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Sample records for advanced levels specific

  1. Serum neuron specific enolase levels correlate with patient prognosis for advanced lung cancer

    PubMed Central

    Xue, Feng; Zhu, Lin; Wang, Liyan; Wang, Quan

    2015-01-01

    To analyze the clinical and prognostic value of neuron specific enolase (NSE) levels in serum of advanced lung cancer patients, we analyzed serum NSE level of 110 advanced lung cancer patients (case group), 100 benign lung disease patients (benign disease group), and 100 healthy persons (control group). Case group patients were divided by NSE level into ≥25 ng/mL (52 cases) and <25 ng/mL (58 cases) groups to analyze overall survival (OS) and progression-free survival (PFS). The results showed the serum NSE levels of case group patients were significantly higher than those of control or benign disease group patients (P<0.05). Serum NSE levels of small cell lung cancer patients were significantly higher than those of patients with other tumor pathologies (all P<0.05). Median OS significantly differed between patients with NSE levels ≥25 ng/mL (23.7 months) and <25 ng/mL (31.4 months) (P<0.05). Median PFS also significantly differed between patients with NSE levels ≥25 ng/mL (13.5 months) and <25 ng/mL (17.6 months) (χ 2=9.992; P<0.05). Tumor pathology (RR=4.136), patient performance status score (RR=2.903), and serum NSE level (RR=2.338) were factors influencing OS (P<0.05). Patient performance status score (RR=2.903), number of chemotherapy lines (RR=1.776), and serum NSE level (RR=2.075) were influencing factors in patients’ PFS (P<0.05). In brief, serum NSE level significantly correlates with advanced lung cancer patient prognosis and may be useful as an auxiliary index to predict prognosis. PMID:26309614

  2. Drilling at Advanced Levels

    ERIC Educational Resources Information Center

    Case, Doug

    1977-01-01

    Instances where drilling is useful for advanced language are discussed. Several types of drills are recommended, with the philosophy that advanced level drills should have a lighter style and be regarded as a useful, occasional means of practicing individual new items. (CHK)

  3. Skimming & Scanning. Advanced Level.

    ERIC Educational Resources Information Center

    Fry, Edward B.

    Part of a series intended to develop essential specialized reading skills, this text/workbook is designed to provide instruction and practice in skimming and scanning for students reading at the seventh through tenth grade reading levels, considered the advanced level. Part 1 of the book deals with skimming. A lesson defines skimming (the rapid…

  4. Designing and Implementing a New Advanced Level Biology Course

    ERIC Educational Resources Information Center

    Hall, Angela; Reiss, Michael J.; Rowell, Cathy; Scott, Anne

    2003-01-01

    Salters-Nuffield Advanced Biology is a new advanced level biology course, piloted from September 2002 in England with around 1200 students. This paper discusses the reasons for developing a new advanced biology course at this time, the philosophy of the project and how the materials are being written and the specification devised. The aim of the…

  5. SNAB: A New Advanced Level Biology Course

    ERIC Educational Resources Information Center

    Reiss, Michael J.

    2005-01-01

    Of all the sciences, biology has probably made the most rapid progress in recent years and the need for this to be reflected in a new Advanced Level biology course has long been recognised in the UK. After wide-ranging consultation and successful piloting in over 50 schools and colleges in England and Wales, the new Salters-Nuffield Advanced…

  6. Advanced supersonic propulsion study. [with emphasis on noise level reduction

    NASA Technical Reports Server (NTRS)

    Sabatella, J. A. (Editor)

    1974-01-01

    A study was conducted to determine the promising propulsion systems for advanced supersonic transport application, and to identify the critical propulsion technology requirements. It is shown that noise constraints have a major effect on the selection of the various engine types and cycle parameters. Several promising advanced propulsion systems were identified which show the potential of achieving lower levels of sideline jet noise than the first generation supersonic transport systems. The non-afterburning turbojet engine, utilizing a very high level of jet suppression, shows the potential to achieve FAR 36 noise level. The duct-heating turbofan with a low level of jet suppression is the most attractive engine for noise levels from FAR 36 to FAR 36 minus 5 EPNdb, and some series/parallel variable cycle engines show the potential of achieving noise levels down to FAR 36 minus 10 EPNdb with moderate additional penalty. The study also shows that an advanced supersonic commercial transport would benefit appreciably from advanced propulsion technology. The critical propulsion technology needed for a viable supersonic propulsion system, and the required specific propulsion technology programs are outlined.

  7. Second Language Vocabulary Growth at Advanced Level

    ERIC Educational Resources Information Center

    Ozturk, Meral

    2016-01-01

    This study investigated the receptive vocabulary growth of advanced EFL learners in an English-medium degree programme. The study used the Vocabulary Size Test in a cross-sectional design to measure the vocabulary size of learners at various stages of study. The effect of word frequency on vocabulary development and the presence of an…

  8. Assessing an Advanced Level Introductory Sociology Course

    ERIC Educational Resources Information Center

    Keesler, Venessa A.; Fermin, Baranda J.; Schneider, Barbara

    2008-01-01

    In 2001, the governing council of the American Sociological Association (ASA) appointed Professor Caroline Persell of New York University to launch a task force with the goal of creating an advanced high school sociology curriculum that would also be a model for introductory sociology courses in colleges and universities. The principle goal of the…

  9. Realistic Specific Power Expectations for Advanced Radioisotope Power Systems

    NASA Technical Reports Server (NTRS)

    Mason, Lee S.

    2006-01-01

    Radioisotope Power Systems (RPS) are being considered for a wide range of future NASA space science and exploration missions. Generally, RPS offer the advantages of high reliability, long life, and predictable power production regardless of operating environment. Previous RPS, in the form of Radioisotope Thermoelectric Generators (RTG), have been used successfully on many NASA missions including Apollo, Viking, Voyager, and Galileo. NASA is currently evaluating design options for the next generation of RPS. Of particular interest is the use of advanced, higher efficiency power conversion to replace the previous thermoelectric devices. Higher efficiency reduces the quantity of radioisotope fuel and potentially improves the RPS specific power (watts per kilogram). Power conversion options include Segmented Thermoelectric (STE), Stirling, Brayton, and Thermophotovoltaic (TPV). This paper offers an analysis of the advanced 100 watt-class RPS options and provides credible projections for specific power. Based on the analysis presented, RPS specific power values greater than 10 W/kg appear unlikely.

  10. Nonnative Teachers Teaching at the Advanced Level: Challenges and Opportunities.

    ERIC Educational Resources Information Center

    Byrnes, Heidi; Crane, Cori; Sprang, Katherine A.

    2002-01-01

    Discusses whether students can learn a second language well enough to teach at advanced academic levels and if so, what program would help them achieve this level. Proposes that by teaching advanced courses, graduate students, whose language development usually receives scant attention, will have the opportunity to improve their linguistic…

  11. Comparing Content in Selected GCE A Levels and Advanced GNVQs.

    ERIC Educational Resources Information Center

    Holding, Gordon; And Others

    1996-01-01

    In an action research project, four British further education colleges compared mandatory units of three Advanced General National Vocational Qualifications (GNVQs)--business, art and design, and health and social care--with related General Certificate of Education Advanced Level (GCE A-level) syllabuses. Activities included a detailed comparison…

  12. Advanced Wet Tantalum Capacitors: Design, Specifications and Performance

    NASA Technical Reports Server (NTRS)

    Teverovsky, Alexander

    2016-01-01

    Insertion of new types of commercial, high volumetric efficiency wet tantalum capacitors in space systems requires reassessment of the existing quality assurance approaches that have been developed for capacitors manufactured to MIL-PRF-39006 requirements. The specifics of wet electrolytic capacitors is that leakage currents flowing through electrolyte can cause gas generation resulting in building up of internal gas pressure and rupture of the case. The risk associated with excessive leakage currents and increased pressure is greater for high value advanced wet tantalum capacitors, but it has not been properly evaluated yet. This presentation gives a review of specifics of the design, performance, and potential reliability risks associated with advanced wet tantalum capacitors. Problems related to setting adequate requirements for DPA, leakage currents, hermeticity, stability at low and high temperatures, ripple currents for parts operating in vacuum, and random vibration testing are discussed. Recommendations for screening and qualification to reduce risks of failures have been suggested.

  13. Advanced computer architecture specification for automated weld systems

    NASA Technical Reports Server (NTRS)

    Katsinis, Constantine

    1994-01-01

    This report describes the requirements for an advanced automated weld system and the associated computer architecture, and defines the overall system specification from a broad perspective. According to the requirements of welding procedures as they relate to an integrated multiaxis motion control and sensor architecture, the computer system requirements are developed based on a proven multiple-processor architecture with an expandable, distributed-memory, single global bus architecture, containing individual processors which are assigned to specific tasks that support sensor or control processes. The specified architecture is sufficiently flexible to integrate previously developed equipment, be upgradable and allow on-site modifications.

  14. Advance care planning: identifying system-specific barriers and facilitators

    PubMed Central

    Hagen, N.A.; Howlett, J.; Sharma, N.C.; Biondo, P.; Holroyd-Leduc, J.; Fassbender, K.; Simon, J.

    2015-01-01

    Background Advance care planning (acp) is an important process in health care today. How to prospectively identify potential local barriers and facilitators to uptake of acp across a complex, multi-sector, publicly funded health care system and how to develop specific mitigating strategies have not been well characterized. Methods We surveyed a convenience sample of clinical and administrative health care opinion leaders across the province of Alberta to characterize system-specific barriers and facilitators to uptake of acp. The survey was based on published literature about the barriers to and facilitators of acp and on the Michie Theoretical Domains Framework. Results Of 88 surveys, 51 (58%) were returned. The survey identified system-specific barriers that could challenge uptake of acp. The factors were categorized into four main domains. Three examples of individual system-specific barriers were “insufficient public engagement and misunderstanding,” “conflict among different provincial health service initiatives,” and “lack of infrastructure.” Local system-specific barriers and facilitators were subsequently explored through a semi-structured informal discussion group involving key informants. The group identified approaches to mitigate specific barriers. Conclusions Uptake of acp is a priority for many health care systems, but bringing about change in multi-sector health care systems is complex. Identifying system-specific barriers and facilitators to the uptake of innovation are important elements of successful knowledge translation. We developed and successfully used a simple and inexpensive process to identify local system-specific barriers and enablers to uptake of acp, and to identify specific mitigating strategies. PMID:26300673

  15. Advances in early kidney specification, development and patterning

    PubMed Central

    Dressler, Gregory R.

    2009-01-01

    The kidney is a model developmental system for understanding mesodermal patterning and organogenesis, a process that requires regional specification along multiple body axes, the proliferation and differentiation of progenitor cells, and integration with other tissues. Recent progress in the field has highlighted the essential roles of intrinsic nuclear factors and secreted signaling molecules in specifying renal epithelial stem cells and their self-renewal, in driving the complex dynamics of epithelial cell branching morphogenesis, and in nephron patterning. How these developments influence and advance our understanding of kidney development is discussed. PMID:19906853

  16. Reassessing the Economic Value of Advanced Level Mathematics

    ERIC Educational Resources Information Center

    Adkins, Michael; Noyes, Andrew

    2016-01-01

    In the late 1990s, the economic return to Advanced level (A-level) mathematics was examined. The analysis was based upon a series of log-linear models of earnings in the 1958 National Child Development Survey (NCDS) and the National Survey of 1980 Graduates and Diplomates. The core finding was that A-level mathematics had a unique earnings premium…

  17. Fraction of the theoretical specific energy achieved on pack level for hypothetical battery chemistries

    NASA Astrophysics Data System (ADS)

    Eroglu, Damla; Ha, Seungbum; Gallagher, Kevin G.

    2014-12-01

    In valuing new active materials chemistries for advanced batteries, the theoretical specific energy is commonly used to motivate research and development. A packaging factor is then used to relate the theoretical specific energy to the pack-level specific energy. As this factor is typically assumed constant, higher theoretical specific energies are judged to result in higher pack-level specific energies. To test this implicit assumption, we calculated the fraction of the theoretical specific energy achieved on the pack level for hypothetical cell chemistries with various open-circuit voltages and theoretical specific energies using a peer-review bottom-up battery design model. The pack-level specific energy shows significant dependence on the open-circuit voltage and electrochemical impedance due to changes in the quantity of inactive materials required. At low-valued average open-circuit voltages, systems with dramatically different theoretical specific energies may result in battery packs similar in mass and volume. The fraction of the theoretical specific energy achieved on the pack level is higher for the lower theoretical specific energy systems mainly because the active materials mass dominates the pack mass. Finally, low-valued area-specific impedance is shown to be critical for chemistries of high theoretical specific energy and low open-circuit voltage to achieve higher pack-level specific energies.

  18. Systems-Level Synthetic Biology for Advanced Biofuel Production

    SciTech Connect

    Ruffing, Anne; Jensen, Travis J.; Strickland, Lucas Marshall; Meserole, Stephen; Tallant, David

    2015-03-01

    Cyanobacteria have been shown to be capable of producing a variety of advanced biofuels; however, product yields remain well below those necessary for large scale production. New genetic tools and high throughput metabolic engineering techniques are needed to optimize cyanobacterial metabolisms for enhanced biofuel production. Towards this goal, this project advances the development of a multiple promoter replacement technique for systems-level optimization of gene expression in a model cyanobacterial host: Synechococcus sp. PCC 7002. To realize this multiple-target approach, key capabilities were developed, including a high throughput detection method for advanced biofuels, enhanced transformation efficiency, and genetic tools for Synechococcus sp. PCC 7002. Moreover, several additional obstacles were identified for realization of this multiple promoter replacement technique. The techniques and tools developed in this project will help to enable future efforts in the advancement of cyanobacterial biofuels.

  19. Technology Readiness Levels for Advanced Nuclear Fuels and Materials Development

    SciTech Connect

    Jon Carmack

    2014-01-01

    The Technology Readiness Level (TRL) process is used to quantitatively assess the maturity of a given technology. The TRL process has been developed and successfully used by the Department of Defense (DOD) for development and deployment of new technology and systems for defense applications. In addition, NASA has also successfully used the TRL process to develop and deploy new systems for space applications. Advanced nuclear fuels and materials development is a critical technology needed for closing the nuclear fuel cycle. Because the deployment of a new nuclear fuel forms requires a lengthy and expensive research, development, and demonstration program, applying the TRL concept to the advanced fuel development program is very useful as a management and tracking tool. This report provides definition of the technology readiness level assessment process as defined for use in assessing nuclear fuel technology development for the Advanced Fuel Campaign (AFC).

  20. An Intermediate Advanced Level Israeli Hebrew Refresher Course.

    ERIC Educational Resources Information Center

    Blanc, Haim

    "An Intermediate-Advanced Level Israeli Hebrew Refresher Course" comprises an audiolingual course in seven volumes. "Book I" contains introductory notes on Israeli Hebrew, the sound system, and phonology drills. These preface 21 lessons (three units of seven lessons each) which consist of vocabulary practices, narratives, dialogs, grammar notes,…

  1. An Intermediate-Advanced Level Laotian Refresher Course.

    ERIC Educational Resources Information Center

    English Language Services, Inc., Washington, DC.

    These instructional materials have been prepared for students who have completed an introductory college-level Laotian course of one year or more or have had an "intensive" course of several months. The "Refresher" materials contained in Book I are intended to prepare the student for the intermediate-advanced materials in Books II and III. Each of…

  2. An Intermediate-Advanced Level Malay Refresher Course.

    ERIC Educational Resources Information Center

    Rice, Oliver; And Others

    The first unit of this eight-volume refresher course in intermediate-advanced level Malay presents a detailed description of the Malay sound system, with phonological examples in both official (Latin) orthography and phonetic transcription. The remaining units in Book I--Part One (Units 2-4) and the five units in the second volume (Book I--Part…

  3. Teaching Physics at Advanced Level: A Question of Style.

    ERIC Educational Resources Information Center

    Newton, Leonard; Rogers, Laurence

    1996-01-01

    Questions whether didactic methods employed for teaching physics at the advanced level can adequately match the variety of needs of students in the contemporary context. Offers a framework for promoting a style of teaching that is responsive and versatile. Contains 14 references. (Author/JRH)

  4. Advances in the development of SUMO specific protease (SENP) inhibitors.

    PubMed

    Kumar, Ashutosh; Zhang, Kam Y J

    2015-01-01

    Sumoylation is a reversible post-translational modification that involves the covalent attachment of small ubiquitin-like modifier (SUMO) proteins to their substrate proteins. Prior to their conjugation, SUMO proteins need to be proteolytically processed from its precursor form to mature or active form. SUMO specific proteases (SENPs) are cysteine proteases that cleave the pro or inactive form of SUMO at C-terminus using its hydrolase activity to expose two glycine residues. SENPs also catalyze the de-conjugation of SUMO proteins using their isopeptidase activity, which is crucial for recycling of SUMO from substrate proteins. SENPs are important for maintaining the balance between sumoylated and unsumoylated proteins required for normal cellular physiology. Several studies reported the overexpression of SENPs in disease conditions and highlighted their role in the development of various diseases, especially cancer. In this review, we will address the current biological understanding of various SENP isoforms and their role in the pathogenesis of different cancers and other diseases. We will then discuss the advances in the development of protein-based, peptidyl and small molecule inhibitors of various SENP isoforms. Finally, we will summarize successful examples of computational screening that allowed the identification of SENP inhibitors with therapeutic potential. PMID:25893082

  5. Reinforcing Constructivist Teaching in Advanced Level Biochemistry through the Introduction of Case-Based Learning Activities

    ERIC Educational Resources Information Center

    Hartfield, Perry J.

    2010-01-01

    In the process of curriculum development, I have integrated a constructivist teaching strategy into an advanced-level biochemistry teaching unit. Specifically, I have introduced case-based learning activities into the teaching/learning framework. These case-based learning activities were designed to develop problem-solving skills, consolidate…

  6. ESL for Hotel/Hospitality Industry. Level: Advanced Beginner/Intermediate.

    ERIC Educational Resources Information Center

    Western Suffolk County Board of Cooperative Educational Services, Northport, NY.

    This document contains 16 lesson plans for an advanced beginning and intermediate course in work-related English for non-English- or limited-English-speaking entry-level employees in the hotel and hospitality industry. Course objectives are as follows: helping participants understand and use job-specific vocabulary; receive and understand…

  7. Advanced High-Level Waste Glass Research and Development Plan

    SciTech Connect

    Peeler, David K.; Vienna, John D.; Schweiger, Michael J.; Fox, Kevin M.

    2015-07-01

    The U.S. Department of Energy Office of River Protection (ORP) has implemented an integrated program to increase the loading of Hanford tank wastes in glass while meeting melter lifetime expectancies and process, regulatory, and product quality requirements. The integrated ORP program is focused on providing a technical, science-based foundation from which key decisions can be made regarding the successful operation of the Hanford Tank Waste Treatment and Immobilization Plant (WTP) facilities. The fundamental data stemming from this program will support development of advanced glass formulations, key process control models, and tactical processing strategies to ensure safe and successful operations for both the low-activity waste (LAW) and high-level waste (HLW) vitrification facilities with an appreciation toward reducing overall mission life. The purpose of this advanced HLW glass research and development plan is to identify the near-, mid-, and longer-term research and development activities required to develop and validate advanced HLW glasses and their associated models to support facility operations at WTP, including both direct feed and full pretreatment flowsheets. This plan also integrates technical support of facility operations and waste qualification activities to show the interdependence of these activities with the advanced waste glass (AWG) program to support the full WTP mission. Figure ES-1 shows these key ORP programmatic activities and their interfaces with both WTP facility operations and qualification needs. The plan is a living document that will be updated to reflect key advancements and mission strategy changes. The research outlined here is motivated by the potential for substantial economic benefits (e.g., significant increases in waste throughput and reductions in glass volumes) that will be realized when advancements in glass formulation continue and models supporting facility operations are implemented. Developing and applying advanced

  8. Advanced Free Flight Planner and Dispatcher's Workstation: Preliminary Design Specification

    NASA Technical Reports Server (NTRS)

    Wilson, J.; Wright, C.; Couluris, G. J.

    1997-01-01

    The National Aeronautics and Space Administration (NASA) has implemented the Advanced Air Transportation Technology (AATT) program to investigate future improvements to the national and international air traffic management systems. This research, as part of the AATT program, developed preliminary design requirements for an advanced Airline Operations Control (AOC) dispatcher's workstation, with emphasis on flight planning. This design will support the implementation of an experimental workstation in NASA laboratories that would emulate AOC dispatch operations. The work developed an airline flight plan data base and specified requirements for: a computer tool for generation and evaluation of free flight, user preferred trajectories (UPT); the kernel of an advanced flight planning system to be incorporated into the UPT-generation tool; and an AOC workstation to house the UPT-generation tool and to provide a real-time testing environment. A prototype for the advanced flight plan optimization kernel was developed and demonstrated. The flight planner uses dynamic programming to search a four-dimensional wind and temperature grid to identify the optimal route, altitude and speed for successive segments of a flight. An iterative process is employed in which a series of trajectories are successively refined until the LTPT is identified. The flight planner is designed to function in the current operational environment as well as in free flight. The free flight environment would enable greater flexibility in UPT selection based on alleviation of current procedural constraints. The prototype also takes advantage of advanced computer processing capabilities to implement more powerful optimization routines than would be possible with older computer systems.

  9. Specification of advanced safety modeling requirements (Rev. 0).

    SciTech Connect

    Fanning, T. H.; Tautges, T. J.

    2008-06-30

    The U.S. Department of Energy's Global Nuclear Energy Partnership has lead to renewed interest in liquid-metal-cooled fast reactors for the purpose of closing the nuclear fuel cycle and making more efficient use of future repository capacity. However, the U.S. has not designed or constructed a fast reactor in nearly 30 years. Accurate, high-fidelity, whole-plant dynamics safety simulations will play a crucial role by providing confidence that component and system designs will satisfy established design limits and safety margins under a wide variety of operational, design basis, and beyond design basis transient conditions. Current modeling capabilities for fast reactor safety analyses have resulted from several hundred person-years of code development effort supported by experimental validation. The broad spectrum of mechanistic and phenomenological models that have been developed represent an enormous amount of institutional knowledge that needs to be maintained. Complicating this, the existing code architectures for safety modeling evolved from programming practices of the 1970s. This has lead to monolithic applications with interdependent data models which require significant knowledge of the complexities of the entire code in order for each component to be maintained. In order to develop an advanced fast reactor safety modeling capability, the limitations of the existing code architecture must be overcome while preserving the capabilities that already exist. To accomplish this, a set of advanced safety modeling requirements is defined, based on modern programming practices, that focuses on modular development within a flexible coupling framework. An approach for integrating the existing capabilities of the SAS4A/SASSYS-1 fast reactor safety analysis code into the SHARP framework is provided in order to preserve existing capabilities while providing a smooth transition to advanced modeling capabilities. In doing this, the advanced fast reactor safety models will

  10. Advancing the Science of Community-Level Interventions

    PubMed Central

    Beehler, Sarah; Deutsch, Charles; Green, Lawrence W.; Hawe, Penelope; McLeroy, Kenneth; Miller, Robin Lin; Rapkin, Bruce D.; Schensul, Jean J.; Schulz, Amy J.; Trimble, Joseph E.

    2011-01-01

    Community interventions are complex social processes that need to move beyond single interventions and outcomes at individual levels of short-term change. A scientific paradigm is emerging that supports collaborative, multilevel, culturally situated community interventions aimed at creating sustainable community-level impact. This paradigm is rooted in a deep history of ecological and collaborative thinking across public health, psychology, anthropology, and other fields of social science. The new paradigm makes a number of primary assertions that affect conceptualization of health issues, intervention design, and intervention evaluation. To elaborate the paradigm and advance the science of community intervention, we offer suggestions for promoting a scientific agenda, developing collaborations among professionals and communities, and examining the culture of science. PMID:21680923

  11. Advanced biologically plausible algorithms for low-level image processing

    NASA Astrophysics Data System (ADS)

    Gusakova, Valentina I.; Podladchikova, Lubov N.; Shaposhnikov, Dmitry G.; Markin, Sergey N.; Golovan, Alexander V.; Lee, Seong-Whan

    1999-08-01

    At present, in computer vision, the approach based on modeling the biological vision mechanisms is extensively developed. However, up to now, real world image processing has no effective solution in frameworks of both biologically inspired and conventional approaches. Evidently, new algorithms and system architectures based on advanced biological motivation should be developed for solution of computational problems related to this visual task. Basic problems that should be solved for creation of effective artificial visual system to process real world imags are a search for new algorithms of low-level image processing that, in a great extent, determine system performance. In the present paper, the result of psychophysical experiments and several advanced biologically motivated algorithms for low-level processing are presented. These algorithms are based on local space-variant filter, context encoding visual information presented in the center of input window, and automatic detection of perceptually important image fragments. The core of latter algorithm are using local feature conjunctions such as noncolinear oriented segment and composite feature map formation. Developed algorithms were integrated into foveal active vision model, the MARR. It is supposed that proposed algorithms may significantly improve model performance while real world image processing during memorizing, search, and recognition.

  12. Sex-Specific Parental Effects on Offspring Lipid Levels

    PubMed Central

    Predazzi, Irene M; Sobota, Rafal S; Sanna, Serena; Bush, William S; Bartlett, Jacquelaine; Lilley, Jessica S; Linton, MacRae F; Schlessinger, David; Cucca, Francesco; Fazio, Sergio; Williams, Scott M

    2015-01-01

    Background Plasma lipid levels are highly heritable traits, but known genetic loci can only explain a small portion of their heritability. Methods and Results In this study, we analyzed the role of parental levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) in explaining the values of the corresponding traits in adult offspring. We also evaluated the contribution of nongenetic factors that influence lipid traits (age, body mass index, smoking, medications, and menopause) alone and in combination with variability at the genetic loci known to associate with TC, LDL-C, HDL-C, and TG levels. We performed comparisons among different sex-specific regression models in 416 families from the Framingham Heart Study and 304 from the SardiNIA cohort. Models including parental lipid levels explain significantly more of the trait variation than models without these measures, explaining up to ≈39% of the total trait variation. Of this variation, the parent-of-origin effect explains as much as ≈15% and it does so in a sex-specific way. This observation is not owing to shared environment, given that spouse-pair correlations were negligible (<1.5% explained variation in all cases) and is distinct from previous genetic and acquired factors that are known to influence serum lipid levels. Conclusions These findings support the concept that unknown genetic and epigenetic contributors are responsible for most of the heritable component of the plasma lipid phenotype, and that, at present, the clinical utility of knowing age-matched parental lipid levels in assessing risk of dyslipidemia supersedes individual locus effects. Our results support the clinical utility of knowing parental lipid levels in assessing future risk of dyslipidemia. PMID:26126546

  13. Advanced Initiation Systems Manufacturing Level 2 Milestone Completion Summary

    SciTech Connect

    Chow, R; Schmidt, M

    2009-10-01

    Milestone Description - Advanced Initiation Systems Detonator Design and Prototype. Milestone Grading Criteria - Design new generation chip slapper detonator and manufacture a prototype using advanced manufacturing processes, such as all-dry chip metallization and solvent-less flyer coatings. The advanced processes have been developed for manufacturing detonators with high material compatibility and reliability to support future LEPs, e.g. the B61, and new weapons systems. Perform velocimetry measurements to determine slapper velocity as a function of flight distance. A prototype detonator assembly and stripline was designed for low-energy chip slappers. Pictures of the prototype detonator and stripline are shown. All-dry manufacturing processes were used to address compatibility issues. KCP metallized the chips in a physical vapor deposition system through precision-aligned shadow masks. LLNL deposited a solvent-less polyimide flyer with a processes called SLIP, which stands for solvent-less vapor deposition followed by in-situ polymerization. LANL manufactured the high-surface-area (HSA) high explosive (HE) pellets. Test fires of two chip slapper designs, radius and bowtie, were performed at LLNL in the High Explosives Application Facility (HEAF). Test fires with HE were conducted to establish the threshold firing voltages. pictures of the chip slappers before and after test fires are shown. Velocimetry tests were then performed to obtain slapper velocities at or above the threshold firing voltages. Figure 5 shows the slapper velocity as a function of distance and time at the threshold voltage, for both radius and bowtie bridge designs. Both designs were successful at initiating the HE at low energy levels. Summary of Accomplishments are: (1) All-dry process for chip manufacture developed; (2) Solventless process for slapper materials developed; (3) High-surface area explosive pellets developed; (4) High performance chip slappers developed; (5) Low-energy chip

  14. Specification, Design, and Analysis of Advanced HUMS Architectures

    NASA Technical Reports Server (NTRS)

    Mukkamala, Ravi

    2004-01-01

    During the two-year project period, we have worked on several aspects of domain-specific architectures for HUMS. In particular, we looked at using scenario-based approach for the design and designed a language for describing such architectures. The language is now being used in all aspects of our HUMS design. In particular, we have made contributions in the following areas. 1) We have employed scenarios in the development of HUMS in three main areas. They are: (a) To improve reusability by using scenarios as a library indexing tool and as a domain analysis tool; (b) To improve maintainability by recording design rationales from two perspectives - problem domain and solution domain; (c) To evaluate the software architecture. 2) We have defined a new architectural language called HADL or HUMS Architectural Definition Language. It is a customized version of xArch/xADL. It is based on XML and, hence, is easily portable from domain to domain, application to application, and machine to machine. Specifications written in HADL can be easily read and parsed using the currently available XML parsers. Thus, there is no need to develop a plethora of software to support HADL. 3) We have developed an automated design process that involves two main techniques: (a) Selection of solutions from a large space of designs; (b) Synthesis of designs. However, the automation process is not an absolute Artificial Intelligence (AI) approach though it uses a knowledge-based system that epitomizes a specific HUMS domain. The process uses a database of solutions as an aid to solve the problems rather than creating a new design in the literal sense. Since searching is adopted as the main technique, the challenges involved are: (a) To minimize the effort in searching the database where a very large number of possibilities exist; (b) To develop representations that could conveniently allow us to depict design knowledge evolved over many years; (c) To capture the required information that aid the

  15. Joint Leveling for Advanced Kienbock’s Disease

    PubMed Central

    Calfee, Ryan P.; Van Steyn, Marlo O.; Gyuricza, Cassie; Adams, Amelia; Weiland, Andrew J.; Gelberman, Richard H.

    2010-01-01

    PURPOSE The use of joint leveling procedures to treat Kienbock’s disease has been limited by the degree of disease advancement. This study was designed to compare clinical and radiographic outcomes of wrists with more advanced Kienbock’s disease (stage IIIB) to wrists with less advanced disease (stage II/IIIA) following radius shortening osteotomy. METHODS This retrospective study enrolled 31 adult wrists (30 patients, mean age 39 years), treated by radius shortening osteotomy between two institutions for either stage IIIB (n=14) or stage II/IIIA (n=17) disease. Evaluation was carried out at a mean of 74 months (IIIB, 77 months; II/IIIA, 72 months). Radiographic assessment determined disease progression. Clinical outcomes were determined by validated patient-based and objective measures. RESULTS Patient-based outcome ratings of wrists treated for stage IIIB were similar to those with stage II/IIIA [QuickDASH (15 vs 12:p=.63), MMWS (84 vs 87:p=.59), VAS pain (1.2 vs 1.7:p=.45), VAS function (2.6 vs 2.1:p=.59)]. The average flexion/extension arc was 102° for wrists with stage IIIB and 106° for wrists with stage II/IIIA Kienbock’s (p=.70). Grip strength was 77% of the opposite side for stage IIIB wrists versus 85% for stage II/IIIA (p=.25). Postoperative carpal height ratio and radioscaphoid angle were worse (p<.05) for wrists treated for stage IIIB (0.46:65°) than stage II/IIIA (0.53:53°) disease. Radiographic disease progression occurred in 7 wrists (6 stage II/IIIA: 1 stage IIIB). The one stage IIIB wrist that progressed underwent wrist arthrodesis. CONCLUSIONS In this limited series, clinical outcomes of radius shortening using validated, patient-based assessment instruments and objective measures failed to demonstrate predicted “clinically relevant” differences between stage II/IIIA and IIIB Kienbock’s. Provided the high percentage successful clinical outcomes in this case series of 14 stage IIIB wrists, we believe that static carpal malalignment

  16. Advanced teleradiology: a specification of a DICOM teleradiology application profile

    NASA Astrophysics Data System (ADS)

    von Gehlen, Sandra; Fritz, Steven L.; Eichelberg, Marco; Hewett, Andrew J.; Boesenberg, Holger; Jensch, Peter F.

    1998-07-01

    The functionality of many teleradiology systems is limited to image transfer to a remote workstation. It is not possible to access reports or images from older studies, or to create new reports of current cases. Additionally, teleradiology systems from different vendors are usually not interoperable. Future teleradiology systems should provide bi-directional image transfer as well as image annotation, the possibility to create and send back text reports, and access to previous reports. Furthermore, it becomes increasingly important that teleradiology systems are conformant to the DICOM standard. The advanced teleradiology service (ATS) is compatible to the DICOM standard and is based on the functional model of the standard. In addition to receiving current images which is straightforward, the ATS supports retrieving of correlative images, studies and reports. One further feature of ATS is the review of images which is supported with flexible image compression to keep the demand for bandwidth minimal. Additionally, creating and modifying multimedia results is supported. The multimedia results are based on 'Structured Reporting' (SR) which is a supplement of the DICOM standard. SR offers a mechanism to represent results for many fields of application in medicine. The types of documents supported by SR range from simple text descriptions to multimedia interpretation reports. For this reason it is important to evaluate scenarios and to define the requirements of SR in the radiological environment. The definition of ATS is intended to provide a tested reference architecture for teleradiology to which vendors can adhere in order to develop teleradiology systems with DICOM 'plug and play' capability.

  17. Disease-specific mutations in mature lymphoid neoplasms: Recent advances

    PubMed Central

    Sakata-Yanagimoto, Mamiko; Enami, Terukazu; Yokoyama, Yasuhisa; Chiba, Shigeru

    2014-01-01

    Mature lymphoid neoplasms (MLN) are clinically and pathologically more complex than precursor lymphoid neoplasms. Until recently, molecular characterization of MLN was mainly based on cytogenetics/fluorescence in situ hybridization, allele copy number, and mRNA expression, approaches that yielded scanty gene mutation information. Use of massive parallel sequencing technologies has changed this outcome, and now many gene mutations have been discovered. Some of these are considerably frequent in, and substantially specific to, distinct MLN subtypes, and occur at single or several hotspots. They include the V600E BRAF mutation in hairy cell leukemia, the L265P MYD88 mutation in Waldenström macroglobulinemia, the G17V RHOA mutation in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified, and the Y640F//D661Y/V/H/I//N647I STAT3 mutations in T-cell large granular lymphocytic leukemia. Detecting these mutations is highly valuable in diagnosing MLN subtypes. Defining these mutations also sheds light on the molecular pathogenesis of MLN, furthering development of molecular targeting therapies. In this review, we focus on the disease-specific gene mutations in MLN discovered by recent massive sequencing technologies. PMID:24689848

  18. Prototype Operational Advances for Atmospheric Radiation Dose Rate Specification

    NASA Astrophysics Data System (ADS)

    Tobiska, W. K.; Bouwer, D.; Bailey, J. J.; Didkovsky, L. V.; Judge, K.; Garrett, H. B.; Atwell, W.; Gersey, B.; Wilkins, R.; Rice, D.; Schunk, R. W.; Bell, D.; Mertens, C. J.; Xu, X.; Crowley, G.; Reynolds, A.; Azeem, I.; Wiltberger, M. J.; Wiley, S.; Bacon, S.; Teets, E.; Sim, A.; Dominik, L.

    2014-12-01

    effective dose rate measurements and a thermal neutron monitor to characterize Single Event Effects (SEEs) in avionics. In this presentation we describe recent ARMAS and USEWX advances that will ultimately provide operational users with real-time dose and dose rate data for human tissue and avionics exposure risk mitigation.

  19. Five levels of PACS modularity: integrating 3D and other advanced visualization tools.

    PubMed

    Wang, Kenneth C; Filice, Ross W; Philbin, James F; Siegel, Eliot L; Nagy, Paul G

    2011-12-01

    The current array of PACS products and 3D visualization tools presents a wide range of options for applying advanced visualization methods in clinical radiology. The emergence of server-based rendering techniques creates new opportunities for raising the level of clinical image review. However, best-of-breed implementations of core PACS technology, volumetric image navigation, and application-specific 3D packages will, in general, be supplied by different vendors. Integration issues should be carefully considered before deploying such systems. This work presents a classification scheme describing five tiers of PACS modularity and integration with advanced visualization tools, with the goals of characterizing current options for such integration, providing an approach for evaluating such systems, and discussing possible future architectures. These five levels of increasing PACS modularity begin with what was until recently the dominant model for integrating advanced visualization into the clinical radiologist's workflow, consisting of a dedicated stand-alone post-processing workstation in the reading room. Introduction of context-sharing, thin clients using server-based rendering, archive integration, and user-level application hosting at successive levels of the hierarchy lead to a modularized imaging architecture, which promotes user interface integration, resource efficiency, system performance, supportability, and flexibility. These technical factors and system metrics are discussed in the context of the proposed five-level classification scheme. PMID:21301923

  20. Advanced level set segmentation of the right atrium in MR

    NASA Astrophysics Data System (ADS)

    Chen, Siqi; Kohlberger, Timo; Kirchberg, Klaus J.

    2011-03-01

    Atrial fibrillation is a common heart arrhythmia, and can be effectively treated with ablation. Ablation planning requires 3D models of the patient's left atrium (LA) and/or right atrium (RA), therefore an automatic segmentation procedure to retrieve these models is desirable. In this study, we investigate the use of advanced level set segmentation approaches to automatically segment RA in magnetic resonance angiographic (MRA) volume images. Low contrast to noise ratio makes the boundary between the RA and the nearby structures nearly indistinguishable. Therefore, pure data driven segmentation approaches such as watershed and ChanVese methods are bound to fail. Incorporating training shapes through PCA modeling to constrain the segmentation is one popular solution, and is also used in our segmentation framework. The shape parameters from PCA are optimized with a global histogram based energy model. However, since the shape parameters span a much smaller space, it can not capture fine details of the shape. Therefore, we employ a second refinement step after the shape based segmentation stage, which follows closely the recent work of localized appearance model based techniques. The local appearance model is established through a robust point tracking mechanism and is learned through landmarks embedded on the surface of training shapes. The key contribution of our work is the combination of a statistical shape prior and a localized appearance prior for level set segmentation of the right atrium from MRA. We test this two step segmentation framework on porcine RA to verify the algorithm.

  1. The Advanced Labs Website: resources for upper-level laboratories

    NASA Astrophysics Data System (ADS)

    Torres-Isea, Ramon

    2012-03-01

    The Advanced Labs web resource collection is an effort to create a central, comprehensive information base for college/university faculty who teach upper-level undergraduate laboratories. The website is produced by the American Association of Physics Teachers (AAPT). It is a part of ComPADRE, the online collection of resources in physics and astronomy education, which itself is a part of the National Science Foundation-funded National Science Digital Library (NSDL). After a brief review of its history, we will discuss the current status of the website while describing the various types of resources available at the site and presenting examples of each. We will detail a step-by-step procedure for submitting resources to the website. The resource collection is designed to be a community effort and thus welcomes input and contributions from its users. We will also present plans, and will seek audience feedback, for additional website services and features. The constraints, roadblocks, and rewards of this project will also be addressed.

  2. Using Speaking Test Data to Define the Advanced Proficiency Level for L2 Arabic Speakers

    ERIC Educational Resources Information Center

    Loomis, Summer

    2015-01-01

    Reaching the Advanced level of proficiency in speaking is a common goal of second language learners, but data on advanced learners of less commonly taught languages such as Arabic are scarce. This mixed-methods study reports words-per-minute and type-token ratios for three ACTFL levels--10 Intermediate Mid, 10 Advanced Mid, and 8…

  3. Relationship between prostate-specific antigen levels and ambient temperature

    NASA Astrophysics Data System (ADS)

    Ohwaki, Kazuhiro; Endo, Fumiyasu; Hattori, Kazunori; Muraishi, Osamu

    2014-07-01

    We examined the association between prostate-specific antigen (PSA) and daily mean ambient temperature on the day of the test in healthy men who had three annual checkups. We investigated 9,694 men who visited a hospital for routine health checkups in 2007, 2008, and 2009. Although the means and medians of ambient temperature for the three years were similar, the mode in 2008 (15.8 °C) was very different from those in 2007 and 2009 (22.4 °C and 23.2 °C). After controlling for age, body mass index, and hematocrit, a multiple regression analysis revealed a U-shaped relationship between ambient temperature and PSA in 2007 and 2009 ( P < 0.001 and P = 0.004, respectively), but not in 2008 ( P = 0.779). In 2007, PSA was 13.5 % higher at 5 °C and 10.0 % higher at 30 °C than that at 18.4 °C (nadir). In 2009, PSA was 7.3 % higher at 5 °C and 6.8 % at 30 °C compared with the level at 17.7 °C (nadir). In logistic regression analysis, a U-shaped relationship was found for the prevalence of a higher PSA (> 2.5 ng/mL) by ambient temperature, with the lowest likelihood of having a high PSA at 17.8 °C in 2007 ( P = 0.038) and 15.5 °C in 2009 ( P = 0.033). When tested at 30 °C, there was a 57 % excess risk of having a high PSA in 2007 and a 61 % higher risk in 2009 compared with those at each nadir temperature. We found a U-shaped relationship between PSA and ambient temperature with the lowest level of PSA at 15-20 °C.

  4. Relationship between prostate-specific antigen levels and ambient temperature

    NASA Astrophysics Data System (ADS)

    Ohwaki, Kazuhiro; Endo, Fumiyasu; Hattori, Kazunori; Muraishi, Osamu

    2013-05-01

    We examined the association between prostate-specific antigen (PSA) and daily mean ambient temperature on the day of the test in healthy men who had three annual checkups. We investigated 9,694 men who visited a hospital for routine health checkups in 2007, 2008, and 2009. Although the means and medians of ambient temperature for the three years were similar, the mode in 2008 (15.8 °C) was very different from those in 2007 and 2009 (22.4 °C and 23.2 °C). After controlling for age, body mass index, and hematocrit, a multiple regression analysis revealed a U-shaped relationship between ambient temperature and PSA in 2007 and 2009 (P < 0.001 and P = 0.004, respectively), but not in 2008 (P = 0.779). In 2007, PSA was 13.5 % higher at 5 °C and 10.0 % higher at 30 °C than that at 18.4 °C (nadir). In 2009, PSA was 7.3 % higher at 5 °C and 6.8 % at 30 °C compared with the level at 17.7 °C (nadir). In logistic regression analysis, a U-shaped relationship was found for the prevalence of a higher PSA (> 2.5 ng/mL) by ambient temperature, with the lowest likelihood of having a high PSA at 17.8 °C in 2007 (P = 0.038) and 15.5 °C in 2009 (P = 0.033). When tested at 30 °C, there was a 57 % excess risk of having a high PSA in 2007 and a 61 % higher risk in 2009 compared with those at each nadir temperature. We found a U-shaped relationship between PSA and ambient temperature with the lowest level of PSA at 15-20 °C.

  5. Advanced accident sequence precursor analysis level 1 models

    SciTech Connect

    Sattison, M.B.; Thatcher, T.A.; Knudsen, J.K.; Schroeder, J.A.; Siu, N.O.

    1996-03-01

    INEL has been involved in the development of plant-specific Accident Sequence Precursor (ASP) models for the past two years. These models were developed for use with the SAPHIRE suite of PRA computer codes. They contained event tree/linked fault tree Level 1 risk models for the following initiating events: general transient, loss-of-offsite-power, steam generator tube rupture, small loss-of-coolant-accident, and anticipated transient without scram. Early in 1995 the ASP models were revised based on review comments from the NRC and an independent peer review. These models were released as Revision 1. The Office of Nuclear Regulatory Research has sponsored several projects at the INEL this fiscal year to further enhance the capabilities of the ASP models. Revision 2 models incorporates more detailed plant information into the models concerning plant response to station blackout conditions, information on battery life, and other unique features gleaned from an Office of Nuclear Reactor Regulation quick review of the Individual Plant Examination submittals. These models are currently being delivered to the NRC as they are completed. A related project is a feasibility study and model development of low power/shutdown (LP/SD) and external event extensions to the ASP models. This project will establish criteria for selection of LP/SD and external initiator operational events for analysis within the ASP program. Prototype models for each pertinent initiating event (loss of shutdown cooling, loss of inventory control, fire, flood, seismic, etc.) will be developed. A third project concerns development of enhancements to SAPHIRE. In relation to the ASP program, a new SAPHIRE module, GEM, was developed as a specific user interface for performing ASP evaluations. This module greatly simplifies the analysis process for determining the conditional core damage probability for a given combination of initiating events and equipment failures or degradations.

  6. Specification for procurement of water-level sensing instrumentation, specification number HIF-I-1

    USGS Publications Warehouse

    Rapp, D.H.

    1982-01-01

    This specification is to communicate to instrument manufacturers the U.S. Geological Survey 's requirements. It covers systems for sensing the elevation of the water surface on open channels, rivers, lakes, reservoirs, storm-sewer pipes, and observation wells at Survey data-collection sites. The signal output (mechanical or electrical) must meet the signal input requirements of analog to digital and digital input recorders in use by the Survey. A classification of stage-sensing systems by common characteristics is used to aid Survey people making system selections. These characteristics are (1) system type (contact or noncontact), (2) sensor type and sensing distance, (3) accuracy, (4) range, (5) power requirements, (6) system size and weight, and (7) data output signal. Acceptable system requirements cover system configurations, signal outputs, materials, operation manuals, detailed environmental conditions, calibration procedures, system accuracy, power requirements, installation limitations, maintainability, safety, and workmanship. An outline of the qualification test procedures and failure criteria are also given. The Hydrologic Instrumentation Facility at NSTL Station, Mississippi will test available systems to determine if they meet the specification in this report for inclusion in the Survey 's 'Qualified Products List'. This list will be used for future procurement of water-level sensing systems by the Survey. (USGS)

  7. Some Specific CASL Requirements for Advanced Multiphase Flow Simulation of Light Water Reactors

    SciTech Connect

    R. A. Berry

    2010-11-01

    Because of the diversity of physical phenomena occuring in boiling, flashing, and bubble collapse, and of the length and time scales of LWR systems, it is imperative that the models have the following features: • Both vapor and liquid phases (and noncondensible phases, if present) must be treated as compressible. • Models must be mathematically and numerically well-posed. • The models methodology must be multi-scale. A fundamental derivation of the multiphase governing equation system, that should be used as a basis for advanced multiphase modeling in LWR coolant systems, is given in the Appendix using the ensemble averaging method. The remainder of this work focuses specifically on the compressible, well-posed, and multi-scale requirements of advanced simulation methods for these LWR coolant systems, because without these are the most fundamental aspects, without which widespread advancement cannot be claimed. Because of the expense of developing multiple special-purpose codes and the inherent inability to couple information from the multiple, separate length- and time-scales, efforts within CASL should be focused toward development of a multi-scale approaches to solve those multiphase flow problems relevant to LWR design and safety analysis. Efforts should be aimed at developing well-designed unified physical/mathematical and high-resolution numerical models for compressible, all-speed multiphase flows spanning: (1) Well-posed general mixture level (true multiphase) models for fast transient situations and safety analysis, (2) DNS (Direct Numerical Simulation)-like models to resolve interface level phenmena like flashing and boiling flows, and critical heat flux determination (necessarily including conjugate heat transfer), and (3) Multi-scale methods to resolve both (1) and (2) automatically, depending upon specified mesh resolution, and to couple different flow models (single-phase, multiphase with several velocities and pressures, multiphase with single

  8. Advanced Placement Course Enrollment and School-Level Characteristics

    ERIC Educational Resources Information Center

    Barnard-Brak, Lucy; McGaha-Garnett, Valerie; Burley, Hansel

    2011-01-01

    The current study examined access to Advanced Placement (AP) courses as a function of these school characteristics (e.g., percentage of ethnic minority and lower socioeconomic status) and then examined AP course enrollment as a function of both access to AP courses and these school characteristics. Using structural equation modeling techniques,…

  9. Advanced Inverter Functions to Support High Levels of Distributed Solar: Policy and Regulatory Considerations (Brochure)

    SciTech Connect

    Not Available

    2014-11-01

    This paper explains how advanced inverter functions (sometimes called 'smart inverters') contribute to the integration of high levels of solar PV generation onto the electrical grid and covers the contributions of advanced functions to maintaining grid stability. Policy and regulatory considerations associated with the deployment of advanced inverter functions are also introduced.

  10. Selecting Level-Specific Specialized Vocabulary Using Statistical Measures

    ERIC Educational Resources Information Center

    Chujo, Kiyomi; Utiyama, Masao

    2006-01-01

    To find an easy-to-use, automated tool to identify technical vocabulary applicable to learners at various levels, nine statistical measures were applied to the 7.3-million-word "commerce and finance" component of the British National Corpus. The resulting word lists showed that each statistical measure extracted a different level of specialized…

  11. Development and evaluation of an aged care specific Advance Care Plan

    PubMed Central

    Silvester, William; Parslow, Ruth A; Lewis, Virginia J; Fullam, Rachael S; Sjanta, Rebekah; Jackson, Lynne; White, Vanessa; Hudson, Rosalie

    2013-01-01

    Objectives To report on the quality of advance care planning (ACP) documents in use in residential aged care facilities (RACF) in areas of Victoria Australia prior to a systematic intervention; to report on the development and performance of an aged care specific Advance Care Plan template used during the intervention. Design An audit of the quality of pre-existing documentation used to record resident treatment preferences and end-of-life wishes at participating RACFs; development and pilot of an aged care specific Advance Care Plan template; an audit of the completeness and quality of Advance Care Plans completed on the new template during a systematic ACP intervention. Participants and setting 19 selected RACFs (managed by 12 aged care organisations) in metropolitan and regional areas of Victoria. Results Documentation in use at facilities prior to the ACP intervention most commonly recorded preferences regarding hospital transfer, life prolonging treatment and personal/cultural/religious wishes. However, 7 of 12 document sets failed to adequately and clearly specify the resident's preferences as regards life prolonging medical treatment. The newly developed aged care specific Advance Care Plan template was met with approval by participating RACFs. Of 203 Advance Care Plans completed on the template throughout the project period, 49% included the appointment of a Medical Enduring Power of Attorney. Requests concerning medical treatment were specified in almost all completed documents (97%), with 73% nominating the option of refusal of life-prolonging treatment. Over 90% of plans included information concerning residents’ values and beliefs, and future health situations that the resident would find to be unacceptable were specified in 78% of completed plans. Conclusions Standardised procedures and documentation are needed to improve the quality of processes, documents and outcomes of ACP in the residential aged care sector. PMID:23626906

  12. Advancement of Bi-Level Integrated System Synthesis (BLISS)

    NASA Technical Reports Server (NTRS)

    Sobieszczanski-Sobieski, J.; Emiley, Mark S.; Agte, Jeremy S.; Sandusky, Robert R., Jr.

    2000-01-01

    Bi-Level Integrated System Synthesis (BLISS) is a method for optimization of an engineering system, e.g., an aerospace vehicle. BLISS consists of optimizations at the subsystem (module) and system levels to divide the overall large optimization task into sets of smaller ones that can be executed concurrently. In the initial version of BLISS that was introduced and documented in previous publications, analysis in the modules was kept at the early conceptual design level. This paper reports on the next step in the BLISS development in which the fidelity of the aerodynamic drag and structural stress and displacement analyses were upgraded while the method's satisfactory convergence rate was retained.

  13. Specificity of peripheral nerve regeneration: interactions at the axon level.

    PubMed

    Allodi, Ilary; Udina, Esther; Navarro, Xavier

    2012-07-01

    Peripheral nerves injuries result in paralysis, anesthesia and lack of autonomic control of the affected body areas. After injury, axons distal to the lesion are disconnected from the neuronal body and degenerate, leading to denervation of the peripheral organs. Wallerian degeneration creates a microenvironment distal to the injury site that supports axonal regrowth, while the neuron body changes in phenotype to promote axonal regeneration. The significance of axonal regeneration is to replace the degenerated distal nerve segment, and achieve reinnervation of target organs and restitution of their functions. However, axonal regeneration does not always allows for adequate functional recovery, so that after a peripheral nerve injury, patients do not recover normal motor control and fine sensibility. The lack of specificity of nerve regeneration, in terms of motor and sensory axons regrowth, pathfinding and target reinnervation, is one the main shortcomings for recovery. Key factors for successful axonal regeneration include the intrinsic changes that neurons suffer to switch their transmitter state to a pro-regenerative state and the environment that the axons find distal to the lesion site. The molecular mechanisms implicated in axonal regeneration and pathfinding after injury are complex, and take into account the cross-talk between axons and glial cells, neurotrophic factors, extracellular matrix molecules and their receptors. The aim of this review is to look at those interactions, trying to understand if some of these molecular factors are specific for motor and sensory neuron growth, and provide the basic knowledge for potential strategies to enhance and guide axonal regeneration and reinnervation of adequate target organs. PMID:22609046

  14. GNVQ science at advanced level: motivation and self-esteem

    NASA Astrophysics Data System (ADS)

    Solomon, J.

    1995-07-01

    An interview study carried out in the pilot year of the new GNVQ in science at A-level has shown that the use of grading criteria, which require independent learning, as a method of assessment is better for students' motivation and self-esteem.

  15. An Intermediate-Advanced Level Dutch Refresher Course.

    ERIC Educational Resources Information Center

    English Language Services, Inc., Washington, DC.

    This refresher course in Dutch consists of eight volumes (Books I-IV, each in two parts). Book I, which begins on the intermediate level, presents the sound system of Dutch with accompanying drills. These provide practice in sound-to-spelling correspondence, and contrastive English-Dutch phonology. Books II and III are comprised of six units of…

  16. An Intermediate-Advanced Level Cambodian Refresher Course.

    ERIC Educational Resources Information Center

    Purtle, Dale I.; And Others

    This eight-volume audiolingual course in Standard Cambodian has been prepared for students who have completed either an introductory college-level course of one year or have had an intensive course of several months. Material in the first two volumes, "Book I--Part One" and "Book I--Part Two," introduces the sound system with phonology drills and…

  17. An Intermediate-Advanced Level Thai Refresher Course.

    ERIC Educational Resources Information Center

    Shaweevongs, Chuan: And Others

    The audiolingual materials in this six-volume Thai series have been prepared for students who have either completed an introductory college-level Thai course of one year or more, or have had an intensive course of several months. The first two volumes, Books I and II, consist of five units each, with each unit containing the following lessons--(1)…

  18. Application of PSA to review and define technical specifications for advanced nuclear power plants

    SciTech Connect

    Kim, I.S.; Samanta, P.K.; Reinhart, F.M.; Wohl, M.L.

    1995-11-01

    As part of the design certification process, probabilistic safety assessments (PSAS) are performed at the design stage for each advanced nuclear power plant. Among other usages, these PSAs are important inputs in defining the Technical Specifications (TSs) for these plants. Knowledge gained from their use in improving the TSs for operating nuclear power plants is providing methods and insights for using PSAs at this early stage. Evaluating the safety or the risk significance of the TSs to be defined for an advanced plant encompasses diverse aspects: (a) determining the basic limiting condition for operation (LCO); (b) structuring conditions associated with the LCO; (c) defining completion times (equivalent to allowed outage times in the TS for conventional plants); and, (d) prescribing required actions to be taken within the specified completion times. In this paper, we consider the use of PSA in defining the TSs for an advanced nuclear plant, namely General Electric`s Advanced Boiling Water Reactor (ABWR). Similar approaches are being taken for ABB-CE`s System 80+ and Westinghouse`s AP-600. We discuss the general features of an advanced reactor`s TS, how PSA is being used in reviewing the TSs, and we give an example where the TS submittal was reviewed using a PSA-based analysis to arrive at the requirements for the plant.

  19. Mild neurotrauma indicates a range-specific pressure response to low level shock wave exposure.

    PubMed

    Vandevord, Pamela J; Bolander, Richard; Sajja, Venkata Siva Sai Sujith; Hay, Kathryn; Bir, Cynthia A

    2012-01-01

    Identifying the level of overpressure required to create physiological deficits is vital to advance prevention, diagnostic, and treatment strategies for individuals exposed to blasts. In this study, a rodent model of primary blast neurotrauma was employed to determine the pressure at which acute neurological alterations occurred. Rats were exposed to a single low intensity shock wave at a pressure of 0, 97, 117, or 153 kPa. Following exposure, rats were assessed for acute cognitive alterations using the Morris water maze and motor dysfunction using the horizontal ladder test. Subsequently, histological analyses of three brain regions (primary motor cortex, the hippocampal dentate gyrus region, and the posteromedial cortical amygdala) were conducted. Histological parameters included measuring the levels of glial fibrillary acidic protein (GFAP) to identify astrocyte activation, cleaved caspase-3 for early apoptosis identification and Fluoro-Jade B (FJB) which labels degenerating neurons within the brain tissue. The results demonstrated that an exposure to a single 117 kPa shock wave revealed a significant change in overall neurological deficits when compared to controls and the other pressures. The animals showed significant alterations in water maze parameters and a histological increase in the number of GFAP, caspase-3, and FJB-positive cells. It is suggested that when exposed to a low level shock wave, there may be a biomechanical response elicited by a specific pressure range which can cause low level neurological deficits within the rat. These data indicate that neurotrauma induced from a shock wave may lead to cognitive deficits in short-term learning and memory of rats. Additional histological evidence supports significant and diffuse glial activation and cellular damage. Further investigation into the biomechanical aspects of shock wave exposure is required to elucidate this pressure range-specific phenomenon. PMID:21994066

  20. Recent advances in active specific cancer vaccine treatment for colorectal cancer.

    PubMed

    Okuno, Kiyotaka; Sugiura, Fumiaki; Itoh, Kyogo; Yoshida, Koji; Tsunoda, Takuya; Nakamura, Yusuke

    2012-06-01

    Cloning techniques to identify genes and peptides of tumor-associated antigens have created new possibilities for the immunotherapy of patients with advanced cancer. Here, we review recent clinical trials of specific cancer vaccines, mainly HLA-restricted peptides, and epitope-encoding vectors for advanced colorectal cancer (CRC). Many researchers initially focused on carcinoembryonic antigen (CEA) as an immunologic target antigen that is overexpressed on virtually all CRCs. A recombinant vaccine containing the CEA gene and dendritic cells (DCs) loaded with CEA peptide was administered to patients with CEA-elevated CRC. Although CEA-specific responses were detected, the clinical responses were limited. Recently, new types of clinical trials--namely, a personalized protocol to take into account the immunological diversity of cytotoxic T cell responses among patients and a novel cancer-testis antigen protocol that uses multiple peptides derived from genes identified by the cDNA array method--have been introduced. The personalized protocol seemed to be better than the classical (non-personalized) protocol in terms of clinical response and survival. Novel cancer-testis antigen protocols that use multiple CRC-derived peptides were recently conducted in patients with advanced CRC. The preliminary study yielded promising results regarding specific T cell responses to peptides and survival benefits. In this review, we summarize these results and discuss future perspectives. PMID:22339221

  1. Advanced accident sequence precursor analysis level 2 models

    SciTech Connect

    Galyean, W.J.; Brownson, D.A.; Rempe, J.L.

    1996-03-01

    The U.S. Nuclear Regulatory Commission Accident Sequence Precursor program pursues the ultimate objective of performing risk significant evaluations on operational events (precursors) occurring in commercial nuclear power plants. To achieve this objective, the Office of Nuclear Regulatory Research is supporting the development of simple probabilistic risk assessment models for all commercial nuclear power plants (NPP) in the U.S. Presently, only simple Level 1 plant models have been developed which estimate core damage frequencies. In order to provide a true risk perspective, the consequences associated with postulated core damage accidents also need to be considered. With the objective of performing risk evaluations in an integrated and consistent manner, a linked event tree approach which propagates the front end results to back end was developed. This approach utilizes simple plant models that analyze the response of the NPP containment structure in the context of a core damage accident, estimate the magnitude and timing of a radioactive release to the environment, and calculate the consequences for a given release. Detailed models and results from previous studies, such as the NUREG-1150 study, are used to quantify these simple models. These simple models are then linked to the existing Level 1 models, and are evaluated using the SAPHIRE code. To demonstrate the approach, prototypic models have been developed for a boiling water reactor, Peach Bottom, and a pressurized water reactor, Zion.

  2. High Achievement on Advanced Placement Exams: The Relationship of School-Level Contextual Factors to Performance

    ERIC Educational Resources Information Center

    Burney, Virginia H.

    2010-01-01

    The purpose of the study was to identify school- and district-level variables that relate to advanced academic achievement, as defined by the ratio of number of scores of 3, 4, or 5 on Advanced Placement exams to school enrollment. The study initially included 46 variables for 339 public high schools in one Midwestern state. Hierarchical linear…

  3. BOOK REVIEW: New Understanding Physics for Advanced Level

    NASA Astrophysics Data System (ADS)

    Breithaupt, Jim

    2000-09-01

    Breithaupt's new book is big: at 727 pages, it will be a hefty addition to any student's bag. According to the preface, the book is designed to help students achieve the transition from GCSE to A-level and to succeed well at this level. It also aims to cover the requirements of the compulsory parts of all new syllabuses and to cover most of the optional material, too. The book is organized into seven themes along traditional lines: mechanics, materials, fields, waves, electricity, inside the atom, and physics in medicine. Each theme begins with a colourful title page that outlines what the theme is about, lists the applications that students will meet in their reading, identifies prior learning from GCSE and gives a checklist of what students should be able to do once they have finished their reading of the theme. This is all very useful. The text of the book is illustrated with many colourful photographs, pictures and cartoons, but despite this it looks very dense. There are a lot of words on every page in a small font that makes them seem very unfriendly, and although the book claims to be readable I rather doubt that the layout will encourage voluntary reading of the text. Each chapter ends with a useful summary and a selection of short questions that allow students to test their understanding. Each theme has a set of multiple choice and long questions. Some of the questions have an icon referring the student to the accompanying CD (more of this later). There is much up-to-date material in the book. For example, the section on cosmology gives a brief description of the inflationary scenario within the Big Bang model of the origin of the universe, although no mechanism for the inflation is given, which might prove unsatisfying to some students. I do have some reservations about the presentation of some topics within the book: the discussion of relativistic mass, for example, states that `Einstein showed that the mass ... is given by the formula ...' and quotes

  4. ADVANCED UTILITY SIMULATION MODEL DESCRIPTION OF MODIFICATIONS TO THE STATE LEVEL MODEL (VERSION 3.0)

    EPA Science Inventory

    The report documents modifications to the state level model portion of the Advanced Utility Simulation Model (AUSM), one of four stationary source emission and control cost forecasting models developed for the National Acid Precipitation Assessment Program (NAPAP). The AUSM model...

  5. Advances in low-level jet research and future prospects

    NASA Astrophysics Data System (ADS)

    Liu, Hongbo; He, Mingyang; Wang, Bin; Zhang, Qinghong

    2014-02-01

    The low-level jet (LLJ) is closely related to severe rainfall events, air pollution, wind energy utilization, aviation safety, sandstorms, forest fire, and other weather and climate phenomena. Therefore, it has attracted considerable attention since its discovery. Scientists have carried out many studies on LLJs and made significant achievements during the past five or six decades. This article summarizes and assesses the current knowledge on this subject, and focuses in particular on three aspects: 1) LLJ classification, definition, distribution, and structure; 2) LLJ formation and evolutionary mechanisms; and 3) relationships between LLJ and rainfall, as well as other interdisciplinary fields. After comparing the status of LLJ research at home (China) and abroad, we then discuss the shortcomings of LLJ research in China. We suggest that this includes: coarse definitions of the LLJ, lack of observations and inadequate quality control, few thorough explorations of LLJ characteristics and formation mechanisms, and limited studies in interdisciplinary fields. The future prospects for several LLJ research avenues are also speculated.

  6. Recent Advances in Site Specific Conjugations of Antibody Drug Conjugates (ADCs).

    PubMed

    Gao, Wenlong; Zhang, Jingxin; Xiang, Jun; Zhang, Lei; Wu, Chengbin; Dhal, Pradeep K; Chen, Bo

    2016-01-01

    Antibody-drug conjugates (ADCs) take the advantage of antigen specificity of monoclonal antibodies to deliver highly potent cytotoxic drugs selectively to antigen-expressing tumor cells. The recent approval of Adcetris™ and Kadcyla™ as well as emerging data from numerous ongoing clinical trials underscore the role of ADCs as a new therapeutic option for cancer patients. However, conventional conjugation methods generally result in a heterogeneous mixture of ADCs, which can result in significant therapeutic liabilities and can lead to complicated manufacturing processes. The increased understanding from the clinical investigation of current ADCs and site-specific bioconjugation technologies has enabled scientists to accelerate the discovery and development of the next generation ADCs with defined and homogeneous composition. The present manuscript reviews the recent advances and trends in the research and development of novel ADCs obtained by site-specific conjugation method. PMID:27174056

  7. Mechanisms Underpinning Increased Plasma Creatinine Levels in Patients Receiving Vemurafenib for Advanced Melanoma

    PubMed Central

    Hurabielle, Charlotte; Pillebout, Evangéline; Stehlé, Thomas; Pagès, Cécile; Roux, Jennifer; Schneider, Pierre; Chevret, Sylvie; Chaffaut, Cendrine; Boutten, Anne; Mourah, Samia; Basset-Seguin, Nicole; Vidal-Petiot, Emmanuelle; Lebbé, Céleste; Flamant, Martin

    2016-01-01

    Context Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known. Objective We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma. Methods We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow-up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients. Results 70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion. Conclusion Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective. PMID:26930506

  8. Comparison of the EO-1 Advanced Land Imager Performance With the Landsat Data Continuity Mission Specification

    NASA Technical Reports Server (NTRS)

    Mendenhall, J. A.; Hearn, D. R.; Lencioni, D. E.

    2002-01-01

    The performance requirements for the Advanced Land Imager were developed under NASA's New Millennium Program and were intended to facilitate the validation of new sensor technologies and architectures for potential application in future remote sensing missions. The Advanced Land Imager (ALI) was designed and flown well before the Landsat Data Continuity Mission (LDCM) specifications were developed. Nevertheless, the science focus of the ALI technology validation was Landsat data continuity. Therefore, although exact compliance by ALI is not expected, the performance should demonstrate a path to a compliant sensor system. The performance of the ALI, as determined from preflight and flight data, is compared to the LDCM specification. Twenty-one noncompliances have been identified: four data collection, four spectral, six spatial, and seven radiometric (Table I). All but six of these are considered minor. The six major noncompliances are the result of stray light, leaky detectors, and contamination. Appendix A replicates the LDCM specification and contains ALI compliance notes where appropriate. Details of the ALI stray light, contamination, and leaky detectors are provided in Appendix B, C, and D respectively. Additional information pertaining to the calculation of the ALI edge response and coherent noise is presented in Appendix E and F. A list of ALI related publications is provided in Appendix G.

  9. Advanced Nanoporous Materials for Micro-Gravimetric Sensing to Trace-Level Bio/Chemical Molecules

    PubMed Central

    Xu, Pengcheng; Li, Xinxin; Yu, Haitao; Xu, Tiegang

    2014-01-01

    Functionalized nanoporous materials have been developed recently as bio/chemical sensing materials. Due to the huge specific surface of the nano-materials for molecular adsorption, high hopes have been placed on gravimetric detection with micro/nano resonant cantilevers for ultra-sensitive sensing of low-concentration bio/chemical substances. In order to enhance selectivity of the gravimetric resonant sensors to the target molecules, it is crucial to modify specific groups onto the pore-surface of the nano-materials. By loading the nanoporous sensing material onto the desired region of the mass-type transducers like resonant cantilevers, the micro-gravimetric bio/chemical sensors can be formed. Recently, such micro-gravimetric bio/chemical sensors have been successfully applied for rapid or on-the-spot detection of various bio/chemical molecules at the trace-concentration level. The applicable nanoporous sensing materials include mesoporous silica, zeolite, nanoporous graphene oxide (GO) and so on. This review article focuses on the recent achievements in design, preparation, functionalization and characterization of advanced nanoporous sensing materials for micro-gravimetric bio/chemical sensing. PMID:25313499

  10. Characteristics of advanced-level dietetics practice: a model and empirical results.

    PubMed

    Bradley, R T; Young, W Y; Ebbs, P; Martin, J

    1993-02-01

    This article, which is the first of a two-part series, presents results for the first objective of The American Dietetic Association (ADA) 1991 Dietetic Practice Study: to determine the characteristics of advanced-level dietetics practice. A nationwide mail survey of ADA members was conducted on a stratified random sample of 8,012 beyond-entry-level (registered before April 1988) registered dietitians who were members of dietetic practice groups (DPGs). The sample was supplemented with two randomly selected control groups of 1,000 entry-level and 1,000 beyond-entry-level registered dietitians. The overall response rate was 63.1%. The 5,852 usable returns were representative of the dietetics population surveyed. A model of advanced-level professional practice was developed that specified minimum necessary requirements for advanced practitioners on five components: education and experience, professional achievement, approach to practice, professional role positions, and professional role contacts; measurement of a sixth component, advanced-level practice performance, was unsuccessful. A series of validation analyses found the model to be a statistically sound and reliable means of distinguishing advanced practitioners from other groups of dietitians in 8 of every 10 cases. A total of 461 (8.9%) dietitians met all requirements of the model and were classified as advanced practitioners. Projected estimations of advanced practitioners in the population of beyond-entry-level ADA members who are also members of DPGs ranged between 2,126 and 2,640 dietitians (3.5% to 4.3% of the ADA membership).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8423288

  11. Levels of acute inflammatory biomarkers in advanced prostate cancer patients with α2-macroglobulin deficiency.

    PubMed

    Kanoh, Yuhsaku; Ohtani, Hideki; Egawa, Shin; Baba, Shiro; Akahoshi, Tohru

    2011-12-01

    C-reactive protein (CRP), serum amyloid A (SAA), interleukin-6 (IL-6), α1-antitrypsin (α1AT), α1-acid glycoprotein (α1AG) and ceruloplasmin (CP) are acute inflammatory biomarkers that increase in various conditions including infection, inflammation, malignancy and tissue disturbance. In contrast, α2-macroglobulin (α2M) is involved in inflammation through its function as a carrier protein of IL-6. We had previously reported on advanced prostate cancer (PCa) patients with multiple distant bone metastases in whom serum α2M levels were markedly decreased (α2M deficiency). However, the relationship between serum levels of α2M and acute inflammatory biomarkers in PCa patients with or without α2M deficiency has not been demonstrated. In the present study, we examined serum levels of CRP, SAA, IL-6, α1AT, α1AG and CP in PCa patients with or without α2M deficiency to establish clinical significance and changes in these biomarkers during PCa disease progression. We found that upon addition of recombinant IL-6 (rIL-6) to serum from PCa patients with α2M deficiency, since a function of α2M is to bind and stabilize IL-6, the α2M-IL-6 complex and free endogenous IL-6 were not detectable. Serum levels of the α2M-independent markers, α1AT, α1AG and CP, in all PCa patients regardless of α2M deficiency were significantly higher than in healthy controls, but those of the α2M-dependent molecules, CRP, SAA and IL-6, were not increased in PCa patients with α2M deficiency. Therefore, quantitation of both α2M-dependent (CRP, SAA and IL-6) and α2M-independent (α1AT, α1AG and CP) acute inflammatory biomarkers in advanced PCa patients may be an auxiliary indicator, together with prostate-specific antigen (PSA), to monitor PCa disease progression. PMID:21894431

  12. Evaluation of Salivary Leptin Levels in Healthy Subjects and Patients with Advanced Periodontitis

    PubMed Central

    Khorsand, Afshin; Bayani, Mojtaba; Torabi, Sepehr; Kharrazifard, Mohammad Javad; Mohammadnejhad, Fatemeh

    2016-01-01

    Objectives: Leptin is a hormone-like protein produced by the adipose tissue. It plays an important role in protection of host against inflammation and infection. Some studies have reported changes in leptin levels in the gingival crevicular fluid (GCF), saliva and blood serum of patients with periodontal disease compared to healthy individuals. The aim of the present study was to compare the salivary leptin levels in patients with advanced periodontitis and healthy individuals. Materials and Methods: In this case-control study, the salivary samples of healthy individuals and patients with advanced periodontitis with clinical attachment loss >5mm were obtained using a standardized method and the leptin levels were measured in the salivary samples by means of ELISA. The effects of the periodontal status and sex on the salivary leptin levels of both groups were statistically analyzed by two-way ANOVA. Results: The means ± standard deviation (SD) of salivary leptin levels in healthy subjects and patients with advanced periodontitis were 34.27±6.88 and 17.87±5.89 pg/mL, respectively. Statistical analysis showed that the effect of sex on the salivary leptin levels was not significant (P=0.91), while the effect of advanced periodontitis on the salivary leptin levels was significant compared to healthy individuals (P<0.0001). Conclusions: In patients with advanced periodontitis, the salivary leptin levels were significantly lower compared to healthy individuals. Thus, assessment of salivary leptin can be done as a non-invasive and simple method to determine the susceptibility of patients to advanced periodontitis. PMID:27536322

  13. Advances in Instrumentation for Quantification of Isotopic Nitrous Oxide from ppb levels to 100%

    NASA Astrophysics Data System (ADS)

    Dong, F.; Gupta, M.; Leen, J.; Provencal, R. A.; Owano, T. G.; Baer, D. S.

    2013-12-01

    The isotopic composition of trace gases provides information of their origin and fate that cannot be determined from their concentration measurements alone. Biological source and loss processes, like bacterial production of nitrous oxide, are typically accompanied by isotopic selectivity associated with the kinetics of bond formation and destruction. Of the three important biologically mediated greenhouse gases (CO2, CH4 and N2O), the understanding of nitrous oxide isotopic budget in air lags behind the other two gases primarily due to the relatively low concentration of N2O in ambient air (~320 ppb). Furthermore, the origin of nitrates in rivers, lakes, ocean and other water supplies may be determined from analyses of isotopic nitrous oxide produced via chemical reduction or biological conversion. These processes can produce nitrous oxide at levels considerably greater than those present in ambient air. To date, analyses of isotopic nitrous oxide requires either pre-concentration of samples containing low concentrations or dilution of samples with high concentrations. We report significant advances of instrumentation for real-time measurements of site-specific isotopic nitrogen (δ15Nα, δ15Nβ, δ15N, δ18O) and mixing ratio [N2O] of nitrous oxide over a very wide range of mole fractions in air. Specifically, LGR's Isotopic N2O Analyzer can report site-specific isotopic nitrogen and isotopic oxygen continuously in flows ranging from 0.2 to over 20 ppm (parts per million) nitrous oxide in air (with preconcentration or dilution). Furthermore, for samples of limited volume, a batch technique may be used for similar isotopic measurements in discrete samples containing 0.2 ppm to 100% nitrous oxide (e.g., sample volumes from bacterial digestion can be as little as 1-10 mL). This novel technology, which employs cavity enhanced absorption spectroscopy (Off-Axis ICOS) and a mid-infrared laser (4.56 microns) and does not require any cryogenic components, has been

  14. Educating advanced level practice within complex health care workplace environments through transformational practice development.

