96ER54375 and DE-SC0006928.

Integrated Service Provisioning in an Ipv6 over ATM Research Network

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

Eli Dart; Helen Chen; Jerry Friesen

1999-02-01

During the past few years, the worldwide Internet has grown at a phenomenal rate, which has spurred the proposal of innovative network technologies to support the fast, efficient and low-latency transport of a wide spectrum of multimedia traffic types. Existing network infrastructures have been plagued by their inability to provide for real-time application traffic as well as their general lack of resources and resilience to congestion. This work proposes to address these issues by implementing a prototype high-speed network infrastructure consisting of Internet Protocol Version 6 (IPv6) on top of an Asynchronous Transfer Mode (ATM) transport medium. Since ATM ismore » connection-oriented whereas IP uses a connection-less paradigm, the efficient integration of IPv6 over ATM is especially challenging and has generated much interest in the research community. We propose, in collaboration with an industry partner, to implement IPv6 over ATM using a unique approach that integrates IP over fast A TM hardware while still preserving IP's connection-less paradigm. This is achieved by replacing ATM's control software with IP's routing code and by caching IP's forwarding decisions in ATM's VPI/VCI translation tables. Prototype ''VR'' and distributed-parallel-computing applications will also be developed to exercise the realtime capability of our IPv6 over ATM network.« less

Expression and high glucose-mediated regulation of K+ channel interacting protein 3 (KChIP3) and KV4 channels in retinal Müller glial cells.

PubMed

Chavira-Suárez, Erika; Sandoval, Alejandro; Felix, Ricardo; Lamas, Mónica

2011-01-14

Normal vision depends on the correct function of retinal neurons and glia and it is impaired in the course of diabetic retinopathy. Müller cells, the main glial cells of the retina, suffer morphological and functional alterations during diabetes participating in the pathological retinal dysfunction. Recently, we showed that Müller cells express the pleiotropic protein potassium channel interacting protein 3 (KChIP3), an integral component of the voltage-gated K(+) channels K(V)4. Here, we sought to analyze the role of KChIP3 in the molecular mechanisms underlying hyperglycemia-induced phenotypic changes in the glial elements of the retina. The expression and function of KChIp3 was analyzed in vitro in rat Müller primary cultures grown under control (5.6 mM) or high glucose (25 mM) (diabetic-like) conditions. We show the up-regulation of KChIP3 expression in Müller cell cultures under high glucose conditions and demonstrate a previously unknown interaction between the K(V)4 channel and KChIP3 in Müller cells. We show evidence for the expression of a 4-AP-sensitive transient outward voltage-gated K(+) current and an alteration in the inactivation of the macroscopic outward K(+) currents expressed in high glucose-cultured Müller cells. Our data support the notion that induction of KChIP3 and functional changes of K(V)4 channels in Müller cells could exert a physiological role in the onset of diabetic retinopathy. Copyright © 2010 Elsevier Inc. All rights reserved.

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.

Primary medical care in Irish prisons.

PubMed

Barry, Joe M; Darker, Catherine D; Thomas, David E; Allwright, Shane P A; O'Dowd, Tom

2010-03-22

An industrial dispute between prison doctors and the Irish Prison Service (IPS) took place in 2004. Part of the resolution of that dispute was that an independent review of prison medical and support services be carried out by a University Department of Primary Care. The review took place in 2008 and we report here on the principal findings of that review. This study utilised a mixed methods approach. An independent expert medical evaluator (one of the authors, DT) inspected the medical facilities, equipment and relevant custodial areas in eleven of the fourteen prisons within the IPS. Semistructured interviews took place with personnel who had operational responsibility for delivery of prison medical care. Prison doctors completed a questionnaire to elicit issues such as allocation of clinician's time, nurse and administrative support and resources available. There was wide variation in the standard of medical facilities and infrastructure provided across the IPS. The range of medical equipment available was generally below that of the equivalent general practice scheme in the community. There is inequality within the system with regard to the ratio of doctor-contracted time relative to the size of the prison population. There is limited administrative support, with the majority of prisons not having a medical secretary. There are few psychiatric or counselling sessions available. People in prison have a wide range of medical care needs and there is evidence to suggest that these needs are being met inconsistently in Irish prisons.

Seven years of clinical experience with teleconsultation in craniomaxillofacial surgery.

PubMed

Ewers, Rolf; Schicho, Kurt; Wagner, Arne; Undt, Gerhard; Seemann, Rudolf; Figl, Michael; Truppe, Michael

2005-10-01

In this work the experiences from 50 telemedically supported treatments in craniomaxillofacial surgery are summarized and different setups for their technical realization are described. Furthermore, for the first time the innovative UMTS (universal mobile telecommunication system) is applied for the transmission of arthroscopic videos of the temporomandibular joint and other craniomaxillofacial structures. The combination of computer-assisted navigation technology in augmented reality environments with telecommunication is used for execution of interactive stereotaxic teleconsultation. Furthermore, treatments without navigation are telemedically supported. This study is composed of 4 technical system configurations: 1) integrated services digital network (ISDN)-based videoconferencing without remote control of the navigation computer; 2) transmission control protocol/internet protocol (TCP/IP)-based interactive teleconsultation via bundled ISDN lines (including remote control of the navigation computer); 3) TCP/IP-based interactive teleconsultation via network; 4) combination of TCP/IP-connection and ISDN-based videoconferencing. The telemedically supported treatments are: orbitozygomatic osteotomies, positioning of the mandibular condyle in orthognathic surgery, insertion of implants, positioning of the maxilla in orthognathic surgery, distraction osteogenesis, arthroscopies of the temporomandibular joint, and operation simulations on stereolithographic models. The surgical interventions are evaluated on a 5-level system performance scale from the technical point of view. In a separate trial 20 videosequences of arthroscopies of the temporomandibular joint are transmitted via UMTS cellular phones and independently evaluated by 3 experts (ie, a total of 60 streamings) to investigate feasibility of this technology in the field of craniomaxillofacial surgery. In the years from 1996 to 2002 a total of 50 treatments were telemedically supported. All intraoperative applications were successfully finished; 48 of 60 UMTS transmissions were finished without any interruptions in constant quality, slight interruptions were observed in 8 tests, and a complete breakdown was observed during 4 streamings that required a restart of the transmission. Resolution was sufficient to diagnose even tiny anatomic structures inside the temporomandibular joint, but orientation was hardly recognizable. In many applications telecommunication technology can contribute to a quality improvement in cranio- and maxillofacial surgery because of the global availability of specialized knowledge. The required technical expenditure for teleconsultation crucially depends on the infrastructure that is already available at the clinic and the remote site. UMTS is a promising technology with the potential to be valuable in numerous craniomaxillofacial applications.

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.

Models for IP/MPLS routing performance: convergence, fast reroute, and QoS impact

NASA Astrophysics Data System (ADS)

Choudhury, Gagan L.

2004-09-01

We show how to model the black-holing and looping of traffic during an Interior Gateway Protocol (IGP) convergence event at an IP network and how to significantly improve both the convergence time and packet loss duration through IGP parameter tuning and algorithmic improvement. We also explore some congestion avoidance and congestion control algorithms that can significantly improve stability of networks in the face of occasional massive control message storms. Specifically we show the positive impacts of prioritizing Hello and Acknowledgement packets and slowing down LSA generation and retransmission generation on detecting congestion in the network. For some types of video, voice signaling and circuit emulation applications it is necessary to reduce traffic loss durations following a convergence event to below 100 ms and we explore that using Fast Reroute algorithms based on Multiprotocol Label Switching Traffic Engineering (MPLS-TE) that effectively bypasses IGP convergence. We explore the scalability of primary and backup MPLS-TE tunnels where MPLS-TE domain is in the backbone-only or edge-to-edge. We also show how much extra backbone resource is needed to support Fast Reroute and how can that be reduced by taking advantage of Constrained Shortest Path (CSPF) routing of MPLS-TE and by reserving less than 100% of primary tunnel bandwidth during Fast Reroute.

