Sample records for molecules technical progress

  1. 48 CFR 2052.211-71 - Technical progress report.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Technical progress report... Technical progress report. As prescribed at 2011.104-70(b), the contracting officer shall insert the... solicitation. Technical Progress Report (JAN 1993) The contractor shall provide a monthly Technical Progress...

  2. 48 CFR 2052.211-71 - Technical progress report.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Technical progress report... Technical progress report. As prescribed at 2011.104-70(b), the contracting officer shall insert the... solicitation. Technical Progress Report (JAN 1993) The contractor shall provide a monthly Technical Progress...

  3. 48 CFR 2052.211-71 - Technical progress report.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Technical progress report... Technical progress report. As prescribed at 2011.104-70(b), the contracting officer shall insert the... solicitation. Technical Progress Report (JAN 1993) The contractor shall provide a monthly Technical Progress...

  4. 48 CFR 2052.211-71 - Technical progress report.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Technical progress report... Technical progress report. As prescribed at 2011.104-70(b), the contracting officer shall insert the... solicitation. Technical Progress Report (JAN 1993) The contractor shall provide a monthly Technical Progress...

  5. Progress in Computational Electron-Molecule Collisions

    NASA Astrophysics Data System (ADS)

    Rescigno, Tn

    1997-10-01

    The past few years have witnessed tremendous progress in the development of sophisticated ab initio methods for treating collisions of slow electrons with isolated small molecules. Researchers in this area have benefited greatly from advances in computer technology; indeed, the advent of parallel computers has made it possible to carry out calculations at a level of sophistication inconceivable a decade ago. But bigger and faster computers are only part of the picture. Even with today's computers, the practical need to study electron collisions with the kinds of complex molecules and fragments encountered in real-world plasma processing environments is taxing present methods beyond their current capabilities. Since extrapolation of existing methods to handle increasingly larger targets will ultimately fail as it would require computational resources beyond any imagined, continued progress must also be linked to new theoretical developments. Some of the techniques recently introduced to address these problems will be discussed and illustrated with examples of electron-molecule collision calculations we have carried out on some fairly complex target gases encountered in processing plasmas. Electron-molecule scattering continues to pose many formidable theoretical and computational challenges. I will touch on some of the outstanding open questions.

  6. Education, Technical Progress, and Economic Growth: The Case of Taiwan.

    ERIC Educational Resources Information Center

    Lin, T.-C.

    2003-01-01

    Investigates the effect of education and the role of technical progress on economic growth in Taiwan from 1965-2000. Finds that education has a positive and significant effect on growth, but the role of technical progress does not appear to be extraordinarily important. Furthermore, no markedly significant relationships exist between capital and…

  7. Webinar May 17: Fuel Cell Electric Bus Progress Toward Meeting Technical

    Science.gov Websites

    Targets | News | NREL Webinar May 17: Fuel Cell Electric Bus Progress toward Meeting Technical Targets Webinar May 17: Fuel Cell Electric Bus Progress toward Meeting Technical Targets May 14, 2018 The U.S. Department of Energy's (DOE's) Fuel Cell Technologies Office will present a live webinar titled

  8. Progress in Scientific and Technical Communications, 1968 Annual Report.

    ERIC Educational Resources Information Center

    Federal Council for Science and Technology, Washington, DC. Committee on Scientific and Technical Information.

    This sixth annual report describes progress achieved by the Federal Government in improving the communication of scientific and technical information to support and enhance national science and technology. Included in the report are details regarding the scientific and technical activities of individual Federal Agencies, such as the Atomic Energy…

  9. Assessment Program Technical Progress Report, 1996-1997.

    ERIC Educational Resources Information Center

    McCown, Laurie; Fanning, Erin; Eickmeyer, Barbara

    Coconino Community College (CCC) annually assesses its institutional effectiveness to demonstrate its commitment to improving programs and services to students. The 1996-97 Assessment Program Technical Progress Report records the assessment and institutional activities enacted during the academic year, detailing the assessment model, timelines,…