    PubMed

    Hardy, Sally; Jackson, Carrie; Webster, Jonathan; Manley, Kim

    2013-10-01

    Over the past 20 years health care reform has influenced the development of advanced level practitioner roles and expectations. How advanced level practitioners work to survive the highly stimulating, yet sometimes overwhelming aspects of balancing high quality provision with political reform agendas, amidst economic constraint is considered. Transformational approaches (encompassing education and practice led service development) can provide, promote and 'provoke' a harnessing of complex issues workplace environment to produce creative solutions. Transformational Practice Development provides a structured, rigorous, systematic approach that practitioners, teams and health care consumers alike can utilise to achieve skills and attributes needed for successful innovation. The authors present case study materials from action orientated locally delivered Practice Development, as a complex strategic intervention approach to influence and promote advanced level practice expertise. Initiated through facilitation of transformational leadership, and resultant team based improvements, we present how strategic collaborative processes can harness work chaos and complexity to provide sustainable and productive workplace cultures of effectiveness. PMID:23453607

  15. Identifying components of advanced-level clinical nutrition practice: a Delphi study.

    PubMed

    Brody, Rebecca A; Byham-Gray, Laura; Touger-Decker, Riva; Passannante, Marian R; O'Sullivan Maillet, Julie

    2012-06-01

    The dietetics profession lacks a comprehensive definition of advanced-level practice. Using a three-round Delphi study with mailed surveys, expert consensus on four dimensions of advanced-level practice that define advanced practice registered dietitians (RDs) in clinical nutrition was explored. Purposive sampling identified 117 RDs who met advanced-level practice criteria. In round 1, experts rated the essentiality of statements on a 7-point ordinal scale and generated open-ended practice activity statements regarding the following four dimensions of advanced-level practice: professional knowledge, abilities and skills, approaches to practice, roles and relationships, and practice behaviors. Median ratings of 1.0 to 3.0 were defined as essential, 4.0 was neutral, and 5.0 to 7.0 were nonessential. In rounds 2 and 3, experts re-rated statements not reaching consensus by evaluating their previous responses, group median rating, and comments. Consensus was reached when the interquartile range of responses to a statement was ≤2.0. Eighty-five experts enrolled (72.6%); 76 (89.4%) completed all rounds. In total, 233 statements were rated, with 100% achieving consensus; 211 (90.6%) were essential to advanced practice RD clinical practice. Having a master's degree; completing an advanced practice residency; research coursework; and advanced continuing education were essential, as were having 8 years of experience; clinical nutrition knowledge/expertise; specialization; participation in research activities; and skills in technology and communication. Highly essential approaches to practice were systematic yet adaptable and used critical thinking and intuition and highly essential values encompassed professional growth and service to patients. Roles emphasized patient care and leadership. Essential practice activities within the nutrition care process included provision of complex patient-centered nutrition care using application of advanced knowledge/expertise and

  16. Phase advancement and nucleus-specific timing of thalamocortical activity during slow cortical oscillation

    PubMed Central

    Slézia, Andrea; Hangya, Balázs; Ulbert, István; Acsády, László

    2011-01-01

    The exact timing of cortical afferent activity is instrumental for the correct coding and retrieval of internal and external stimuli. Thalamocortical inputs represent the most significant subcortical pathway to the cortex, but the precise timing and temporal variability of thalamocortical activity is not known. To examine this question, we studied the phase of thalamic action potentials relative to cortical oscillations and established correlations among phase, the nuclear location of the thalamocortical neurons and the frequency of cortical activity. The phase of thalamic action potentials depended on the exact frequency of the slow cortical oscillation both on long (minutes) and short (single wave) time scales. Faster waves were accompanied by phase advancement in both cases. Thalamocortical neurons located in different nuclei fired at significantly different phases of the slow waves but were active at similar phase of spindle oscillations. Different thalamic nuclei displayed distinct burst patterns. Bursts with higher number of action potentials displayed progressive phase advancement in a nucleus-specific manner. Thalamic neurons located along nuclear borders were characterized by mixed burst and phase properties. Our data demonstrate that the temporal relationship between cortical and thalamic activity is not fixed but displays dynamic changes during oscillatory activity. The timing depends on the precise location and exact activity of thalamocortical cells and the ongoing cortical network pattern. This variability of thalamic output and its coupling to cortical activity can enable thalamocortical neurons to actively participate in the coding and retrieval of complex cortical signals. PMID:21228169

  17. Site-specific analysis of advanced glycation end products in plasma proteins of type 2 diabetes mellitus patients.

    PubMed

    Greifenhagen, Uta; Frolov, Andrej; Blüher, Matthias; Hoffmann, Ralf

    2016-08-01

    Advanced glycation end products (AGEs) are posttranslational modifications formed non-enzymatically from the reaction of carbohydrates and their degradation products with proteins. Accumulation of AGEs is associated with the progression of severe diabetic complications, for example, and elevated tissue levels of AGEs might even predict these pathologies. As AGE formation is often site-specific, mapping of these modification sites may reveal more sensitive and specific markers than the global tissue level. Here, 42 AGE modifications were identified in a bottom-up proteomic approach by tandem mass spectrometry, which corresponded to 36 sites in 22 high to medium abundant proteins in individual plasma samples obtained from type 2 diabetes mellitus (T2DM) patients with long disease duration (>10 years). Major modifications were glarg (11 modification sites) and carboxymethylation (5) of arginine and formylation (8), acetylation (7), and carboxymethylation (7) of lysine residues. Relative quantification of these sites in plasma samples obtained from normoglycemic individuals (n = 47) and patients with T2DM being newly diagnosed (n = 47) or of medium (2-5 years, n = 20) and long disease duration (>10 years, n = 20) did not reveal any significant differences. PMID:27236317

  18. Intercultural Language Learning through Translation and Interpreting: A Study of Advanced-Level Japanese Learners

    ERIC Educational Resources Information Center

    Takimoto, Masato; Hashimoto, Hiroko

    2011-01-01

    The paper examines the appropriateness of translation and interpreting tasks for language teaching. To this end, it analyses an advanced-level Japanese language subject taught at an Australian university, utilising the concept of intercultural language learning (ICLL) as a theoretical framework. The study also investigates the learning experience…

  19. Guide for the Training and Qualification of Welding Personnel. Level II - Advanced Welders.

    ERIC Educational Resources Information Center

    American Welding Society, Miami, FL.

    This guide is designed to help education and training facilities develop and administer competency-based training programs to qualify and certify trainees in accordance with the American Welding Society (AWS) requirements for level II (advanced) welders. Presented first are the scope, objectives, and requirements of the AWS…

  20. The Relationship between Teaching Styles and Autonomy among Iranian Female EFL Teachers, Teaching at Advanced Levels

    ERIC Educational Resources Information Center

    Baradaran, Abdollah

    2016-01-01

    The current research aimed at inspecting the existence of a significant relationship between teachers' teaching styles and their Autonomy. For this reason, two questionnaires with regard to the main variables were given to 175 female English language teachers, teaching at advanced levels. Moreover, non-parametric Mann Whitney and Kruskal Wallis…

  1. An Intermediate-Advanced Level German Refresher Course: Book 3, Part 2.

    ERIC Educational Resources Information Center

    Defense Language Inst., Monterey, CA.

    Book three, part two, of an intermediate-advanced level German refresher course for college students is presented. The volume consists of 42 lessons of text material and 42 prerecorded tapes. A typical unit is made up of spontaneous dialogues, substitution drills, and tests. A dialogue for listening is a short conversation between German speakers…

  2. An Intermediate-Advanced Level German Refresher Course: Book 4, Part 2.

    ERIC Educational Resources Information Center

    Defense Language Inst., Monterey, CA.

    Book four, part two, of an intermediate-advanced level German refresher course for college students is presented. The volume consists of 25 lessons of text material and 50 prerecorded tapes. A typical lesson with its two accompanying tapes is made up of interrogation, military terminology drill, and a comprehension test. The materials of the first…

  3. An Intermediate-Advanced Level German Refresher Course: Book 4, Part 1.

    ERIC Educational Resources Information Center

    Defense Language Inst., Monterey, CA.

    Book four, part one, of an intermediate-advanced level German refresher course for college students is presented. The volume consists of 25 lessons of text material and 50 prerecorded tapes. A typical lesson with its two accompanying tapes is made up of interrogation, military terminology drill, and a comprehension test. The materials of the first…

  4. An Intermediate-Advanced Level German Refresher Course: Book 2, Part 2.

    ERIC Educational Resources Information Center

    Defense Language Inst., Monterey, CA.

    Book two, part two, of an intermediate-advanced level German refresher course for college students is presented. The volume consists of 42 lessons of text material and 42 prerecorded tapes. A typical unit is made up of spontaneous dialogues, substitution drills, and tests. A dialogue for listening is a short conversation between German speakers…

  5. An Intermediate-Advanced Level German Refresher Course: Book 3, Part 1.

    ERIC Educational Resources Information Center

    Defense Language Inst., Monterey, CA.

    Book three, part one, of an intermediate-advanced level German refresher course for college students ls presented. The volume consists of 42 lessons of text material and 42 prerecorded tapes. A typical unit is made up of spontaneous dialogues, substitution drills, and tests. A dialogue for listening is a short conversation between German speakers…

  6. An Intermediate-Advanced Level German Refresher Course: Book 2, Part 1.

    ERIC Educational Resources Information Center

    Defense Language Inst., Monterey, CA.

    Book two, part one, of an intermediate-advanced level German refresher course for college students is presented. The volume consists of 42 lessons of text material and 42 prerecorded tapes. A typical unit is made up of spontaneous dialogues, substitution drills, and tests. A dialogue for listening is a short conversation between German speakers…

  7. Saving Lower-Enrollment, Advanced-Level Elective Programs: A Way to Get Blood from Turnips.

    ERIC Educational Resources Information Center

    Book, Leon C.

    An innovative, flexible scheduling technique for advanced levels of a foreign language program is described. The technique, predicated on individualized pacing and continuous progress, is generalizable to all elective programs, and offers a workable solution to satisfy the enrollment "numbers game" and to lend breadth and depth to the curricula of…

  8. Advancing Ecological Models to Compare Scale in Multi-Level Educational Change

    ERIC Educational Resources Information Center

    Woo, David James

    2016-01-01

    Education systems as units of analysis have been metaphorically likened to ecologies to model change. However, ecological models to date have been ineffective in modelling educational change that is multi-scale and occurs across multiple levels of an education system. Thus, this paper advances two innovative, ecological frameworks that improve on…

  9. The Singapore-Cambridge General Certificate of Education Advanced-Level General Paper Examination

    ERIC Educational Resources Information Center

    Hassan, Nurul Huda; Shih, Chih-Min

    2013-01-01

    This article describes and reviews the Singapore-Cambridge General Certificate of Education Advanced Level General Paper (GP) examination. As a written test that is administered to preuniversity students, the GP examination is internationally recognised and accepted by universities and employers as proof of English competence. In this article, the…

  10. Advanced Level Biology Teachers' Attitudes towards Assessment and Their Engagement in Assessment for Learning

    ERIC Educational Resources Information Center

    Bramwell-Lalor, Sharon; Rainford, Marcia

    2015-01-01

    This paper reports on a Mixed Methods study involving an investigation into the attitudes of advanced level biology teachers towards assessment and describes the teachers' experiences while being engaged in Assessment for Learning (AfL) practices such as sharing of learning objectives and peer- and self-assessment. Quantitative data were collected…

  11. Cognitive Levels of Questions Used by Iranian EFL Teachers in Advanced Reading Comprehension Tests

    ERIC Educational Resources Information Center

    Khorsand, Narjess

    2009-01-01

    This study examined the cognitive levels of questions used by Iranian EFL teachers in advanced reading comprehension tests. Twenty teachers participated in this study and generated 215 questions which were then categorized according to Bloom's taxonomy. This taxonomy consists of six major categories which starts from the simplest behavior to the…

  12. Impact of Differing Levels of Tobacco-Specific Nitrosamines in Cigarette Smoke on the Levels of Biomarkers in Smokers

    PubMed Central

    Ashley, David L.; O’Connor, Richard J.; Bernert, John T.; Watson, Clifford H.; Polzin, Gregory M.; Jain, Ram B.; Hammond, David; Hatsukami, Dorothy K.; Giovino, Gary A.; Cummings, K. Michael; McNeill, Ann; Shahab, Lion; King, Bill; Fong, Geoffrey T.; Zhang, Liqin; Xia, Yang; Yan, Xizheng; McCraw, Joan M.

    2010-01-01

    BACKGROUND Smokers are exposed to significant doses of carcinogens, including tobacco-specific nitrosamines (TSNAs). Previous studies have shown significant global differences in the levels of TSNAs in cigarette smoke because of the variation in tobacco blending and curing practices around the world. METHODS Mouth-level exposure to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) measured in cigarette butts and urinary concentrations of its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) were examined among 126 daily smokers in four countries over a 24-hour study period. RESULTS As mouth-level exposure of NNK increased, the urinary NNAL increased, even after adjustment for other covariates (β=0.46, p=0.004). The relationship between mouth-level exposure to nicotine and its salivary metabolite, cotinine, was not statistically significant (β=0.29, p=0.057), likely because of the very limited range of differences in mouth-level nicotine exposure in this population. CONCLUSIONS We have demonstrated a direct association between the 24-hour mouth level exposure of NNK resulting from cigarette smoking and the concentration of its primary metabolite, NNAL, in the urine of smokers. Internal dose concentrations of urinary NNAL are significantly lower in smokers in countries which have lower TSNA levels in cigarettes such as Canada and Australia in contrast to countries which have high levels of these carcinogens in cigarettes, such as the United States. IMPACT Lowering the levels of NNK in the mainstream smoke of cigarettes through the use of specific tobacco types and known curing practices can significantly impact the exposure of smokers to this known carcinogen. PMID:20501750

  13. Designing Peace and Conflict Exercises: Level of Analysis, Scenario, and Role Specification

    ERIC Educational Resources Information Center

    Bartels, Elizabeth; McCown, Margaret; Wilkie, Timothy

    2013-01-01

    Attentiveness to and transparency about the methodological implications of the level of analysis selected for peace and conflict exercises constitute essential elements of good game design. The article explores the impact of level of analysis choices in the context of two key portions of exercises, scenario construction and role specification. It…

  14. The relationship of certified flight instructors' emotional intelligence levels on flight student advancement

    NASA Astrophysics Data System (ADS)

    Hokeness, Mark Merrill

    Aviation researchers estimate airline companies will require nearly 500,000 pilots in the next 20 years. The role of a Certified Flight Instructor (CFI) is to move student pilots to professional pilots with training typically conducted in one-on-one student and instructor sessions. The knowledge of aviation, professionalism as a teacher, and the CFI’s interpersonal skills can directly affect the successes and advancement of a student pilot. A new and emerging assessment of people skills is known as emotional intelligence (EI). The EI of the CFI can and will affect a flight students’ learning experiences. With knowledge of emotional intelligence and its effect on flight training, student pilot dropouts from aviation may be reduced, thus helping to ensure an adequate supply of pilots. Without pilots, the growth of the commercial aviation industry will be restricted. This mixed method research study established the correlation between a CFI’s measured EI levels and the advancement of flight students. The elements contributing to a CFI’s EI level were not found to be teaching or flight-related experiences, suggesting other life factors are drawn upon by the CFI and are reflected in their emotional intelligence levels presented to flight students. Students respond positively to CFIs with higher levels of emotional intelligence. Awareness of EI skills by both the CFI and flight student contribute to flight student successes and advancement.

  15. Decreased melatonin levels and increased levels of advanced oxidation protein products in the seminal plasma are related to male infertility.

    PubMed

    Kratz, Ewa Maria; Piwowar, Agnieszka; Zeman, Michal; Stebelová, Katarína; Thalhammer, Theresia

    2016-03-01

    Melatonin, an indolamine secreted by the pineal gland, is known as a powerful free-radical scavenger and wide-spectrum antioxidant. Therefore, the aim of this study was to correlate markers of oxidative protein damage (advanced oxidation protein products, AOPPs) and the total antioxidant capacity (TAC) with melatonin levels in the seminal plasma of men with azoospermia (n=37), theratozoospermia (n=29) and fertile controls (normozoospermia, n=37). Melatonin concentration was measured by radioimmunoassay. The levels of AOPP as well as TAC efficiency (determined by the ferric reducing antioxidant power, FRAP) were estimated by spectrophotometric methods. The concentration of melatonin and AOPP significantly differed in azoospermic (P<0.0001) and theratozoospermic (P<0.0001) patients versus fertile men, and correlated negatively (r=-0.33, P=0.0016). The TAC levels were significantly higher in azoospermia than in theratozoospermia (P=0.0022) and the control group (P=0.00016). In azoospermia, the AOPP concentration was also significantly higher than that observed in theratozoospermia (P=0.00029). Decreased levels of melatonin together with elevated AOPP altered the oxidative-antioxidative balance in the ejaculate, thereby reducing fertility. Therefore, melatonin and AOPP levels may serve as additional diagnostic markers of semen quality and male reproductive potential. PMID:25218686

  16. Prostate-Specific Antigen Velocity Before and After Elimination of Factors That Can Confound the Prostate-Specific Antigen Level

    SciTech Connect

    Park, Jessica J.; Chen, Ming-Hui; Loffredo, Marian; D'Amico, Anthony V.

    2012-03-01

    Purpose: Prostate-specific antigen (PSA) velocity, like PSA level, can be confounded. In this study, we estimated the impact that confounding factors could have on correctly identifying a patient with a PSA velocity >2 ng/ml/y. Methods and Materials: Between 2006 and 2010, a total of 50 men with newly diagnosed PC comprised the study cohort. We calculated and compared the false-positive and false-negative PSA velocity >2 ng/ml/y rates for all men and those with low-risk disease using two approaches to calculate PSA velocity. First, we used PSA values obtained within 18 months of diagnosis; second, we used values within 18 months of diagnosis, substituting the prebiopsy PSA for a repeat, nonconfounded PSA that was obtained using the same assay and without confounders. Results: Using PSA levels pre-biopsy, 46% of all men had a PSA velocity >2 ng/ml/y; whereas this value declined to 32% when substituting the last prebiopsy PSA for a repeat, nonconfounded PSA using the same assay and without confounders. The false-positive rate for PSA velocity >2 ng/ml/y was 43% as compared with a false-negative rate of PSA velocity >2 ng/ml/y of 11% (p = 0.0008) in the overall cohort. These respective values in the low-risk subgroup were 60% and 16.7% (p = 0.09). Conclusion: This study provides evidence to explain the discordance in cancer-specific outcomes among groups investigating the prognostic significance of PSA velocity >2 ng/ml/y, and highlights the importance of patient education on potential confounders of the PSA test before obtaining PSA levels.

  17. Impaired clearance of accumulated lysosomal glycogen in advanced Pompe disease despite high-level vector-mediated transgene expression

    PubMed Central

    Sun, Baodong; Zhang, Haoyue; Bird, Andrew; Li, Songtao; Young, Sarah P.; Koeberl, Dwight D.

    2013-01-01

    Background Infantile-onset glycogen storage disease type II (GSD-II; Pompe disease; MIM 232300) causes death early in childhood from cardiorespiratory failure in absence of effective treatment, whereas late-onset Pompe disease causes a progressive skeletal myopathy. The limitations of enzyme replacement therapy could potentially be addressed with adeno-associated virus (AAV) vector-mediated gene therapy. Methods AAV vectors containing tissue-specific regulatory cassettes, either liver-specific or muscle-specific, were administered to 12 and 17 month old Pompe disease mice to evaluate the efficacy of gene therapy in advanced Pompe disease. Biochemical correction was evaluated through GAA activity and glycogen content analyses of the heart and skeletal muscle. Western blotting, urinary biomarker, and Rotarod performance were evaluated following vector administration. Results The AAV vector containing the liver-specific regulatory cassette secreted high-level hGAA into the blood and corrected glycogen storage in the heart and diaphragm. The biochemical correction of the heart and diaphragm was associated with efficacy, as reflected by increased Rotarod performance; however, the clearance of glycogen from skeletal muscles was relatively impaired, in comparison with younger Pompe disease mice. An alternative vector containing a muscle-specific regulatory cassette transduced skeletal muscle with high efficiency, but also failed to achieve complete clearance of accumulated glycogen. Decreased transduction of the heart and liver in older mice, especially in females, was implicated as a cause for reduced efficacy in advanced Pompe disease. Conclusion The impaired efficacy of AAV vector-mediated gene therapy in old Pompe disease mice emphasized the need for early treatment to achieve full efficacy. PMID:19621331

  18. Class- and subclass-specific pneumococcal antibody levels and response to immunization after bone marrow transplantation.

    PubMed Central

    Lortan, J E; Vellodi, A; Jurges, E S; Hugh-Jones, K

    1992-01-01

    Immunoglobulin class- and subclass-specific antibodies to a polyvalent pneumococcal capsular polysaccharide vaccine (Pneumovax II) were measured before and after immunization in children, 1 year or more after bone marrow transplantation for a variety of genetic disorders. The median titres of specific IgG, IgG1 and IgG2 pneumococcal antibodies fell significantly (P less than 0.05) from pre-transplantation levels. The levels of pneumococcal antibodies in the patients before immunization were markedly lower than those in control children of comparable age, for antibodies of IgM, IgG, IgG1 and IgG2 classes (P = less than 0.001 in each case). Apart from IgG2 antibodies, the median response to immunization with Pneumovax II was not significantly different from the controls (P greater than 0.05). However, because of the lower pre-immunization levels, the patients did not achieve a high post-immunization-specific antibody titre in any immunoglobulin class or subclass, when compared with normal children. Neither the pre-immunization specific antibody levels nor the response to immunization were affected by splenectomy or the presence of chronic graft-versus-host disease. Immunization of the donor before bone marrow harvest did not influence the level of specific antibody 1 year or more after transplantation. No significant correlation was found between the total serum IgG2, the patients' age at the time of assessment, or time after transplantation, and the IgG2-specific antibody response. The lack of specific antibodies and the poor IgG2 response to pneumococcal antigens may contribute towards the occurrence of infection with Streptococcus pneumoniae in the late post-transplantation period. PMID:1606736

  19. Does advancing male age influence the expression levels and localisation patterns of phospholipase C zeta (PLCζ) in human sperm?

    PubMed Central

    Yeste, Marc; Jones, Celine; Amdani, Siti Nornadhirah; Yelumalai, Suseela; Mounce, Ginny; da Silva, Sarah J. Martins; Child, Tim; Coward, Kevin

    2016-01-01

    Socio-economic factors have led to an increasing trend for couples to delay parenthood. However, advancing age exerts detrimental effects upon gametes which can have serious consequences upon embryo viability. While such effects are well documented for the oocyte, relatively little is known with regard to the sperm. One fundamental role of sperm is to activate the oocyte at fertilisation, a process initiated by phospholipase C zeta (PLCζ), a sperm-specific protein. While PLCζ deficiency can lead to oocyte activation deficiency and infertility, it is currently unknown whether the expression or function of PLCζ is compromised by advancing male age. Here, we evaluate sperm motility and the proportion of sperm expressing PLCζ in 71 males (22–54 years; 44 fertile controls and 27 infertile patients), along with total levels and localisation patterns of PLCζ within the sperm head. Three different statistical approaches were deployed with male age considered both as a categorical and a continuous factor. While progressive motility was negatively correlated with male age, all three statistical models concurred that no PLCζ–related parameter was associated with male age, suggesting that advancing male age is unlikely to cause problems in terms of the sperm’s fundamental ability to activate an oocyte. PMID:27270687

  20. Does advancing male age influence the expression levels and localisation patterns of phospholipase C zeta (PLCζ) in human sperm?

    PubMed

    Yeste, Marc; Jones, Celine; Amdani, Siti Nornadhirah; Yelumalai, Suseela; Mounce, Ginny; da Silva, Sarah J Martins; Child, Tim; Coward, Kevin

    2016-01-01

    Socio-economic factors have led to an increasing trend for couples to delay parenthood. However, advancing age exerts detrimental effects upon gametes which can have serious consequences upon embryo viability. While such effects are well documented for the oocyte, relatively little is known with regard to the sperm. One fundamental role of sperm is to activate the oocyte at fertilisation, a process initiated by phospholipase C zeta (PLCζ), a sperm-specific protein. While PLCζ deficiency can lead to oocyte activation deficiency and infertility, it is currently unknown whether the expression or function of PLCζ is compromised by advancing male age. Here, we evaluate sperm motility and the proportion of sperm expressing PLCζ in 71 males (22-54 years; 44 fertile controls and 27 infertile patients), along with total levels and localisation patterns of PLCζ within the sperm head. Three different statistical approaches were deployed with male age considered both as a categorical and a continuous factor. While progressive motility was negatively correlated with male age, all three statistical models concurred that no PLCζ-related parameter was associated with male age, suggesting that advancing male age is unlikely to cause problems in terms of the sperm's fundamental ability to activate an oocyte. PMID:27270687

  1. Impact of a Disease-Specific Advance Care Planning Intervention on End-of-life Care

    PubMed Central

    Kirchhoff, Karin T.; Hammes, Bernard J.; Kehl, Karen A.; Briggs, Linda A.; Brown, Roger L.

    2012-01-01

    Background/Objectives Advance Care Planning (ACP) allows patients to state preferences for their end of life care but these preferences are frequently ignored. Following a Patient-Centered ACP interview (PC-ACP), patients’ preferences were compared to care received at end of life. Design A randomized controlled trial was conducted with patients with Congestive Heart Failure or End-stage Renal Disease and their surrogates who were randomized to receive either PC-ACP or usual care. Setting Two centers in Wisconsin with associated clinics/dialysis units provided patients. Participants Of the 313 patients and their surrogates who completed entry data, 110 died. Intervention During PC-ACP the trained facilitator assessed the patient and surrogate understanding of and experiences with the illness, provided information about disease-specific treatment options and their benefits and burden, assisted in documentation of patient treatment preferences, and assisted the surrogates in understanding the patient’s preferences and their role. Measurements Preferences were documented and then compared to the care received at end of life determined by surrogate interviews or medical charts. Results Patients (74%) frequently continued to make their own decisions about care to the end. The experimental group had fewer (1/62) but not significantly so cases where the patients could not get their wishes met about CPR than control (6/48). Significantly more experimental patients withdrew from dialysis than control. Conclusions Patients and their surrogates were generally willing to discuss preferences with a trained facilitator. Most patients received the care they desired at end of life or altered their preferences to be in accord with the care they could receive. A larger sample with surrogate decision makers is needed to detect significance. PMID:22458336

  2. A Graphical Framework for Specification of Clinical Guidelines at Multiple Representation Levels

    PubMed Central

    Shalom, Erez; Shahar, Yuval

    2005-01-01

    Formalization of a clinical guideline for purposes of automated application and quality assessment mainly involves conversion of its free-text representation into a machine comprehensible representation, i.e., a formal language, thus enabling automated support. The main issues involved in this process are related to the collaboration between the expert physician and the knowledge engineer. We introduce GESHER - a graphical framework for specification of clinical guidelines at multiple representation levels. The GESHER architecture facilitates incremental specification through a set of views adapted to each representation level, enabling this process to proceed smoothly and in a transparent fashion, fostering extensive collaboration among the various types of users. The GESHER framework supports specification of guidelines at multiple representation levels, in more than one specification language, and uses the DeGeL digital guideline library architecture as its knowledge base. The GESHER architecture also uses a temporal abstraction knowledge base to store its declarative knowledge, and a standard medical-vocabularies server for generic specification of key terms, thus enabling reuse of the specification at multiple sites. PMID:16779126

  3. Sensitivity and specificity of fluid-blood levels for coagulopathy in acute intracerebral hematomas

    SciTech Connect

    Pfleger, M.J.; Hardee, E.P.; Hayman, L.A.; Contant, C.F. Jr. )

    1994-02-01

    To characterize the imaging features of intracerebral hemorrhages in patients with coagulopathies that alter prothrombin time or partial thromboplastin time. A fluid-blood level was defined as a horizontal interface between hypodense bloody serum layered above hyperdense settled blood. The prevalence of fluid-blood levels in acute intracerebral hemorrhages was determined on third-generation CT scans in 32 patients with elevation in prothrombin time or partial thromboplastin time. This was compared with the frequency of fluid-blood levels in 185 patients with intracerebral hemorrhage in which there was no laboratory evidence of coagulopathy. The probability of finding a fluid-blood level in an intracerebral hemorrhage of a patient with abnormal prothrombin time or partial thromboplastin time was 59% (sensitivity). The probability that there will be no fluid-blood level in a patient with a normal prothrombin time and partial thromboplastin time was 98% (specificity). Fluid-blood levels in acute intracerebral hemorrhage are moderately sensitive to the presence of coagulopathy (i.e., abnormal prothrombin time and partial thromboplastin time) and highly specific for this condition. Thus, an intracerebral hemorrhage with a fluid-blood level should prompt a thorough search for coagulopathy because early treatment of this condition may improve the 40% mortality in these patients. Caution should be used to distinguish the horizontal interface of a fluid-blood level from a clot with a flat top. A decubitus CT is useful in these rare instances. 20 refs., 5 figs., 2 tabs.

  4. The low-abundance transcriptome reveals novel biomarkers, specific intracellular pathways and targetable genes associated with advanced gastric cancer.

    PubMed

    Bizama, Carolina; Benavente, Felipe; Salvatierra, Edgardo; Gutiérrez-Moraga, Ana; Espinoza, Jaime A; Fernández, Elmer A; Roa, Iván; Mazzolini, Guillermo; Sagredo, Eduardo A; Gidekel, Manuel; Podhajcer, Osvaldo L

    2014-02-15

    Studies on the low-abundance transcriptome are of paramount importance for identifying the intimate mechanisms of tumor progression that can lead to novel therapies. The aim of the present study was to identify novel markers and targetable genes and pathways in advanced human gastric cancer through analyses of the low-abundance transcriptome. The procedure involved an initial subtractive hybridization step, followed by global gene expression analysis using microarrays. We observed profound differences, both at the single gene and gene ontology levels, between the low-abundance transcriptome and the whole transcriptome. Analysis of the low-abundance transcriptome led to the identification and validation by tissue microarrays of novel biomarkers, such as LAMA3 and TTN; moreover, we identified cancer type-specific intracellular pathways and targetable genes, such as IRS2, IL17, IFNγ, VEGF-C, WISP1, FZD5 and CTBP1 that were not detectable by whole transcriptome analyses. We also demonstrated that knocking down the expression of CTBP1 sensitized gastric cancer cells to mainstay chemotherapeutic drugs. We conclude that the analysis of the low-abundance transcriptome provides useful insights into the molecular basis and treatment of cancer. PMID:23907728

  5. Upscaling the niche variation hypothesis from the intra- to the inter-specific level.

    PubMed

    Bison, Marjorie; Ibanez, Sébastien; Redjadj, Claire; Boyer, Frédéric; Coissac, Eric; Miquel, Christian; Rioux, Delphine; Said, Sonia; Maillard, Daniel; Taberlet, Pierre; Yoccoz, Nigel Gilles; Loison, Anne

    2015-11-01

    The "niche variation hypothesis" (NVH) predicts that populations with wider niches should display higher among-individual variability. This prediction originally stated at the intra-specific level may be extended to the inter-specific level: individuals of generalist species may differ to a greater extent than individuals of a specialist species. We tested the NVH at intra- and inter-specific levels based on a large diet database of three large herbivore feces collected in the field and analyzed using DNA metabarcoding. The three herbivores (roe deer Capreolus capreolus, chamois Rupicapra rupicapra and mouflon Ovis musimon) are highly contrasted in terms of sociality (solitary to highly gregarious) and diet. The NVH at the intraspecific level was tested by relating, for the same population, diet breadth and inter-individual variation across the four seasons. Compared to null models, our data supported the NVH both at the intra- and inter-specific levels. Inter-individual variation of the diet of solitary species was not larger than in social species, although social individuals feed together and could therefore have more similar diets. Hence, the NVH better explained diet breadth than other factors such as sociality. The expansion of the population niche of the three species was driven by resource availability, and achieved by an increase in inter-individual variation, and the level of inter-individual variability was larger in the generalist species (mouflon) than in the specialist one (roe deer). This mechanism at the base of the NVH appears at play at different levels of biological organization, from populations to communities. PMID:26198049

  6. An end-to-end workflow for engineering of biological networks from high-level specifications.

    PubMed

    Beal, Jacob; Weiss, Ron; Densmore, Douglas; Adler, Aaron; Appleton, Evan; Babb, Jonathan; Bhatia, Swapnil; Davidsohn, Noah; Haddock, Traci; Loyall, Joseph; Schantz, Richard; Vasilev, Viktor; Yaman, Fusun

    2012-08-17

    We present a workflow for the design and production of biological networks from high-level program specifications. The workflow is based on a sequence of intermediate models that incrementally translate high-level specifications into DNA samples that implement them. We identify algorithms for translating between adjacent models and implement them as a set of software tools, organized into a four-stage toolchain: Specification, Compilation, Part Assignment, and Assembly. The specification stage begins with a Boolean logic computation specified in the Proto programming language. The compilation stage uses a library of network motifs and cellular platforms, also specified in Proto, to transform the program into an optimized Abstract Genetic Regulatory Network (AGRN) that implements the programmed behavior. The part assignment stage assigns DNA parts to the AGRN, drawing the parts from a database for the target cellular platform, to create a DNA sequence implementing the AGRN. Finally, the assembly stage computes an optimized assembly plan to create the DNA sequence from available part samples, yielding a protocol for producing a sample of engineered plasmids with robotics assistance. Our workflow is the first to automate the production of biological networks from a high-level program specification. Furthermore, the workflow's modular design allows the same program to be realized on different cellular platforms simply by swapping workflow configurations. We validated our workflow by specifying a small-molecule sensor-reporter program and verifying the resulting plasmids in both HEK 293 mammalian cells and in E. coli bacterial cells. PMID:23651286

  7. Specifications for the Ginn Reading 360 Learning Mastery System (Levels 1-10).

    ERIC Educational Resources Information Center

    Okada, Masahito; And Others

    This document describes the rationale and specifications for the Ginn Reading 360 Learning Mastery System (LMS) (levels 1 through 10). The LMS is a set of materials and procedures prepared by the Southwest Regional Laboratory (SWRL) as an objectives-based framework to assist in managing the learning activities of existing instructional materials.…

  8. Levels and Growth of Specific and General Norms for Nonviolence among Middle School Students

    ERIC Educational Resources Information Center

    Dymnicki, Allison B.; Antonio, Tiago; Henry, David B.

    2011-01-01

    This study examined the levels and growth of specific and general normative beliefs about nonviolence (called norms for nonviolence). The sample consisted of 1254 middle school students from four metropolitan areas who participated in the control condition of the Multisite Violence Prevention Project. We predicted that the association and…

  9. Response to Specific Training for Students with Different Levels of Mathematical Difficulties

    ERIC Educational Resources Information Center

    Re, Anna Maria; Pedron, Martina; Tressoldi, Patrizio Emanuele; Lucangeli, Daniela

    2014-01-01

    The purpose of this study was to determine the efficacy of specific, individualized training for students with different levels of mathematical difficulties. Fifty-four students, with either severe or mild math difficulties, were assigned to individualized training or to a control condition. Ten students with severe math difficulties…

  10. Rapid perceptual adaptation to high gravitoinertial force levels Evidence for context-specific adaptation

    NASA Technical Reports Server (NTRS)

    Lackner, J. R.; Graybiel, A.

    1982-01-01

    Subjects exposed to periodic variations in gravitoinertial force (2-G peak) in parabolic flight maneuvers quickly come to perceive the peak force level as having decreased in intensity. By the end of a 40-parabola flight, the decrease in apparent force is approximately 40%. On successive flight days, the apparent intensity of the force loads seems to decrease as well, indicating a cumulative adaptive effect. None of the subjects reported feeling abnormally 'light' for more than a minute or two after return to 1-G background force levels. The pattern of findings suggests a context-specific adaptation to high-force levels.

  11. Helicopter far-field acoustic levels as a function of reduced main-rotor advancing blade-tip Mach number

    NASA Astrophysics Data System (ADS)

    Mueller, Arnold W.; Smith, Charles D.; Lemasurier, Philip

    1990-07-01

    During the design of a helicopter, the weight, engine, rotor speed, and rotor geometry are given significant attention when considering the specific operations for which the helicopter will be used. However, the noise radiated from the helicopter and its relationship to the design variables is currently not well modeled with only a limited set of full-scale field test data to study. In general, limited field data have shown that reduced main-rotor advancing blade-tip Mach numbers result in reduced far-field noise levels. The status of a recent helicopter noise research project is reviewed. It is designed to provide flight experimental data which may be used to further understand helicopter main-rotor advancing blade-tip Mach number effects on far-field acoustic levels. Preliminary results are presented relative to tests conducted with a Sikorsky S-76A helicopter operating with both the rotor speed and the flight speed as the control variable. The rotor speed was operated within the range of 107 to 90 percent NR at nominal forward speeds of 35, 100, and 155 knots.

  12. Helicopter far-field acoustic levels as a function of reduced main-rotor advancing blade-tip Mach number

    NASA Technical Reports Server (NTRS)

    Mueller, Arnold W.; Smith, Charles D.; Lemasurier, Philip

    1990-01-01

    During the design of a helicopter, the weight, engine, rotor speed, and rotor geometry are given significant attention when considering the specific operations for which the helicopter will be used. However, the noise radiated from the helicopter and its relationship to the design variables is currently not well modeled with only a limited set of full-scale field test data to study. In general, limited field data have shown that reduced main-rotor advancing blade-tip Mach numbers result in reduced far-field noise levels. The status of a recent helicopter noise research project is reviewed. It is designed to provide flight experimental data which may be used to further understand helicopter main-rotor advancing blade-tip Mach number effects on far-field acoustic levels. Preliminary results are presented relative to tests conducted with a Sikorsky S-76A helicopter operating with both the rotor speed and the flight speed as the control variable. The rotor speed was operated within the range of 107 to 90 percent NR at nominal forward speeds of 35, 100, and 155 knots.

  13. A new hydrostatic leveling system developed for the Advanced Photon Source.

    SciTech Connect

    Kivioja, L. A.

    1998-09-18

    As a result of the calibration tests performed with the first prototype units using the new measurement principle, we believe that the described leveling method is stable and accurate to the micron level with a sufficiently large range for the expected elevation changes of the support girders used in the Advanced Photon Source (APS) storage ring. Although long-term studies with this system have not been conducted, we believe that after installation this system requires little or no servicing for long periods of time. The methods described in this paper cover only the elevation changes of individual vessels. However, changes in the tilt of a girder must also be known. Therefore, a combination of tiltmeters in conjunction with this hydrostatic level system (HLS) would be most suitable for measuring the tilt and elevation changes of the APS girders.

  14. Advancing drug discovery for neuropsychiatric disorders using patient-specific stem cell models.

    PubMed

    Haggarty, Stephen J; Silva, M Catarina; Cross, Alan; Brandon, Nicholas J; Perlis, Roy H

    2016-06-01

    Compelling clinical, social, and economic reasons exist to innovate in the process of drug discovery for neuropsychiatric disorders. The use of patient-specific, induced pluripotent stem cells (iPSCs) now affords the ability to generate neuronal cell-based models that recapitulate key aspects of human disease. In the context of neuropsychiatric disorders, where access to physiologically active and relevant cell types of the central nervous system for research is extremely limiting, iPSC-derived in vitro culture of human neurons and glial cells is transformative. Potential applications relevant to early stage drug discovery, include support of quantitative biochemistry, functional genomics, proteomics, and perhaps most notably, high-throughput and high-content chemical screening. While many phenotypes in human iPSC-derived culture systems may prove adaptable to screening formats, addressing the question of which in vitro phenotypes are ultimately relevant to disease pathophysiology and therefore more likely to yield effective pharmacological agents that are disease-modifying treatments requires careful consideration. Here, we review recent examples of studies of neuropsychiatric disorders using human stem cell models where cellular phenotypes linked to disease and functional assays have been reported. We also highlight technical advances using genome-editing technologies in iPSCs to support drug discovery efforts, including the interpretation of the functional significance of rare genetic variants of unknown significance and for the purpose of creating cell type- and pathway-selective functional reporter assays. Additionally, we evaluate the potential of in vitro stem cell models to investigate early events of disease pathogenesis, in an effort to understand the underlying molecular mechanism, including the basis of selective cell-type vulnerability, and the potential to create new cell-based diagnostics to aid in the classification of patients and subsequent

  15. Effects of site-specific level adjustments on speech recognition with cochlear implants

    PubMed Central

    Zhou, Ning; Pfingst, Bryan E.

    2013-01-01

    Objectives Modulation detection thresholds (MDTs) vary across stimulation sites in a cochlear implant electrode array in a manner that is subject and ear specific. Previous studies have demonstrated that speech recognition with a cochlear implant can be improved by site-selection strategies, where selected stimulation sites with poor modulation sensitivity are removed from a subject’s processor MAP1. Limitations of site-selection strategies are that they can compromise spectral resolution and distort frequency-place mapping since the frequencies assigned to the removed sites are usually reallocated to other sites and site bandwidths are broadened. The objective of the current study was to test an alternative approach for rehabilitation that aimed at improving the across-site mean (ASM) MDTs by adjusting stimulation parameters at the poorly-performing sites. Based on previous findings that modulation detection contributes to speech recognition and improves significantly with stimulus level, we hypothesized that modulation sensitivity at the poor sites can be improved by artificially increasing stimulation levels at those sites in the speech processor, which then leads to improved speech recognition. Design Nine postlingually deafened ears implanted with Nucleus cochlear implants were evaluated for MDTs, absolute-detection threshold levels (T levels) and the maximum loudness levels (C levels) on each of the available stimulation sites. For each ear, the minimum stimulation level settings in the speech processor MAP were raised by 5%, and alternatively by 10%, of the dynamic range (DR) from true thresholds on 5 stimulation sites with the poorest MDTs. For comparison, a 5% level raise was globally applied to all stimulation sites. The C levels were fixed during these level manipulations. MDTs at the 5 poorest stimulation sites were compared at 20% DR before and after the level adjustments. Speech reception thresholds (SRTs), i.e., signal to noise ratios (SNRs

  16. Drought Prediction Site Specific and Regional up to Three Years in Advance

    NASA Astrophysics Data System (ADS)

    Suhler, G.; O'Brien, D. P.

    2002-12-01

    Dynamic Predictables has developed proprietary software that analyzes and predicts future climatic behavior based on past data. The programs employ both a regional thermodynamic model together with a unique predictive algorithm to achieve a high degree of prediction accuracy up to 36 months. The thermodynamic model was developed initially to explain the results of a study on global circulation models done at SUNY-Stony Brook by S. Hameed, R.G. Currie, and H. LaGrone (Int. Jour. Climatology, 15, pp.852-871, 1995). The authors pointed out that on a time scale of 2-70 months the spectrum of sea level pressure is dominated by the harmonics and subharmonics of the seasonal cycle and their combination tones. These oscillations are fundamental to an understanding of climatic variations on a sub-regional to continental basis. The oscillatory nature of these variations allows them to be used as broad based climate predictors. In addition, they can be subtracted from the data to yield residuals. The residuals are then analyzed to determine components that are predictable. The program then combines both the thermodynamic model results (the primary predictive model) with those from the residual data (the secondary model) to yield an estimate of the future behavior of the climatic variable. Spatial resolution is site specific or aggregated regional based upon appropriate length (45 years or more monthly data) and reasonable quality weather observation records. Most climate analysis has been based on monthly time-step data, but time scales on the order of days can be used. Oregon Climate Division 1 (Coastal) precipitation provides an example relating DynaPred's method to nature's observed elements in the early 2000s. The prediction's leading dynamic factors are the strong seasonal in the primary model combined with high secondary model contributions from planet Earth's Chandler Wobble (near 15 months) and what has been called the Quasi-Triennial Oscillation (QTO, near 36 months

  17. High-Level Functional and Operational Requirements for the Advanced Fuel Cycle Facilty

    SciTech Connect

    Charles Park

    2006-12-01

    High-Level Functional & Operational Requirements for the AFCF -This document describes the principal functional and operational requirements for the proposed Advanced Fuel Cycle Facility (AFCF). The AFCF is intended to be the world's foremost facility for nuclear fuel cycle research, technology development, and demonstration. The facility will also support the near-term mission to develop and demonstrate technology in support of fuel cycle needs identified by industry, and the long-term mission to retain and retain U.S. leadership in fuel cycle operations. The AFCF is essential to demonstrate a more proliferation-resistant fuel cycle and make long-term improvements in fuel cycle effectiveness, performance and economy.

  18. The GLAS Standard Data Products Specification--Level 2, Version 9. Volume 14

    NASA Technical Reports Server (NTRS)

    Lee, Jeffrey E.

    2013-01-01

    The Geoscience Laser Altimeter System (GLAS) is the primary instrument for the ICESat (Ice, Cloud and Land Elevation Satellite) laser altimetry mission. ICESat was the benchmark Earth Observing System (EOS) mission for measuring ice sheet mass balance, cloud and aerosol heights, as well as land topography and vegetation characteristics. From 2003 to 2009, the ICESat mission provided multi-year elevation data needed to determine ice sheet mass balance as well as cloud property information, especially for stratospheric clouds common over polar areas. It also provided topography and vegetation data around the globe, in addition to the polar-specific coverage over the Greenland and Antarctic ice sheets.This document defines the Level-2 GLAS standard data products. This document addresses the data flow, interfaces, record and data formats associated with the GLAS Level 2 standard data products. The term standard data products refers to those EOS instrument data that are routinely generated for public distribution. The National Snow and Ice Data Center (NSDIC) distribute these products. Each data product has a unique Product Identification code assigned by the Senior Project Scientist. The Level 2 Standard Data Products specifically include those derived geophysical data values (i.e., ice sheet elevation, cloud height, vegetation height, etc.). Additionally, the appropriate correction elements used to transform the Level 1A and Level 1B Data Products into Level 2 Data Products are included. The data are packaged with time tags, precision orbit location coordinates, and data quality and usage flags.

  19. Preliminary level 2 specification for the nested, fixed-depth sampling system

    SciTech Connect

    BOGER, R.M.

    1999-02-08

    This preliminary Level 2 Component Specification establishes the performance, design, development, and test requirements for the in-tank sampling system which will support the BNFL contract in the final disposal of Hanford's High Level Wastes (HLW) and Low Activity Wastes (LAW). The PHMC will provide Low Activity Wastes (LAW) tank wastes for final treatment by BNFL from double-shell feed tanks. Concerns about the inability of the baseline ''grab'' sampling to provide large volume samples within time constraints has led to the development of a nested, fixed-depth sampling system. This sampling system will provide large volume? representative samples without the environmental, radiation exposure, and sample volume Impacts of the current base-line ''grab'' sampling method. This preliminary Level 2 Component Specification is not a general specification for tank sampling, but is based on a ''record of decision'', AGA (HNF-SD-TWR-AGA-001 ), the System Specification for the Double Shell Tank System (HNF-SD-WM-TRD-O07), and the BNFL privatization contract.

  20. Serum Prosaposin Levels Are Increased in Patients with Advanced Prostate Cancer

    PubMed Central

    Koochekpour, Shahriar; Hu, Siyi; Vellasco-Gonzalez, Cruz; Bernardo, Ruiz; Azabdaftari, Gissue; Dalin, Guo-xiang; Zhau, Haiyen E.; Chung, Leland W.; Vessella, Robert L.

    2012-01-01

    BACKGROUND We previously cloned prosaposin (PSAP) from metastatic castrate-resistant prostate cancer (mCRPCa) cells and demonstrated its genomic amplification and/or overexpression in metastatic PCa cell lines, xenografts, and lymph node metastases. The clinicohistopathological significance of serum-PSAP levels and its tissue expression and association with predictive or prognostic variable in primary or advanced PCa are not known. METHODS We examined PSAP expression by immunohistochemical staining during early embryogenic development of the prostate and within a large tissue microarray which included 266 benign and malignant prostate tissues. In addition, serum PSAP levels in the age-adjusted normal male population and in 154 normal individuals and patients with primary or mCRPCa were measured by an ELISA assay. RESULTS Univariate and multivariate analyses revealed a significant and inverse association between PSAP expression and clinical stage II and III tumors, dominant Gleason patterns 3 and 4, and seminal vesicle invasion. In the normal male population, the lowest serum-PSAP level was detected before puberty, peaked at the most reproductive age group (20–39 years old), and then, decreased to a range between the two groups for men above 40 years old. Regardless of age and when compared with normal individuals, serum-PSAP levels significantly decreased in primary organ-confined PCa, but increased in those with mCRPCa. CONCLUSION Our results show that PSAP has the potential to differentiate between primary and advanced PCa. Additional large-scale studies are needed to define the usefulness of tissue expression or serum-PSAP levels as a diagnostic or prognostic marker or as a therapeutic target in PCa. PMID:21630292

  1. Effect of natural gas exsolution on specific storage in a confined aquifer undergoing water level decline

    USGS Publications Warehouse

    Yager, R.M.; Fountain, J.C.

    2001-01-01

    The specific storage of a porous medium, a function of the compressibility of the aquifer material and the fluid within it, is essentially constant under normal hydrologic conditions. Gases dissolved in ground water can increase the effective specific storage of a confined aquifer, however, during water level declines. This causes a reduction in pore pressure that lowers the gas solubility and results in exsolution. The exsolved gas then displaces water from storage, and the specific storage increases because gas compressibility is typically much greater than that of water or aquifer material. This work describes the effective specific storage of a confined aquifer exsolving dissolved gas as a function of hydraulic head and the dimensionless Henry's law constant for the gas. This relation is applied in a transient simulation of ground water discharge from a confined aquifer system to a collapsed salt mine in the Genesee Valley in western New York. Results indicate that exsolution of gas significantly increased the effective specific storage in the aquifer system, thereby decreasing the water level drawdown.

  2. Relationship of species-specific filament levels to filamentous bulking in activated sludge.

    PubMed

    Liao, Jiangying; Lou, Inchio; de los Reyes, Francis L

    2004-04-01

    To examine the relationship between activated-sludge bulking and levels of specific filamentous bacteria, we developed a statistics-based quantification method for estimating the biomass levels of specific filaments using 16S rRNA-targeted fluorescent in situ hybridization (FISH) probes. The results of quantitative FISH for the filament Sphaerotilus natans were similar to the results of quantitative membrane hybridization in a sample from a full-scale wastewater treatment plant. Laboratory-scale reactors were operated under different flow conditions to develop bulking and nonbulking sludge and were bioaugmented with S. natans cells to stimulate bulking. Instead of S. natans, the filament Eikelboom type 1851 became dominant in the reactors. Levels of type 1851 filaments extending out of the flocs correlated strongly with the sludge volume index, and extended filament lengths of approximately 6 x 10(8) micro m ml(-1) resulted in bulking in laboratory-scale and full-scale activated-sludge samples. Quantitative FISH showed that high levels of filaments occurred inside the flocs in nonbulking sludge, supporting the "substrate diffusion limitation" hypothesis for bulking. The approach will allow the monitoring of incremental improvements in bulking control methods and the delineation of the operational conditions that lead to bulking due to specific filaments. PMID:15066840

  3. Circulating APRIL levels are correlated with advanced disease and prognosis in rectal cancer patients.

    PubMed

    Lascano, V; Hahne, M; Papon, L; Cameron, K; Röeder, C; Schafmayer, C; Driessen, L; van Eenennaam, H; Kalthoff, H; Medema, J P

    2015-01-01

    We have previously shown that the tumor necrosis factor family member a proliferation-inducing ligand (APRIL) enhances intestinal tumor growth in various preclinical tumor models. Here, we have investigated whether APRIL serum levels at time of surgery predict survival in a large cohort of colorectal cancer (CRC) patients. We measured circulating APRIL levels in a cohort of CRC patients (n=432) using a novel validated monoclonal APRIL antibody (hAPRIL.133) in an enzyme-linked immunosorbent assay (ELISA) setup. APRIL levels were correlated with clinicopathological features and outcome. Overall survival was examined with Kaplan-Meier survival analysis, and Cox proportional hazards ratios were calculated. We observed that circulating APRIL levels were normally distributed among CRC patients. High APRIL expression correlated significantly with poor outcome measures, such as higher stage at presentation and development of lymphatic and distant metastases. Within the group of rectal cancer patients, higher circulating APRIL levels at time of surgery were correlated with poor survival (log-rank analysis P-value 0.008). Univariate Cox regression analysis for overall survival in rectal cancer patients showed that patients with elevated circulating APRIL levels had an increased risk of poor outcome (hazard ratio (HR) 1.79; 95% confidence interval (CI) 1.16-2.76; P-value 0.009). Multivariate analysis in rectal cancer patients showed that APRIL as a prognostic factor was dependent on stage of disease (HR 1.25; 95% CI 0.79-1.99; P-value 0.340), which was related to the fact that stage IV rectal cancer patients had significantly higher levels of APRIL. Our results revealed that APRIL serum levels at time of surgery were associated with features of advanced disease and prognosis in rectal cancer patients, which strengthens the previously reported preclinical observation of increased APRIL levels correlating with disease progression. PMID:25622308

  4. Specification and verification of gate-level VHDL models of synchronous and asynchronous circuits

    NASA Technical Reports Server (NTRS)

    Russinoff, David M.

    1995-01-01

    We present a mathematical definition of hardware description language (HDL) that admits a semantics-preserving translation to a subset of VHDL. Our HDL includes the basic VHDL propagation delay mechanisms and gate-level circuit descriptions. We also develop formal procedures for deriving and verifying concise behavioral specifications of combinational and sequential devices. The HDL and the specification procedures have been formally encoded in the computational logic of Boyer and Moore, which provides a LISP implementation as well as a facility for mechanical proof-checking. As an application, we design, specify, and verify a circuit that achieves asynchronous communication by means of the biphase mark protocol.

  5. The GLAS Standard Data Products Specification-Level 1, Version 9

    NASA Technical Reports Server (NTRS)

    Lee, Jeffrey E.

    2013-01-01

    The Geoscience Laser Altimeter System (GLAS) is the primary instrument for the ICESat (Ice, Cloud and Land Elevation Satellite) laser altimetry mission. ICESat was the benchmark Earth Observing System (EOS) mission for measuring ice sheet mass balance, cloud and aerosol heights, as well as land topography and vegetation characteristics. From 2003 to 2009, the ICESat mission provided multi-year elevation data needed to determine ice sheet mass balance as well as cloud property information, especially for stratospheric clouds common over polar areas. It also provided topography and vegetation data around the globe, in addition to the polar-specific coverage over the Greenland and Antarctic ice sheets.This document defines the Level-1 GLAS standard data products. This document addresses the data flow, interfaces, record and data formats associated with the GLAS Level 1 standard data products. GLAS Level 1 standard data products are composed of Level 1A and Level 1B data products. The term standard data products refers to those EOS instrument data that are routinely generated for public distribution. The National Snow and Ice Data Center (NSDIC) distribute these products. Each data product has a unique Product Identification code assigned by the Senior Project Scientist. GLAS Level 1A and Level 1B Data Products are composed from those Level 0 data that have been reformatted or transformed to corrected and calibrated data in physical units at the full instrument rate and resolution.

  6. Advanced waste form and melter development for treatment of troublesome high-level wastes

    SciTech Connect

    Marra, James; Kim, Dong -Sang; Maio, Vincent

    2015-09-02

    A number of waste components in US defense high level radioactive wastes (HLW) have proven challenging for current Joule heated ceramic melter (JHCM) operations and have limited the ability to increase waste loadings beyond already realized levels. Many of these "troublesome" waste species cause crystallization in the glass melt that can negatively impact product quality or have a deleterious effect on melter processing. Recent efforts at US Department of Energy laboratories have focused on understanding crystallization behavior within HLW glass melts and investigating approached to mitigate the impacts of crystallization so that increases in waste loading can be realized. Advanced glass formulations have been developed to highlight the unique benefits of next-generation melter technologies such as the Cold Crucible Induction Melter (CCIM). Crystal-tolerant HLW glasses have been investigated to allow sparingly soluble components such as chromium to crystallize in the melter but pass out of the melter before accumulating.

  7. System-level performance of LTE-Advanced with joint transmission and dynamic point selection schemes

    NASA Astrophysics Data System (ADS)

    Määttänen, Helka-Liina; Hämäläinen, Kari; Venäläinen, Juha; Schober, Karol; Enescu, Mihai; Valkama, Mikko

    2012-12-01

    In this article, we present a practical coordinated multipoint (CoMP) system for LTE-Advanced. In this CoMP system, cooperation is enabled for cell-edge users via dynamic switching between the normal single-cell operation and CoMP. We first formulate a general CoMP system model of several CoMP schemes. We then investigate a practical finite-rate feedback design that simultaneously supports interference coordination, joint transmission (JT), and dynamic point selection (DPS) with a varying number of cooperating transmission points while operating a single-cell transmission as a fallback mode. We provide both link-level and system-level results for the evaluation of different feedback options for general CoMP operation. The results show that there are substantial performance gains in cell-edge throughputs for both JT and DPS CoMP over the baseline Release 10 LTE-Advanced with practical feedback options. We also show that CoMP can enable improved mobility management in real networks.

  8. Water level, specific conductance, and water temperature data, San Francisco Bay, California, for Water Year 2000

    USGS Publications Warehouse

    Buchanan, P.A.

    2002-01-01

    Time series of water-level, specific-conductance, and watertemperature data were collected at seven sites in San Francisco Bay during water year 2000 (October 1, 1999 through September 30, 2000). Water-level data were recorded only at Point San Pablo. Specific-conductance and water-temperature data were recorded at 15-minute intervals at the following locations (Figure 1): • Carquinez Strait at Carquinez Bridge • Napa River at Mare Island Causeway near Vallejo • San Pablo Bay at Petaluma River Channel Marker 9 • San Pablo Strait at Point San Pablo • Central San Francisco Bay at Presidio Military Reservation • Central San Francisco Bay at Pier 24 • South San Francisco Bay at San Mateo Bridge near Foster City.

  9. Pakistan-Specific Cases for the Advanced Management Course in Public Administration.

    ERIC Educational Resources Information Center

    McLean, Gary N., Ed.

    A compilation of management case studies concerning public administration in Pakistan and accompanying teaching notes, this document is intended to foster discussion in classes such as the advanced management course in public administration at the National Institute of Public Administration in Lahore, Pakistan. Included are case studies entitled…

  10. Extracellular stimuli specifically regulate localized levels of individual neuronal mRNAs

    PubMed Central

    Willis, Dianna E.; van Niekerk, Erna A.; Sasaki, Yukio; Mesngon, Mariano; Merianda, Tanuja T.; Williams, Gervan G.; Kendall, Marvin; Smith, Deanna S.; Bassell, Gary J.; Twiss, Jeffery L.

    2007-01-01

    Subcellular regulation of protein synthesis requires the correct localization of messenger RNAs (mRNAs) within the cell. In this study, we investigate whether the axonal localization of neuronal mRNAs is regulated by extracellular stimuli. By profiling axonal levels of 50 mRNAs detected in regenerating adult sensory axons, we show that neurotrophins can increase and decrease levels of axonal mRNAs. Neurotrophins (nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3) regulate axonal mRNA levels and use distinct downstream signals to localize individual mRNAs. However, myelin-associated glycoprotein and semaphorin 3A regulate axonal levels of different mRNAs and elicit the opposite effect on axonal mRNA levels from those observed with neurotrophins. The axonal mRNAs accumulate at or are depleted from points of ligand stimulation along the axons. The translation product of a chimeric green fluorescent protein–β-actin mRNA showed similar accumulation or depletion adjacent to stimuli that increase or decrease axonal levels of endogenous β-actin mRNA. Thus, extracellular ligands can regulate protein generation within subcellular regions by specifically altering the localized levels of particular mRNAs. PMID:17785519

  11. Prostate specific antigen levels after definitive irradiation for carcinoma of the prostate

    SciTech Connect

    Schellhammer, P.F.; Schlossberg, S.M.; el-Mahdi, A.M.; Wright, G.L.; Brassil, D.N. )

    1991-05-01

    Prostate specific antigen (PSA) levels were determined in 78 patients judged clinically to be free of disease at intervals of 36 or more months (range 38 to 186 months, median 87 months) after completion of irradiation therapy by 125-iodine implantation or external beam radiation. Of this select group of patients 38% had undetectable serum PSA levels (0.5 ng./ml. or less) and 38% had PSA levels that were within normal limits (4.0 ng./ml. or less). All stages and grades were represented. Undetectable PSA levels were only rarely found (3%) in patients with carcinoma of the prostate before treatment. In 24 of these 78 patients a negative biopsy of the irradiated prostate had been obtained 18 to 42 months after treatment. When the PSA level was drawn, which ranged from 7 to 16 years after treatment, an equal percentage of these biopsied patients had either an undetectable, normal or elevated level. Irradiation is able to decrease PSA to undetectable levels in some patients with prostatic carcinoma. Whether this reflects suppression of marker production alone or, more importantly, ablation of prostate cancer producing that marker remains to be determined.

  12. Protein Domain-Level Landscape of Cancer-Type-Specific Somatic Mutations

    PubMed Central

    Yang, Fan; Petsalaki, Evangelia; Rolland, Thomas; Hill, David E.; Vidal, Marc; Roth, Frederick P.

    2015-01-01

    Identifying driver mutations and their functional consequences is critical to our understanding of cancer. Towards this goal, and because domains are the functional units of a protein, we explored the protein domain-level landscape of cancer-type-specific somatic mutations. Specifically, we systematically examined tumor genomes from 21 cancer types to identify domains with high mutational density in specific tissues, the positions of mutational hotspots within these domains, and the functional and structural context where possible. While hotspots corresponding to specific gain-of-function mutations are expected for oncoproteins, we found that tumor suppressor proteins also exhibit strong biases toward being mutated in particular domains. Within domains, however, we observed the expected patterns of mutation, with recurrently mutated positions for oncogenes and evenly distributed mutations for tumor suppressors. For example, we identified both known and new endometrial cancer hotspots in the tyrosine kinase domain of the FGFR2 protein, one of which is also a hotspot in breast cancer, and found new two hotspots in the Immunoglobulin I-set domain in colon cancer. Thus, to prioritize cancer mutations for further functional studies aimed at more precise cancer treatments, we have systematically correlated mutations and cancer types at the protein domain level. PMID:25794154

  13. Human fibroblast collagenase: glycosylation and tissue-specific levels of enzyme synthesis.

    PubMed Central

    Wilhelm, S M; Eisen, A Z; Teter, M; Clark, S D; Kronberger, A; Goldberg, G

    1986-01-01

    Human skin fibroblasts secrete collagenase as two proenzyme forms (57 and 52 kDa). The minor (57-kDa) proenzyme form is the result of a partial posttranslational modification of the major (52-kDa) proenzyme through the addition of N-linked complex oligosaccharides. Human endothelial cells as well as fibroblasts from human colon, cornea, gingiva, and lung also secrete collagenase in two forms indistinguishable from those of the skin fibroblast enzyme. In vitro tissue culture studies have shown that the level of constitutive synthesis of this fibroblast-type interstitial collagenase is tissue specific, varies widely, and correlates with the steady-state level of a single collagenase-specific mRNA of 2.5 kilobases. The tumor promoter, phorbol 12-myristate 13-acetate, apparently blocks the control of collagenase synthesis resulting in a similarly high level of collagenase expression (approximately equal to 3-7 micrograms of collagenase per 10(6) cells per 24 hr) in all examined cells. The constitutive level of synthesis of a 28-kDa collagenase inhibitor does not correlate with that of the enzyme. Phorbol 12-myristate 13-acetate stimulates the production of this inhibitor that in turn modulates the activity of collagenase in the conditioned media. As a result, the apparent activity of the enzyme present in the medium does not accurately reflect the rate of its synthesis and secretion. Images PMID:3012533

  14. Advancing Recovery: Implementing Evidence-Based Treatment for Substance Use Disorders at the Systems Level

    PubMed Central

    Schmidt, Laura A.; Rieckmann, Traci; Abraham, Amanda; Molfenter, Todd; Capoccia, Victor; Roman, Paul; Gustafson, David H.; McCarty, Dennis

    2012-01-01

    Objective: A multisite evaluation examined the process and outcomes of Advancing Recovery, a Robert Wood Johnson Foundation initiative to overcome barriers to implementing evidence-based treatments within alcohol and drug treatment systems. Method: We report findings from a 3-year, mixed-method study of how treatment systems promoted two evidence-based practices: medication-assisted treatment and continuing care management. We compared outcomes and implementation strategies across 12 state/county agencies responsible for alcohol and drug treatment and their selected treatment centers. Each partnership received 2 years of financial and technical support to increase adoption of evidence-based treatments. Results: Partnerships flexibly applied the Advancing Recovery model to promote the adoption of evidence-based treatments. Most sites achieved a measurable increase in the numbers of patients served with evidence-based practices, up from a baseline of virtually no use. Rates of adopting medication-based treatments were higher than those for continuing care management. Partnerships used a menu of top-down and bottom-up strategies that varied in specifics across sites but shared a general process of incremental testing and piecemeal adaptation. Conclusions: Supported partnerships between providers and policymakers can achieve wider adoption of evidence-based treatment practices. Systems change unfolds through a trial-and-error process of adaptation and political learning that is unique to each treatment system. This leads to considerable state and local variation in implementation strategies and outcomes. PMID:22456246

  15. Increased Levels of Circulating Advanced Glycation End-Products in Menopausal Women with Osteoporosis

    PubMed Central

    Yang, Deng-Ho; Chiang, Tsay-I; Chang, I-Chang; Lin, Fu-Huang; Wei, Cheng-Chung; Cheng, Ya-Wen

    2014-01-01

    Background: Advanced glycation end-products (AGEs) can accumulate in organs and tissues during ageing and diabetes. Increased levels of AGEs are found in the bone tissue of patients with osteoporosis. The purpose of this study was to evaluate circulating AGEs in patients with osteoporosis. Methods: We evaluated plasma AGEs, osteoporosis-related biomarkers, and bone mass in 82 menopausal women with osteoporosis or osteopenia, 16 young women with osteopenia, and 43 healthy women without osteoporosis or osteopenia. Results: Higher levels of serum AGEs were found in the osteoporosis or osteopenia group compared to healthy women (P < 0.0001). A negative correlation was observed between serum AGEs and lumbar spine bone density (BMD of lumbar spine, r = -0.249, P = 0.028; T-score of lumbar spine, r = -0.261, P = 0.021). Women with a increased level of serum AGEs (> 8.12 U/mL) had a 5.34-fold risk of osteopenia regarding lumbar spine T-score and a 3.31-fold risk of osteopenia regarding the hip T-score. Conclusion: Serum AGEs could be used to monitor the severity and progression of osteoporosis. An increased serum level of AGEs was associated with impaired bone formation and was a risk factor for the development of osteoporosis. Targeting AGEs may represent a novel therapeutic approach for primary or secondary osteoporosis. PMID:24688308

  16. General Anthropometric and Specific Physical Fitness Profile of High-Level Junior Water Polo Players

    PubMed Central

    Kondrič, Miran; Uljević, Ognjen; Gabrilo, Goran; Kontić, Dean; Sekulić, Damir

    2012-01-01

    The aim of this study was to investigate the status and playing position differences in anthropometric measures and specific physical fitness in high-level junior water polo players. The sample of subjects comprised 110 water polo players (17 to 18 years of age), including one of the world’s best national junior teams for 2010. The subjects were divided according to their playing positions into: Centers (N = 16), Wings (N = 28), perimeter players (Drivers; N = 25), Points (N = 19), and Goalkeepers (N = 18). The variables included body height, body weight, body mass index, arm span, triceps- and subscapular-skinfold. Specific physical fitness tests comprised: four swimming tests, namely: 25m, 100m, 400m and a specific anaerobic 4x50m test (average result achieved in four 50m sprints with a 30 sec pause), vertical body jump (JUMP; maximal vertical jump from the water starting from a water polo defensive position) and a dynamometric power achieved in front crawl swimming (DYN). ANOVA with post-hoc comparison revealed significant differences between positions for most of the anthropometrics, noting that the Centers were the heaviest and had the highest BMI and subscapular skinfold. The Points achieved the best results in most of the swimming capacities and JUMP test. No significant group differences were found for the 100m and 4x50m tests. The Goalkeepers achieved the lowest results for DYN. Given the representativeness of the sample of subjects, the results of this study allow specific insights into the physical fitness and anthropometric features of high-level junior water polo players and allow coaches to design a specific training program aimed at achieving the physical fitness results presented for each playing position. PMID:23487152

  17. Barriers and Facilitators to Career Advancement by Top-Level, Entry-Level and Non-Administrative Women in Public School Districts: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Ahmed, Eman Ibrahim El-Desouki

    2011-01-01

    The purpose of this study was to investigate the barriers and facilitators to career advancement among women administrators occupying top-level positions, those occupying entry-level positions and those in non-administrative positions in both rural and urban public school districts in central Pennsylvania. The need to increase the awareness of the…

  18. A Suggested Syllabus for the Advanced Level English Course at Gendarmerie Schools Command in Accordance with NATO STANAG 6001 Level 3 Perspective

    ERIC Educational Resources Information Center

    Solak, Ekrem

    2010-01-01

    The aim of this study is to prepare a suggested syllabus in accordance with NATO Stanag 6001 Level 3 perspective for the Advanced Level English Course at Gendarmerie Schools Command which is subordinate to Gendarmerie General Command. It is believed that this study will contribute to other studies in the context of NATO Stanag 6001 language…

  19. Region-specific changes in presynaptic agmatine and glutamate levels in the aged rat brain.

    PubMed

    Jing, Y; Liu, P; Leitch, B

    2016-01-15

    During the normal aging process, the brain undergoes a range of biochemical and structural alterations, which may contribute to deterioration of sensory and cognitive functions. Age-related deficits are associated with altered efficacy of synaptic neurotransmission. Emerging evidence indicates that levels of agmatine, a putative neurotransmitter in the mammalian brain, are altered in a region-specific manner during the aging process. The gross tissue content of agmatine in the prefrontal cortex (PFC) of aged rat brains is decreased whereas levels in the temporal cortex (TE) are increased. However, it is not known whether these changes in gross tissue levels are also mirrored by changes in agmatine levels at synapses and thus could potentially contribute to altered synaptic function with age. In the present study, agmatine levels in presynaptic terminals in the PFC and TE regions (300 terminals/region) of young (3month; n=3) and aged (24month; n=3) brains of male Sprague-Dawley rats were compared using quantitative post-embedding immunogold electron-microscopy. Presynaptic levels of agmatine were significantly increased in the TE region (60%; p<0.001) of aged rats compared to young rats, however no significant differences were detected in synaptic levels in the PFC region. Double immunogold labeling indicated that agmatine and glutamate were co-localized in the same synaptic terminals, and quantitative analyses revealed significantly reduced glutamate levels in agmatine-immunopositive synaptic terminals in both regions in aged rats compared to young animals. This study, for the first time, demonstrates differential effects of aging on agmatine and glutamate in the presynaptic terminals of PFC and TE. Future research is required to understand the functional significance of these changes and the underlying mechanisms. PMID:26548412

  20. [Advances in the study of site-specific antibody-drug conjugates].

    PubMed

    Sun, Yu; Huang, Rong; Sun, Bai-wang

    2015-10-01

    Antibody drug conjugates (ADCs) are an emerging class of targeted therapeutics with the potential to improve therapeutic index over the traditional chemotherapy. However, it is difficult to control the site and stoichiometry of conjugation in mAb, typically resulting in heterogeneous mixtures of ADCs that are difficult to optimize. New methods for site-specific drug attachment allow development of more homogeneous conjugates and control of the site of drug attachment. In this article, the new literature on development of ADCs and site-specific ADCs is reviewed. In addition, we summarized the various strategies in production of site-specific ADCs. PMID:26837166

  1. Biomonitoring Hexamethylene Diisocyanate (HDI) Exposure Based on Serum Levels of HDI-Specific IgG

    PubMed Central

    Wisnewski, Adam V.; Stowe, Meredith H.; Nerlinger, Abby; Opare-addo, Paul; Decamp, David; Kleinsmith, Christopher R.; Redlich, Carrie A.

    2012-01-01

    Objectives: Isocyanate chemicals essential for polyurethane production are widely used industrially, and are increasingly found in consumer products. Asthma and other adverse health effects of isocyanates are well-documented and exposure surveillance is crucial to disease prevention. Hexamethylene diisocyanate (HDI)-specific serum immunoglobulin G (IgG) was evaluated as an exposure biomarker among workers at a US Air Force Air Logistics Center, which includes a large aircraft maintenance facility. Methods: HDI-specific IgG (HDI-IgG) titers in serum samples (n = 74) were measured using an enzyme-linked immunosorbent assay based upon the biuret form of HDI conjugated to human albumin. Information on personal protective equipment (PPE), work location/tasks, smoking, asthma history, basic demographics, and HDI skin exposure was obtained through questionnaire. Results: HDI-specific serum IgG levels were elevated in n = 17 (23%) of the workers studied. The prevalence and/or end-titer of the HDI-IgG was significantly (P < 0.05) associated with specific job titles, self-reported skin exposure, night-shift work, and respirator use, but not atopy, asthma, or other demographic information. The highest titers were localized to specific worksites (C-130 painting), while other worksites (generator painting) had no or few workers with detectable HDI-IgG. Conclusions: HDI-specific immune responses (IgG) provide a practical biomarker to aid in exposure surveillance and ongoing industrial hygiene efforts. The strategy may supplement current air sampling approaches, which do not assess exposures via skin, or variability in PPE use or effectiveness. The approach may also be applicable to evaluating isocyanate exposures in other settings, and may extend to other chemical allergens. PMID:22449630

  2. A Specific Association between Facial Disgust Recognition and Estradiol Levels in Naturally Cycling Women

    PubMed Central

    Kamboj, Sunjeev K.; Krol, Kathleen M.; Curran, H. Valerie

    2015-01-01

    Subtle changes in social cognition are associated with naturalistic fluctuations in estrogens and progesterone over the course of the menstrual cycle. Using a dynamic emotion recognition task we aimed to provide a comprehensive description of the association between ovarian hormone levels and emotion recognition performance using a variety of performance metrics. Naturally cycling, psychiatrically healthy women attended a single experimental session during a follicular (days 7–13; n = 16), early luteal (days 15–19; n = 14) or late luteal phase (days 22–27; n = 14) of their menstrual cycle. Correct responses and reaction times to dynamic facial expressions were recorded and a two-high threshold analysis was used to assess discrimination and response bias. Salivary progesterone and estradiol were assayed and subjective measures of premenstrual symptoms, anxiety and positive and negative affect assessed. There was no interaction between cycle phase (follicular, early luteal, late luteal) and facial expression (sad, happy, fearful, angry, neutral and disgusted) on any of the recognition performance metrics. However, across the sample as a whole, progesterone levels were positively correlated with reaction times to a variety of facial expressions (anger, happiness, sadness and neutral expressions). In contrast, estradiol levels were specifically correlated with disgust processing on three performance indices (correct responses, response bias and discrimination). Premenstrual symptoms, anxiety and positive and negative affect were not associated with emotion recognition indices or hormone levels. The study highlights the role of naturalistic variations in ovarian hormone levels in modulating emotion recognition. In particular, progesterone seems to have a general slowing effect on facial expression processing. Our findings also provide the first behavioural evidence of a specific role for estrogens in the processing of disgust in humans. PMID:25874795

  3. Association of Census Tract-Level Socioeconomic Status with Disparities in Prostate Cancer-Specific Survival

    PubMed Central

    Freeman, Vincent L.; Ricardo, Ana C.; Campbell, Richard T.; Barrett, Richard E.; Warnecke, Richard B.

    2011-01-01

    Background Social determinants of prostate cancer survival and their relation to racial/ethnic disparities thereof are poorly understood. We analyzed whether census tract-level socioeconomic status (SES) at diagnosis is a prognostic factor in men with prostate cancer and helps explain racial/ethnic disparities in survival. Methods We used a retrospective cohort of 833 African-American and white, non-Hispanic men diagnosed with prostate cancer at four Chicago-area medical centers between 1986 and 1990. Tract-level concentrated disadvantage (CD), a multi-dimensional area-based measure of SES, was calculated for each case using 1990 U.S. census data. Its association with prostate cancer-specific survival was measured using Cox proportional hazard models adjusted for case and tumor characteristics, treatment, and healthcare system (private sector vs. Veterans Administration [VA]). Results Tract-level CD associated with an increased risk of death from prostate cancer (highest vs. lowest quartile, hazard ratio [HR] = 2.37, p < .0001). However, the association was observed in the private sector and not in the VA (per 1 standard deviation [SD] increase, HR = 1.33, p < .0001 and HR = 0.93, p = .46, respectively). The multivariate HR for African Americans before and after accounting for tract-level CD was 1.30 (p = .0036) and 0.96 (p = .82), respectively. Conclusion Census tract-level SES is a social determinant of prostate-specific mortality and helps account for racial/ethnic disparities in survival. An equal-access healthcare system may moderate this association. Impact This study identifies a potential pathway for minimizing disparities in prostate cancer control. The findings need confirmation in a population-based study. PMID:21784953

  4. Near real-time monitoring and mapping of specific conductivity levels across Lake Texoma, USA

    USGS Publications Warehouse

    Atkinson, S.F.; Mabe, J.A.

    2006-01-01

    A submersible sonde equipped with a specific conductivity probe, linked with a global positioning satellite receiver was developed, deployed on a small boat, and used to map spatial and temporal variations in specific conductivity in a large reservoir. 7,695 sample points were recorded during 8 sampling trips. Specific conductivity ranged from 442 uS/cm to 3,378 uS/cm over the nine-month study. The data showed five statistically different zones in the reservoir: 2 different riverine zones, 2 different riverine transition zones, and a lacustrine zone (the main lake zone). These data were imported to a geographic information system where they were spatially interpolated to generate 8 maps showing specific conductivity levels across the entire surface of the lake. The highly dynamic nature of water quality, due to the widely differing nature of the rivers that flow into the reservoir and the effect of large inflows of fresh water during winter storms is easily captured and visualized using this approach. ?? Springer Science+Business Media, Inc. 2006.