Quality of Service in Networks Supporting Cultural Multimedia Applications

ERIC Educational Resources Information Center

Kanellopoulos, Dimitris N.

2011-01-01

Purpose: This paper aims to provide an overview of representative multimedia applications in the cultural heritage sector, as well as research results on quality of service (QoS) mechanisms in internet protocol (IP) networks that support such applications. Design/methodology/approach: The paper's approach is a literature review. Findings: Cultural…

Voice Over Internet Protocol (VoIP) in a Control Center Environment

NASA Technical Reports Server (NTRS)

Pirani, Joseph; Calvelage, Steven

2010-01-01

The technology of transmitting voice over data networks has been available for over 10 years. Mass market VoIP services for consumers to make and receive standard telephone calls over broadband Internet networks have grown in the last 5 years. While operational costs are less with VoIP implementations as opposed to time division multiplexing (TDM) based voice switches, is it still advantageous to convert a mission control center s voice system to this newer technology? Marshall Space Flight Center (MSFC) Huntsville Operations Support Center (HOSC) has converted its mission voice services to a commercial product that utilizes VoIP technology. Results from this testing, design, and installation have shown unique considerations that must be addressed before user operations. There are many factors to consider for a control center voice design. Technology advantages and disadvantages were investigated as they refer to cost. There were integration concerns which could lead to complex failure scenarios but simpler integration for the mission infrastructure. MSFC HOSC will benefit from this voice conversion with less product replacement cost, less operations cost and a more integrated mission services environment.

The Integrated Plasma Simulator: A Flexible Python Framework for Coupled Multiphysics Simulation

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

Foley, Samantha S; Elwasif, Wael R; Bernholdt, David E

2011-11-01

High-fidelity coupled multiphysics simulations are an increasingly important aspect of computational science. In many domains, however, there has been very limited experience with simulations of this sort, therefore research in coupled multiphysics often requires computational frameworks with significant flexibility to respond to the changing directions of the physics and mathematics. This paper presents the Integrated Plasma Simulator (IPS), a framework designed for loosely coupled simulations of fusion plasmas. The IPS provides users with a simple component architecture into which a wide range of existing plasma physics codes can be inserted as components. Simulations can take advantage of multiple levels ofmore » parallelism supported in the IPS, and can be controlled by a high-level ``driver'' component, or by other coordination mechanisms, such as an asynchronous event service. We describe the requirements and design of the framework, and how they were implemented in the Python language. We also illustrate the flexibility of the framework by providing examples of different types of simulations that utilize various features of the IPS.« less

Auditory Spatial Attention Representations in the Human Cerebral Cortex

PubMed Central

Kong, Lingqiang; Michalka, Samantha W.; Rosen, Maya L.; Sheremata, Summer L.; Swisher, Jascha D.; Shinn-Cunningham, Barbara G.; Somers, David C.

2014-01-01

Auditory spatial attention serves important functions in auditory source separation and selection. Although auditory spatial attention mechanisms have been generally investigated, the neural substrates encoding spatial information acted on by attention have not been identified in the human neocortex. We performed functional magnetic resonance imaging experiments to identify cortical regions that support auditory spatial attention and to test 2 hypotheses regarding the coding of auditory spatial attention: 1) auditory spatial attention might recruit the visuospatial maps of the intraparietal sulcus (IPS) to create multimodal spatial attention maps; 2) auditory spatial information might be encoded without explicit cortical maps. We mapped visuotopic IPS regions in individual subjects and measured auditory spatial attention effects within these regions of interest. Contrary to the multimodal map hypothesis, we observed that auditory spatial attentional modulations spared the visuotopic maps of IPS; the parietal regions activated by auditory attention lacked map structure. However, multivoxel pattern analysis revealed that the superior temporal gyrus and the supramarginal gyrus contained significant information about the direction of spatial attention. These findings support the hypothesis that auditory spatial information is coded without a cortical map representation. Our findings suggest that audiospatial and visuospatial attention utilize distinctly different spatial coding schemes. PMID:23180753

47 CFR 54.503 - Other supported special services.

Code of Federal Regulations, 2010 CFR

2010-10-01

... telecommunications carriers include voice mail, interconnected voice over Internet protocol (VoIP), text messaging, Internet access, and installation and maintenance of internal connections in addition to all reasonable...

Herpes simplex virus triggers activation of calcium-signaling pathways

PubMed Central

Cheshenko, Natalia; Del Rosario, Brian; Woda, Craig; Marcellino, Daniel; Satlin, Lisa M.; Herold, Betsy C.

2003-01-01

The cellular pathways required for herpes simplex virus (HSV) invasion have not been defined. To test the hypothesis that HSV entry triggers activation of Ca2+-signaling pathways, the effects on intracellular calcium concentration ([Ca2+]i) after exposure of cells to HSV were examined. Exposure to virus results in a rapid and transient increase in [Ca2+]i. Pretreatment of cells with pharmacological agents that block release of inositol 1,4,5-triphosphate (IP3)–sensitive endoplasmic reticulum stores abrogates the response. Moreover, treatment of cells with these pharmacological agents inhibits HSV infection and prevents focal adhesion kinase (FAK) phosphorylation, which occurs within 5 min after viral infection. Viruses deleted in glycoprotein L or glycoprotein D, which bind but do not penetrate, fail to induce a [Ca2+]i response or trigger FAK phosphorylation. Together, these results support a model for HSV infection that requires activation of IP3-responsive Ca2+-signaling pathways and that is associated with FAK phosphorylation. Defining the pathway of viral invasion may lead to new targets for anti-viral therapy. PMID:14568989

An Architecture for SCADA Network Forensics

NASA Astrophysics Data System (ADS)

Kilpatrick, Tim; Gonzalez, Jesus; Chandia, Rodrigo; Papa, Mauricio; Shenoi, Sujeet

Supervisory control and data acquisition (SCADA) systems are widely used in industrial control and automation. Modern SCADA protocols often employ TCP/IP to transport sensor data and control signals. Meanwhile, corporate IT infrastructures are interconnecting with previously isolated SCADA networks. The use of TCP/IP as a carrier protocol and the interconnection of IT and SCADA networks raise serious security issues. This paper describes an architecture for SCADA network forensics. In addition to supporting forensic investigations of SCADA network incidents, the architecture incorporates mechanisms for monitoring process behavior, analyzing trends and optimizing plant performance.

CANOPEN Controller IP Core

NASA Astrophysics Data System (ADS)

Caramia, Maurizio; Montagna, Mario; Furano, Gianluca; Winton, Alistair

2010-08-01

This paper will describe the activities performed by Thales Alenia Space Italia supported by the European Space Agency in the definition of a CAN bus interface to be used on Exomars. The final goal of this activity is the development of an IP core, to be used in a slave node, able to manage both the CAN bus Data Link and Application Layer totally in hardware. The activity has been focused on the needs of the EXOMARS mission where devices with different computational performances are all managed by the onboard computer through the CAN bus.

The design, fabrication and delivery of a spacelab neutral buoyancy Instrument Pointing System (IPS) mockup. [underwater training simulator

NASA Technical Reports Server (NTRS)

Vanvalkenburgh, C. N.