  10. Single-molecule techniques in biophysics: a review of the progress in methods and applications.

    PubMed

    Miller, Helen; Zhou, Zhaokun; Shepherd, Jack; Wollman, Adam J M; Leake, Mark C

    2018-02-01

    Single-molecule biophysics has transformed our understanding of biology, but also of the physics of life. More exotic than simple soft matter, biomatter lives far from thermal equilibrium, covering multiple lengths from the nanoscale of single molecules to up to several orders of magnitude higher in cells, tissues and organisms. Biomolecules are often characterized by underlying instability: multiple metastable free energy states exist, separated by levels of just a few multiples of the thermal energy scale k B T, where k B is the Boltzmann constant and T absolute temperature, implying complex inter-conversion kinetics in the relatively hot, wet environment of active biological matter. A key benefit of single-molecule biophysics techniques is their ability to probe heterogeneity of free energy states across a molecular population, too challenging in general for conventional ensemble average approaches. Parallel developments in experimental and computational techniques have catalysed the birth of multiplexed, correlative techniques to tackle previously intractable biological questions. Experimentally, progress has been driven by improvements in sensitivity and speed of detectors, and the stability and efficiency of light sources, probes and microfluidics. We discuss the motivation and requirements for these recent experiments, including the underpinning mathematics. These methods are broadly divided into tools which detect molecules and those which manipulate them. For the former we discuss the progress of super-resolution microscopy, transformative for addressing many longstanding questions in the life sciences, and for the latter we include progress in 'force spectroscopy' techniques that mechanically perturb molecules. We also consider in silico progress of single-molecule computational physics, and how simulation and experimentation may be drawn together to give a more complete understanding. Increasingly, combinatorial techniques are now used, including

  11. Single-molecule techniques in biophysics: a review of the progress in methods and applications

    NASA Astrophysics Data System (ADS)

    Miller, Helen; Zhou, Zhaokun; Shepherd, Jack; Wollman, Adam J. M.; Leake, Mark C.

    2018-02-01

    Single-molecule biophysics has transformed our understanding of biology, but also of the physics of life. More exotic than simple soft matter, biomatter lives far from thermal equilibrium, covering multiple lengths from the nanoscale of single molecules to up to several orders of magnitude higher in cells, tissues and organisms. Biomolecules are often characterized by underlying instability: multiple metastable free energy states exist, separated by levels of just a few multiples of the thermal energy scale k B T, where k B is the Boltzmann constant and T absolute temperature, implying complex inter-conversion kinetics in the relatively hot, wet environment of active biological matter. A key benefit of single-molecule biophysics techniques is their ability to probe heterogeneity of free energy states across a molecular population, too challenging in general for conventional ensemble average approaches. Parallel developments in experimental and computational techniques have catalysed the birth of multiplexed, correlative techniques to tackle previously intractable biological questions. Experimentally, progress has been driven by improvements in sensitivity and speed of detectors, and the stability and efficiency of light sources, probes and microfluidics. We discuss the motivation and requirements for these recent experiments, including the underpinning mathematics. These methods are broadly divided into tools which detect molecules and those which manipulate them. For the former we discuss the progress of super-resolution microscopy, transformative for addressing many longstanding questions in the life sciences, and for the latter we include progress in ‘force spectroscopy’ techniques that mechanically perturb molecules. We also consider in silico progress of single-molecule computational physics, and how simulation and experimentation may be drawn together to give a more complete understanding. Increasingly, combinatorial techniques are now used, including

  12. Technical Progress of the New Worlds Observer Mission

    NASA Astrophysics Data System (ADS)

    Lo, Amy; Noecker, C.; Cash, W.; NWO Study Team

    2009-01-01

    We report on the technical progress of the New Worlds Observer (NWO) mission concept. NWO is a two spacecraft mission that is capable of detecting and characterizing extra-solar, terrestrial planets and planetary systems. NWO consists of an external starshade and an UV-optical space telescope, flying in tandem. The starshade is a petal-shaped, opaque screen that creates an extremely dark shadow large enough to shade the telescope aperture from the target star. The NWO team has been addressing the top technology challenges of the concept, and report here our progress. We will present the current mission configuration best suited to address Terrestrial Planet Finding requirements, and highlight the technological breakthroughs that we have achieved this year. In particular, we will report on progress made in precision deployables for the large starshade, and the trajectory & alignment control system for NWO. We will also briefly highlight advances in understanding the starshade optical performance.

  13. Evaporation by mechanical vapor recompression. Technical progress report, September 1-December 31, 1979

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

    Iverson, C.H.; Coury, G.E.

    1979-01-01

    Progress to date in the development of a study of the application of the technologies of mechanical vapor recompression and falling film evaporators as applied to the beet sugar industry is reported. Progress is reported in the following areas: technical literature search and plant visitations of existing applications of VR/FFE.