  5. Toward Vocabulary Domain Specifications for Health Level 7—coded Data Elements

    PubMed Central

    Bakken, Suzanne; Campbell, Keith E.; Cimino, James J.; Huff, Stanley M.; Hammond, W. Ed

    2000-01-01

    The “vocabulary problem” has long plagued the developers, implementers, and users of computer-based systems. The authors review selected activities of the Health Level 7 (HL7) Vocabulary Technical Committee that are related to vocabulary domain specification for HL7 coded data elements. These activities include: 1) the development of two sets of principles to provide guidance to terminology stakeholders, including organizations seeking to deploy HL7-compliant systems, terminology developers, and terminology integrators; 2) the completion of a survey of terminology developers; 3) the development of a process for HL7 registration of terminologies; and 4) the maintenance of vocabulary domain specification tables. As background, vocabulary domain specification is defined and the relationship between the HL7 Reference Information Model and vocabulary domain specification is described. The activities of the Vocabulary Technical Committee complement the efforts of terminology developers and other stakeholders. These activities are aimed at realizing semantic interoperability in the context of the HL7 Message Development Framework, so that information exchange and use among disparate systems can occur for the delivery and management of direct clinical care as well as for purposes such as clinical research, outcome research, and population health management. PMID:10887162

  6. High plasma levels of vitamin E forms and reduced Alzheimer's disease risk in advanced age.

    PubMed

    Mangialasche, Francesca; Kivipelto, Miia; Mecocci, Patrizia; Rizzuto, Debora; Palmer, Katie; Winblad, Bengt; Fratiglioni, Laura

    2010-01-01

    In this study we investigated the association between plasma levels of eight forms of vitamin E and incidence of Alzheimer's disease (AD) among oldest-old individuals in a population-based setting. A dementia-free sample of 232 subjects aged 80+ years, derived from the Kungsholmen Project, was followed-up to 6 years to detect incident AD. Plasma levels of vitamin E (alpha-, beta-, gamma, and delta-tocopherol; alpha-, beta-, gamma-, and delta-tocotrienol) were measured at baseline. Vitamin E forms-AD association was analyzed with Cox proportional hazard model after adjustment for several potential confounders. Subjects with plasma levels of total tocopherols, total tocotrienols, or total vitamin E in the highest tertile had a reduced risk of developing AD in comparison to persons in the lowest tertile. Multi-adjusted hazard ratios (HRs) and 95% confidence interval (CI) were 0.55 (0.32-0.94) for total tocopherols, 0.46 (0.23-0.92) for total tocotrienols, and 0.55 (0.32-0.94) for total vitamin E. When considering each vitamin E form, the risk of developing AD was reduced only in association with high plasma levels of beta-tocopherol (HR: 0.62, 95% CI 0.39-0.99), whereas alpha-tocopherol, alpha- tocotrienol, and beta-tocotrienol showed only a marginally significant effect in the multiadjusted model [HR (95% CI): alpha-tocopherol: 0.72 (0.48-1.09); alpha-tocotrienol: 0.70 (0.44-1.11); beta-tocotrienol: 0.69 (0.45-1.06)]. In conclusion, high plasma levels of vitamin E are associated with a reduced risk of AD in advanced age. The neuroprotective effect of vitamin E seems to be related to the combination of different forms, rather than to alpha-tocopherol alone, whose efficacy in interventions against AD is currently debated. PMID:20413888

  7. Circulating growth arrest-specific protein 6 levels are associated with erythropoietin resistance in hemodialysis patients.

    PubMed

    Chen, Miao-Pei; Chen, Chien-Wen; Chen, Jin-Shuen; Mao, Hung-Chung; Chou, Chu-Lin

    2016-01-01

    Growth arrest-specific protein 6 (Gas6) works synergistically with erythropoietin (EPO) to increase the proliferation and maturation of erythroblasts. However, the role of Gas 6 levels on EPO resistance in hemodialysis (HD) patients remains unclear. Therefore, the objective of this study was the first to examine the correlation between plasma Gas6 levels and EPO resistance in HD patients. We enrolled 134 HD patients and 85 healthy individuals. The HD patients were divided into 2 groups: 98 non-EPO-resistant patients and 36 EPO-resistant patients. Plasma levels of Gas6, interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and albumin were quantified. Compared with non-EPO-resistant patients, EPO-resistant patients had elevated plasma concentrations of Gas6 (15.4 ± 3.3 vs. 13.7 ± 3.2 ng/mL, P = 0.006), IL-6 (3.1 ± 3.1 vs. 2.1 ± 1.5 pg/mL, P = 0.009), and hs-CRP (12.7 ± 25.2 vs. 4.5 ± 5.5 mg/L, P = 0.002). In EPO-resistant HD patients, plasma Gas6 levels were negatively correlated with albumin levels (r = -0.388, P < 0.021). Elevated Gas6 levels are associated with EPO resistance in HD patients. Also, EPO resistance is related to inflammation and malnutrition. Thus, circulating Gas6 levels could be used as the potential marker in HD patients with EPO resistance. PMID:26788441

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

    NASA Technical Reports Server (NTRS)

    2008-01-01

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

  9. Design and Specification of Optical Bandpass Filters for Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS)

    NASA Technical Reports Server (NTRS)

    Leviton, Douglas B.; Tsevetanov, Zlatan; Woodruff, Bob; Mooney, Thomas A.

    1998-01-01

    Advanced optical bandpass filters for the Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS) have been developed on a filter-by-filter basis through detailed studies which take into account the instrument's science goals, available optical filter fabrication technology, and developments in ACS's charge-coupled-device (CCD) detector technology. These filters include a subset of filters for the Sloan Digital Sky Survey (SDSS) which are optimized for astronomical photometry using today's charge-coupled-devices (CCD's). In order for ACS to be truly advanced, these filters must push the state-of-the-art in performance in a number of key areas at the same time. Important requirements for these filters include outstanding transmitted wavefront, high transmittance, uniform transmittance across each filter, spectrally structure-free bandpasses, exceptionally high out of band rejection, a high degree of parfocality, and immunity to environmental degradation. These constitute a very stringent set of requirements indeed, especially for filters which are up to 90 mm in diameter. The highly successful paradigm in which final specifications for flight filters were derived through interaction amongst the ACS Science Team, the instrument designer, the lead optical engineer, and the filter designer and vendor is described. Examples of iterative design trade studies carried out in the context of science needs and budgetary and schedule constraints are presented. An overview of the final design specifications for the ACS bandpass and ramp filters is also presented.

  10. Soil Moisture Active Passive (SMAP) Mission Level 4 Carbon (L4_C) Product Specification Document

    NASA Technical Reports Server (NTRS)

    Glassy, Joe; Kimball, John S.; Jones, Lucas; Reichle, Rolf H.; Ardizzone, Joseph V.; Kim, Gi-Kong; Lucchesi, Robert A.; Smith, Edmond B.; Weiss, Barry H.

    2015-01-01

    This is the Product Specification Document (PSD) for Level 4 Surface and Root Zone Soil Moisture (L4_SM) data for the Science Data System (SDS) of the Soil Moisture Active Passive (SMAP) project. The L4_SM data product provides estimates of land surface conditions based on the assimilation of SMAP observations into a customized version of the NASA Goddard Earth Observing System, Version 5 (GEOS-5) land data assimilation system (LDAS). This document applies to any standard L4_SM data product generated by the SMAP Project.

  11. On geoeffective solar variability signature in Northern temperate climate zone at specific atmospheric levels

    NASA Astrophysics Data System (ADS)

    Dobrica, Venera; Pirloaga, Razvan; Stefan, Cristiana; Demetrescu, Crisan

    2015-04-01

    Solar signals at Schwabe (11 years) and Hale (22 years) solar cycles timescales in the reanalyzed temperature data from NCEP/NCAR database for Northern temperate climate zone at specific levels in troposphere and stratosphere will be discussed by means of long-term statistical correlations between stratospheric and tropospheric temperature and solar variability proxies (indices). It seems that the 11-year signal is more pronounced in the troposphere, while the 22-year signal becomes important in the stratosphere. In this study features of these signals will be also discussed on several continental scales of the Northern temperate zone. The seasonal dependence of the long-term correlations is discussed as well.

  12. Communication: Application of state-specific multireference coupled cluster methods to core-level excitations

    SciTech Connect

    Brabec, Jiri; Bhaskaran-Nair, Kiran; Govind, Niranjan; Pittner, Jiri; Kowalski, Karol

    2012-11-07

    The concept of the model space underlying multireference coupled-cluster (MRCC) formulations is a powerful tool to deal with complex correlation effects for various electronic states. Here, we demonstrate that iterative state-specific MRCC methods (SS-MRCC) based on properly defined model spaces can be used to describe core-level excited states even when canonical Hartree-Fock orbitals are utilized. We show that the SS-MRCC models with single and double excitations (SSMRCCSD) are comparable in accuracy to high-level single reference equation-of-motion coupled cluster (EOMCC) formalism. We also demonstrate that the SS-MRCC methods are capable of providing high accuracy results without experiencing numerical problems of the EOMCC methods.

  13. Molecular Basis of Signaling Specificity of Insulin and IGF Receptors: Neglected Corners and Recent Advances

    PubMed Central

    Siddle, Kenneth

    2011-01-01

    Insulin and insulin-like growth factor (IGF) receptors utilize common phosphoinositide 3-kinase/Akt and Ras/extracellular signal-regulated kinase signaling pathways to mediate a broad spectrum of “metabolic” and “mitogenic” responses. Specificity of insulin and IGF action in vivo must in part reflect expression of receptors and responsive pathways in different tissues but it is widely assumed that it is also determined by the ligand binding and signaling mechanisms of the receptors. This review focuses on receptor-proximal events in insulin/IGF signaling and examines their contribution to specificity of downstream responses. Insulin and IGF receptors may differ subtly in the efficiency with which they recruit their major substrates (IRS-1 and IRS-2 and Shc) and this could influence effectiveness of signaling to “metabolic” and “mitogenic” responses. Other substrates (Grb2-associated binder, downstream of kinases, SH2Bs, Crk), scaffolds (RACK1, β-arrestins, cytohesins), and pathways (non-receptor tyrosine kinases, phosphoinositide kinases, reactive oxygen species) have been less widely studied. Some of these components appear to be specifically involved in “metabolic” or “mitogenic” signaling but it has not been shown that this reflects receptor-preferential interaction. Very few receptor-specific interactions have been characterized, and their roles in signaling are unclear. Signaling specificity might also be imparted by differences in intracellular trafficking or feedback regulation of receptors, but few studies have directly addressed this possibility. Although published data are not wholly conclusive, no evidence has yet emerged for signaling mechanisms that are specifically engaged by insulin receptors but not IGF receptors or vice versa, and there is only limited evidence for differential activation of signaling mechanisms that are common to both receptors. Cellular context, rather than intrinsic receptor activity, therefore appears

  14. ASSOCIATION OF OBESITY AND DIABETES WITH SERUM PROSTATE-SPECIFIC ANTIGEN LEVELS IN JAPANESE MALES

    PubMed Central

    NAITO, MARIKO; ASAI, YATAMI; MORI, ATSUYOSHI; FUKADA, YUKO; KUWABARA, MAYUMI; KATASE, SHIRO; HISHIDA, ASAHI; MORITA, EMI; KAWAI, SAYO; OKADA, RIEKO; NISHIO, KAZUKO; TAMAKOSHI, AKIKO; WAKAI, KENJI; HAMAJIMA, NOBUYUKI

    2012-01-01

    ABSTRACT Patients with diabetes have been reported to be at an increased risk for cancers of the pancreas, liver, and colon; however, recent studies have suggested that men with diabetes are at a decreased risk for prostate cancer. Previous studies have found that obese men have lower serum prostate-specific antigen (PSA) concentrations than do non-obese men. Further understanding of how obesity and diabetes affect the PSA concentration may improve our ability to detect clinically relevant prostate tumors. This study examined the relationships among serum PSA level, obesity, and diabetes in apparently healthy Japanese males. We analyzed the baseline data from 2,172 Japanese males (age, 56.8 ± 6.1 years [mean ± SD]) who participated in the Japan Multi-Institutional Collaborative Cohort Study. Diabetes was defined as the presence of both a hemoglobin A1c (JDS) of ≥6.1% and a fasting plasma glucose level of ≥126 mg/dL, or a positive medical history. After adjusting for age, the PSA levels were elevated among males with a higher normal BMI (ranging from 23.0 to 24.9) and lowered among men with a BMI of ≥25.0. In the stratified analysis, these significant differences in BMI categories were absent among diabetics. The mean PSA levels were significantly lower in diabetics than in non-diabetics among subjects aged 60 and over. Our findings suggest that the pre-overweight men had increased PSA levels, and the diabetes was associated with a reduction of PSA levels in elderly. PMID:23092101

  15. Homing in on the hepatic scar: recent advances in cell-specific targeting of liver fibrosis

    PubMed Central

    Dobie, Ross; Henderson, Neil C.

    2016-01-01

    Despite the high prevalence of liver disease globally, there are currently no approved anti-fibrotic therapies to treat patients with liver fibrosis. A major goal in anti-fibrotic therapy is the development of drug delivery systems that allow direct targeting of the major pro-scarring cell populations within the liver (hepatic myofibroblasts) whilst not perturbing the homeostatic functions of other mesenchymal cell types present within both the liver and other organ systems. In this review we will outline some of the recent advances in our understanding of myofibroblast biology, discussing both the origin of myofibroblasts and possible myofibroblast fates during hepatic fibrosis progression and resolution. We will then discuss the various strategies currently being employed to increase the precision with which we deliver potential anti-fibrotic therapies to patients with liver fibrosis. PMID:27508067

  16. Advanced systems demonstration for utilization of biomass as an energy source. Volume 3: Equipment specifications

    NASA Astrophysics Data System (ADS)

    1980-10-01

    Specifications are given for the shipping, marking, inspection, testing, and start up of equipment to be used in a proposed wood fuel cogeneration system in Maine. Couplings, mechanical drives, electric motors, spare parts, coatings, assembling, and materials handling and packaging are covered. Both OSHA and noise control regulations are included along with the ASME code.

  17. Work/Life Satisfaction Policy in ADVANCE Universities: Assessing Levels of Flexibility

    ERIC Educational Resources Information Center

    Tower, Leslie E.; Dilks, Lisa M.

    2015-01-01

    Work/life satisfaction policies are seen as key to recruiting, retaining, and advancing high quality faculty. This article explores the work/life policies prevalent at NSF ADVANCE institutions (PAID, Catalyst, and IT). We systematically review ADVANCE university websites (N = 124) and rank 9 categories of work/life policy including dual career…

  18. Postmortem serum protein growth arrest-specific 6 levels in sepsis-related deaths.

    PubMed

    Palmiere, Cristian; Augsburger, Marc

    2015-09-01

    Growth arrest-specific 6 (Gas6) is widely expressed in leukocytes, platelets, endothelial cells, and monocytes. It regulates various processes including granulocyte adhesion to the endothelium, cell migration, thrombus stabilization, and cytokine release. In humans, increased plasma Gas6 levels have been described in patients with sepsis and septic shock. In this study, Gas6 concentrations were measured in postmortem serum from femoral blood in a series of sepsis-related fatalities and control cases. The aims were twofold: first, to determine whether Gas6 can be reliably determined in postmortem serum; and second, to assess its diagnostic potential in identifying sepsis-related deaths. Two study groups were prospectively formed, a sepsis-related fatalities group (24 cases) and a control group (24 cases) including cases of deep vein thrombosis and fatal pulmonary embolism, cases of systemic inflammatory response syndrome in severe trauma, cases of end-stage renal failure, and cases of hanging (non-septic, non-SIRS, non-end stage renal failure cases). The preliminary results of this study seem to indicate that Gas6 can be effectively measured in postmortem serum. However, Gas6 levels in sepsis-related fatalities do not appear to be clearly distinguishable from concentrations in pulmonary embolism, severe trauma, and end-stage renal failure cases. These findings tend to support previous reports that indicated that Gas6 behaves as an acute phase reactant and can be considered a general marker of inflammation rather than a specific biomarker of sepsis. PMID:26233610

  19. Preliminary level 2 specification for the nested, fixed-depth sampling system

    SciTech Connect

    BOGER, R.M.

    1999-05-26

    This revision 1 Level 2 Specification establishes the performance, design, development, and test requirements for a sampling system and for an at-tank analysis system that will support the BNFL, Inc. privatization contract in the final disposal of Hanford's high level waste (HLW) and low activity waste (LAW). The sampling system will quickly provide large volume, representative waste samples for validating the chemical, radiological, and physical properties of the tank waste without the exposure and time concerns of the baseline grab sampling method. The on-line sensors of the at-tank analysis system will provide data from which the mixing or settling status of the waste can be assessed. This revision 1 document includes functions, requirement, and specifications for the at-tank analysis system, the results of the preliminary outline design, and the FY 1998 validation testing. The sample container filling system will comply with RCRA criteria for samples with volatile organic constituents, include empty container and swipe input ports, use Hanford's Steel Pig radioactive sample package, comply with Hanford's flammable gas criteria, and have the means to recover from broken sample containers.

  20. System-Level Testing of the Advanced Stirling Radioisotope Generator Engineering Hardware

    NASA Technical Reports Server (NTRS)

    Chan, Jack; Wiser, Jack; Brown, Greg; Florin, Dominic; Oriti, Salvatore M.

    2014-01-01

    To support future NASA deep space missions, a radioisotope power system utilizing Stirling power conversion technology was under development. This development effort was performed under the joint sponsorship of the Department of Energy and NASA, until its termination at the end of 2013 due to budget constraints. The higher conversion efficiency of the Stirling cycle compared with that of the Radioisotope Thermoelectric Generators (RTGs) used in previous missions (Viking, Pioneer, Voyager, Galileo, Ulysses, Cassini, Pluto New Horizons and Mars Science Laboratory) offers the advantage of a four-fold reduction in Pu-238 fuel, thereby extending its limited domestic supply. As part of closeout activities, system-level testing of flight-like Advanced Stirling Convertors (ASCs) with a flight-like ASC Controller Unit (ACU) was performed in February 2014. This hardware is the most representative of the flight design tested to date. The test fully demonstrates the following ACU and system functionality: system startup; ASC control and operation at nominal and worst-case operating conditions; power rectification; DC output power management throughout nominal and out-of-range host voltage levels; ACU fault management, and system command / telemetry via MIL-STD 1553 bus. This testing shows the viability of such a system for future deep space missions and bolsters confidence in the maturity of the flight design.

  1. The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 1 Core.

    PubMed

    Hucka, Michael; Bergmann, Frank T; Hoops, Stefan; Keating, Sarah M; Sahle, Sven; Schaff, James C; Smith, Lucian P; Wilkinson, Darren J

    2015-01-01

    Computational models can help researchers to interpret data, understand biological function, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that can be exchanged between different software systems. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 1 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML as well as their encoding in XML, the eXtensible Markup Language. This specification also defines validation rules that determine the validity of an SBML document, and provides many examples of models in SBML form. Other materials and software are available from the SBML project web site, http://sbml.org/. PMID:26528564

  2. Conversion of transuranic waste to low level waste by decontamination: a site specific update

    SciTech Connect

    Allen, R.P.; Hazelton, R.F.

    1985-09-01

    As a followup to an FY-1984 cost/benefit study, a program was conducted in FY-1985 to transfer to the relevant DOE sites the information and technology for the direct conversion of transuranic (TRU) waste to low-level waste (LLW) by decontamination. As part of this work, the economic evaluation of the various TRUW volume reduction and conversion options was updated and expanded to include site-specific factors. The results show, for the assumptions used, that size reduction, size reduction followed by decontamination, or in situ decontamination are cost effective compared with the no-processing option. The technology transfer activities included site presentations and discussions with operations and waste management personnel to identify application opportunities and site-specific considerations and constraints that could affect the implementation of TRU waste conversion principles. These discussions disclosed definite potential for the beneficial application of these principles at most of the sites, but also confirmed the existence of site-specific factors ranging from space limitations to LLW disposal restrictions that could preclude particular applications or diminish expected benefits. 8 refs., 2 figs., 4 tabs.

  3. A two-level structure for advanced space power system automation

    NASA Technical Reports Server (NTRS)

    Loparo, Kenneth A.; Chankong, Vira

    1990-01-01

    The tasks to be carried out during the three-year project period are: (1) performing extensive simulation using existing mathematical models to build a specific knowledge base of the operating characteristics of space power systems; (2) carrying out the necessary basic research on hierarchical control structures, real-time quantitative algorithms, and decision-theoretic procedures; (3) developing a two-level automation scheme for fault detection and diagnosis, maintenance and restoration scheduling, and load management; and (4) testing and demonstration. The outlines of the proposed system structure that served as a master plan for this project, work accomplished, concluding remarks, and ideas for future work are also addressed.

  4. Region-Specific Dissociation between Cortical Noradrenaline Levels and the Sleep/Wake Cycle

    PubMed Central

    Bellesi, Michele; Tononi, Giulio; Cirelli, Chiara; Serra, Pier Andrea

    2016-01-01

    Study Objectives: The activity of the noradrenergic system of the locus coeruleus (LC) is high in wake and low in sleep. LC promotes arousal and EEG activation, as well as attention, working memory, and cognitive flexibility. These functions rely on prefrontal cortex and are impaired by sleep deprivation, but the extent to which LC activity changes during wake remains unclear. Moreover, it is unknown whether noradrenergic neurons can sustain elevated firing during extended wake. Recent studies show that relative to LC neurons targeting primary motor cortex (M1), those projecting to medial prefrontal cortex (mPFC) have higher spontaneous firing rates and are more excitable. These results suggest that noradrenaline (NA) levels should be higher in mPFC than M1, and that during prolonged wake LC cells targeting mPFC may fatigue more, but direct evidence is lacking. Methods: We performed in vivo microdialysis experiments in adult (9–10 weeks old) C57BL/6 mice implanted for chronic electroencephalographic recordings. Cortical NA levels were measured during spontaneous sleep and wake (n = 8 mice), and in the course of sleep deprivation (n = 6). Results: We found that absolute NA levels are higher in mPFC than in M1. Moreover, in both areas they decline during sleep and increase during wake, but these changes are faster in M1 than mPFC. Finally, by the end of sleep deprivation NA levels decline only in mPFC. Conclusions: Locus coeruleus (LC) neurons targeting prefrontal cortex may fatigue more markedly, or earlier, than other LC cells, suggesting one of the mechanisms underlying the cognitive impairment and the increased sleep presure associated with sleep deprivation. Commentary: A commentary on this article appears in this issue on page 11. Citation: Bellesi M, Tononi G, Cirelli C, Serra PA. Region-specific dissociation between cortical noradrenaline levels and the sleep/wake cycle. SLEEP 2016;39(1):143–154. PMID:26237776

  5. Isoform-specific inhibitors of ACATs: recent advances and promising developments.

    PubMed

    Ohshiro, Taichi; Tomoda, Hiroshi

    2011-12-01

    Acyl-CoA:cholesterol acyltransferase (ACAT) is a promising therapeutic target for cardiovascular diseases. Although a number of synthetic ACAT inhibitors have been developed, they have failed to show efficacy in clinical trials. Now, the presence of two ACAT isoforms with distinct functions, ACAT1 and ACAT2, has been discovered. Thus, the selectivity of ACAT inhibitors toward the two isoforms is important for their development as novel anti-atherosclerotic agents. The selectivity study indicated that fungal pyripyropene A (PPPA) is only an ACAT2-specific inhibitor. Furthermore, PPPA proved orally active in atherogenic mouse models, indicating it possessed cholesterol-lowering and atheroprotective activities. Certain PPPA derivatives, semi-synthetically prepared, possessed more potent and selective in vitro activity than PPPA against ACAT2. This review covers these studies and describes the future prospects of ACAT2-specific inhibitors. PMID:22098352

  6. Advanced Gestational Age Increases Serum Carbohydrate-Deficient Transferrin Levels in Abstinent Pregnant Women

    PubMed Central

    Bakhireva, Ludmila N.; Cano, Sandra; Rayburn, William F.; Savich, Renate D.; Leeman, Lawrence; Anton, Raymond F.; Savage, Daniel D.

    2012-01-01

    Aims: Carbohydrate-deficient transferrin (%CDT) is a well-established and highly specific biomarker for sustained heavy consumption of alcohol. However, in pregnant women, the specificity of this biomarker might be affected by advanced gestational age, even after accounting for increased transferrin concentrations in pregnancy. The goal of this prospective study was to assess the variability in %CDT during pregnancy among alcohol-abstaining patients. Methods: Patients were recruited during one of the first prenatal care visits and followed-up to term. Abstinence was confirmed by maternal self-report and by alcohol biomarkers. Biomarkers assessed in the mother included serum gamma-glutamyltranspeptidase, urine ethyl glucuronide and ethyl sulfate, and whole blood phosphatidylethanol (PEth). In addition, PEth was measured in a dry blood spot card obtained from a newborn. For %CDT analysis, serum samples were collected at baseline and at term and analyzed by an internationally validated high-performance liquid chromatography and spectrophotometric detection method. Results: At recruitment (mean gestational age 22.6 ± 7.3 weeks), the mean %CDT concentration was 1.49 ± 0.30%, while at term, it increased to 1.67 ± 0.28% (P = 0.001). Using a conventional cutoff concentration %CDT >1.7%, 22.9 and 45.7% of the sample would be classified as ‘positive’ for this biomarker at recruitment and at term, respectively (P = 0.011 ). Conclusion: These results suggest that a conventional cutoff of 1.7% might be too low for pregnant women and would generate false-positive results. We propose that %CDT >2.0% be used as a cutoff concentration indicative of alcohol exposure in pregnant women. The sensitivity of %CDT at this cutoff for heavy drinking during pregnancy needs to be assessed further. PMID:22878591

  7. Development of specific enzyme-linked immunosorbent assay for determining LH and FSH levels in tilapia, using recombinant gonadotropins.

    PubMed

    Aizen, Joseph; Kasuto, Harel; Levavi-Sivan, Berta

    2007-01-01

    We recently produced Oreochromis niloticus recombinant LH and FSH as single-chain polypeptides in the methylotrophic yeast Pichia pastoris. Glycoprotein subunit alpha was joined with tilapia (t) LHbeta or tFSHbeta mature protein-coding sequences to form a fusion gene that encodes a ;;tethered" polypeptide, in which the gonadotropin beta-subunit forms the N-terminal part and the alpha-subunit forms the C-terminal part. Recombinant (r) gonadotropins were used to develop specific and homologous competitive ELISAs for measurements of FSH and LH in the plasma and pituitary of tilapia, using primary antibodies against rtLHbeta or rtFSHbeta, respectively, and rtLHbetaalpha or rtFSHbetaalpha for the standard curves. The wells were coated with either rtLHbeta (2ng/ml) or rtFSHbeta (0.5ng/well), and the final concentrations of the antisera were 1:5000 (for tLH) or 1:50,000 (for tFSH). The sensitivity of the assay was 15.84pg/ml for tLH and 0.24pg/ml for tFSH measurements in the plasma, whereas for the measurements in the pituitary, the sensitivity was 2.43ng/ml and 1.52ng/ml for tLH and tFSH, respectively. The standard curves for tFSH and tLH paralleled those of serially diluted pituitary extracts of other cichlids, as well as of serially diluted pituitary extract of seabream, European seabass and hybrid bass. We examined plasma tFSH and tLH levels in the course of one reproductive cycle, between two successive spawnings, in three individual tilapia females. Plasma levels of both FSH and LH increased during the second day after the eggs had been removed, probably related to the vitellogenic phase. LH levels increased toward spawning, which occurred on the 11th day. FSH levels also increased on day of cycle, probably due to recruitment of a new generation of follicles for the successive spawning. The development of specific ELISAs using recombinant gonadotropins is expected to advance the study of the distinct functions of each of these important hormones. PMID:17507016

  8. Discovery of Nigri/nox and Panto/pox site-specific recombinase systems facilitates advanced genome engineering.

    PubMed

    Karimova, Madina; Splith, Victoria; Karpinski, Janet; Pisabarro, M Teresa; Buchholz, Frank

    2016-01-01

    Precise genome engineering is instrumental for biomedical research and holds great promise for future therapeutic applications. Site-specific recombinases (SSRs) are valuable tools for genome engineering due to their exceptional ability to mediate precise excision, integration and inversion of genomic DNA in living systems. The ever-increasing complexity of genome manipulations and the desire to understand the DNA-binding specificity of these enzymes are driving efforts to identify novel SSR systems with unique properties. Here, we describe two novel tyrosine site-specific recombination systems designated Nigri/nox and Panto/pox. Nigri originates from Vibrio nigripulchritudo (plasmid VIBNI_pA) and recombines its target site nox with high efficiency and high target-site selectivity, without recombining target sites of the well established SSRs Cre, Dre, Vika and VCre. Panto, derived from Pantoea sp. aB, is less specific and in addition to its native target site, pox also recombines the target site for Dre recombinase, called rox. This relaxed specificity allowed the identification of residues that are involved in target site selectivity, thereby advancing our understanding of how SSRs recognize their respective DNA targets. PMID:27444945

  9. Discovery of Nigri/nox and Panto/pox site-specific recombinase systems facilitates advanced genome engineering

    PubMed Central

    Karimova, Madina; Splith, Victoria; Karpinski, Janet; Pisabarro, M. Teresa; Buchholz, Frank

    2016-01-01

    Precise genome engineering is instrumental for biomedical research and holds great promise for future therapeutic applications. Site-specific recombinases (SSRs) are valuable tools for genome engineering due to their exceptional ability to mediate precise excision, integration and inversion of genomic DNA in living systems. The ever-increasing complexity of genome manipulations and the desire to understand the DNA-binding specificity of these enzymes are driving efforts to identify novel SSR systems with unique properties. Here, we describe two novel tyrosine site-specific recombination systems designated Nigri/nox and Panto/pox. Nigri originates from Vibrio nigripulchritudo (plasmid VIBNI_pA) and recombines its target site nox with high efficiency and high target-site selectivity, without recombining target sites of the well established SSRs Cre, Dre, Vika and VCre. Panto, derived from Pantoea sp. aB, is less specific and in addition to its native target site, pox also recombines the target site for Dre recombinase, called rox. This relaxed specificity allowed the identification of residues that are involved in target site selectivity, thereby advancing our understanding of how SSRs recognize their respective DNA targets. PMID:27444945

  10. Providing a navigable route for acute medicine nurses to advance their practice: a framework of ascending levels of practice.

    PubMed

    Lees-Deutsch, Liz; Christian, Jan; Setchfield, Ian

    2016-01-01

    This article conveys concerns raised by delegates at the International SAM Conference (Manchester, 2015) regarding how to advance nursing practice in acute medicine. It endeavors to capture the essence of 'how to advance practice' and 'how to integrate advanced practice' within the workforce structures of an acute medicine unit (AMU). It addresses the production of tacit knowledge and the recognition and integration of this to developing the nursing workforce. The current context of NHS efficiencies and recruitment issues emphasize the value of retaining tacit knowledge. Uniquely, this article offers an early conceptual framework through which levels of advancement and potential transition points to advance nursing practice in acute medicine are articulated. Determining how to advance requires identification of prior accomplishments such as, tacit knowledge, experiential learning, CPD, specialist courses and management experience. This requires nurses to make judicious decisions to advance their practice and the distinction between 'amassing experience' and 'career progression'. It aims to stimulate thinking around the practicalities of advancement, the value of tacit knowledge and potential realization through the framework trajectory. PMID:27441313

  11. An Advanced User Interface Approach for Complex Parameter Study Process Specification in the Information Power Grid

    NASA Technical Reports Server (NTRS)

    Yarrow, Maurice; McCann, Karen M.; Biswas, Rupak; VanderWijngaart, Rob; Yan, Jerry C. (Technical Monitor)

    2000-01-01

    The creation of parameter study suites has recently become a more challenging problem as the parameter studies have now become multi-tiered and the computational environment has become a supercomputer grid. The parameter spaces are vast, the individual problem sizes are getting larger, and researchers are now seeking to combine several successive stages of parameterization and computation. Simultaneously, grid-based computing offers great resource opportunity but at the expense of great difficulty of use. We present an approach to this problem which stresses intuitive visual design tools for parameter study creation and complex process specification, and also offers programming-free access to grid-based supercomputer resources and process automation.

  12. Recent advances in the fabrication and structure-specific applications of graphene-based inorganic hybrid membranes

    NASA Astrophysics Data System (ADS)

    Zhao, Xinne; Zhang, Panpan; Chen, Yuting; Su, Zhiqiang; Wei, Gang

    2015-03-01

    The preparation and applications of graphene (G)-based materials are attracting increasing interests due to their unique electronic, optical, magnetic, thermal, and mechanical properties. Compared to G-based hybrid and composite materials, G-based inorganic hybrid membrane (GIHM) offers enormous advantages ascribed to their facile synthesis, planar two-dimensional multilayer structure, high specific surface area, and mechanical stability, as well as their unique optical and mechanical properties. In this review, we report the recent advances in the technical fabrication and structure-specific applications of GIHMs with desirable thickness and compositions. In addition, the advantages and disadvantages of the methods utilized for creating GIHMs are discussed in detail. Finally, the potential applications and key challenges of GIHMs for future technical applications are mentioned.

  13. Biological Effects Induced by Specific Advanced Glycation End Products in the Reconstructed Skin Model of Aging.

    PubMed

    Pageon, Hervé; Zucchi, Hélène; Dai, Zhenyu; Sell, David R; Strauch, Christopher M; Monnier, Vincent M; Asselineau, Daniel

    2015-01-01

    Advanced glycation end products (AGEs) accumulate in the aging skin. To understand the biological effects of individual AGEs, skin reconstructed with collagen selectively enriched with N(ɛ)-(carboxymethyl)-lysine (CML), N(ɛ)-(carboxyethyl)-lysine (CEL), methylglyoxal hydroimidazolone (MG-H1), or pentosidine was studied. Immunohistochemistry revealed increased expression of α6 integrin at the dermal epidermal junction by CEL and CML (p<0.01). Laminin 5 was diminished by CEL and MG-H1 (p<0.05). Both CML and CEL induced a robust increase (p<0.01) in procollagen I. In the culture medium, IL-6, VEGF, and MMP1 secretion were significantly decreased (p<0.05) by MG-H1. While both CEL and CML decreased MMP3, only CEL decreased IL-6 and TIMP1, while CML stimulated TIMP1 synthesis significantly (p<0.05). mRNA expression studies using qPCR in the epidermis layer showed that CEL increased type 7 collagen (COL7A1), β1, and α6 integrin, while CML increased only COL7A1 (p<0.05). MG-H1-modified collagen had no effect. Importantly, in the dermis layer, MMP3 mRNA expression was increased by both CML and MG-H1. CML also significantly increased the mRNAs of MMP1, TIMP1, keratinocyte growth factor (KGF), IL-6, and monocyte chemoattractant protein 1 (MCP1) (p<0.05). Mixed effects were present in CEL-rich matrix. Minimally glycoxidized pentosidine-rich collagen suppressed most mRNAs of the genes studied (p<0.05) and decreased VEGF and increased MCP1 protein expression. Taken together, this model of the aging skin suggests that a combination of AGEs tends to counterbalance and thus minimizes the detrimental biological effects of individual AGEs. PMID:26309782

  14. Functional specificity for high-level linguistic processing in the human brain

    PubMed Central

    Fedorenko, Evelina; Behr, Michael K.; Kanwisher, Nancy

    2011-01-01

    Neuroscientists have debated for centuries whether some regions of the human brain are selectively engaged in specific high-level mental functions or whether, instead, cognition is implemented in multifunctional brain regions. For the critical case of language, conflicting answers arise from the neuropsychological literature, which features striking dissociations between deficits in linguistic and nonlinguistic abilities, vs. the neuroimaging literature, which has argued for overlap between activations for linguistic and nonlinguistic processes, including arithmetic, domain general abilities like cognitive control, and music. Here, we use functional MRI to define classic language regions functionally in each subject individually and then examine the response of these regions to the nonlinguistic functions most commonly argued to engage these regions: arithmetic, working memory, cognitive control, and music. We find little or no response in language regions to these nonlinguistic functions. These data support a clear distinction between language and other cognitive processes, resolving the prior conflict between the neuropsychological and neuroimaging literatures. PMID:21885736

  15. Waste acceptance product specifications for vitrified high-level waste forms. Revision 1

    SciTech Connect

    Applewhite-Ramsey, A.; Sproull, J.F.

    1993-06-01

    The Nuclear Waste Policy Act of 1982 mandated that all high-level waste (HLW) be sent to a federal geologic repository for permanent disposal. DOE published the Environmental Assessment in 1982 which identified borosilicate glass as the chosen HLW form.{sup 1} In 1985 the Department of Energy instituted a Waste Acceptance Process to assure that DWPF glass waste forms would be acceptable to such a repository. This assurance was important since production of waste forms will precede repository construction and licensing. As part of this Waste Acceptance Process, the DOE Office of Civilian Radioactive Waste Management (RW) formed the Waste Acceptance Committee (WAC). The WAC included representatives from the candidate repository sites, the waste producing sites and DOE. The WAC was responsible for developing the Waste Acceptance Preliminary Specifications (WAPS) which defined the requirements the waste forms must meet to be compatible with the candidate repository geologies.

  16. Specific conductance, water temperature, and water level data, San Francisco Bay, California, water year 1998

    USGS Publications Warehouse

    Buchanan, Paul A.

    1999-01-01

    Specific conductance and water temperature data are continuously recorded at four sites in San Francisco Bay, California: San Pablo Strait at Point San Pablo, Central San Francisco Bay at Presidio Military Reservation, Pier 24 at Bay Bridge, and South San Francisco Bay at San Mateo Bridge near Foster City (Figure 1). Water level data are recorded only at San Pablo Strait at Point San Pablo. These data were recorded by the Department of Water Resources (DWR) before 1988, by the US Geological Survey (USGS) National Research Program from 1988 to 1989, and by the USGS-DWR cooperative program since 1990. This article presents time-series plots of data from the four sites in San Francisco Bay during water year 1998 (1 October 1997 through 30 September 1998).

  17. Specific regions within the embryonic midbrain and cerebellum require different levels of FGF signaling during development

    PubMed Central

    Basson, M. Albert; Echevarria, Diego; Ahn, Christina Petersen; Sudarov, Anamaria; Joyner, Alexandra L.; Mason, Ivor J.; Martinez, Salvador; Martin, Gail R.

    2008-01-01

    SUMMARY Development of the prospective midbrain and cerebellum are coordinated by FGF ligands produced by the isthmic organizer. Previous studies have suggested that the midbrain and cerebellum require different levels of FGF signaling for their development. However, little is known about the extent to which specific regions within these two parts of the brain differ in their requirement for FGF signaling during embryogenesis. In this study, we have explored the effects of inhibiting FGF signaling within the embryonic midbrain (mesencephalon) and cerebellum (rhombomere 1) by misexpressing Sprouty2 (Spry2) specifically in the mouse mesencephalon and rhombomere 1 from an early stage. We show that such Spry2 misexpression moderately reduces FGF signaling, and that this reduction causes the death of cells in the anterior mesencephalon, the region furthest from the source of FGF ligands. Interestingly, the remaining cells in the posterior mesencephalon develop into anterior midbrain, indicating that a low level of FGF signaling is sufficient to promote only anterior midbrain development. Spry2 misexpression also affects development of the vermis, the medial part of the cerebellum that spans the midline. We found that whereas misexpression of Spry2 alone caused loss of the anterior vermis, reducing FGF signaling further, by decreasing Fgf8 gene dosage, resulted in loss of the entire vermis. We provide evidence that cell death is not responsible for this tissue loss. Instead, our data suggest that the vermis fails to develop because reducing FGF signaling perturbs the balance between vermis and roof plate development in rhombomere 1. We suggest a molecular explanation for this phenomenon by providing evidence that FGF signaling functions to inhibit the BMP signaling that promotes roof plate development. PMID:18216176

  18. Psychological Balance in High Level Athletes: Gender-Based Differences and Sport-Specific Patterns

    PubMed Central

    Schaal, Karine; Tafflet, Muriel; Nassif, Hala; Thibault, Valérie; Pichard, Capucine; Alcotte, Mathieu; Guillet, Thibaut; El Helou, Nour; Berthelot, Geoffroy; Simon, Serge; Toussaint, Jean-François

    2011-01-01

    Objectives Few epidemiological studies have focused on the psychological health of high level athletes. This study aimed to identify the principal psychological problems encountered within French high level athletes, and the variations in their prevalence based on sex and the sport practiced. Methods Multivariate analyses were conducted on nationwide data obtained from the athletes' yearly psychological evaluations. Results A representative sample of 13% of the French athlete population was obtained. 17% of athletes have at least one ongoing or recent disorder, generalized anxiety disorder (GAD) being the most prevalent (6%), followed by non-specific eating disorders (4.2%). Overall, 20.2% of women had at least one psychopathology, against 15.1% in men. This female predominance applied to anxiety and eating disorders, depression, sleep problems and self-harming behaviors. The highest rates of GAD appeared in aesthetic sports (16.7% vs. 6.8% in other sports for men and 38.9% vs. 10.3% for women); the lowest prevalence was found in high risk sports athletes (3.0% vs. 3.5%). Eating disorders are most common among women in racing sports (14% vs. 9%), but for men were found mostly in combat sports (7% vs. 4.8%). Discussion This study highlights important differences in psychopathology between male and female athletes, demonstrating that the many sex-based differences reported in the general population apply to elite athletes. While the prevalence of psychological problems is no higher than in the general population, the variations in psychopathology in different sports suggest that specific constraints could influence the development of some disorders. PMID:21573222

  19. Fuzzy logic control of water level in advanced boiling water reactor

    SciTech Connect

    Lin, Chaung; Lee, Chi-Szu; Raghavan, R.; Fahrner, D.M.

    1995-12-31

    The feedwater control system in the Advanced Boiling Water Reactor (ABWR) is more challenging to design compared to other control systems in the plant, due to the possible change in level from void collapses and swells during transient events. A basic fuzzy logic controller is developed using a simplified ABWR mathematical model to demonstrate and compare the performance of this controller with a simplified conventional controller. To reduce the design effort, methods are developed to automatically tune the scaling factors and control rules. As a first step in developing the fuzzy controller, a fuzzy controller with a limited number of rules is developed to respond to normal plant transients such as setpoint changes of plant parameters and load demand changes. Various simulations for setpoint and load demand changes of plant performances were conducted to evaluate the modeled fuzzy logic design against the simplified ABWR model control system. The simulation results show that the performance of the fuzzy logic controller is comparable to that of the Proportional-Integral (PI) controller, However, the fuzzy logic controller produced shorter settling time for step setpoint changes compared to the simplified conventional controller.

  20. Which Advanced Mathematics Courses Influence ACT Score? A State Level Analysis of the Iowa Class of 2012

    ERIC Educational Resources Information Center

    Grinstead, Mary L.

    2013-01-01

    This study explores the relationship between specific advanced mathematics courses and college readiness (as determined by ACT score). The ACT organization has found a consistent relationship between taking a minimum core number of mathematics courses and higher ACT scores (mathematics and composite) (ACT, Inc., 2012c). However, the extent to…

  1. Semen Levels of Spermatid-Specific Thioredoxin-3 Correlate with Pregnancy Rates in ART Couples

    PubMed Central

    Qiu, Jing; Sutovsky, Miriam; Rawe, Vanesa Y.; Manandhar, Gaurishankar; Miranda-Vizuete, Antonio; Sutovsky, Peter

    2013-01-01

    Spermatid specific thioredoxin-3 (SPTRX3 or TXNDC8) is a testis/male germ line specific member of thioredoxin family that accumulates in the superfluous cytoplasm of defective human spermatozoa. We hypothesized that semen levels of SPTRX3 are reflective of treatment outcome in assisted reproductive therapy (ART) couples treated by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Relationship between SPTRX3 and treatment outcome was investigated in 239 couples undergoing ART at an infertility clinic. Sperm content of SPTRX3 was evaluated by flow cytometry and epifluorescence microscopy, and correlated with clinical semen analysis parameters, and data on embryo development and pregnancy establishment. High SPTRX3 levels (>15% SPTRX3-positive spermatozoa) were found in 51% of male infertility patients (n = 72), in 20% of men from couples with unexplained, idiopathic infertility (n = 61) and in 14% of men from couples previously diagnosed with female-only infertility (n = 85). Couples with high SPTRX3 produced fewer two-pronuclear zygotes and had a reduced pregnancy rate (19.2% pregnant with >15% SPTRX3-positive spermatozoa vs. 41.2% pregnant with <5% SPTRX3-positive sperm; one-sided p<0.05). The average pregnancy rate of all 239 couples was 25.1%. Live birth rate was 19.2% and lowest average SPTRX3 levels were found in couples that delivered twins. Men with >15% of SPTRX3-positive spermatozoa, a cutoff value established by ROC analysis, had their chance of fathering children by IVF or ICSI reduced by nearly two-thirds. The percentage of SPTRX3-positive spermatozoa had predictive value for pregnancy after ART. Gradient purification and sperm swim-up failed to remove all SPTRX3-positive spermatozoa from semen prepared for ART. In summary, the elevated semen content of SPTRX3 in men from ART couples coincided with reduced incidence of pregnancy by IVF or ICSI, identifying SPTRX3 as a candidate biomarker reflective of ART outcome. PMID

  2. Body mass index in relation to serum prostate-specific antigen levels and prostate cancer risk.

    PubMed

    Bonn, Stephanie E; Sjölander, Arvid; Tillander, Annika; Wiklund, Fredrik; Grönberg, Henrik; Bälter, Katarina

    2016-07-01

    High Body mass index (BMI) has been directly associated with risk of aggressive or fatal prostate cancer. One possible explanation may be an effect of BMI on serum levels of prostate-specific antigen (PSA). To study the association between BMI and serum PSA as well as prostate cancer risk, a large cohort of men without prostate cancer at baseline was followed prospectively for prostate cancer diagnoses until 2015. Serum PSA and BMI were assessed among 15,827 men at baseline in 2010-2012. During follow-up, 735 men were diagnosed with prostate cancer with 282 (38.4%) classified as high-grade cancers. Multivariable linear regression models and natural cubic linear regression splines were fitted for analyses of BMI and log-PSA. For risk analysis, Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) and natural cubic Cox regression splines producing standardized cancer-free probabilities were fitted. Results showed that baseline Serum PSA decreased by 1.6% (95% CI: -2.1 to -1.1) with every one unit increase in BMI. Statistically significant decreases of 3.7, 11.7 and 32.3% were seen for increasing BMI-categories of 25 < 30, 30 < 35 and ≥35 kg/m(2) , respectively, compared to the reference (18.5 < 25 kg/m(2) ). No statistically significant associations were seen between BMI and prostate cancer risk although results were indicative of a positive association to incidence rates of high-grade disease and an inverse association to incidence of low-grade disease. However, findings regarding risk are limited by the short follow-up time. In conclusion, BMI was inversely associated to PSA-levels. BMI should be taken into consideration when referring men to a prostate biopsy based on serum PSA-levels. PMID:26914149

  3. ENHANCING THE ATOMIC-LEVEL UNDERSTANDING OF CO2 MINERAL SEQUESTRATION MECHANISMS VIA ADVANCED COMPUTATIONAL MODELING

    SciTech Connect

    A.V.G. Chizmeshya

    2002-12-19

    /NETL managed National Mineral Sequestration Working Group we have already significantly improved our understanding of mineral carbonation. Group members at the Albany Research Center have recently shown that carbonation of olivine and serpentine, which naturally occurs over geological time (i.e., 100,000s of years), can be accelerated to near completion in hours. Further process refinement will require a synergetic science/engineering approach that emphasizes simultaneous investigation of both thermodynamic processes and the detailed microscopic, atomic-level mechanisms that govern carbonation kinetics. Our previously funded Phase I Innovative Concepts project demonstrated the value of advanced quantum-mechanical modeling as a complementary tool in bridging important gaps in our understanding of the atomic/molecular structure and reaction mechanisms that govern CO{sub 2} mineral sequestration reaction processes for the model Mg-rich lamellar hydroxide feedstock material Mg(OH){sub 2}. In the present simulation project, improved techniques and more efficient computational schemes have allowed us to expand and augment these capabilities and explore more complex Mg-rich, lamellar hydroxide-based feedstock materials, including the serpentine-based minerals. These feedstock materials are being actively investigated due to their wide availability, and low-cost CO{sub 2} mineral sequestration potential. Cutting-edge first principles quantum chemical, computational solid-state and materials simulation methodology studies proposed herein, have been strategically integrated with our new DOE supported (ASU-Argonne National Laboratory) project to investigate the mechanisms that govern mineral feedstock heat-treatment and aqueous/fluid-phase serpentine mineral carbonation in situ. This unified, synergetic theoretical and experimental approach will provide a deeper understanding of the key reaction mechanisms than either individual approach can alone. Ab initio techniques will also

  4. ENHANCING THE ATOMIC-LEVEL UNDERSTANDING OF CO2 MINERAL SEQUESTRATION MECHANISMS VIA ADVANCED COMPUTATIONAL MODELING

    SciTech Connect

    A.V.G. Chizmeshya; M.J. McKelvy; G.H. Wolf; R.W. Carpenter; D.A. Gormley; J.R. Diefenbacher; R. Marzke

    2006-03-01

    significantly improved our understanding of mineral carbonation. Group members at the Albany Research Center have recently shown that carbonation of olivine and serpentine, which naturally occurs over geological time (i.e., 100,000s of years), can be accelerated to near completion in hours. Further process refinement will require a synergetic science/engineering approach that emphasizes simultaneous investigation of both thermodynamic processes and the detailed microscopic, atomic-level mechanisms that govern carbonation kinetics. Our previously funded Phase I Innovative Concepts project demonstrated the value of advanced quantum-mechanical modeling as a complementary tool in bridging important gaps in our understanding of the atomic/molecular structure and reaction mechanisms that govern CO2 mineral sequestration reaction processes for the model Mg-rich lamellar hydroxide feedstock material Mg(OH)2. In the present simulation project, improved techniques and more efficient computational schemes have allowed us to expand and augment these capabilities and explore more complex Mg-rich, lamellar hydroxide-based feedstock materials, including the serpentine-based minerals. These feedstock materials are being actively investigated due to their wide availability, and low-cost CO2 mineral sequestration potential. Cutting-edge first principles quantum chemical, computational solid-state and materials simulation methodology studies proposed herein, have been strategically integrated with our new DOE supported (ASU-Argonne National Laboratory) project to investigate the mechanisms that govern mineral feedstock heat-treatment and aqueous/fluid-phase serpentine mineral carbonation in situ. This unified, synergetic theoretical and experimental approach has provided a deeper understanding of the key reaction mechanisms than either individual approach can alone. We used ab initio techniques to significantly advance our understanding of atomic-level processes at the solid/solution interface by

  5. ENHANCING THE ATOMIC-LEVEL UNDERSTANDING OF CO2 MINERAL SEQUESTRATION MECHANISMS VIA ADVANCED COMPUTATIONAL MODELING

    SciTech Connect

    A.V.G. Chizmeshya

    2003-12-19

    /NETL managed National Mineral Sequestration Working Group we have already significantly improved our understanding of mineral carbonation. Group members at the Albany Research Center have recently shown that carbonation of olivine and serpentine, which naturally occurs over geological time (i.e., 100,000s of years), can be accelerated to near completion in hours. Further process refinement will require a synergetic science/engineering approach that emphasizes simultaneous investigation of both thermodynamic processes and the detailed microscopic, atomic-level mechanisms that govern carbonation kinetics. Our previously funded Phase I Innovative Concepts project demonstrated the value of advanced quantum-mechanical modeling as a complementary tool in bridging important gaps in our understanding of the atomic/molecular structure and reaction mechanisms that govern CO{sub 2} mineral sequestration reaction processes for the model Mg-rich lamellar hydroxide feedstock material Mg(OH){sub 2}. In the present simulation project, improved techniques and more efficient computational schemes have allowed us to expand and augment these capabilities and explore more complex Mg-rich, lamellar hydroxide-based feedstock materials, including the serpentine-based minerals. These feedstock materials are being actively investigated due to their wide availability, and low-cost CO{sub 2} mineral sequestration potential. Cutting-edge first principles quantum chemical, computational solid-state and materials simulation methodology studies proposed herein, have been strategically integrated with our new DOE supported (ASU-Argonne National Laboratory) project to investigate the mechanisms that govern mineral feedstock heat-treatment and aqueous/fluid-phase serpentine mineral carbonation in situ. This unified, synergetic theoretical and experimental approach will provide a deeper understanding of the key reaction mechanisms than either individual approach can alone. Ab initio techniques will also

  6. Improved locus-specific database for OPA1 mutations allows inclusion of advanced clinical data.

    PubMed

    Ferré, Marc; Caignard, Angélique; Milea, Dan; Leruez, Stéphanie; Cassereau, Julien; Chevrollier, Arnaud; Amati-Bonneau, Patrizia; Verny, Christophe; Bonneau, Dominique; Procaccio, Vincent; Reynier, Pascal

    2015-01-01

    Autosomal-dominant optic atrophy (ADOA) is the most common inherited optic neuropathy, due to mutations in the optic atrophy 1 gene (OPA1) in about 60%-80% of cases. At present, the clinical heterogeneity of patients carrying OPA1 variants renders genotype-phenotype correlations difficulty. Since 2005, when we published the first locus-specific database (LSDB) dedicated to OPA1, a large amount of new clinical and genetic knowledge has emerged, prompting us to update this database. We have used the Leiden Open-Source Variation Database to develop a clinico-biological database, aiming to add clinical phenotypes related to OPA1 variants. As a first step, we validated this new database by registering several patients previously reported in the literature, as well as new patients from our own institution. Contributors may now make online submissions of clinical and molecular descriptions of phenotypes due to OPA1 variants, including detailed ophthalmological and neurological data, with due respect to patient anonymity. The updated OPA1 LSDB (http://opa1.mitodyn.org/) should prove useful for molecular diagnoses, large-scale variant statistics, and genotype-phenotype correlations in ADOA studies. PMID:25243597

  7. Ecological Effects of Sea Level Rise: Advancing coastal management through integrated research and engagement

    NASA Astrophysics Data System (ADS)

    Kidwell, D. M.

    2012-12-01

    Rising sea level represents a significant threat to coastal communities and ecosystems through land loss, altered habitats, and increased vulnerability to coastal storms and inundation. This threat is exemplified in the northern Gulf of Mexico where low topography, expansive marshes, and a prevalence of tropical storms have already resulted in extensive coastal impacts. The development of robust predictive capabilities that incorporate complex biological processes with physical dynamics are critical for informed planning and restoration efforts for coastal ecosystems. Looking to build upon existing predictive modeling capabilities and allow for use of multiple model (i.e., ensemble) approaches, NOAA initiated the Ecological Effects of Sea Level Rise program in 2010 to advance physical/biological integrative modeling capabilities in the region with a goal to provide user friendly predictive tools for coastal ecosystem management. Focused on the northern Gulf of Mexico, this multi-disciplinary project led by the University of Central Florida will use in situ field studies to parameterize physical and biological models. These field studies will also result in a predictive capability for overland sediment delivery and transport that will further enhance marsh, oyster, and submerged aquatic vegetation models. Results from this integrated modeling effort are envisioned to inform management strategies for reducing risk, restoration and breakwater guidelines, and resource sustainability for project planning, among other uses. In addition to the science components, this project incorporates significant engagement of the management community through a management applications principle investigator and an advisory management committee. Routine engagement between the science team and the management committee, including annual workshops, are focused on ensuring the development of applicable, relevant, and useable products and tools at the conclusion of this project. Particular

  8. Integration of patient specific modeling and advanced image processing techniques for image-guided neurosurgery

    NASA Astrophysics Data System (ADS)

    Archip, Neculai; Fedorov, Andriy; Lloyd, Bryn; Chrisochoides, Nikos; Golby, Alexandra; Black, Peter M.; Warfield, Simon K.

    2006-03-01

    A major challenge in neurosurgery oncology is to achieve maximal tumor removal while avoiding postoperative neurological deficits. Therefore, estimation of the brain deformation during the image guided tumor resection process is necessary. While anatomic MRI is highly sensitive for intracranial pathology, its specificity is limited. Different pathologies may have a very similar appearance on anatomic MRI. Moreover, since fMRI and diffusion tensor imaging are not currently available during the surgery, non-rigid registration of preoperative MR with intra-operative MR is necessary. This article presents a translational research effort that aims to integrate a number of state-of-the-art technologies for MRI-guided neurosurgery at the Brigham and Women's Hospital (BWH). Our ultimate goal is to routinely provide the neurosurgeons with accurate information about brain deformation during the surgery. The current system is tested during the weekly neurosurgeries in the open magnet at the BWH. The preoperative data is processed, prior to the surgery, while both rigid and non-rigid registration algorithms are run in the vicinity of the operating room. The system is tested on 9 image datasets from 3 neurosurgery cases. A method based on edge detection is used to quantitatively validate the results. 95% Hausdorff distance between points of the edges is used to estimate the accuracy of the registration. Overall, the minimum error is 1.4 mm, the mean error 2.23 mm, and the maximum error 3.1 mm. The mean ratio between brain deformation estimation and rigid alignment is 2.07. It demonstrates that our results can be 2.07 times more precise then the current technology. The major contribution of the presented work is the rigid and non-rigid alignment of the pre-operative fMRI with intra-operative 0.5T MRI achieved during the neurosurgery.

  9. Specific Safety Profile of Bevacizumab in Asian Patients With Advanced NSCLC

    PubMed Central

    Chen, Zhenguang; Zhong, Beilong; Lun, Xueping; Lai, Yingrong; Bella, Amos Ela; Yang, Weilin; Wu, Jiabin

    2015-01-01

    Abstract Randomized studies have obtained varying findings regarding the benefits and toxicities of bevacizumab in the treatment of nonsmall cell lung cancer (NSCLC). It is unclear whether the discrepancies among trials are due to ethnic/racial differences. We therefore performed a meta-analysis of all published, randomized, controlled clinical trials involving bevacizumab in patients with NSCLC to assess its effectiveness and safety in Asian and non-Asian populations. Results from the phase II JO19907 trial, the phase III AVAiL and ECOG 4599 trials, and the phase IV SAiL trials were used to calculate the benefits and toxicities of bevacizumab in Asian and non-Asian patients. Combined statistical estimates, including hazard ratios and odds ratios, were calculated using fixed-effects and random-effects models. A total of 4308 patients were evaluated. Combining bevacizumab with different chemotherapy regimens resulted in similar objective response rates, overall survival, and progression-free survival in Asian and non-Asian populations. Disease control rates, however, were only reported in Asian populations. The rates of severe bleeding (relative risk [RR], 2.17; P = 0.02) and thromboembolism (RR, 3.65; P < 0.0001) were significantly higher, while the rate of severe proteinuria was significantly lower (RR, 0.43; P < 0.0001), in non-Asian than in Asian populations. The rates of severe hypertension (P = 0.71) and hemoptysis (P = 0.66) were similar in Asian and non-Asian populations. Bevacizumab combined with chemotherapy for first-line NSCLC treatment showed similar benefits in Asian and non-Asian populations, but had specific safety profiles in each.

  10. An Investigation to Advance the Technology Readiness Level of the Centaur Derived On-orbit Propellant Storage and Transfer System

    NASA Astrophysics Data System (ADS)

    Silvernail, Nathan L.

    This research was carried out in collaboration with the United Launch Alliance (ULA), to advance an innovative Centaur-based on-orbit propellant storage and transfer system that takes advantage of rotational settling to simplify Fluid Management (FM), specifically enabling settled fluid transfer between two tanks and settled pressure control. This research consists of two specific objectives: (1) technique and process validation and (2) computational model development. In order to raise the Technology Readiness Level (TRL) of this technology, the corresponding FM techniques and processes must be validated in a series of experimental tests, including: laboratory/ground testing, microgravity flight testing, suborbital flight testing, and orbital testing. Researchers from Embry-Riddle Aeronautical University (ERAU) have joined with the Massachusetts Institute of Technology (MIT) Synchronized Position Hold Engage and Reorient Experimental Satellites (SPHERES) team to develop a prototype FM system for operations aboard the International Space Station (ISS). Testing of the integrated system in a representative environment will raise the FM system to TRL 6. The tests will demonstrate the FM system and provide unique data pertaining to the vehicle's rotational dynamics while undergoing fluid transfer operations. These data sets provide insight into the behavior and physical tendencies of the on-orbit refueling system. Furthermore, they provide a baseline for comparison against the data produced by various computational models; thus verifying the accuracy of the models output and validating the modeling approach. Once these preliminary models have been validated, the parameters defined by them will provide the basis of development for accurate simulations of full scale, on-orbit systems. The completion of this project and the models being developed will accelerate the commercialization of on-orbit propellant storage and transfer technologies as well as all in

  11. Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer.

    PubMed Central

    Howell, A.; DeFriend, D. J.; Robertson, J. F.; Blamey, R. W.; Anderson, L.; Anderson, E.; Sutcliffe, F. A.; Walton, P.

    1996-01-01

    We have assessed the pharmacokinetics, pharmacological and anti-tumour effects of the specific steroidal anti-oestrogen ICI 182780 in 19 patients with advanced breast cancer resistant to tamoxifen. The agent was administered as a monthly depot intramuscular injection. Peak levels of ICI 182780 occurred a median of 8-9 days after dosing and then declined but were above the projected therapeutic threshold at day 28. Cmax during the first month was 10.5 ng/ml-1 and during the sixth month was 12.6 ng ml-1. The AUCs were 140.5 and 206.8 ng day ml-1 on the first and sixth month of dosing respectively, suggesting some drug accumulation. Luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels rose after withdrawal of tamoxifen and then plateaued, suggesting no effect of ICI 182780 on the pituitary-hypothalamic axis. There were no significant changes in serum levels of prolactin, sex hormone-binding globulin (SHBG) or lipids. Side-effects were infrequent. Hot-flushes and sweats were not induced and there was no apparent effect of treatment upon the endometrium or vagina. Thirteen (69%) patients responded (seven had partial responses and six showed "no change' responses) to ICI 182780, after progression on tamoxifen, for a median duration of 25 months. Thus ICI 182780, given by monthly depot injection, and at the drug levels described, is an active second-line anti-oestrogen without apparent negative effects on the liver, brain or genital tract and warrants further evaluation in patients with advanced breast cancer. PMID:8688341

  12. Advanced-Level Testing of Foreign Language Proficiency: An Interim Report of the Post A-Level Spanish Project.

    ERIC Educational Resources Information Center

    Ife, Anne E.; Standish, Peter

    This is a preliminary report concerning the development of tests which measure the linguistic ability in Spanish of English students at the beginning of their post A-level courses. The Palspan (Post A-level Spanish project) pilot test battery is comprised of five sub-tests of between 45 and 90 minutes in length which test for speaking, listening,…

  13. Advanced waste form and Melter development for treatment of troublesome high-level wastes

    SciTech Connect

    Marra, James; Kim, Dong -Sang; Maio, Vincent

    2015-10-01

    A number of waste components in US defense high level radioactive wastes (HLW) have proven challenging for current Joule heated ceramic melter (JHCM) operations and have limited the ability to increase waste loadings beyond already realized levels. Many of these “troublesome" waste species cause crystallization in the glass melt that can negatively impact product quality or have a deleterious effect on melter processing. Recent efforts at US Department of Energy laboratories have focused on understanding crystallization behavior within HLW glass melts and investigating approaches to mitigate the impacts of crystallization so that increases in waste loading can be realized. Advanced glass formulations have been developed to highlight the unique benefits of next-generation melter technologies such as the Cold Crucible Induction Melter (CCIM). Crystal-tolerant HLW glasses have been investigated to allow sparingly soluble components such as chromium to crystallize in the melter but pass out of the melter before accumulating.The Hanford site AZ-101 tank waste composition represents a waste group that is waste loading limited primarily due to high concentrations of Fe2O3 (also with high Al2O3 concentrations). Systematic glass formulation development utilizing slightly higher process temperatures and higher tolerance to spinel crystals demonstrated that an increase in waste loading of more than 20% could be achieved for this waste composition, and by extension higher loadings for wastes in the same group. An extended duration CCIM melter test was conducted on an AZ-101 waste simulant using the CCIM platform at the Idaho National Laboratory (INL). The melter was continually operated for approximately 80 hours demonstrating that the AZ-101 high waste loading glass composition could be readily processed using the CCIM technology. The resulting glass was close to the targeted composition and exhibited excellent durability in both

  14. Teaching Groups as Foci for Evaluating Performance in Cost-Effectiveness of GCE Advanced Level Provision: Some Practical Methodological Innovations.

    ERIC Educational Resources Information Center

    Fielding, Antony

    2002-01-01

    Analyzes subject teaching-group effectiveness in English and Welsh General Certification of Education (GCE) Advanced Level prior to a linking to resources; suggests cross-classified multilevel models with weighted random effects for disentangling student, group, and teacher effects; finds that teacher effects are considerable, but cannot find…

  15. Low Endogenous Secretory Receptor for Advanced Glycation End-Products Levels Are Associated With Inflammation and Carotid Atherosclerosis in Prediabetes.

    PubMed

    Di Pino, Antonino; Urbano, Francesca; Zagami, Rose Maria; Filippello, Agnese; Di Mauro, Stefania; Piro, Salvatore; Purrello, Francesco; Rabuazzo, Agata Maria

    2016-04-01

    Pre-diabetes is associated with advanced vascular damage. Our data shows that subjects with pre-diabetes exhibited low esRAGE plasma levels and gene expression, which are inversely related with markers of inflammation and atherosclerotic risk. PMID:26885882

  16. 34 CFR 350.65 - What level of participation is required of trainees in an Advanced Rehabilitation Research...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 2 2014-07-01 2013-07-01 true What level of participation is required of trainees in an Advanced Rehabilitation Research Training Project? 350.65 Section 350.65 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION DISABILITY...

  17. Strategic Alliance to Advanced Technological Education through Enhanced Mathematics, Science, Technology, and English Education at the Secondary Level

    ERIC Educational Resources Information Center

    Scarborough, Jule Dee

    2004-01-01

    This document (book) reports on the Strategic Alliance to Advance Technological Education through Enhanced Mathematics, Science, Technology, and English Education at the Secondary Level, funded by National Science Foundation. It was a collaborative partnership involving the Rockford Public Schools, Rock Valley College, and Northern Illinois…

  18. Overview of the 2006 NCHEC Advanced-Level Certification Feasibility Study Results: The Impetus of a Positive Legacy

    ERIC Educational Resources Information Center

    Dennis, Dixie L.; Alley, Kelly Bishop; Aduroja, Amos

    2008-01-01

    Through the 6-year National Health Educator Competencies Update Project (CUP), in 2004, the National Commission for Health Education Credentialing, Inc. (NCHEC), American Association for Health Education (AAHE), and Society for Public Health Education (SOPHE) completed verification of advanced-level competencies and subcompetencies for health…

  19. Finding a Balance: Fifteen Institutional Case Studies on the Relationship between Part-Time Work and Advanced Level Study. Report.

    ERIC Educational Resources Information Center

    Hodgson, Ann, Ed.; Spours, Ken, Ed.

    This document presents and discusses case studies that examined the relationship between part-time employment and advanced level study at 15 schools in Essex, England. "Foreword" (David Jones) provides a brief overview of the project. "Finding a Balance--Fifteen Institutional Case Studies on the Relationship between Part-time Work and Advanced…

  20. Some Misconceptions in Meiosis Shown by Students Responding to an Advanced Level Practical Examination Question in Biology.

    ERIC Educational Resources Information Center

    Brown, C. R.

    1990-01-01

    Discussed are problems revealed in student responses to a practical task which formed part of an advanced level examination. The frequencies with which some misconceptions about cell reproduction and genetics occurred are presented. The nature of these misconceptions is analyzed and their implications discussed. (CW)

  1. The Extraction and Partial Purification of Bacterial DNA as a Practical Exercise for GCE Advanced Level Students.

    ERIC Educational Resources Information Center

    Falconer, A. C.; Hayes, L. J.

    1986-01-01

    Describes a relatively simple method of extraction and purification of bacterial DNA. This technique permits advanced secondary-level science students to obtain adequate amounts of DNA from very small pellets of bacteria and to observe some of its polymer properties. (ML)

  2. Ontario Basic Skills. Career Planning. A Thematic Unit for Integrated Curriculum: Advanced Level. [Student Workbook and] Teacher's Manual.

    ERIC Educational Resources Information Center

    Anderson, Marcia; And Others

    This set of publications, consisting of a student workbook and teacher's manual, is designed for use by adult learners registered in the advanced level of the career planning course of the Ontario (Canada) Basic Skills program. The student workbook contains units on the following topics: introduction to career planning, self-assessment for…

  3. Sport-Specific Conditioning Variables Predict Offensive and Defensive Performance in High-Level Youth Water Polo Athletes.

    PubMed

    Sekulic, Damir; Kontic, Dean; Esco, Michael R; Zenic, Natasa; Milanovic, Zoran; Zvan, Milan

    2016-05-01

    Specific-conditioning capacities (SCC) are known to be generally important in water polo (WP), yet the independent associations to offensive and defensive performance is unknown. This study aimed to determine whether offense and defense abilities in WP were independently associated with SCC and anthropometrics. The participants were 82 high-level male youth WP players (all 17-19 years of age; body height, 186.3 ± 6.07 cm; body mass, 84.8 ± 9.6 kg). The independent variables were body height and body mass, and 5 sport-specific fitness tests: sprint swimming over 15 meters; 4 × 50-meter anaerobic-endurance test; vertical in-water-jump; maximum intensity isometric force in upright swimming using an eggbeater kick; and test of throwing velocity. The 6 dependent variables comprised parameters of defensive and offensive performance, such as polyvalence, i.e., ability to play on different positions in defensive tasks (PD) and offensive tasks (PO), efficacy in primary playing position in defensive (ED) and offensive (EO) tasks, and agility in defensive (AD) and offensive (AO) tasks. Analyses showed appropriate reliability for independent (intraclass coefficient of 0.82-0.91) and dependent variables (Cronbach alpha of 0.81-0.95). Multiple regressions were significant for ED (R = 0.25; p < 0.01), EO (R = 0.21; p < 0.01), AD (R = 0.40; p < 0.01), and AO (R = 0.35; p < 0.01). Anaerobic-swimming performance was positively related to AD (β = -0.26; p ≤ 0.05), whereas advanced sprint swimming was related to better AO (β = -0.38; p ≤ 0.05). In-water-jumping performance held the significant positive relationship to EO (β = 0.31; p ≤ 0.05), ED (β = 0.33; p ≤ 0.05), and AD (β = 0.37; p ≤ 0.05). Strength and conditioning professionals working in WP should be aware of established importance of SCC in performing unique duties in WP. The SCC should be specifically developed to meet the needs of offensive and defensive performance in young WP athletes. PMID:26439788

  4. The association between interleukin-4 -590C/T genetic polymorphism, IL-4 serum level, and advanced endometriosis

    PubMed Central

    Malutan, Andrei M.; Drugan, Tudor; Ciortea, Razvan; Mihu, Dan

    2016-01-01

    Aim of the study Aim of the study was to investigate interleukin (IL)-4 serum levels in patients with advanced endometriosis and whether IL-4 promoter region (-590C/T) genetic polymorphism is involved in genetic susceptibility to endometriosis. Material and methods IL-4 serum levels and IL-4 -590C/T genetic polymorphism were determined for 80 patients with advanced endometriosis and 85 healthy fertile women using a multiplex cytokine kit, with a Luminex 200 system; high molecular weight genomic DNA was extracted from peripheral blood leukocytes, and further analyzed by PCR amplification and restriction fragment length polymorphism (PCR-PFLP). The relationship between IL-4 serum levels, genotypes and haplotypes and the presence of endometriosis was explored. Results Interleukin 4 serum levels were significantly higher in the endometriosis group compared to controls (138,459 compared to 84,710, p < 0.001). No significant difference was observed in IL-4 serum levels between genotypes. There were no differences in IL-4 -590C/T genotypes and allele frequencies between control women and patients with endometriosis (χ2 = 0.496, and χ2 = 0.928, OR = 1.3636, CI: 0.725-2.564). Conclusions The results suggest that in patients with advanced stages of endometriosis there is a higher serum level of IL-4, and that this value, or the presence of the disease, is not influenced by the presence of IL-4 -590C/T genetic polymorphism. PMID:27536203

  5. Advanced Inverter Technology for High Penetration Levels of PV Generation in Distribution Systems

    SciTech Connect

    Schauder, C.

    2014-03-01

    This subcontract report was completed under the auspices of the NREL/SCE High-Penetration Photovoltaic (PV) Integration Project, which is co-funded by the U.S. Department of Energy (DOE) Office of Energy Efficiency and Renewable Energy (EERE) and the California Solar Initiative (CSI) Research, Development, Demonstration, and Deployment (RD&D) program funded by the California Public Utility Commission (CPUC) and managed by Itron. This project is focused on modeling, quantifying, and mitigating the impacts of large utility-scale PV systems (generally 1-5 MW in size) that are interconnected to the distribution system. This report discusses the concerns utilities have when interconnecting large PV systems that interconnect using PV inverters (a specific application of frequency converters). Additionally, a number of capabilities of PV inverters are described that could be implemented to mitigate the distribution system-level impacts of high-penetration PV integration. Finally, the main issues that need to be addressed to ease the interconnection of large PV systems to the distribution system are presented.

  6. Cloning-free genome engineering in Sinorhizobium meliloti advances applications of Cre/loxP site-specific recombination.

    PubMed

    Döhlemann, Johannes; Brennecke, Meike; Becker, Anke

    2016-09-10

    The soil-dwelling α-proteobacterium Sinorhizobium meliloti serves as model for studies of symbiotic nitrogen fixation, a highly important process in sustainable agriculture. Here, we report advancements of the genetic toolbox accelerating genome editing in S. meliloti. The hsdMSR operon encodes a type-I restriction-modification (R-M) system. Transformation of S. meliloti is counteracted by the restriction endonuclease HsdR degrading DNA which lacks the appropriate methylation pattern. We provide a stable S. meliloti hsdR deletion mutant showing enhanced transformation with Escherichia coli-derived plasmid DNA and demonstrate that using an E. coli plasmid donor, expressing S. meliloti methyl transferase genes, is an alternative strategy of increasing the transformation efficiency of S. meliloti. Furthermore, we devise a novel cloning-free genome editing (CFGE) method for S. meliloti, Agrobacterium tumefaciens and Xanthomonas campestris, and demonstrate the applicability of this method for intricate applications of the Cre/lox recombination system in S. meliloti. An enhanced Cre/lox system, allowing for serial deletions of large genomic regions, was established. An assay of lox spacer mutants identified a set of lox sites mediating specific recombination. The availability of several non-promiscuous Cre recognition sites enables simultaneous specific Cre/lox recombination events. CFGE combined with Cre/lox recombination is put forward as powerful approach for targeted genome editing, involving serial steps of manipulation to expedite the genetic accessibility of S. meliloti as chassis. PMID:27393468

  7. Exploratory Analysis of the Effects of Anxiety on Specific Quantifiable Variables of African-American High School Students Enrolled in Advanced Academics

    ERIC Educational Resources Information Center

    James, Carmela N.

    2013-01-01

    The purpose of this study was to examine the attrition rate of the African American high school student enrolled in advanced academics by looking at the effects of specific quantifiable variables on state-trait anxiety scores. More specifically, this study was concerned with the influence of demographic and school related factors on the…

  8. Final Report Full-Scale Test of DWPF Advanced Liquid-Level and Density Measurement Bubblers

    SciTech Connect

    Duignan, M.R.; Weeks, G.E.

    1999-07-01

    As requested by the Technical Task Request (1), a full-scale test was carried out on several different liquid-level measurement bubblers as recommended from previous testing (2). This final report incorporates photographic evidence (Appendix B) of the bubblers at different stages of testing, along with the preliminary results (Appendix C) which were previously reported (3), and instrument calibration data (Appendix D); while this report contains more detailed information than previously reported (3) the conclusions remain the same. The test was performed under highly prototypic conditions from November 26, 1996 to January 23, 1997 using the full-scale SRAT/SME tank test facilities located in the 672-T building at TNX. Two different types of advanced bubblers were subjected to approximately 58 days of slurry operation; 14 days of which the slurry was brought to boiling temperatures.The test showed that the large diameter tube bubbler (2.64 inches inside diameter) operated successfully throughout the2-month test by not plugging with the glass-frit ladened slurry which was maintained at a minimum temperature of 50 deg Cand several days of boiling temperatures. However, a weekly blow-down with air or water is recommended to minimize the slurry which builds up.The small diameter porous tube bubbler (0.62 inch inside diameter; water flow {gt} 4 milliliters/hour = 1.5 gallons/day) operated successfully on a daily basis in the glass-frit ladened slurry which was maintained at a minimum temperature of 50 degrees C and several days of boiling temperatures. However, a daily blow-down with air, or air and water, is necessary to maintain accurate readings.For the small diameter porous tube bubbler (0.62 inch inside diameter; water flow {gt} 4 milliliters/hour = 1.5 gallons/day) there were varying levels of success with the lower water-flow tubes and these tubes would have to be cleaned by blowing with air, or air and water, several times a day to maintain them plug free. This

  9. Barriers to Advanced Placement for Latino Students at the High-School Level

    ERIC Educational Resources Information Center

    Walker, Susan A.; Pearsall, Laura D.

    2012-01-01

    In order to gain a better understanding about Latino student underrepresentation in advanced placement (AP) coursework, this investigation explored the factors that inhibit and/or encourage Latino student enrollment in AP coursework at one suburban public high school in the Western United States. Latino high-school students and their parents…

  10. An Exploration of Learners' Conceptions of Language, Culture, and Learning in Advanced-Level Spanish Courses

    ERIC Educational Resources Information Center

    Drewelow, Isabelle; Mitchell, Claire

    2015-01-01

    This article reports on an exploratory study, which examines learners' rating of culture in relation to other concepts in advanced Spanish courses and their justification of the ratings attributed. Open-ended responses, elicited from a questionnaire completed by 179 respondents, were analysed line by line using an interpretive approach. Data…

  11. Advanced Placement Strategy: A Framework for Identifying School-Level Barriers to AP Success. Policy Brief

    ERIC Educational Resources Information Center

    Batiwalla, Mary

    2014-01-01

    In 2013, Tennessee counted nearly 7,000 students in the senior cohort whose academic skills when they entered high school suggested they were on track to earn college credits through Advanced Placement (AP) exams. Yet just over half of these students actually graduated with an AP credit, and less than a third of the economically disadvantaged…

  12. Travel and Tourism Module. An Advanced-Level Option For Distribution and Marketing.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Bureau of Occupational Education Curriculum Development.