1984-01-01

Underwater simulations of EVA contingency operations such as manual jettison, payload disconnect, and payload clamp actuation were used to define crew aid needs and mockup pecularities and characteristics to verify the validity of simulation using the trainer. A set of mockup instrument pointing system tests was conducted and minor modifications and refinements were made. Flight configuration struts were tested and verified to be operable by the flight crew. Tasks involved in developing the following end items are described: IPS gimbal system, payload, and payload clamp assembly; the igloos (volumetric); spacelab pallets, experiments, and hardware; experiment, and hardware; experiment 7; and EVA hand tools, support hardware (handrails and foot restraints). The test plan preparation and test support are also covered.

Shuttle infrared telescope facility (SIRTF) preliminary design study

NASA Technical Reports Server (NTRS)

1976-01-01

An overall picture of the SIRTF system is first presented, including the telescope, focal plane instruments, cryogen supply, shuttle and spacelab support subsystems, mechanical and data interfaces with the vehicles, ground support equipment, and system requirements. The optical, mechanical, and thermal characteristics of the telescope are then evaluated, followed by a description of the SIRTF internal stabilization subsystem and its interface with the IPS. Expected performance in the shuttle environment is considered. Tradeoff studies are described, including the Gregorian versus the Cassegrain telescope, aperture diameter tradeoff, a CCD versus an image dissector for the star tracker, the large ambient telescope versus the SIRTF, and a dedicated gimbal versus the IPS. Operations from integration through launch and recovery are also discussed and cost estimates for the program are presented.

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.

Fast-Solving Quasi-Optimal LS-S3VM Based on an Extended Candidate Set.

PubMed

Ma, Yuefeng; Liang, Xun; Kwok, James T; Li, Jianping; Zhou, Xiaoping; Zhang, Haiyan

2018-04-01

The semisupervised least squares support vector machine (LS-S 3 VM) is an important enhancement of least squares support vector machines in semisupervised learning. Given that most data collected from the real world are without labels, semisupervised approaches are more applicable than standard supervised approaches. Although a few training methods for LS-S 3 VM exist, the problem of deriving the optimal decision hyperplane efficiently and effectually has not been solved. In this paper, a fully weighted model of LS-S 3 VM is proposed, and a simple integer programming (IP) model is introduced through an equivalent transformation to solve the model. Based on the distances between the unlabeled data and the decision hyperplane, a new indicator is designed to represent the possibility that the label of an unlabeled datum should be reversed in each iteration during training. Using the indicator, we construct an extended candidate set consisting of the indices of unlabeled data with high possibilities, which integrates more information from unlabeled data. Our algorithm is degenerated into a special scenario of the previous algorithm when the extended candidate set is reduced into a set with only one element. Two strategies are utilized to determine the descent directions based on the extended candidate set. Furthermore, we developed a novel method for locating a good starting point based on the properties of the equivalent IP model. Combined with the extended candidate set and the carefully computed starting point, a fast algorithm to solve LS-S 3 VM quasi-optimally is proposed. The choice of quasi-optimal solutions results in low computational cost and avoidance of overfitting. Experiments show that our algorithm equipped with the two designed strategies is more effective than other algorithms in at least one of the following three aspects: 1) computational complexity; 2) generalization ability; and 3) flexibility. However, our algorithm and other algorithms have similar levels of performance in the remaining aspects.

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.

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

Statistical mechanical analysis of linear programming relaxation for combinatorial optimization problems

NASA Astrophysics Data System (ADS)

Takabe, Satoshi; Hukushima, Koji

2016-05-01

Typical behavior of the linear programming (LP) problem is studied as a relaxation of the minimum vertex cover (min-VC), a type of integer programming (IP) problem. A lattice-gas model on the Erdös-Rényi random graphs of α -uniform hyperedges is proposed to express both the LP and IP problems of the min-VC in the common statistical mechanical model with a one-parameter family. Statistical mechanical analyses reveal for α =2 that the LP optimal solution is typically equal to that given by the IP below the critical average degree c =e in the thermodynamic limit. The critical threshold for good accuracy of the relaxation extends the mathematical result c =1 and coincides with the replica symmetry-breaking threshold of the IP. The LP relaxation for the minimum hitting sets with α ≥3 , minimum vertex covers on α -uniform random graphs, is also studied. Analytic and numerical results strongly suggest that the LP relaxation fails to estimate optimal values above the critical average degree c =e /(α -1 ) where the replica symmetry is broken.

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.

Statistical mechanical analysis of linear programming relaxation for combinatorial optimization problems.

PubMed

Takabe, Satoshi; Hukushima, Koji

2016-05-01

Typical behavior of the linear programming (LP) problem is studied as a relaxation of the minimum vertex cover (min-VC), a type of integer programming (IP) problem. A lattice-gas model on the Erdös-Rényi random graphs of α-uniform hyperedges is proposed to express both the LP and IP problems of the min-VC in the common statistical mechanical model with a one-parameter family. Statistical mechanical analyses reveal for α=2 that the LP optimal solution is typically equal to that given by the IP below the critical average degree c=e in the thermodynamic limit. The critical threshold for good accuracy of the relaxation extends the mathematical result c=1 and coincides with the replica symmetry-breaking threshold of the IP. The LP relaxation for the minimum hitting sets with α≥3, minimum vertex covers on α-uniform random graphs, is also studied. Analytic and numerical results strongly suggest that the LP relaxation fails to estimate optimal values above the critical average degree c=e/(α-1) where the replica symmetry is broken.

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.

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

Cost-utility analysis of individual psychosocial support interventions for breast cancer patients in a randomized controlled study.

PubMed

Arving, Cecilia; Brandberg, Yvonne; Feldman, Inna; Johansson, Birgitta; Glimelius, Bengt

2014-03-01

The aim was to explore the cost-utility in providing complementary individual psychosocial support to breast cancer patients compared with standard care (SC). Patients just starting adjuvant therapy (n = 168) at Uppsala University Hospital, Sweden, were consecutively included and randomized into three groups: psychosocial support from a specially trained nurse (INS), from a psychologist (IPS), or SC. Psychological effects and healthcare utilization were monitored during a 2-year period. The hospital billing system provided cost estimates. Quality-adjusted life years (QALYs) were calculated using health-related quality of life data from the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ C-30) translated into the Euro Quality of Life- 5-Dimensional classification. On the basis of the medical cost offset, a cost-utility analysis was performed. Health care utilization was mainly related to the breast cancer diagnosis and treatment. The intervention costs amounted to about €500 or 3% of the total costs. Total health care costs, including interventions cost, were lower in the INS (€18,670) and IPS (€20,419) groups than in the SC group (€25,800). The number of QALYs were also higher in the INS (1.52 QALY) and IPS (1.59 QALY) groups, compared with the SC group (1.43 QALY). The cost-utility analysis revealed that, during adjuvant treatment for breast cancer, the individual psychosocial support interventions provided here was cost effective because the health care costs were lower and QALYs were higher compared to SC alone. Copyright © 2013 John Wiley & Sons, Ltd.

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

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

Illness and injury in athletes during the competition period at the London 2012 Paralympic Games: development and implementation of a web-based surveillance system (WEB-IISS) for team medical staff.