  14. Electron Interactions with Non-Linear Polyatomic Molecules and Their Radicals

    DTIC Science & Technology

    1993-12-01

    developed which generates SCE quantities from molecular wave functions. This progress was realized in terms of some actual calculations on some molecules...section 4.A describes the basics of the Partial Differential Equation Theory; section 4.B describes the generalization to a finite element...Information Service (NTIS). At NTIS, it will be available to the general public, including foreign nations. This technical report has been reviewed and

  15. Single molecule microscopy in 3D cell cultures and tissues.

    PubMed

    Lauer, Florian M; Kaemmerer, Elke; Meckel, Tobias

    2014-12-15

    From the onset of the first microscopic visualization of single fluorescent molecules in living cells at the beginning of this century, to the present, almost routine application of single molecule microscopy, the method has well-proven its ability to contribute unmatched detailed insight into the heterogeneous and dynamic molecular world life is composed of. Except for investigations on bacteria and yeast, almost the entire story of success is based on studies on adherent mammalian 2D cell cultures. However, despite this continuous progress, the technique was not able to keep pace with the move of the cell biology community to adapt 3D cell culture models for basic research, regenerative medicine, or drug development and screening. In this review, we will summarize the progress, which only recently allowed for the application of single molecule microscopy to 3D cell systems and give an overview of the technical advances that led to it. While initially posing a challenge, we finally conclude that relevant 3D cell models will become an integral part of the on-going success of single molecule microscopy. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Titin domains progressively unfolded by force are homogenously distributed along the molecule.

    PubMed

    Bianco, Pasquale; Mártonfalvi, Zsolt; Naftz, Katalin; Kőszegi, Dorina; Kellermayer, Miklós

    2015-07-21

    Titin is a giant filamentous protein of the muscle sarcomere in which stretch induces the unfolding of its globular domains. However, the mechanisms of how domains are progressively selected for unfolding and which domains eventually unfold have for long been elusive. Based on force-clamp optical tweezers experiments we report here that, in a paradoxical violation of mechanically driven activation kinetics, neither the global domain unfolding rate, nor the folded-state lifetime distributions of full-length titin are sensitive to force. This paradox is reconciled by a gradient of mechanical stability so that domains are gradually selected for unfolding as the magnitude of the force field increases. Atomic force microscopic screening of extended titin molecules revealed that the unfolded domains are distributed homogenously along the entire length of titin, and this homogeneity is maintained with increasing overstretch. Although the unfolding of domains with progressively increasing mechanical stability makes titin a variable viscosity damper, the spatially randomized variation of domain stability ensures that the induced structural changes are not localized but are distributed along the molecule's length. Titin may thereby provide complex safety mechanims for protecting the sarcomere against structural disintegration under excessive mechanical conditions. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  17. Education, Industrialization and Technical Progress in Mexico. IIEP Research Report No. 6.

    ERIC Educational Resources Information Center

    Padua, Jorge

    This report attempts to analyze the contributions of the educational system and job training programs to industrialization and technical progress in the Conubal zone of the Lower Balsas River of Mexico. The first of the study's three sections consists of two chapters that provide general background. Chapter 1, "Theories of Development and the…

  18. Monitoring the Durability Performance of Concrete in Nuclear Waste Containment. Technical Progress Report No. 4

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

    Ulm, Franz-Josef

    2000-06-30

    OAK-B135 Monitoring the Durability Performance of Concrete in Nuclear Waste Containment. Technical Progress Report No. 4. The analysis of the effect of cracks on the acceleration of the calcium leaching process of cement-based materials has been pursued. During the last period (Technical Progress Report No 3), we have introduced a modeling accounting for the high diffusivity of fractures in comparison with the weak solid material diffusivity. It has been shown through dimensional and asymptotic analysis that small fractures do not significantly accelerate the material aging process. This important result for the overall structural aging kinetics of containment structure has beenmore » developed in a paper submitted to the international journal ''Transport in Porous Media''.« less

  19. Monitoring the Durability Performance of Concrete in Nuclear Waste Containment. Technical Progress Report No. 3

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

    Ulm, Franz-Josef

    2000-03-31

    OAK-B135 Monitoring the Durability Performance of Concrete in Nuclear Waste Containment. Technical Progress Report No. 3(NOTE: Part II A item 1 indicates ''PAPER'', but a report is attached electronically)