    Intended as an advanced option for distributive education students in the twelfth grade, this travel and tourism module is designed to cover a minimum of ten weeks or a maximum of twenty weeks. Introductory material includes information on employment demands, administrative considerations, course format, teaching suggestions, expected outcomes,…

  13. The Science Advancement through Group Engagement Program: Leveling the Playing Field and Increasing Retention in Science

    ERIC Educational Resources Information Center

    Hall, Donna M.; Curtin-Soydan, Amanda J.; Canelas, Dorian A.

    2014-01-01

    How can colleges and universities keep an open gateway to the science disciplines for the least experienced first-year science students while also maintaining high standards that challenge the students with the strongest possible high school backgrounds? The Science Advancement through Group Engagement (SAGE) project targets cohorts of less…

  14. Biotechnology Apprenticeship for Secondary-Level Students: Teaching Advanced Cell Culture Techniques for Research

    ERIC Educational Resources Information Center

    Lewis, Jennifer R.; Kotur, Mark S.; Butt, Omar; Kulcarni, Sumant; Riley, Alyssa A.; Ferrell, Nick; Sullivan, Kathryn D.; Ferrari, Mauro

    2002-01-01

    The purpose of this article is to discuss "small-group apprenticeships (SGAs)" as a method to instruct cell culture techniques to high school participants. The study aimed to teach cell culture practices and to introduce advanced imaging techniques to solve various biomedical engineering problems. Participants designed and completed experiments…

  15. Biotechnology Apprenticeship for Secondary-Level Students: Teaching Advanced Cell Culture Techniques for Research.

    ERIC Educational Resources Information Center

    Lewis, Jennifer R.; Kotur, Mark S.; Butt, Omar; Kulcarni, Sumant; Riley, Alyssa A.; Ferrell, Nick; Sullivan, Kathryn D.; Ferrari, Mauro

    2002-01-01

    Discusses small-group apprenticeships (SGAs) as a method for introducing cell culture techniques to high school participants. Teaches cell culture practices and introduces advance imaging techniques to solve various biomedical engineering problems. Clarifies and illuminates the value of small-group laboratory apprenticeships. (Author/KHR)

  16. Core Principles and Test Item Development for Advanced High School and Introductory University Level Food Science

    ERIC Educational Resources Information Center

    Laing-Kean, Claudine A. M.

    2010-01-01

    Programs supported by the Carl D. Perkins Act of 2006 are required to operate under the state or national content standards, and are expected to carry out evaluation procedures that address accountability. The Indiana high school course, "Advanced Life Science: Foods" ("ALS: Foods") operates under the auspices of the Perkins Act. However, no broad…

  17. Gender, Academics and Interscholastic Sports Participation at the School Level: A Gender-specific Analysis of the Relationship between Interscholastic Sports Participation and AP Enrollment.

    PubMed

    Veliz, Philip; Shakib, Sohaila

    2014-01-01

    While literature demonstrates that interscholastic sports participation is associated with positive academic outcomes, this relationship is rarely analyzed at a macro-level (the school-level). To date, there is no research examining whether increases in schools' female and male interscholastic sports participation rates is associated with increases in female and male AP enrollment rates. Using a national sample of 4,644 public high schools during the 2009-2010 school year, we test several gender-specific hypotheses linked with the association between schools' sport participation rates and advanced placement enrollment rates (AP math, AP science, AP foreign language, and overall AP enrollment). The findings reveal that schools' female and male sports participation rates have a positive association with schools' female and male AP math, AP science, AP foreign language, and overall AP enrollment rates. Moreover, the findings suggest that females benefit more than males in regard to the positive relationship between interscholastic sports and AP enrollment. PMID:24910475

  18. Gender, Academics and Interscholastic Sports Participation at the School Level: A Gender-specific Analysis of the Relationship between Interscholastic Sports Participation and AP Enrollment

    PubMed Central

    Veliz, Philip; Shakib, Sohaila

    2014-01-01

    While literature demonstrates that interscholastic sports participation is associated with positive academic outcomes, this relationship is rarely analyzed at a macro-level (the school-level). To date, there is no research examining whether increases in schools’ female and male interscholastic sports participation rates is associated with increases in female and male AP enrollment rates. Using a national sample of 4,644 public high schools during the 2009-2010 school year, we test several gender-specific hypotheses linked with the association between schools’ sport participation rates and advanced placement enrollment rates (AP math, AP science, AP foreign language, and overall AP enrollment). The findings reveal that schools’ female and male sports participation rates have a positive association with schools’ female and male AP math, AP science, AP foreign language, and overall AP enrollment rates. Moreover, the findings suggest that females benefit more than males in regard to the positive relationship between interscholastic sports and AP enrollment. PMID:24910475

  19. The value of lactate dehydrogenase serum levels as a prognostic and predictive factor for advanced pancreatic cancer patients receiving sorafenib

    PubMed Central

    Faloppi, Luca; Bianconi, Maristella; Giampieri, Riccardo; Sobrero, Alberto; Labianca, Roberto; Ferrari, Daris; Barni, Sandro; Aitini, Enrico; Zaniboni, Alberto; Boni, Corrado; Caprioni, Francesco; Mosconi, Stefania; Fanello, Silvia; Berardi, Rossana; Bittoni, Alessandro; Andrikou, Kalliopi; Cinquini, Michela; Torri, Valter; Scartozzi, Mario; Cascinu, Stefano

    2015-01-01

    Although lactate dehydrogenase (LDH) serum levels, indirect markers of angiogenesis, are associated with a worse outcome in several tumours, their prognostic value is not defined in pancreatic cancer. Moreover, high levels are associated even with a lack of efficacy of tyrosine kinase inhibitors, contributing to explain negative results in clinical trials. We assessed the role of LDH in advanced pancreatic cancer receiving sorafenib. Seventy-one of 114 patients included in the randomised phase II trial MAPS (chemotherapy plus or not sorafenib) and with available serum LDH levels, were included in this analysis. Patients were categorized according to serum LDH levels (LDH ≤vs.> upper normal rate). A significant difference was found in progression free survival (PFS) and in overall survival (OS) between patients with LDH values under or above the cut-off (PFS: 5.2 vs. 2.7 months, p = 0.0287; OS: 10.7 vs. 5.9 months, p = 0.0021). After stratification according to LDH serum levels and sorafenib treatment, patients with low LDH serum levels treated with sorafenib showed an advantage in PFS (p = 0.05) and OS (p = 0.0012). LDH appears to be a reliable parameter to assess the prognosis of advanced pancreatic cancer patients, and it may be a predictive parameter to select patients candidate to receive sorafenib. PMID:26397228

  20. The value of lactate dehydrogenase serum levels as a prognostic and predictive factor for advanced pancreatic cancer patients receiving sorafenib.

    PubMed

    Faloppi, Luca; Bianconi, Maristella; Giampieri, Riccardo; Sobrero, Alberto; Labianca, Roberto; Ferrari, Daris; Barni, Sandro; Aitini, Enrico; Zaniboni, Alberto; Boni, Corrado; Caprioni, Francesco; Mosconi, Stefania; Fanello, Silvia; Berardi, Rossana; Bittoni, Alessandro; Andrikou, Kalliopi; Cinquini, Michela; Torri, Valter; Scartozzi, Mario; Cascinu, Stefano

    2015-10-27

    Although lactate dehydrogenase (LDH) serum levels, indirect markers of angiogenesis, are associated with a worse outcome in several tumours, their prognostic value is not defined in pancreatic cancer. Moreover, high levels are associated even with a lack of efficacy of tyrosine kinase inhibitors, contributing to explain negative results in clinical trials. We assessed the role of LDH in advanced pancreatic cancer receiving sorafenib. Seventy-one of 114 patients included in the randomised phase II trial MAPS (chemotherapy plus or not sorafenib) and with available serum LDH levels, were included in this analysis. Patients were categorized according to serum LDH levels (LDH ≤ vs.> upper normal rate). A significant difference was found in progression free survival (PFS) and in overall survival (OS) between patients with LDH values under or above the cut-off (PFS: 5.2 vs. 2.7 months, p = 0.0287; OS: 10.7 vs. 5.9 months, p = 0.0021). After stratification according to LDH serum levels and sorafenib treatment, patients with low LDH serum levels treated with sorafenib showed an advantage in PFS (p = 0.05) and OS (p = 0.0012). LDH appears to be a reliable parameter to assess the prognosis of advanced pancreatic cancer patients, and it may be a predictive parameter to select patients candidate to receive sorafenib. PMID:26397228

  1. Claims, Evidence and Achievement Level Descriptors as a Foundation for Item Design and Test Specifications

    ERIC Educational Resources Information Center

    Hendrickson, Amy; Huff, Kristen; Luecht, Ric

    2009-01-01

    [Slides] presented at the Annual Meeting of National Council on Measurement in Education (NCME) in San Diego, CA in April 2009. This presentation describes how the vehicles for gathering student evidence--task models and test specifications--are developed.

  2. Defining cell-type specificity at the transcriptional level in human disease

    PubMed Central

    Ju, Wenjun; Greene, Casey S.; Eichinger, Felix; Nair, Viji; Hodgin, Jeffrey B.; Bitzer, Markus; Lee, Young-suk; Zhu, Qian; Kehata, Masami; Li, Min; Jiang, Song; Rastaldi, Maria Pia; Cohen, Clemens D.; Troyanskaya, Olga G.; Kretzler, Matthias

    2013-01-01

    Cell-lineage–specific transcripts are essential for differentiated tissue function, implicated in hereditary organ failure, and mediate acquired chronic diseases. However, experimental identification of cell-lineage–specific genes in a genome-scale manner is infeasible for most solid human tissues. We developed the first genome-scale method to identify genes with cell-lineage–specific expression, even in lineages not separable by experimental microdissection. Our machine-learning–based approach leverages high-throughput data from tissue homogenates in a novel iterative statistical framework. We applied this method to chronic kidney disease and identified transcripts specific to podocytes, key cells in the glomerular filter responsible for hereditary and most acquired glomerular kidney disease. In a systematic evaluation of our predictions by immunohistochemistry, our in silico approach was significantly more accurate (65% accuracy in human) than predictions based on direct measurement of in vivo fluorescence-tagged murine podocytes (23%). Our method identified genes implicated as causal in hereditary glomerular disease and involved in molecular pathways of acquired and chronic renal diseases. Furthermore, based on expression analysis of human kidney disease biopsies, we demonstrated that expression of the podocyte genes identified by our approach is significantly related to the degree of renal impairment in patients. Our approach is broadly applicable to define lineage specificity in both cell physiology and human disease contexts. We provide a user-friendly website that enables researchers to apply this method to any cell-lineage or tissue of interest. Identified cell-lineage–specific transcripts are expected to play essential tissue-specific roles in organogenesis and disease and can provide starting points for the development of organ-specific diagnostics and therapies. PMID:23950145

  3. Laying-sequence-specific variation in yolk oestrogen levels, and relationship to plasma oestrogen in female zebra finches (Taeniopygia guttata)

    PubMed Central

    Williams, Tony D.; Ames, Caroline E.; Kiparissis, Yiannis; Wynne-Edwards, Katherine E.

    2005-01-01

    We investigated the relationship between plasma and yolk oestrogens in laying female zebra finches (Taeniopygia guttata) by manipulating plasma oestradiol (E2) levels, via injection of oestradiol-17β, in a sequence-specific manner to maintain chronically high plasma levels for later-developing eggs (contrasting with the endogenous pattern of decreasing plasma E2 concentrations during laying). We report systematic variation in yolk oestrogen concentrations, in relation to laying sequence, similar to that widely reported for androgenic steroids. In sham-manipulated females, yolk E2 concentrations decreased with laying sequence. However, in E2-treated females plasma E2 levels were higher during the period of rapid yolk development of later-laid eggs, compared with control females. As a consequence, we reversed the laying-sequence-specific pattern of yolk E2: in E2-treated females, yolk E2 concentrations increased with laying-sequence. In general therefore, yolk E2 levels were a direct reflection of plasma E2 levels. However, in control females there was some inter-individual variability in the endogenous pattern of plasma E2 levels through the laying cycle which could generate variation in sequence-specific patterns of yolk hormone levels even if these primarily reflect circulating steroid levels. PMID:15695208

  4. Innovative Training Experience for Advancing Entry Level, Mid-Skilled and Professional Level URM Participation in the Geosciences Workforce

    NASA Astrophysics Data System (ADS)

    Okoro, M. H.; Johnson, A.

    2015-12-01

    The representation of URMs in the U.S. Geosciences workforce remains proportionally low compared to their representation in the general population (Bureau of Labor Sta.s.cs, 2014). Employment in this and related industries is projected to grow 32% by 2030 for minority workers (Gillula and Fullenbaum, 2014), corresponding to an additional 48,000 jobs expected to be filled by minorities (National Research Council, 2014). However, there is a shortage of employees with proper training in the hard sciences (Holeywell, 2014; Ganzglass, 2011), as well as craft skills (Hoover and Duncan, 2013), both important for middle skill employment. Industry recognizes the need for developing and retaining a diverse workforce, therefore we hightlight a program to serve as a potential vanguard initative for developing an innovative training experience for URM and underserved middle skilled workers with essential knowledge, experience and skills necessary to meet the demands of the Geosciences industry's growing need for a safe, productive and diverse workforce. Objectives are for participants to achieve the following: understanding of geosciences workforce trends and associated available opportunities; mastery of key environmental, health and safety topics; improvements in decision making skills and preparedness for responding to potential environmental, health and safety related situations; and engagement in one-on-one coaching sessions focused on resume writing, job interviewing and key "soft skills" (including conflict resolution, problem solving and critical observation, representing 3 major skills that entry- level workers typically lack.

  5. Engineered glycated amino dendritic polymers as specific nonviral gene delivery vectors targeting the receptor for advanced glycation end products.

    PubMed

    Giron-Gonzalez, M Dolores; Morales-Portillo, Arturo; Salinas-Castillo, Alfonso; Lopez-Jaramillo, F Javier; Hernandez-Mateo, Fernando; Santoyo-Gonzalez, Francisco; Salto-Gonzalez, Rafael

    2014-06-18

    The receptor for advanced glycation end products (RAGE) is involved in diabetes or angiogenesis in tumors. Under pathological conditions, RAGE is overexpressed and upon ligand binding and internalization stimulates signaling pathways that promote cell proliferation. In this work, amino dendritic polymers PEI 25 kDa and alkylated derivatives of PAMAM-G2 were engineered by the nonenzymatic Maillard glycation reaction to generate novel AGE-containing gene delivery vectors targeting the RAGE. The glycated dendritic polymers were easily prepared and retained the capability to bind and protect DNA from endonucleases. Furthermore, while glycation decreased the transfection efficiency of the dendriplexes in CHO-k1 cells which do not express RAGE, glycated dendriplexes acted as efficient transfection reagents in CHO-k1 cells which stably express recombinant RAGE. In addition, preincubation with BSA-AGEs, a natural ligand of the RAGE, or dansyl cadaverine, an inhibitor of the RAGE internalization, blocked transfection, confirming their specificity toward RAGE. The results were confirmed in NRK and RAW264.7 cell lines, which naturally express the receptor. The glycated compounds retain their transfection efficiency in the presence of serum and promote in vivo transfection in a mouse model. Accordingly, RAGE is a suitable molecular target for the development of site-directed engineered glycated nonviral gene vectors. PMID:24852962

  6. 9p21 locus rs10757278 is associated with advanced carotid atherosclerosis in a gender-specific manner.

    PubMed

    Zivotić, Ivan; Djurić, Tamara; Stanković, Aleksandra; Djordjević, Ana; Končar, Igor; Davidović, Lazar; Alavantić, Dragan; Zivković, Maja

    2016-06-01

    Single nucleotide polymorphisms from the chromosome locus 9p21 are reported to carry a risk for various cardiovascular diseases. One of the lead single nucleotide polymorphisms, rs10757278, was mostly investigated in association with coronary artery disease but rarely with carotid atherosclerosis. In this study, we aimed to analyze the association of rs10757278 A/G polymorphism with carotid plaque presence in advanced carotid atherosclerosis. The study included 803 participants, 486 patients with high-grade stenosis (>70%) who were undergoing carotid endarterectomy and 317 controls from Serbian population. Genotypes were determined using the real-time polymerase chain reaction. According to the recessive model of inheritance, GG genotype was significantly and independently associated with carotid plaque in females only (odds ratio 2.42, CI = 1.20-4.90, P = 0.013). Odds ratio was adjusted for age, body mass index, hypertension, TC, LDLC, HDLC and TG, and P value was corrected for multiple comparisons. Our preliminary findings suggest a gender-specific association of rs10757278 polymorphism with carotid plaque. Further studies on larger sample and in genetically and environmentally similar populations are needed. PMID:26941057

  7. On the levels of enzymatic substrate specificity: Implications for the early evolution of metabolic pathways

    NASA Technical Reports Server (NTRS)

    Lazcano, A.; Diaz-Villagomez, E.; Mills, T.; Oro, J.

    1995-01-01

    The most frequently invoked explanation for the origin of metabolic pathways is the retrograde evolution hypothesis. In contrast, according to the so-called 'patchwork' theory, metabolism evolved by the recruitment of relatively inefficient small enzymes of broad specificity that could react with a wide range of chemically related substrates. In this paper it is argued that both sequence comparisons and experimental results on enzyme substrate specificity support the patchwork assembly theory. The available evidence supports previous suggestions that gene duplication events followed by a gradual neoDarwinian accumulation of mutations and other minute genetic changes lead to the narrowing and modification of enzyme function in at least some primordial metabolic pathways.

  8. Korean Secondary School Students' Occupational Preferences across School Types: Specificity Versus Broad Levels

    ERIC Educational Resources Information Center

    Kim, Kyung-Nyun

    2015-01-01

    This study considers the specificity of 3,136 Korean students' occupational preferences during secondary school and examines whether the types of high school are related to the crystallization in occupational preferences by applying binary growth models. Based on Super's developmental stage, this study shows that students largely formulate solid…

  9. Specific siRNA Targeting Receptor for Advanced Glycation End Products (RAGE) Decreases Proliferation in Human Breast Cancer Cell Lines

    PubMed Central

    Radia, AL-Madhagi; Yaser, AL-Madhagi; Ma, Xiaoqian; Zhang, Juan; Yang, Cejun; Dong, Qiong; Rong, Pengfei; Ye, Bin; Liu, Sheng; Wang, Wei

    2013-01-01

    Receptor for Advanced Glycation End Products (RAGE) is an oncogenic trans-membranous receptor overexpressed in various human cancers. However, the role of RAGE in breast cancer development and proliferation is still unclear. In this study, we demonstrated that RAGE expression levels are correlated to the degree of severity of breast cancer. Furthermore, there is a decrease in the proliferation of all sub-types of breast cancer, MCF-7, SK-Br-3 and MDA-MB-231, as a result of the effect of RAGE siRNA. RAGE siRNA arrested cells in the G1 phase and inhibited DNA synthesis (p < 0.05). Moreover, qRT-PCR and Western Blot results demonstrated that RAGE siRNA decreases the expression of transcriptional factor NF-κB p65 as well as the expression of cell proliferation markers PCNA and cyclinD1. RAGE and RAGE ligands can thus be considered as possible targets for breast cancer management and therapy. PMID:23579957

  10. Specific siRNA targeting receptor for advanced glycation end products (RAGE) decreases proliferation in human breast cancer cell lines.

    PubMed

    Radia, Al-Madhagi; Yaser, Al-Madhagi; Ma, Xiaoqian; Zhang, Juan; Yang, Cejun; Dong, Qiong; Rong, Pengfei; Ye, Bin; Liu, Sheng; Wang, Wei

    2013-01-01

    Receptor for Advanced Glycation End Products (RAGE) is an oncogenic trans-membranous receptor overexpressed in various human cancers. However, the role of RAGE in breast cancer development and proliferation is still unclear. In this study, we demonstrated that RAGE expression levels are correlated to the degree of severity of breast cancer. Furthermore, there is a decrease in the proliferation of all sub-types of breast cancer, MCF-7, SK-Br-3 and MDA-MB-231, as a result of the effect of RAGE siRNA. RAGE siRNA arrested cells in the G1 phase and inhibited DNA synthesis (p < 0.05). Moreover, qRT-PCR and Western Blot results demonstrated that RAGE siRNA decreases the expression of transcriptional factor NF-κB p65 as well as the expression of cell proliferation markers PCNA and cyclinD1. RAGE and RAGE ligands can thus be considered as possible targets for breast cancer management and therapy. PMID:23579957

  11. Induction and maintenance of anti‐influenza antigen‐specific nasal secretory IgA levels and serum IgG levels after influenza infection in adults

    PubMed Central

    Fujimoto, Chisa; Takeda, Noriaki; Matsunaga, Atsushi; Sawada, Ayako; Tanaka, Takeshi; Kimoto, Takashi; Shinahara, Wakako; Sawabuchi, Takako; Yamaguchi, Miyoko; Hayama, Masaki; Yanagawa, Hiroaki; Yano, Mihiro; Kido, Hiroshi

    2012-01-01

    Please cite this paper as: Fujimoto et al. (2012) Induction and maintenance of anti‐influenza antigen‐specific nasal secretory IgA levels and serum IgG levels after influenza infection in adults. Influenza and Other Respiratory Viruses 6(6), 396–403. Objectives  To determine the induction and changes in anti‐influenza virus secretory IgA (s‐IgA) levels in nasal washes and serum IgG levels in patients with influenza. Methods  The study recruited 16 patients with influenza aged 35·6 ± 9·6 years in 2007/2008 and 2008/2009 seasons. Nasal washes and serum were obtained throughout the first year. Anti‐viral s‐IgA levels and neutralization activities in nasal washes, and serum anti‐viral IgG levels and hemagglutination inhibition (HI) titers were measured. Results  Anti‐viral(H1N1) s‐IgA to total IgA ratio and neutralizing antibody titer were low in nasal washes of all patients, whereas serum levels of anti‐viral IgG and HI titers varied widely at day 1·4 ± 1·0 postinfection. Both nasal s‐IgA and serum IgG levels later increased significantly, reaching peak levels at day 9·6 ± 3·3 postinfection. The induced nasal s‐IgA then returned toward the initial levels within 300 days, although the levels at day 143 ± 70 were 3·03‐fold of the initial. Individual serum IgG levels also returned toward the initial levels within 300 days, although the mean levels remained high probably because of re‐infection in a subgroup of patients. Although influenza A (H3N2) was a minor epidemic subtype in both flu seasons, a significant rise in nasal anti‐viral (H3N2) s‐IgA levels and a slightly increase in serum IgG levels were noted. Conclusion  Low levels of nasal anti‐viral s‐IgA and neutralizing antibody were noted compared with a wide range of serum anti‐viral IgG and HI titers at the onset of infection. Elevated s‐IgA and IgG returned toward the initial levels within 300 days of infection with minor

  12. Efficacy of pemetrexed-based regimen in relapsed advanced thymic epithelial tumors and its association with thymidylate synthetase level

    PubMed Central

    Qian, Xinyu; Song, Zhengbo

    2016-01-01

    Purpose Due to the rarity of thymic epithelial tumors (TET), no standard chemotherapy regimen has been identified in the relapsed setting. The aim of this study was to investigate the activity of a pemetrexed-based regimen in advanced TET as palliative treatment after failure of previous chemotherapy, and to detect its association with thymidylate synthetase (TS) level. Methods Patients with pathologically confirmed TET and treated with pemetrexed-based regimen were evaluated from 2006 to 2014 in Zhejiang Cancer Hospital. TS mRNA level was detected by real-time polymerase chain reaction. The Kaplan–Meier method was used for survival analysis. Results A total of 22 TET patients were identified, of whom eight had thymoma and 14 had thymic carcinoma. In total, the objective response rate and disease control rate of the 22 patients were 22.7% and 68.2%, respectively. Median progression-free survival and overall survival were 4.5 months and 34.9 months, respectively. A trend of lower TS mRNA levels existed in patients with disease control compared to those with progressive disease (268.0±160.5×10−4 vs 567.0±445.0×10−4, P=0.065). Conclusion Patients with advanced TET may benefit from pemetrexed-based regimen therapy. TS mRNA level is valuable for predicting the efficacy of pemetrexed in TET. PMID:27524908

  13. Atomic level understanding of site-specific interactions in Polyaniline/TiO2 composite

    NASA Astrophysics Data System (ADS)

    Chabungbam, Satyananda; Loh, G. C.; Sahariah, Munima B.; Pal, Arup R.; Pandey, Ravindra

    2016-02-01

    Spin-polarized density functional theory calculations have been performed to understand the interactions in polyaniline (PAni) and TiO2 composite at the atomic level. Binding energy calculation shows that composite structure is energetically more stable when Ti atom of TiO2 sits on top of PAni. It is also found that there is a dependency of the CBM on the site of TiO2 interaction in this composite system. The results suggest that optimization of the synthesis parameters at atomic level can be an effective way to improve the performance of a photovoltaic device based on PAni-TiO2 composite.

  14. Development of standardized specifications for screening space level integrated circuits and semiconductors

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Standardized methods are established for screening of JAN B microcircuits and JANTXV semiconductor components for space mission or other critical applications when JAN S devices are not available. General specifications are provided which outline the DPA (destructive physical analysis), environmental, electrical, and data requirements for screening of various component technologies. This standard was developed for Air Force Space Division, and is available for use by other DOD agencies, NASA, and space systems contractors for establishing common screening methods for electronic components.

  15. SPECIFIC SITES OF BONE EXPANSION DEPEND ON THE LEVEL OF VOLLEYBALL PRACTICE IN PREPUBESCENT BOYS

    PubMed Central

    Zouch, M.; Zribi, A.; Bouajina, E.; Zaouali, M.; Tabka, Z.

    2013-01-01

    The purpose of this study was to investigate the effect of 18 months of high and low levels of volleyball practice on bone acquisition. 130 prepubescent boys (mean age 11.4 ± 0.7) were divided into a high-level training group (HLG), low-level training group (LLG), and controls. Bone mineral content (BMC) and bone area at the whole body, lumbar spine L2-L4, femoral neck of the dominant leg, and right and left radius were measured using dual-photon X-ray absorptiometry. Enhanced BMC resulted from high-training volleyball activity in all measured sites except the third left and right distal radius, which is not modified by low-level training in prepubescent players but it was accompanied by a bone area expansion in radius and weight-bearing sites for the HLG, and in legs, whole right and left radius for the LLG. Significant improvement of skeletal tissues is associated with the intensity and duration of volleyball training. PMID:24744493

  16. Research in Workplace Literacy: The Level of Literacy Required in Specific Occupations. Final Report.

    ERIC Educational Resources Information Center

    Grover, Jane G.; And Others

    A study identified trends influencing the literacy requirements of two entry-level jobs at each of three manufacturing sites and three hospital sites. Data were collected through observation, interviews, and focus groups with workers, employers, and union representatives. Materials that workers were expected to read were analyzed. The study…

  17. Association between the Advanced Glycosylation End Product-Specific Receptor Gene and Cardiovascular Death in Older Men

    PubMed Central

    Biros, Erik; Moran, Corey S.; Norman, Paul E.; Hankey, Graeme J.; Yeap, Bu B.; Almeida, Osvaldo P.; Flicker, Leon; White, Richard; Jones, Rhondda; Golledge, Jonathan

    2015-01-01

    Advanced glycosylation end product-specific receptor (AGER) signaling has been implicated in atherosclerosis. The aim of this study was to evaluate whether a common genetic variation in the AGER gene is associated with cardiovascular (CV) death. We included 1304 older men who were genotyped for rs1035798:C>T, which is a single nucleotide polymorphism (SNP) mapped to the third intron of AGER. Cox proportional hazard analysis was used to estimate the association of rs1035798:C>T with CV death. In addition we analyzed total RNA extracted from carotid atherosclerosis biopsies of 18 patients that did or did not have recent symptoms of cerebral embolization by quantitative real-time reverse transcription PCR (qRT-PCR). The minor T-allele of rs1035798:C>T was found to be associated with CV death under dominant (HR = 1.43, 95% CI: 1.01–2.02, P = 0.04) and recessive (HR = 2.05, 95% CI: 1.11–3.81, P = 0.02) models of inheritance even after adjustment for traditional cardiovascular risk factors. No association was found between rs1035798:C>T and non-CV death. qRT-PCR results suggested that median relative expression of AGER isoform 1 and isoform 6 transcripts were approximately 6- (P = 0.01) and 2-fold (P = 0.02) greater, respectively, within carotid biopsies of symptomatic compared to asymptomatic patients. These data suggest that the minor (T) allele of rs1035798:C>T represents an independent susceptibility factor for CV death. The expression of AGER isoforms is different in atheroma from patients with recent symptoms. Further studies are needed to investigate if rs1035798:C>T influences the alternative splicing of AGER. PMID:26226616

  18. Research, development and demonstration of advanced lead-acid batteries for utility load leveling

    NASA Astrophysics Data System (ADS)

    1983-08-01

    An advanced lead acid storage battery was developed to the preprototype cell and module design stage. Each module is equipped with a low cost tray, automatic watering system, and air-lift pumps for increased acid circulation in each cell. With the qualified alloy catastrophic positive grid corrosion will not limit cell cycle life. An accelerated shallow cycle regime at room ambient tested 60 cell designs for the active material shedding failure mode. It is found that an antishedding active material additive reduces positive active material shedding significantly and extend the cycle life of both the positive and the negative plate. Equations relating cell design to deep cycle life are developed from the factorial tests on the 60 cells.

  19. Prompting Secondary Students' Use of Criteria, Feedback Specificity and Feedback Levels during an Investigative Task

    ERIC Educational Resources Information Center

    Gan, Mark J. S.; Hattie, John

    2014-01-01

    This study investigates the effects of prompting on secondary students' written peer feedback in chemistry investigation reports. In particular, we examined students' feedback features in relation to the use of criteria, feedback specificity, and feedback levels. A quasi-experimental pre-test post-test design was adopted. Reviewers in…

  20. Individual Participation in Organizational Information Commons: The Impact of Team Level Social Influence and Technology-Specific Competence

    ERIC Educational Resources Information Center

    Yuan, Yu; Fulk, Janet; Shumate, Michelle; Monge, Peter R.; Bryant, J. Alison; Matsaganis, Matthew

    2005-01-01

    This research extended earlier public goods research on individual incentives to use an organizational information commons that was based in Marwell and Oliver's (1993) collective action model. A revised theoretical model that incorporated team-level social influence and technology-specific competence was proposed. The model was tested using…

  1. Genome of The Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels.

    PubMed

    van Leeuwen, Elisabeth M; Karssen, Lennart C; Deelen, Joris; Isaacs, Aaron; Medina-Gomez, Carolina; Mbarek, Hamdi; Kanterakis, Alexandros; Trompet, Stella; Postmus, Iris; Verweij, Niek; van Enckevort, David J; Huffman, Jennifer E; White, Charles C; Feitosa, Mary F; Bartz, Traci M; Manichaikul, Ani; Joshi, Peter K; Peloso, Gina M; Deelen, Patrick; van Dijk, Freerk; Willemsen, Gonneke; de Geus, Eco J; Milaneschi, Yuri; Penninx, Brenda W J H; Francioli, Laurent C; Menelaou, Androniki; Pulit, Sara L; Rivadeneira, Fernando; Hofman, Albert; Oostra, Ben A; Franco, Oscar H; Mateo Leach, Irene; Beekman, Marian; de Craen, Anton J M; Uh, Hae-Won; Trochet, Holly; Hocking, Lynne J; Porteous, David J; Sattar, Naveed; Packard, Chris J; Buckley, Brendan M; Brody, Jennifer A; Bis, Joshua C; Rotter, Jerome I; Mychaleckyj, Josyf C; Campbell, Harry; Duan, Qing; Lange, Leslie A; Wilson, James F; Hayward, Caroline; Polasek, Ozren; Vitart, Veronique; Rudan, Igor; Wright, Alan F; Rich, Stephen S; Psaty, Bruce M; Borecki, Ingrid B; Kearney, Patricia M; Stott, David J; Adrienne Cupples, L; Jukema, J Wouter; van der Harst, Pim; Sijbrands, Eric J; Hottenga, Jouke-Jan; Uitterlinden, Andre G; Swertz, Morris A; van Ommen, Gert-Jan B; de Bakker, Paul I W; Eline Slagboom, P; Boomsma, Dorret I; Wijmenga, Cisca; van Duijn, Cornelia M

    2015-01-01

    Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of The Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value <6.61 × 10(-4)), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (βLDL-C=0.135, βTC=0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR. PMID:25751400

  2. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

    PubMed Central

    van Leeuwen, Elisabeth M.; Karssen, Lennart C.; Deelen, Joris; Isaacs, Aaron; Medina-Gomez, Carolina; Mbarek, Hamdi; Kanterakis, Alexandros; Trompet, Stella; Postmus, Iris; Verweij, Niek; van Enckevort, David J.; Huffman, Jennifer E.; White, Charles C.; Feitosa, Mary F.; Bartz, Traci M.; Manichaikul, Ani; Joshi, Peter K.; Peloso, Gina M.; Deelen, Patrick; van Dijk, Freerk; Willemsen, Gonneke; de Geus, Eco J.; Milaneschi, Yuri; Penninx, Brenda W.J.H.; Francioli, Laurent C.; Menelaou, Androniki; Pulit, Sara L.; Rivadeneira, Fernando; Hofman, Albert; Oostra, Ben A.; Franco, Oscar H.; Leach, Irene Mateo; Beekman, Marian; de Craen, Anton J.M.; Uh, Hae-Won; Trochet, Holly; Hocking, Lynne J.; Porteous, David J.; Sattar, Naveed; Packard, Chris J.; Buckley, Brendan M.; Brody, Jennifer A.; Bis, Joshua C.; Rotter, Jerome I.; Mychaleckyj, Josyf C.; Campbell, Harry; Duan, Qing; Lange, Leslie A.; Wilson, James F.; Hayward, Caroline; Polasek, Ozren; Vitart, Veronique; Rudan, Igor; Wright, Alan F.; Rich, Stephen S.; Psaty, Bruce M.; Borecki, Ingrid B.; Kearney, Patricia M.; Stott, David J.; Adrienne Cupples, L.; Neerincx, Pieter B.T.; Elbers, Clara C.; Francesco Palamara, Pier; Pe'er, Itsik; Abdellaoui, Abdel; Kloosterman, Wigard P.; van Oven, Mannis; Vermaat, Martijn; Li, Mingkun; Laros, Jeroen F.J.; Stoneking, Mark; de Knijff, Peter; Kayser, Manfred; Veldink, Jan H.; van den Berg, Leonard H.; Byelas, Heorhiy; den Dunnen, Johan T.; Dijkstra, Martijn; Amin, Najaf; Joeri van der Velde, K.; van Setten, Jessica; Kattenberg, Mathijs; van Schaik, Barbera D.C.; Bot, Jan; Nijman, Isaäc J.; Mei, Hailiang; Koval, Vyacheslav; Ye, Kai; Lameijer, Eric-Wubbo; Moed, Matthijs H.; Hehir-Kwa, Jayne Y.; Handsaker, Robert E.; Sunyaev, Shamil R.; Sohail, Mashaal; Hormozdiari, Fereydoun; Marschall, Tobias; Schönhuth, Alexander; Guryev, Victor; Suchiman, H. Eka D.; Wolffenbuttel, Bruce H.; Platteel, Mathieu; Pitts, Steven J.; Potluri, Shobha; Cox, David R.; Li, Qibin; Li, Yingrui; Du, Yuanping; Chen, Ruoyan; Cao, Hongzhi; Li, Ning; Cao, Sujie; Wang, Jun; Bovenberg, Jasper A.; Jukema, J. Wouter; van der Harst, Pim; Sijbrands, Eric J.; Hottenga, Jouke-Jan; Uitterlinden, Andre G.; Swertz, Morris A.; van Ommen, Gert-Jan B.; de Bakker, Paul I.W.; Eline Slagboom, P.; Boomsma, Dorret I.; Wijmenga, Cisca; van Duijn, Cornelia M.

    2015-01-01

    Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value <6.61 × 10−4), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (βLDL-C=0.135, βTC=0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR. PMID:25751400

  3. Educational level and risk of colorectal cancer in EPIC with specific reference to tumor location.

    PubMed

    Leufkens, Anke M; Van Duijnhoven, Fränzel J B; Boshuizen, Hendriek C; Siersema, Peter D; Kunst, Anton E; Mouw, Traci; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Morois, Sophie; Krogh, Vittorio; Tumino, Rosario; Panico, Salvatore; Polidoro, Silvia; Palli, Domenico; Kaaks, Rudolf; Teucher, Birgit; Pischon, Tobias; Trichopoulou, Antonia; Orfanos, Philippos; Goufa, Ioulia; Peeters, Petra H M; Skeie, Guri; Braaten, Tonje; Rodríguez, Laudina; Lujan-Barroso, Leila; Sánchez-Pérez, Maria-José; Navarro, Carmen; Barricarte, Aurelio; Zackrisson, Sophia; Almquist, Martin; Hallmans, Goran; Palmqvist, Richard; Tsilidis, Konstantinos K; Khaw, Kay-Tee; Wareham, Nick; Gallo, Valentina; Jenab, Mazda; Riboli, Elio; Bueno-de-Mesquita, H Bas

    2012-02-01

    Existing evidence is inconclusive on whether socioeconomic status (SES) and educational inequalities influence colorectal cancer (CRC) risk, and whether low or high SES/educational level is associated with developing CRC. The aim of our study was to investigate the relationship between educational level and CRC. We studied data from 400,510 participants in the EPIC (European Prospective Investigation into Cancer and Nutrition) study, of whom 2,447 developed CRC (colon: 1,551, rectum: 896, mean follow-up 8.3 years). Cox proportional hazard regression analysis stratified by age, gender and center, and adjusted for potential confounders were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI). Relative indices of inequality (RII) for education were estimated using Cox regression models. We conducted separate analyses for tumor location, gender and geographical region. Compared with participants with college/university education, participants with vocational secondary education or less had a nonsignificantly lower risk of developing CRC. When further stratified for tumor location, adjusted risk estimates for the proximal colon were statistically significant for primary education or less (HR 0.73, 95%CI 0.57-0.94) and for vocational secondary education (HR 0.76, 95%CI 0.58-0.98). The inverse association between low education and CRC risk was particularly found in women and Southern Europe. These associations were statistically significant for CRC, for colon cancer and for proximal colon cancer. In conclusion, CRC risk, especially in the proximal colon, is lower in subjects with a lower educational level compared to those with a higher educational level. This association is most pronounced in women and Southern Europe. PMID:21412763

  4. Molecular epidemiology and strain-specific characteristics of Streptococcus agalactiae at the herd and cow level.

    PubMed

    Mahmmod, Y S; Klaas, I C; Katholm, J; Lutton, M; Zadoks, R N

    2015-10-01

    Host-adaptation of Streptococcus agalactiae subpopulations has been described whereby strains that are commonly associated with asymptomatic carriage or disease in people differ phenotypically and genotypically from those causing mastitis in dairy cattle. Based on multilocus sequence typing (MLST), the most common strains in dairy herds in Denmark belong to sequence types (ST) that are also frequently found in people. The aim of this study was to describe epidemiological and diagnostic characteristics of such strains in relation to bovine mastitis. Among 1,199 cattle from 6 herds, cow-level prevalence of S. agalactiae was estimated to be 27.4% based on PCR and 7.8% based on bacteriological culture. Quarter-level prevalence was estimated at 2.8% based on bacteriological culture. Per herd, between 2 and 26 isolates were characterized by pulsed-field gel electrophoresis (PFGE) and MLST. Within each herd, a single PFGE type and ST predominated, consistent with a contagious mode of transmission or point source infection within herds. Evidence of within-herd evolution of S. agalactiae was detected with both typing methods, although ST belonged to a single clonal complex (CC) per herd. Detection of CC23 (3 herds) was associated with significantly lower approximate count (colony-forming units) at the quarter level and significantly lower cycle threshold value at the cow level than detection of CC1 (2 herds) or CC19 (1 herd), indicating a lower bacterial load in CC23 infections. Median values for the number of infected quarters and somatic cell count (SCC) were numerically but not significantly lower for cows infected with CC23 than for cows with CC1 or CC19. For all CC, an SCC threshold of 200,000 cells/mL was an unreliable indicator of infection status, and prescreening of animals based on SCC as part of S. agalactiae detection and eradication campaigns should be discouraged. PMID:26233443

  5. Ground-water levels, flow, and specific conductance in unconsolidated aquifers near Lake Erie, Cleveland to Conneaut, Ohio, September 1984

    USGS Publications Warehouse

    Coen, A. W., III

    1990-01-01

    This report described ground-water levels, flow, and specific conductance in aquifer along the southern shore of Lake Erie from Cleveland to Conneaut, Ohio. The data were collected in September 1984 as part of the U.S Geological Survey's Northeast Glacial Buried Valley Regional Aquifer-System Analysis. The study area is about 60 miles long, extends inland from the lake about 10 miles, and encompasses parts of Cuyahoga, Lake, and Ashtabula Counties. Water levels were measured in 202 existing wells, all of which were completed in the glacial deposits or at the contact with the underlying shale. Specific conductance was measured in 59 of the wells. Results o the survey are presented in table and map form. Unconsolidated material throughout the area consists primarily of till, whereas the bedrock consists of Devonian shale. The till is composed chiefly o silt and clay with some sand and gravel, and is less than 50 feet thick in most areas. Some valleys are filled with as much as 200 feet of glacial till and outwash deposits that are mainly sand and gravel. Ground-water levels in much of the area within 20 feet of the land surface. Contours of ground-water levels resemble a subdued version of those of the land surface, which indicates that ground water generally flows from high areas to low areas following the land-surface gradient. Locally, ground water discharges into streams. Regionally, flow is towards the north-northeast, to Lake Erie. Specific conductance ranged from 160 to 2,900 ?S/cm (microsiemens per centimeter at 25 degrees Celsius) with a median of 540 ?S/cm. Ground water with a specific conductance greater than 650 ?S/cm is localized, with no specific spatial pattern; possible sources of elevated specific conductance are road-deicing salt, leachate from landfills, natural brings associated with oil and gas drilling, and the leakage of saline water from bedrock.

  6. Spaceflight has compartment- and gene-specific effects on mRNA levels for bone matrix proteins in rat femur

    NASA Technical Reports Server (NTRS)

    Evans, G. L.; Morey-Holton, E.; Turner, R. T.

    1998-01-01

    In the present study, we evaluated the possibility that the abnormal bone matrix produced during spaceflight may be associated with reduced expression of bone matrix protein genes. To test this possibility, we investigated the effects of a 14-day spaceflight (SLS-2 experiment) on steady-state mRNA levels for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), osteocalcin, osteonectin, and prepro-alpha(1) subunit of type I collagen in the major bone compartments of rat femur. There were pronounced site-specific differences in the steady-state levels of expression of the mRNAs for the three bone matrix proteins and GAPDH in normal weight-bearing rats, and these relationships were altered after spaceflight. Specifically, spaceflight resulted in decreases in mRNA levels for GAPDH (decreased in proximal metaphysis), osteocalcin (decreased in proximal metaphysis), osteonectin (decreased in proximal and distal metaphysis), and collagen (decreased in proximal and distal metaphysis) compared with ground controls. There were no changes in mRNA levels for matrix proteins or GAPDH in the shaft and distal epiphysis. These results demonstrate that spaceflight leads to site- and gene-specific decreases in mRNA levels for bone matrix proteins. These findings are consistent with the hypothesis that spaceflight-induced decreases in bone formation are caused by concomitant decreases in expression of genes for bone matrix proteins.

  7. Activity Level-Dependent Synapse-Specific AMPA Receptor Trafficking Regulates Transmission Kinetics

    PubMed Central

    Zhu, J. Julius

    2009-01-01

    Central glutamatergic synapses may express AMPA-sensitive glutamate receptors (AMPA-Rs) with distinct gating properties and exhibit different transmission dynamics, which are important for computing various synaptic inputs received at different populations of synapses. However, how glutamatergic synapses acquire AMPA-Rs with distinct kinetics to influence synaptic integration remains poorly understood. Here I report synapse-specific trafficking of distinct AMPA-Rs in rat cortical layer 4 stellate and layer 5 pyramidal neurons. The analysis indicates that in single layer 4 stellate neurons thalamocortical synapses generate faster synaptic responses than intracortical synapses. Moreover, GluR1-containing AMPA-Rs traffic selectively into intracortical synapses, and this process requires sensory experience-dependent activity and slows down transmission kinetics. GluR4-containing AMPA-Rs traffic more heavily into thalamocortical synapses than intracortical synapses, and this process requires spontaneous synaptic activity and speeds up transmission kinetics. GluR2-containing AMPA-Rs traffic equally into both thalamocortical and intracortical synapses, and this process requires no synaptic activity and resets transmission kinetics. Notably, synaptic trafficking of distinct AMPA-Rs differentially regulates synaptic integration. Thus, synapse-specific AMPA-R trafficking coarsely sets and synaptic activity finely tunes transmission kinetics and integration properties at different synapses in central neurons. PMID:19439609

  8. The relative effectiveness of segment specific level and non-specific level spinal joint mobilization on pain and range of motion: results of a systematic review and meta-analysis

    PubMed Central

    Slaven, Emily Joan; Goode, Adam P; Coronado, Rogelio A; Poole, Charles; Hegedus, Eric J

    2013-01-01

    Study design: Systematic literature review and meta-analysis. Objective: In symptomatic subjects to: (1) examine the effects of a single session of joint mobilization on pain at rest and with most painful movement, and (2) compare the effects when joint mobilization is provided to a specific or non-specific spinal level. Background: Joint mobilization is routinely used for treating spinal pain in conjunction with other interventions, but its unique effect is not well understood. Further, there is controversy about the role of ‘specific level’ techniques in producing benefit. Methods: Searches were performed for randomized controlled trials (RCTs) using electronic databases (MEDLINE, CINAHL, and PEDro) from 1966 through November 2010. Methodological quality was assessed using previously detailed criteria. Meta-analysis and meta-regression were conducted on eligible studies. Results: Eight RCTs with a mean methodological score of 10/12 were included. Significant heterogeneity (P = 0.075) was found in the overall meta-analysis estimate. When stratified by body location, no significant individual effect was found for pain at rest. However, there was a statistical mean difference [0.71 (95% confidence interval: 0.13–1.28)] between pain at rest for the cervical and lumbar individual means. Conclusions: We found multiple studies which provided evidence that a single session of joint mobilization can lead to a reduction of pain at rest and with most painful movement. When using joint mobilization, the need for specific versus non-specific level mobilization may be influenced by anatomical region; the direction of effect in the cervical spine was toward specific mobilization and in the lumbar spine towards non-specific mobilization. PMID:24421608

  9. Plasma Proteins Modified by Advanced Glycation End Products (AGEs) Reveal Site-specific Susceptibilities to Glycemic Control in Patients with Type 2 Diabetes.

    PubMed

    Greifenhagen, Uta; Frolov, Andrej; Blüher, Matthias; Hoffmann, Ralf

    2016-04-29

    Protein glycation refers to the reversible reaction between aldoses (or ketoses) and amino groups yielding relatively stable Amadori (or Heyns) products. Consecutive oxidative cleavage reactions of these products or the reaction of amino groups with other reactive substances (e.g. α-dicarbonyls) yield advanced glycation end products (AGEs) that can alter the structures and functions of proteins. AGEs have been identified in all organisms, and their contents appear to rise with some diseases, such as diabetes and obesity. Here, we report a pilot study using highly sensitive and specific proteomics approach to identify and quantify AGE modification sites in plasma proteins by reversed phase HPLC mass spectrometry in tryptic plasma digests. In total, 19 AGE modification sites corresponding to 11 proteins were identified in patients with type 2 diabetes mellitus under poor glycemic control. The modification degrees of 15 modification sites did not differ among cohorts of normoglycemic lean or obese and type 2 diabetes mellitus patients under good and poor glycemic control. The contents of two amide-AGEs in human serum albumin and apolipoprotein A-II were significantly higher in patients with poor glycemic control, although the plasma levels of both proteins were similar among all plasma samples. These two modification sites might be useful to predict long term, AGE-related complications in diabetic patients, such as impaired vision, increased arterial stiffness, or decreased kidney function. PMID:26933035

  10. Age-specific profiles of tissue-level composition and mechanical properties in murine cortical bone

    PubMed Central

    Raghavan, Mekhala; Sahar, Nadder D.; Kohn, David H.; Morris, Michael D.

    2012-01-01

    There is growing evidence that bone composition and tissue-level mechanical properties are significant determinants of skeletal integrity. In the current study, Raman spectroscopy and nanoindentation testing were co-localized to analyze tissue-level compositional and mechanical properties in skeletally mature young (4 or 5 months) and old (19 months) murine femora at similar spatial scales. Standard multivariate linear regression analysis revealed age-dependent patterns in the relationships between mechanical and compositional properties at the tissue scale. However, changes in bone material properties with age are often complex and nonlinear, and can be missed with linear regression and correlation-based methods. A retrospective data mining approach was implemented using non-linear multidimensional visualization and classification to identify spectroscopic and nanoindentation metrics that best discriminated bone specimens of different age-classes. The ability to classify the specimens into the correct age group increased by using combinations of Raman and nanoindentation variables (86–96% accuracy) as compared to using individual measures (59–79% accuracy). Metrics that best classified 4 or 5 month and 19 month specimens (2-age classes) were mineral to matrix ratio, crystallinity, modulus and plasticity index. Metrics that best distinguished between 4, 5 and 19 month specimens (3-age classes) were mineral to matrix ratio, crystallinity, modulus, hardness, cross-linking, carbonate to phosphate ratio, creep displacement and creep viscosity. These findings attest to the complexity of mechanisms underlying bone tissue properties and draw attention to the importance of considering non-linear interactions between tissue-level composition and mechanics that may work together to influence material properties with age. The results demonstrate that a few non-linearly combined compositional and mechanical metrics provide better discriminatory information than a single

  11. Axial level-specific regulation of neuronal development: lessons from PITX2.

    PubMed

    Waite, Mindy R; Martin, Donna M

    2015-02-01

    Transcriptional regulation of gene expression is vital for proper control of proliferation, migration, differentiation, and survival of developing neurons. Pitx2 encodes a homeodomain transcription factor that is highly expressed in the developing and adult mammalian brain. In humans, mutations in PITX2 result in Rieger syndrome, characterized by defects in the development of the eyes, umbilicus, and teeth and variable abnormalities in the brain, including hydrocephalus and cerebellar hypoplasia. Alternative splicing of Pitx2 in the mouse results in three isoforms, Pitx2a, Pitx2b, and Pitx2c, each of which is expressed symmetrically along the left-right axis of the brain throughout development. Here, we review recent evidence for axial and brain region-specific requirements for Pitx2 during neuronal migration and differentiation, highlighting known isoform contributions. PMID:25124216

  12. Ferulenol specifically inhibits succinate ubiquinone reductase at the level of the ubiquinone cycle

    SciTech Connect

    Lahouel, Mesbah; Zini, Roland; Zellagui, Ammar; Rhouati, Salah; Carrupt, Pierre-Alain; Morin, Didier; E-mail: didier.morin@creteil.inserm.fr

    2007-03-30

    The natural compound ferulenol, a sesquiterpene prenylated coumarin derivative, was purified from Ferula vesceritensis and its mitochondrial effects were studied. Ferulenol caused inhibition of oxidative phoshorylation. At low concentrations, ferulenol inhibited ATP synthesis by inhibition of the adenine nucleotide translocase without limitation of mitochondrial respiration. At higher concentrations, ferulenol inhibited oxygen consumption. Ferulenol caused specific inhibition of succinate ubiquinone reductase without altering succinate dehydrogenase activity of the complex II. This inhibition results from a limitation of electron transfers initiated by the reduction of ubiquinone to ubiquinol in the ubiquinone cycle. This original mechanism of action makes ferulenol a useful tool to study the physiological role and the mechanism of electron transfer in the complex II. In addition, these data provide an additional mechanism by which ferulenol may alter cell function and demonstrate that mitochondrial dysfunction is an important determinant in Ferula plant toxicity.

  13. An advanced static var compensator based on a three level IGBT inverter modelling analysis and active power filtering

    NASA Astrophysics Data System (ADS)

    Draou, Azeddine

    2012-12-01

    This paper presents the dynamic performance analysis of an Advanced Static Var Compensator (ASVC) using three-level neutral point-clamped voltage source inverter. The paper presents the principles of operating and the method of reference currents generation. The dynamic behaviour of the system is further analysed using Matlab/Simulink with SimPower Systems toolbox through a set of simulation tests. The results obtained have been applied to an active power filter which might lead to the design of a robust controller for current harmonics and reactive power applications

  14. Contact, Attitude and Motivation in the Learning of Catalan at Advanced Levels

    ERIC Educational Resources Information Center

    Hamilton, Colleen; Serrano, Raquel

    2015-01-01

    The theoretical complexity of current understandings of second language (L2) identity has brought the study of language learning motivations from basic concepts of intrinsic, integrative and instrumental motives to a more dynamic construct that interacts with background factors, learning contexts and proficiency levels. This cross-sectional study…

  15. Advanced Monitoring Initiative Project: US-Mexico Border Ground-level Ozone

    EPA Science Inventory

    Ground-Level Ozone Concentrations Based on Satellite Observations and Ground Surface Monitoring Data in Support of Environmental Health Decisions U.S. - Mexico Border 2012 Program - The U.S.-Mexico border is a dynamic region extending more than 3,100 kilometers from the Gulf of M...

  16. Homemade Equipment for the Teaching of Electrochemistry at Advanced Level. Part II.

    ERIC Educational Resources Information Center

    Chan, K. M.

    1985-01-01

    Provides a detailed description for the construction of equipment needed to investigate acid/base equilibria through the measurement of pH and potentiometric titrations. Suggested experiments and calibration techniques are explained. This information helps to solve the problems of inadequate, expensive equipment required for A-level chemistry…

  17. Methods for Determining the Level of Autonomy to Design into a Human Spaceflight Vehicle: A Function Specific Approach

    NASA Technical Reports Server (NTRS)

    Proud, Ryan W.; Hart, Jeremy J.; Mrozinski, Richard B.

    2003-01-01

    The next-generation human spaceflight vehicle is in a unique position to realize the benefits of more than thirty years of technological advancements since the Space Shuttle was designed. Computer enhancements, the emergence of highly reliable decision-making algorithms, and an emphasis on efficiency make an increased use of autonomous systems highly likely. NASA is in a position to take advantage of these advances and apply them to the human spaceflight environment. One of the key paradigm shifts will be the shift, where appropriate, of monitoring, option development, decision-making, and execution responsibility from humans to an Autonomous Flight Management (AFM) system. As an effort to reduce risk for development of an AFM system, NASA engineers are developing a prototype to prove the utility of previously untested autonomy concepts. This prototype, called SMART (Spacecraft Mission Assessment and Replanning Tool), is a functionally decomposed flight management system with an appropriate level of autonomy for each of its functions. As the development of SMART began, the most important and most often asked question was, How autonomous should an AFM system be? A thorough study of the literature through 2002 surrounding autonomous systems has not yielded a standard method for designing a level of autonomy into either a crewed vehicle or an uncrewed vehicle. The current focus in the literature on defining autonomy is centered on developing IQ tests for built systems. The literature that was analyzed assumes that the goal of all systems is to strive for complete autonomy from human intervention, rather than identifying how autonomous each function within the system should have been. In contrast, the SMART team developed a method for determining the appropriate level of autonomy to be designed into each function within a system. This paper summarizes the development of the Level of Autonomy Assessment Tool and its application to the SMART project.

  18. Developing patient-specific dose protocols for a CT scanner and exam using diagnostic reference levels.

    PubMed

    Strauss, Keith J

    2014-10-01

    The management of image quality and radiation dose during pediatric CT scanning is dependent on how well one manages the radiographic techniques as a function of the type of exam, type of CT scanner, and patient size. The CT scanner's display of expected CT dose index volume (CTDIvol) after the projection scan provides the operator with a powerful tool prior to the patient scan to identify and manage appropriate CT techniques, provided the department has established appropriate diagnostic reference levels (DRLs). This paper provides a step-by-step process that allows the development of DRLs as a function of type of exam, of actual patient size and of the individual radiation output of each CT scanner in a department. Abdomen, pelvis, thorax and head scans are addressed. Patient sizes from newborns to large adults are discussed. The method addresses every CT scanner regardless of vendor, model or vintage. We cover adjustments to techniques to manage the impact of iterative reconstruction and provide a method to handle all available voltages other than 120 kV. This level of management of CT techniques is necessary to properly monitor radiation dose and image quality during pediatric CT scans. PMID:25037975

  19. The Expression of c-Myb Correlates with the Levels of Rhabdomyosarcoma-specific Marker Myogenin

    PubMed Central

    Kaspar, Petr; Zikova, Martina; Bartunek, Petr; Sterba, Jaroslav; Strnad, Hynek; Kren, Leos; Sedlacek, Radislav

    2015-01-01

    The transcription factor c-Myb is required for modulation of progenitor cells in several tissues, including skeletal muscle and its upregulation is observed in many human malignancies. Rhabdomyosarcomas (RMS) are a heterogeneous group of mesodermal tumors with features of developing skeletal muscle. Several miRNAs are downregulated in RMS, including miR-150, a negative regulator of c-Myb expression. Using the C2C12 myoblast cell line, a cellular model of skeletal muscle differentiation, we showed that miR-150 controls c-Myb expression mainly at the level of translation. We hypothesized that a similar mechanism of c-Myb regulation operates in RMS tumors. We examined expression of c-Myb by immunohistochemistry and revealed c-Myb positivity in alveolar and embryonal tumors, the two most common subgroups of RMS. Furthermore, we showed direct correlation between c-Myb production and myogenin expression. Interestingly, high myogenin levels indicate poor prognosis in RMS patients. c-Myb could, therefore, contribute to the tumor phenotype by executing its inhibitory role in skeletal muscle differentiation. We also showed that c-Myb protein is abundant in migratory C2C12 myoblasts and its ectopic expression potentiates cell motility. In summary, our results implicate that metastatic properties of some RMS subtypes might be linked to c-Myb function. PMID:26462877

  20. The Expression of c-Myb Correlates with the Levels of Rhabdomyosarcoma-specific Marker Myogenin.

    PubMed

    Kaspar, Petr; Zikova, Martina; Bartunek, Petr; Sterba, Jaroslav; Strnad, Hynek; Kren, Leos; Sedlacek, Radislav

    2015-01-01

    The transcription factor c-Myb is required for modulation of progenitor cells in several tissues, including skeletal muscle and its upregulation is observed in many human malignancies. Rhabdomyosarcomas (RMS) are a heterogeneous group of mesodermal tumors with features of developing skeletal muscle. Several miRNAs are downregulated in RMS, including miR-150, a negative regulator of c-Myb expression. Using the C2C12 myoblast cell line, a cellular model of skeletal muscle differentiation, we showed that miR-150 controls c-Myb expression mainly at the level of translation. We hypothesized that a similar mechanism of c-Myb regulation operates in RMS tumors. We examined expression of c-Myb by immunohistochemistry and revealed c-Myb positivity in alveolar and embryonal tumors, the two most common subgroups of RMS. Furthermore, we showed direct correlation between c-Myb production and myogenin expression. Interestingly, high myogenin levels indicate poor prognosis in RMS patients. c-Myb could, therefore, contribute to the tumor phenotype by executing its inhibitory role in skeletal muscle differentiation. We also showed that c-Myb protein is abundant in migratory C2C12 myoblasts and its ectopic expression potentiates cell motility. In summary, our results implicate that metastatic properties of some RMS subtypes might be linked to c-Myb function. PMID:26462877

  1. The relationship of the urinary ascorbate metabolites to specific levels of ascorbate supplementation in the monkey

    SciTech Connect

    Tillotson, J.A.; McGown, E.L.

    1981-11-01

    This study was designed to investigate urinary ascorbic acid (AA) and its metabolites derived from (1-14C) AA administered to trained monkeys fed different levels of ascorbate for extended periods of time. A chromatographic procedure was developed which rapidly separates the urinary compounds into four major fractions with minimal degradation. The distribution of 14C in the four peaks was dependent upon the ascorbate nutritional status of the monkey and remained constant for at least 30 days postlabel. The two major fractions were identified as oxalate and unmetabolized ascorbate. The ascorbate metabolites in the two minor fractions have not been identified. In monkeys maintained on low ascorbate intakes, unmetabolized ascorbate accounted for 10 to 20% and oxalate 25 to 48% of the urinary 14C. The average percentages of 14C in the urine of monkeys fed high levels of ascorbate were 75% for ascorbate and 7% for oxalate. The urine also contained an ascorbate metabolite which degraded during storage and/or chromatography, yielding 14CO2. Ascorbate sulfate was not detected as a urinary metabolite.

  2. Serum levels of rubella-specific antibodies in Swedish women following three decades of vaccination programmes.

    PubMed

    Kakoulidou, Maria; Forsgren, Marianne; Lewensohn-Fuchs, Ilona; Johansen, Kari

    2010-01-22

    In Sweden, more than 30 years after the introduction of vaccination for 12-year-old girls and post-partum mothers against rubella and 22 years after the introduction of routine MMR vaccination for all children at the ages of 18 months and 12 years, we have evaluated the rubella IgG activity in antenatal sera. 95.8% (39,890/41,637) of all women had anti-rubella IgG levels >or=10IU/mL. Levels <10IU/mL were more frequent in certain subcohorts: 8.2% (153/1870) of the Swedish women born after the introduction of the programme of childhood vaccination, 7.7% (616/8025) of women born outside the Nordic countries and 10.2% (118/1155) of recent immigrants and refugees to Sweden. In order to attain the goal of protecting the unborn, we propose alternative strategies to be evaluated: routine screening for rubella immunity prior to the first pregnancy, offering individuals with uncertain immunity a booster dose, and/or routine administration of an additional dose of MMR vaccine to all young adults before they leave the educational system. PMID:19925909

  3. Biotechnology Apprenticeship for Secondary-Level Students: Teaching Advanced Cell Culture Techniques for Research

    PubMed Central

    Lewis, Jennifer R.; Kotur, Mark S.; Butt, Omar; Kulcarni, Sumant; Riley, Alyssa A.; Ferrell, Nick; Sullivan, Kathryn D.; Ferrari, Mauro

    2002-01-01

    The purpose of this article is to discuss small-group apprenticeships (SGAs) as a method to instruct cell culture techniques to high school participants. The study aimed to teach cell culture practices and to introduce advanced imaging techniques to solve various biomedical engineering problems. Participants designed and completed experiments using both flow cytometry and laser scanning cytometry during the 1-month summer apprenticeship. In addition to effectively and efficiently teaching cell biology laboratory techniques, this course design provided an opportunity for research training, career exploration, and mentoring. Students participated in active research projects, working with a skilled interdisciplinary team of researchers in a large research institution with access to state-of-the-art instrumentation. The instructors, composed of graduate students, laboratory managers, and principal investigators, worked well together to present a real and worthwhile research experience. The students enjoyed learning cell culture techniques while contributing to active research projects. The institution's researchers were equally enthusiastic to instruct and serve as mentors. In this article, we clarify and illuminate the value of small-group laboratory apprenticeships to the institution and the students by presenting the results and experiences of seven middle and high school participants and their instructors. PMID:12587031

  4. Biotechnology apprenticeship for secondary-level students: teaching advanced cell culture techniques for research.

    PubMed

    Lewis, Jennifer R; Kotur, Mark S; Butt, Omar; Kulcarni, Sumant; Riley, Alyssa A; Ferrell, Nick; Sullivan, Kathryn D; Ferrari, Mauro

    2002-01-01

    The purpose of this article is to discuss small-group apprenticeships (SGAs) as a method to instruct cell culture techniques to high school participants. The study aimed to teach cell culture practices and to introduce advanced imaging techniques to solve various biomedical engineering problems. Participants designed and completed experiments using both flow cytometry and laser scanning cytometry during the 1-month summer apprenticeship. In addition to effectively and efficiently teaching cell biology laboratory techniques, this course design provided an opportunity for research training, career exploration, and mentoring. Students participated in active research projects, working with a skilled interdisciplinary team of researchers in a large research institution with access to state-of-the-art instrumentation. The instructors, composed of graduate students, laboratory managers, and principal investigators, worked well together to present a real and worthwhile research experience. The students enjoyed learning cell culture techniques while contributing to active research projects. The institution's researchers were equally enthusiastic to instruct and serve as mentors. In this article, we clarify and illuminate the value of small-group laboratory apprenticeships to the institution and the students by presenting the results and experiences of seven middle and high school participants and their instructors. PMID:12587031

  5. Advanced age and the mechanics of uphill walking: a joint-level, inverse dynamic analysis

    PubMed Central

    Franz, Jason R.; Kram, Rodger

    2013-01-01

    We sought to gain insight into age-related muscular limitations that may restrict the uphill walking ability of old adults. We hypothesized that: 1) old adults would exhibit smaller peak ankle joint kinetics and larger peak hip joint kinetics than young adults during both level and uphill walking and 2) these age-related differences in ankle and hip joint kinetics would be greatest during uphill vs. level walking. We quantified the sagittal plane ankle, knee, and hip joint kinetics of 10 old adults (mean ± SD, age: 72 ± 5 yrs) and 8 young adults (age: 27 ± 5 yrs) walking at 1.25 m/s on a dual-belt, force-measuring treadmill at four grades (0°, +3°, +6°, +9°). As hypothesized, old adults walked with smaller peak ankle joint kinetics (e.g., power generation: −18% at +9°) and larger peak hip joint kinetics (e.g., power generation: +119% at +9°) than young adults, most evident during the late stance phase of both level and uphill conditions. Old adults performed two to three times more single support positive work than young adults via muscles crossing the knee. In partial support of our second hypothesis, the age-related reduction in peak ankle joint moments was greater during uphill (−0.41 Nm/kg) vs. level (−0.30 Nm/kg) walking. However, old adults that exhibited reduced propulsive ankle function during level walking could perform 44% more trailing leg positive ankle joint work to walk uphill. Our findings indicate that maintaining ankle power generation and trailing leg propulsive function should be the primary focus of “prehabilitation” strategies for old adults to preserve their uphill walking ability. PMID:23850328

  6. Sequence-specific fluorescent labeling of double-stranded DNA observed at the single molecule level

    PubMed Central

    Géron-Landre, Bénédicte; Roulon, Thibaut; Desbiolles, Pierre; Escudé, Christophe

    2003-01-01

    Fluorescent labeling of a short sequence of double-stranded DNA (dsDNA) was achieved by ligating a labeled dsDNA fragment to a stem–loop triplex forming oligonucleotide (TFO). After the TFO has wound around the target sequence by ligand-induced triple helix formation, its extremities hybridize to each other, leaving a dangling single-stranded sequence, which is then ligated to a fluorescent dsDNA fragment using T4 DNA ligase. A non-repeated 15 bp sequence present on lambda DNA was labeled and visualized by fluorescence microscopy after DNA combing. The label was found to be attached at a specific position located at 4.2 ± 0.5 kb from one end of the molecule, in agreement with the location of the target sequence for triple helix formation (4.4 kb from one end). In addition, an alternative combing process was noticed in which a DNA molecule becomes attached to the combing slide from the label rather than from one of its ends. The method described herein provides a new tool for the detection of very short sequences of dsDNA and offers various perspectives in the micromanipulation of single DNA molecules. PMID:14530458

  7. Incident-specific and individual-level moderators of brief intervention effects with mandated college students.

    PubMed

    Mastroleo, Nadine R; Murphy, James G; Colby, Suzanne M; Monti, Peter M; Barnett, Nancy P

    2011-12-01

    Brief Motivational Interventions (BMI) and Computer-delivered interventions (CDI) have been successful in reducing drinking behaviors with mandated college students. However, research examining moderators of intervention effects have found mixed results. The current study sought to replicate and extend the research on moderators of intervention efficacy with mandated students. Baseline alcohol-related problems, readiness to change, gender, incident consequences, and participant responses to the event (personal attributions about the incident, aversiveness of the incident) were examined as moderators of intervention and booster condition efficacy on alcohol use and problems. Mandated students (N = 225) were randomized to complete either a BMI or CDI (Alcohol 101; Century Council, 1998), with or without a 1-month booster session, following a campus alcohol sanction. Outcomes were measured three months after baseline. Attributions moderated intervention condition such that participants low in personal attributions for their incident showed significantly less drinking following a CDI than a BMI. Men and individuals who reported low incident aversiveness showed higher drinks per occasion after receiving a booster, while individuals high in alcohol-related problems reported fewer heavy drinking days after completing a booster session. Findings suggest that identifying specific characteristics related to the precipitating event may inform intervention approaches in this high-risk population; however, additional research is needed to offer concrete guidance to practitioners in the field. PMID:21766975

  8. Restoring specific lactobacilli levels decreases inflammation and muscle atrophy markers in an acute leukemia mouse model.

    PubMed

    Bindels, Laure B; Beck, Raphaël; Schakman, Olivier; Martin, Jennifer C; De Backer, Fabienne; Sohet, Florence M; Dewulf, Evelyne M; Pachikian, Barbara D; Neyrinck, Audrey M; Thissen, Jean-Paul; Verrax, Julien; Calderon, Pedro Buc; Pot, Bruno; Grangette, Corinne; Cani, Patrice D; Scott, Karen P; Delzenne, Nathalie M

    2012-01-01

    The gut microbiota has recently been proposed as a novel component in the regulation of host homeostasis and immunity. We have assessed for the first time the role of the gut microbiota in a mouse model of leukemia (transplantation of BaF3 cells containing ectopic expression of Bcr-Abl), characterized at the final stage by a loss of fat mass, muscle atrophy, anorexia and inflammation. The gut microbial 16S rDNA analysis, using PCR-Denaturating Gradient Gel Electrophoresis and quantitative PCR, reveals a dysbiosis and a selective modulation of Lactobacillus spp. (decrease of L. reuteri and L. johnsonii/gasseri in favor of L. murinus/animalis) in the BaF3 mice compared to the controls. The restoration of Lactobacillus species by oral supplementation with L. reuteri 100-23 and L. gasseri 311476 reduced the expression of atrophy markers (Atrogin-1, MuRF1, LC3, Cathepsin L) in the gastrocnemius and in the tibialis, a phenomenon correlated with a decrease of inflammatory cytokines (interleukin-6, monocyte chemoattractant protein-1, interleukin-4, granulocyte colony-stimulating factor, quantified by multiplex immuno-assay). These positive effects are strain- and/or species-specific since L. acidophilus NCFM supplementation does not impact on muscle atrophy markers and systemic inflammation. Altogether, these results suggest that the gut microbiota could constitute a novel therapeutic target in the management of leukemia-associated inflammation and related disorders in the muscle. PMID:22761662

  9. Recent advances in the compilation of holocene relative Sea-level database in North America

    NASA Astrophysics Data System (ADS)

    Horton, B.; Vacchi, M.; Engelhart, S. E.; Nikitina, D.

    2015-12-01

    Reconstruction of relative sea level (RSL) has implications for investigation of crustal movements, calibration of earth rheology models and the reconstruction of ice sheets. In recent years, efforts were made to create RSL databases following a standardized methodology. These regional databases provided a framework for developing our understanding of the primary mechanisms of RSL change since the Last Glacial Maximum and a long-term baseline against which to gauge changes in sea-level during the 20th century and forecasts for the 21st. Here we present two quality-controlled Holocene RSL database compiled for North America. Along the Pacific coast of North America (British Columbia, Canada to California, USA), our re-evaluation of sea-level indicators from geological and archaeological investigations yield 841 RSL data-points mainly from salt and freshwater wetlands or adjacent estuarine sediment as well as from isolation basin. Along the Atlantic coast of North America (Hudson Bay, Canada to South Carolina, USA), we are currently compiling a database including more than 2000 RSL data-points from isolation basin, salt and freshwater wetlands, beach ridges and intratidal deposits. We outline the difficulties and solutions we made to compile databases in such different depostional environment. We address complex tectonics and the framework to compare such large variability of RSL data-point. We discuss the implications of our results for the glacio-isostatic adjustment (GIA) models in the two studied regions.

  10. Neuron-specific enolase levels in drug-naïve young adults with major depressive disorder.

    PubMed

    Wiener, Carolina David; Molina, Mariane Lopez; Passos, Miguel; Moreira, Fernanda Pedrotti; Bittencourt, Guilherme; de Mattos Souza, Luciano Dias; da Silva, Ricardo Azevedo; Jansen, Karen; Oses, Jean Pierre

    2016-05-01

    The aim of this study is to assess neuron-specific enolase (NSE) levels and clinical features in subjects with major depressive disorder (MDD). This is a cross-sectional study with drug-naïve young adults with MDD (aged 18-29 years). Serum levels of NSE were assessed using the electrochemiluminescence method. MDD diagnosis, suicidal ideation, and time of disease were assessed using the Structured Clinical Interview for DSM-IV (SCID). The Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) were used to assess depressive and anxiety symptoms. No relationship was observed between NSE levels and severity of depressive and anxiety symptoms, time of disease, and suicidal ideation. These results suggest that NSE serum levels were not associated with clinical features of MDD among drug-naïve young adults. PMID:27026487

  11. Different levels of food restriction reveal genotype-specific differences in learning a visual discrimination task.

    PubMed

    Makowiecki, Kalina; Hammond, Geoff; Rodger, Jennifer

    2012-01-01

    In behavioural experiments, motivation to learn can be achieved using food rewards as positive reinforcement in food-restricted animals. Previous studies reduce animal weights to 80-90% of free-feeding body weight as the criterion for food restriction. However, effects of different degrees of food restriction on task performance have not been assessed. We compared learning task performance in mice food-restricted to 80 or 90% body weight (BW). We used adult wildtype (WT; C57Bl/6j) and knockout (ephrin-A2⁻/⁻) mice, previously shown to have a reverse learning deficit. Mice were trained in a two-choice visual discrimination task with food reward as positive reinforcement. When mice reached criterion for one visual stimulus (80% correct in three consecutive 10 trial sets) they began the reverse learning phase, where the rewarded stimulus was switched to the previously incorrect stimulus. For the initial learning and reverse phase of the task, mice at 90%BW took almost twice as many trials to reach criterion as mice at 80%BW. Furthermore, WT 80 and 90%BW groups significantly differed in percentage correct responses and learning strategy in the reverse learning phase, whereas no differences between weight restriction groups were observed in ephrin-A2⁻/⁻ mice. Most importantly, genotype-specific differences in reverse learning strategy were only detected in the 80%BW groups. Our results indicate that increased food restriction not only results in better performance and a shorter training period, but may also be necessary for revealing behavioural differences between experimental groups. This has important ethical and animal welfare implications when deciding extent of diet restriction in behavioural studies. PMID:23144936

  12. Levels of Soluble Receptor for Advanced Glycation End Products in Bronchoalveolar Lavage Fluid in Patients with Various Inflammatory Lung Diseases.