PubMed

Derman, Wayne; Schwellnus, Martin; Jordaan, Esme; Blauwet, Cheri A; Emery, Carolyn; Pit-Grosheide, Pia; Marques, Norma-Angelica Patino; Martinez-Ferrer, Oriol; Stomphorst, Jaap; Van de Vliet, Peter; Webborn, Nick; Willick, Stuart E

2013-05-01

In this study we describe (1) the implementation of a novel web-based injury and illness surveillance system (WEB-IISS) for use by a team of physicians at multisport events and (2) the incidence and characteristics of injuries and illness in athletes during the London 2012 Paralympic Games. Overall, 3565 athletes from 160 of the 164 participating countries were followed daily over a 14-day period, consisting of a precompetition period (3 days), and a competition period (11 days) (49 910 athlete-days). Daily injury and illness data were obtained from teams with their own medical support (78 teams, 3329 athletes) via the WEB-IISS, and without their own medical support through the London Organising Committee of the Olympic Games and Paralympic Games database (82 teams and 236 athletes). There were no differences between incidence rates (IR) of injury and illness, or between the precompetition and competition periods. The IR of injury during the competition period was 12.1/1000 athlete-days, with an incidence proportion (IP) of 11.6% (95% CI 11.0% to 13.3%). Upper limb injuries (35%), particularly of the shoulder (17%) were most common. The IR of illness during the competition period was 12.8/1000 athlete-days (95% CI 12.18 to 1421), with an IP of 10.2%. The IP was highest in the respiratory system (27.4%), skin (18.3%) and the gastrointestinal (14.5%) systems. During the competition period, the IR and IP of illness and injury at the Games were similar and comparable to the observed rates in other elite competitions. In Paralympic athletes, the IP of upper limb injuries is higher than that of lower limb injuries and non-respiratory illnesses are more common.

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.

5-HT6 receptor agonists and antagonists enhance learning and memory in a conditioned emotion response paradigm by modulation of cholinergic and glutamatergic mechanisms

PubMed Central

Woods, S; Clarke, NN; Layfield, R; Fone, KCF

2012-01-01

BACKGROUND AND PURPOSE 5-HT6 receptors are abundant in the hippocampus, nucleus accumbens and striatum, supporting their role in learning and memory. Selective 5-HT6 receptor antagonists produce pro-cognitive effects in several learning and memory paradigms while 5-HT6 receptor agonists have been found to enhance and impair memory. EXPERIMENTAL APPROACH The conditioned emotion response (CER) paradigm was validated in rats. Then we examined the effect of the 5-HT6 receptor antagonist, EMD 386088 (10 mg·kg−1, i.p.), and agonists, E-6801 (2.5 mg·kg−1, i.p.) and EMD 386088 (5 mg·kg−1, i.p.) on CER-induced behaviour either alone or after induction of memory impairment by the muscarinic receptor antagonist, scopolamine (0.3 mg·kg−1, i.p) or the NMDA receptor antagonist, MK-801 (0.1 mg·kg−1, i.p). KEY RESULTS Pairing unavoidable foot shocks with a light and tone cue during CER training induced a robust freezing response, providing a quantitative index of contextual memory when the rat was returned to the shock chamber 24 h later. Pretreatment (−20 min pre-training) with scopolamine or MK-801 reduced contextual freezing 24 h after CER training, showing production of memory impairment. Immediate post-training administration of 5-HT6 receptor antagonist, SB-270146, and agonists, EMD 386088 and E-6801, had little effect on CER freezing when given alone, but all significantly reversed scopolamine- and MK-801-induced reduction in freezing. CONCLUSION AND IMPLICATIONS Both the 5-HT6 receptor agonists and antagonist reversed cholinergic- and glutamatergic-induced deficits in associative learning. These findings support the therapeutic potential of 5-HT6 receptor compounds in the treatment of cognitive dysfunction, such as seen in Alzheimer's disease and schizophrenia. PMID:22568655

The status of interprofessional education and interprofessional prevention education in academic health centers: a national baseline study.

PubMed

Greer, Annette G; Clay, Maria; Blue, Amy; Evans, Clyde H; Garr, David

2014-05-01

Given the emphasis on prevention in U.S. health care reform efforts, the importance of interprofessional education (IPE) that prepares health professions students to be part of effective health care teams is greater than ever. This study examined the prevalence and nature of IPE and interprofessional (IP) prevention education in U.S. academic health centers. The authors extracted a 10-item survey from the longer published IPE Assessment and Planning Instrument. In September 2010, they sent the survey to 346 health professions leaders in health sciences schools and colleges at 100 academic health centers. These institutions were identified via the online membership list of the Association of Academic Health Centers. The authors conducted descriptive statistical analysis and cross-tabulations. Surveys were completed by 127 contacts at 68 universities in 31 states and the District of Columbia. IPE was more prevalent than IP prevention education in all categories of measurement. Respondents affirmed existence of IPE in courses (85.0%) and in clinical rotations/internships (80.3%). The majority reported personnel with responsibility for IPE (68.5%) or prevention education (59.8%) at their institutional unit, and 59.8% reported an IPE office or center. This study provides evidence that IPE and IP prevention education exist in academic health centers, but additional attention should be paid to the development of IP prevention education. Sample syllabi, job descriptions, and policies may be available to support adoption of IPE and IP prevention education. Further effort is needed to increase the integration of IP and prevention education into practice.

Comparison of Gated Audiovisual Speech Identification in Elderly Hearing Aid Users and Elderly Normal-Hearing Individuals: Effects of Adding Visual Cues to Auditory Speech Stimuli.

PubMed

Moradi, Shahram; Lidestam, Björn; Rönnberg, Jerker

2016-06-17

The present study compared elderly hearing aid (EHA) users (n = 20) with elderly normal-hearing (ENH) listeners (n = 20) in terms of isolation points (IPs, the shortest time required for correct identification of a speech stimulus) and accuracy of audiovisual gated speech stimuli (consonants, words, and final words in highly and less predictable sentences) presented in silence. In addition, we compared the IPs of audiovisual speech stimuli from the present study with auditory ones extracted from a previous study, to determine the impact of the addition of visual cues. Both participant groups achieved ceiling levels in terms of accuracy in the audiovisual identification of gated speech stimuli; however, the EHA group needed longer IPs for the audiovisual identification of consonants and words. The benefit of adding visual cues to auditory speech stimuli was more evident in the EHA group, as audiovisual presentation significantly shortened the IPs for consonants, words, and final words in less predictable sentences; in the ENH group, audiovisual presentation only shortened the IPs for consonants and words. In conclusion, although the audiovisual benefit was greater for EHA group, this group had inferior performance compared with the ENH group in terms of IPs when supportive semantic context was lacking. Consequently, EHA users needed the initial part of the audiovisual speech signal to be longer than did their counterparts with normal hearing to reach the same level of accuracy in the absence of a semantic context. © The Author(s) 2016.

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

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.

Performance of a Regional Aeronautical Telecommunications Network

NASA Technical Reports Server (NTRS)

Bretmersky, Steven C.; Ripamonti, Claudio; Konangi, Vijay K.; Kerczewski, Robert J.

2001-01-01

This paper reports the findings of the simulation of the ATN (Aeronautical Telecommunications Network) for three typical average-sized U.S. airports and their associated air traffic patterns. The models of the protocols were designed to achieve the same functionality and meet the ATN specifications. The focus of this project is on the subnetwork and routing aspects of the simulation. To maintain continuous communication between the aircrafts and the ground facilities, a model based on mobile IP is used. The results indicate that continuous communication is indeed possible. The network can support two applications of significance in the immediate future FTP and HTTP traffic. Results from this simulation prove the feasibility of development of the ATN concept for AC/ATM (Advanced Communications for Air Traffic Management).

Comparison of Traditional and ADRI Based Teaching Approaches in an Introductory Programming Course

ERIC Educational Resources Information Center

Malik, Sohail Iqbal; Coldwell-Neilson, Jo

2017-01-01

Aim/Purpose: This study introduced a new teaching and learning approach based on an ADRI (Approach, Deployment, Result, Improvement) model in an introductory programming (IP) course. The effectiveness of the new teaching and learning process was determined by collecting feedback from the IP instructors and by analyzing the final exam grades of the…

Chromatin immunoprecipitation assays: application of ChIP-on-chip for defining dynamic transcriptional mechanisms in bone cells.

PubMed

van der Deen, Margaretha; Hassan, Mohammad Q; Pratap, Jitesh; Teplyuk, Nadiya M; Young, Daniel W; Javed, Amjad; Zaidi, Sayyed K; Lian, Jane B; Montecino, Martin; Stein, Janet L; Stein, Gary S; van Wijnen, Andre J

2008-01-01

Normal cell growth and differentiation of bone cells requires the sequential expression of cell type specific genes to permit lineage specification and development of cellular phenotypes. Transcriptional activation and repression of distinct sets of genes support the anabolic functions of osteoblasts and the catabolic properties of osteoclasts. Furthermore, metastasis of tumors to the bone environment is controlled by transcriptional mechanisms. Insights into the transcriptional regulation of genes in bone cells may provide a conceptual basis for improved therapeutic approaches to treat bone fractures, genetic osteopathologies, and/or cancer metastases to bone. Chromatin immunoprecipitation (ChIP) is a powerful technique to establish in vivo binding of transcription factors to the promoters of genes that are either activated or repressed in bone cells. Combining ChIP with genomic microarray analysis, colloquially referred to as "ChIP-on-chip," has become a valuable method for analysis of endogenous protein/DNA interactions. This technique permits assessment of chromosomal binding sites for transcription factors or the location of histone modifications at a genomic scale. This chapter discusses protocols for performing chromatin immunoprecipitation experiments, with a focus on ChIP-on-chip analysis. The information presented is based on the authors' experience with defining interactions of Runt-related (RUNX) transcription factors with bone-related genes within the context of the native nucleosomal organization of intact osteoblastic cells.

Genotoxicity of three food processing contaminants in transgenic mice expressing human sulfotransferases 1A1 and 1A2 as assessed by the in vivo alkaline single cell gel electrophoresis assay

PubMed Central

Høie, Anja Hortemo; Svendsen, Camilla; Brunborg, Gunnar; Glatt, Hansruedi; Alexander, Jan; Meinl, Walter

2015-01-01

The food processing contaminants 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), 5‐hydroxymethylfurfural (HMF) and 2,5 dimethylfuran (DMF) are potentially both mutagenic and carcinogenic in vitro and/or in vivo, although data on DMF is lacking. The PHIP metabolite N‐hydroxy‐PhIP and HMF are bioactivated by sulfotransferases (SULTs). The substrate specificity and tissue distribution of SULTs differs between species. A single oral dose of PhIP, HMF or DMF was administered to wild‐type (wt) mice and mice expressing human SULT1A1/1A2 (hSULT mice). DNA damage was studied using the in vivo alkaline single cell gel electrophoresis (SCGE) assay. No effects were detected in wt mice. In the hSULT mice, PhIP and HMF exposure increased the levels of DNA damage in the liver and kidney, respectively. DMF was not found to be genotoxic. The observation of increased DNA damage in hSULT mice compared with wt mice supports the role of human SULTs in the bioactivation of N‐hydroxy‐PhIP and HMF in vivo. Environ. Mol. Mutagen. 56:709–714, 2015. © 2015 The Authors. Environmental and Molecular Mutagenesis Published by Wiley Periodicals, Inc. PMID:26270892

Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells

PubMed Central

Mach, François; Sauty, Alain; Iarossi, Albert S.; Sukhova, Galina K.; Neote, Kuldeep; Libby, Peter; Luster, Andrew D.

1999-01-01

Activated T lymphocytes accumulate early in atheroma formation and persist at sites of lesion growth and rupture, suggesting that they may play an important role in the pathogenesis of atherosclerosis. Moreover, atherosclerotic lesions contain the Th1-type cytokine IFN-γ, a potentiator of atherosclerosis. The present study demonstrates the differential expression of the 3 IFN-γ–inducible CXC chemokines — IFN-inducible protein 10 (IP-10), monokine induced by IFN-γ (Mig), and IFN-inducible T-cell α chemoattractant (I-TAC) — by atheroma-associated cells, as well as the expression of their receptor, CXCR3, by all T lymphocytes within human atherosclerotic lesions in situ. Atheroma-associated endothelial cells (ECs), smooth muscle cells (SMCs), and macrophages (MØ) all expressed IP-10, whereas Mig and I-TAC were mainly expressed in ECs and MØ, as detected by double immunofluorescence staining. ECs of microvessels within lesions also expressed abundant I-TAC. In vitro experiments supported these results and showed that IL-1β, TNF-α, and CD40 ligand potentiated IP-10 expression from IFN-γ–stimulated ECs. In addition, nitric oxide (NO) treatment decreased IFN-γ induction of IP-10. Our findings suggest that the differential expression of IP-10, Mig, and I-TAC by atheroma-associated cells plays a role in the recruitment and retention of activated T lymphocytes observed within vascular wall lesions during atherogenesis. PMID:10525042

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.

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.

Network Configuration Analysis for Formation Flying Satellites

NASA Technical Reports Server (NTRS)

Knoblock, Eric J.; Wallett, Thomas M.; Konangi, Vijay K.; Bhasin, Kul B.

2001-01-01

The performance of two networks to support autonomous multi-spacecraft formation flying systems is presented. Both systems are comprised of a ten-satellite formation, with one of the satellites designated as the central or 'mother ship.' All data is routed through the mother ship to the terrestrial network. The first system uses a TCP/EP over ATM protocol architecture within the formation, and the second system uses the IEEE 802.11 protocol architecture within the formation. The simulations consist of file transfers using either the File Transfer Protocol (FTP) or the Simple Automatic File Exchange (SAFE) Protocol. The results compare the IP queuing delay, IP queue size and IP processing delay at the mother ship as well as end-to-end delay for both systems. In all cases, using IEEE 802.11 within the formation yields less delay. Also, the throughput exhibited by SAFE is better than FTP.

Image motion compensation on the Spacelab 2 Solar Optical Universal Polarimeter /SL2 SOUP/

NASA Technical Reports Server (NTRS)

Tarbell, T. D.; Duncan, D. W.; Finch, M. L.; Spence, G.

1981-01-01

The SOUP experiment on Spacelab 2 includes a 30 cm visible light telescope and focal plane package mounted on the Instrument Pointing System (IPS). Scientific goals of the experiment dictate pointing stability requirements of less than 0.05 arcsecond jitter over periods of 5-20 seconds. Quantitative derivations of these requirements from two different aspects are presented: (1) avoidance of motion blurring of diffraction-limited images; (2) precise coalignment of consecutive frames to allow measurement of small image differences. To achieve this stability, a fine guider system capable of removing residual jitter of the IPS and image motions generated on the IPS cruciform instrument support structure has been constructed. This system uses solar limb detectors in the prime focal plane to derive an error signal. Image motion due to pointing errors is compensated by the agile secondary mirror mounted on piezoelectric transducers, controlled by a closed-loop servo system.

Specificity of interpersonal problems in generalized anxiety disorder versus other anxiety disorders and depression.

PubMed

Uhmann, Stefan; Beesdo-Baum, Katja; Becker, Eni S; Hoyer, Jürgen

2010-11-01

We examined the diagnostic specificity of interpersonal problems (IP) in generalized anxiety disorder (GAD). We expected generally higher interpersonal distress, and specifically higher levels of nonassertive, exploitable, overly nurturant, and intrusive behavior in n = 58 patients with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition GAD compared with patients with post-traumatic stress disorder (n = 46), other anxiety disorders (n = 47), and unipolar depressive disorders (n = 47). IP were assessed with the Inventory of Interpersonal Problems. Specificity in the sense of heightened interpersonal distress for GAD was not supported in any of the aforementioned scales, neither for pure nor for comorbid GAD. This finding persisted after accounting for the degree of depressiveness (Beck Depression Inventory). GAD patients are rather not characterized by more self-ascribed IPs although they may worry more about interpersonal issues in general.