    PubMed

    Kamo, Tetsuro; Tasaka, Sadatomo; Tokuda, Yuriko; Suzuki, Shoji; Asakura, Takanori; Yagi, Kazuma; Namkoong, Ho; Ishii, Makoto; Hasegawa, Naoki; Betsuyaku, Tomoko

    2015-01-01

    Receptor for advanced glycation end products (RAGE) is a multiligand receptor of S100/calgranulins, high-mobility group box 1, and others, and it is associated with the pathogenesis of various inflammatory and circulatory diseases. The soluble form of RAGE (sRAGE) is a decoy receptor and competitively inhibits membrane-bound RAGE activation. In this study, we measured sRAGE levels in bronchoalveolar lavage fluid (BALF) of 78 patients, including 41 with interstitial pneumonia, 11 with sarcoidosis, 9 with respiratory infection, 7 with ARDS, 5 with lung cancer, and 5 with vasculitis. Among them, sRAGE was detectable in BALF of 73 patients (94%). In patients with ARDS and vasculitis, the sRAGE levels were significantly higher than in the control subjects and those with interstitial pneumonia. The sRAGE levels were positively correlated with total cell counts in BALF and serum levels of surfactant protein-D, lactate dehydrogenase, and C-reactive protein. There was an inverse correlation between PaO2/FIO2 ratio and sRAGE levels. These results indicate that sRAGE in BALF might be considered as a biomarker of lung inflammatory disorders, especially ARDS and vasculitis. PMID:27147899

  13. Levels of Soluble Receptor for Advanced Glycation End Products in Bronchoalveolar Lavage Fluid in Patients with Various Inflammatory Lung Diseases

    PubMed Central

    Kamo, Tetsuro; Tasaka, Sadatomo; Tokuda, Yuriko; Suzuki, Shoji; Asakura, Takanori; Yagi, Kazuma; Namkoong, Ho; Ishii, Makoto; Hasegawa, Naoki; Betsuyaku, Tomoko

    2015-01-01

    Receptor for advanced glycation end products (RAGE) is a multiligand receptor of S100/calgranulins, high-mobility group box 1, and others, and it is associated with the pathogenesis of various inflammatory and circulatory diseases. The soluble form of RAGE (sRAGE) is a decoy receptor and competitively inhibits membrane-bound RAGE activation. In this study, we measured sRAGE levels in bronchoalveolar lavage fluid (BALF) of 78 patients, including 41 with interstitial pneumonia, 11 with sarcoidosis, 9 with respiratory infection, 7 with ARDS, 5 with lung cancer, and 5 with vasculitis. Among them, sRAGE was detectable in BALF of 73 patients (94%). In patients with ARDS and vasculitis, the sRAGE levels were significantly higher than in the control subjects and those with interstitial pneumonia. The sRAGE levels were positively correlated with total cell counts in BALF and serum levels of surfactant protein-D, lactate dehydrogenase, and C-reactive protein. There was an inverse correlation between PaO2/FIO2 ratio and sRAGE levels. These results indicate that sRAGE in BALF might be considered as a biomarker of lung inflammatory disorders, especially ARDS and vasculitis. PMID:27147899

  14. The Effects of Using Concept Mapping for Improving Advanced Level Biology Students' Lower- and Higher-Order Cognitive Skills

    NASA Astrophysics Data System (ADS)

    Bramwell-Lalor, Sharon; Rainford, Marcia

    2014-03-01

    This paper reports on teachers' use of concept mapping as an alternative assessment strategy in advanced level biology classes and its effects on students' cognitive skills on selected biology concepts. Using a mixed methods approach, the study employed a pre-test/post-test quasi-experimental design involving 156 students and 8 teachers from intact classes. A researcher-constructed Biology Cognitive Skills Test was used to collect the quantitative data. Qualitative data were collected through interviews and students' personal documents. The data showed that the participants utilized concept mapping in various ways and they described positive experiences while being engaged in its use. The main challenge cited by teachers was the limited time available for more consistent use. The results showed that the use of concept mapping in advanced level biology can lead to learning gains that exceed those achieved in classes where mainly traditional methods are used. The students in the concept mapping experimental groups performed significantly better than their peers in the control group on both the lower-order (F(1) = 21.508; p < .001) and higher-order (F(1) = 42.842, p < .001) cognitive items of the biology test. A mean effect size of .56 was calculated representing the contribution of treatment to the students' performance on the test items.

  15. TGF-β receptor levels regulate the specificity of signaling pathway activation and biological effects of TGF-β

    PubMed Central

    Rojas, Andres; Padidam, Malla; Cress, Dean; Grady, William M.

    2009-01-01

    TGF-β is a pluripotent cytokine that mediates its effects through a receptor composed of TGF-β receptor type II (TGFBR2) and type I (TGFBR1). The TGF-β receptor can regulate Smad and nonSmad signaling pathways, which then ultimately dictate TGF-β's biological effects. We postulated that control of the level of TGFBR2 is a mechanism for regulating the specificity of TGF-β signaling pathway activation and TGF-β's biological effects. We used a precisely regulatable TGFBR2 expression system to assess the effects of TGFBR2 expression levels on signaling and TGF-β mediated apoptosis. We found Smad signaling and MAPK-ERK signaling activation levels correlate directly with TGFBR2 expression levels. Furthermore, p21 levels and TGF-β induced apoptosis appear to depend on relatively high TGFBR2 expression and on the activation of the MAPK-ERK and SMAD pathways. Thus, control of TGFBR2 expression and the differential activation of TGF-β signaling pathways appears to be a mechanism for regulating the specificity of the biological effects of TGF-β. PMID:19339207

  16. The Fading Affect Bias shows healthy coping at the general level, but not the specific level for religious variables across religious and non-religious events.

    PubMed

    Gibbons, Jeffrey A; Hartzler, Jennifer K; Hartzler, Andrew W; Lee, Sherman A; Walker, W Richard

    2015-11-01

    The research on fading emotions has shown that unpleasant emotions fade more over time than pleasant emotions, which is a phenomenon referred to as the Fading Affect Bias (FAB). Based on the negative relation between the FAB and dysphoria (Walker, Skowronski, Gibbons, Vogl, & Thompson, 2003), some researchers have argued that the FAB is a healthy coping mechanism (Walker, Skowronski, & Thompson, 2003). As religious variables are related to positive emotions and emotional coping (e.g., Cohen, 2002; Pargament, Smith, Koenig, & Perez, 1998), we examined the FAB as a healthy coping mechanism at the general and specific levels of analysis in the context of religion. General healthy coping was supported by (1) FAB effects across both religious events (REs) and non-religious events (NREs) and (2) a positive relation for spirituality and the FAB. However, specific healthy coping was not supported by a small FAB for (1) REs at high levels of positive religious coping (PRC) for NREs, (2) NREs at low levels of PRC for NREs, and (3) purely REs relative to REs involving spirituality. Other implications are discussed. PMID:26196449

  17. Neuron-specific stimulus masking reveals interference in spike timing at the cortical level.

    PubMed

    Larson, Eric; Maddox, Ross K; Perrone, Ben P; Sen, Kamal; Billimoria, Cyrus P

    2012-02-01

    The auditory system is capable of robust recognition of sounds in the presence of competing maskers (e.g., other voices or background music). This capability arises despite the fact that masking stimuli can disrupt neural responses at the cortical level. Since the origins of such interference effects remain unknown, in this study, we work to identify and quantify neural interference effects that originate due to masking occurring within and outside receptive fields of neurons. We record from single and multi-unit auditory sites from field L, the auditory cortex homologue in zebra finches. We use a novel method called spike timing-based stimulus filtering that uses the measured response of each neuron to create an individualized stimulus set. In contrast to previous adaptive experimental approaches, which have typically focused on the average firing rate, this method uses the complete pattern of neural responses, including spike timing information, in the calculation of the receptive field. When we generate and present novel stimuli for each neuron that mask the regions within the receptive field, we find that the time-varying information in the neural responses is disrupted, degrading neural discrimination performance and decreasing spike timing reliability and sparseness. We also find that, while removing stimulus energy from frequency regions outside the receptive field does not significantly affect neural responses for many sites, adding a masker in these frequency regions can nonetheless have a significant impact on neural responses and discriminability without a significant change in the average firing rate. These findings suggest that maskers can interfere with neural responses by disrupting stimulus timing information with power either within or outside the receptive fields of neurons. PMID:21964794

  18. Tumor Vascular Permeability to a Nanoprobe Correlates to Tumor-Specific Expression Levels of Angiogenic Markers

    PubMed Central

    Karathanasis, Efstathios; Chan, Leslie; Karumbaiah, Lohitash; McNeeley, Kathleen; D'Orsi, Carl J.; Annapragada, Ananth V.; Sechopoulos, Ioannis; Bellamkonda, Ravi V.

    2009-01-01

    Background Vascular endothelial growth factor (VEGF) receptor-2 is the major mediator of the mitogenic, angiogenic, and vascular hyperpermeability effects of VEGF on breast tumors. Overexpression of VEGF and VEGF receptor-2 is associated with the degree of pathomorphosis of the tumor tissue and unfavorable prognosis. In this study, we demonstrate that non-invasive quantification of the degree of tumor vascular permeability to a nanoprobe correlates with the VEGF and its receptor levels and tumor growth. Methodology/Principal Findings We designed an imaging nanoprobe and a methodology to detect the intratumoral deposition of a 100 nm-scale nanoprobe using mammography allowing measurement of the tumor vascular permeability in a rat MAT B III breast tumor model. The tumor vascular permeability varied widely among the animals. Notably, the VEGF and VEGF receptor-2 gene expression of the tumors as measured by qRT-PCR displayed a strong correlation to the imaging-based measurements of vascular permeability to the 100 nm-scale nanoprobe. This is in good agreement with the fact that tumors with high angiogenic activity are expected to have more permeable blood vessels resulting in high intratumoral deposition of a nanoscale agent. In addition, we show that higher intratumoral deposition of the nanoprobe as imaged with mammography correlated to a faster tumor growth rate. This data suggest that vascular permeability scales to the tumor growth and that tumor vascular permeability can be a measure of underlying VEGF and VEGF receptor-2 expression in individual tumors. Conclusions/Significance This is the first demonstration, to our knowledge, that quantitative imaging of tumor vascular permeability to a nanoprobe represents a form of a surrogate, functional biomarker of underlying molecular markers of angiogenesis. PMID:19513111

  19. Levels and actions of neuroactive steroids in the nervous system under physiological and pathological conditions: Sex-specific features.

    PubMed

    Melcangi, Roberto C; Giatti, Silvia; Garcia-Segura, Luis M

    2016-08-01

    Neuroactive steroids regulate the physiology of the central and peripheral nervous system, exert neuroprotective actions and represent interesting tools for therapeutic strategies against neurodegenerative and psychiatric disorders. Sex differences in their levels are detected not only under physiological conditions but are also modified in a sex-dependent way in different pathological alterations such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, traumatic brain injury, spinal cord injury, stroke, diabetic encephalopathy, psychiatric disorders and peripheral neuropathy. Interestingly, many of these disorders show sex differences in their incidence, symptomatology and/or neurodegenerative outcome. The neuroprotective actions of neuroactive steroids, together with the sex specific regulation of its levels might provide the basis to design sex-specific neuroprotective therapies. Indeed, some experiments here discussed suggest the viability of this approach. PMID:26657814

  20. Influence of dioxin exposure upon levels of prostate-specific antigen and steroid hormones in Vietnamese men.

    PubMed

    Sun, Xian Liang; Kido, Teruhiko; Honma, Seijiro; Okamoto, Rie; Manh, Ho Dung; Maruzeni, Shoko; Nishijo, Muneko; Nakagawa, Hideaki; Nakano, Takeshi; Koh, Eitetsu; Takasuga, Takumi; Nhu, Dang Duc; Hung, Nguyen Ngoc; Son, Le Ke

    2016-04-01

    Most studies on the relationship between Agent Orange and prostate cancer have focused on US veterans of the Vietnam War. There have been few studies focusing on the relationship between levels of prostate-specific antigen (PSA) and dioxins or steroid hormones in Vietnamese men. In 2009-2011, we collected blood samples from 97 men who had resided in a "dioxin hotspot" and 85 men from a non-sprayed region in Vietnam. Then levels of PSA, dioxins, and steroid hormones were analyzed. Levels of most dioxins, furans, and non-ortho polychlorinated biphenyls were higher in the hotspot than those in the non-sprayed region. Levels of testosterone, dehydroepiandrosterone, and estradiol differed significantly between the hotspot and the non-sprayed region, but there were no correlations between levels of PSA and steroid hormones and dioxins in either of the two regions. Our findings suggest that PSA levels in Vietnamese men are not associated with levels of dioxin or steroid hormones in these two regions. PMID:26758301

  1. Phytochrome Control of Specific mRNA levels in Developing Pea Buds 1

    PubMed Central

    Kaufman, Lon S.; Roberts, Linda L.; Briggs, Winslow R.; Thompson, William F.

    1986-01-01

    We have examined the time course for accumulation of each of 12 different nuclear gene transcripts in pea buds after irradiating dark grown seedlings with a single pulse low fluence red light (103 micromoles per square meter delivered in 100 seconds). The 12 time courses can be grouped into four general classes. Six transcripts (including RNAs coding for the chlorophyll a/b binding protein and ribulose-1,5-bisphosphate carboxylase) accumulate at a linear rate during 24 hours in darkness following the light pulse. Two transcripts increase rapidly at first but then reach a plateau after 3 hours and remain at that level for the next 21 hours. Another two transcripts exhibit a prolonged lag period before beginning to accumulate, and do not reach significant accumulation rates until 12 to 16 hours after the red light pulse. One transcript appears to undergo a transient increase in abundance in response to red light, but this is superimposed on a background of slowly increasing abundance of this RNA in control plants. This response, unlike all the others, exhibits reciprocity failure in experiments in which the same fluence of light is given over periods ranging between 50 and 4000 seconds. We have also examined the kinetics with which each of these 12 responses escapes from phytochrome-far-red absorbing form control by attempting to reverse the induction with far-red light given at various times after the red light pulse. Again, several different patterns are apparent for the different transcripts. The time at which far red reversibility first begins to be lost, the rate at which it is lost, and the final extent of reversibility remaining after 7 hours in the dark all differ for different transcripts. In addition, we have observed that some responses retain virtually complete photoreversibility for at least 7 hours. In some cases, a comparison of the time course and escape kinetic data indicates that relatively rapid turnover of the RNA must occur. It is not clear

  2. Anaemia, Haemoglobin Level and Cause-Specific Mortality in People with and without Diabetes

    PubMed Central

    Kengne, Andre Pascal; Czernichow, Sébastien; Hamer, Mark; Batty, G. David; Stamatakis, Emmanuel

    2012-01-01

    Background Both anaemia and cardiovascular disease (CVD) are common in people with diabetes. While individually both characteristics are known to raise mortality risk, their combined influence has yet to be quantified. In this pooling project, we examined the combined impact of baseline haemoglobin levels and existing CVD on all-cause and CVD mortality in people with diabetes. We draw comparison of these effects with those apparent in diabetes-free individuals. Methods/Principal Findings A combined analyses of 7 UK population-based cohorts resulted in 26,480 study members. There were 946 participants with physician-diagnosed diabetes, 2227 with anaemia [haemoglobin<13 g/dl (men) or <12 (women)], 2592 with existing CVD (stroke, ischaemic heart disease), and 21,396 with none of the conditions. Across diabetes and anaemia subgroups, and using diabetes-free, non-anaemic participants as the referent group, the adjusted hazard ratios (HR) were 1.46 (95% CI: 1.30–1.63) for anaemia, 1.67 (1.45–1.92) for diabetes, and 2.10 (1.55–2.85) for diabetes and anaemia combined. Across combined diabetes, anaemia and CVD subgroups, and compared with non-anaemic, diabetes-free and CVD-free participants, HR (95% CI) for all-cause mortality were 1.49 (1.32–1.69) anaemia, 1.60 (1.46–1.76) for existing CVD, and 1.66 (1.39–1.97) for diabetes alone. Equivalents were 2.13 (1.48–3.07) for anaemia and diabetes, 2.68 (2.14–3.36) for diabetes and existing CVD, and 3.25 (1.88–5.62) for the three combined. Patterns were similar for CVD mortality. Conclusions/Significance Individually, anaemia and CVD confer similar mortality risks in people with diabetes, and are excessively fatal in combination. Screening for anaemia would identify vulnerable diabetic patients whose outcomes can potentially be improved. PMID:22876293

  3. S`COOL: Leveraging Information Technology Advances to Present K-12 Students with Specifically Relevant Satellite Data

    NASA Astrophysics Data System (ADS)

    Chambers, L. H.; Rogerson, T. M.; Fischer, J. D.; Moore, S. W.

    2007-12-01

    The Students` Cloud Observations On-Line (S`COOL) Project began in 1997 as a way to connect K-12 classrooms directly with ongoing NASA Earth Science research. Through the Clouds and the Earth's Radiant Energy System (CERES) project, students as young as kindergarten have been involved for more than 10 years in providing ground truth observations of cloud cover and type. NASA scientists use these observations as part of the validation effort for understanding cloud effects on the Earth's energy budget. In addition, since the beginning, the project has also focused on students doing their own data analysis. However, not very many S`COOL participants actually performed much data analysis in the first years of the project. Over the last year and a half, the S`COOL team has worked to provide additional scaffolding for student data analysis, by leveraging emerging information technology developments to select and present specifically relevant satellite data to the students. In addition to the simple, standard visualization of the ground and satellite cloud information, we have provided a direct link to the specific 5-minute MODIS image, through the MODIS Rapid Response website. Over the summer, we added tutorials explaining how students can also bring in the atmospheric profiles from CALIPSO and/or CloudSat, when there is a near overhead pass of these satellites. In addition to the direct links to satellite imagery and data, we have also implemented a web-based classification and comment system. S`COOL participants can provide additional comments on the ground to satellite correspondence, after the satellite data are processed by FLASHFlux about a week after the student ground observation. Comments are emailed to the S`COOL team and enable additional interaction with the participants. Finally, new data analysis tools focusing on commonly-used spreadsheet software were developed over the summer by a team of college student interns. The addition of all these new resources

  4. Specific responses in rat small intestinal epithelial mRNA expression and protein levels during chemotherapeutic damage and regeneration.

    PubMed

    Verburg, Melissa; Renes, Ingrid B; Van Nispen, Danielle J P M; Ferdinandusse, Sacha; Jorritsma, Marieke; Büller, Hans A; Einerhand, Alexandra W C; Dekker, Jan

    2002-11-01

    The rapidly dividing small intestinal epithelium is very sensitive to the cytostatic drug methotrexate. We investigated the regulation of epithelial gene expression in rat jejunum during methotrexate-induced damage and regeneration. Ten differentiation markers were localized on tissue sections and quantified at mRNA and protein levels relative to control levels. We analyzed correlations in temporal expression patterns between markers. mRNA expression of enterocyte and goblet cell markers decreased significantly during damage for a specific period. Of these, sucrase-isomaltase (-62%) and CPS (-82%) were correlated. Correlations were also found between lactase (-76%) and SGLT1 (-77%) and between I-FABP (-52%) and L-FABP (-45%). Decreases in GLUT5 (-53%), MUC2 (-43%), and TFF3 (-54%) mRNAs occurred independently of any of the other markers. In contrast, lysozyme mRNA present in Paneth cells increased (+76%). At the protein level, qualitative and quantitative changes were in agreement with mRNA expression, except for Muc2 (+115%) and TFF3 (+81%), which increased significantly during damage, following independent patterns. During regeneration, expression of each marker returned to control levels. The enhanced expression of cytoprotective molecules (Muc2, TFF3, lysozyme) during damage represents maintenance of goblet cell and Paneth cell functions, most likely to protect the epithelium. Decreased expression of enterocyte-specific markers represents decreased enterocyte function, of which fatty acid transporters were least affected. PMID:12417619

  5. Development and Deployment of Advanced Corrosion Monitoring Systems for High-Level Waste Tanks

    SciTech Connect

    Terry, M. T.; Edgemon, G. L.; Mickalonis, J. I.; Mizia, R. E.

    2002-02-26

    This paper describes the results of a collaborative technology development program, sponsored by the Tanks Focus Area, to use electrochemical noise (EN) for corrosion monitoring in underground storage tanks. These tanks, made of carbon or stainless steels, contain high-level radioactive liquid waste (HLW) generated by weapons production or radioactive liquid waste from nuclear fuel reprocessing activities at several Department of Energy (DOE) sites. The term EN is used to describe low frequency fluctuations in current and voltage measurements associated with corrosion. In their most basic form, EN-based corrosion monitoring systems measure and record these fluctuations over time from electrodes immersed in the environment of interest--in this case, radioactive tank waste. The resulting EN signals have characteristic patterns for different corrosion mechanisms. In recent years, engineers and scientists from several DOE sites, in collaboration with several private companies, have conducted laboratory studies and field applications to correlate the EN signals with corrosion mechanisms active in the radioactive waste tanks. The participating DOE sites are Hanford, Savannah River, Oak Ridge Reservation and the Idaho National Engineering and Environmental Laboratory. The commercial vendors have included HiLine Engineering and Fabrication, Inc., EIC Laboratories, Inc., and AEA Technologies. Successful deployment of the EN technology will yield improved information of waste tank corrosion conditions, better tank management, and lower overall cost.

  6. Development and deployment of advanced corrosion monitoring systems for high-level waste tanks.

    SciTech Connect

    Terry, M. T.; Edgemon, G. L.; Mickalonis, J. I.; Mizia, R. E.

    2002-01-01

    This paper describes the results of a collaborative technology development program, sponsored by the Tanks Focus Area, to use electrochemical noise (EN) for corrosion monitoring in underground storage tanks. These tanks, made of carbon or stainless steels, contain high-level radioactive liquid waste (HLW) generated by weapons production or radioactive liquid waste from nuclear fuel reprocessing activities at several Department of Energy (DOE) sites. The term EN is used to describe low frequency fluctuations in current and voltage measurements associated with corrosion. In their most basic form, EN-based corrosion monitoring systems measure and record these fluctuations over time from electrodes immersed in the environment of interest - in this case, radioactive tank waste. The resulting EN signals have characteristic patterns for different corrosion mechanisms. In recent years, engineers and scientists from several DOE sites, in collaboration with several private companies, have conducted laboratory studies and field applications to correlate the EN signals with corrosion mechanisms active in the radioactive waste tanks. The participating DOE sites are Hanford, Savannah River, Oak Ridge Reservation and the Idaho National Engineering and Environmental Laboratory. The commercial vendors have included HiLine Engineering and Fabrication, Inc., EIC Laboratories, Inc., and M A Technologies. Successful deployment of the EN technology will yield improved information of waste tank corrosion conditions, better tank management, and lower overall cost.

  7. Advancing reference emission levels in subnational and national REDD+ initiatives: a CLASlite approach

    PubMed Central

    2015-01-01

    Conservation and monitoring of tropical forests requires accurate information on their extent and change dynamics. Cloud cover, sensor errors and technical barriers associated with satellite remote sensing data continue to prevent many national and sub-national REDD+ initiatives from developing their reference deforestation and forest degradation emission levels. Here we present a framework for large-scale historical forest cover change analysis using free multispectral satellite imagery in an extremely cloudy tropical forest region. The CLASlite approach provided highly automated mapping of tropical forest cover, deforestation and degradation from Landsat satellite imagery. Critically, the fractional cover of forest photosynthetic vegetation, non-photosynthetic vegetation, and bare substrates calculated by CLASlite provided scene-invariant quantities for forest cover, allowing for systematic mosaicking of incomplete satellite data coverage. A synthesized satellite-based data set of forest cover was thereby created, reducing image incompleteness caused by clouds, shadows or sensor errors. This approach can readily be implemented by single operators with highly constrained budgets. We test this framework on tropical forests of the Colombian Pacific Coast (Chocó) – one of the cloudiest regions on Earth, with successful comparison to the Colombian government’s deforestation map and a global deforestation map. PMID:25678933

  8. Atmospheric fluidized bed combustion advanced system concepts applicable to small industrial and commercial markets. Topical report, Level 2

    SciTech Connect

    Ake, T.R.; Dixit, V.B.; Mongeon, R.K.

    1992-09-01

    As part of an overall strategy to promote FBC coal combustion and to improve the marketability of the eastern coals, the US Department of Energy`s Morgantown Energy Research Center awarded a three level contract to Riley Stoker Corporation to develop advanced Multi Solids Fluidized Bed (MSFB) boiler designs. The first level of this contract targeted the small package boiler (10,000--50,000 lb/hr steam) and industrial size boiler (75,000--150,000 lb/hr steam) markets. Two representative sizes, 30,000 lb/hr and 110,000 lb/hr of steam, were selected for the two categories for a detailed technical and economic evaluation. Technically, both the designs showed promise, however, the advanced industrial design was favored on economic considerations. It was thus selected for further study in the second level of the contract. Results of this Level-2 effort, presented in this report, consisted of testing the design concept in Riley`s 4.4 MBtu/hr pilot MSFB facility located at Riley Research Center in Worcester, Mass. The design and economics of the proof of concept facility developed in Level-1 of the contract were then revised in accordance with the findings of the pilot test program. A host site for commercial demonstration in Level-3 of the contract was also secured. It was determined that co-firing coal in combination with paper de-inking sludge will broaden the applicability of the design beyond conventional markets. International Paper (IP), the largest paper company in the world, is willing to participate in this part of the program. IP has offered its Hammermill operation at Lockhaven, Pa, site of a future paper de-inking plant, for the proof of concept installation. This plant will go in operation in 1994. It is recommended that METC proceed to the commercial demonstration of the design developed. The approach necessary to satisfy the needs of the customer while meeting the objectives of this program is presented along with a recommended plan of action.

  9. Reduced level of sex-specific antigen (H-Y antigen) on lymphocytes in some patients with bilateral cryptorchidism.

    PubMed

    Fedder, J; Hansen, L G; Hjort, T

    1989-01-01

    Sex-specific (Sxs) antigen on the surface of nucleated cells from normal human males seems to be essential for the formation of testes. The relative quantity of the antigen on lymphocytes was evaluated by absorption experiments in a complement-dependent cytotoxicity test or in an ELISA technique using antisera against Sxs antigen produced by immunization of female rats. Lymphocytes from 13 normal males were Sxs-antigen positive, and cells from 12 normal females were characterized as Sxs-antigen negative. However, in the testing of lymphocytes from nine boys with bilateral cryptorchidism, only six revealed a normal male absorption pattern, whereas the antigen level on cells from three boys, all of them with normal karyotype, was reduced compared with the normal male level. No correlation between Sxs-antigen level and testosterone response after treatment with hCG could be demonstrated. PMID:2565709

  10. Predictors of survival in prostate cancer patients with bone metastasis and extremely high prostate-specific antigen levels

    PubMed Central

    Koo, Kyo Chul; Park, Sang Un; Kim, Ki Hong; Rha, Koon Ho; Hong, Sung Joon; Yang, Seung Choul; Chung, Byung Ha

    2015-01-01

    Purpose Prostate-specific antigen (PSA) is a surrogate marker of disease progression; however, its predictive ability in the extreme ranges is unknown. We determined the predictors of survival in patients with bone metastatic prostate cancer (BMPCa) and with extremely high PSA levels. Methods Treatment-naïve patients (n = 248) diagnosed with BMPCa between December 2002 and June 2012 were retrospectively analyzed. Clinicopathological features at diagnosis, namely age, body mass index, serum alkaline phosphatase (ALP) and PSA levels, PSA nadir, time to PSA nadir and its maintenance period, PSA declining velocity, Gleason grade, clinical T stage, pain score, Eastern Cooperative Oncology Group performance score (ECOG PS), and the number of bone metastases were assessed. The patients were stratified according to PSA ranges of <20 ng/mL, 20–100 ng/mL, 100–1000 ng/mL, and 1000–10,000 ng/mL. Study endpoints were castration-resistant PCa (CRPC)-free survival and cancer-specific survival (CSS). Results Patients with higher PSA and ALP levels showed more bone lesions (P < 0.001). During the follow-up period (median, 39.9 months; interquartile range, 21.5–65.9 months), there were no differences between the groups in terms of the survival endpoints. High ALP levels, shorter time to PSA nadir, and pain were associated with an increased risk of progression to CRPC, and high ALP levels, ECOG PS ≥ 1, and higher PSA nadir independently predicted CSS. Conclusions PSA response to androgen deprivation therapy and serum ALP are reliable predictors of survival in patients with BMPCa presenting with extremely high PSA levels. These patients should not be deterred from active treatment based on baseline PSA values. PMID:26157761

  11. Complex I and complex III inhibition specifically increase cytosolic hydrogen peroxide levels without inducing oxidative stress in HEK293 cells

    PubMed Central

    Forkink, Marleen; Basit, Farhan; Teixeira, José; Swarts, Herman G.; Koopman, Werner J.H.; Willems, Peter H.G.M.

    2015-01-01

    Inhibitor studies with isolated mitochondria demonstrated that complex I (CI) and III (CIII) of the electron transport chain (ETC) can act as relevant sources of mitochondrial reactive oxygen species (ROS). Here we studied ROS generation and oxidative stress induction during chronic (24 h) inhibition of CI and CIII using rotenone (ROT) and antimycin A (AA), respectively, in intact HEK293 cells. Both inhibitors stimulated oxidation of the ROS sensor hydroethidine (HEt) and increased mitochondrial NAD(P)H levels without major effects on cell viability. Integrated analysis of cells stably expressing cytosolic- or mitochondria-targeted variants of the reporter molecules HyPer (H2O2-sensitive and pH-sensitive) and SypHer (H2O2-insensitive and pH-sensitive), revealed that CI- and CIII inhibition increased cytosolic but not mitochondrial H2O2 levels. Total and mitochondria-specific lipid peroxidation was not increased in the inhibited cells as reported by the C11-BODIPY581/591 and MitoPerOx biosensors. Also expression of the superoxide-detoxifying enzymes CuZnSOD (cytosolic) and MnSOD (mitochondrial) was not affected. Oxyblot analysis revealed that protein carbonylation was not stimulated by CI and CIII inhibition. Our findings suggest that chronic inhibition of CI and CIII: (i) increases the levels of HEt-oxidizing ROS and (ii) specifically elevates cytosolic but not mitochondrial H2O2 levels, (iii) does not induce oxidative stress or substantial cell death. We conclude that the increased ROS levels are below the stress-inducing level and might play a role in redox signaling. PMID:26516986

  12. Groundwater level and specific conductance monitoring at Marine Corps Base, Camp Lejeune, Onslow County, North Carolina, 2007-2008

    USGS Publications Warehouse

    McSwain, Kristen Bukowski

    2010-01-01

    The U.S. Geological Survey, in cooperation with the Marine Corps Base, Camp Lejeune, monitored water-resources conditions in the surficial, Castle Hayne, Peedee, and Black Creek aquifers in Onslow County, North Carolina, from November 2007 through September 2008. To comply with North Carolina Central Coastal Plain Capacity Use Area regulations, large-volume water suppliers in Onslow County must reduce their dependency on the Black Creek aquifer as a water-supply source and have, instead, proposed using the Castle Hayne aquifer as an alternative water-supply source. The Marine Corps Base, Camp Lejeune, uses water obtained from the unregulated surficial and Castle Hayne aquifers for drinking-water supply. Water-level data were collected and field measurements of physical properties were made at 19 wells at 8 locations spanning the Marine Corps Base, Camp Lejeune. These wells were instrumented with near real-time monitoring equipment to collect hourly measurements of water level. Additionally, specific conductance and water temperature were measured hourly in 16 of the 19 wells. Graphs are presented relating altitude of groundwater level to water temperature and specific conductance measurements collected during the study, and the relative vertical gradients between aquifers are discussed. The period-of-record normal (25th to 75th percentile) monthly mean groundwater levels at two well clusters were compared to median monthly mean groundwater levels at these same well clusters for 2008 to determine groundwater-resources conditions. In 2008, water levels were below normal in the 3 wells at one of the well clusters and were normal in 4 wells at the other cluster.

  13. Clinical Significance of CA125 Level after the First Cycle of Chemotherapy on Survival of Patients with Advanced Ovarian Cancer

    PubMed Central

    Lee, Maria; Chang, Min Young; Yoo, Hanna; Lee, Kyung Eun; Chay, Doo Byung; Cho, Hanbyoul; Kim, Young Tae

    2016-01-01

    Purpose To determine the most powerful cancer antigen 125 (CA125)-related prognostic factor for advanced epithelial ovarian cancer (EOC) and to identify cut-off values that distinguish patients with a poor prognosis from those with a good prognosis. Materials and Methods We included 223 patients who received staging laparotomy and were diagnosed with stage IIC–IV serous EOC. Cox regression analysis was used to determine the most significant prognostic factor among the following variables: serum CA125 before surgery and after the first, second, and sixth cycles of chemotherapy; the nadir CA125 value; the relative percentage change in CA125 levels after the first and second cycles of chemotherapy compared to baseline CA125; CA125 half-life; time to nadir; and time to normalization of the CA125 level. Results The CA125 level after the first chemotherapy cycle was the most significant independent prognostic factor for overall survival (OS). Time to normalization (p=0.028) and relative percentage change between CA125 levels at baseline and after the first chemotherapy cycle (p=0.021) were additional independent prognostic factors in terms of OS. The CA125 level after the first chemotherapy cycle (p=0.001) and time to normalization (p<0.001) were identified as independent prognostic factors for progression free survival (PFS). Conclusion Among well-established CA125-related prognostic factors, serum CA125 levels after the first cycle of chemotherapy and time to normalization were the most significant prognostic factors for both OS and PFS. PMID:26996555

  14. Muscle disuse alters skeletal muscle contractile function at the molecular and cellular levels in older adult humans in a sex-specific manner

    PubMed Central

    Callahan, Damien M; Miller, Mark S; Sweeny, Andrew P; Tourville, Timothy W; Slauterbeck, James R; Savage, Patrick D; Maugan, David W; Ades, Philip A; Beynnon, Bruce D; Toth, Michael J

    2014-01-01

    Physical inactivity that accompanies ageing and disease may hasten disability by reducing skeletal muscle contractility. To characterize skeletal muscle functional adaptations to muscle disuse, we compared contractile performance at the molecular, cellular and whole-muscle levels in healthy active older men and women (n = 15) and inactive older men and women with advanced-stage, symptomatic knee osteoarthritis (OA) (n = 16). OA patients showed reduced (P < 0.01) knee extensor function. At the cellular level, single muscle fibre force production was reduced in OA patients in myosin heavy chain (MHC) I and IIA fibres (both P < 0.05) and differences in IIA fibres persisted after adjustments for fibre cross-sectional area (P < 0.05). Although no group differences in contractile velocity or power output were found for any fibre type, sex was found to modify the effect of OA, with a reduction in MHC IIA power output and a trend towards reduced shortening velocity in women, but increases in both variables in men (P < 0.05 and P = 0.07, respectively). At the molecular level, these adaptations in MHC IIA fibre function were explained by sex-specific differences (P ≤ 0.05) in myosin–actin cross-bridge kinetics. Additionally, cross-bridge kinetics were slowed in MHC I fibres in OA patients (P < 0.01), attributable entirely to reductions in women with knee OA (P < 0.05), a phenotype that could be reproduced in vitro by chemical modification of protein thiol residues. Our results identify molecular and cellular functional adaptations in skeletal muscle that may contribute to reduced physical function with knee OA-associated muscle disuse, with sex-specific differences that may explain a greater disposition towards disability in women. PMID:25038243

  15. Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks

    PubMed Central

    2012-01-01

    Background Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes. Methods RPE-choroid and retina tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11 potential pre-AMD human donor eyes. Transcriptome profiles were generated for macular and extramacular regions, and statistical and bioinformatic methods were employed to identify disease-associated gene signatures and functionally enriched protein association networks. Selected genes of high significance were validated using an independent donor cohort. Results We identified over 50 annotated genes enriched in cell-mediated immune responses that are globally over-expressed in RPE-choroid AMD phenotypes. Using a machine learning model and a second donor cohort, we show that the top 20 global genes are predictive of AMD clinical diagnosis. We also discovered functionally enriched gene sets in the RPE-choroid that delineate the advanced AMD phenotypes, neovascular AMD and geographic atrophy. Moreover, we identified a graded increase of transcript levels in the retina related to wound response, complement cascade, and neurogenesis that strongly correlates with decreased levels of phototransduction transcripts and increased AMD severity. Based on our findings, we assembled protein-protein interactomes that highlight functional networks likely to be

  16. In vitro-activated tumor-specific T lymphocytes prolong the survival of patients with advanced gastric cancer: a retrospective cohort study

    PubMed Central

    Kuai, Jun; Yang, Fang; Li, Guang-Jun; Fang, Xiang-Jie; Gao, Bao-Qin

    2016-01-01

    Background Conventional tumor managements have limited survival benefits and cause severely impaired immune function in patients with advanced gastric cancer (GC) whereas immunotherapies could restore antitumor immunity. This prospective cohort study was aimed at investigating the efficacy of in vitro-activated tumor-specific T lymphocytes combined with chemotherapy on the survival of patients with advanced GC. Patients and methods Two hundred and seventy-four postoperative patients were enrolled in this study to receive either activated T lymphocytes immunotherapy combining chemotherapy (71 patients) or only receive postoperative chemotherapy (203 patients). Overall survival was analyzed by the Kaplan–Meier with log-rank test and Cox’s regression methods. Results The immunotherapy prolonged 9.8-month median survival for advanced gastric cancer (29.70 vs 19.70 months, P=0.036). Furthermore, immunotherapy significantly benefited the survival of patients who underwent radical, palliative resection, and stage III malignancy. No serious adverse effect was observed in the immunotherapy group. Conclusion In vitro-activated tumor-specific T lymphocytes prolonged survival in patients with advanced GC. PMID:27382313

  17. A specific phospholipase C activity regulates phosphatidylinositol levels in lung surfactant of patients with acute respiratory distress syndrome.

    PubMed

    Spyridakis, Spyros; Leondaritis, George; Nakos, George; Lekka, Marilena E; Galanopoulou, Dia

    2010-03-01

    Lung surfactant (LS) is a lipid-rich material lining the inside of the lungs. It reduces surface tension at the liquid/air interface and thus, it confers protection of the alveoli from collapsing. The surface-active component of LS is dipalmitoyl-phosphatidylcholine, while anionic phospholipids such as phosphatidylinositol (PtdIns) and primarily phosphatidylglycerol are involved in the stabilization of the LS monolayer. The exact role of PtdIns in this system is not well-understood; however, PtdIns levels change dramatically during the acute respiratory distress syndrome (ARDS) evolution. In this report we present evidence of a phosphoinositide-specific phospholipase C (PI-PLC) activity in bronchoalveolar lavage (BAL) fluid, which may regulate PtdIns levels. Characterization of this extracellular activity showed specificity for PtdIns and phosphatidylinositol 4,5-bisphosphate, sharing the typical substrate concentration-, pH-, and calcium-dependencies with mammalian PI-PLCs. Fractionation of BAL fluid showed that PI-PLC did not co-fractionate with large surfactant aggregates, but it was found mainly in the soluble fraction. Importantly, analysis of BAL samples from control subjects and from patients with ARDS showed that the PI-PLC specific activity was decreased by 4-fold in ARDS samples concurrently with the increase in BAL PtdIns levels. Thus, we have identified for the first time an extracellular PI-PLC enzyme activity that may be acutely involved in the regulation of PtdIns levels in LS. PMID:19491339

  18. Serum sex hormone and growth arrest-specific protein 6 levels in male patients with coronary heart disease

    PubMed Central

    Zhao, Rui; Li, Yan; Dai, Wen

    2016-01-01

    Epidemiological studies have shown a high prevalence of low serum testosterone levels in men with cardiovascular disease. Moreover, the tyrosine kinase receptor Axl, the ligand of which is growth arrest-specific protein 6 (GAS6), is expressed in the vasculature, and serum GAS6 levels are associated with endothelial dysfunction and cardiovascular events. Testosterone regulates GAS6 gene transcription directly, which inhibits calcification of vascular smooth muscle cells and provides a mechanistic insight into the cardioprotective action of androgens. This study was designed to determine the correlation between serum GAS6 and testosterone levels in male patients with coronary heart disease (CHD). We recruited 225 patients with CHD and 102 apparently healthy controls. Serum concentrations of GAS6 and soluble Axl were quantified by an enzyme-linked immunosorbent assay. Levels of high-sensitivity C-reactive protein, testosterone, estradiol, and other routine biochemical markers were also measured. Testosterone decreased from 432.69 ± 14.40 to 300.76 ± 6.23 ng dl−1 (P < 0.001) and GAS6 decreased from 16.20 ± 0.31 to 12.51 ± 0.19 ng ml−1 (P < 0.001) in patients with CHD, compared with control subjects. Multiple linear regression analysis showed that serum testosterone and GAS6 levels were positively associated in male patients with CHD. Alterations in GAS6 levels may influence the development of CHD. Downregulation of GAS6/Axl signaling in the presence of low sex hormone levels during disease progression is a potential mechanism by which GAS6 affects CHD. This study provides novel results regarding the influence of sex hormones on serum GAS6 levels in patients with CHD. PMID:26924277

  19. Sex-Specific Regulation of Mitochondrial DNA Levels: Genome-Wide Linkage Analysis to Identify Quantitative Trait Loci

    PubMed Central

    López, Sonia; Buil, Alfonso; Souto, Juan Carlos; Casademont, Jordi; Blangero, John; Martinez-Perez, Angel; Fontcuberta, Jordi; Lathrop, Mark; Almasy, Laura; Soria, Jose Manuel

    2012-01-01

    Altered mitochondrial DNA (mtDNA) levels have been associated with common diseases in humans. We investigated the genetic mechanism that controls mtDNA levels using genome-wide linkage analyses in families from the Genetic Analysis of Idiopathic Thrombophilia Project (GAIT). We measure mtDNA levels by quantitative real-time PCR in 386 subjects from 21 extended Spanish families. A variance component linkage method using 485 microsatellites was conducted to evaluate linkage and to detect quantitative trait loci (QTLs) involved in the control of mtDNA levels. The heritalibility of mtDNA levels was 0.33 (p = 1.82e-05). We identified a QTL on Chromosome 2 (LOD = 2.21) using all of the subjects, independently on their sex. When females and males were analysed separately, three QTLs were identified. Females showed the same QTL on Chromosome 2 (LOD = 3.09), indicating that the QTL identified in the analysis using all of the subjects was a strong female QTL, and another one on Chromosome 3 (LOD = 2.67), whereas in males a QTL was identified on Chromosome 1 (LOD = 2.81). These QTLs were fine-mapped to find associations with mtDNA levels. The most significant SNP association was for the rs10888838 on Chromosome 1 in males. This SNP mapped to the gene MRPL37, involved in mitochondrial protein translation. The rs2140855 on Chromosome 2 showed association in the analysis using all of the subjects. It was near the gene CMPK2, which encodes a mitochondrial enzyme of the salvage pathway of deoxyribonucleotide synthesis. Our results provide evidence of a sex-specific genetic mechanism for the control of mtDNA levels and provide a framework to identify new genes that influence mtDNA levels. PMID:22916149

  20. Sex-specific regulation of mitochondrial DNA levels: genome-wide linkage analysis to identify quantitative trait loci.

    PubMed

    López, Sonia; Buil, Alfonso; Souto, Juan Carlos; Casademont, Jordi; Blangero, John; Martinez-Perez, Angel; Fontcuberta, Jordi; Lathrop, Mark; Almasy, Laura; Soria, Jose Manuel

    2012-01-01

    Altered mitochondrial DNA (mtDNA) levels have been associated with common diseases in humans. We investigated the genetic mechanism that controls mtDNA levels using genome-wide linkage analyses in families from the Genetic Analysis of Idiopathic Thrombophilia Project (GAIT). We measure mtDNA levels by quantitative real-time PCR in 386 subjects from 21 extended Spanish families. A variance component linkage method using 485 microsatellites was conducted to evaluate linkage and to detect quantitative trait loci (QTLs) involved in the control of mtDNA levels. The heritalibility of mtDNA levels was 0.33 (p=1.82e-05). We identified a QTL on Chromosome 2 (LOD=2.21) using all of the subjects, independently on their sex. When females and males were analysed separately, three QTLs were identified. Females showed the same QTL on Chromosome 2 (LOD=3.09), indicating that the QTL identified in the analysis using all of the subjects was a strong female QTL, and another one on Chromosome 3 (LOD=2.67), whereas in males a QTL was identified on Chromosome 1 (LOD=2.81). These QTLs were fine-mapped to find associations with mtDNA levels. The most significant SNP association was for the rs10888838 on Chromosome 1 in males. This SNP mapped to the gene MRPL37, involved in mitochondrial protein translation. The rs2140855 on Chromosome 2 showed association in the analysis using all of the subjects. It was near the gene CMPK2, which encodes a mitochondrial enzyme of the salvage pathway of deoxyribonucleotide synthesis. Our results provide evidence of a sex-specific genetic mechanism for the control of mtDNA levels and provide a framework to identify new genes that influence mtDNA levels. PMID:22916149

  1. Serum sex hormone and growth arrest-specific protein 6 levels in male patients with coronary heart disease.

    PubMed

    Zhao, Rui; Li, Yan; Dai, Wen

    2016-01-01

    Epidemiological studies have shown a high prevalence of low serum testosterone levels in men with cardiovascular disease. Moreover, the tyrosine kinase receptor Axl, the ligand of which is growth arrest-specific protein 6 (GAS6), is expressed in the vasculature, and serum GAS6 levels are associated with endothelial dysfunction and cardiovascular events. Testosterone regulates GAS6 gene transcription directly, which inhibits calcification of vascular smooth muscle cells and provides a mechanistic insight into the cardioprotective action of androgens. This study was designed to determine the correlation between serum GAS6 and testosterone levels in male patients with coronary heart disease (CHD). We recruited 225 patients with CHD and 102 apparently healthy controls. Serum concentrations of GAS6 and soluble Axl were quantified by an enzyme-linked immunosorbent assay. Levels of high-sensitivity C-reactive protein, testosterone, estradiol, and other routine biochemical markers were also measured. Testosterone decreased from 432.69 ± 14.40 to 300.76 ± 6.23 ng dl-1 (P < 0.001) and GAS6 decreased from 16.20 ± 0.31 to 12.51 ± 0.19 ng ml-1 (P < 0.001) in patients with CHD, compared with control subjects. Multiple linear regression analysis showed that serum testosterone and GAS6 levels were positively associated in male patients with CHD. Alterations in GAS6 levels may influence the development of CHD. Downregulation of GAS6/Axl signaling in the presence of low sex hormone levels during disease progression is a potential mechanism by which GAS6 affects CHD. This study provides novel results regarding the influence of sex hormones on serum GAS6 levels in patients with CHD. PMID:26924277

  2. Specific absorption spectra of hemoglobin at different PO2 levels: potential noninvasive method to detect PO2 in tissues

    NASA Astrophysics Data System (ADS)

    Liu, Peipei; Zhu, Zhirong; Zeng, Changchun; Nie, Guang

    2012-12-01

    Hemoglobin (Hb), as one of main components of blood, has a unique quaternary structure. Its release of oxygen is controlled by oxygen partial pressure (PO2). We investigate the specific spectroscopic changes in Hb under different PO2 levels to optimize clinical methods of measuring tissue PO2. The transmissivity of Hb under different PO2 levels is measured with a UV/Vis fiber optic spectrometer. Its plotted absorption spectral curve shows two high absorption peaks at 540 and 576 nm and an absorption valley at 560 nm when PO2 is higher than 100 mm Hg. The two high absorption peaks decrease gradually with a decrease in PO2, whereas the absorption valley at 560 nm increases. When PO2 decreases to approximately 0 mm Hg, the two high absorption peaks disappear completely, while the absorption valley has a hypochromic shift (8 to 10 nm) and forms a specific high absorption peak at approximately 550 nm. The same phenomena can be observed in visible reflectance spectra of finger-tip microcirculation. Specific changes in extinction coefficient and absorption spectra of Hb occur along with variations in PO2, which could be used to explain pathological changes caused by tissue hypoxia and for early detection of oxygen deficiency diseases in clinical monitoring.

  3. Diastolic Dysfunction of Aging Is Independent of Myocardial Structure but Associated with Plasma Advanced Glycation End-Product Levels

    PubMed Central

    Campbell, Duncan J.; Somaratne, Jithendra B.; Jenkins, Alicia J.; Prior, David L.; Yii, Michael; Kenny, James F.; Newcomb, Andrew E.; Schalkwijk, Casper G.; Black, Mary Jane; Kelly, Darren J.

    2012-01-01

    Background Heart failure is associated with abnormalities of myocardial structure, and plasma levels of the advanced glycation end-product (AGE) Nε-(carboxymethyl)lysine (CML) correlate with the severity and prognosis of heart failure. Aging is associated with diastolic dysfunction and increased risk of heart failure, and we investigated the hypothesis that diastolic dysfunction of aging humans is associated with altered myocardial structure and plasma AGE levels. Methods We performed histological analysis of non-ischemic left ventricular myocardial biopsies and measured plasma levels of the AGEs CML and low molecular weight fluorophores (LMWFs) in 26 men undergoing coronary artery bypass graft surgery who had transthoracic echocardiography before surgery. None had previous cardiac surgery, myocardial infarction, atrial fibrillation, or heart failure. Results The patients were aged 43–78 years and increasing age was associated with echocardiographic indices of diastolic dysfunction, with higher mitral Doppler flow velocity A wave (r = 0.50, P = 0.02), lower mitral E/A wave ratio (r = 0.64, P = 0.001), longer mitral valve deceleration time (r = 0.42, P = 0.03) and lower early diastolic peak velocity of the mitral septal annulus, e’ (r = 0.55, P = 0.008). However, neither mitral E/A ratio nor mitral septal e’ was correlated with myocardial total, interstitial or perivascular fibrosis (picrosirius red), immunostaining for collagens I and III, CML, and receptor for AGEs (RAGE), cardiomyocyte width, capillary length density, diffusion radius or arteriolar dimensions. Plasma AGE levels were not associated with age. However, plasma CML levels were associated with E/A ratio (r = 0.44, P = 0.04) and e’ (r = 0.51, P = 0.02) and LMWF levels were associated with E/A ratio (r = 0.49, P = 0.02). Moreover, the mitral E/A ratio remained correlated with plasma LMWF levels in all patients (P = 0.04) and the mitral

  4. Sex-specific association of the SPTY2D1 rs7934205 polymorphism and serum lipid levels

    PubMed Central

    Guo, Tao; Yin, Rui-Xing; Chen, Xia; Bin, Yuan; Nie, Rong-Jun; Li, Hui

    2015-01-01

    The objective of the present study was to detect the association of the rs7934205 single nucleotide polymorphism (SNP) near the Suppressor of Ty, domain containing 1 gene (SPTY2D1) and serum lipid levels between males and females in the Mulao and Han populations. Genotyping of SPTY2D1 rs7934205 SNP was performed in 933 of Mulao and 865 of Han participants using polymerase chain reaction and restriction fragment length polymorphism. The T allele frequency was different between Mulao males and females (23.2% vs. 27.9%, P = 0.018). The genotype and allele frequencies were also different between Han males and females (P = 0.020 and P = 0.004; respectively). Serum levels of apolipoprotein (Apo) A1 in Mulao males; and total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), ApoA1 and ApoB in Mulao females were different between the CC and CT/TT genotypes (P < 0.05). Serum TC, ApoB levels in Han males, and ApoB levels in Han females were different between the CC and CT/TT genotypes (P < 0.05). The subjects with CT/TT genotype in both Mulao and Han males and females have more favorable lipid profiles than those with CC genotype. These findings suggest that the association between the SPTY2D1 rs7934205 SNP and serum lipid levels might have ethnic- and/or sex-specificity. PMID:25755761

  5. Effect of Intensive Non-Surgical Treatment on the Level of Serum Inflammatory Markers in Advanced Periodontitis

    PubMed Central

    Radafshar, G.; Shad, B.; Ariamajd, E.; Geranmayeh, S.

    2010-01-01

    Objective: To assess whether non-surgical periodontal treatment is associated with changes in serological markers of systemic inflammation. Materials and Methods: Thirty-five systemically healthy subjects with severe generalized periodontitis meeting the inclusion criteria participated in a four-month single blind interventional trial of which thirty-two completed the study. Periodontal parameters and inflammatory markers [C-reactive protein (CRP) and plasma fibrinogen] and also the white blood cell count (WBC) were evaluated prior to and four months after delivery of intensive non-surgical periodontal therapy with simultaneous lavage of chlorhexidine 0.1% from the tip of the ultrasonic instrument into the pockets. Results: Significant differences in serum CRP levels were observed four months after treatment compared to the baseline (1.85, SD=1.93 vs 2.46, SD=2.32, respectively, P<0.0001). Periodontal treatment also resulted in a significant difference in WBC and neutrophil counts compared to the baseline (P<0.0001). The reduction in fibrinogen levels was not significant at the end of the research period. Significant improvement in the pocket probing depth and clinical attachment level for pockets with initially 4–6 mm and then more than 7 mm depth was observed. Changes in plaque and bleeding scores were also statistically significant (82.75 vs. 35.84 and 19.03 vs. 1.81, respectively). Conclusion: Periodontal treatment is effective in reducing CRP levels and white blood cell count, while fibrinogen levels are not influenced by periodontal therapy. Periodontal treatment may therefore decrease the systemic inflammatory burden in patients with advanced periodontitis. PMID:21998772

  6. Comparison of parasite-specific immunoglobulin levels in two chicken lines during sustained infection with Ascaridia galli.

    PubMed

    Norup, Liselotte Rothmann; Dalgaard, Tina S; Pleidrup, Janne; Permin, Anders; Schou, Torben W; Jungersen, Gregers; Fink, Dorte R; Juul-Madsen, Helle R

    2013-01-16

    Increasingly large numbers of poultry are held in production systems with access to outdoor areas. In these systems intestinal helminths are found with flock prevalences of up to 100%. Helminth infections influence chicken health negatively, which is why the following investigation has been performed. In the present experiment, 20 chickens of two inbred chicken lines containing the major histocompatibility complex (MHC) haplotypes, B14 and R5, were inoculated with 500 embryonated Ascaridia galli eggs. The A. galli-specific IgG titres of serum samples and the excretion of A. galli eggs in chicken faeces were measured for a period of 81 weeks. The level of excreted A. galli eggs measured as eggs per gram chicken faeces (EPG) varied greatly between chickens in each line. Significant differences were found between the two lines and with the R5 chickens reaching the highest levels. Likewise, the A. galli-specific IgG titres in serum differed significantly between the two lines, and an inverse relationship between infection level (EPG) and antibody titres was found. Although this inverse relationship suggests that humoral immunity may be involved in protection against A. galli infection, the high antibody titres did not prevent continued infection. PMID:22981407

  7. Evaluation of in utero sensitization by screening antigen-specific immunoglobulin E levels in umbilical cord blood

    PubMed Central

    Karakol, Burcu; Önal, Zehra Esra; Tabak, Yonca; Nuhoğlu, Çağatay; Ceran, Ömer

    2015-01-01

    Introduction The incidence of asthma and atopic reactions is increasing worldwide. Previous reports have suggested that maternal exposure to allergens during pregnancy may have potential effects on allergic sensitization in infants. Aim To evaluate the effects of maternal exposure to environmental allergens during pregnancy on in-utero sensitization. Material and methods Two hundred mothers and their infants were analyzed in this cross-sectional study. Mothers were given a questionnaire that had a series of questions to evaluate the maternal allergic status and environmental exposures during pregnancy. Plasma specific immunoglobulin E (IgE) levels to pets, grass, food (nuts) of all mothers and their infants were analyzed by an immune-enzymatic assay. Results There was no significant correlation between plasma specific IgE positivity in mothers, with regard to keeping indoor domestic pets, living in grass habitat, eating nuts in diet. A significant correlation was found between specific IgE presence in mothers and allergic reactions; however, there was no correlation between plasma specific IgE positivity of mothers and infants. Conclusions We concluded that prenatal maternal sensitivity to environmental allergens could not be evaluated as a predictive factor for in-utero sensitization. PMID:26161059

  8. Molecular-Level Thermodynamic Switch Controls Chemical Equilibrium in Sequence-Specific Hydrophobic Interaction of 35 Dipeptide Pairs

    PubMed Central

    Chun, Paul W.

    2003-01-01

    Applying the Planck-Benzinger methodology, the sequence-specific hydrophobic interactions of 35 dipeptide pairs were examined over a temperature range of 273–333 K, based on data reported by Nemethy and Scheraga in 1962. The hydrophobic interaction in these sequence-specific dipeptide pairs is highly similar in its thermodynamic behavior to that of other biological systems. The results imply that the negative Gibbs free energy change minimum at a well-defined stable temperature, 〈Ts〉, where the bound unavailable energy, TΔSo = 0, has its origin in the sequence-specific hydrophobic interactions, are highly dependent on details of molecular structure. Each case confirms the existence of a thermodynamic molecular switch wherein a change of sign in ΔCpo(T)reaction (change in specific heat capacity of reaction at constant pressure) leads to true negative minimum in the Gibbs free energy change of reaction, ΔGo(T)reaction, and hence a maximum in the related equilibrium constant, Keq. Indeed, all interacting biological systems examined to date by Chun using the Planck-Benzinger methodology have shown such a thermodynamic switch at the molecular level, suggesting its existence may be universal. PMID:12547816

  9. An analysis of the association between prostate cancer risk loci, PSA levels, disease aggressiveness and disease-specific mortality

    PubMed Central

    Sullivan, J; Kopp, R; Stratton, K; Manschreck, C; Corines, M; Rau-Murthy, R; Hayes, J; Lincon, A; Ashraf, A; Thomas, T; Schrader, K; Gallagher, D; Hamilton, R; Scher, H; Lilja, H; Scardino, P; Eastham, J; Offit, K; Vijai, J; Klein, R J

    2015-01-01

    Background: Genome-wide association studies have identified multiple single-nucleotide polymorphsims (SNPs) associated with prostate cancer (PCa). Although these SNPs have been clearly associated with disease risk, their relationship with clinical outcomes is less clear. Our aim was to assess the frequency of known PCa susceptibility alleles within a single institution ascertainment and to correlate risk alleles with disease-specific outcomes. Methods: We genotyped 1354 individuals treated for localised PCa between June 1988 and December 2007. Blood samples were prospectively collected and de-identified before being genotyped and matched to phenotypic data. We investigated associations between 61 SNPs and disease-specific end points using multivariable analysis and also determined if SNPs were associated with PSA at diagnosis. Results: Seven SNPs showed associations on multivariable analysis (P<0.05), rs13385191 with both biochemical recurrence (BR) and castrate metastasis (CM), rs339331 (BR), rs1894292, rs17178655 and rs11067228 (CM), and rs11902236 and rs4857841 PCa-specific mortality. After applying a Bonferroni correction for number of SNPs (P<0.0008), the only persistent significant association was between rs17632542 (KLK3) and PSA levels at diagnosis (P=1.4 × 10−5). Conclusions: We confirmed that rs17632542 in KLK3 is associated with PSA at diagnosis. No significant association was seen between loci and disease-specific end points when accounting for multiple testing. This provides further evidence that known PCa risk SNPs do not predict likelihood of disease progression. PMID:26068399

  10. Investigating the clinical usefulness of the Social Responsiveness Scale (SRS) in a tertiary level, autism spectrum disorder specific assessment clinic.

    PubMed

    Aldridge, Fiona J; Gibbs, Vicki M; Schmidhofer, Katherine; Williams, Megan

    2012-02-01

    The Social Responsiveness Scale (SRS; Constantino and Gruber in Social Responsiveness Scale (SRS). Western Psychological Services, Los Angeles, 2005) is a commonly used screening tool for identifying children with possible autism spectrum disorder (ASD). This study investigated the relationship between SRS scores and eventual diagnostic outcome for children referred to a tertiary level, autism specific assessment service. Forty eight children (mean age = 8.10; 92% male) underwent a comprehensive ASD assessment. Parent and teacher SRS scores were subsequently compared with diagnostic outcome. Sensitivity was high (91% for parent report; 84% for teacher report), however specificity was much lower (8% for parent report; 41% for teacher report). Results demonstrate a need for caution when interpreting SRS results based on current cut-off scores, particularly in children with previously identified social developmental problems. PMID:21516433

  11. Age and Prostate-Specific Antigen Level Prior to Diagnosis Predict Risk of Death from Prostate Cancer

    PubMed Central

    MacKintosh, F. Roy; Sprenkle, Preston C.; Walter, Louise C.; Rawson, Lori; Karnes, R. Jeffrey; Morrell, Christopher H.; Kattan, Michael W.; Nawaf, Cayce B.; Neville, Thomas B.

    2016-01-01

    A single early prostate-specific antigen (PSA) level has been correlated with a higher likelihood of prostate cancer diagnosis and death in younger men. PSA testing in older men has been considered of limited utility. We evaluated prostate cancer death in relation to age and PSA level immediately prior to prostate cancer diagnosis. Using the Veterans Affairs database, we identified 230,081 men aged 50–89 years diagnosed with prostate cancer and at least one prior PSA test between 1999 and 2009. Prostate cancer-specific death over time was calculated for patients stratified by age group (e.g., 50–59 years, through 80–89 years) and PSA range at diagnosis (10 ranges) using Kaplan–Meier methods. Risk of 10-year prostate cancer mortality across age and PSA was compared using log-rank tests with a Bonferroni adjustment for multiple testing. 10.5% of men diagnosed with prostate cancer died of cancer during the 10-year study period (mean follow-up = 3.7 years). Higher PSA values prior to diagnosis predict a higher risk of death in all age groups (p < 0.0001). Within the same PSA range, older age groups are at increased risk for death from prostate cancer (p < 0.0001). For PSA of 7–10 ng/mL, cancer-specific death, 10 years after diagnosis, increased from 7% for age 50–59 years to 51% for age 80–89 years. Men older than 70 years are more likely to die of prostate cancer at any PSA level than younger men, suggesting prostate cancer remains a significant problem among older men (even those aged 80+) and deserves additional study. PMID:27446803

  12. High Level Requirements for the Nuclear Energy -- Knowledge Base for Advanced Modeling and Simulation (NE-KAMS)

    SciTech Connect

    Rich Johnson; Hyung Lee; Kimberlyn C. Mousseau

    2011-09-01

    The US Department of Energy, Office of Nuclear Energy (DOE-NE), has been tasked with the important mission of ensuring that nuclear energy remains a compelling and viable energy source in the U.S. The motivations behind this mission include cost-effectively meeting the expected increases in the power needs of the country, reducing carbon emissions and reducing dependence on foreign energy sources. In the near term, to ensure that nuclear power remains a key element of U.S. energy strategy and portfolio, the DOE-NE will be working with the nuclear industry to support safe and efficient operations of existing nuclear power plants. In the long term, to meet the increasing energy needs of the U.S., the DOE-NE will be investing in research and development (R&D) and working in concert with the nuclear industry to build and deploy new, safer and more efficient nuclear power plants. The safe and efficient operations of existing nuclear power plants and designing, licensing and deploying new reactor designs, however, will require focused R&D programs as well as the extensive use and leveraging of advanced modeling and simulation (M&S). M&S will play a key role in ensuring safe and efficient operations of existing and new nuclear reactors. The DOE-NE has been actively developing and promoting the use of advanced M&S in reactor design and analysis through its R&D programs, e.g., the Nuclear Energy Advanced Modeling and Simulation (NEAMS) and Consortium for Advanced Simulation of Light Water Reactors (CASL) programs. Also, nuclear reactor vendors are already using CFD and CSM, for design, analysis, and licensing. However, these M&S tools cannot be used with confidence for nuclear reactor applications unless accompanied and supported by verification and validation (V&V) and uncertainty quantification (UQ) processes and procedures which provide quantitative measures of uncertainty for specific applications. The Nuclear Energy Knowledge base for Advanced Modeling and Simulation

  13. Gene-Specific DNA Methylation Association with Serum Levels of C-Reactive Protein in African Americans

    PubMed Central

    Sun, Yan V.; Lazarus, Alicia; Smith, Jennifer A.; Chuang, Yu-Hsuan; Zhao, Wei; Turner, Stephen T.; Kardia, Sharon L. R.

    2013-01-01

    A more thorough understanding of the differences in DNA methylation (DNAm) profiles in populations may hold promise for identifying molecular mechanisms through which genetic and environmental factors jointly contribute to human diseases. Inflammation is a key molecular mechanism underlying several chronic diseases including cardiovascular disease, and it affects DNAm profile on both global and locus-specific levels. To understand the impact of inflammation on the DNAm of the human genome, we investigated DNAm profiles of peripheral blood leukocytes from 966 African American participants in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. By testing the association of DNAm sites on CpG islands of over 14,000 genes with C-reactive protein (CRP), an inflammatory biomarker of cardiovascular disease, we identified 257 DNAm sites in 240 genes significantly associated with serum levels of CRP adjusted for age, sex, body mass index and smoking status, and corrected for multiple testing. Of the significantly associated DNAm sites, 80.5% were hypomethylated with higher CRP levels. The most significant Gene Ontology terms enriched in the genes associated with the CRP levels were immune system process, immune response, defense response, response to stimulus, and response to stress, which are all linked to the functions of leukocytes. While the CRP-associated DNAm may be cell-type specific, understanding the DNAm association with CRP in peripheral blood leukocytes of multi-ethnic populations can assist in unveiling the molecular mechanism of how the process of inflammation affects the risks of developing common disease through epigenetic modifications. PMID:23977389

  14. The correlation between LDH serum levels and clinical outcome in advanced biliary tract cancer patients treated with first line chemotherapy

    PubMed Central

    Faloppi, Luca; Del Prete, Michela; Gardini, Andrea Casadei; Santini, Daniele; Silvestris, Nicola; Bianconi, Maristella; Giampieri, Riccardo; Valgiusti, Martina; Brunetti, Oronzo; Bittoni, Alessandro; Andrikou, Kalliopi; Lai, Eleonora; Dessì, Alessandra; Cascinu, Stefano; Scartozzi, Mario

    2016-01-01

    LDH may represent an indirect marker of neo-angiogenesis and worse prognosis in many tumour types. We assessed the correlation between LDH and clinical outcome for biliary tract cancer (BTC) patients treated with first-line chemotherapy. Overall, 114 advanced BTC patients treated with first-line gemcitabine and cisplatin were included. Patients were divided into two groups (low vs. high LDH), according to pre-treatment LDH values. Patients were also classified according to pre- and post-treatment variation in LDH serum levels (increased vs. decreased). Median progression free survival (PFS) was 5.0 and 2.6 months respectively in patients with low and high pre-treatment LDH levels (p = 0.0042, HR = 0.56, 95% CI: 0.37–0.87). Median overall survival (OS) was 7.7 and 5.6 months (low vs. high LDH) (p = 0.324, HR = 0.81, 95% CI: 0.54–1.24). DCR was 71% vs. 43% (low vs. high LDH) (p = 0.002). In 38 patients with decreased LDH values after treatment, PFS and OS were respectively 6.2 and 12.1 months, whereas in 76 patients with post-treatment increased LDH levels, PFS and OS were respectively 3.0 and 5.1 months (PFS: p = 0.0009; HR = 0.49; 95% IC: 0.33–0.74; OS: p < 0.0001; HR = 0.42; 95% IC: 0.27–0.63). Our data seem to suggest that LDH serum level may predict clinical outcome in BTC patients receiving first-line chemotherapy. PMID:27063994

  15. The predictability of serum anti-Müllerian level in IVF/ICSI outcomes for patients of advanced reproductive age

    PubMed Central

    2011-01-01

    Background The role of serum anti-Müllerian hormone (AMH) as predictor of in-vitro fertilization outcomes has been much debated. The aim of the present study is to investigate the practicability of combining serum AMH level with biological age as a simple screening method for counseling IVF candidates of advanced reproductive age with potential poor outcomes prior to treatment initiation. Methods A total of 1,538 reference patients and 116 infertile patients aged greater than or equal to 40 years enrolled in IVF/ICSI cycles were recruited in this retrospective analysis. A reference chart of the age-related distribution of serum AMH level for Asian population was first created. IVF/ICSI patients aged greater than or equal to 40 years were then divided into three groups according to the low, middle and high tertiles the serum AMH tertiles derived from the reference population of matching age. The cycle outcomes were analyzed and compared among each individual group. Results For reference subjects aged greater than or equal to 40 years, the serum AMH of the low, middle and high tertiles were equal or lesser than 0.48, 0.49-1.22 and equal or greater than 1.23 ng/mL respectively. IVF/ICSI patients aged greater than or equal to 40 years with AMH levels in the low tertile had the highest cycle cancellation rate (47.6%) with zero clinical pregnancy. The nadir AMH level that has achieved live birth was 0.56 ng/mL, which was equivalent to the 36.4th percentile of AMH level from the age-matched reference group. The optimum cut-off levels of AMH for the prediction of nonpregnancy and cycle cancellation were 1.05 and 0.68 ng/mL, respectively. Conclusions Two criteria: (1) age greater than or equal to 40 years and (2) serum AMH level in the lowest tertile (equal or lesser than 33.3rd percentile) of the matching age group, may be used as markers of futility for counseling IVF/ICSI candidates. PMID:21843363

  16. Levels of synthesis of primate-specific nuclear proteins differ between growth-arrested and proliferating cells

    SciTech Connect

    Celis, J.E.; Madsen, P.; Nielsen, S.; Ratz, G.P.; Lauridsen, J.B.; Celis, A.

    1987-02-01

    A monoclonal antibody that reacts specifically with the proliferation-sensitive nuclear proteins, isoelectric focusing (IEF) 8Z31 (molecular weight (MW), 76,000 charge variants, HeLa protein catalogue number) has been characterized. As determined by indirect immunofluorescence, the antibody stains the nucleolus and nucleoplasm of interphase-cultured cells of primate origin, but does not react with cells of other species. Proteins having similar MWs and isoelectric points as the human or monkey (primates) proteins were not observed in cultured cells of the following species: aves, bat, dog, dolphin, goat, hamster, mink, mouse, pisces, potoroo, rabbit and rat. Quantitative two-dimensional (2D) gel electrophoretic analysis of (/sup 35/S)methionine-labelled proteins synthesized by normal (quiescent, proliferating) and SV40-transformed human MRC-5 fibroblasts revealed significant differences in the levels of synthesis of both IEF 8Z30 and 8Z31. In quiescent cells the main labelled product corresponded to IEF 8Z31 (ratio IEF 8Z31/8Z30, 2.3), while in the transformed cells the major product was IEF 8Z30 (ratio, 0.62). Normal proliferating fibroblasts exhibited similar levels of both proteins (ratio, 1.21). Combined levels of synthesis of both proteins were 1.50 and 1.20 times as high in the transformed cells as in the quiescent and proliferating cells, respectively. Modulation of the levels of synthesis of these proteins may play a role in cell proliferation.

  17. DEVELOPING SITE-SPECIFIC DERIVED CONCENTRATION GUIDELINE LEVELS FOR MULTIPLE MEDIA AT THE CONNECTICUT YANKEE HADDAM NECK PLANT

    SciTech Connect

    Taylor, S.W.; Smith, L.C.; Carr, R.K.; Carson, A.; Darois, E.

    2003-02-27

    As part of the license termination process, site-specific Derived Concentration Guideline Levels for the Haddam Neck Plant site are developed for soil, groundwater, concrete left standing, and concrete demolished that satisfy the radiological criteria for unrestricted use as defined in 10 CFR 20.1402. Background information on the license termination process and characteristics of the Haddam Neck Plant site are presented. The dose models and associated resident farmer and building occupancy scenarios, applicable pathways, and critical groups developed to establish the Derived Concentration Guideline Levels are described. A parameter assignment process is introduced wherein general population values are used to establish behavioral and metabolic parameters representative of an average member of the critical group, while the uncertainty associated with important physical parameters is considered. A key element of the parameter assignment process is the use of sensitivity analysis to identify the dose sensitive physical parameters and to ensure that such parameters are assigned conservative values. Structuring the parameter assignment process, completing the formal sensitivity analyses, and assigning conservative values to the sensitive physical parameters in a consistent way establishes a calculation framework that lead to Derived Concentration Guideline Levels with a uniform level of conservatism across all media and all radionuclides.

  18. Tobacco-specific N-nitrosamines NNN and NNK levels in cigarette brands between 2000 and 2014.

    PubMed

    Gunduz, I; Kondylis, A; Jaccard, G; Renaud, J-M; Hofer, R; Ruffieux, L; Gadani, F

    2016-04-01

    The evolution of the levels of tobacco-specific N-nitrosamines (TSNA), N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in mainstream (MS) cigarette smoke is investigated based on smoke and tobacco chemistry data of cigarette brands sold by Philip Morris International (PMI) between 2000 and 2014. A total of 315 cigarette samples representing a wide range of product and design characteristics manufactured by PMI between 2008 and 2014 were analyzed and compared to a previously published dataset of PMI brands manufactured in 2000. The data indicate that there is a substantial reduction of NNN and NNK levels in tobacco fillers and MS cigarette smoke per mg of tar and per mg of nicotine using Health Canada Intense (HCI) machine-smoking regime. This observed reduction in NNN and NNK levels in MS cigarette smoke is also supported by the downward trend observed on NNN and NNK levels in USA flue-cured Virginia and Burley tobacco lots from 2000 to 2014 crops, reflecting effectiveness of measures taken on curing and agricultural practices designed to minimize TSNA formation in tobacco. PMID:26806560

  19. CEA serum level as early predictive marker of outcome during EGFR-TKI therapy in advanced NSCLC patients.

    PubMed

    Facchinetti, Francesco; Aldigeri, Raffaella; Aloe, Rosalia; Bortesi, Beatrice; Ardizzoni, Andrea; Tiseo, Marcello

    2015-08-01

    Considering the role of carcinoembryonic antigen (CEA) serum levels as potential useful predictive marker during chemotherapy treatment, we studied its applicability in advanced non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs). Our retrospective cohort consists of 79 patients (33 EGFR mutated and 46 EGFR wild type or unknown) affected by advanced NSCLC, for whom CEA serum values at the beginning of TKI therapy and after the first month of treatment were available, regardless of treatment line. Baseline CEA value, percentage of CEA reduction after 1 month, and percentage of patients with ≥20 % CEA decrease after 1 month (CEA response) were correlated with disease control rate (DCR), progression-free (PFS), and overall (OS) survival, according to EGFR mutational status. Median baseline CEA levels were significantly higher in EGFR mutated (40.9 ng/ml; interquartile range (IQR) 8.9-197.6) than in wild-type cases (6.2 ng/ml; IQR 2.8-12.8; p = 0.003). Both percentage reduction in CEA levels (-10.7 vs. +13.4 %) and percentage of cases with CEA response (42 vs. 20 %) were significantly higher in mutated vs. wild-type/unknown patients (p = 0.007 and p = 0.027, respectively). In wild-type/unknown patients, CEA response was significantly correlated with DCR (p = 0.001) and resulted as a significant predictor of PFS both in univariate (p = 0.002) and in multivariate analyses (hazard ratio (HR) 0.27; 95 % confidence interval (CI) 0.11-0.66; p = 0.004); only a trend was found for OS prediction (p = 0.082). In EGFR-mutated group, CEA reduction did not show any correlation either with PFS or OS. CEA response after 1 month of EGFR-TKI therapy could be a useful marker, worthy to further studies, as early predictor of treatment outcome in EGFR wild-type/unknown unselected NSCLC cases for which no molecular predictor is yet available. PMID:25731731

  20. Generic versus specific competencies of entry-level public health graduates: employers' perceptions in Poland, the UK, and the Netherlands.

    PubMed

    Biesma, Regien G; Pavlova, Milena; Vaatstra, Rina; van Merode, Godefridus G; Czabanowska, Katarzyna; Smith, Tony; Groot, Wim

    2008-08-01

    Constant changes in society and the public health domain force public health professionals into new roles and the development of new competencies. Public health professionals will need to be trained to respond to this challenge. The aim of this comparative study among Poland, the UK and the Netherlands is to identify competence needs for Master of Public Health graduates entering the labour market from a European perspective. A self-administered questionnaire was sent to employers in the three countries, rating the importance of competency in public health on a master's level. In all three countries, interpersonal competencies, like team working and communication skills, are rated as highly important. However, employers in the UK and Poland generally rate public health specific competencies as much more important than their Dutch colleagues. It is concluded that while public health specific knowledge is providing a useful starting point for entry-level public health professionals, employers increasingly recognise the value of generic competencies such as communication and team working skills. The results suggest a stronger emphasis on teaching methods that encourage active learning and the integration of skills, which is crucial for enhancing graduates' employability, and foster an open attitude to multidisciplinary working, which is essential in modern health care. PMID:17151830

  1. Regulation of mRNA Levels by Decay-Promoting Introns that Recruit the Exosome Specificity Factor Mmi1

    PubMed Central

    Kilchert, Cornelia; Wittmann, Sina; Passoni, Monica; Shah, Sneha; Granneman, Sander; Vasiljeva, Lidia

    2015-01-01

    Summary In eukaryotic cells, inefficient splicing is surprisingly common and leads to the degradation of transcripts with retained introns. How pre-mRNAs are committed to nuclear decay is unknown. Here, we uncover a mechanism by which specific intron-containing transcripts are targeted for nuclear degradation in fission yeast. Sequence elements within these “decay-promoting” introns co-transcriptionally recruit the exosome specificity factor Mmi1, which induces degradation of the unspliced precursor and leads to a reduction in the levels of the spliced mRNA. This mechanism negatively regulates levels of the RNA helicase DDX5/Dbp2 to promote cell survival in response to stress. In contrast, fast removal of decay-promoting introns by co-transcriptional splicing precludes Mmi1 recruitment and relieves negative expression regulation. We propose that decay-promoting introns facilitate the regulation of gene expression. Based on the identification of multiple additional Mmi1 targets, including mRNAs, long non-coding RNAs, and sn/snoRNAs, we suggest a general role in RNA regulation for Mmi1 through transcript degradation. PMID:26670050

  2. Regulation of mRNA Levels by Decay-Promoting Introns that Recruit the Exosome Specificity Factor Mmi1.

    PubMed

    Kilchert, Cornelia; Wittmann, Sina; Passoni, Monica; Shah, Sneha; Granneman, Sander; Vasiljeva, Lidia

    2015-12-22

    In eukaryotic cells, inefficient splicing is surprisingly common and leads to the degradation of transcripts with retained introns. How pre-mRNAs are committed to nuclear decay is unknown. Here, we uncover a mechanism by which specific intron-containing transcripts are targeted for nuclear degradation in fission yeast. Sequence elements within these "decay-promoting" introns co-transcriptionally recruit the exosome specificity factor Mmi1, which induces degradation of the unspliced precursor and leads to a reduction in the levels of the spliced mRNA. This mechanism negatively regulates levels of the RNA helicase DDX5/Dbp2 to promote cell survival in response to stress. In contrast, fast removal of decay-promoting introns by co-transcriptional splicing precludes Mmi1 recruitment and relieves negative expression regulation. We propose that decay-promoting introns facilitate the regulation of gene expression. Based on the identification of multiple additional Mmi1 targets, including mRNAs, long non-coding RNAs, and sn/snoRNAs, we suggest a general role in RNA regulation for Mmi1 through transcript degradation. PMID:26670050

  3. An Investigation of the Relationship between Performance Appraisal and Career Development and Advancement of Mid-Level Women in Student Affairs Administration

    ERIC Educational Resources Information Center

    Corral, Christine R.