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.

ELRIS2D: A MATLAB Package for the 2D Inversion of DC Resistivity/IP Data

NASA Astrophysics Data System (ADS)

Akca, Irfan

2016-04-01

ELRIS2D is an open source code written in MATLAB for the two-dimensional inversion of direct current resistivity (DCR) and time domain induced polarization (IP) data. The user interface of the program is designed for functionality and ease of use. All available settings of the program can be reached from the main window. The subsurface is discre-tized using a hybrid mesh generated by the combination of structured and unstructured meshes, which reduces the computational cost of the whole inversion procedure. The inversion routine is based on the smoothness constrained least squares method. In order to verify the program, responses of two test models and field data sets were inverted. The models inverted from the synthetic data sets are consistent with the original test models in both DC resistivity and IP cases. A field data set acquired in an archaeological site is also used for the verification of outcomes of the program in comparison with the excavation results.

Observations of Heliospheric Faraday Rotation (FR) and Interplanetary Scintillation (IPS) with the LOw Frequency ARray (LOFAR): Steps Towards Improving Space-Weather Forecasting Capabilities

NASA Astrophysics Data System (ADS)

Bisi, M. M.; Fallows, R. A.; Sobey, C.; Eftekhari, T.; Jensen, E. A.; Jackson, B. V.; Yu, H. S.; Hick, P. P.; Odstrcil, D.; Tokumaru, M.

2015-12-01

The phenomenon of space weather - analogous to terrestrial weather which describes the changing pressure, temperature, wind, and humidity conditions on Earth - is essentially a description of the changes in velocity, density, magnetic field, high-energy particles, and radiation in the near-Earth space environment including the effects of such changes on the Earth's magnetosphere, radiation belts, ionosphere, and thermosphere. Space weather can be considered to have two main strands: (i) scientific research, and (ii) applications. The former is self-explanatory, but the latter covers operational aspects which includes its forecasting. Understanding and forecasting space weather in the near-Earth environment is vitally important to protecting our modern-day reliance (militarily and commercially) on satellites, global-communication and navigation networks, high-altitude air travel (radiation concerns particularly on polar routes), long-distance power/oil/gas lines and piping, and for any future human exploration of space to list but a few. Two ground-based radio-observing remote-sensing techniques that can aid our understanding and forecasting of heliospheric space weather are those of interplanetary scintillation (IPS) and heliospheric Faraday rotation (FR). The LOw Frequency ARray (LOFAR) is a next-generation 'software' radio telescope centered in The Netherlands with international stations spread across central and northwest Europe. For several years, scientific observations of IPS on LOFAR have been undertaken on a campaign basis and the experiment is now well developed. More recently, LOFAR has been used to attempt scientific heliospheric FR observations aimed at remotely sensing the magnetic field of the plasma traversing the inner heliosphere. We present our latest progress using these two radio heliospheric-imaging remote-sensing techniques including the use of three-dimensional (3-D) modeling and reconstruction techniques using other, additional data as input (such as IPS data from the Solar Terrestrial Environment Laboratory - STELab) to support and better-interpret the LOFAR results.

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.

The development of a supportive care needs assessment tool for Indigenous people with cancer

PubMed Central

2012-01-01

Background Little is known about the supportive care needs of Indigenous people with cancer and to date, existing needs assessment tools have not considered cultural issues for this population. We aimed to adapt an existing supportive care needs assessment tool for use with Indigenous Australians with cancer. Methods Face-to-face interviews with Indigenous cancer patients (n = 29) and five focus groups with Indigenous key-informants (n = 23) were conducted to assess the face and content validity, cultural acceptability, utility and relevance of the Supportive Care Needs Survey - Short Form 34 (SCNS-SF34) for use with Indigenous patients with cancer. Results All items from the SCNS-SF34 were shortened and changed to use more appropriate language (e.g. the word 'anxiety' was substituted with 'worry'). Seven questions were omitted (e.g. items on death and future considerations) as they were deemed culturally inappropriate or irrelevant and 12 items were added (e.g. accessible transport). Optional instructions were added before the sexual items. The design and response format of the SCNS-SF34 was modified to make it easier to use for Indigenous cancer patients. Given the extensive modifications to the SCNS-SF34 and the liklihood of a different factor structure we consider this tool to be a new tool rather than a modification. The Supportive care needs assessment tool for Indigenous people (SCNAT-IP) shows promising face and content validity and will be useful in informing services where they need to direct their attention for these patients. Conclusions Indigenous people with cancer have language, customs and specific needs that are not accommodated within the standard SCNS-SF34. Our SCNAT-IP improves acceptability, relevance and face validity for Indigenous-specific concerns. Our SCNAT-IP will allow screening for supportive care needs that are specific to Indigenous cancer patients' and greatly inform targeted policy development and practice. PMID:22817614

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...

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.

Primary medical care in Irish prisons

PubMed Central

2010-01-01

Background An industrial dispute between prison doctors and the Irish Prison Service (IPS) took place in 2004. Part of the resolution of that dispute was that an independent review of prison medical and support services be carried out by a University Department of Primary Care. The review took place in 2008 and we report here on the principal findings of that review. Methods This study utilised a mixed methods approach. An independent expert medical evaluator (one of the authors, DT) inspected the medical facilities, equipment and relevant custodial areas in eleven of the fourteen prisons within the IPS. Semistructured interviews took place with personnel who had operational responsibility for delivery of prison medical care. Prison doctors completed a questionnaire to elicit issues such as allocation of clinician's time, nurse and administrative support and resources available. Results There was wide variation in the standard of medical facilities and infrastructure provided across the IPS. The range of medical equipment available was generally below that of the equivalent general practice scheme in the community. There is inequality within the system with regard to the ratio of doctor-contracted time relative to the size of the prison population. There is limited administrative support, with the majority of prisons not having a medical secretary. There are few psychiatric or counselling sessions available. Conclusions People in prison have a wide range of medical care needs and there is evidence to suggest that these needs are being met inconsistently in Irish prisons. PMID:20307311

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.

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 impact of large-scale circulation patterns on summer crop yields in IP

NASA Astrophysics Data System (ADS)