    2009-01-01

    The purpose of this study was to explore the performance appraisal experience of 14 mid-level women in student affairs administration at four-year colleges and universities in Northern Illinois using a qualitative research approach involving personal interviews. Previous research on career development and advancement of mid-level women in student…

  4. Low-dose cyclophosphamide enhances antigen-specific CD4(+) T cell responses to NY-ESO-1/ISCOMATRIX™ vaccine in patients with advanced melanoma.

    PubMed

    Klein, Oliver; Davis, Ian D; McArthur, Grant A; Chen, Li; Haydon, Andrew; Parente, Phillip; Dimopoulos, Nektaria; Jackson, Heather; Xiao, Kun; Maraskovsky, Eugene; Hopkins, Wendie; Stan, Rodica; Chen, Weisan; Cebon, Jonathan

    2015-04-01

    Clinical outcomes from cancer vaccine trials in patients with advanced melanoma have so far been disappointing. This appears at least partially due to a state of immunosuppression in these patients induced by an expansion of regulatory cell populations including regulatory T cells (Tregs). We have previously demonstrated potent immunogenicity of the NY-ESO-1/ISCOMATRIX™ vaccine in patients with resected melanoma (study LUD99-08); however, the same vaccine induced only a few vaccine antigen-specific immune responses in patients with advanced disease (study LUD2002-013). Pre-clinical models suggest that the alkylating agent cyclophosphamide can enhance immune responses by depleting Tregs. Therefore, we have enrolled a second cohort of patients with advanced melanoma in the clinical trial LUD2002-013 to investigate whether pre-treatment with cyclophosphamide could improve the immunogenicity of the NY-ESO-1/ISCOMATRIX™ vaccine. The combination treatment led to a significant increase in vaccine-induced NY-ESO-1-specific CD4(+) T cell responses compared with the first trial cohort treated with vaccine alone. We could not detect a significant decline in regulatory T cells in peripheral blood of patients 14 days after cyclophosphamide administration, although a decline at an earlier time point cannot be excluded. Our observations support the inclusion of cyclophosphamide in combination trials with vaccines and other immune-modulatory agents. PMID:25662405

  5. Iron Levels in Hepatocytes and Portal Tract Cells Predict Progression and Outcome of Patients with Advanced Chronic Hepatitis C1

    PubMed Central

    Lambrecht, Richard W.; Sterling, Richard K.; Naishadham, Deepa; Stoddard, Anne M.; Rogers, Thomas; Morishima, Chihiro; Morgan, Timothy R.; Bonkovsky, Herbert L.

    2011-01-01

    Background & Aims Iron might influence severity and progression of non-hemochromatotic liver diseases. We assessed the relationships between iron, variants in HFE, and progression and outcomes using data from the HALT-C Trial. We determined whether therapy with pegylated interferon (PegIFN) affects iron variables. Methods Participants were randomly assigned to groups given long-term therapy with PegIFN (n=400) or no therapy (n=413) for 3.5 y and followed for up to 8.7 y (median 6.0 y). Associations between patient characteristics and iron variables, at baseline and over time, were made using Kaplan-Meier analyses, Cox regression models, and repeated measures analysis of covariance. Iron was detected by Prussian blue staining. Results Patients with poor outcomes (increase in Child-Turcotte-Pugh score to ≥ 7, development of ascites, encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, hepatocellular carcinoma, death) had significantly higher baseline scores for stainable iron in hepatocytes and cells in portal tracts than those without outcomes. Staining for iron in portal triads correlated with lobular and total Ishak inflammatory and fibrosis scores (P<0.0001). High baseline levels of iron in triads increased the risk for poor outcome (hazard ratio=1.35, P=0.02). Iron staining decreased in hepatocytes but increased in portal stromal cells over time (P<0.0001). Serum levels of iron and total iron binding capacity decreased significantly over time (P <0.0001), as did serum ferritin (P=0.0003). Long-term therapy with PegIFN did not affect levels of iron staining. Common variants in HFE did not correlate with outcomes, including development of hepatocellular carcinoma. Conclusions Degree of stainable iron in hepatocytes and portal tract cells predicts progression and clinical and histological outcomes of patients with advanced chronic hepatitis C. Long-term therapy with low-dose PegIFN did not improve outcomes or iron variables. PMID:21335007

  6. Outcome After Conformal Salvage Radiotherapy in Patients With Rising Prostate-Specific Antigen Levels After Radical Prostatectomy

    SciTech Connect

    Geinitz, Hans; Riegel, Martina G.; Thamm, Reinhard; Astner, Sabrina T.; Lewerenz, Carolin; Zimmermann, Frank; Molls, Michael; Nieder, Carsten

    2012-04-01

    Purpose: This study attempts to improve our understanding of the role of salvage radiotherapy (SRT) in patients with prostate-specific antigen (PSA) relapse after radical prostatectomy with regard to biochemical control, rate of distant metastasis, and survival. Methods and Materials: We performed a retrospective analysis of 96 men treated with conformal prostate bed SRT (median, 64.8 Gy) at a single institution (median follow-up, 70 months). The majority had intermediate- or high-risk prostate cancer. Fifty-four percent underwent a resection with positive margins (R1 resection). The median time interval between surgery and SRT was 22 months. Results: After SRT, 66% of patients reached a PSA nadir of less than 0.2 ng/mL. However, the 5-year biochemical no evidence of disease rate was 35%. Seminal vesicle involvement was predictive for a significantly lower biochemical no evidence of disease rate. All patients with a preoperative PSA level greater than 50 ng/mL relapsed biochemically within 2 years. The 5-year distant metastasis rate was 18%, the 5-year prostate cancer-specific survival rate was 90%, and the 5-year overall survival rate was 88%. Significantly more distant metastases developed in patients with a PSA nadir greater than 0.05 ng/mL after SRT, and they had significantly inferior prostate cancer-specific and overall survival rates. Resection status (R1 vs. R0) was not predictive for any of the endpoints. Conclusions: Men with postoperative PSA relapse can undergo salvage treatment by prostate bed radiotherapy, but durable PSA control is maintained only in about one-third of the patients. Despite a high biochemical failure rate after SRT, prostate cancer-specific survival does not decrease rapidly.

  7. Highly specific fiber optic immunosensor coupled with immunomagnetic separation for detection of low levels of Listeria monocytogenes and L. ivanovii

    PubMed Central

    2012-01-01

    Background Immunomagnetic separation (IMS) and immunoassays are widely used for pathogen detection. However, novel technology platforms with highly selective antibodies are essential to improve detection sensitivity, specificity and performance. In this study, monoclonal antibodies (MAbs) against Internalin A (InlA) and p30 were generated and used on paramagnetic beads of varying diameters for concentration, as well as on fiber-optic sensor for detection. Results Anti-InlA MAb-2D12 (IgG2a subclass) was specific for Listeria monocytogenes and L. ivanovii, and p30-specific MAb-3F8 (IgM) was specific for the genus Listeria. At all bacterial concentrations (103–108 CFU/mL) tested in the IMS assay; the 1-μm diameter MyOne beads had significantly higher capture efficiency (P < 0.05) than the 2.8-μm diameter M-280 beads with both antibodies. The highest capture efficiency for MyOne-2D12 (49.2% for 105 CFU/mL) was significantly higher (P < 0.05) than that of MyOne-3F8 (16.6 %) and Dynabeads anti-Listeria antibody (9 %). Furthermore, capture efficiency for MyOne-2D12 was highly specific for L. monocytogenes and L. ivanovii. Subsequently, we captured L. monocytogenes by MyOne-2D12 and MyOne-3F8 from hotdogs inoculated with mono- or co-cultures of L. monocytogenes and L. innocua (10–40 CFU/g), enriched for 18 h and detected by fiber-optic sensor and confirmed by plating, light-scattering, and qPCR assays. The detection limit for L. monocytogenes and L. ivanovii by the fiber-optic immunosensor was 3 × 102 CFU/mL using MAb-2D12 as capture and reporter antibody. Selective media plating, light-scattering, and qPCR assays confirmed the IMS and fiber-optic results. Conclusions IMS coupled with a fiber-optic sensor using anti-InlA MAb is highly specific for L. monocytogenes and L. ivanovii and enabled detection of these pathogens at low levels from buffer or food. PMID:23176167

  8. An advanced understanding of the specific effects of xylan and surface lignin contents on enzymatic hydrolysis of lignocellulosic biomass

    SciTech Connect

    Ju, Xiaohui; Engelhard, Mark H.; Zhang, Xiao

    2013-01-17

    A deep understanding of biomass recalcitrance has been hampered by the intricate and heterogeneous nature of pretreated biomass substrates obtained from random deconstruction methods. In this study, we established a unique methodology based on chemical pulping principles to create "reference substrates" with intact cellulose fibers and controlled morphological and chemical properties that enable us to investigate the individual effect of xylan, bulk, and surface lignin content on enzymatic hydrolysis. We also developed and demonstrated an X-ray photoelectron spectroscopy (XPS) technique for quantifying surface lignin content on biomass substrates. The results from this study show that, apart from its hindrance effect, xylan can facilitate cellulose fibril swelling and thus create more accessible surface area, which improves enzyme and substrate interactions. Surface lignin has a significant impact on enzyme adsorption kinetics and hydrolysis rate. Advanced understanding of xylan, bulk, and surface lignin effects provides critical information for an effective biomass conversion process.

  9. The Effect of Testosterone Replacement Therapy on Prostate-Specific Antigen (PSA) Levels in Men Being Treated for Hypogonadism

    PubMed Central

    Kang, De-Ying; Li, Hong-Jun

    2015-01-01

    Abstract Testosterone replacement therapy is used for the treatment of age-related male hypogonadism, and prostate-specific antigen (PSA) is a primary screening tool for prostate cancer. The systematic review and meta-analysis aimed to determine the effect of testosterone replacement therapy on PSA levels. Medline, Cochrane Library, EMBASE, and Google Scholar databases were searched until February 28, 2014, and inclusion criteria were as follows: randomized controlled trial; intervention group received testosterone/androgen replacement therapy; control group did not receive treatment; and no history of prostate cancer. The primary outcome was change of PSA level between before and after treatment. Secondary outcomes were elevated PSA level after treatment, and the number of patients who developed prostate cancer. After initially identifying 511 articles, 15 studies with a total of 739 patients that received testosterone replacement and 385 controls were included. The duration of treatment ranged from 3 to 12 months. Patients treated with testosterone tended to have higher PSA levels, and thus a greater change than those that received control treatments (difference in means of PSA levels = 0.154, 95% confidence interval [CI] 0.069 to 0.238, P < 0.001). The difference in means of PSA levels were significant higher for patients that received testosterone intramuscularly (IM) than controls (difference in means of PSA levels = 0.271, 95% CI 0.117–0.425, P = 0.001). Elevated PSA levels after treatment were similar between patients that received treatment and controls (odds ratio [OR] = 1.02, 95% CI 0.48–2.20, P = 0.953). Only 3 studies provided data with respect to the development of prostate cancer, and rates were similar between those that received treatment and controls. Testosterone replacement therapy does not increase PSA levels in men being treated for hypogonadism, except when it is given IM and even the increase with IM administration

  10. Are Total, Intensity- and Domain-Specific Physical Activity Levels Associated with Life Satisfaction among University Students?

    PubMed Central

    Pedišić, Željko; Greblo, Zrinka; Phongsavan, Philayrath; Milton, Karen; Bauman, Adrian E.

    2015-01-01

    Background Thorough information about the relationship between physical activity (PA) and life satisfaction is still lacking. Therefore, this study examined the cross-sectional relationships between life satisfaction and meeting the World Health Organization (WHO) moderate to vigorous-intensity PA recommendations, total volume and duration of PA, intensity-specific PA (walking, moderate- and vigorous-intensity), domain-specific PA (work, transport-related, domestic, and leisure-time), and 11 domain and intensity-specific PA types among university students. Additionally, we examined the associations between life satisfaction and gender, age, disposable income, community size, smoking, alcohol intake, body mass index (BMI), and self-rated health. Methods The study included a random sample of 1750 university students in Zagreb, Croatia (response rate = 71.7%; 62.4% females; mean age 21.5 ± 1.8 years), using the International Physical Activity Questionnaire — long form and the Satisfaction with Life Scale. Results Higher life satisfaction was associated with female gender (β = 0.13; p = <0.001), younger age (β = -0.07; p = 0.024), higher disposable income (β = 0.10; p = 0.001), and better self-rated health (β = 0.30; p = <0.001). No significant association was found between life satisfaction and size of community (p = 0.567), smoking status (p = 0.056), alcohol consumption (p = 0.058), or BMI (p = 0.508). Among all PA variables, only leisure-time vigorous-intensity PA was significantly associated with life satisfaction after adjustments for socio-demographic characteristics, lifestyle and self-rated general health (β = 0.06; p = 0.045). Conclusions This study indicated a weak positive relationship between leisure-time vigorous-intensity PA and life satisfaction, whilst no such association was found for other PA variables. These findings underscore the importance of analyzing domain and intensity-specific PA levels in future studies among university students, as

  11. Levels of Serum Immunoglobulin G Specific to Bacterial Surface Protein A of Tannerella forsythia are Related to Periodontal Status

    PubMed Central

    Hall, Lindsay M.; Dunford, Robert G.; Genco, Robert J.; Sharma, Ashu

    2015-01-01

    Background Tannerella forsythia (Tf) is a Gram-negative anaerobe implicated in the development of periodontal disease. Bacterial surface protein A (BspA) is a surface-expressed and -secreted protein that is recognized as an important virulence factor of Tf. This study was undertaken to determine whether Tf BspA induces an antibody response in periodontal disease. We hypothesized that serum immunoglobulin (Ig)G antibody levels against BspA correlate with the disease of patients. Methods Sera were obtained from 100 patients with cardiac disorders and periodontal disease and 73 patients who experienced myocardial infarction but were periodontally healthy. Sera samples were assayed for anti-BspA antibody (total IgG and IgG subtypes) by enzyme-linked immunosorbent assay (ELISA). Antibody levels were measured in ELISA units by using an arbitrary patient as a standard. Results A negative correlation was found with BspA-specific total IgG antibody titers and the severity of disease measured as the clinical attachment level (CAL) when healthy and diseased groups were analyzed separately (healthy group: [−0.23, correlation value] Student’s t value [73 degrees of freedom] = 1.99; P = 0.05; diseased group: [−0.21] t [100 degrees of freedom] = 2.12; P = 0.03]). However, there was a positive correlation ([0.18 correlation value] Student’s t value [173 degrees of freedom] = 2.39; P = 0.017) when healthy and diseased groups were combined. A strong positive correlation ([0.338 correlation value] Student’s t value [173 degrees of freedom] = 4.69; P <0.0001) between the BspA-specific IgG titers and periodontal probing depth was observed when healthy and disease groups were combined. Conclusions Data demonstrated that antibodies to Tf BspA were elicited in patients with periodontal disease, and antibody levels were associated with the disease severity. Furthermore, data suggested that anti-BspA IgG might have a protective function in periodontal disease by minimizing the

  12. Predicting homophobic behavior among heterosexual youth: domain general and sexual orientation-specific factors at the individual and contextual level.

    PubMed

    Poteat, V Paul; DiGiovanni, Craig D; Scheer, Jillian R

    2013-03-01

    As a form of bias-based harassment, homophobic behavior remains prominent in schools. Yet, little attention has been given to factors that underlie it, aside from bullying and sexual prejudice. Thus, we examined multiple domain general (empathy, perspective-taking, classroom respect norms) and sexual orientation-specific factors (sexual orientation identity importance, number of sexual minority friends, parents' sexual minority attitudes, media messages). We documented support for a model in which these sets of factors converged to predict homophobic behavior, mediated through bullying and prejudice, among 581 students in grades 9-12 (55 % female). The structural equation model indicated that, with the exception of media messages, these additional factors predicted levels of prejudice and bullying, which in turn predicted the likelihood of students to engage in homophobic behavior. These findings highlight the importance of addressing multiple interrelated factors in efforts to reduce bullying, prejudice, and discrimination among youth. PMID:22956337

  13. Creating a lesson that addresses gender differences in physics testing a specific instructional technique in college level physics education

    NASA Astrophysics Data System (ADS)

    Lincoln, James J.

    Research-based instructional methods are applied in an effort to close the persistent gender gap in physics. Creating a short text on a limited topic using some of these methods could benefit female students specifically. A literature review showed research on the gender gap in physics and updated instructional methods for females. Two female physics students were interviewed and observations were conducted at a high performing all-girls school. A physics lab dialogue between two female physics students was recorded and analyzed, which informed the style and voice of the interactive dialogue lesson. An original written lesson intended to engage female physics students was created and tested on three classes of college-level physics students. The survey data, based on multiple choice and essay responses, measured the students' opinions of the lesson and their current textbook. Results showed the interactive lesson was preferred over the current text, and some students requested similar lessons.

  14. Executive functions and Prader-Willi syndrome: global deficit linked with intellectual level and syndrome-specific associations.

    PubMed

    Chevalère, Johann; Postal, Virginie; Jauregui, Joseba; Copet, Pierre; Laurier, Virginie; Thuilleaux, Denise

    2015-05-01

    The aim of this study was to support the growing evidence suggesting that Prader-Willi Syndrome (PWS) might present with an impairment of executive functions (EFs) and to investigate whether this impairment is specific to patients with PWS or due to their intellectual disability (ID). Six tasks were administered to assess EFs (inhibition, switching, updating, cognitive estimation, and planning) to 17 patients with PWS and 17 age-matched healthy individuals. Performance was significantly impaired in the PWS group on all EFs and after controlling for IQ level, intergroup differences remained only for switching and cognitive estimation. In conclusion, PWS seems to be associated with a global impairment of EFs that appears to be closely linked with intellectual impairment but also with the PWS itself. PMID:25928434

  15. A Specific miRNA Signature Correlates With Complete Pathological Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

    SciTech Connect

    Della Vittoria Scarpati, Giuseppina; Falcetta, Francesca; Carlomagno, Chiara; Ubezio, Paolo; Marchini, Sergio; De Stefano, Alfonso; Singh, Vijay Kumar; D'Incalci, Maurizio; De Placido, Sabino; Pepe, Stefano

    2012-07-15

    Purpose: MicroRNAs (miRNAs) are small, noncoding RNA molecules that can be down- or upregulated in colorectal cancer and have been associated to prognosis and response to treatment. We studied miRNA expression in tumor biopsies of patients with rectal cancer to identify a specific 'signature' correlating with pathological complete response (pCR) after neoadjuvant chemoradiotherapy. Methods and Materials: A total of 38 T3-4/N+ rectal cancer patients received capecitabine-oxaliplatin and radiotherapy followed by surgery. Pathologic response was scored according to the Mandard TRG scale. MiRNA expression was analyzed by microarray and confirmed by real-time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) on frozen biopsies obtained before treatment. The correlation between miRNA expression and TRG, coded as TRG1 (pCR) vs. TRG >1 (no pCR), was assessed by methods specifically designed for this study. Results: Microarray analysis selected 14 miRNAs as being differentially expressed in TRG1 patients, and 13 were confirmed by qRT-PCR: 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909 Asterisk-Operator , miR-630, miR-765) were significantly upregulated in TRG1 patients, 2 (miR-1274b, miR-720) were downexpressed. MiR-622 and miR-630 had a 100% sensitivity and specificity in selecting TRG1 cases. Conclusions: A set of 13 miRNAs is strongly associated with pCR and may represent a specific predictor of response to chemoradiotherapy in rectal cancer patients.

  16. GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients

    PubMed Central

    Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo JV; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

    2013-01-01

    α-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as “incurable” diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy. PMID:24179708

  17. GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients.

    PubMed

    Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo Jv; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

    2013-08-01

    α-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as "incurable" diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy. PMID:24179708

  18. Assessing the effectiveness of interventions to promote advance directives among older adults: a systematic review and multi-level analysis.

    PubMed

    Bravo, Gina; Dubois, Marie-France; Wagneur, Bernard

    2008-10-01

    Many studies have investigated the effectiveness of interventions in promoting advance directives (ADs) but there is uncertainty as to what works best, and in whom. We conducted a systematic review of the evidence in this regard, using both classical meta-analysis approaches and multi-level analyses. Eleven databases were searched for relevant reports published through March 2007. All prospective studies were eligible, whether involving a single group or several and, in the latter case, regardless of the allocation mechanism. Outcomes included formal and informal ADs assessed by chart review or self-report. Heterogeneous sets of outcomes were pooled under a random-effects model. The search yielded 55 studies, half of which targeted outpatients. Most groups of subjects were educated in a single session led by one healthcare professional. Outcomes were measured within six months of the intervention in 73% of cases. The largest set of single-arm studies yielded an overall AD completion rate of 45.6%. Across randomized trials, the largest pooled odds ratio was 4.0, decreasing to 2.6 when all comparative studies were included. Multi-variable analyses identified the provision of oral information over multiple sessions as the most successful intervention. This was true regardless of the target population. These findings support the effectiveness of educational interventions in increasing the formulation of ADs and provide practical advice on how best to achieve this goal. PMID:18644667

  19. Pushing CT and MR Imaging to the Molecular Level for Studying the “Omics”: Current Challenges and Advancements

    PubMed Central

    Huang, Hsuan-Ming; Shih, Yi-Yu

    2014-01-01

    During the past decade, medical imaging has made the transition from anatomical imaging to functional and even molecular imaging. Such transition provides a great opportunity to begin the integration of imaging data and various levels of biological data. In particular, the integration of imaging data and multiomics data such as genomics, metabolomics, proteomics, and pharmacogenomics may open new avenues for predictive, preventive, and personalized medicine. However, to promote imaging-omics integration, the practical challenge of imaging techniques should be addressed. In this paper, we describe key challenges in two imaging techniques: computed tomography (CT) and magnetic resonance imaging (MRI) and then review existing technological advancements. Despite the fact that CT and MRI have different principles of image formation, both imaging techniques can provide high-resolution anatomical images while playing a more and more important role in providing molecular information. Such imaging techniques that enable single modality to image both the detailed anatomy and function of tissues and organs of the body will be beneficial in the imaging-omics field. PMID:24738056

  20. mRNA and Protein levels of rat pancreas specific protein disulphide isomerase are downregulated during Hyperglycemia.

    PubMed

    Gupta, Rajani; Bhar, Kaushik; Sen, Nandini; Bhowmick, Debajit; Mukhopadhyay, Satinath; Panda, Koustubh; Siddhanta, Anirban

    2016-02-01

    Diabetes (Type I and Type II) which affects nearly every organ in the body is a multi-factorial non-communicable disorder. Hyperglycemia is the most characteristic feature of this disease. Loss of beta cells is common in both types of diabetes whose detailed cellular and molecular mechanisms are yet to be elucidated. As this disease is complex, identification of specific biomarkers for its early detection, management and devising new therapies is challenging. Based on the fact that functionally defective proteins provide the biochemical basis for many diseases, in this study, we tried to identify differentially expressed proteins during hyperglycemia. For that, hyperglycemia was induced in overnight fasted rats by intra-peritoneal injection of streptozotocin (STZ). The pancreas was isolated from control and treated rats for subsequent analyses. The 2D-gel electrophoresis followed by MALDI-TOF-MS-MS analyses revealed several up- and down-regulated proteins in hyperglycemic rat pancreas including the downregulation of a pancreas specific isoform of protein disulphide isomerase a2 (Pdia2).This observation was validated by western blot. Quantitative PCR experiments showed that the level of Pdia2 mRNA is also proportionally reduced in hyperglycemic pancreas. PMID:26934777

  1. Genetic variants of MAOB affect serotonin level and specific behavioral attributes to increase autism spectrum disorder (ASD) susceptibility in males.

    PubMed

    Chakraborti, Barnali; Verma, Deepak; Karmakar, Arijit; Jaiswal, Preeti; Sanyal, Aritrika; Paul, Debarshi; Sinha, Swagata; Singh, Asem Surindro; Guhathakurta, Subhrangshu; Roychowdhury, Anirban; Panda, Chinmoy Kumar; Ghosh, Saurabh; Mohanakumar, Kochupurackal P; Mukhophadhyay, Kanchan; Rajamma, Usha

    2016-11-01

    Serotonergic system participates in various developmental processes and modulation of behaviour. Autism Spectrum Disorder (ASD) is characterized by a range of behavioral symptoms scaling from mild to severe. Abnormal 5-HT synthesis and signalling, platelet hyperserotonemia and amelioration of repetitive behaviours by SSRI are some of the key findings, which reinforced the hypothesis that serotonergic genes might act as ASD susceptible genes. Therefore, genes encoding monoamine oxidases A/B (MAOA/MAOB) received special attention as these genes are located on the X-chromosome and the gene products are responsible for 5-HT degradation. In the present study, we conducted population-based association analysis of eight markers of MAOB with ASD in a study cohort of 203 cases and 236 controls form India and examined its effect on platelet 5-HT content and behaviour. Gender-specific changes were observed for the contrasting LD between pair of markers among cases and controls. Case-control analysis demonstrated over-distribution of major C allele of rs2283728 and rs2283727 in male and female ASD cases respectively. Haplotypic distribution and interaction among markers showed more robust effect in male cases. Interestingly, male ASD cases displayed higher platelet 5-HT content in comparison to the respective controls. Quantitative trait analysis revealed significant correlation of genetic variants and haplotypes of MAOB markers, rs1799836 and rs6324 with increased platelet 5-HT level and CARS scores for specific behavioral symptoms respectively in males. This study suggests that MAOB increases ASD risk in males, possibly through its sex-specific regulatory effect on 5-HT metabolism and behavior. PMID:27381555

  2. Asthma Symptoms and Specific IgE Levels among Toluene Diisocyanate (TDI) Exposed Workers in Tehran, Iran

    PubMed Central

    SHARIFI, Laleh; KARIMI, Akram; SHOKOUHI SHOORMASTI, Raheleh; MIRI, Sara; HEYDAR NAZHAD, Hassan; BOKAIE, Saied; FAZLOLLAHI, Mohammad Reza; SADEGHNIIAT HAGHIGHI, Khosro; POURPAK, Zahra; MOIN, Mostafa

    2013-01-01

    Background Toluene diisocyanate (TDI) is an imperative chemical substance used in the production of polyurethane foams, elastomers, paints and coatings that cause a variety of health problems in workers who are exposed in work places. This study aimed to determine the asthma symptoms and serum specific IgE levels in TDI exposed workers and comparing the results with healthy control group. Methods: All the plants that use TDI in the manufacturing of paint and glue in the west of Tehran Province entered to the study and all the workers (550) completed modified initial questionnaire of the NIOSH, the questions were consisted of asthma symptoms. For each symptomatic exposed worker one healthy, sex and age matched control selected. Total IgE and Specific TDI IgE tests were done for each case and control groups. Results: Among 550 TDI exposed workers, 26(4.7%) had asthma symptoms. Nine (34.6%) of symptomatic workers who were exposed to TDI were active cigarette consumer versus 3(11.5%) unexposed workers, P=0.049(CI= 0.953–17.29) OR=4.059. Nine (34.6%) workers had positive family history of atopy versus 1(3.8%) unexposed workers, P=0.0138 (CI= 1.45–305.41) OR=13.24. TDI specific IgE was found in 2 TDI exposed workers and 1 unexposed worker (P=0.5). Mean of total IgE was 339.05 in exposed workers (P=0.201). Conclusion: This study provides clinical and paraclinical data of workers exposed to TDI and points to a relation between atopy and smoking habit with asthma symptoms that offer preventing recommendations for TDI exposed workers and their heath administrators. PMID:23785679

  3. Analyzing the Relationship of Geographic Mobility and Institutional Prestige to Career Advancement of Women in Academic Medicine Pursuing Midcareer-, Senior-, or Executive-Level Administrative Positions: Implications for Career Advancement Strategies

    ERIC Educational Resources Information Center

    McLean, Marsha Renee

    2010-01-01

    The purpose of this study was to explore the relationship of geographic mobility and institutional prestige to career advancement defined as administrative promotions of women seeking midcareer-, senior-, or executive-level positions at academic health centers (AHCs) and their medical schools or in non-AHC related medical schools in the United…

  4. Unique Inflammatory Mediators and Specific IgE Levels Distinguish Local from Systemic Reactions after Anthrax Vaccine Adsorbed Vaccination.

    PubMed

    Garman, Lori; Smith, Kenneth; Muns, Emily E; Velte, Cathy A; Spooner, Christina E; Munroe, Melissa E; Farris, A Darise; Nelson, Michael R; Engler, Renata J M; James, Judith A

    2016-08-01

    Although the U.S. National Academy of Sciences concluded that anthrax vaccine adsorbed (AVA) has an adverse event (AE) profile similar to those of other adult vaccines, 30 to 70% of queried AVA vaccinees report AEs. AEs appear to be correlated with certain demographic factors, but the underlying immunologic pathways are poorly understood. We evaluated a cohort of 2,421 AVA vaccinees and found 153 (6.3%) reported an AE. Females were more likely to experience AEs (odds ratio [OR] = 6.0 [95% confidence interval {CI} = 4.2 to 8.7]; P < 0.0001). Individuals 18 to 29 years of age were less likely to report an AE than individuals aged 30 years or older (OR = 0.31 [95% CI = 0.22 to 0.43]; P < 0.0001). No significant effects were observed for African, European, Hispanic, American Indian, or Asian ancestry after correcting for age and sex. Additionally, 103 AEs were large local reactions (LLRs), whereas 53 AEs were systemic reactions (SRs). In a subset of our cohort vaccinated 2 to 12 months prior to plasma sample collection (n = 75), individuals with LLRs (n = 33) had higher protective-antigen (PA)-specific IgE levels than matched, unaffected vaccinated individuals (n = 50; P < 0.01). Anti-PA IgE was not associated with total plasma IgE, hepatitis B-specific IgE, or anti-PA IgG in individuals who reported an AE or in matched, unaffected AVA-vaccinated individuals. IP-10 was also elevated in sera of individuals who developed LLRs (P < 0.05). Individuals reporting SRs had higher levels of systemic inflammation as measured from C-reactive protein (P < 0.01). Thus, LLRs and SRs are mediated by distinct pathways. LLRs are associated with a vaccine-specific IgE response and IP-10, whereas SRs demonstrate increased systemic inflammation without a skewed cytokine profile. PMID:27280620

  5. Sex-specific chronic stress response at the level of adrenal gland modifies sexual hormone and leptin receptors

    PubMed Central

    Balog, Marta; Miljanović, Milan; Blažetić, Senka; Labak, Irena; Ivić, Vedrana; Viljetić, Barbara; Borbely, Attila; Papp, Zoltán; Blažeković, Robert; Vari, Sandor G.; Fagyas, Miklós; Heffer, Marija

    2015-01-01

    Aim To compare cardiometabolic risk-related biochemical markers and sexual hormone and leptin receptors in the adrenal gland of rat males, non-ovariectomized females (NON-OVX), and ovariectomized females (OVX) under chronic stress. Methods Forty six 16-week-old Sprague-Dawley rats were divided into male, NON-OVX, and OVX group and exposed to chronic stress or kept as controls. Weight, glucose tolerance test (GTT), serum concentration of glucose, and cholesterol were measured. Adrenal glands were collected at the age of 28 weeks and immunohistochemical staining against estrogen beta (ERβ), progesterone (PR), testosterone (AR), and leptin (Ob-R) receptors was performed. Results Body weight, GTT, serum cholesterol, and glucose changed in response to stress as expected and validated the applied stress protocol. Stressed males had significantly higher number of ERβ receptors in comparison to control group (P = 0.028). Stressed NON-OVX group had significantly decreased AR in comparison to control group (P = 0.007). The levels of PR did not change in any consistent pattern. The levels of Ob-R increased upon stress in all groups, but the significant difference was reached only in the case of stressed OVX group compared to control (P = 0.033). Conclusion Chronic stress response was sex specific. OVX females had similar biochemical parameters as males. Changes upon chronic stress in adrenal gland were related to a decrease in testosterone receptor in females and increase in estrogen receptor in males. PMID:25891869

  6. Compound-specific carbon and hydrogen isotope analysis of sub-parts per billion level waterborne petroleum hydrocarbons

    USGS Publications Warehouse

    Wang, Y.; Huang, Y.; Huckins, J.N.; Petty, J.D.

    2004-01-01

    Compound-specific carbon and hydrogen isotope analysis (CSCIA and CSHIA) has been increasingly used to study the source, transport, and bioremediation of organic contaminants such as petroleum hydrocarbons. In natural aquatic systems, dissolved contaminants represent the bioavailable fraction that generally is of the greatest toxicological significance. However, determining the isotopic ratios of waterborne hydrophobic contaminants in natural waters is very challenging because of their extremely low concentrations (often at sub-parts ber billion, or even lower). To acquire sufficient quantities of polycyclic aromatic hydrocarbons with 10 ng/L concentration for CSHIA, more than 1000 L of water must be extracted. Conventional liquid/liquid or solid-phase extraction is not suitable for such large volume extractions. We have developed a new approach that is capable of efficiently sampling sub-parts per billion level waterborne petroleum hydrocarbons for CSIA. We use semipermeable membrane devices (SPMDs) to accumulate hydrophobic contaminants from polluted waters and then recover the compounds in the laboratory for CSIA. In this study, we demonstrate, under a variety of experimental conditions (different concentrations, temperatures, and turbulence levels), that SPMD-associated processes do not induce C and H isotopic fractionations. The applicability of SPMD-CSIA technology to natural systems is further demonstrated by determining the ??13C and ??D values of petroleum hydrocarbons present in the Pawtuxet River, RI. Our results show that the combined SPMD-CSIA is an effective tool to investigate the source and fate of hydrophobic contaminants in the aquatic environments.

  7. Endocavity Ultrasound Hyperthermia for Locally Advanced Cervical Cancer: Patient-specific Modeling, Experimental Verification, and Combination with HDR Brachytherapy

    SciTech Connect

    Wootton, Jeffery; Diederich, Chris; Chen Xin; Prakash, Punit; Juang, Titania

    2010-03-09

    The feasibility of targeted hyperthermia delivery by an intrauterine ultrasound applicator to patient-specific treatment volumes in conjunction with HDR brachytherapy was investigated using theory and experiment. 30 HDR brachytherapy treatment plans were inspected to define hyperthermia treatment volumes (HTVs) based on tumor and radiation target volumes. Several typical cases were imported into a patient-specific treatment planning platform that optimized acoustic output power from an endocavity multisectored tubular array to conform temperature and thermal dose to HTVs. Perfusion was within a clinical range of 0.5-3 kg m{sup -3} s{sup -1}. Applicators were constructed with 1-3 elements at 6.5-8 MHz with 90 deg. -360 deg. sectoring and 25-35 mm heating length housed in a water-cooled PET catheter. Acoustic output was compared to heating in ex vivo tissue assessed with implanted thermometry. Radiation attenuation through the device was measured in an ionization chamber. The HTV extends 2-4 cm in diameter and 2-4 cm in length. The bladder and rectum can be within 10-12 mm. HTV targets can be covered with temperature clouds >41 deg. and thermal dose t{sup 43}>5 min with 45 deg. C maximum temperature and rectal temperature <41.5 deg. C. Sectored applicators preferentially direct energy laterally into the parametrium to limit heating of rectum and bladder. Interstitial brachytherapy catheters within the HTV could be used for thermal feedback during HT treatment. Temperature distributions in phantom show preferential heating within sectors and align well with acoustic output. Heating control along the device length and in angle is evident. A 4-6% reduction in radiation transmission through the transducers was observed, which could likely be compensated for in planning. Patient-specific modeling and experimental heating demonstrated 3-D conformal heating capabilities of endocavity ultrasound applicators.

  8. Advanced MicroObserver UGS integration with and cueing of the BattleHawk squad level loitering munition and UAV

    NASA Astrophysics Data System (ADS)

    Steadman, Bob; Finklea, John; Kershaw, James; Loughman, Cathy; Shaffner, Patti; Frost, Dean; Deller, Sean

    2014-06-01

    Textron's Advanced MicroObserver(R) is a next generation remote unattended ground sensor system (UGS) for border security, infrastructure protection, and small combat unit security. The original MicroObserver(R) is a sophisticated seismic sensor system with multi-node fusion that supports target tracking. This system has been deployed in combat theaters. The system's seismic sensor nodes are uniquely able to be completely buried (including antennas) for optimal covertness. The advanced version adds a wireless day/night Electro-Optic Infrared (EOIR) system, cued by seismic tracking, with sophisticated target discrimination and automatic frame capture features. Also new is a field deployable Gateway configurable with a variety of radio systems and flexible networking, an important upgrade that enabled the research described herein. BattleHawkTM is a small tube launched Unmanned Air Vehicle (UAV) with a warhead. Using transmitted video from its EOIR subsystem an operator can search for and acquire a target day or night, select a target for attack, and execute terminal dive to destroy the target. It is designed as a lightweight squad level asset carried by an individual infantryman. Although BattleHawk has the best loiter time in its class, it's still relatively short compared to large UAVs. Also it's a one-shot asset in its munition configuration. Therefore Textron Defense Systems conducted research, funded internally, to determine if there was military utility in having the highly persistent MicroObserver(R) system cue BattleHawk's launch and vector it to beyond visual range targets for engagement. This paper describes that research; the system configuration implemented, and the results of field testing that was performed on a government range early in 2013. On the integrated system that was implemented, MicroObserver(R) seismic detections activated that system's camera which then automatically captured images of the target. The geo-referenced and time-tagged Micro

  9. Quantitative changes in Galphaolf protein levels, but not D1 receptor, alter specifically acute responses to psychostimulants.

    PubMed

    Corvol, Jean-Christophe; Valjent, Emmanuel; Pascoli, Vincent; Robin, Aurélie; Stipanovich, Alexandre; Luedtke, Robert R; Belluscio, Leonardo; Girault, Jean-Antoine; Hervé, Denis

    2007-05-01

    Striatal dopamine D1 receptors (D1R) are coupled to adenylyl cyclase through Galphaolf. Although this pathway is involved in important brain functions, the consequences of quantitative alterations of its components are not known. We explored the biochemical and behavioral responses to cocaine and D-amphetamine (D-amph) in mice with heterozygous mutations of genes encoding D1R and Galphaolf (Drd1a+/- and Gnal+/-), which express decreased levels of the corresponding proteins in the striatum. Dopamine-stimulated cAMP production in vitro and phosphorylation of AMPA receptor GluR1 subunit in response to D-amph in vivo were decreased in Gnal+/-, but not Drd1a+/- mice. Acute locomotor responses to D1 agonist SKF81259, D-amph and cocaine were altered in Gnal+/- mice, and not in Drd1a+/- mice. This haploinsufficiency showed that Galphaolf but not D1R protein levels are limiting for D1R-mediated biochemical and behavioral responses. Gnal+/- mice developed pronounced locomotor sensitization and conditioned locomotor responses after repeated injections of D-amph (2 mg/kg) or cocaine (20 mg/kg). They also developed normal D-amph-conditioned place preference. The D1R/cAMP pathway remained blunted in repeatedly treated Gnal+/- mice. In contrast, D-amph-induced ERK activation was normal in the striatum of these mice, possibly accounting for the normal development of long-lasting behavioral responses to psychostimulants. Our results clearly dissociate biochemical mechanisms involved in acute and delayed behavioral effects of psychostimulants. They identify striatal levels of Galphaolf as a key factor for acute responses to psychostimulants and suggest that quantitative alterations of its expression may alter specific responses to drugs of abuse, or possibly other behavioral responses linked to dopamine function. PMID:17063155

  10. Salvage Radiotherapy for Rising Prostate-Specific Antigen Levels After Radical Prostatectomy for Prostate Cancer: Dose-Response Analysis

    SciTech Connect

    Bernard, Johnny Ray; Buskirk, Steven J.; Heckman, Michael G.; Diehl, Nancy N.; Ko, Stephen J.; Macdonald, Orlan K.; Schild, Steven E.; Pisansky, Thomas M.

    2010-03-01

    Purpose: To investigate the association between external beam radiotherapy (EBRT) dose and biochemical failure (BcF) of prostate cancer in patients who received salvage prostate bed EBRT for a rising prostate-specific antigen (PSA) level after radical prostatectomy. Methods and Materials: We evaluated patients with a rising PSA level after prostatectomy who received salvage EBRT between July 1987 and October 2007. Patients receiving pre-EBRT androgen suppression were excluded. Cox proportional hazards models were used to investigate the association between EBRT dose and BcF. Dose was considered as a numeric variable and as a categoric variable (low, <64.8 Gy; moderate, 64.8-66.6 Gy; high, >66.6 Gy). Results: A total of 364 men met study selection criteria and were followed up for a median of 6.0 years (range, 0.1-19.3 years). Median pre-EBRT PSA level was 0.6 ng/mL. The estimated cumulative rate of BcF at 5 years after EBRT was 50% overall and 57%, 46%, and 39% for the low-, moderate-, and high-dose groups, respectively. In multivariable analysis adjusting for potentially confounding variables, there was evidence of a linear trend between dose and BcF, with risk of BcF decreasing as dose increased (relative risk [RR], 0.77 [5.0-Gy increase]; p = 0.05). Compared with the low-dose group, there was evidence of a decreased risk of BcF for the high-dose group (RR, 0.60; p = 0.04), but no difference for the moderate-dose group (RR, 0.85; p = 0.41). Conclusions: Our results suggest a dose response for salvage EBRT. Doses higher than 66.6 Gy result in decreased risk of BcF.

  11. Specific absorption rate levels measured in a phantom head exposed to radio frequency transmissions from analog hand-held mobile phones

    SciTech Connect

    Anderson, V.; Joyner, K.H.

    1995-05-01

    Electric fields (E-fields) induced within a phantom head from exposure to three different advanced mobile phone system (AMPS) hand-held telephones were measured using an implantable E-Field probe. Measurements were taken in the eye nearest the phone and along a lateral scan through the brain from its center to the side nearest the phone. During measurement, the phones were positioned alongside the phantom head as in typical use and were configured to transmit at maximum power (600 mW nominal). The specific absorption rate (SAR) was calculated from the in situ E-field measurements, which varied significantly between phone models and antenna configuration. The SARs induced in the eye ranged from 0.007 to 0.21 W/kg. Metal-framed spectacles enhanced SAR levels in the eye by 9--29%. In the brain, maximum levels were recorded at the measurement point closest to the phone and ranged from 0.12 to 0.83 W/kg. These SARs are below peak spatial limits recommended in the US and Australian national standards and the IRPA guidelines for safe exposure to radio frequency (RF) electromagnetic fields. Furthermore, a detailed thermal analysis of the eye indicated only a 0.022 C maximum steady-state temperature rise in the eye from a uniform SAR loading of 0.21 W/kg. A more approximate thermal analysis in the brain also indicated only a small maximum temperature rise of 0.034 C for a local SAR loading of 0.83 W/kg.

  12. 34 CFR 350.65 - What level of participation is required of trainees in an Advanced Rehabilitation Research...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SERVICES, DEPARTMENT OF EDUCATION DISABILITY AND REHABILITATION RESEARCH PROJECTS AND CENTERS PROGRAM What... an Advanced Rehabilitation Research Training Project? 350.65 Section 350.65 Education Regulations of... Advanced Rehabilitation Research Training Project? Individuals who are receiving training under an...

  13. 34 CFR 350.65 - What level of participation is required of trainees in an Advanced Rehabilitation Research...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... SERVICES, DEPARTMENT OF EDUCATION DISABILITY AND REHABILITATION RESEARCH PROJECTS AND CENTERS PROGRAM What... an Advanced Rehabilitation Research Training Project? 350.65 Section 350.65 Education Regulations of... Advanced Rehabilitation Research Training Project? Individuals who are receiving training under an...

  14. 34 CFR 350.65 - What level of participation is required of trainees in an Advanced Rehabilitation Research...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... SERVICES, DEPARTMENT OF EDUCATION DISABILITY AND REHABILITATION RESEARCH PROJECTS AND CENTERS PROGRAM What... an Advanced Rehabilitation Research Training Project? 350.65 Section 350.65 Education Regulations of... Advanced Rehabilitation Research Training Project? Individuals who are receiving training under an...

  15. 34 CFR 350.65 - What level of participation is required of trainees in an Advanced Rehabilitation Research...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... SERVICES, DEPARTMENT OF EDUCATION DISABILITY AND REHABILITATION RESEARCH PROJECTS AND CENTERS PROGRAM What... an Advanced Rehabilitation Research Training Project? 350.65 Section 350.65 Education Regulations of... Advanced Rehabilitation Research Training Project? Individuals who are receiving training under an...

  16. An advanced approach for the generation of complex cellular material representative volume elements using distance fields and level sets

    NASA Astrophysics Data System (ADS)

    Sonon, B.; François, B.; Massart, T. J.

    2015-08-01

    A general and widely tunable method for the generation of representative volume elements for cellular materials based on distance and level set functions is presented. The approach is based on random tessellations constructed from random inclusion packings. A general methodology to obtain arbitrary-shaped tessellations to produce disordered foams is presented and illustrated. These tessellations can degenerate either in classical Voronoï tessellations potentially additively weighted depending on properties of the initial inclusion packing used, or in Laguerre tessellations through a simple modification of the formulation. A versatile approach to control the particular morphology of the obtained foam is introduced. Specific local features such as concave triangular Plateau borders and non-constant thickness heterogeneous coatings can be built from the tessellation in a straightforward way and are tuned by a small set of parameters with a clear morphological interpretation.

  17. Investigation of an Immunoassay with Broad Specificity to Quinolone Drugs by Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Data Sets and Advanced Quantitative Structure-Activity Relationship Analysis.

    PubMed

    Chen, Jiahong; Lu, Ning; Shen, Xing; Tang, Qiushi; Zhang, Chijian; Xu, Jun; Sun, Yuanming; Huang, Xin-An; Xu, Zhenlin; Lei, Hongtao

    2016-04-01

    A polyclonal antibody against the quinolone drug pazufloxacin (PAZ) but with surprisingly broad specificity was raised to simultaneously detect 24 quinolones (QNs). The developed competitive indirect enzyme-linked immunosorbent assay (ciELISA) exhibited limits of detection (LODs) for the 24 QNs ranging from 0.45 to 15.16 ng/mL, below the maximum residue levels (MRLs). To better understand the obtained broad specificity, a genetic algorithm with linear assignment of hypermolecular alignment of data sets (GALAHAD) was used to generate the desired pharmacophore model and superimpose the QNs, and then advanced comparative molecular field analysis (CoMFA) and advanced comparative molecular similarity indices analysis (CoMSIA) models were employed to study the three-dimensional quantitative structure-activity relationship (3D QSAR) between QNs and the antibody. It was found that the QNs could interact with the antibody with different binding poses, and cross-reactivity was mainly positively correlated with the bulky substructure containing electronegative atom at the 7-position, while it was negatively associated with the large bulky substructure at the 1-position of QNs. PMID:26982746

  18. Ethylene Glycol Intercalated Cobalt/Nickel Layered Double Hydroxide Nanosheet Assemblies with Ultrahigh Specific Capacitance: Structural Design and Green Synthesis for Advanced Electrochemical Storage.

    PubMed

    Wang, Changhui; Zhang, Xiong; Xu, Zhongtang; Sun, Xianzhong; Ma, Yanwei

    2015-09-01

    Because of the rapid depletion of fossil fuels and severe environmental pollution, more advanced energy-storage systems need to possess dramatically improved performance and be produced on a large scale with high efficiency while maintaining low-enough costs to ensure the higher and wider requirements. A facile, energy-saving process was successfully adopted for the synthesis of ethylene glycol intercalated cobalt/nickel layered double hydroxide (EG-Co/Ni LDH) nanosheet assembly variants with higher interlayer distance and tunable transitional-metal composition. At an optimized starting Co/Ni ratio of 1, the nanosheet assemblies display a three-dimensional, spongelike network, affording a high specific surface area with advantageous mesopore structure in 2-5 nm containing large numbers of about 1.2 nm micropores for promoting electrochemical reaction. An unprecedented electrochemical performance was achieved, with a specific capacitance of 4160 F g(-1) at a discharge current density of 1 A g(-1) and of 1313 F g(-1) even at 50 A g(-1), as well as excellent cycling ability. The design and optimization of EG-Co/Ni LDH nanosheets in compositions, structures, and performances, in conjunction with the easy and relatively "green" synthetic process, will play a pivotal role in meeting the needs of large-scale manufacture and widespread application for advanced electrochemical storage. PMID:26258432

  19. Specific pathogen free macaque colonies: a review of principles and recent advances for viral testing and colony management.

    PubMed

    Yee, JoAnn L; Vanderford, Thomas H; Didier, Elizabeth S; Gray, Stanton; Lewis, Anne; Roberts, Jeffrey; Taylor, Kerry; Bohm, Rudolf P

    2016-04-01

    Specific pathogen free (SPF) macaques provide valuable animal models for biomedical research. In 1989, the National Center for Research Resources [now Office of Research Infrastructure Programs (ORIP)] of the National Institutes of Health initiated experimental research contracts to establish and maintain SPF colonies. The derivation and maintenance of SPF macaque colonies is a complex undertaking requiring knowledge of the biology of the agents for exclusion and normal physiology and behavior of macaques, application of the latest diagnostic technology, facilitiy management, and animal husbandry. This review provides information on the biology of the four viral agents targeted for exclusion in ORIP SPF macaque colonies, describes current state-of-the-art viral diagnostic algorithms, presents data from proficiency testing of diagnostic assays between laboratories at institutions participating in the ORIP SPF program, and outlines management strategies for maintaining the integrity of SPF colonies using results of diagnostic testing as a guide to decision making. PMID:26932456

  20. Operational specification and forecasting advances for Dst, LEO thermospheric densities, and aviation radiation dose and dose rate

    NASA Astrophysics Data System (ADS)

    Tobiska, W.; Knipp, D. J.; Burke, W. J.; Bouwer, D.; Bailey, J. J.; Hagan, M. P.; Didkovsky, L. V.; Garrett, H. B.; Bowman, B. R.; Gannon, J. L.; Atwell, W.; Blake, J. B.; Crain, W.; Rice, D.; Schunk, R. W.; Fulgham, J.; Bell, D.; Gersey, B.; Wilkins, R.; Fuschino, R.; Flynn, C.; Cecil, K.; Mertens, C. J.; Xu, X.; Crowley, G.; Reynolds, A.; Azeem, S. I.; Wiley, S.; Holland, M.; Malone, K.

    2013-12-01

    . Many of the data products from MAPS, LAPS, and ARMAS are available on the SpaceWx smartphone app for iPhone, iPad, iPod, and Android professional users and public space weather education. We describe recent forecasting advances for moving the space weather information from these automated systems into operational, derivative products for communications, aviation, and satellite operations uses.

  1. Operational specification and forecasting advances for Dst, LEO thermospheric densities, and aviation radiation dose and dose rate

    NASA Astrophysics Data System (ADS)

    Tobiska, W. Kent

    smart phone apps. ARMAS provides the “weather” of the radiation environment to improve air-crew and passenger safety. Many of the data products from MAPS, LAPS, and ARMAS are available on the SpaceWx smartphone app for iPhone, iPad, iPod, and Android professional users and public space weather education. We describe recent forecasting advances for moving the space weather information from these automated systems into operational, derivative products for communications, aviation, and satellite operations uses.

  2. Electrokinetic treatment of polluted soil at pilot level coupled to an advanced oxidation process of its wastewater

    NASA Astrophysics Data System (ADS)

    Ochoa, B.; Ramos, L.; Garibay, A.; Pérez-Corona, M.; Cuevas, M. C.; Cárdenas, J.; Teutli, M.; Bustos, E.

    2016-02-01

    Soil contaminated with hydrocarbons is a current problem of great importance. These contaminants may be toxic, can retain water and block gas exchange with the atmosphere, which produces a poor-quality soil unsuitable for ecological health. Electroremediation is among the treatments for the removal of such contaminants. In this research, a pilot-level electroremediation test was applied using a circular arrangement of electrodes with a Ti cathode at the middle of the cell surrounded by six IrO2-Ta2O5 | Ti anodes. The presence of an NaOH electrolyte helps to develop the electromigration and electro-osmosis of gasoline molecules (at 1126 mg kg-1) surrounded by Na+ ions. The hydrocarbons are directed towards the cathode and subsequently removed in an aqueous Na+ - hydrocarbon solution, and the -OH migrates to the anode. During electrokinetic treatment, the physicochemical characteristics of the soil close to either the cathode or anode and at the half-cell were evaluated during the three weeks of treatment. During that time, more than 80% of hydrocarbons were removed. Hydrocarbons removed by the electrokinetic treatment of gasoline-polluted soil were collected in a central wastewater compartment and subsequently treated with a Fenton-type advanced oxidation process. This achieved more than 70% mineralization of the hydrocarbons to CO2 and H2O within 1.5 h; its low toxicity status was verified using the Deltatox® kit test. With this approach, the residual water complied with the permissible limits of COD, pH, and electrical conductivity for being discharged into water bodies, according to Mexican norm NOM-001-SEMARNAT-1996.

  3. A screening level fate model of organic contaminants from advanced water treatment in a potable water supply reservoir.

    PubMed

    Hawker, Darryl W; Cumming, Janet L; Neale, Peta A; Bartkow, Michael E; Escher, Beate I

    2011-01-01

    Augmentation of potable water sources by planned indirect potable reuse of wastewater is being widely considered to address growing water shortages. Environmental buffers such as lakes and dams may act as one of a series of barriers to potable water contamination stemming from micropollutants in wastewater. In South-East Queensland, Australia, current government policy is to begin indirect potable reuse of water from reverse osmosis equipped advanced water treatment plants (AWTPs) when the combined capacity of its major storages is at 40% capacity. A total of 15 organic contaminants including NDMA and bisphenol A have been publically reported as detected in recycled water from one of South-East Queensland's AWTPs, while another 98 chemicals were analysed for, but found to be below their detection limit. To assess the natural attenuation in Lake Wivenhoe, a Level III fugacity based evaluative fate model was constructed using the maximum concentrations of these contaminants detected as input data. A parallel aquivalence based model was constructed for those contaminants, such as dichloroacetic acid, dalapon and triclopyr, which are ionised in the environment of Lake Wivenhoe. A total of 247 organic chemicals of interest, including disinfection by-products, pesticides, pharmaceuticals and personal care products, xenoestrogens and industrial chemicals, were evaluated with the model to assess their potential for natural attenuation. Out of the 15 detected chemicals, trihalomethanes are expected to volatilise with concentrations in the outflow from the dam approximately 400 times lower than influent from the AWTPs. Transformation processes in water are likely to be more significant for NDMA and pharmaceuticals such as salicylic acid and paracetamol as well as for caffeine and the herbicides dalapon and triclopyr. For hydrophobic contaminants such as cholesterol and phenolic xenoestrogens such as 4-nonylphenol, 4-t-octylphenol and bisphenol A, equilibrium between water

  4. Pharmacological levels of Withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells.

    PubMed

    Szarc vel Szic, Katarzyna; Op de Beeck, Ken; Ratman, Dariusz; Wouters, An; Beck, Ilse M; Declerck, Ken; Heyninck, Karen; Fransen, Erik; Bracke, Marc; De Bosscher, Karolien; Lardon, Filip; Van Camp, Guy; Vanden Berghe, Wim

    2014-01-01

    Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy

  5. Specific biomarkers for stochastic division patterns and starvation-induced quiescence under limited glucose levels in fission yeast

    PubMed Central

    Pluskal, Tomáš; Hayashi, Takeshi; Saitoh, Shigeaki; Fujisawa, Asuka; Yanagida, Mitsuhiro

    2011-01-01

    Glucose as a source of energy is centrally important to our understanding of life. We investigated the cell division–quiescence behavior of the fission yeast Schizosaccharomyces pombe under a wide range of glucose concentrations (0–111 mm). The mode of S. pombe cell division under a microfluidic perfusion system was surprisingly normal under highly diluted glucose concentrations (5.6 mm, 1/20 of the standard medium, within human blood sugar levels). Division became stochastic, accompanied by a curious division-timing inheritance, in 2.2–4.4 mm glucose. A critical transition from division to quiescence occurred within a narrow range of concentrations (2.2–1.7 mm). Under starvation (1.1 mm) conditions, cells were mostly quiescent and only a small population of cells divided. Under fasting (0 mm) conditions, division was immediately arrested with a short chronological lifespan (16 h). When cells were first glucose starved prior to fasting, they possessed a substantially extended lifespan (∼14 days). We employed a quantitative metabolomic approach for S. pombe cell extracts, and identified specific metabolites (e.g. biotin, trehalose, ergothioneine, S-adenosyl methionine and CDP-choline), which increased or decreased at different glucose concentrations, whereas nucleotide triphosphates, such as ATP, maintained high concentrations even under starvation. Under starvation, the level of S-adenosyl methionine increased sharply, accompanied by an increase in methylated amino acids and nucleotides. Under fasting, cells rapidly lost antioxidant and energy compounds, such as glutathione and ATP, but, in fasting cells after starvation, these and other metabolites ensuring longevity remained abundant. Glucose-starved cells became resistant to 40 mm H2O2 as a result of the accumulation of antioxidant compounds. PMID:21306563

  6. Pharmacological Levels of Withaferin A (Withania somnifera) Trigger Clinically Relevant Anticancer Effects Specific to Triple Negative Breast Cancer Cells

    PubMed Central

    Szarc vel Szic, Katarzyna; Op de Beeck, Ken; Ratman, Dariusz; Wouters, An; Beck, Ilse M.; Declerck, Ken; Heyninck, Karen; Fransen, Erik; Bracke, Marc; De Bosscher, Karolien; Lardon, Filip; Van Camp, Guy; Berghe, Wim Vanden

    2014-01-01

    Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy

  7. Determination of risk-based, site-specific cleanup levels for an industrial site in Seattle, Washington

    SciTech Connect

    Birkner, P.D.; Gaulke, S.W.; Tirao, A.C.; Veilleux, A.L.

    1997-12-31

    Risk-based, site-specific cleanup criteria were developed for an active industrial site where shallow soil was contaminated with bunker fuel. This approach resulted in defensible cleanup levels that eliminated the need for complicated and disruptive remedial measures and is expediting site closure under Washington State Department of Ecology`s (Ecology) Independent Remedial Action Program. Initially, in anticipation of the sale of the property, a site investigation was conducted to provide information on the extent of contamination resulting from a leaking underground storage tank. Results of the investigation indicated that at least 3,600 cubic yards of soil contained bunker fuel at concentrations exceeding Ecology`s Model Toxics Control Act (MTCA) default Method A cleanup value for heavy oil of 200 milligrams per kilogram. The contamination extended under two of the site structures. Following Ecology`s new interim policy for cleanup of total petroleum hydrocarbons under MTCA, a risk-based cleanup criterion was calculated using an approach in which aliphatic and aromatic fractions of weathered bunker fuel were represented by surrogates of known toxicity. The cleanup criterion yielded by the quantitative evaluation was more than an order of magnitude higher than the default MTCA Method A value for heavy oil. Cleanup criteria for carcinogenic polynuclear aromatic hydrocarbons (cPAHs) were also derived. Use of these risk-based cleanup levels eliminated the need for remedial measures outside of the immediate vicinity of the former tank location, reducing the volume of soil that required remediation from 3,600 cubic yards to 70 cubic yards.

  8. Quantitative analysis of commensal Escherichia coli populations reveals host-specific enterotypes at the intra-species level

    PubMed Central

    Smati, Mounira; Clermont, Olivier; Bleibtreu, Alexandre; Fourreau, Frédéric; David, Anthony; Daubié, Anne-Sophie; Hignard, Cécile; Loison, Odile; Picard, Bertrand; Denamur, Erick

    2015-01-01

    The primary habitat of the Escherichia coli species is the gut of warm-blooded vertebrates. The E. coli species is structured into four main phylogenetic groups A, B1, B2, and D. We estimated the relative proportions of these phylogroups in the feces of 137 wild and domesticated animals with various diets living in the Ile de France (Paris) region by real-time PCR. We distinguished three main clusters characterized by a particular abundance of two or more phylogroups within the E. coli animal commensal populations, which we called “enterocolitypes” by analogy with the enterotypes defined in the human gut microbiota at the genus level. These enterocolitypes were characterized by a dominant (>50%) B2, B1, or A phylogroup and were associated with different host species, diets, and habitats: wild and herbivorous species (wild rabbits and deer), domesticated herbivorous species (domesticated rabbits, horses, sheep, and cows), and omnivorous species (boar, pigs, and chickens), respectively. By analyzing retrospectively the data obtained using the same approach from 98 healthy humans living in Ile de France (Smati et al. 2013, Appl. Environ. Microbiol. 79, 5005–5012), we identified a specific human enterocolitype characterized by the dominant and/or exclusive (>90%) presence of phylogroup B2. We then compared B2 strains isolated from animals and humans, and revealed that human and animal strains differ regarding O-type and B2 subgroup. Moreover, two genes, sfa/foc and clbQ, were associated with the exclusive character of strains, observed only in humans. In conclusion, a complex network of interactions exists at several levels (genus and intra-species) within the intestinal microbiota. PMID:26033772

  9. Modes of Governmentality in an Online Space: A Case Study of Blog Activities in an Advanced Level Japanese-as-a-Foreign-Language Classroom

    ERIC Educational Resources Information Center

    Doerr, Neriko M.; Sato, Shinji

    2011-01-01

    This article discusses the validity of the incorporation of online communication in language education classes as a practice free of power politics. By examining blog activities in an advanced-level Japanese-as-a-Foreign-Language classroom at a university in the USA, we show that the blog's postings and readers' comments evoke certain modes of…

  10. Integrated Advanced Microwave Sounding Unit-A (AMSU-A) METOP Stress Analysis Report (Qual Level Random Vibration) A1 Module

    NASA Technical Reports Server (NTRS)

    Mehitretter, R.

    1996-01-01

    Stress analysis of the primary structure of the Meteorological Satellites Project (METSAT) Advanced Microwave Sounding Units-A, A1 Module performed using the Meteorological Operational (METOP) Qualification Level 9.66 grms Random Vibration PSD Spectrum is presented. The random vibration structural margins of safety and natural frequency predictions are summarized.

  11. The Effects of Using Concept Mapping for Improving Advanced Level Biology Students' Lower- and Higher-Order Cognitive Skills

    ERIC Educational Resources Information Center

    Bramwell-Lalor, Sharon; Rainford, Marcia

    2014-01-01

    This paper reports on teachers' use of concept mapping as an alternative assessment strategy in advanced level biology classes and its effects on students' cognitive skills on selected biology concepts. Using a mixed methods approach, the study employed a pre-test/post-test quasi-experimental design involving 156 students and 8 teachers…

  12. Elapid snake venom analyses show the specificity of the peptide composition at the level of genera Naja and Notechis.

    PubMed

    Munawar, Aisha; Trusch, Maria; Georgieva, Dessislava; Hildebrand, Diana; Kwiatkowski, Marcel; Behnken, Henning; Harder, Sönke; Arni, Raghuvir; Spencer, Patrick; Schlüter, Hartmut; Betzel, Christian

    2014-03-01

    Elapid snake venom is a highly valuable, but till now mainly unexplored, source of pharmacologically important peptides. We analyzed the peptide fractions with molecular masses up to 10 kDa of two elapid snake venoms-that of the African cobra, N. m. mossambica (genus Naja), and the Peninsula tiger snake, N. scutatus, from Kangaroo Island (genus Notechis). A combination of chromatographic methods was used to isolate the peptides, which were characterized by combining complimentary mass spectrometric techniques. Comparative analysis of the peptide compositions of two venoms showed specificity at the genus level. Three-finger (3-F) cytotoxins, bradykinin-potentiating peptides (BPPs) and a bradykinin inhibitor were isolated from the Naja venom. 3-F neurotoxins, Kunitz/basic pancreatic trypsin inhibitor (BPTI)-type inhibitors and a natriuretic peptide were identified in the N. venom. The inhibiting activity of the peptides was confirmed in vitro with a selected array of proteases. Cytotoxin 1 (P01467) from the Naja venom might be involved in the disturbance of cellular processes by inhibiting the cell 20S-proteasome. A high degree of similarity between BPPs from elapid and viperid snake venoms was observed, suggesting that these molecules play a key role in snake venoms and also indicating that these peptides were recruited into the snake venom prior to the evolutionary divergence of the snakes. PMID:24590383

  13. Elapid Snake Venom Analyses Show the Specificity of the Peptide Composition at the Level of Genera Naja and Notechis

    PubMed Central

    Munawar, Aisha; Trusch, Maria; Georgieva, Dessislava; Hildebrand, Diana; Kwiatkowski, Marcel; Behnken, Henning; Harder, Sönke; Arni, Raghuvir; Spencer, Patrick; Schlüter, Hartmut; Betzel, Christian

    2014-01-01

    Elapid snake venom is a highly valuable, but till now mainly unexplored, source of pharmacologically important peptides. We analyzed the peptide fractions with molecular masses up to 10 kDa of two elapid snake venoms—that of the African cobra, N. m. mossambica (genus Naja), and the Peninsula tiger snake, N. scutatus, from Kangaroo Island (genus Notechis). A combination of chromatographic methods was used to isolate the peptides, which were characterized by combining complimentary mass spectrometric techniques. Comparative analysis of the peptide compositions of two venoms showed specificity at the genus level. Three-finger (3-F) cytotoxins, bradykinin-potentiating peptides (BPPs) and a bradykinin inhibitor were isolated from the Naja venom. 3-F neurotoxins, Kunitz/basic pancreatic trypsin inhibitor (BPTI)-type inhibitors and a natriuretic peptide were identified in the N. venom. The inhibiting activity of the peptides was confirmed in vitro with a selected array of proteases. Cytotoxin 1 (P01467) from the Naja venom might be involved in the disturbance of cellular processes by inhibiting the cell 20S-proteasome. A high degree of similarity between BPPs from elapid and viperid snake venoms was observed, suggesting that these molecules play a key role in snake venoms and also indicating that these peptides were recruited into the snake venom prior to the evolutionary divergence of the snakes. PMID:24590383

  14. Elevated levels of callous unemotional traits are associated with reduced attentional cueing, with no specificity for fear or eyes.

    PubMed

    Dawel, Amy; McKone, Elinor; O'Kearney, Richard; Sellbom, Martin; Irons, Jessica; Palermo, Romina

    2015-07-01

    Three theoretical explanations for the affective facet of psychopathy were tested in individuals with high levels of callous unemotional (CU) traits. Theory 1 (Blair) proposes specific difficulties in processing others' distress (particularly fear). Theory 2 (Dadds) argues for lack of attention to the eyes of faces. Theory 3 (Newman) proposes enhanced selective attention. The theories make contrasting predictions about how CU traits would affect cueing of attention from eye-gaze direction in distressed (i.e., fearful) faces; eye-gaze direction in nondistressed (i.e., happy, neutral) faces; and nonsocial stimuli (arrows). High CU adults (n = 33) showed reduced attentional cueing compared with low CU adults (n = 75) equally across all conditions (eye-gaze in distressed and nondistressed faces, arrows). The high CU group's ability to suppress following of eye-gaze emerged with practice while the low CU group showed no such reduction in gaze-cueing with practice. Overall accuracy and RTs were not different for the low and high CU groups indicating equivalent task engagement. Results support an enhanced selective attention account-consistent with Newman and colleagues' Response Modulation Hypothesis--in which high CU individuals are able to suppress goal-irrelevant social and nonsocial information. The current study also provides novel evidence regarding the nature of gaze-following by tracking practice effects across blocks. While supporting the common assumption that following of gaze is typically mandatory, the results also imply this can be modified by individual differences in personality. PMID:25705978

  15. Use of tactual materials on the achievement of content specific vocabulary and terminology acquisition within an intermediate level science curriculum

    NASA Astrophysics Data System (ADS)

    Terry, Brian H.

    In this quasi-experimental study, the researcher investigated the effectiveness of three tactual strategies and one non-tactual strategy of content specific vocabulary acquisition. Flash cards, task cards, and learning wheels served as the tactual strategies, and vocabulary review sheets served as a non-tactual strategy. The sample (n=85) consisted of all middle school students in a small high performing middle school located in the northern suburbs of New York City. All of the vocabulary words and terms came from the New York State Intermediate Level Science Core Curriculum. Pre-tests and post-tests were used to collect the data. A repeated measures ANOVA was conducted on the gain scores from each of the treatments. Multiple paired sample t-tests were conducted to analyze the results. Repeated measures ANOVAs were used to determine if there was a variance between the academic achievement levels of the students, gender, and grade level for each of the treatments. All of the treatments significantly improved the science achievement of the students, but significance was found between them. Significance was found between the achievement groups with the above average students attaining a higher mean on the pre-test and post-test for each treatment, whereas the below average students had the lowest mean on both assessments. The sixth grade students showed significant improvement over the seventh grade students while using the flash cards (p=.004) and learning wheel (p=.007). During the learning wheel treatment, the males scored significantly better (p=.021) than the females on the pre-test and post-test. During the worksheet treatment, significance (p=.034) was found between gender and achievement group. The below average male students had the greatest gain from the pre-test to the post-test, but the post-test mean was still the lowest of the groups. Limitations, implications for future research and current practice are discussed. Key words are: flash cards, task cards

  16. Advanced quadrupole ion trap instrumentation for low level vehicle emissions measurements. CRADA final report for number ORNL93-0238

    SciTech Connect

    McLuckey, S.A.; Buchanan, M.V.; Asano, K.G.; Hart, K.J.; Goeringer, D.E.; Dearth, M.A.

    1997-09-01

    Quadrupole ion trap mass spectrometry has been evaluated for its potential use in vehicle emissions measurements in vehicle test facilities as an analyzer for the top 15 compounds contributing to smog generation. A variety of ionization methods were explored including ion trap in situ chemical ionization, atmospheric sampling glow discharge ionization, and nitric oxide chemical ionization in a glow discharge ionization source coupled with anion trap mass spectrometer. Emphasis was placed on the determination of hydrocarbons and oxygenated hydrocarbons at parts per million to parts per billion levels. Ion trap in situ water chemical ionization and atmospheric sampling glow discharge ionization were both shown to be amenable to the analysis of arenes, alcohols, aldehydes and, to some degree, alkenes. Atmospheric sampling glow discharge also generated molecular ions of methyl-t-butyl ether (MTBE). Neither of these ionization methods, however, were found to generate diagnostic ions for the alkanes. Nitric oxide chemical ionization, on the other hand, was found to yield diagnostic ions for alkanes, alkenes, arenes, alcohols, aldehydes, and MTBE. The ability to measure a variety of hydrocarbons present at roughly 15 parts per billion at measurement rates of 3 Hz was demonstrated. These results have demonstrated that the ion trap has an excellent combination of sensitivity, specificity, speed, and flexibility with respect to the technical requirements of the top 15 analyzer.

  17. Comprehensively Evaluating cis-Regulatory Variation in the Human Prostate Transcriptome by Using Gene-Level Allele-Specific Expression

    PubMed Central

    Larson, Nicholas B.; McDonnell, Shannon; French, Amy J.; Fogarty, Zach; Cheville, John; Middha, Sumit; Riska, Shaun; Baheti, Saurabh; Nair, Asha A.; Wang, Liang; Schaid, Daniel J.; Thibodeau, Stephen N.

    2015-01-01

    The identification of cis-acting regulatory variation in primary tissues has the potential to elucidate the genetic basis of complex traits and further our understanding of transcriptomic diversity across cell types. Expression quantitative trait locus (eQTL) association analysis using RNA sequencing (RNA-seq) data can improve upon the detection of cis-acting regulatory variation by leveraging allele-specific expression (ASE) patterns in association analysis. Here, we present a comprehensive evaluation of cis-acting eQTLs by analyzing RNA-seq gene-expression data and genome-wide high-density genotypes from 471 samples of normal primary prostate tissue. Using statistical models that integrate ASE information, we identified extensive cis-eQTLs across the prostate transcriptome and found that approximately 70% of expressed genes corresponded to a significant eQTL at a gene-level false-discovery rate of 0.05. Overall, cis-eQTLs were heavily concentrated near the transcription start and stop sites of affected genes, and effects were negatively correlated with distance. We identified multiple instances of cis-acting co-regulation by using phased genotype data and discovered 233 SNPs as the most strongly associated eQTLs for more than one gene. We also noted significant enrichment (25/50, p = 2E−5) of previously reported prostate cancer risk SNPs in prostate eQTLs. Our results illustrate the benefit of assessing ASE data in cis-eQTL analyses by showing better reproducibility of prior eQTL findings than of eQTL mapping based on total expression alone. Altogether, our analysis provides extensive functional context of thousands of SNPs in prostate tissue, and these results will be of critical value in guiding studies examining disease of the human prostate. PMID:25983244

  18. Soil Moisture Active Passive (SMAP) Mission Level 4 Surface and Root Zone Soil Moisture (L4_SM) Product Specification Document

    NASA Technical Reports Server (NTRS)

    Reichle, Rolf H.; Ardizzone, Joseph V.; Kim, Gi-Kong; Lucchesi, Robert A.; Smith, Edmond B.; Weiss, Barry H.

    2015-01-01

    This is the Product Specification Document (PSD) for Level 4 Surface and Root Zone Soil Moisture (L4_SM) data for the Science Data System (SDS) of the Soil Moisture Active Passive (SMAP) project. The L4_SM data product provides estimates of land surface conditions based on the assimilation of SMAP observations into a customized version of the NASA Goddard Earth Observing System, Version 5 (GEOS-5) land data assimilation system (LDAS). This document applies to any standard L4_SM data product generated by the SMAP Project. The Soil Moisture Active Passive (SMAP) mission will enhance the accuracy and the resolution of space-based measurements of terrestrial soil moisture and freeze-thaw state. SMAP data products will have a noteworthy impact on multiple relevant and current Earth Science endeavors. These include: Understanding of the processes that link the terrestrial water, the energy and the carbon cycles, Estimations of global water and energy fluxes over the land surfaces, Quantification of the net carbon flux in boreal landscapes Forecast skill of both weather and climate, Predictions and monitoring of natural disasters including floods, landslides and droughts, and Predictions of agricultural productivity. To provide these data, the SMAP mission will deploy a satellite observatory in a near polar, sun synchronous orbit. The observatory will house an L-band radiometer that operates at 1.40 GHz and an L-band radar that operates at 1.26 GHz. The instruments will share a rotating reflector antenna with a 6 meter aperture that scans over a 1000 km swath.

  19. Dynamic compartment specific changes in glutathione and ascorbate levels in Arabidopsis plants exposed to different light intensities

    PubMed Central

    2013-01-01

    Background Excess light conditions induce the generation of reactive oxygen species (ROS) directly in the chloroplasts but also cause an accumulation and production of ROS in peroxisomes, cytosol and vacuoles. Antioxidants such as ascorbate and glutathione occur in all cell compartments where they detoxify ROS. In this study compartment specific changes in antioxidant levels and related enzymes were monitored among Arabidopsis wildtype plants and ascorbate and glutathione deficient mutants (vtc2-1 and pad2-1, respectively) exposed to different light intensities (50, 150 which was considered as control condition, 300, 700 and 1,500 μmol m-2 s-1) for 4 h and 14 d. Results The results revealed that wildtype plants reacted to short term exposure to excess light conditions with the accumulation of ascorbate and glutathione in chloroplasts, peroxisomes and the cytosol and an increased activity of catalase in the leaves. Long term exposure led to an accumulation of ascorbate and glutathione mainly in chloroplasts. In wildtype plants an accumulation of ascorbate and hydrogen peroxide (H2O2) could be observed in vacuoles when exposed to high light conditions. The pad2-1 mutant reacted to long term excess light exposure with an accumulation of ascorbate in peroxisomes whereas the vtc2-1 mutant reacted with an accumulation of glutathione in the chloroplasts (relative to the wildtype) and nuclei during long term high light conditions indicating an important role of these antioxidants in these cell compartments for the protection of the mutants against high light stress. Conclusion The results obtained in this study demonstrate that the accumulation of ascorbate and glutathione in chloroplasts, peroxisomes and the cytosol is an important reaction of plants to short term high light stress. The accumulation of ascorbate and H2O2 along the tonoplast and in vacuoles during these conditions indicates an important route for H2O2 detoxification under these conditions. PMID

  20. High serum level of C-reactive protein is associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib.

    PubMed

    Fiala, Ondrej; Pesek, Milos; Finek, Jindrich; Topolcan, Ondrej; Racek, Jaroslav; Minarik, Marek; Benesova, Lucie; Bortlicek, Zbynek; Poprach, Alexandr; Buchler, Tomas

    2015-12-01

    Erlotinib is a low molecular weight tyrosine kinase inhibitor (TKI) directed at epidermal growth factor receptor (EGFR), widely used in the treatment of locally advanced or metastatic-stage non-small cell lung cancer (NSCLC). Although introduction of EGFR-TKIs have significantly extended survival of advanced-stage NSCLC patients, their efficacy in the entire patient population is relatively low. Aside from activating EGFR mutations, no reliable biochemical or molecular predictors of response to erlotinib have been established. The aim of our retrospective study was to evaluate the association of baseline serum levels of C-reactive protein (CRP) with outcomes in patients with advanced-stage NSCLC treated with erlotinib. We retrospectively analyzed clinical data of 595 patients with advanced-stage NSCLC (IIIB or IV) treated with erlotinib. Serum CRP was measured using an immunoturbidimetric method. High baseline levels of CRP (≥10 mg/l) were measured in 387 (65 %) patients, and normal levels (<10 mg/l) were measured in 208 (35 %) patients. The median progression-free survival (PFS) and overall survival (OS) for patients with high CRP was 1.8 and 7.7 compared to 2.8 and 14.4 months for patients with low CRP (p < 0.001 and p < 0.001). The multivariable Cox proportional hazards model revealed that CRP was significantly associated with PFS and also with OS (hazard ratio (HR) = 1.57, p < 0.001, and HR = 1.63, p < 0.001, respectively). In conclusion, the results of the conducted retrospective study suggest that high baseline level of CRP was independently associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib. CRP is a commonly used biomarker which is simple and easy to detect, and thus, it is feasible for the use in the routine clinical practice. PMID:26088452

  1. The Process of Advance Care Planning in HCT Candidates and Proxies: Self-Efficacy, Locus of Control, and Anxiety Levels

    PubMed Central

    Duckworth, Katharine E.; Forti, Allison M.; Russell, Gregory B.; Naik, Seema; Hurd, David; McQuellon, Richard P.

    2013-01-01

    The purpose of this study was to examine the relationship between hematopoietic cell transplant candidate and proxy advance care planning (ACP) behavior and attitudes. A total of 49 candidates and 44 proxies completed the Advance Directive Attitudes Survey, Multidimensional Health Locus of Control Scale, Family Decision Making Self-Efficacy Scale, and the State-Trait Anxiety Inventory. In all, 45% of candidates reported completing an advance directive (AD), while only 26% had ADs on file; 80% of candidates discussed ACP wishes with their loved ones and 15% discussed ACP wishes with their medical team. The AD completers were significantly (1) older, (2) more positive about ADs, and (3) were less likely to believe that health events happen by chance. Discrepancies between reported ACP behavior and communication with health care practitioners have implications for end-of-life care. PMID:23946253

  2. The process of advance care planning in HCT candidates and proxies: self-efficacy, locus of control, and anxiety levels.

    PubMed

    Duckworth, Katharine E; Forti, Allison M; Russell, Gregory B; Naik, Seema; Hurd, David; McQuellon, Richard P

    2014-11-01

    The purpose of this study was to examine the relationship between hematopoietic cell transplant candidate and proxy advance care planning (ACP) behavior and attitudes. A total of 49 candidates and 44 proxies completed the Advance Directive Attitudes Survey, Multidimensional Health Locus of Control Scale, Family Decision Making Self-Efficacy Scale, and the State-Trait Anxiety Inventory. In all, 45% of candidates reported completing an advance directive (AD), while only 26% had ADs on file; 80% of candidates discussed ACP wishes with their loved ones and 15% discussed ACP wishes with their medical team. The AD completers were significantly (1) older, (2) more positive about ADs, and (3) were less likely to believe that health events happen by chance. Discrepancies between reported ACP behavior and communication with health care practitioners have implications for end-of-life care. PMID:23946253

  3. Enabling more capability within smaller pixels: advanced wafer-level process technologies for integration of focal plane arrays with readout electronics

    NASA Astrophysics Data System (ADS)

    Temple, Dorota S.; Vick, Erik P.; Lueck, Matthew R.; Malta, Dean; Skokan, Mark R.; Masterjohn, Christopher M.; Muzilla, Mark S.

    2014-05-01

    Over the past decade, the development of infrared focal plane arrays (FPAs) has seen two trends: decreasing of the pixel size and increasing of signal-processing capability at the device level. Enabling more capability within smaller pixels can be achieved through the use of advanced wafer-level processes for the integration of FPAs with silicon (Si) readout integrated circuits (ROICs). In this paper, we review the development of these wafer-level integration technologies, highlighting approaches in which the infrared sensor is integrated with three-dimensional ROIC stacks composed of multiple layers of Si circuitry interconnected using metal-filled through-silicon vias.

  4. Reference ranges and cutoff levels of pneumococcal antibody global serum assays (IgG and IgG2) and specific antibodies in healthy children and adults.

    PubMed

    Rose, M A; Buess, J; Ventur, Y; Zielen, S; Herrmann, E; Schulze, J; Schubert, R

    2013-08-01

    Pneumococcal antibodies represent the acquisition of natural immunity. Determination of pneumococcal antibodies is an important screening tool for immunodeficiencies. Our study generated reference ranges and cutoff levels for pneumococcal antibody global serum assays correlated to a specific pneumococcal antibody ELISA. Specific pneumococcal antibody levels were measured from 457 children undergoing elective surgery and 46 healthy adult volunteers (88 with previous pneumococcal immunization from both groups), 22 severe immunodeficient subjects with ataxia telangiectasia (A-T, negative controls), and age-matched 36 healthy allergic asthmatics. We determined a representative panel of serotype-specific pneumococcal antibodies (serotype 4, 5, 6B, 7F, 14, 18C, 19F, 23F) by ELISA and global pneumococcal IgG and IgG2 antibodies by EIA. In vaccine-naïve healthy subjects, initial pneumococcal IgG geometric mean concentrations of 13.1 μg/ml were low in the first year of life and increased over the time, reaching adult levels (70.5 μg/ml) at age 8-12 years. In parallel, IgG2 antibodies increased from 20.7 % (0.5-1 year old) to adult proportions (>30 %) in preschoolers. Correlation between the pneumococcal IgG screening assay and specific pneumococcal antibody levels was acceptable (Pearson's coefficient r = 0.4455; p = 0.001). Cutoff levels showed high sensitivity, whereas specificity was high to moderate calculated from correlations with the specific ELISA. We provide reference ranges and cutoff levels for the interpretation of specific antibody determinations in the clinical setting. The global pneumococcal IgG/IgG2 assay is a suitable screening tool and correlates with the ELISA serotype-specific pneumococcal antibodies. However, results below our cutoff values should be re-evaluated by serotype-specific ELISA testing. PMID:23529214

  5. May serum levels of advanced oxidized protein products serve as a prognostic marker of disease duration in patients with idiopathic Parkinson's disease?

    PubMed

    García-Moreno, José-Manuel; Martín de Pablos, Angel; García-Sánchez, María-Isabel; Méndez-Lucena, Carolina; Damas-Hermoso, Fátima; Rus, Macarena; Chacón, José; Fernández, Emilio

    2013-04-10

    Protein and amine halogenation is a type of oxidative stress induced by phagocytic overstimulation, and its role in Parkinson's disease (PD) has not been discerned. We have detected that advanced oxidized protein products, markers of protein halogenation, are reliably enhanced in serum of patients with PD (n=60) relative to control subjects (n=45, p<0.012), and to a lesser extent in the cerebrospinal fluid. Amine halogenation, as evaluated through 3-chlorotyrosine, is not affected. Mieloperoxidase and hydrogen peroxide levels, halogenative factors of phagocytes, are devoid of changes. Levels of advanced oxidized protein products are progressively reduced over time, and the duration of PD is larger in the Hoehn-Yahr-stage-2/3 patients (n=34) with low serum levels (R(2)=0.0145, p<0.003). Levodopa treatment contributes to this reduction (R(2)=0.259, p<0.001). These protein products are not cytotoxic, unlike 3-chlorotyrosine, but they are known to form inflammatory mediators after conjugation with serum albumin. Our observations lead to the hypothesis that the serum level of advanced oxidized protein products is a prognostic marker of PD duration, and these oxidized proteins could participate in the development of parkinsonian neurodegeneration. PMID:23121480

  6. Effects of Levels of Automation for Advanced Small Modular Reactors: Impacts on Performance, Workload, and Situation Awareness

    SciTech Connect

    Johanna Oxstrand; Katya Le Blanc

    2014-07-01

    The Human-Automation Collaboration (HAC) research effort is a part of the Department of Energy (DOE) sponsored Advanced Small Modular Reactor (AdvSMR) program conducted at Idaho National Laboratory (INL). The DOE AdvSMR program focuses on plant design and management, reduction of capital costs as well as plant operations and maintenance costs (O&M), and factory production costs benefits.

  7. Utilizing Computer and Multimedia Technology in Generating Choreography for the Advanced Dance Student at the High School Level.

    ERIC Educational Resources Information Center

    Griffin, Irma Amado

    This study describes a pilot program utilizing various multimedia computer programs on a MacQuadra 840 AV. The target group consisted of six advanced dance students who participated in the pilot program within the dance curriculum by creating a database of dance movement using video and still photography. The students combined desktop publishing,…

  8. Early Identification of Students Predicted to Enroll in Advanced, Upper-Level High School Courses: An Examination of Validity

    ERIC Educational Resources Information Center

    DeRose, Diego S.; Clement, Russell W.

    2011-01-01

    Broward County Public Schools' Research Services department uses logistic regression analysis to compute an indicator to predict student enrollment in advanced high school courses, for students entering ninth grade for the first time. This prediction indicator, along with other student characteristics, supports high school guidance staffs in…

  9. Structure and Complexity of Oral Narratives in Advanced-Level Spanish: A Comparison of Three Learning Backgrounds

    ERIC Educational Resources Information Center

    Rubio, Fernando

    2003-01-01

    This study compared the narratives of three groups of advanced speakers of Spanish with different learning backgrounds. The first group was made up of heritage speakers; the second group was composed of missionaries that had recently returned from a two-year sojourn in a Spanish-speaking country; and the third group comprised students who had…

  10. Advanced ramjet concepts program

    NASA Technical Reports Server (NTRS)

    Leingang, J. L.

    1992-01-01

    Uniquely advantageous features, on both the performance and weight sides of the ledger, can be achieved through synergistic design integration of airbreathing and rocket technologies in the development of advanced orbital space transport propulsion systems of the combined cycle type. In the context of well understood advanced airbreathing and liquid rocket propulsion principles and practices, this precept of synergism is advanced mainly through six rather specific examples. These range from the detailed component level to the overall vehicle system level as follows: using jet compression; achieving a high area ratio rocket nozzle; ameliorating gas generator cycle rocket system deficiencies; using the in-duct special rocket thrust chamber assembly as the principal scramjet fuel injection operation; using the unstowed, covered fan as a duct closure for effecting high area ratio rocket mode operation; and creating a unique airbreathing rocket system via the onboard, cryogenic hydrogen induced air liquefaction process.

  11. Overall Response Rate, Progression-Free Survival, and Overall Survival With Targeted and Standard Therapies in Advanced Non–Small-Cell Lung Cancer: US Food and Drug Administration Trial-Level and Patient-Level Analyses

    PubMed Central

    Blumenthal, Gideon M.; Karuri, Stella W.; Zhang, Hui; Zhang, Lijun; Khozin, Sean; Kazandjian, Dickran; Tang, Shenghui; Sridhara, Rajeshwari; Keegan, Patricia; Pazdur, Richard

    2015-01-01

    Purpose To conduct analyses exploring trial-level and patient-level associations between overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in advanced non–small-cell lung cancer (NSCLC) trials. Methods We identified 14 trials (N = 12,567) submitted to US Food and Drug Administration since 2003 of treatments for advanced NSCLC. Only randomized, active-controlled trials with more than 150 patients were included. Associations between trial-level PFS hazard ratio (HR), OS HR, and ORR odds ratio were analyzed using a weighted linear regression model. Patient-level responder analyses comparing PFS and OS between patients with and without an objective response were performed using pooled data from all studies. Results In the trial-level analysis, the association between PFS and ORR was strong (R2 = 0.89; 95% CI, 0.80 to 0.98). There was no association between OS and ORR (R2 = 0.09; 95% CI, 0 to 0.33) and OS and PFS (R2 = 0.08; 95% CI, 0 to 0.31). In the patient-level responder analyses, patients who achieved a response had better PFS and OS compared with nonresponders (PFS: HR, 0.40; 95% CI, 0.38 to 0.42; OS: HR, 0.40; 95% CI, 0.38 to 0.43). Conclusion On a trial level, there is a strong association between ORR and PFS. An association between ORR and OS and between PFS and OS was not established, possibly because of cross-over and longer survival after progression in the targeted therapy and first-line trials. The patient-level analysis showed that responders have a better PFS and OS compared with nonresponders. A therapy in advanced NSCLC with a large magnitude of effect on ORR may have a large PFS effect. PMID:25667291

  12. Advanced 3D mesh manipulation in stereolithographic files and post-print processing for the manufacturing of patient-specific vascular flow phantoms

    NASA Astrophysics Data System (ADS)

    O'Hara, Ryan P.; Chand, Arpita; Vidiyala, Sowmya; Arechavala, Stacie M.; Mitsouras, Dimitrios; Rudin, Stephen; Ionita, Ciprian N.

    2016-03-01

    Complex vascular anatomies can cause the failure of image-guided endovascular procedures. 3D printed patient-specific vascular phantoms provide clinicians and medical device companies the ability to preemptively plan surgical treatments, test the likelihood of device success, and determine potential operative setbacks. This research aims to present advanced mesh manipulation techniques of stereolithographic (STL) files segmented from medical imaging and post-print surface optimization to match physiological vascular flow resistance. For phantom design, we developed three mesh manipulation techniques. The first method allows outlet 3D mesh manipulations to merge superfluous vessels into a single junction, decreasing the number of flow outlets and making it feasible to include smaller vessels. Next we introduced Boolean operations to eliminate the need to manually merge mesh layers and eliminate errors of mesh self-intersections that previously occurred. Finally we optimize support addition to preserve the patient anatomical geometry. For post-print surface optimization, we investigated various solutions and methods to remove support material and smooth the inner vessel surface. Solutions of chloroform, alcohol and sodium hydroxide were used to process various phantoms and hydraulic resistance was measured and compared with values reported in literature. The newly mesh manipulation methods decrease the phantom design time by 30 - 80% and allow for rapid development of accurate vascular models. We have created 3D printed vascular models with vessel diameters less than 0.5 mm. The methods presented in this work could lead to shorter design time for patient specific phantoms and better physiological simulations.

  13. Low Levels of IgM Antibodies against an Advanced Glycation Endproduct-Modified Apolipoprotein B100 Peptide Predict Cardiovascular Events in Nondiabetic Subjects.

    PubMed

    Engelbertsen, Daniel; Vallejo, Jenifer; Quách, Tâm Dan; Fredrikson, Gunilla Nordin; Alm, Ragnar; Hedblad, Bo; Björkbacka, Harry; Rothstein, Thomas L; Nilsson, Jan; Bengtsson, Eva

    2015-10-01

    Increased glucose levels are associated with the generation of advanced glycation endproduct (AGE) modifications. Interaction between AGE-modified plaque components and immune cells is believed to have an important role in the development of vascular complications in diabetes. Methylglyoxal (MGO) is one type of reactive aldehyde that gives rise to AGE modification. The present study analyzed whether autoantibodies against MGO-modified epitopes of the low-density lipoprotein apolipoprotein B (apoB) 100 predict cardiovascular events. A library consisting of 302 peptides comprising the complete apoB100 molecule was screened to identify peptides targeted by MGO-specific autoantibodies. Peptide (p) 220 (apoB amino acids 3286-3305) was identified as a major target. Baseline IgM and IgG against MGO-peptide 220 (p220) were measured in 700 individuals from the Malmö Diet and Cancer Cohort. A total of 139 cardiovascular events were registered during the 15-y follow-up period. Controlling for major cardiovascular risk factors demonstrated that subjects in the lowest tertile of MGO-p220 IgM had an increased risk for cardiovascular events (hazard ratio [95% confidence interval]: 2.07 [1.22-3.50]; p(trend) = 0.004). Interestingly, the association between MGO-p220 IgM and cardiovascular events remained and even tended to become stronger when subjects with prevalent diabetes were excluded from the analysis (2.51 [1.37-4.61]; p(trend) = 0.002). MGO-p220 IgM was inversely associated with blood glucose, but not with oxidized low-density lipoprotein. Finally, we demonstrate that anti-MGO-p220 IgM is produced by B1 cells. These data show that subjects with low levels of IgM recognizing MGO-modified p220 in apoB have an increased risk to develop cardiovascular events and that this association is present in nondiabetic subjects. PMID:26290603

  14. A Phase 1 Study of a Vaccine Targeting Preferentially Expressed Antigen in Melanoma and Prostate-specific Membrane Antigen in Patients With Advanced Solid Tumors

    PubMed Central

    Weber, Jeffrey S.; Vogelzang, Nicholas J.; Ernstoff, Marc S.; Goodman, Oscar B.; Cranmer, Lee D.; Marshall, John L.; Miles, Sabrina; Rosario, Dar; Diamond, David C.; Qiu, Zhiyong; Obrocea, Mihail; Bot, Adrian

    2013-01-01

    Summary Preferentially expressed antigen in melanoma (PRAME) and prostate-specific membrane antigen (PSMA) are tumor-associated antigens implicated in cellular differentiation, genetic stability, and angiogenesis. MKC1106-PP is an immunotherapeutic regimen cotargeting PRAME and PSMA, comprised of a recombinant plasmid (pPRA-PSM encoding fragments derived from both antigens) and 2 peptides (E-PRA and E-PSM derived from PRAME and PSMA, respectively). This multicenter study evaluated MKC1106-PP with a fixed plasmid dose and 2 different peptide doses, administered by intralymph node injection in a prime-boost sequence in human leukocyte antigen-A*0201 and tumor-antigen-positive patients with progressing metastatic solid tumors who had failed standard therapy. Immune monitoring was done by tetramer and enzymatic-linked immune spot analysis. The treatment was well tolerated, with no significant differences in safety, immune response, and clinical outcome relative to peptide doses. Fifteen of 24 evaluable patients showed an immune response, as defined by the expansion of PRAME-specific or PSMA-specific T cells in the blood. There were no partial or complete responses by the Response Evaluation Criteria in Solid Tumors. Seven patients showed stable disease (SD) for 6 months or longer, or prostate specific antigen decline: 4 of 10 with prostate carcinoma, 2 of 2 with renal clear cell carcinoma, and 1 of 10 with metastatic melanoma. In addition, there was an association between the induction and persistence of antigen-specific T cells in blood above baseline levels and disease control, defined as SD for 6 months or longer. These results support further development of MKC1106-PP in specific clinical indications. PMID:21760528

  15. Multi-element compound specific stable isotope analysis of volatile organic compounds at trace levels in groundwater samples

    NASA Astrophysics Data System (ADS)

    Herrero-Martín, Sara; Nijenhuis, Ivonne; Schmidt, Marie; Wolfram, Diana; Richnow, Hans. H.; Gehre, Matthias

    2013-04-01

    Groundwater pollution remains one of the major environmental and health concerns. A thorough understanding of sources, sinks and transformation processes of groundwater contaminants is needed to improve risk management evaluation, and to design efficient remediation and water treatment strategies. Isotopic tools provide unique information for an in-depth understanding of the fate of organic chemicals in the environment. During the last decades compound specific isotope analysis (CSIA) of complex mixtures, using gas chromatography-isotope ratio mass spectrometry (GC-IRMS), has gained popularity for the characterization and risk assessment of hazardous waste sites and for isotope forensics of organic contaminants. Multi-element isotope fingerprinting of organic substances provides a more robust framework for interpretation than the isotope analysis of only one element. One major challenge for application of CSIA is the analysis of trace levels of organic compounds in environmental matrices. It is necessary to inject 1 nmol carbon or 8 nmol hydrogen on column, to obtain an accurate and precise measurement of the isotope ratios, which is between two and three orders of magnitude larger than the amount of compound needed for conventional analysis of compound concentrations. Therefore, efficient extraction and pre-concentration techniques have to be integrated with GC-IRMS. Further research is urgently needed in this field, to evaluate the potential of novel and environmental-friendly sample pre-treatment techniques for CSIA to lower the detection limits and extending environmental applications. In this study, the novel coupling of a headspace autosampler (HS) with a programmed temperature vaporizer (PTV), allowing large volume injection of headspace samples, is proposed to improve the sensitivity of CSIA. This automatic, fast and solvent free strategy provides a significant increase on the sensitivity of GC-based methods maintaining the simple headspace instrumentation

  16. Advanced methods for modeling water-levels and estimating drawdowns with SeriesSEE, an Excel add-in

    USGS Publications Warehouse

    Halford, Keith; Garcia, C. Amanda; Fenelon, Joe; Mirus, Benjamin B.

    2012-01-01

    Water-level modeling is used for multiple-well aquifer tests to reliably differentiate pumping responses from natural water-level changes in wells, or “environmental fluctuations.” Synthetic water levels are created during water-level modeling and represent the summation of multiple component fluctuations, including those caused by environmental forcing and pumping. Pumping signals are modeled by transforming step-wise pumping records into water-level changes by using superimposed Theis functions. Water-levels can be modeled robustly with this Theis-transform approach because environmental fluctuations and pumping signals are simulated simultaneously. Water-level modeling with Theis transforms has been implemented in the program SeriesSEE, which is a Microsoft® Excel add-in. Moving average, Theis, pneumatic-lag, and gamma functions transform time series of measured values into water-level model components in SeriesSEE. Earth tides and step transforms are additional computed water-level model components. Water-level models are calibrated by minimizing a sum-of-squares objective function where singular value decomposition and Tikhonov regularization stabilize results. Drawdown estimates from a water-level model are the summation of all Theis transforms minus residual differences between synthetic and measured water levels. The accuracy of drawdown estimates is limited primarily by noise in the data sets, not the Theis-transform approach. Drawdowns much smaller than environmental fluctuations have been detected across major fault structures, at distances of more than 1 mile from the pumping well, and with limited pre-pumping and recovery data at sites across the United States. In addition to water-level modeling, utilities exist in SeriesSEE for viewing, cleaning, manipulating, and analyzing time-series data.

  17. The association between metabolic syndrome and the risk of prostate cancer, high-grade prostate cancer, advanced prostate cancer, prostate cancer-specific mortality and biochemical recurrence

    PubMed Central

    2013-01-01

    Background Although a previous meta-analysis reported no association between metabolic syndrome (MetS) and prostate cancer risk, a number of studies suggest that MetS may be associated with the aggressiveness and progression of prostate cancer. However, these results have been inconsistent. This systematic review and meta-analysis investigated the nature of this association. Methods We systematically searched MEDLINE, EMBASE and bibliographies of retrieved studies up to January 2013 using the keywords “metabolic syndrome” and “prostate cancer”. We assessed relative risks (RRs) of the prostate cancer, several parameters of prostate cancer aggressiveness and progression associated with MetS using 95% confidence intervals (95% CIs). Results The literature search produced 547 hits from which 19 papers were extracted for the meta-analysis. In cancer-free population with and without MetS, the combined adjusted RR (95% CI) of prostate cancer risk and prostate cancer-specific mortality in longitudinal cohort studies is 0.96 (0.85 ~ 1.09) and 1.12 (1.02 ~ 1.23) respectively. In the prostate cancer patients with and without MetS, the combined unadjusted OR (95% CI) of high grade Gleason prostate cancer is 1.44 (1.20 ~ 1.72), the OR of advanced prostate cancer is 1.37 (1.12 ~ 1.68) and the OR of biochemical recurrence is 2.06 (1.43 ~ 2.96). Conclusions The overall analyses revealed no association between MetS and prostate cancer risk, although men with MetS appear more likely to have high-grade prostate cancer and more advanced disease, were at greater risk of progression after radical prostatectomy and were more likely to suffer prostate cancer-specific death. Further primary studies with adjustment for appropriate confounders and larger, prospective, multicenter investigations are required. PMID:23406686

  18. Impacts of climate-change-driven sea level rise on intertidal rocky reef habitats will be variable and site specific.

    PubMed

    Thorner, Jaqueline; Kumar, Lalit; Smith, Stephen D A

    2014-01-01

    Intertidal rocky reefs are complex and rich ecosystems that are vulnerable to even the smallest fluctuations in sea level. We modelled habitat loss associated with sea level rise for intertidal rocky reefs using GIS, high-resolution digital imagery, and LIDAR technology at fine-scale resolution (0.1 m per pixel). We used projected sea levels of +0.3 m, +0.5 m and +1.0 m above current Mean Low Tide Level (0.4 m). Habitat loss and changes were analysed for each scenario for five headlands in the Solitary Islands Marine Park (SIMP), Australia. The results indicate that changes to habitat extent will be variable across different shores and will not necessarily result in net loss of area for some habitats. In addition, habitat modification will not follow a regular pattern over the projected sea levels. Two of the headlands included in the study currently have the maximum level of protection within the SIMP. However, these headlands are likely to lose much of the habitat known to support biodiverse assemblages and may not continue to be suitable sanctuaries into the future. The fine-scale approach taken in this study thus provides a protocol not only for modelling habitat modification but also for future proofing conservation measures under a scenario of changing sea levels. PMID:24465915

  19. Impacts of Climate-Change-Driven Sea Level Rise on Intertidal Rocky Reef Habitats Will Be Variable and Site Specific

    PubMed Central

    Thorner, Jaqueline; Kumar, Lalit; Smith, Stephen D. A.

    2014-01-01

    Intertidal rocky reefs are complex and rich ecosystems that are vulnerable to even the smallest fluctuations in sea level. We modelled habitat loss associated with sea level rise for intertidal rocky reefs using GIS, high-resolution digital imagery, and LIDAR technology at fine-scale resolution (0.1 m per pixel). We used projected sea levels of +0.3 m, +0.5 m and +1.0 m above current Mean Low Tide Level (0.4 m). Habitat loss and changes were analysed for each scenario for five headlands in the Solitary Islands Marine Park (SIMP), Australia. The results indicate that changes to habitat extent will be variable across different shores and will not necessarily result in net loss of area for some habitats. In addition, habitat modification will not follow a regular pattern over the projected sea levels. Two of the headlands included in the study currently have the maximum level of protection within the SIMP. However, these headlands are likely to lose much of the habitat known to support biodiverse assemblages and may not continue to be suitable sanctuaries into the future. The fine-scale approach taken in this study thus provides a protocol not only for modelling habitat modification but also for future proofing conservation measures under a scenario of changing sea levels. PMID:24465915

  20. Predicting Homophobic Behavior among Heterosexual Youth: Domain General and Sexual Orientation-Specific Factors at the Individual and Contextual Level

    ERIC Educational Resources Information Center

    Poteat, V. Paul; DiGiovanni, Craig D.; Scheer, Jillian R.

    2013-01-01

    As a form of bias-based harassment, homophobic behavior remains prominent in schools. Yet, little attention has been given to factors that underlie it, aside from bullying and sexual prejudice. Thus, we examined multiple domain general (empathy, perspective-taking, classroom respect norms) and sexual orientation-specific factors (sexual…

  1. Executive Functions and Prader-Willi Syndrome: Global Deficit Linked with Intellectual Level and Syndrome-Specific Associations

    ERIC Educational Resources Information Center

    Chevalère, Johann; Postal, Virginie; Jauregui, Joseba; Copet, Pierre; Laurier, Virginie; Thuilleaux, Denise

    2015-01-01

    The aim of this study was to support the growing evidence suggesting that Prader-Willi Syndrome (PWS) might present with an impairment of executive functions (EFs) and to investigate whether this impairment is specific to patients with PWS or due to their intellectual disability (ID). Six tasks were administered to assess EFs (inhibition,…

  2. Use of Tactual Materials on the Achievement of Content Specific Vocabulary and Terminology Acquisition within an Intermediate Level Science Curriculum

    ERIC Educational Resources Information Center

    Terry, Brian H.

    2012-01-01

    In this quasi-experimental study, the researcher investigated the effectiveness of three tactual strategies and one non-tactual strategy of content specific vocabulary acquisition. Flash cards, task cards, and learning wheels served as the tactual strategies, and vocabulary review sheets served as a non-tactual strategy. The sample (n = 85)…

  3. Conceptual waste package interim product specifications and data requirements for disposal of borosilicate glass defense high-level waste forms in salt geologic repositories

    SciTech Connect

    Not Available

    1983-06-01

    The conceptual waste package interim product specifications and data requirements presented are applicable specifically to the normal borosilicate glass product of the Defense Waste Processing Facility (DWPF). They provide preliminary numerical values for the defense high-level waste form parameters and properties identified in the waste form performance specification for geologic isolation in salt repositories. Subject areas treated include containment and isolation, operational period safety, criticality control, waste form/production canister identification, and waste package performance testing requirements. This document was generated for use in the development of conceptual waste package designs in salt. It will be revised as additional data, analyses, and regulatory requirements become available.

  4. Localization of the human gene for advanced glycosylation end product-specific receptor (AGER) to chromosome 6p21.3

    SciTech Connect

    Vissing, H.; Aagaard, L.; Boel, E.

    1994-12-01

    Advanced glycosylation end products (AGEs), which are the result of nonenzymatic glycosylation and oxidation of proteins exposed to aldoses, are present in plasma and accumulate in the tissues during aging and at an accelerated rate in diabetes as a result of hyperglycemia. A cell surface receptor for AGE (RAGE) with homology to the immunoglobulin superfamily of receptors has been isolated, and both RAGE antigen and mRNA have been identified in the endothelium, vascular smooth muscle cells, cardiac myocytes, monocyte-derived macrophages, and neural tissue. AGEs modulate a variety of biological reactions in tissues, such as monocyte/macrophage migration and production of cytokine-growth factors in mononuclear cells, as well as permeability, growth, and thrombogenicity of endothelia cells. Although AGEs interact specifically with RAGE, it has been suggested that AGEs are accidental and potentially pathogenic ligands for this receptor. In this study, we have used fluorescence in situ hybridization (FISH) to assign the human RAGE (AGER) gene to chromosome 6p21.3. 9 refs., 1 fig.

  5. Growth arrest-specific gene 6 (Gas6) levels are elevated in patients with chronic renal failure

    PubMed Central

    Lee, Iris J.; Hilliard, Brendan; Swami, Abhishek; Madara, John C.; Rao, Swati; Patel, Tapan; Gaughan, John P.; Lee, Jean; Gadegbeku, Crystal A.; Choi, Eric T.; Cohen, Philip L.

    2012-01-01

    Background The TAM receptors (tyro3, axl and mer) and their ligands (vitamin K-dependent proteins—Gas6 and Protein S) are crucial modulators of inflammation, which may be relevant in chronic kidney disease (CKD). Gas6 and axl have multiple roles in mediating vascular atherosclerosis and injury, thrombosis and inflammation, yet nothing is known about the Gas6–axl pathway in humans with CKD. Given the prevalence of chronic inflammation and vascular disease in this population, we measured TAM ligands in patients with various levels of renal function. Methods Gas6 and protein S were quantified in the plasma by ELISA in three patient groups: end-stage renal disease on chronic hemodialysis (HD), CKD and normal controls. Results Significantly increased levels of Gas6 and protein S were found in CKD patients compared with normal controls (P < 0.01 and <0.001, respectively). In HD patients, Gas6 levels were elevated compared with controls (P < 0.001) and positively associated with low albumin (r= 0.33; P = 0.01), dialysis vintage (r= 0.36; P = 0.008) and IV iron administration (r= 0.33; P = 0.01). The levels of Gas6 rose with CKD stage and were inversely associated with estimated GFR (P < 0.0001). Conclusions Dysregulation of circulating Gas6 is associated with renal disease and inversely proportional to renal function. Low albumin and higher IV iron administration were associated with higher Gas6 levels, suggesting a possible connection between inflammation and oxidative stress mediated by iron. Protein S levels were also elevated in CKD patients, but the relevance of this finding needs to be further investigated. PMID:22907951

  6. DNA barcodes reveal species-specific mercury levels in tuna sushi that pose a health risk to consumers.

    PubMed

    Lowenstein, Jacob H; Burger, Joanna; Jeitner, Christian W; Amato, George; Kolokotronis, Sergios-Orestis; Gochfeld, Michael

    2010-10-23

    Excessive ingestion of mercury--a health hazard associated with consuming predatory fishes--damages neurological, sensory-motor and cardiovascular functioning. The mercury levels found in Bigeye Tuna (Thunnus obesus) and bluefin tuna species (Thunnus maccoyii, Thunnus orientalis, and Thunnus thynnus), exceed or approach levels permissible by Canada, the European Union, Japan, the US, and the World Health Organization. We used DNA barcodes to identify tuna sushi samples analysed for mercury and demonstrate that the ability to identify cryptic samples in the market place allows regulatory agencies to more accurately measure the risk faced by fish consumers and enact policies that better safeguard their health. PMID:20410032

  7. The Relationship between Listening Comprehension of Text and Sentences in Preschoolers: Specific or Mediated by Lower and Higher Level Components?

    ERIC Educational Resources Information Center

    Florit, Elena; Roch, Maja; Levorato, M. Chiara

    2013-01-01

    Two studies explored the relation between listening comprehension of text and listening comprehension of sentences in preschoolers aged 4 to 5 years, 11 months. The first study analyzed this relationship taking into account the role of lower level components, namely, word knowledge and verbal working memory, as possible mediators. These components…

  8. The Decision-Adoption of Software Currency and Specificity Levels: A Quantitative Study of Information Technology (IT) Training

    ERIC Educational Resources Information Center

    Somsen, W. Randy

    2009-01-01

    IT educators and learners are continually challenged to adapt to software changes and remain current in software applications. This study researched if it is necessary for IT educators to prepare IT students in the most current software releases--i.e., at the highest software currency preparation level and in the same software application that the…

  9. Elevated Serum Levels of the Antiapoptotic Protein Decoy-Receptor 3 Are Associated with Advanced Liver Disease

    PubMed Central

    Gizis, Michalis; Delladetsima, Ioanna; Laoudi, Eyfrosyni; Siakavellas, Spyros I.; Kaltsa, Garyfallia; Vlachogiannakos, John; Vafiadis-Zouboulis, Irene; Daikos, George L.; Papatheodoridis, George V.

    2016-01-01

    Background. Decoy-receptor 3 (DcR3) exerts antiapoptotic and immunomodulatory function and is overexpressed in neoplastic and inflammatory conditions. Serum DcR3 (sDcR3) levels during the chronic hepatitis/cirrhosis/hepatocellular carcinoma (HCC) sequence have not been explored. Objective. To assess the levels and significance of sDcR3 protein in various stages of chronic liver disease. Methods. We compared sDcR3 levels between healthy controls and patients with chronic viral hepatitis (CVH), decompensated cirrhosis (DC), and HCC. Correlations between sDcR3 levels and various patient- and disease-related factors were analyzed. Results. sDcR3 levels were significantly higher in patients with CVH than in controls (P < 0.01). sDcR3 levels were elevated in DC and HCC, being significantly higher compared not only to controls (P < 0.001 for both) but to CVH patients as well (P < 0.001 for both). In addition, DcR3 protein was detected in large quantities in the ascitic fluid of cirrhotics. In patients with CVH, sDcR3 significantly correlated to fibrosis severity, as estimated by Ishak score (P = 0.019) or by liver stiffness measured with elastography (Spearman r = 0.698, P < 0.001). In cirrhotic patients, significant positive correlations were observed between sDcR3 levels and markers of severity of hepatic impairment, including MELD score (r = 0.653, P < 0.001). Conclusions. Circulating levels of DcR3 are elevated during chronic liver disease and correlate with severity of liver damage. sDcR3 may serve as marker for liver fibrosis severity and progression to end-stage liver disease. PMID:27595094

  10. Elevated Serum Levels of the Antiapoptotic Protein Decoy-Receptor 3 Are Associated with Advanced Liver Disease.

    PubMed

    Bamias, Giorgos; Gizis, Michalis; Delladetsima, Ioanna; Laoudi, Eyfrosyni; Siakavellas, Spyros I; Koutsounas, Ioannis; Kaltsa, Garyfallia; Vlachogiannakos, John; Vafiadis-Zouboulis, Irene; Daikos, George L; Papatheodoridis, George V; Ladas, Spiros D

    2016-01-01

    Background. Decoy-receptor 3 (DcR3) exerts antiapoptotic and immunomodulatory function and is overexpressed in neoplastic and inflammatory conditions. Serum DcR3 (sDcR3) levels during the chronic hepatitis/cirrhosis/hepatocellular carcinoma (HCC) sequence have not been explored. Objective. To assess the levels and significance of sDcR3 protein in various stages of chronic liver disease. Methods. We compared sDcR3 levels between healthy controls and patients with chronic viral hepatitis (CVH), decompensated cirrhosis (DC), and HCC. Correlations between sDcR3 levels and various patient- and disease-related factors were analyzed. Results. sDcR3 levels were significantly higher in patients with CVH than in controls (P < 0.01). sDcR3 levels were elevated in DC and HCC, being significantly higher compared not only to controls (P < 0.001 for both) but to CVH patients as well (P < 0.001 for both). In addition, DcR3 protein was detected in large quantities in the ascitic fluid of cirrhotics. In patients with CVH, sDcR3 significantly correlated to fibrosis severity, as estimated by Ishak score (P = 0.019) or by liver stiffness measured with elastography (Spearman r = 0.698, P < 0.001). In cirrhotic patients, significant positive correlations were observed between sDcR3 levels and markers of severity of hepatic impairment, including MELD score (r = 0.653, P < 0.001). Conclusions. Circulating levels of DcR3 are elevated during chronic liver disease and correlate with severity of liver damage. sDcR3 may serve as marker for liver fibrosis severity and progression to end-stage liver disease. PMID:27595094

  11. A thick photoresist process for advanced wafer level packaging applications using JSR THB-151N negative tone UV photoresist

    NASA Astrophysics Data System (ADS)

    Srinivasa Rao, Vempati; Kripesh, Vaidyanathan; Yoon, Seung Wook; Tay, Andrew A. O.

    2006-09-01

    The development of thick photoresist molds using JSR THB-151N negative tone UV photoresist for the electroplating of interconnects in advanced packaging technologies has been demonstrated. Two different thick photoresist molds 65 and 130 µm high with aspect ratios of up to 2.6 have been fabricated with good reproducibility using single and double coating processes. Optimized lithography parameters using a UV aligner to achieve straight and near-vertical side-wall profiles are also reported. Near-vertical side walls similar to that obtained using SU-8 photoresist have been obtained. JSR photoresist has been found to be easily striped with no residues in solvent stripper solutions, making it suitable for wafer bumping applications and the processing of MEMS devices. Through-mold electroplating of copper and solder is also demonstrated. The simultaneous fabrication of 1167 000 high density interconnects on 8 inch wafers, using lithography and electroplating technologies, is also reported.

  12. Biomarkers of respiratory syncytial virus (RSV) infection: specific neutrophil and cytokine levels provide increased accuracy in predicting disease severity.

    PubMed

    Brown, Paul M; Schneeberger, Dana L; Piedimonte, Giovanni

    2015-09-01

    Despite fundamental advances in the research on respiratory syncytial virus (RSV) since its initial identification almost 60 years ago, recurring failures in developing vaccines and pharmacologic strategies effective in controlling the infection have allowed RSV to become a leading cause of global infant morbidity and mortality. Indeed, the burden of this infection on families and health care organizations worldwide continues to escalate and its financial costs are growing. Furthermore, strong epidemiologic evidence indicates that early-life lower respiratory tract infections caused by RSV lead to the development of recurrent wheezing and childhood asthma. While some progress has been made in the identification of reliable biomarkers for RSV bronchiolitis, a "one size fits all" biomarker capable of accurately and consistently predicting disease severity and post-acute outcomes has yet to be discovered. Therefore, it is of great importance on a global scale to identify useful biomarkers for this infection that will allow pediatricians to cost-effectively predict the clinical course of the disease, as well as monitor the efficacy of new therapeutic strategies. PMID:26074450

  13. Gender specific effect of LIPC C-514T polymorphism on obesity and relationship with plasma lipid levels in Chinese children

    PubMed Central

    Wang, Hao; Zhang, Dandan; Ling, Jie; Lu, Wenhui; Zhang, Shuai; Zhu, Yimin; Lai, Maode

    2015-01-01

    Hepatic lipase (LIPC) is a key rate-limiting enzyme in lipoprotein catabolism pathways involved in the development of obesity. The C-514T polymorphism in the promoter region is associated with decreased LIPC activity. We performed a case-controlled study (850 obese children and 2119 controls) and evaluated the association between LIPC C-514T polymorphism, obesity and plasma lipid profile in Chinese children and adolescents. Additionally, we conducted a meta-analysis of all results from published studies as well as our own data. A significant association between the polymorphism and obesity is observed in boys (P = 0.042), but not in girls. And we observed a significant relationship of the polymorphism with total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) independent of obesity in boys. The T allele carriers have higher levels of low density lipoprotein cholesterol (LDL-C) in obese boys, and triglyceride (TG), TC and LDL-C in non-obese girls (all P < 0.05). In the meta-analysis, under dominant model the T allele increased body mass index (BMI) level in boys, while it decreased BMI in girls, and increased the levels of TC both in the overall and subgroups, TG and HDL-C in the overall and boys, and LDL-C in the overall (all P < 0.05). Our results suggest that the T allele might carry an increased risk of obesity in Chinese boys. The meta-analysis suggests that T allele acts as a risk allele for higher BMI levels in male childhood, while it is a protective allele in female childhood. And the polymorphism is associated with the levels of plasma lipids, which may be modulated by obesity and gender. PMID:26282880

  14. An Online Task-Based Language Learning Environment: Is It Better for Advanced- or Intermediate-Level Second Language Learners?

    ERIC Educational Resources Information Center

    Arslanyilmaz, Abdurrahman

    2012-01-01

    This study investigates the relationship of language proficiency to language production and negotiation of meaning that non-native speakers (NNSs) produced in an online task-based language learning (TBLL) environment. Fourteen NNS-NNS dyads collaboratively completed four communicative tasks, using an online TBLL environment specifically designed…

  15. EOSCUBE: A Constraint Database System for High-Level Specification and Efficient Generation of EOSDIS Products. Phase 1; Proof-of-Concept

    NASA Technical Reports Server (NTRS)

    Brodsky, Alexander; Segal, Victor E.

    1999-01-01

    The EOSCUBE constraint database system is designed to be a software productivity tool for high-level specification and efficient generation of EOSDIS and other scientific products. These products are typically derived from large volumes of multidimensional data which are collected via a range of scientific instruments.

  16. Advanced rocket propulsion

    NASA Technical Reports Server (NTRS)

    Obrien, Charles J.

    1993-01-01

    Existing NASA research contracts are supporting development of advanced reinforced polymer and metal matrix composites for use in liquid rocket engines of the future. Advanced rocket propulsion concepts, such as modular platelet engines, dual-fuel dual-expander engines, and variable mixture ratio engines, require advanced materials and structures to reduce overall vehicle weight as well as address specific propulsion system problems related to elevated operating temperatures, new engine components, and unique operating processes. High performance propulsion systems with improved manufacturability and maintainability are needed for single stage to orbit vehicles and other high performance mission applications. One way to satisfy these needs is to develop a small engine which can be clustered in modules to provide required levels of total thrust. This approach should reduce development schedule and cost requirements by lowering hardware lead times and permitting the use of existing test facilities. Modular engines should also reduce operational costs associated with maintenance and parts inventories.

  17. Advanced rocket propulsion

    NASA Astrophysics Data System (ADS)

    Obrien, Charles J.

    1993-02-01

    Existing NASA research contracts are supporting development of advanced reinforced polymer and metal matrix composites for use in liquid rocket engines of the future. Advanced rocket propulsion concepts, such as modular platelet engines, dual-fuel dual-expander engines, and variable mixture ratio engines, require advanced materials and structures to reduce overall vehicle weight as well as address specific propulsion system problems related to elevated operating temperatures, new engine components, and unique operating processes. High performance propulsion systems with improved manufacturability and maintainability are needed for single stage to orbit vehicles and other high performance mission applications. One way to satisfy these needs is to develop a small engine which can be clustered in modules to provide required levels of total thrust. This approach should reduce development schedule and cost requirements by lowering hardware lead times and permitting the use of existing test facilities. Modular engines should also reduce operational costs associated with maintenance and parts inventories.

  18. Systems level approach reveals the correlation of endoderm differentiation of mouse embryonic stem cells with specific microstructural cues of fibrin gels

    PubMed Central

    Task, Keith; D'Amore, Antonio; Singh, Satish; Candiello, Joe; Jaramillo, Maria; Wagner, William R.; Kumta, Prashant; Banerjee, Ipsita

    2014-01-01

    Stem cells receive numerous cues from their associated substrate that help to govern their behaviour. However, identification of influential substrate characteristics poses difficulties because of their complex nature. In this study, we developed an integrated experimental and systems level modelling approach to investigate and identify specific substrate features influencing differentiation of mouse embryonic stem cells (mESCs) on a model fibrous substrate, fibrin. We synthesized a range of fibrin gels by varying fibrinogen and thrombin concentrations, which led to a range of substrate stiffness and microstructure. mESCs were cultured on each of these gels, and characterization of the differentiated cells revealed a strong influence of substrate modulation on gene expression patterning. To identify specific substrate features influencing differentiation, the substrate microstructure was quantified by image analysis and correlated with stem cell gene expression patterns using a statistical model. Significant correlations were observed between differentiation and microstructure features, specifically fibre alignment. Furthermore, this relationship occurred in a lineage-specific manner towards endoderm. This systems level approach allows for identification of specific substrate features from a complex material which are influential to cellular behaviour. Such analysis may be effective in guiding the design of scaffolds with specific properties for tissue engineering applications. PMID:24718448

  19. Descriptive Epidemiology of Unintentional Burn Injuries Admitted to a Tertiary-Level Government Hospital in Nepal: Gender-Specific Patterns.

    PubMed

    Sharma, Narayan Prasad; Duke, Janine M; Lama, Bir Bahadur; Thapa, Buland; Dahal, Peeyush; Bariya, Nara Devi; Marston, Wendy; Wallace, Hilary J

    2015-07-01

    This study describes the epidemiology of unintentional adult burn injury admissions in a tertiary hospital in Nepal, from 2002 to 2013, focusing on gender-specific patterns. Chi-square tests and Wilcoxon Rank Sum tests were performed. There were 819 unintentional burn admissions: 52% were male and 58% younger than 35 years. The median percentage total body surface area burned (interquartile range) was greater in females than in males (P < .001): 28% (17-40) versus 20% (12-35), and female mortality was higher (32% vs 11%). A higher proportion females were illiterate than males (48% vs 17%). Burns occurred at home (67%), work (28%), and public places (5%); gender-specific patterns were observed. Flame burns accounted for 77%, electricity 13%, and scalds 8%. Kerosene (31%) and biomass (27%) were the major fuels. Cooking, heating, and lighting were the main activities associated with burn injury. Results support interventions to reduce the use of open fires and kerosene and to promote electrical safety. PMID:25957289

  20. Cis-Regulatory Elements Determine Germline Specificity and Expression Level of an Isopentenyltransferase Gene in Sperm Cells of Arabidopsis.

    PubMed

    Zhang, Jinghua; Yuan, Tong; Duan, Xiaomeng; Wei, Xiaoping; Shi, Tao; Li, Jia; Russell, Scott D; Gou, Xiaoping

    2016-03-01

    Flowering plant sperm cells transcribe a divergent and complex complement of genes. To examine promoter function, we chose an isopentenyltransferase gene known as PzIPT1. This gene is highly selectively transcribed in one sperm cell morphotype of Plumbago zeylanica, which preferentially fuses with the central cell during fertilization and is thus a founding cell of the primary endosperm. In transgenic Arabidopsis (Arabidopsis thaliana), PzIPT1 promoter displays activity in both sperm cells and upon progressive promoter truncation from the 5'-end results in a progressive decrease in reporter production, consistent with occurrence of multiple enhancer sites. Cytokinin-dependent protein binding motifs are identified in the promoter sequence, which respond with stimulation by cytokinin. Expression of PzIPT1 promoter in sperm cells confers specificity independently of previously reported Germline Restrictive Silencer Factor binding sequence. Instead, a cis-acting regulatory region consisting of two duplicated 6-bp Male Gamete Selective Activation (MGSA) motifs occurs near the site of transcription initiation. Disruption of this sequence-specific site inactivates expression of a GFP reporter gene in sperm cells. Multiple copies of the MGSA motif fused with the minimal CaMV35S promoter elements confer reporter gene expression in sperm cells. Similar duplicated MGSA motifs are also identified from promoter sequences of sperm cell-expressed genes in Arabidopsis, suggesting selective activation is possibly a common mechanism for regulation of gene expression in sperm cells of flowering plants. PMID:26739233

  1. Teaching Thermodynamics and Kinetics to Advanced General Chemistry Students and to Upper-Level Undergraduate Students Using PV Diagrams

    ERIC Educational Resources Information Center

    Iyengar, Srinivasan S.; deSouza, Romualdo T.

    2014-01-01

    We describe how complex concepts in macroscopic chemistry, namely, thermodynamics and kinetics, can be taught at considerable depth both at the first-year undergraduate as well as upper levels. We begin with a careful treatment of PV diagrams, and by pictorially integrating the appropriate area in a PV diagram, we introduce work. This starting…

  2. Water Relations and the Vacuolated Plant Cell: A Brief Study of the Topic at Advanced Level in School Biology.

    ERIC Educational Resources Information Center

    Gayford, C. G.

    1984-01-01

    Discusses concepts needed to understand plant water relations and results of a study designed to examine the understanding of these concepts by students preparing for A-level examinations. Focuses on students who have learned the topic using the old terminology compared with students adopting the new suggested terms. (Author/JN)

  3. Can neck exercises enhance the activation of the semispinalis cervicis relative to the splenius capitis at specific spinal levels?

    PubMed

    Schomacher, Jochen; Erlenwein, Joachim; Dieterich, Angela; Petzke, Frank; Falla, Deborah

    2015-10-01

    The deep cervical extensor, semispinalis cervicis, displays changes in behaviour and structure in people with chronic neck pain yet there is limited knowledge on how activation of this muscle can be emphasized during training. Using intramuscular electromyography (EMG), this study investigated the activity of the deep semispinalis cervicis and the superficial splenius capitis muscle at two spinal levels (C2 and C5) in ten healthy volunteers during a series of neck exercises: 1. Traction and compression, 2. Resistance applied in either flexion or extension at the occiput, at the level of the vertebral arch of C1 and of C4, and 3. Maintaining the neck in neutral while inclined on the elbows, with and without resistance at C4. The ratio between semispinalis cervicis and the splenius capitis EMG amplitude was quantified as an indication of whether the exercise could emphasize the activation of the semispinalis cervicis muscle relative to the splenius capitis. Manual resistance applied in extension over the vertebral arch emphasized the activation of the semispinalis cervicis relative to the splenius capitis at the spinal level directly caudal to the site of resistance (ratio: 2.0 ± 1.1 measured at C5 with resistance at C4 and 2.1 ± 1.2 measured at C2 with resistance at C1). This study confirmed the possibility of emphasizing the activation of the semispinalis cervicis relative to the splenius capitis which may be relevant for targeted exercise interventions for this deep extensor muscle. Further studies are required to investigate the clinical efficacy of these exercises for people with neck pain. PMID:25935795

  4. Differential levels of specific cytochrome c biogenesis proteins in response to oxygen: analysis of the ccl operon in Rhodobacter capsulatus.

    PubMed Central

    Gabbert, K K; Goldman, B S; Kranz, R G

    1997-01-01

    The photosynthetic bacterium Rhodobacter capsulatus synthesizes c-type cytochromes under a variety of growth conditions. For example, under aerobic growth, c-type cytochromes are synthesized as part of an electron transport pathway, using oxygen as the terminal electron acceptor. Anaerobically in the light, R. capsulatus requires cytochrome bc1 and other c-type cytochromes for the photosynthetic electron transport pathway. It is shown here that the ccl1 and ccl2 genes of R. capsulatus are required for the synthesis of all c-type cytochromes, including the cytochrome c' protein of unknown function but of structural similarity to cytochrome b562. Polar and nonpolar mutations constructed in each gene demonstrated that the ccl12 genes form an operon. Expression of the ccl12 genes was examined by using lacZ and phoA fusions as translational reporters. Primer extension analysis was used to determine transcriptional control and the start site of the ccl12 promoter. Finally, antiserum to the Ccl2 protein was used to quantitate levels of Ccl2 under six different growth conditions. The Ccl2 protein is present at 20-fold-higher levels under conditions where oxygen is present. In contrast, other cytochromes c biogenesis proteins, HelA and HelX, previously shown to be part of an helABCDX operon, are at relatively similar levels under these six growth conditions. This discovery is discussed in terms of the physiology and evolution of cytochromes c biogenesis, with particular attention to oxidative environments. PMID:9286996

  5. Variation in the levels of pregnancy-specific beta-1-glycoprotein in maternal serum from chromosomally abnormal pregnancies.

    PubMed

    Graham, G W; Crossley, J A; Aitken, D A; Connor, J M

    1992-06-01

    Human pregnancy-specific beta-1-glycoprotein (SP1) was assayed retrospectively in stored maternal serum (MS) samples from 82 chromosomally abnormal pregnancies and 377 matched controls. The median MSSP1 concentration in 48 Down's syndrome pregnancies was significantly elevated at 1.17 multiples of the control median (MOM), and significantly reduced (0.5 MOM) in a group of eight cases of unbalanced translocations. There was no significant difference in median SP1 concentrations in cases of trisomy 18, trisomy 13, balanced translocations, or sex chromosome abnormalities. A comparison with human chorionic gonadotrophin results in the same series of samples indicates that SP1 is a less sensitive predictor of Down's syndrome pregnancies. PMID:1387478

  6. Instrumentation report 1: specification, design, calibration, and installation of instrumentation for an experimental, high-level, nuclear waste storage facility

    SciTech Connect

    Brough, W.G.; Patrick, W.C.

    1982-01-01

    The Spent Fuel Test-Climax (SFT-C) is being conducted 420 m underground at the Nevada Test Site under the auspices of the US Department of Energy. The test facility houses 11 spent fuel assemblies from an operating commercial nuclear reactor and numerous other thermal sources used to simulate the near-field effects of a large repository. We developed a large-scale instrumentation plan to ensure that a sufficient quality and quantity of data were acquired during the three- to five-year test. These data help satisfy scientific, operational, and radiation safety objectives. Over 800 data channels are being scanned to measure temperature, electrical power, radiation, air flow, dew point, stress, displacement, and equipment operation status (on/off). This document details the criteria, design, specifications, installation, calibration, and current performance of the entire instrumentation package.

  7. Exon-Level Transcriptome Profiling in Murine Breast Cancer Reveals Splicing Changes Specific to Tumors with Different Metastatic Abilities

    PubMed Central

    Bemmo, Amandine; Dias, Christel; Rose, April A. N.; Russo, Caterina; Siegel, Peter; Majewski, Jacek

    2010-01-01

    Background Breast cancer is the second most frequent type of cancer affecting women. We are increasingly aware that changes in mRNA splicing are associated with various characteristics of cancer. The most deadly aspect of cancer is metastasis, the process by which cancer spreads from the primary tumor to distant organs. However, little is known specifically about the involvement of alternative splicing in the formation of macroscopic metastases. Our study investigates transcript isoform changes that characterize tumors of different abilities to form growing metastases. Methods and Findings To identify alternative splicing events (ASEs) that are associated with the fully metastatic phenotype in breast cancer, we used Affymetrix Exon Microarrays to profile mRNA isoform variations genome-wide in weakly metastatic (168FARN and 4T07) and highly metastatic (4T1) mammary carcinomas. Statistical analysis identified significant expression changes in 7606 out of 155,994 (4%) exons and in 1725 out of 189,460 (1%) intronic regions, which affect 2623 out of 16,654 (16%) genes. These changes correspond to putative alternative isoforms—several of which are novel—that are differentially expressed between tumors of varying metastatic phenotypes. Gene pathway analysis showed that 1224 of genes expressing alternative isoforms were involved in cell growth, cell interactions, cell proliferation, cell migration and cell death and have been previously linked to cancers and genetic disorders. We chose ten predicted splice variants for RT-PCR validation, eight of which were successfully confirmed (MED24, MFI2, SRRT, CD44, CLK1 and HNRNPH1). These include three novel intron retentions in CD44, a gene in which isoform variations have been previously associated with the metastasis of several cancers. Conclusion Our findings reveal that various genes are differently spliced and/or expressed in association with the metastatic phenotype of tumor cells. Identification of metastasis-specific

  8. Community-Level and Species-Specific Associations between Phytoplankton and Particle-Associated Vibrio Species in Delaware's Inland Bays.

    PubMed

    Main, Christopher R; Salvitti, Lauren R; Whereat, Edward B; Coyne, Kathryn J

    2015-09-01

    Vibrio species are an abundant and diverse group of bacteria that form associations with phytoplankton. Correlations between Vibrio and phytoplankton abundance have been noted, suggesting that growth is enhanced during algal blooms or that association with phytoplankton provides a refuge from predation. Here, we investigated relationships between particle-associated Vibrio spp. and phytoplankton in Delaware's inland bays (DIB). The relative abundances of particle-associated Vibrio spp. and algal classes that form blooms in DIB (dinoflagellates, diatoms, and raphidophytes) were determined using quantitative PCR. The results demonstrated a significant correlation between particle-associated Vibrio abundance and phytoplankton, with higher correlations to diatoms and raphidophytes than to dinoflagellates. Species-specific associations were examined during a mixed bloom of Heterosigma akashiwo and Fibrocapsa japonica (Raphidophyceae) and indicated a significant positive correlation for particle-associated Vibrio abundance with H. akashiwo but a negative correlation with F. japonica. Changes in Vibrio assemblages during the bloom were evaluated using automated ribosomal intergenic spacer analysis (ARISA), which revealed significant differences between each size fraction but no significant change in Vibrio assemblages over the course of the bloom. Microzooplankton grazing experiments showed that losses of particle-associated Vibrio spp. may be offset by increased growth in the Vibrio population. Moreover, analysis of Vibrio assemblages by ARISA also indicated an increase in the relative abundance for specific members of the Vibrio community despite higher grazing pressure on the particle-associated population as a whole. The results of this investigation demonstrate links between phytoplankton and Vibrio that may lead to predictions of potential health risks and inform future management practices in this region. PMID:26070682

  9. Community-Level and Species-Specific Associations between Phytoplankton and Particle-Associated Vibrio Species in Delaware's Inland Bays

    PubMed Central

    Main, Christopher R.; Salvitti, Lauren R.; Whereat, Edward B.

    2015-01-01

    Vibrio species are an abundant and diverse group of bacteria that form associations with phytoplankton. Correlations between Vibrio and phytoplankton abundance have been noted, suggesting that growth is enhanced during algal blooms or that association with phytoplankton provides a refuge from predation. Here, we investigated relationships between particle-associated Vibrio spp. and phytoplankton in Delaware's inland bays (DIB). The relative abundances of particle-associated Vibrio spp. and algal classes that form blooms in DIB (dinoflagellates, diatoms, and raphidophytes) were determined using quantitative PCR. The results demonstrated a significant correlation between particle-associated Vibrio abundance and phytoplankton, with higher correlations to diatoms and raphidophytes than to dinoflagellates. Species-specific associations were examined during a mixed bloom of Heterosigma akashiwo and Fibrocapsa japonica (Raphidophyceae) and indicated a significant positive correlation for particle-associated Vibrio abundance with H. akashiwo but a negative correlation with F. japonica. Changes in Vibrio assemblages during the bloom were evaluated using automated ribosomal intergenic spacer analysis (ARISA), which revealed significant differences between each size fraction but no significant change in Vibrio assemblages over the course of the bloom. Microzooplankton grazing experiments showed that losses of particle-associated Vibrio spp. may be offset by increased growth in the Vibrio population. Moreover, analysis of Vibrio assemblages by ARISA also indicated an increase in the relative abundance for specific members of the Vibrio community despite higher grazing pressure on the particle-associated population as a whole. The results of this investigation demonstrate links between phytoplankton and Vibrio that may lead to predictions of potential health risks and inform future management practices in this region. PMID:26070682

  10. Pathogen group specific risk factors at herd, heifer and quarter levels for intramammary infections in early lactating dairy heifers.

    PubMed

    Piepers, S; Peeters, K; Opsomer, G; Barkema, H W; Frankena, K; De Vliegher, S

    2011-05-01

    Risk factors for intramammary infections caused by coagulase-negative staphylococci, contagious major pathogens and environmental major pathogens in early lactating heifers were evaluated at the herd, heifer and quarter levels. In total, 764 quarters of 191 dairy heifers in 20 randomly selected farms in Flanders (Belgium) were sampled. Quarter milk samples were collected between 1 and 4 days in milk and between 5 and 8 days in milk for bacteriological culture. Data were analyzed using multivariable, multilevel logistic regression analysis. Higher average herd milk somatic cell count (>200,000 cells/mL), not having an effective fly control strategy, contact with lactating cows prior to calving and moderate to severe udder edema prior to calving increased the odds of intramammary infections caused by contagious major pathogens. Poor heifer hygiene and lack of mineral/vitamin supplementation prior to calving were risk factors for intramammary infection caused by environmental major pathogens. Teat apex colonization with coagulase-negative staphylococci prior to calving seemed to protect quarters against intramammary infections caused by major pathogens. Poor heifer hygiene before calving, a non-clipped udder and not practicing of teat dipping prior to calving increased the odds of intramammary infection with coagulase-negative staphylococci. Although management is important in the prevention and control of intramammary infections in early lactating heifers, most variation in the prevalence of intramammary infections resided at the heifer and quarter levels, indicating that the susceptibility for intramammary infections around calving is mainly determined by heifer and quarter characteristics. PMID:21411160

  11. Annual Variation in the Levels of Transcripts of Sex-Specific Genes in the Mantle of the Common Mussel, Mytilus edulis

    PubMed Central

    Anantharaman, Sandhya; Craft, John A.

    2012-01-01

    Mytilus species are used as sentinels for the assessment of environmental health but sex or stage in the reproduction cycle is rarely considered even though both parameters are likely to influence responses to pollution. We have validated the use of a qPCR assay for sex identification and related the levels of transcripts to the reproductive cycle. A temporal study of mantle of Mytilus edulis found transcripts of male-specific vitelline coat lysin (VCL) and female-specific vitelline envelope receptor for lysin (VERL) could identify sex over a complete year. The levels of VCL/VERL were proportional to the numbers of sperm/ova and are indicative of the stage of the reproductive cycle. Maximal levels of VCL and VERL were found in February 2009 declining to minima between July – August before increasing and re-attaining a peak in February 2010. Water temperature may influence these transitions since they coincide with minimal water temperature in February and maximal temperature in August. An identical pattern of variation was found for a cryptic female-specific transcript (H5) but a very different pattern was observed for oestrogen receptor 2 (ER2). ER2 varied in a sex-specific way with male > female for most of the cycle, with a female maxima in July and a male maxima in December. Using artificially spawned animals, the transcripts for VCL, VERL and H5 were shown to be present in gametes and thus their disappearance from mantle is indicative of spawning. VCL and VERL are present at equivalent levels in February and July–August but during gametogenesis (August to January) and spawning (March to June) VCL is present at lower relative amounts than VERL. This may indicate sex-specific control mechanisms for these processes and highlight a potential pressure point leading to reduced reproductive output if environmental factors cause asynchrony to gamete maturation or release. PMID:23226407

  12. Annual variation in the levels of transcripts of sex-specific genes in the mantle of the common mussel, Mytilus edulis.

    PubMed

    Anantharaman, Sandhya; Craft, John A

    2012-01-01

    Mytilus species are used as sentinels for the assessment of environmental health but sex or stage in the reproduction cycle is rarely considered even though both parameters are likely to influence responses to pollution. We have validated the use of a qPCR assay for sex identification and related the levels of transcripts to the reproductive cycle. A temporal study of mantle of Mytilus edulis found transcripts of male-specific vitelline coat lysin (VCL) and female-specific vitelline envelope receptor for lysin (VERL) could identify sex over a complete year. The levels of VCL/VERL were proportional to the numbers of sperm/ova and are indicative of the stage of the reproductive cycle. Maximal levels of VCL and VERL were found in February 2009 declining to minima between July - August before increasing and re-attaining a peak in February 2010. Water temperature may influence these transitions since they coincide with minimal water temperature in February and maximal temperature in August. An identical pattern of variation was found for a cryptic female-specific transcript (H5) but a very different pattern was observed for oestrogen receptor 2 (ER2). ER2 varied in a sex-specific way with male > female for most of the cycle, with a female maxima in July and a male maxima in December. Using artificially spawned animals, the transcripts for VCL, VERL and H5 were shown to be present in gametes and thus their disappearance from mantle is indicative of spawning. VCL and VERL are present at equivalent levels in February and July-August but during gametogenesis (August to January) and spawning (March to June) VCL is present at lower relative amounts than VERL. This may indicate sex-specific control mechanisms for these processes and highlight a potential pressure point leading to reduced reproductive output if environmental factors cause asynchrony to gamete maturation or release. PMID:23226407

  13. Advanced chronic kidney disease populations have elevated trimethylamine N-oxide levels associated with increased cardiovascular events.

    PubMed

    Kim, Richard B; Morse, Bridget L; Djurdjev, Ognjenka; Tang, Mila; Muirhead, Norman; Barrett, Brendan; Holmes, Daniel T; Madore, Francois; Clase, Catherine M; Rigatto, Claudio; Levin, Adeera

    2016-05-01

    Cardiovascular disease is more common in patients with chronic kidney disease (CKD), and traditional risk factors do not adequately predict those at risk for cardiovascular (CV) events. Recent evidence suggests elevated trimethylamine N-oxide (TMAO), created by gut microflora from dietary L-carnitine and choline, is associated with CV events. We investigated the relationship of TMAO levels in patients with stages 3b and 4 CKD to ischemic CV events using the CanPREDDICT cohort, a Canada-wide observational study with prospective 3-year follow-up of adjudicated CV events. Baseline samples were obtained for 2529 CKD patients. TMAO, choline, and L-carnitine levels were measured using tandem mass spectrometry. Baseline median TMAO level was high for the whole cohort (20.41 μM; interquartile range [IQR]: 12.82-32.70 μM). TMAO was independently associated with CV events (hazard ratio 1.23; 95% confidence interval: 1.06-1.42 / 1 SD lnTMAO) after adjusting for all potential CV risk factors. Those in the highest TMAO quartile had significantly higher risk of CV events (adjusted hazard ratio 1.59; 95% confidence interval: 1.04-2.43; P = 0.0351) in the analysis of recurring ischemic events. Among those with stage 3b CKD (hazard ratio 1.45; 95% confidence interval: 1.12-1.87 / 1 SD lnTMAO), independent of kidney function, TMAO levels identified those at highest risk for events. Our results suggest that TMAO may represent a new potentially modifiable CV risk factor for CKD patients. Further studies are needed to determine sources of variability and if lowering of TMAO reduces CV risk in CKD. PMID:27083288

  14. Muscle co-activity tuning in Parkinsonian hand movement: disease-specific changes at behavioral and cerebral level.

    PubMed

    van der Stouwe, A M M; Toxopeus, C M; de Jong, B M; Yavuz, P; Valsan, G; Conway, B A; Leenders, K L; Maurits, N M

    2015-01-01

    We investigated simple directional hand movements based on different degrees of muscle co-activity, at behavioral and cerebral level in healthy subjects and Parkinson's disease (PD) patients. We compared "singular" movements, dominated by the activity of one agonist muscle, to "composite" movements, requiring conjoint activity of multiple muscles, in a center-out (right hand) step-tracking task. Behavioral parameters were obtained by EMG and kinematic recordings. fMRI was used to investigate differences in underlying brain activations between PD patients (N = 12) and healthy (age-matched) subjects (N = 18). In healthy subjects, composite movements recruited the striatum and cortical areas comprising bilaterally the supplementary motor area and premotor cortex, contralateral medial prefrontal cortex, primary motor cortex, primary visual cortex, and ipsilateral superior parietal cortex. Contrarily, the ipsilateral cerebellum was more involved in singular movements. This striking dichotomy between striatal and cortical recruitment vs. cerebellar involvement was considered to reflect the complementary roles of these areas in motor control, in which the basal ganglia are involved in movement selection and the cerebellum in movement optimization. Compared to healthy subjects, PD patients showed decreased activation of the striatum and cortical areas in composite movement, while performing worse at behavioral level. This implies that PD patients are especially impaired on tasks requiring highly tuned muscle co-activity. Singular movement, on the other hand, was characterized by a combination of increased activation of the ipsilateral parietal cortex and left cerebellum. As singular movement performance was only slightly compromised, we interpret this as a reflection of increased visuospatial processing, possibly as a compensational mechanism. PMID:26300761

  15. Muscle co-activity tuning in Parkinsonian hand movement: disease-specific changes at behavioral and cerebral level

    PubMed Central

    van der Stouwe, A. M. M.; Toxopeus, C. M.; de Jong, B. M.; Yavuz, P.; Valsan, G.; Conway, B. A.; Leenders, K. L.; Maurits, N. M.

    2015-01-01

    We investigated simple directional hand movements based on different degrees of muscle co-activity, at behavioral and cerebral level in healthy subjects and Parkinson's disease (PD) patients. We compared “singular” movements, dominated by the activity of one agonist muscle, to “composite” movements, requiring conjoint activity of multiple muscles, in a center-out (right hand) step-tracking task. Behavioral parameters were obtained by EMG and kinematic recordings. fMRI was used to investigate differences in underlying brain activations between PD patients (N = 12) and healthy (age-matched) subjects (N = 18). In healthy subjects, composite movements recruited the striatum and cortical areas comprising bilaterally the supplementary motor area and premotor cortex, contralateral medial prefrontal cortex, primary motor cortex, primary visual cortex, and ipsilateral superior parietal cortex. Contrarily, the ipsilateral cerebellum was more involved in singular movements. This striking dichotomy between striatal and cortical recruitment vs. cerebellar involvement was considered to reflect the complementary roles of these areas in motor control, in which the basal ganglia are involved in movement selection and the cerebellum in movement optimization. Compared to healthy subjects, PD patients showed decreased activation of the striatum and cortical areas in composite movement, while performing worse at behavioral level. This implies that PD patients are especially impaired on tasks requiring highly tuned muscle co-activity. Singular movement, on the other hand, was characterized by a combination of increased activation of the ipsilateral parietal cortex and left cerebellum. As singular movement performance was only slightly compromised, we interpret this as a reflection of increased visuospatial processing, possibly as a compensational mechanism. PMID:26300761

  16. The Dynamics of Eukaryotic Replication Initiation: Origin Specificity, Licensing, and Firing at the Single-molecule Level

    PubMed Central

    Duzdevich, Daniel; Warner, Megan D.; Ticau, Simina; Ivica, Nikola A.; Bell, Stephen P.; Greene, Eric C.

    2015-01-01

    SUMMARY Eukaryotic replication initiation is highly regulated and dynamic. It begins with the Origin Recognition Complex (ORC) binding DNA sites called origins of replication. ORC, together with Cdc6 and Cdt1, mediate pre-Replicative Complex (pre-RC) assembly by loading a double hexamer of Mcm2-7: the core of the replicative helicase. Here, we use single-molecule imaging to directly visualize Saccharomyces cerevisiae pre-RC assembly and replisome firing in real time. We show that ORC can locate and stably bind origins within large tracts of non-origin DNA, and that Cdc6 drives ordered pre-RC assembly. We further show that the dynamics of the ORC-Cdc6 interaction dictate Mcm2-7 loading specificity and that Mcm2-7 double hexamers form preferentially at a native origin sequence. Finally, we demonstrate that single Mcm2-7 hexamers propagate bidirectionally, monotonically, and processively as constituents of active replisomes. PMID:25921072

  17. Hairpin oligonucleotides anchored terbium ion: a fluorescent probe to specifically detect lead(II) at sub-nM levels.

    PubMed

    Wei, Yueteng; Liu, Ru; Wang, Yaling; Zhao, Yuliang; Cai, Zhifang; Gao, Xueyun

    2013-04-21

    A terbium based fluorescent probe was synthesized by coordinating terbium ions with a designed oligonucleotides (5'-ATATGGGGGATAT-3', termed GH5). GH5 improved the fluorescence of terbium ions by four orders of magnitude. The fluorescence enhancement of terbium ions by different oligonucleotides sequences indicated that the polyguanine loop of the hairpin GH5 is key to enhance terbium ion emission. The quantum yield of Tb-GH5 probe was 10.5% and the probe was photo-stable. The result of conductivity titration indicated that the stoichiometry of the probe is 3.5 Tb: 1 GH5, which is confirmed by fluorescence titration. This probe had high sensitivity and specificity for the detection of lead ions. The fluorescence intensity of this probe was linear with respect to lead concentration over a range 0.3-2.1 nM (R(2) = 0.99). The limit of detection for lead ions was 0.1 nM at a signal-to-noise ratio of 3. PMID:23446487

  18. Differential effects of "Advanced glycation endproducts" and beta-amyloid peptide on glucose utilization and ATP levels in the neuronal cell line SH-SY5Y.

    PubMed

    Kuhla, B; Loske, C; Garcia De Arriba, S; Schinzel, R; Huber, J; Münch, G

    2004-03-01

    Beta-amyloid peptide (Abeta) and "Advanced glycation endproducts" (AGEs) are components of the senile plaques in Alzheimer's disease patients. It has been proposed that both AGEs and Abeta exert many of their effects, which include the upregulation of pro-inflammatory cytokines, through RAGE ("receptor for advanced glycation endproducts"). To investigate whether Abeta and AGEs cause similar or identical effects on cell survival and energy metabolism, we have compared the effects of a model-AGE and Abeta on cell viability, ATP level, glucose consumption and lactate production in the neuroblastoma cell line SH-SY5Y. The results show that AGEs and Abeta increase glucose consumption and decrease ATP levels in a dose dependent manner. Furthermore, both compounds decrease mitochondrial activity measured by the MTT assay. However, only AGEs decrease the number of cells and significantly increase lactate production. These data indicate that both AGEs and Abeta can cause differential disturbances in neuronal metabolism, which may contribute to the pathophysiological findings in Alzheimer's disease. However, their signalling pathways are apparently quite distinct, a fact which should stimulate a more detailed investigation in this field, e.g. for the purpose of a rational design of potential "neuroprotective" RAGE antagonists. PMID:14991463

  19. Scaling up health knowledge at European level requires sharing integrated data: an approach for collection of database specification.

    PubMed

    Menditto, Enrica; Bolufer De Gea, Angela; Cahir, Caitriona; Marengoni, Alessandra; Riegler, Salvatore; Fico, Giuseppe; Costa, Elisio; Monaco, Alessandro; Pecorelli, Sergio; Pani, Luca; Prados-Torres, Alexandra

    2016-01-01

    Computerized health care databases have been widely described as an excellent opportunity for research. The availability of "big data" has brought about a wave of innovation in projects when conducting health services research. Most of the available secondary data sources are restricted to the geographical scope of a given country and present heterogeneous structure and content. Under the umbrella of the European Innovation Partnership on Active and Healthy Ageing, collaborative work conducted by the partners of the group on "adherence to prescription and medical plans" identified the use of observational and large-population databases to monitor medication-taking behavior in the elderly. This article describes the methodology used to gather the information from available databases among the Adherence Action Group partners with the aim of improving data sharing on a European level. A total of six databases belonging to three different European countries (Spain, Republic of Ireland, and Italy) were included in the analysis. Preliminary results suggest that there are some similarities. However, these results should be applied in different contexts and European countries, supporting the idea that large European studies should be designed in order to get the most of already available databases. PMID:27358570

  20. Specific accumulation of organochlorines in human breast milk from Indonesia: levels, distribution, accumulation kinetics and infant health risk.