Capa Morocho, Mirian; Rodríguez Fonseca, Belén; Ruiz Ramos, Margarita

2014-05-01

Large-scale circulations patterns (ENSO, NAO) have been shown to have a significant impact on seasonal weather, and therefore on crop yield over many parts of the world(Garnett and Khandekar, 1992; Aasa et al., 2004; Rozas and Garcia-Gonzalez, 2012). In this study, we analyze the influence of large-scale circulation patterns and regional climate on the principal components of maize yield variability in Iberian Peninsula (IP) using reanalysis datasets. Additionally, we investigate the modulation of these relationships by multidecadal patterns. This study is performed analyzing long time series of maize yield, only climate dependent, computed with the crop model CERES-maize (Jones and Kiniry, 1986) included in Decision Support System for Agrotechnology Transfer (DSSAT v.4.5). To simulate yields, reanalysis daily data of radiation, maximum and minimum temperature and precipitation were used. The reanalysis climate data were obtained from National Center for Environmental Prediction (20th Century and NCEP) and European Centre for Medium-Range Weather Forecasts (ECMWF) data server (ERA 40 and ERA Interim). Simulations were run at five locations: Lugo (northwestern), Lerida (NE), Madrid (central), Albacete (southeastern) and Córdoba (S IP) (Gabaldón et al., 2013). From these time series standardized anomalies were calculated. Afterwards, time series were time filtered to focus on the interannual-to-multiannual variability, splitting up in two components: low frequency (LF) and high frequency (HF) time scales. The principal components of HF yield anomalies in IP were compared with a set of documented patterns. These relationships were compared with multidecadal patterns, as Atlanctic Multidecadal Oscillations (AMO) and Interdecadal Pacific Oscillations (IPO). The results of this study have important implications in crop forecasting. In this way, it may have a positive impact on both public (agricultural planning) and private (decision support to farmers, insurance companies) sectors, to take advantage of favorable conditions or reduce the effect of adverse conditions. Acknowledgements Research by M. Capa-Morocho has been partly supported by a PICATA predoctoral fellowship of the Moncloa Campus of International Excellence (UCM-UPM) and MULCLIVAR project (CGL2012-38923-C02-02) References Aasa, A., Jaagus, J., Ahas, R. and Sepp, M. 2004. The influence of atmospheric circulation on plant phenological phases in central and eastern Europe. International Journal of Climatology 24, 1551-1564. Gabaldón, C. et al. 2013. Evaluation of local strategies to climate change of maize crop in Andalusia for the first half of 21st century. European Geosciences Union - General Assembly2013 Vol. 15 (Vienna - Austria, 2013). Garnett, E. R. and Khandekar, M. L. 1992. The impact of large-scale atmospheric circulations and anomalies on Indian monsoon droughts and floods and on world grain yields-a statistical analysis. Agricultural and Forest Meteorology 61, 113-128. Jones, C. and Kiniry, J. 1986. CERES-Maize: A Simulation Model of Maize Growth and Development. Texas A&M University Press, 194. Rozas, V. and Garcia-Gonzalez, I. 2012. Non-stationary influence of El Nino-Southern Oscillation and winter temperature on oak latewood growth in NW Iberian Peninsula. Int J Biometeorol 56, 787-800.

Functional Polarity of Microvascular Brain Endothelial Cells Supported by Neurovascular Unit Computational Model of Large Neutral Amino Acid Homeostasis

PubMed Central

Taslimifar, Mehdi; Buoso, Stefano; Verrey, Francois; Kurtcuoglu, Vartan

2018-01-01

The homeostatic regulation of large neutral amino acid (LNAA) concentration in the brain interstitial fluid (ISF) is essential for proper brain function. LNAA passage into the brain is primarily mediated by the complex and dynamic interactions between various solute carrier (SLC) transporters expressed in the neurovascular unit (NVU), among which SLC7A5/LAT1 is considered to be the major contributor in microvascular brain endothelial cells (MBEC). The LAT1-mediated trans-endothelial transport of LNAAs, however, could not be characterized precisely by available in vitro and in vivo standard methods so far. To circumvent these limitations, we have incorporated published in vivo data of rat brain into a robust computational model of NVU-LNAA homeostasis, allowing us to evaluate hypotheses concerning LAT1-mediated trans-endothelial transport of LNAAs across the blood brain barrier (BBB). We show that accounting for functional polarity of MBECs with either asymmetric LAT1 distribution between membranes and/or intrinsic LAT1 asymmetry with low intraendothelial binding affinity is required to reproduce the experimentally measured brain ISF response to intraperitoneal (IP) L-tyrosine and L-phenylalanine injection. On the basis of these findings, we have also investigated the effect of IP administrated L-tyrosine and L-phenylalanine on the dynamics of LNAAs in MBECs, astrocytes and neurons. Finally, the computational model was shown to explain the trans-stimulation of LNAA uptake across the BBB observed upon ISF perfusion with a competitive LAT1 inhibitor. PMID:29593549

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.

Decisional needs assessment of patients with complex care needs in primary care: a participatory systematic mixed studies review protocol

PubMed Central

Pluye, Pierre; Légaré, France; Haggerty, Jeannie; Gore, Genevieve C; Sherif, Reem El; Poitras, Marie-Ève; Beaulieu, Marie-Claude; Beaulieu, Marie-Dominique; Bush, Paula L; Couturier, Yves; Débarges, Béatrice; Gagnon, Justin; Giguère, Anik; Grad, Roland; Granikov, Vera; Goulet, Serge; Hudon, Catherine; Kremer, Bernardo; Kröger, Edeltraut; Kudrina, Irina; Lebouché, Bertrand; Loignon, Christine; Lussier, Marie-Thérèse; Martello, Cristiano; Nguyen, Quynh; Pratt, Rebekah; Rihoux, Benoit; Rosenberg, Ellen; Samson, Isabelle; Senn, Nicolas; Li Tang, David; Tsujimoto, Masashi; Vedel, Isabelle; Ventelou, Bruno; Wensing, Michel; Bigras, Magali

2017-01-01

Introduction Patients with complex care needs (PCCNs) often suffer from combinations of multiple chronic conditions, mental health problems, drug interactions and social vulnerability, which can lead to healthcare services overuse, underuse or misuse. Typically, PCCNs face interactional issues and unmet decisional needs regarding possible options in a cascade of interrelated decisions involving different stakeholders (themselves, their families, their caregivers, their healthcare practitioners). Gaps in knowledge, values clarification and social support in situations where options need to be deliberated hamper effective decision support interventions. This review aims to (1) assess decisional needs of PCCNs from the perspective of stakeholders, (2) build a taxonomy of these decisional needs and (3) prioritise decisional needs with knowledge users (clinicians, patients and managers). Methods and analysis This review will be based on the interprofessional shared decision making (IP-SDM) model and the Ottawa Decision Support Framework. Applying a participatory research approach, we will identify potentially relevant studies through a comprehensive literature search; select relevant ones using eligibility criteria inspired from our previous scoping review on PCCNs; appraise quality using the Mixed Methods Appraisal Tool; conduct a three-step synthesis (sequential exploratory mixed methods design) to build taxonomy of key decisional needs; and integrate these results with those of a parallel PCCNs’ qualitative decisional need assessment (semistructured interviews and focus group with stakeholders). Ethics and dissemination This systematic review, together with the qualitative study (approved by the Centre Intégré Universitaire de Santé et Service Sociaux du Saguenay-Lac-Saint-Jean ethical committee), will produce a working taxonomy of key decisional needs (ontological contribution), to inform the subsequent user-centred design of a support tool for addressing PCCNs’ decisional needs (practical contribution). We will adapt the IP-SDM model, normally dealing with a single decision, for PCCNs who experience cascade of decisions involving different stakeholders (theoretical contribution). Knowledge users will facilitate dissemination of the results in the Canadian primary care network. PROSPERO registration number CRD42015020558. PMID:29133314

Decisional needs assessment of patients with complex care needs in primary care: a participatory systematic mixed studies review protocol.

PubMed

Bujold, Mathieu; Pluye, Pierre; Légaré, France; Haggerty, Jeannie; Gore, Genevieve C; Sherif, Reem El; Poitras, Marie-Eve; Beaulieu, Marie-Claude; Beaulieu, Marie-Dominique; Bush, Paula L; Couturier, Yves; Débarges, Beatrice; Gagnon, Justin; Giguère, Anik; Grad, Roland; Granikov, Vera; Goulet, Serge; Hudon, Catherine; Kremer, Bernardo; Kröger, Edeltraut; Kudrina, Irina; Lebouché, Bertrand; Loignon, Christine; Lussier, Marie-Therese; Martello, Cristiano; Nguyen, Quynh; Pratt, Rebekah; Rihoux, Benoit; Rosenberg, Ellen; Samson, Isabelle; Senn, Nicolas; Li Tang, David; Tsujimoto, Masashi; Vedel, Isabelle; Ventelou, Bruno; Wensing, Michel

2017-11-12

Patients with complex care needs (PCCNs) often suffer from combinations of multiple chronic conditions, mental health problems, drug interactions and social vulnerability, which can lead to healthcare services overuse, underuse or misuse. Typically, PCCNs face interactional issues and unmet decisional needs regarding possible options in a cascade of interrelated decisions involving different stakeholders (themselves, their families, their caregivers, their healthcare practitioners). Gaps in knowledge, values clarification and social support in situations where options need to be deliberated hamper effective decision support interventions. This review aims to (1) assess decisional needs of PCCNs from the perspective of stakeholders, (2) build a taxonomy of these decisional needs and (3) prioritise decisional needs with knowledge users (clinicians, patients and managers). This review will be based on the interprofessional shared decision making (IP-SDM) model and the Ottawa Decision Support Framework. Applying a participatory research approach, we will identify potentially relevant studies through a comprehensive literature search; select relevant ones using eligibility criteria inspired from our previous scoping review on PCCNs; appraise quality using the Mixed Methods Appraisal Tool; conduct a three-step synthesis (sequential exploratory mixed methods design) to build taxonomy of key decisional needs; and integrate these results with those of a parallel PCCNs' qualitative decisional need assessment (semistructured interviews and focus group with stakeholders). This systematic review, together with the qualitative study (approved by the Centre Intégré Universitaire de Santé et Service Sociaux du Saguenay-Lac-Saint-Jean ethical committee), will produce a working taxonomy of key decisional needs (ontological contribution), to inform the subsequent user-centred design of a support tool for addressing PCCNs' decisional needs (practical contribution). We will adapt the IP-SDM model, normally dealing with a single decision, for PCCNs who experience cascade of decisions involving different stakeholders (theoretical contribution). Knowledge users will facilitate dissemination of the results in the Canadian primary care network. CRD42015020558. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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.

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.

Cross-layer restoration with software defined networking based on IP over optical transport networks

NASA Astrophysics Data System (ADS)

Yang, Hui; Cheng, Lei; Deng, Junni; Zhao, Yongli; Zhang, Jie; Lee, Young

2015-10-01

The IP over optical transport network is a very promising networking architecture applied to the interconnection of geographically distributed data centers due to the performance guarantee of low delay, huge bandwidth and high reliability at a low cost. It can enable efficient resource utilization and support heterogeneous bandwidth demands in highly-available, cost-effective and energy-effective manner. In case of cross-layer link failure, to ensure a high-level quality of service (QoS) for user request after the failure becomes a research focus. In this paper, we propose a novel cross-layer restoration scheme for data center services with software defined networking based on IP over optical network. The cross-layer restoration scheme can enable joint optimization of IP network and optical network resources, and enhance the data center service restoration responsiveness to the dynamic end-to-end service demands. We quantitatively evaluate the feasibility and performances through the simulation under heavy traffic load scenario in terms of path blocking probability and path restoration latency. Numeric results show that the cross-layer restoration scheme improves the recovery success rate and minimizes the overall recovery time.

Altered plasma levels of chemokines in autism and their association with social behaviors.

PubMed

Shen, Yidong; Ou, JInajun; Liu, Mengmeng; Shi, Lijuan; Li, Yamin; Xiao, Lu; Dong, Huixi; Zhang, Fengyu; Xia, Kun; Zhao, Jingping

2016-10-30

Autism Spectrum Disorder (ASD) is a group of neurodevelopment disorders with an unclear etiology. Chemokines have been implicated in the etiology and pathogenesis of ASD. The current study investigated the plasma levels of seven chemokines (RANTES, Eotaxin, MIP-1 α, MIP-1 β, MCP-1, IP-10, and MIG) in 42 young autistic patients and 35 age-matched typically developing (TD) children. The study also tested the association between these chemokine levels and social behaviors, as measured by the Social Responsiveness Scale (SRS). Compared to the TD children, RANTES, MIP-1α, and MIP-1β were higher, while IP-10 and MIG were lower in the autistic patients, after correcting for multiple comparisons. Among these seven chemokines, MIP-1α, MIP-1β and IP-10 levels were found to be associated with social behaviors in all the participants. Moreover, MIP-1α and IP-10 were found to be independent predictors of social behaviors. The results of our study support the hypothesis that altered chemokine levels are involved in the pathophysiology of ASD and they indicate that chemokines plasma levels could be potential biomarkers for ASD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Left Posterior Parietal Cortex Participates in Both Task Preparation and Episodic Retrieval

PubMed Central

Phillips, Jeffrey S.; Velanova, Katerina; Wolk, David A.; Wheeler, Mark E.

2012-01-01

Optimal memory retrieval depends not only on the fidelity of stored information, but also on the attentional state of the subject. Factors such as mental preparedness to engage in stimulus processing can facilitate or hinder memory retrieval. The current study used functional magnetic resonance imaging (fMRI) to distinguish preparatory brain activity before episodic and semantic retrieval tasks from activity associated with retrieval itself. A catch-trial imaging paradigm permitted separation of neural responses to preparatory task cues and memory probes. Episodic and semantic task preparation engaged a common set of brain regions, including the bilateral intraparietal sulcus (IPS), left fusiform gyrus (FG), and the pre-supplementary motor area (pre-SMA). In the subsequent retrieval phase, the left IPS was among a set of frontoparietal regions that responded differently to old and new stimuli. In contrast, the right IPS responded to preparatory cues with little modulation during memory retrieval. The findings support a strong left-lateralization of retrieval success effects in left parietal cortex, and further indicate that left IPS performs operations that are common to both task preparation and memory retrieval. Such operations may be related to attentional control, monitoring of stimulus relevance, or retrieval. PMID:19285142

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.

Utilization of Internet Protocol-Based Voice Systems in Remote Payload Operations

NASA Technical Reports Server (NTRS)

Chamberlain, jim; Bradford, Bob; Best, Susan; Nichols, Kelvin

2002-01-01

Due to limited crew availability to support science and the large number of experiments to be operated simultaneously, telescience is key to a successful International Space Station (ISS) science program. Crew, operations personnel at NASA centers, and researchers at universities and companies around the world must work closely together to per orm scientific experiments on-board ISS. The deployment of reliable high-speed Internet Protocol (IP)-based networks promises to greatly enhance telescience capabilities. These networks are now being used to cost-effectively extend the reach of remote mission support systems. They reduce the need for dedicated leased lines and travel while improving distributed workgroup collaboration capabilities. NASA has initiated use of Voice over Internet Protocol (VoIP) to supplement the existing mission voice communications system used by researchers at their remote sites. The Internet Voice Distribution System (IVoDS) connects remote researchers to mission support "loopsll or conferences via NASA networks and Internet 2. Researchers use NODS software on personal computers to talk with operations personnel at NASA centers. IVoDS also has the ;capability, if authorized, to allow researchers to communicate with the ISS crew during experiment operations. NODS was developed by Marshall Space Flight Center with contractors & Technology, First Virtual Communications, Lockheed-Martin, and VoIP Group. NODS is currently undergoing field-testing with full deployment for up to 50 simultaneous users expected in 2002. Research is being performed in parallel with IVoDS deployment for a next-generation system to qualitatively enhance communications among ISS operations personnel. In addition to the current voice capability, video and data/application-sharing capabilities are being investigated. IVoDS technology is also being considered for mission support systems for programs such as Space Launch Initiative and Homeland Defense.

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...