    PubMed

    Sudaryanto, Agus; Kunisue, Tatsuya; Kajiwara, Natsuko; Iwata, Hisato; Adibroto, Tussy A; Hartono, Phillipus; Tanabe, Shinsuke

    2006-01-01

    This study determined concentrations of polychlorinated biphenyls (PCBs) and organochlorine compound (OC) pesticides in the milk samples of women from the general population in four locations of Indonesia. The most prevalent residues of OCs were DDTs, PCBs and hexachlorocyclohexane isomers (HCHs), whereas other OCs such as chlordane compounds (CHLs), tris(4-chlorophenyl)methane and hexachlorobenzene were lower. The levels of OCs varied between locations and individuals, with DDTs higher in suburban and rural areas than urban localities, may be due to the differences in food habits and sources between the individuals and locations. Data from Purwakarta site indicated continuing DDT exposure, which may confirm recent usage of DDT in Indonesia. A positive correlation was observed between concentration of OCs in human milk and age of mothers, primiparas women having higher OCs than multiparas, suggesting these parameters play an important role influencing the OC burdens in lactating women. Some individuals accumulated DDTs and HCHs in breast milk close to or even higher than the TDI (tolerable daily intake) guidelines proposed by Health Canada. PMID:15992976

  1. Scaling up health knowledge at European level requires sharing integrated data: an approach for collection of database specification

    PubMed Central

    Menditto, Enrica; Bolufer De Gea, Angela; Cahir, Caitriona; Marengoni, Alessandra; Riegler, Salvatore; Fico, Giuseppe; Costa, Elisio; Monaco, Alessandro; Pecorelli, Sergio; Pani, Luca; Prados-Torres, Alexandra

    2016-01-01

    Computerized health care databases have been widely described as an excellent opportunity for research. The availability of “big data” has brought about a wave of innovation in projects when conducting health services research. Most of the available secondary data sources are restricted to the geographical scope of a given country and present heterogeneous structure and content. Under the umbrella of the European Innovation Partnership on Active and Healthy Ageing, collaborative work conducted by the partners of the group on “adherence to prescription and medical plans” identified the use of observational and large-population databases to monitor medication-taking behavior in the elderly. This article describes the methodology used to gather the information from available databases among the Adherence Action Group partners with the aim of improving data sharing on a European level. A total of six databases belonging to three different European countries (Spain, Republic of Ireland, and Italy) were included in the analysis. Preliminary results suggest that there are some similarities. However, these results should be applied in different contexts and European countries, supporting the idea that large European studies should be designed in order to get the most of already available databases. PMID:27358570

  2. Increasing the endogenous NO level causes catalase inactivation and reactivation of intercellular apoptosis signaling specifically in tumor cells

    PubMed Central

    Bauer, Georg

    2015-01-01

    NO metabolism and direct catalase inhibitors. The latter aspect is explicitely studied for the interaction between catalase inhibiting acetylsalicylic acid and an NO donor. It is also shown that hybrid molecules like NO-aspirin utilize this synergistic potential. Our data open novel approaches for rational tumor therapy based on specific ROS signaling and its control in tumor cells. PMID:26342455

  3. Increasing the endogenous NO level causes catalase inactivation and reactivation of intercellular apoptosis signaling specifically in tumor cells.

    PubMed

    Bauer, Georg

    2015-12-01

    NO metabolism and direct catalase inhibitors. The latter aspect is explicitely studied for the interaction between catalase inhibiting acetylsalicylic acid and an NO donor. It is also shown that hybrid molecules like NO-aspirin utilize this synergistic potential. Our data open novel approaches for rational tumor therapy based on specific ROS signaling and its control in tumor cells. PMID:26342455

  4. Cigarette smoking, educational level and total and site-specific cancer: a cohort study in men in Lithuania.

    PubMed

    Everatt, Rūta; Kuzmickienė, Irena; Virvičiūtė, Dalia; Tamošiūnas, Abdonas

    2014-11-01

    Smoking is an established risk factor for cancer. However, most studies have been carried out on western populations, and less is known about the impact in central and eastern Europe. Our objective was to investigate the association between cigarette smoking, educational level and risk of cancer in a Lithuanian population-based cohort study. The study included 6976 men initially free from cancer. During the follow-up (1978-2008), 1780 cancer cases were identified. Cox proportional hazards models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs). In addition, the burden of cancer attributable to smoking was assessed by the population attributable fraction. Following adjustment for age, education, alcohol consumption and BMI, for current compared with never smokers, highly significant and strongly elevated estimates were found for total (HR=1.79, 95% CI 1.59-2.02), tobacco-related (HR=2.52, 95% CI 2.16-2.95), upper aerodigestive tract (UADT) (HR=5.77, 95% CI 2.73-12.21), lung (HR=10.47, 95% CI 6.74-16.25), bladder (HR=3.31, 95% CI 1.71-6.41) and liver (HR=4.64, 95% CI 1.53-14.08) cancer. Findings suggest a lower risk of prostate cancer in current smokers. In addition, the occurrence of lung and UADT cancer was significantly elevated in men in the lowest educational attainment category. If smoking had not occurred, ∼23% of total cancer, 37% of tobacco-related, 77% of lung, 58% of UADT, 43% of liver and 45% of bladder cancer cases could have been prevented in this cohort of men. Cancer-control strategies focused on reducing smoking should be a public health priority. PMID:24589745

  5. Species and gamete-specific fertilization success of two sea urchins under near future levels of pCO2

    NASA Astrophysics Data System (ADS)

    Sung, Chan-Gyung; Kim, Tae Won; Park, Young-Gyu; Kang, Seong-Gil; Inaba, Kazuo; Shiba, Kogiku; Choi, Tae Seob; Moon, Seong-Dae; Litvin, Steve; Lee, Kyu-Tae; Lee, Jung-Suk

    2014-09-01

    Since the Industrial Revolution, rising atmospheric CO2 concentration has driven an increase in the partial pressure of CO2 in seawater (pCO2), thus lowering ocean pH. We examined the separate effects of exposure of gametes to elevated pCO2 and low pH on fertilization success of the sea urchin Strongylocentrotus nudus. Sperm and eggs were independently exposed to seawater with pCO2 levels ranging from 380 (pH 7.96-8.3) to 6000 ppmv (pH 7.15-7.20). When sperm were exposed, fertilization rate decreased drastically with increased pCO2, even at a concentration of 450 ppmv (pH range: 7.94 to 7.96). Conversely, fertilization of Hemicentrotus pulcherrimus was not significantly changed even when sperm was exposed to pCO2 concentrations as high as 750 ppmv. Exposure of S. nudus eggs to seawater with high pCO2 did not affect fertilization success, suggesting that the effect of increased pCO2 on sperm is responsible for reduced fertilization success. Surprisingly, this result was not related to sperm motility, which was insensitive to pCO2. When seawater was acidified using HCl, leaving pCO2 constant, fertilization success in S. nudus remained high (> 80%) until pH decreased to 7.3. While further studies are required to elucidate the physiological mechanism by which elevated pCO2 impairs sperm and reduces S. nudus fertilization, this study suggests that in the foreseeable future, sea urchin survival may be threatened due to lower fertilization success driven by elevated pCO2 rather than by decreased pH in seawater.

  6. The Relationship Between Population-Level Exposure to Alcohol Advertising on Television and Brand-Specific Consumption Among Underage Youth in the US

    PubMed Central

    Ross, Craig S.; Maple, Emily; Siegel, Michael; DeJong, William; Naimi, Timothy S.; Padon, Alisa A.; Borzekowski, Dina L.G.; Jernigan, David H.

    2015-01-01

    Aims: We investigated the population-level relationship between exposure to brand-specific advertising and brand-specific alcohol use among US youth. Methods: We conducted an internet survey of a national sample of 1031 youth, ages 13–20, who had consumed alcohol in the past 30 days. We ascertained all of the alcohol brands respondents consumed in the past 30 days, as well as which of 20 popular television shows they had viewed during that time period. Using a negative binomial regression model, we examined the relationship between aggregated brand-specific exposure to alcohol advertising on the 20 television shows [ad stock, measured in gross rating points (GRPs)] and youth brand-consumption prevalence, while controlling for the average price and overall market share of each brand. Results: Brands with advertising exposure on the 20 television shows had a consumption prevalence about four times higher than brands not advertising on those shows. Brand-level advertising elasticity of demand varied by exposure level, with higher elasticity in the lower exposure range. The estimated advertising elasticity of 0.63 in the lower exposure range indicates that for each 1% increase in advertising exposure, a brand's youth consumption prevalence increases by 0.63%. Conclusions: At the population level, underage youths' exposure to brand-specific advertising was a significant predictor of the consumption prevalence of that brand, independent of each brand's price and overall market share. The non-linearity of the observed relationship suggests that youth advertising exposure may need to be lowered substantially in order to decrease consumption of the most heavily advertised brands. PMID:25754127

  7. Prostate-specific Antigen (PSA) Density and Free to Total PSA Ratio in Diagnosing Prostate Cancer with Prostate-Specific Antigen Levels of 4.0 ng/ml or Less

    PubMed Central

    LIU, Xin; TANG, Jie; FEI, Xiang; LI, Qiu-Yang

    2015-01-01

    Background: We aimed to value the usefulness of free to total prostate-specific antigen and Prostate-specific antigen (PSA) density for prostate cancer in the patients with PSA levels of 4.0 ng/ml or less. Methods: A total of 343 subjects with PSA levels of 4.0 ng/ml or less were biopsied. All patients were divided into four groups according to the PSA levels: 0 to 1.0 ng/ml, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml, and 3.1 to 4.0 ng/ml. The reliability of cancer detection in relation to the f/t PSA ratio and PSAD were estimated. Results: Overall, 65 people were diagnosed with prostate cancer. The detection rate was 16.28%、17.17%, 21.82%, 25.00% in subjects with PSA levels of 0 to 1.0 ng/ml, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml, and 3.1 to 4.0 ng/ml, respectively. The f/t PSA ratio was significantly lower in patients with prostate cancer and PSA levels of 2.1 to 4.0 ng/ml (P<0.05). The PSAD had no statistical significance between the two groups. Conclusions: Routine prostate biopsy should be undertaken if the f/t PSA ratio less than 15% with /without abnormal DRE/TRUS findings. PMID:26744703

  8. Specific glucosinolate analysis reveals variable levels of epimeric glucobarbarins, dietary precursors of 5-phenyloxazolidine-2-thiones, in watercress types with contrasting chromosome numbers.

    PubMed

    Agerbirk, Niels; Olsen, Carl Erik; Cipollini, Don; Ørgaard, Marian; Linde-Laursen, Ib; Chew, Frances S

    2014-10-01

    Watercress obtained in food stores in the United States contained significant levels of epiglucobarbarin [(R)-2-hydroxy-2-phenylethylglucosinolate] and low levels of the 2S-epimer glucobarbarin identified by an HPLC+NMR+MS/MS approach. Typical combined levels were 4-7 μmol/g dry wt. The hydrolysis product, 5-phenyloxazolidine-2-thione (barbarin), was detected at similar levels as the precursor glucosinolates after autolysis of fresh watercress in water. Fragmentation patterns in MS(2) of reference desulfoglucosinolates were side chain specific and suitable for routine identification. Watercress was of two main glucosinolate chemotypes: Material from U.S. food stores had a complex profile including glucobarbarins, gluconasturtiin, indole glucosinolates and high levels (6-28 μmol/g dry wt.) of long-chain methylsulfinylalkyl and methylthioalkyl glucosinolates. Material from European food stores had a simple profile dominated by gluconasturtiin, with low levels of epiglucobarbarin and moderate levels of indole glucosinolates. Some wild U.S. material was similar to the U.S. food store type. Both types were found to be Nasturtium officinale by floral parts morphology. Cytological analysis of one U.S. food store accession indicated that it represented a chromosome-doubled variant within N. officinale. The nutritional consequences and invasive potential of the U.S. food store chemotype are discussed. PMID:25226408

  9. A Level-1 Tracking Trigger for the CMS upgrade using stacked silicon strip detectors and advanced pattern technologies

    NASA Astrophysics Data System (ADS)

    Boudoul, G.

    2013-01-01

    Experience at high luminosity hadrons collider experiments shows that tracking information enhances the trigger rejection capabilities while retaining high efficiency for interesting physics events. The design of a tracking based trigger for the High Luminosity LHC (HL-LHC) is an extremely challenging task, and requires the identification of high-momentum particle tracks as a part of the Level 1 Trigger. Simulation studies show that this can be achieved by correlating hits on two closely spaced silicon strip sensors, and reconstructing tracks at L1 by employing an Associative Memory approach. The progresses on the design and development of this micro-strip stacked prototype modules and the performance of few prototype detectors will be presented. Preliminary results of a simulated tracker layout equipped with stacked modules are discussed in terms of pT resolution and triggering capabilities. Finally, a discussion on the L1 architecture will be given.

  10. Blood Lead Levels and Cause-Specific Mortality of Inorganic Lead-Exposed Workers in South Korea

    PubMed Central

    Kim, Min-Gi; Ryoo, Jae-Hong; Chang, Se-Jin; Kim, Chun-Bae; Park, Jong-Ku; Koh, Sang-Baek; Ahn, Yeon-Soon

    2015-01-01

    The objective of this study was to identify the association of blood lead level (BLL) with mortality in inorganic lead-exposed workers of South Korea. A cohort was compiled comprising 81,067 inorganic lead exposed workers working between January 1, 2000, and December 31, 2004. This cohort was merged with the Korean National Statistical Office to follow-up for mortality between 2000 and 2008. After adjusting for age and other carcinogenic metal exposure, all-cause mortality (Relative risk [RR] 1.36, 95% confidence interval [CI] 1.03–1.79), digestive disease (RR 3.23, 95% CI 1.33–7.86), and intentional self-harm (RR 2.92, 95% CI 1.07–7.81) were statistically significantly higher in males with BLL >20 μg/dl than of those with BLL ≤10μg/dl. The RR of males with BLL of 10–20 μg/dl was statistically higher than of those with BLL ≤10μg/dl in infection (RR 3.73. 95% CI, 1.06–13.06). The RRs of females with 10–20 μg/dl BLL was statistically significantly greater than those with BLL <10μg/dl in all-cause mortality (RR 1.93, 95% CI 1.16–3.20) and colon and rectal cancer (RR 13.42, 95% CI 1.21–149.4). The RRs of females with BLL 10–20 μg/dl (RR 10.45, 95% CI 1.74–62.93) and BLL ≥20 μg/dl (RR 12.68, 95% CI 1.69–147.86) was statistically significantly increased in bronchus and lung cancer. The increased suicide of males with ≥20 μg/dl BLLs, which might be caused by major depression, might be associated with higher lead exposure. Also, increased bronchus and lung cancer mortality in female workers with higher BLL might be related to lead exposure considering low smoking rate in females. The kinds of BLL-associated mortality differed by gender. PMID:26469177

  11. Convergence Revolution Comes to Wearables: Multiple Advances are Taking Biosensor Networks to the Next Level in Health Care.

    PubMed

    Mertz, Leslie

    2016-01-01

    In the field of wearable biomedical sensors, the convergence revolution is more than a fanciful, utopian view of the way innovation should be done. Medical-grade wearable sensors rely on it. Their development requires technical know-how, computing expertise, clinical input, and collaboration-a true meeting of the minds to permit the conversion of wearables from neat gadgets into practical and proficient tools that will propel health care to new heights. Beyond the increasing miniaturization of hardware and the shift to wireless communication technology, flexible electronics and more powerful computing capabilities, including application specific integrated circuits (ASICs) and microelectromechanical systems (MEMS), have enabled new work on body sensor networks (BSNs) that monitor, analyze, and make sense of body signals for the prevention, diagnosis, and treatment of health disorders. Developments in processing, such as sensor-connected nodes combined with evolving algorithms and decreasing power requirements, have also contributed. In addition, new approaches to subjective measures (pain and emotion) have opened possibilities. PMID:26799721

  12. Sex-specific association of the peptidase D gene rs731839 polymorphism and serum lipid levels in the Mulao and Han populations

    PubMed Central

    Lin, Quan-Zhen; Yin, Rui-Xing; Wu, Jian; Guo, Tao; Wang, Wei; Sun, Jia-Qi; Shi, Guang-Yuan; Shen, Shao-Wen; Wu, Jin-Zhen; Pan, Shang-Ling

    2014-01-01

    Little is known about the association of peptidase D (PEPD) gene rs731839 single nucleotide polymorphism (SNP) and serum lipid profiles in the Chinese population. The objective of the present study was to detect the association of the PEPD rs731839 SNP and serum lipid levels in the Mulao and Han populations. Genotyping of the PEPD rs731839 SNP was performed in 751 subjects of Mulao and 762 subjects of Han using polymerase chain reaction and restriction fragment length polymorphism and then confirmed by direct sequencing. The A allele carriers had higher serum high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) AI levels and lower triglyceride (TG) levels in Mulao; and higher HDL-C, low-density lipoprotein cholesterol (LDL-C) and ApoAI levels in Han than the A allele non-carriers. Subgroup analyses showed that the A allele carriers had higher HDL-C, ApoAI levels and lower TG levels in Mulao males but not in females; higher total cholesterol (TC), HDL-C, LDL-C and ApoAI levels in Han males; and higher TG, HDL-C and ApoAI levels in Han females than the A allele non-carriers. Serum lipid parameters were also correlated with several environmental factors in Mulao and Han populations, or in males and females in both ethnic groups. The association of the PEPD rs731839 SNP and serum lipid levels was different between the Mulao and Han populations, and between males and females in the both ethnic groups. There may be an ethnic- and/or sex-specific association of the PEPD rs731839 SNP and serum lipid levels in our study populations. PMID:25120796

  13. Evaluation of Radiation Doses Due to Consumption of Contaminated Food Items and Calculation of Food Class-Specific Derived Intervention Levels

    SciTech Connect

    Heinzelman, K M; Mansfield, W G

    2010-04-27

    This document evaluates the expected radiation dose due to the consumption of several specific food classes (dairy, meat, produce, etc.) contaminated with specific radionuclides, and relates concentration levels in food to the detection abilities of typical aboratory analysis/measurement methods. The attached charts present the limiting organ dose as a function of the radionuclide concentration in a particular food class, and allow the user to compare these concentrations and doses to typical analytical detection apabilities. The expected radiation dose depends on several factors: the age of the individual; the radionuclide present in the food; the concentration of the radionuclide in the food; and the amount of food consumed. Food consumption rates for individuals of various ges were taken from the 1998 United States Food and Drug Administration (FDA) document, Accidental Radioactive Contamination of HUman Food and Animal Feeds: Recommendations for State and Local Agencies. In that document, the FDA defines the erived Intervention Level (DIL), which is the concentration of a particular radionuclide in food that if consumed could result in an individual receiving a radiation dose exceeding the Protection Action Guide (PAG) thresholds for intervention. This document also resents odified, food class specific DIL, which is calculated using a somewhat modified version of the FDA's procedure. This document begins with an overview of the FDA's DIL calculation, followed by a description of the food class specific DIL calculations, and finally charts of the radiation dose per radioactivity concentration for several food class/radionuclide combinations.

  14. LEU3 of Saccharomyces cerevisiae encodes a factor for control of RNA levels of a group of leucine-specific genes.

    PubMed Central

    Friden, P; Schimmel, P

    1987-01-01

    Although the majority of genes for amino acid biosynthesis which have been examined are under general amino acid control, LEU1 and LEU2 of Saccharomyces cerevisiae respond specifically to leucine. We report here an analysis of LEU3, a putative leucine-specific regulatory locus. We show that LEU3 is necessary for expression of wild-type levels of LEU1- and LEU2-specific RNAs and, further, that the levels of LEU4-specific transcripts are also affected by LEU3. We cloned LEU3 and showed by DNA sequence analysis that it contained an open reading frame of 886 amino acids. A striking feature of the predicted LEU3 protein was a cluster of acidic amino acids (19 of 20) located in the C-terminal half of the coding region. The protein also had a repeated cysteine motif which was conserved in a number of other yeast proteins implicated in gene regulation. We show that whole-cell extracts contained a LEU3-dependent DNA-binding activity that interacted with the 5' region of LEU2. Subdivision of the LEU2 5' region established that the LEU3-dependent DNA-binding activity interacted with the segment which had the previously reported homology with LEU1. Images PMID:2823102

  15. Phase I trial of a monoclonal antibody specific for alphavbeta3 integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion.

    PubMed

    McNeel, Douglas G; Eickhoff, Jens; Lee, Fred T; King, David M; Alberti, Dona; Thomas, James P; Friedl, Andreas; Kolesar, Jill; Marnocha, Rebecca; Volkman, Jennifer; Zhang, Jianliang; Hammershaimb, Luz; Zwiebel, James A; Wilding, George

    2005-11-01

    At present, a variety of agents targeting tumor angiogenesis are under clinical investigation as new therapies for patients with cancer. Overexpression of the alpha(v)beta(3) integrin on tumor vasculature has been associated with an aggressive phenotype of several solid tumor types. Murine models have shown that antibodies targeting the alpha(v)beta(3) integrin can affect tumor vasculature and block tumor formation and metastasis. These findings suggest that antibodies directed at alpha(v)beta(3) could be investigated in the treatment of human malignancies. The current phase I dose escalation study evaluated the safety of MEDI-522, a monoclonal antibody specific for the alpha(v)beta(3) integrin, in patients with advanced malignancies. Twenty-five patients with a variety of metastatic solid tumors were treated with MEDI-522 on a weekly basis with doses ranging from 2 to 10 mg/kg/wk. Adverse events were assessed weekly; pharmacokinetic studies were done; and radiographic staging was done every 8 weeks. In addition, dynamic computed tomography imaging was done at baseline and at 8 weeks in patients with suitable target lesions amenable to analysis, to potentially identify the effect of MEDI-522 on tumor perfusion. Treatment was well tolerated, and a maximum tolerated dose was not identified by traditional dose-limiting toxicities. The major adverse events observed were grade 1 and 2 infusion-related reactions (fever, rigors, flushing, injection site reactions, and tachycardia), low-grade constitutional and gastrointestinal symptoms (fatigue, myalgias, and nausea), and asymptomatic hypophosphatemia. Dynamic computed tomography imaging suggested a possible effect on tumor perfusion with an increase in contrast mean transit time from baseline to the 8-week evaluation with increasing doses of MEDI-522. No complete or partial responses were observed. Three patients with metastatic renal cell cancer experienced prolonged stable disease (34 weeks, >1 and >2 years) on

  16. Neuron-Specific Enolase, S100 Calcium-Binding Protein B, and Heat Shock Protein 70 Levels in Patients With Intracranial Hemorrhage

    PubMed Central

    Alatas, Ömer Doğan; Gürger, Mehtap; Ateşçelik, Metin; Yildiz, Mustafa; Demir, Caner Feyzi; Kalayci, Mehmet; Ilhan, Nevin; Acar, Ethem

    2015-01-01

    Abstract The authors evaluated neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B), and heat shock protein 70 (HSP 70) levels and their relationships with in-hospital mortality, Glasgow Coma Scale (GCS) scores, and National Institute of Health Stroke Scale (NIHSS) scores. In total, 35 patients older than 18 years were presented to our emergency department and were diagnosed with non-traumatic intracranial hemorrhage (ICH) and 32 healthy controls were included. Blood samples were drawn on days 0 and 5. S100 calcium-binding protein B and HSP levels were significantly higher in patients than in controls on days 0 and 5. Neuron-specific enolase levels were higher in patients than in controls on day 0, but there was no significant difference on day 5. S100 calcium-binding protein B was negatively correlated with GCS, whereas it was positively correlated with NIHSS and bleeding volume. There was also a negative correlation between NSE and GCS, but it was not statistically significant. In addition, no significant correlation was found in terms of bleeding volume or NIHSS. Heat shock protein 70 was negatively correlated with GCS and positively correlated with bleeding volume and NIHSS, but these results were not statistically significant. S100 calcium-binding protein B and HSP 70 levels were significantly higher in those who died compared with survivors. The areas under the curve of S100 B, NSE, and HSP 70 for mortality were 0.635, 0.477, and 0.770, respectively. Neuron-specific enolase, S100B, and HSP 70 levels are simple, inexpensive, and objective measures in cases of ICH. These tests can be used to support an assessment for screening ICH patients with clinical scoring systems, such as GCS and NIHSS. PMID:26559295

  17. Integrated Advanced Microwave Sounding Unit-A (AMSU-A). Engineering Test Report: AMSU-A1 METSAT Instrument (S/N 105) Qualification, Level Vibration Tests of December 1998 (S/O 605445, OC-419)

    NASA Technical Reports Server (NTRS)

    Heffner, R. J.

    1998-01-01

    This is the Engineering Test Report, AMSU-AL METSAT Instrument (S/N 105) Qualification Level Vibration Tests of December 1998 (S/0 605445, OC-419), for the Integrated Advanced Microwave Sounding Unit-A (AMSU-A).

  18. An Increase of Plasma Advanced Oxidation Protein Products Levels Is Associated with Cardiovascular Risk in Incident Peritoneal Dialysis Patients: A Pilot Study

    PubMed Central

    Gonzalez, Elena; Bajo, Maria-Auxiliadora; Carrero, Juan J.; Lindholm, Bengt; Grande, Cristina; Sánchez-Villanueva, Rafael; Del Peso, Gloria; Díaz-Almirón, Mariana; Iglesias, Pedro; Díez, Juan J.; Selgas, Rafael

    2015-01-01

    Advanced oxidation protein products (AOPPs) are considered as markers and even mediators of the proinflammatory effect of oxidative stress in uremia. We hypothesized that an increase of oxidative stress associated with peritoneal dialysis (PD), estimated by the variation of plasma AOPPs over time, might be associated with cardiovascular (CV) risk and overall prognosis. In 48 PD patients, blood samples were collected on two occasions: the first one in the first six months after starting PD therapy and the second one, one year after. The plasma AOPPs level variation over the first year on PD was significantly associated with CV antecedents and also with CV prognosis. In those patients in whom the AOPPs levels increased more than 50% above the baseline value, a significant association with past and future CV disease was confirmed. These patients had 4.7 times greater risk of suffering later CV disease than those with a smaller increase, even after adjusting for previous CV history. Our data suggest that the increase of AOPPs plasma level over the first year on PD is conditioned by CV antecedents but also independently predicts CV prognosis. AOPPs plasma levels seem to represent the CV status of PD patients with sufficient sensitivity to identify those with a clearly sustained higher CV risk. PMID:26581178

  19. Wuchereria bancrofti filariasis in French Polynesia: age-specific patterns of microfilaremia, circulating antigen, and specific IgG and IgG4 responses according to transmission level.

    PubMed

    Chanteau, S; Glaziou, P; Plichart, C; Luquiaud, P; Moulia-Pelat, J P; N'Guyen, L; Cartel, J L

    1995-01-01

    The age-specific patterns of microfilaremia, Og4C3 antigenemia, anti-Brugia malayi IgG and IgG4 were assessed in 3 villages of low, medium and high transmission level for Wuchereria bancrofti filariasis. The prevalence rates for each of the 4 markers were clearly age dependent and their patterns strongly associated with the transmission level. The antigenemia prevalence rate was consistently higher than the microfilaremia prevalence rate, in all age groups. The prevalences of anti-B. malayi IgG and IgG4 responses were very similar and much higher than those of microfilaremia or antigenemia. Antibody responses reached the plateau at an earlier age and at a higher prevalence with increased intensity of transmission. For all the markers, the prevalence rates were significantly higher in males than in females. PMID:7797377

  20. Assessment of activity in Sarcoidosis. Sensitivity and specificity of 67Gallium scintigraphy, serum ACE levels, chest roentgenography, and blood lymphocyte subpopulations

    SciTech Connect

    Klech, H.; Kohn, H.; Kummer, F.; Mostbeck, A.

    1982-12-01

    The value of different factors are examined to assess activity in 60 patients with biopsy-proven sarcoidosis. In patients with active sarcoidosis (n . 35), /sup 67/Ga scans proved to be the most sensitive method (94 percent sensitivity), followed by serum angiotensin I converting enzyme (S-ACE) levels, chest x-ray films, and lymphocyte assays. In patients with peripheral pulmonary lesions, chest x-ray films failed in 32 percent of cases to document activity (68 percent sensitivity) whereas /sup 67/Ga scans and S-ACE levels remained to give reliable results. Despite poor specificity, negative /sup 67/Ga scans together with normal ACE levels have a high predictive value for exclusion of active sarcoidosis. In patients with peripheral pulmonary lesions, chest roentgenography is of doubtful value for staging lung involvement and assessment of activity including monitoring and control of therapy.

  1. Contribution of genetic variation rs266882 to prostate-specific antigen levels in healthy controls with serum PSA below 2.0 ng/ml.

    PubMed

    Song, Jaeman; Park, Heeyoon; Lee, Gilho

    2013-04-01

    We evaluated the impact of genetic variation in the prostate-specific antigen (PSA) gene (rs266882) on serum PSA levels in healthy men as well as risk factors for benign prostate hypertrophy (BPH) and prostate cancer. The study population comprised 91 men with PSA levels below 2.0 ng/ml as healthy controls, 78 men with PSA 2-10 ng/ml as a BPH group, and 128 prostate cancer patients, all in Korea. DNA was amplified by polymerase chain reaction and the product was sequenced. We found that PSA levels were associated with a G/A polymorphism only in healthy controls. The transition, however, was not associated with PSA levels of BPH and cancer patients, nor was it a risk factor. In conclusion, this genetic factor is important for determining serum PSA levels in the naive group, whereas the disruption of prostatic architecture in BPH or prostate cancer may be a major determining factor for PSA levels. PMID:23315126

  2. Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p

    PubMed Central

    Han, Kihoon; Gennarino, Vincenzo Alessandro; Lee, Yoontae; Pang, Kaifang; Hashimoto-Torii, Kazue; Choufani, Sanaa; Raju, Chandrasekhar S.; Oldham, Michael C.; Weksberg, Rosanna; Rakic, Pasko; Liu, Zhandong; Zoghbi, Huda Y.

    2013-01-01

    Proper neurological function in humans requires precise control of levels of the epigenetic regulator methyl CpG-binding protein 2 (MeCP2). MeCP2 protein levels are low in fetal brains, where the predominant MECP2 transcripts have an unusually long 3′ untranslated region (UTR). Here, we show that miR-483-5p, an intragenic microRNA of the imprinted IGF2, regulates MeCP2 levels through a human-specific binding site in the MECP2 long 3′ UTR. We demonstrate the inverse correlation of miR-483-5p and MeCP2 levels in developing human brains and fibroblasts from Beckwith-Wiedemann syndrome patients. Importantly, expression of miR-483-5p rescues abnormal dendritic spine phenotype of neurons overexpressing human MeCP2. In addition, miR-483-5p modulates the levels of proteins of the MeCP2-interacting corepressor complexes, including HDAC4 and TBL1X. These data provide insight into the role of miR-483-5p in regulating the levels of MeCP2 and interacting proteins during human fetal development. PMID:23431031

  3. Forebrain-specific Expression of Monoamine Oxidase A Reduces Neurotransmitter Levels, Restores the Brain Structure, and Rescues Aggressive Behavior in Monoamine Oxidase A-deficient Mice*

    PubMed Central

    Chen, Kevin; Cases, Olivier; Rebrin, Igor; Wu, Weihua; Gallaher, Timothy K.; Seif, Isabelle; Shih, Jean Chen

    2010-01-01

    Previous studies have established that abrogation of monoamine oxidase (MAO) A expression leads to a neurochemical, morphological, and behavioral specific phenotype with increased levels of serotonin (5-HT), norepinephrine, and dopamine, loss of barrel field structure in mouse somatosensory cortex, and an association with increased aggression in adults. Forebrain-specific MAO A transgenic mice were generated from MAO A knock-out (KO) mice by using the promoter of calcium-dependent kinase IIα (CaMKIIα). The presence of human MAO A transgene and its expression were verified by PCR of genomic DNA and reverse transcription-PCR of mRNA and Western blot, respectively. Significant MAO A catalytic activity, autoradiographic labeling of 5-HT, and immunocytochemistry of MAO A were found in the frontal cortex, striatum, and hippocampus but not in the cerebellum of the forebrain transgenic mice. Also, compared with MAO A KO mice, lower levels of 5-HT, norepinephrine, and DA and higher levels of MAO A metabolite 5-hydroxyin-doleacetic acid were found in the forebrain regions but not in the cerebellum of the transgenic mice. These results suggest that MAO A is specifically expressed in the forebrain regions of transgenic mice. This forebrain-specific differential expression resulted in abrogation of the aggressive phenotype. Furthermore, the disorganization of the somatosensory cortex barrel field structure associated with MAO A KO mice was restored and became morphologically similar to wild type. Thus, the lack of MAO A in the forebrain of MAO A KO mice may underlie their phenotypes. PMID:17090537

  4. Low levels of Caspase-3 predict favourable response to 5FU-based chemotherapy in advanced colorectal cancer: Caspase-3 inhibition as a therapeutic approach

    PubMed Central

    Flanagan, L; Meyer, M; Fay, J; Curry, S; Bacon, O; Duessmann, H; John, K; Boland, K C; McNamara, D A; Kay, E W; Bantel, H; Schulze-Bergkamen, H; Prehn, J H M

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers in the Western world. 5-Fluorouracil (5FU)-based chemotherapy (CT) remains the mainstay treatment of CRC in the advanced setting, and activates executioner caspases in target cells. Executioner caspases are key proteins involved in cell disassembly during apoptosis. Activation of executioner caspases also has a role in tissue regeneration and repopulation by stimulating signal transduction and cell proliferation in neighbouring, non-apoptotic cells as reported recently. Tissue microarrays (TMAs) consisting of tumour tissue from 93 stage II and III colon cancer patients were analysed by immunohistochemistry. Surprisingly, patients with low levels of active Caspase-3 had an increased disease-free survival time. This was particularly pronounced in patients who received 5FU-based adjuvant CT. In line with this observation, lower serum levels of active Caspase-3 were found in patients with metastasised CRC who revealed stable disease or tumour regression compared with those with disease progression. The role of Caspase-3 in treatment responses was explored further in primary human tumour explant cultures from fresh patient tumour tissue. Exposure of explant cultures to 5FU-based CT increased the percentage of cells positive for active Caspase-3 and Terminal Deoxynucleotidyl Transferase dUTP Nick end Labelling (TUNEL), but also the expression of regeneration and proliferation markers β-Catenin and Ki-67, as well as cyclooxygenase-2 (COX-2). Of note, selective inhibition of Caspase-3 with Ac-DNLD-CHO, a selective, reversible inhibitor of Caspase-3, significantly reduced the expression of proliferation markers as well as COX-2. Inhibition of COX-2 with aspirin or celecoxib did not affect Caspase-3 levels but also reduced Ki-67 and β-Catenin levels, suggesting that Caspase-3 acted via COX-2 to stimulate cell proliferation and tissue regeneration. This indicates that low levels of active Caspase-3 may represent a

  5. Low levels of Caspase-3 predict favourable response to 5FU-based chemotherapy in advanced colorectal cancer: Caspase-3 inhibition as a therapeutic approach.

    PubMed

    Flanagan, L; Meyer, M; Fay, J; Curry, S; Bacon, O; Duessmann, H; John, K; Boland, K C; McNamara, D A; Kay, E W; Bantel, H; Schulze-Bergkamen, H; Prehn, J H M

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers in the Western world. 5-Fluorouracil (5FU)-based chemotherapy (CT) remains the mainstay treatment of CRC in the advanced setting, and activates executioner caspases in target cells. Executioner caspases are key proteins involved in cell disassembly during apoptosis. Activation of executioner caspases also has a role in tissue regeneration and repopulation by stimulating signal transduction and cell proliferation in neighbouring, non-apoptotic cells as reported recently. Tissue microarrays (TMAs) consisting of tumour tissue from 93 stage II and III colon cancer patients were analysed by immunohistochemistry. Surprisingly, patients with low levels of active Caspase-3 had an increased disease-free survival time. This was particularly pronounced in patients who received 5FU-based adjuvant CT. In line with this observation, lower serum levels of active Caspase-3 were found in patients with metastasised CRC who revealed stable disease or tumour regression compared with those with disease progression. The role of Caspase-3 in treatment responses was explored further in primary human tumour explant cultures from fresh patient tumour tissue. Exposure of explant cultures to 5FU-based CT increased the percentage of cells positive for active Caspase-3 and Terminal Deoxynucleotidyl Transferase dUTP Nick end Labelling (TUNEL), but also the expression of regeneration and proliferation markers β-Catenin and Ki-67, as well as cyclooxygenase-2 (COX-2). Of note, selective inhibition of Caspase-3 with Ac-DNLD-CHO, a selective, reversible inhibitor of Caspase-3, significantly reduced the expression of proliferation markers as well as COX-2. Inhibition of COX-2 with aspirin or celecoxib did not affect Caspase-3 levels but also reduced Ki-67 and β-Catenin levels, suggesting that Caspase-3 acted via COX-2 to stimulate cell proliferation and tissue regeneration. This indicates that low levels of active Caspase-3 may represent a

  6. Brain-derived neurotrophic factor serum levels in genetically isolated populations: gender-specific association with anxiety disorder subtypes but not with anxiety levels or Val66Met polymorphism.

    PubMed

    Carlino, Davide; Francavilla, Ruggiero; Baj, Gabriele; Kulak, Karolina; d'Adamo, Pio; Ulivi, Sheila; Cappellani, Stefania; Gasparini, Paolo; Tongiorgi, Enrico

    2015-01-01

    Anxiety disorders (ADs) are disabling chronic disorders with exaggerated behavioral response to threats. This study was aimed at testing the hypothesis that ADs may be associated with reduced neurotrophic activity, particularly of Brain-derived neurotrophic factor (BDNF), and determining possible effects of genetics on serum BDNF concentrations. In 672 adult subjects from six isolated villages in North-Eastern Italy with high inbreeding, we determined serum BDNF levels and identified subjects with different ADs subtypes such as Social and Specific Phobias (PHSOC, PHSP), Generalized Anxiety Disorder (GAD), and Panic Disorder (PAD). Analysis of the population as a whole or individual village showed no significant correlation between serum BDNF levels and Val66Met polymorphism and no association with anxiety levels. Stratification of subjects highlighted a significant decrease in serum BDNF in females with GAD and males with PHSP. This study indicates low heritability and absence of any impact of the Val66Met polymorphism on circulating concentrations of BDNF. Our results show that BDNF is not a general biomarker of anxiety but serum BDNF levels correlate in a gender-specific manner with ADs subtypes. PMID:26539329

  7. Brain-derived neurotrophic factor serum levels in genetically isolated populations: gender-specific association with anxiety disorder subtypes but not with anxiety levels or Val66Met polymorphism

    PubMed Central

    Carlino, Davide; Francavilla, Ruggiero; Baj, Gabriele; Kulak, Karolina; d’Adamo, Pio; Ulivi, Sheila; Cappellani, Stefania; Gasparini, Paolo

    2015-01-01

    Anxiety disorders (ADs) are disabling chronic disorders with exaggerated behavioral response to threats. This study was aimed at testing the hypothesis that ADs may be associated with reduced neurotrophic activity, particularly of Brain-derived neurotrophic factor (BDNF), and determining possible effects of genetics on serum BDNF concentrations. In 672 adult subjects from six isolated villages in North-Eastern Italy with high inbreeding, we determined serum BDNF levels and identified subjects with different ADs subtypes such as Social and Specific Phobias (PHSOC, PHSP), Generalized Anxiety Disorder (GAD), and Panic Disorder (PAD). Analysis of the population as a whole or individual village showed no significant correlation between serum BDNF levels and Val66Met polymorphism and no association with anxiety levels. Stratification of subjects highlighted a significant decrease in serum BDNF in females with GAD and males with PHSP. This study indicates low heritability and absence of any impact of the Val66Met polymorphism on circulating concentrations of BDNF. Our results show that BDNF is not a general biomarker of anxiety but serum BDNF levels correlate in a gender-specific manner with ADs subtypes. PMID:26539329

  8. Recent Advances in Analytical Methods on Lipoprotein Subclasses: Calculation of Particle Numbers from Lipid Levels by Gel Permeation HPLC Using "Spherical Particle Model".

    PubMed

    Okazaki, Mitsuyo; Yamashita, Shizuya

    2016-01-01

    Recently, we developed an analytical method for determining the lipid levels and particle numbers in lipoprotein subclasses covering a wide size range from chylomicrons to small high density lipoproteins, by using gel permeation high-performance liquid chromatography (GP-HPLC). The challenges in analytical methods on lipoprotein subclasses have been addressed from 1980 by Hara and Okazaki using commercial TSK gel permeation columns. Later, the improvements in the hardware, separation and detection of lipoproteins, and the data processing software, using a Gaussian distribution approximation to calculate lipid levels of lipoprotein subclasses, have been extensively utilized in these analytical methods for over thirty years. In this review, we describe on the recent advances in analytical methods on lipoprotein subclasses based on various techniques, and the calculation of particle numbers from lipid levels by GPHPLC using the "spherical particle model". Free/ester ratio of cholesterol in particular lipoprotein subclass was accurately estimated from triglyceride, total cholesterol (free and esterified) and the size of the particle based on this model originally proposed by Shen and Kezdy. PMID:27041512

  9. Relations among water levels, specific conductance, and depths of bedrock fractures in four road-salt-contaminated wells in Maine, 2007–9

    USGS Publications Warehouse

    Schalk, Charles W.; Stasulis, Nicholas W.

    2012-01-01

    Data on groundwater-level, specific conductance (a surrogate for chloride), and temperature were collected continuously from 2007 through 2009 at four bedrock wells known to be affected by road salts in an effort to determine the effects of road salting and fractures in bedrock that intersect the well at a depth below the casing on the presence of chloride in groundwater. Dissolved-oxygen data collected periodically also were used to make inferences about the interaction of fractures and groundwater flow. Borehole geophysical tools were used to determine the depths of fractures in each well that were actively contributing flow to the well, under both static and pumped conditions; sample- and measurement-depths were selected to correspond to the depths of these active fractures. Samples of water from the wells, collected at depths corresponding to active bedrock fractures, were analyzed for chloride concentration and specific conductance; from these analyses, a linear relation between chloride concentration and specific conductance was established, and continuous and periodic measurements of specific conductance were assumed to represent chloride concentration of the well water at the depth of measurement. To varying degrees, specific conductance increased in at least two of the wells during winter and spring thaws; the shallowest well, which also was closest to the road receiving salt treatment during the winter, exhibited the largest changes in specific conductance during thaws. Recharge events during summer months, long after application of road salt had ceased for the year, also produced increases in specific conductance in some of the wells, indicating that chloride which had accumulated or sequestered in the overburden was transported to the wells throughout the year. Geophysical data and periodic profiles of water quality along the length of each well’s borehole indicated that the greatest changes in water quality were associated with active fractures; in

  10. Age- and Gender-Specific Reference Intervals for Fasting Blood Glucose and Lipid Levels in School Children Measured With Abbott Architect c8000 Chemistry Analyzer.

    PubMed

    Tamimi, Waleed; Albanyan, Esam; Altwaijri, Yasmin; Tamim, Hani; Alhussein, Fahad

    2012-04-01

    Reference intervals for pubertal characteristics are influenced by genetic, geographic, dietary and socioeconomic factors. Therefore, the aim of this study was to establish age-specific reference intervals of glucose and lipid levels among local school children. This was cross-sectional study, conducted among Saudi school children. Fasting blood samples were collected from 2149 children, 1138 (53%) boys and 1011 (47%) girls, aged 6 to 18 years old. Samples were analyzed on the Architect c8000 Chemistry System (Abbott Diagnostics, USA) for glucose, cholesterol, triglycerides, HDL and LDL. Reference intervals were established by nonparametric methods between the 2.5th and 97.5th percentiles. Significant differences were observed between boys and girls for cholesterol and triglycerides levels in all age groups (P < 0.02). Only at age 6-7 years and at adolescents, HDL and LDL levels were found to be significant (P < 0.001). No significant differences were seen in glucose levels except at age 12 to 13 years. Saudi children have comparable serum cholesterol levels than their Western counterparts. This may reflect changing dietary habits and increasing affluence in Saudi Arabia. Increased lipid screening is anticipated, and these reference intervals will aid in the early assessment of cardiovascular and diabetes risk in Saudi pediatric populations. PMID:23542765

  11. Trauma scores and neuron-specific enolase, cytokine and C-reactive protein levels as predictors of mortality in patients with blunt head trauma.

    PubMed

    Sogut, O; Guloglu, C; Orak, M; Sayhan, M B; Gokdemir, M T; Ustundag, M; Akkus, Z

    2010-01-01

    This study evaluated serum neuron-specific enolase (NSE), cytokine and high-sensitivity C-reactive-protein (hs-CRP) levels, along with the Glasgow Coma Scale (GCS) and Revised Trauma Score (RTS), as predictors of mortality in the early posttraumatic period, in 100 Turkish patients with blunt head trauma. Overall patient mortality was 27%. There was a significant association between age and mortality, and mortality was negatively correlated with GCS and RTS. Head injury severity (GCS) was significantly related to NSE, hs-CRP, interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-alpha levels. Mortality correlated positively with IL-6, IL-8, TNF-alpha and hs-CRP levels. NSE, hs-CRP, IL-6, IL-8 and TNF-alpha levels were significantly higher in non-survivors compared with survivors. GCS score < or =8, younger age and NSE levels were significant independent predictors of mortality. During the early post-traumatic period, NSE may be an objective alternative criterion to the GCS, in the management of patients with blunt head trauma. PMID:21309485

  12. Military specifications

    NASA Technical Reports Server (NTRS)

    Reynolds, Philip

    1987-01-01

    The current situation relative to the military specification is that there is not one specific model of turbulence which people are using. Particular disagreement exists on how turbulence levels will vary with qualitative analysis. It does not tie one down to specifics. When it comes to flying quality specifications, many feel that one should stay with the definitions of the Cooper-Harper rating scale but allow the levels to shift depending on the level of turbulence. There is a ride quality specification in the MIL-SPEC having to do with flight control systems design that is related to a turbulence model. This spec (MIL-F8785C) and others are discussed.

  13. Expression of Telomeres in Astrocytoma WHO Grade 2 to 4: TERRA Level Correlates with Telomere Length, Telomerase Activity, and Advanced Clinical Grade12

    PubMed Central

    Sampl, Sandra; Pramhas, Sibylle; Stern, Christian; Preusser, Matthias; Marosi, Christine; Holzmann, Klaus

    2012-01-01

    Cancer cells bypass replicative senescence, the major barrier to tumor progression, by using telomerase or alternative lengthening of telomeres (ALT) as telomere maintenance mechanisms (TMMs). Correlation between ALT and patient survival was demonstrated for high-grade astrocytomas. Transcription from subtelomeres produces telomeric repeat-containing RNA (TERRA), a natural inhibitor of telomerase activity (TA). This led us to evaluate correlations of TERRA and TMM with tumor grade and outcome in astrocytoma patients. SYBR Green real-time reverse transcription-polymerase chain reaction assays for quantitation of total and chromosome 2p and 18p specific TERRA levels were developed. Tumor samples from 46 patients with astrocytoma grade 2 to 4, tissue controls, and cell lines were assessed. TMMs were evaluated by measuring TA and by detecting long telomeres due to ALT. In glioblastoma multiforme (GBM) grade 4, total TERRA levels were similar to cell lines but 14-, 31-, and 313-fold lower compared with grade 3, grade 2, and nonmalignant tissue, respectively. Total TERRA levels differed from chromosomal levels. Low 2p TERRA levels correlated with dense promoter methylation of subtelomeric CpG islands, indicating that TERRA expression in gliomas may be chromosome specific and epigenetically regulated. Total TERRA levels correlated with diagnosis, with low or absent TA and the presence of ALT, and were tentatively associated with favorable patient prognosis in our cohort (P = .06). TA and short telomeres identified a subset of GBM with a median survival of only 14.8 months. TERRA and TA may be prognostic in astrocytic tumors. PMID:22348177

  14. Decreased specific antibody responses to alpha-Gal-conjugated antigen in animals with preexisting high levels of natural antibodies binding alpha-Gal residues.

    PubMed

    Parmentier, H K; De Vries Reilingh, G; Lammers, A

    2008-05-01

    High levels of natural antibodies (NAb) binding the alpha-Gal residue (Galalpha1-3Galbeta1-4GlcNAc) are found in poultry (and humans), which is probably reflected by high levels of natural agglutinating antibodies (Ab) to rabbit red blood cells (RRBC) in plasma from chickens (and humans). Recently, it was shown that alpha-Gal conjugation of proteins induced higher antiprotein Ab responses in alpha-Gal knockout mice, suggesting immune-enhancing features of preexisting Ab binding carbohydrate-protein conjugates. We challenged chickens s.c. with either alpha-Gal-conjugated human serum albumin (HuSA), beta-Gal-conjugated HuSA, or unconjugated ("native") HuSA, respectively, and measured primary and secondary Ab responses to HuSA, including isotype IgM and IgG responses, and cellular immune responses in vitro (lymphoproliferation) to HuSA or concanavalin A. alpha-Gal conjugation, but not beta-Gal conjugation, of HuSA resulted in significantly decreased primary and secondary Ab responses to HuSA, especially IgG isotype responses, as compared with Ab responses to native HuSA. Lymphoproliferation in vitro was also decreased, although not significantly, in birds challenged with alpha-Gal-conjugated HuSA. High levels of agglutinating Ab levels to RRBC and NAb binding porcine thyroglobulin were detected in all birds, as was true for (natural) Ab levels binding alpha-Gal-conjugated HuSA before immunization, whereas low levels of preexisting (natural) antibodies directed to native HuSA were present in plasma before immunization. Levels of RRBC agglutinins and Ab binding thyroglobulin were not affected by immunization with HuSA, alpha-Gal-conjugated HuSA, or beta-Gal-conjugated HuSA. Our data confirm the presence of high levels of (preexisting) NAb in the plasma of chickens directed to the alpha-Gal residue. The decreased responsiveness to alpha-Gal-bearing antigens in the current study shows that, in addition to immune-enhancing features, NAb may also have suppressive effects on

  15. Prognosis Can Be Predicted More Accurately Using Pre- and Postchemoradiotherapy Carcinoembryonic Antigen Levels Compared to Only Prechemoradiotherapy Carcinoembryonic Antigen Level in Locally Advanced Rectal Cancer Patients Who Received Neoadjuvant Chemoradiotherapy

    PubMed Central

    Sung, SooYoon; Son, Seok Hyun; Kay, Chul Seung; Lee, Yoon Suk

    2016-01-01

    Abstract We aimed to evaluate the prognostic value of a change in the carcinoembryonic antigen (CEA) level during neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer. A total of 110 patients with clinical T3/T4 or node-positive disease underwent nCRT and curative total mesorectal resection from February 2006 to December 2013. Serum CEA level was measured before nCRT, after nCRT, and then again after surgery. A cut-off value for CEA level to predict prognosis was determined using the maximally selected log-rank test. According to the test, patients were classified into 3 groups, based on their CEA levels (Group A: pre-CRT CEA ≤3.2; Group B: pre-CRT CEA level >3.2 and post-CRT CEA ≤2.8; and Group C: pre-CRT CEA >3.2 and post-CRT CEA >2.8). The median follow-up time was 31.1 months. The 3-year disease-free survival (DFS) rates of Group A and Group B were similar, while Group C showed a significantly lower 3-year DFS rate (82.5% vs. 89.5% vs. 55.1%, respectively, P = 0.001). Other clinicopathological factors that showed statistical significance on univariate analysis were pre-CRT CEA, post-CRT CEA, tumor distance from the anal verge, surgery type, downstage, pathologic N stage, margin status and perineural invasion. The CEA group (P = 0.001) and tumor distance from the anal verge (P = 0.044) were significant prognostic factors for DFS on multivariate analysis. Post-CRT CEA level may be a useful prognostic factor in patients whose prognosis cannot be predicted exactly by pre-CRT CEA levels alone in the neoadjuvant treatment era. Combined pre-CRT CEA and post-CRT CEA levels enable us to predict prognosis more accurately and determine treatment and follow-up policies. Further large-scale studies are necessary to validate the prognostic value of CEA levels. PMID:26962798

  16. The impact of hypoxemia on serum total and free prostate-specific antigen levels in patients with chronic obstructive pulmonary disease.

    PubMed

    Ozge, Cengiz; Bozlu, Murat; Ozgur, Eylem Sercan; Tek, Mesut; Tunckiran, Ahmet; Muslu, Necati; Ilvan, Ahmet

    2015-05-01

    Prostate-specific antigen (PSA) is the most important biochemical marker in the diagnosis and follow-up of patients with prostate cancer. In recent years, a relationship between PSA levels and hypoxic conditions has been described. However, no study has investigated the PSA levels in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the impact of hypoxemia on serum total (tPSA) and free PSA (fPSA) levels in patients with COPD. Between January 2010 and January 2014, 95 male patients who hospitalized for acute exacerbations of COPD and 80 control subjects were enrolled in the study. Serum tPSA and fPSA levels and f/tPSA ratios were determined in all patients on the first day of hospitalization (exacerbation) and 7 days after the treatment (stable state). Statistical analysis included paired t test and Mann-Whitney U test. No statistically significant differences were found between COPD and control groups with regard to the baseline characteristics, except for smoking status. The levels of serum tPSA and fPSA during exacerbation of COPD were significantly higher than the levels of the stable period (p < 0.01), whereas f/tPSA ratio did not change (p > 0.05). Hypoxemia during acute exacerbation of COPD can cause a rise in serum tPSA and fPSA levels, but f/tPSA ratio is not affected. Acute exacerbation of COPD may be added to list of the events in which PSA measurements must be interpreted with caution. PMID:25837435

  17. Association of DNA Methylation Levels with Tissue-specific Expression of Adipogenic and Lipogenic Genes in Longissimus dorsi Muscle of Korean Cattle

    PubMed Central

    Baik, M.; Vu, T. T. T.; Piao, M. Y.; Kang, H. J.

    2014-01-01

    Epigenetic factors, such as DNA methylation status, may regulate adipogenesis and lipogenesis, thus affecting intramuscular fat (IMF) deposition in longissimus dorsi muscle (LM) of beef cattle. In Korean cattle steers, the LM consists mainly of muscle tissue. However, the LM tissue also contains IMF. We compared the gene expression levels between the IMF and muscle portions of the LM after tissue separation. Real-time polymerase chain reaction analysis showed that the mRNA levels of both adipogenic peroxisome proliferator-activated receptor gamma isoform 1 (PPARG1) and lipogenic fatty acid binding protein 4 (FABP4) were higher (p<0.01) in the IMF than in the muscle portion of the LM. We determined DNA methylation levels of regulatory regions of the PPARG1 and FABP4 genes by pyrosequencing of genomic DNA. DNA methylation levels of two of three CpG sites in the PPARG1 gene promoter region were lower (p<0.05) in the IMF than in the muscle portion of the LM. DNA methylation levels of all five CpG sites from the FABP4 gene promoter region were also lower (p<0.001) in the IMF than in the muscle portion. Thus, mRNA levels of both PPARG1 and FABP4 genes were inversely correlated with DNA methylation levels in regulatory regions of CpG sites of the corresponding gene. Our findings suggest that DNA methylation status regulates tissue-specific expression of adipogenic and lipogenic genes in the IMF and muscle portions of LM tissue in Korean cattle. PMID:25178302

  18. Is there any association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer?

    PubMed Central

    Doluoglu, Omer Gokhan; Ceylan, Cavit; Kilinc, Fatih; Gazel, Eymen; Resorlu, Berkan; Odabas, Oner

    2016-01-01

    ABSTRACT Purpose We investigated the association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer. Materials and Methods The data of 440 patients who had undergone prostate biopsies due to high PSA levels and suspicious digital rectal examination findings were reviewed retrospectively. The patients were divided into two groups based on the presence of accompanying NIH IV prostatitis. The exclusion criteria were as follows: Gleason score>6, PSA level>20ng/mL, >2 positive cores, >50% cancerous tissue per biopsy, urinary tract infection, urological interventions at least 1 week previously (cystoscopy, urethral catheterization, or similar procedure), history of prostate biopsy, and history of androgen or 5-alpha reductase use. All patient's age, total PSA and free PSA levels, ratio of free to total PSA, PSA density and prostate volume were recorded. Results In total, 101 patients were included in the study. Histopathological examination revealed only PCa in 78 (77.2%) patients and PCa+NIH IV prostatitis in 23 (22.7%) patients. The median total PSA level was 7.4 (3.5–20.0) ng/mL in the PCa+NIH IV prostatitis group and 6.5 (0.6–20.0) ng/mL in the PCa group (p=0.67). The PSA level was≤10ng/mL in 60 (76.9%) patients in the PCa group and in 16 (69.6%) patients in the PCa+NIH IV prostatitis group (p=0.32). Conclusions Our study showed no statistically significant difference in PSA levels between patients with and without NIH IV prostatitis accompanying PCa. PMID:27256190

  19. An upstream regulatory region mediates high-level, tissue-specific expression of the human alpha 1(I) collagen gene in transgenic mice.

    PubMed Central

    Slack, J L; Liska, D J; Bornstein, P

    1991-01-01

    Studies in vitro have not adequately resolved the role of intronic and upstream elements in regulating expression of the alpha 1(I) collagen gene. To address this issue, we generated 12 separate lines of transgenic mice with alpha 1(I) collagen-human growth hormone (hGH) constructs containing different amounts of 5'-flanking sequence, with or without most of the first intron. Transgenes driven by 2.3 kb of alpha 1(I) 5'-flanking sequence, whether or not they contained the first intron, were expressed at a high level and in a tissue-specific manner in seven out of seven independent lines of transgenic mice. In most tissues, the transgene was expressed at levels approaching that of the endogenous alpha 1(I) gene and was regulated identically with the endogenous gene as animals aged. However, in lung, expression of the transgene was anomalously high, and in muscle, expression was lower than that of the endogenous gene, suggesting that in these tissues other regions of the gene may participate in directing appropriate expression. Five lines of mice were generated containing transgenes driven by 0.44 kb of alpha 1(I) 5'-flanking sequence (with or without the first intron), and expression was detected in four out of five of these lines. The level of expression of the 0.44-kb constructs in the major collagen-producing tissues was 15- to 500-fold lower than that observed with the longer 2.3-kb promoter. While transgenes containing the 0.44-kb promoter and the first intron retained a modest degree of tissue-specific expression, those without the first intron lacked tissue specificity and were poorly expressed in all tissues except lung.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:2005897

  20. Analysis of Phase-Specific Gene Expression at the Single-Cell Level in the White-Opaque Switching System of Candida albicans

    PubMed Central

    Strauß, Anja; Michel, Sonja; Morschhäuser, Joachim

    2001-01-01

    The opportunistic fungal pathogen Candida albicans can switch spontaneously and reversibly between different cell forms, a capacity that may enhance adaptation to different host niches and evasion of host defense mechanisms. Phenotypic switching has been studied intensively for the white-opaque switching system of strain WO-1. To facilitate the molecular analysis of phenotypic switching, we have constructed homozygous ura3 mutants from strain WO-1 by targeted gene deletion. The two URA3 alleles were sequentially inactivated using the MPAR-flipping strategy, which is based on the selection of integrative transformants carrying a mycophenolic acid (MPA) resistance marker that is subsequently deleted again by site-specific, FLP-mediated recombination. To investigate a possible cell type-independent switching in the expression of individual phase-specific genes, two different reporter genes that allowed the analysis of gene expression at the single-cell level were integrated into the genome, using URA3 as a selection marker. Fluorescence microscopic analysis of cells in which a GFP reporter gene was placed under the control of phase-specific promoters demonstrated that the opaque-phase-specific SAP1 gene was detectably expressed only in opaque cells and that the white-phase-specific WH11 gene was detectably expressed only in white cells. When MPAR was used as a reporter gene, it conferred an MPA-resistant phenotype on opaque but not white cells in strains expressing it from the SAP1 promoter, which was monitored at the level of single cells by a significantly enlarged size of the corresponding colonies on MPA-containing indicator plates. Similarly, white but not opaque cells became MPA resistant when MPAR was placed under the control of the WH11 promoter. The analysis of these reporter strains showed that cell type-independent phase variation in the expression of the SAP1 and WH11 genes did not occur at a detectable frequency. The expression of these phase-specific

  1. On the derivation of specific yield and soil water retention characteristics in peatlands from rainfall, microrelief and water level data - Theory and Practice

    NASA Astrophysics Data System (ADS)

    Dettmann, Ullrich; Bechtold, Michel

    2016-04-01

    Water level depth is one of the crucial state variables controlling the biogeochemical processes in peatlands. For flat soil surfaces, water level depth dynamics as response to boundary fluxes are primarily controlled by the water retention characteristics of the soil in and above the range of the water level fluctuations. For changing water levels, the difference of the integrals of two soil moisture profiles (∆Asoil), of a lower and a upper water level, is equal to the amount of water received or released by the soil. Dividing ∆Asoil by the water level change, results into a variable that is known as specific yield (Sy). For water level changes approaching the soil surface, changes in soil water storage are small due to the thin unsaturated zone that remains. Consequentially, Sy values approach zero with an abrupt transition to 1 in case of inundation. However, on contrary, observed water level rises due to precipitation events at various locations showed increasing Sy values for water level changes at shallow depths (Sy = precipitation/water level change; Logsdon et al., 2010). The increase of Sy values can be attributed in large parts to the influence of the microrelief on water level changes in these wet landscapes that are characterized by a mosaic of inundated and non-inundated areas. Consequentially, water level changes are dampened by partial inundation. In this situation, total Sy is composed of a spatially-integrated below ground and above ground contribution. We provide a general one-dimensional expression that correctly represents the effect of a microrelief on the total Sy. The one-dimensional expression can be applied for any soil hydraulic parameterizations and soil surface elevation frequency distributions. We demonstrate that Sy is influenced by the microrelief not only when surface storage directly contributes to Sy by (partial) inundation but also when water levels are lower than the minimum surface elevation. With the derived one

  2. Galanin-like peptide (GALP) neurone-specific phosphoinositide 3-kinase signalling regulates GALP mRNA levels in the hypothalamus of males and luteinising hormone levels in both sexes.

    PubMed

    Aziz, R; Beymer, M; Negrón, A L; Newshan, A; Yu, G; Rosati, B; McKinnon, D; Fukuda, M; Lin, R Z; Mayer, C; Boehm, U; Acosta-Martínez, M

    2014-07-01

    Galanin-like peptide (GALP) neurones participate in the metabolic control of reproduction and are targets of insulin and leptin regulation. Phosphoinositide 3-kinase (PI3K) is common to the signalling pathways utilised by both insulin and leptin. Therefore, we investigated whether PI3K signalling in neurones expressing GALP plays a role in the transcriptional regulation of the GALP gene and in the metabolic control of luteinising hormone (LH) release. Accordingly, we deleted PI3K catalytic subunits p110α and p110β via conditional gene targeting (cKO) in mice (GALP-p110α/β cKO). To monitor PI3K signalling in GALP neurones, these animals were also crossed with Cre-dependent FoxO1GFP reporter mice. Compared to insulin-infused control animals, the PI3K-Akt-dependent FoxO1GFP nuclear exclusion in GALP neurones was abolished in GALP-p110α/β cKO mice. We next used food deprivation to investigate whether the GALP-neurone specific ablation of PI3K activity affected the susceptibility of the gonadotrophic axis to negative energy balance. Treatment did not affect LH levels in either sex. However, a significant genotype effect on LH levels was observed in females. By contrast, no genotype effect on LH levels was observed in males. A sex-specific genotype effect on hypothalamic GALP mRNA was observed, with fed and fasted GALP-p110α/β cKO males having lower GALP mRNA expression compared to wild-type fed males. Finally, the effects of gonadectomy and steroid hormone replacement on GALP mRNA levels were investigated. Compared to vehicle-treated mice, steroid hormone replacement reduced mediobasal hypothalamus GALP expression in wild-type and GALP-p110α/β cKO animals. In addition, within the castrated and vehicle-treated group and compared to wild-type mice, LH levels were lower in GALP-p110α/β cKO males. Double immunofluorescence using GALP-Cre/R26-YFP mice showed androgen and oestrogen receptor co-localisation within GALP neurones. Our data demonstrate that GALP

  3. Advanced Rotorcraft Transmission Program

    NASA Technical Reports Server (NTRS)

    Bill, Robert C.

    1990-01-01

    The U.S. Army/NASA Advanced Rotorcraft Transmission (ART) program is charged with developing and demonstrating a light, quiet, and durable drivetrain for next-generation rotorcraft in two classes: a 10,000-20,000 Future Attack Air Vehicle capable of both tactical ground support and air-to-air missions, and a 60,000-80,000 lb Advanced Cargo Aircraft, for heavy-lift field-support operations. Specific ART objectives encompass a 25-percent reduction in drivetrain weight, a 10-dB noise level reduction at the transmission source, and the achievement of a 5000-hr MTBF. Four candidate drivetrain systems have been carried to a conceptual design stage, together with projections of their mission performance and life-cycle costs.

  4. Solitary recurrence of castration-resistant prostate cancer with low or undetectable levels of prostate specific antigen salvaged with local ablative radiation therapy: A case report

    PubMed Central

    WANG, CHIACHIEN JAKE; YING, JAMES; KAPUR, PAYAL; WOHLFELD, BRYAN; ROEHRBORN, CLAUS; KIM, DONG W. NATHAN

    2016-01-01

    Prostate cancer recurrences are usually first detected by increased levels of prostate specific antigen (PSA), and systemic therapy is often initiated if distant metastasis is confirmed. However, low or nearly undetectable levels of PSA in the modern era of ultrasensitive PSA assay may be difficult to interpret in patients with a history of prostate cancer. Deciding whether to initiate additional systemic therapy in limited indolent metastatic disease while balancing the quality of life of the patient and ensuring the oncologic control of the disease may be challenging. In the present study, the case of a biopsy-confirmed solitary spine recurrence of prostate cancer with nearly undetectable but persistent levels of PSA (0.05 ng/ml) is reported. Treatment of the recurrence with local ablative radiotherapy improved the pain experienced by the patient, and reduced his levels of PSA to undetectable limits (<0.05 ng/ml). Repeated imaging analysis, PSA assay and clinical assessment demonstrated durable control of the disease without the requirement for additional systemic treatments. The present case highlighted the importance of initiating appropriate work-up according to the clinical scenario. Local treatment for solitary or oligometastatic recurrence of prostate cancer may enhance the effectiveness of current therapeutic strategies and benefit certain patients. PMID:26870272

  5. Effect of sulfide, osmotic, and thermal stresses on taurine transporter mRNA levels in the gills of the hydrothermal vent-specific mussel Bathymodiolus septemdierum.

    PubMed

    Nakamura-Kusakabe, Ikumi; Nagasaki, Toshihiro; Kinjo, Azusa; Sassa, Mieko; Koito, Tomoko; Okamura, Kei; Yamagami, Shosei; Yamanaka, Toshiro; Tsuchida, Shinji; Inoue, Koji

    2016-01-01

    Hydrothermal vent environmental conditions are characterized by high sulfide concentrations, fluctuating osmolality, and irregular temperature elevations caused by vent effluents. These parameters represent potential stressors for organisms that inhabit the area around hydrothermal vents. Here, we aimed to obtain a better understanding of the adaptation mechanisms of marine species to hydrothermal vent environments. Specifically, we examined the effect of sulfide, osmolality, and thermal stress on the expression of taurine transporter (TAUT) mRNA in the gill of the deep-sea mussel Bathymodiolus septemdierum, which is a dominant species around hydrothermal vent sites. We analyzed TAUT mRNA levels by quantitative real-time polymerase chain reaction (PCR) in the gill of mussels exposed to sulfide (0.1 or 1mg/L Na2S·9H2O), hyper- (115% seawater) and hypo- (97.5%, 95.5%, and 85% seawater) osmotic conditions, and thermal stresses (12°C and 20°C) for 24 and 48h. The results showed that mussels exposed to relatively low levels of sulfide (0.1mg/L) and moderate heat stress (12°C) exhibited higher TAUT mRNA levels than the control. Although hyper- and hypo-osmotic stress did not significantly change TAUT mRNA levels, slight induction was observed in mussels exposed to low osmolality. Our results indicate that TAUT is involved in the coping mechanism of mussels to various hydrothermal vent stresses. PMID:26431911

  6. Field estimation of the flock-level diagnostic specificity of an enzyme-linked immunosorbent assay for Avian metapneumovirus antibodies in turkeys.

    PubMed

    Muñoz-Zanzi, Claudia; Trampel, Darrell; Hanson, Tim; Harrison, Kristen; Goyal, Sagar; Cortinas, Roberto; Lauer, Dale

    2009-03-01

    Routine serologic testing for Avian metapneumovirus (AMPV) infection of turkey flocks at slaughter is currently being used to monitor changes in the occurrence of AMPV infection in endemic areas and can also be used to detect the emergence of infection in currently unaffected areas. Because of the costs associated with false-positive results, particularly in areas that are free of AMPV infection, there is a need to obtain improved estimates of flock-level specificity (SP). The objective of this study was to estimate flock-level SP of a program to monitor AMPV infection in turkey flocks at processing using a standard enzyme-linked immunosorbent assay (ELISA). A study was carried out in which 37 AMPV-free flocks from 7 Midwest operations were followed serologically. Six percent, 3%, and 0.2% of total samples tested AMPV positive at 8 weeks, 12 weeks, and at processing, respectively. Overall, flock-level SP increased as the cutoff increased and as age increased. Flock-level SP at processing was 97%, if a cutoff of 1 was used (the flock was classified as positive if at least 1 sample tested positive), and 100%, if any other cutoff was used. Administration of antibiotics (P = 0.02) and vaccination for Bordetella avium (P = 0.08) were positively associated with the probability of (false) positive test results. These findings suggest possible cross-reactions with other infections and highlight the need to consider variable diagnostic performance depending on farm conditions. PMID:19286505

  7. Contribution of allelic variability in prostate specific antigen (PSA) & androgen receptor (AR) genes to serum PSA levels in men with prostate cancer

    PubMed Central

    Chavan, Sushant V.; Maitra, Anurupa; Roy, Nobhojit; Chavan, Padma R.

    2014-01-01

    Background & objectives: Wide variability in serum prostate specific antigen (PSA) levels exists in malignant conditions of the prostate. PSA is expressed in normal range in 20 to 25 per cent of prostate cancer cases even in presence of high grade Gleason score. This study was aimed to assess the influence of genetic variants exhibited by PSA and androgen receptor (AR) genes towards the variable expression of PSA in prostate cancer. Methods: Pre-treatment serum PSA levels from 101 prostate cancer cases were retrieved from medical record. PSA genotype analysis in promoter region and AR gene microsatellite Cytosine/Adenine/Guanine (CAG) repeat analysis in exon 1 region was performed using DNA sequencing and fragment analysis techniques. Results: A total of seven single nucleotide polymorphisms (SNPs) in the PSA promoter region were noted. Only two SNPs viz., 158G/A (P<0.001) in the proximal promoter region and -3845G/A (P<0.001) in enhancer region showed significant association with serum PSA levels. The carriers of homozygous GG genotype (P<0.001) at both of these polymorphic sites showed higher expression of PSA whereas homozygous AA genotype (P<0.001) carriers demonstrated lower PSA levels. The combination effect of PSA genotypes along with stratified AR CAG repeats lengths (long, intermediate and short) was also studied. The homozygous GG genotype along with AR long CAG repeats and homozygous AA genotype along with AR short CAG repeats at position -3845 and -158 showed strong interaction and thus influenced serum PSA levels. Interpretation & conclusions: The genetic variants exhibited by PSA gene at positions -3845G/A and -158G/A may be accountable towards wide variability of serum PSA levels in prostate cancer. Also the preferential binding of G and A alleles at these polymorphic sites along with AR long and short CAG repeats may contribute towards PSA expression. PMID:24820830

  8. Impact of oral consumption of heat-treated Bacteroides xylanisolvens DSM 23964 on the level of natural TFα-specific antibodies in human adults.

    PubMed

    Ulsemer, P; Toutounian, K; Kressel, G; Goletz, C; Schmidt, J; Karsten, U; Hahn, A; Goletz, S

    2016-09-01

    It is now generally accepted that the human body exists in close synergy with the gut microbiome and that this cross-talk plays an essential role in human health and disease. One facet from the many interactions between the microbiome and the immune system is the induction of natural antibodies to commensal bacterial glycans, such as blood group antigens, the alpha-Gal epitope or the Thomsen-Friedenreich (TFα) antigen. Since we have observed that certain species of the commensal genus Bacteroides express the TFα antigen, we examined whether the oral dietary supplementation of a pasteurised Bacteroides xylanisolvens strain might be able to enhance the level of natural anti-TFα antibodies in healthy adults. The data obtained from a double-blind, placebo-controlled study involving 140 healthy volunteers and lasting 8 weeks revealed that the oral uptake of this strain was indeed able to increase the level of TFα-specific immunoglobulin M serum antibodies. The effect was dose-dependent but remained - at any doses - within the physiological range determined before intervention. Furthermore, the effect reverted after stopping the intake. The results support the idea of the microbiome inducing the generation of systemic antigen-specific antibodies against sugar epitopes. They also demonstrate the possibility to modulate essential regulatory or defence processes through dietary supplementation of selected commensal bacteria with the aim to assist human health. PMID:27048836

  9. Ecological niches of Arctic deep-sea copepods: Vertical partitioning, dietary preferences and different trophic levels minimize inter-specific competition

    NASA Astrophysics Data System (ADS)

    Laakmann, Silke; Kochzius, Marc; Auel, Holger

    2009-05-01

    The biodiversity of pelagic deep-sea ecosystems has received growing scientific interest in the last decade, especially in the framework of international marine biodiversity initiatives, such as Census of Marine Life (CoML). While a growing number of deep-sea zooplankton species has been identified and genetically characterized, little information is available on the mechanisms minimizing inter-specific competition and thus allowing closely related species to co-occur in the deep-sea pelagic realm. Focussing on the two dominant calanoid copepod families Euchaetidae and Aetideidae in Fram Strait, Arctic Ocean, the present study strives to characterize ecological niches of co-occurring species, with regard to vertical distribution, dietary composition as derived from lipid biomarkers, and trophic level on the basis of stable isotope signatures. Closely related species were usually restricted to different depth layers, resulting in a multi-layered vertical distribution pattern. Thus, vertical partitioning was an important mechanism to avoid inter-specific competition. Species occurring in the same depth strata usually belonged to different genera. They differed in fatty acid composition and trophic level, indicating different food preferences. Herbivorous Calanus represent major prey items for many omnivorous and carnivorous species throughout the water column. The seasonal and ontogenetic vertical migration of Calanus acts as a short-cut in food supply for pelagic deep-sea ecosystems in the Arctic.

  10. Specific-conductance, water-temperature, and water-level data, San Francisco Bay, California, for water years 2001-2002

    USGS Publications Warehouse

    Buchanan, P.A.

    2003-01-01

    This article presents time-series plots of specific-conductance, water-temperature, and water-level data collected in San Francisco Bay during water years 2001 and 2002 (October 1, 2000, through September 30, 2002). Specific-conductance and water-temperature data were recorded at 15-minute intervals at the following US Geological Survey (USGS) locations (Figure 1): • Suisun Bay at Benicia Bridge, near Benicia, California (BEN) (site # 11455780) • Carquinez Strait at Carquinez Bridge, near Crockett, California (CARQ) (site # 11455820) • Napa River at Mare Island Causeway, near Vallejo, California (NAP) (site # 11458370) • San Pablo Strait at Point San Pablo, California (PSP) (site # 11181360) • San Pablo Bay at Petaluma River Channel Marker 9, California (SPB) (site # 380519122262901) • San Francisco Bay at Presidio Military Reservation, California (PRES) (site # 11162690) • San Francisco Bay at Pier 24, at San Francisco, California (P24) (site # 11162700) • San Francisco Bay at San Mateo Bridge, near Foster City, California (SMB) (site # 11162765). Water-level data were recorded only at PSP through January 1, 2001. Suspended-sediment concentration data also were collected at most of these sites and were published by Buchanan and Ganju (2003). The data from PSP, PRES, P24, and SMB were recorded by the California Department of Water Resources (DWR) before 1988, by the USGS National Research Program from 1988 to 1989, and by the USGSDWR cooperative program since 1990. BEN, CARQ, NAP, and SPB were established in 1998 by the USGS.

  11. Association between Variants at BCL11A Erythroid-Specific Enhancer and Fetal Hemoglobin Levels among Sickle Cell Disease Patients in Cameroon: Implications for Future Therapeutic Interventions.

    PubMed

    Pule, Gift Dineo; Ngo Bitoungui, Valentina Josiane; Chetcha Chemegni, Bernard; Kengne, Andre Pascal; Antonarakis, Stylianos; Wonkam, Ambroise

    2015-10-01

    Variants in BCL11A were previously associated with fetal hemoglobin (HbF) levels among Cameroonian sickle cell disease (SCD) patients, however explaining only ∼2% of the variance. In the same patients, we have investigated the relationship between HbF and two SNPs in a BCL11A erythroid-specific enhancer (N=626). Minor allele frequencies in rs7606173 and rs1427407 were 0.42 and 0.24, respectively. Both variants were significantly associated with HbF levels (p=3.11e-08 and p=6.04e-06, respectively) and explained 8% and 6.2% variations, respectively. These data have confirmed a stronger effect on HbF of genomic variations at the BCL11A erythroid-specific enhancer among patients with SCD in Cameroon, the first report on a West African population. The relevance of these findings is of prime importance because the disruption of this enhancer would alter BCL11A expression in erythroid precursors and thus HbF expression, while sparing the induced functional challenges of any alterations on the expression of this transcription factor in non-erythroid lineages, thus providing an attractive approach for new treatment strategies of SCD. PMID:26393293

  12. A cell-specific enhancer far upstream of the mouse tyrosinase gene confers high level and copy number-related expression in transgenic mice.

    PubMed Central

    Ganss, R; Montoliu, L; Monaghan, A P; Schütz, G

    1994-01-01

    The tyrosinase gene encodes the key enzyme of melanin production and is tightly regulated during development. A yeast artificial chromosome covering the mouse tyrosinase gene has been shown to rescue completely the albino phenotype of recipient mouse strains, conferring copy number-dependent, position-independent expression. To investigate the presence of cis-acting regulatory elements responsible for the appropriate expression of the tyrosinase gene, DNase I hypersensitive