  20. The Development and Technical Adequacy of Seventh-Grade Reading Comprehension Measures in a Progress Monitoring Assessment System. Technical Report #1102

    ERIC Educational Resources Information Center

    Park, Bitnara Jasmine; Alonzo, Julie; Tindal, Gerald

    2011-01-01

    This technical report describes the process of development and piloting of reading comprehension measures that are appropriate for seventh-grade students as part of an online progress screening and monitoring assessment system, http://easycbm.com. Each measure consists of an original fictional story of approximately 1,600 to 1,900 words with 20…

  1. Annual Technical Progress Report for Emergency School Assistance Program, Title 45, 1970-71.

    ERIC Educational Resources Information Center

    Lindsey, Randall B.

    This paper presents a technical progress report of two programs conducted with funds provided under the Emergency School Assistance Program. One, the Mobile Learning Unit, said to have been designed to measure changes in fourth and fifth grade students' self-concept in a reorganized desegregated school environment, focuses on whether a positive…

  2. Third Progress and Information Report of the Vocational-Technical Education Consortium of States.

    ERIC Educational Resources Information Center

    Lee, Connie W.; And Others

    This description of major activities and accomplishments of the Vocational-Technical Education Consortium of the States (V-TECS) since the second progress report of May, 1975, is designed to provide the reader with a basic understanding of the processes and procedures used by the consortium in achieving its major goal: The production of catalogs…

  3. Total Factor Productivity Growth, Technical Progress & Efficiency Change in Vietnam Coal Industry - Nonparametric Approach

    NASA Astrophysics Data System (ADS)

    Phuong, Vu Hung

    2018-03-01

    This research applies Data Envelopment Analysis (DEA) approach to analyze Total Factor Productivity (TFP) and efficiency changes in Vietnam coal mining industry from 2007 to 2013. The TFP of Vietnam coal mining companies decreased due to slow technological progress and unimproved efficiency. The decadence of technical efficiency in many enterprises proved that the coal mining industry has a large potential to increase productivity through technical efficiency improvement. Enhancing human resource training, technology and research & development investment could help the industry to improve efficiency and productivity in Vietnam coal mining industry.

  4. Decontamination Systems Information and Research Program. Quarterly technical progress report, January 1--March 31, 1994

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

    Not Available

    1994-05-01

    West Virginia University (WVU) and the US DOE Morgantown Energy Technology Center (METC) entered into a Cooperative Agreement on August 29, 1992 entitled ``Decontamination Systems Information and Research Programs.`` Stipulated within the Agreement is the requirement that WVU submit to METC a series of Technical Progress Reports on a quarterly basis. This report comprises the first Quarterly Technical Progress Report for Year 2 of the Agreement. This report reflects the progress and/or efforts performed on the sixteen (16) technical projects encompassed by the Year 2 Agreement for the period of January 1 through March 31, 1994. In situ bioremediation ofmore » chlorinated organic solvents; Microbial enrichment for enhancing in-situ biodegradation of hazardous organic wastes; Treatment of volatile organic compounds (VOCs) using biofilters; Drain-enhanced soil flushing (DESF) for organic contaminants removal; Chemical destruction of chlorinated organic compounds; Remediation of hazardous sites with steam reforming; Soil decontamination with a packed flotation column; Use of granular activated carbon columns for the simultaneous removal of organics, heavy metals, and radionuclides; Monolayer and multilayer self-assembled polyion films for gas-phase chemical sensors; Compact mercuric iodide detector technology development; Evaluation of IR and mass spectrometric techniques for on-site monitoring of volatile organic compounds; A systematic database of the state of hazardous waste clean-up technologies; Dust control methods for insitu nuclear and hazardous waste handling; Winfield Lock and Dam remediation; and Socio-economic assessment of alternative environmental restoration technologies.« less

  5. Technical adequacy of growth estimates from a computer adaptive test: Implications for progress monitoring.

    PubMed

    Van Norman, Ethan R; Nelson, Peter M; Parker, David C

    2017-09-01

    Computer adaptive tests (CATs) hold promise to monitor student progress within multitiered systems of support. However, the relationship between how long and how often data are collected and the technical adequacy of growth estimates from CATs has not been explored. Given CAT administration times, it is important to identify optimal data collection schedules to minimize missed instructional time. We used simulation methodology to investigate how the duration and frequency of data collection influenced the reliability, validity, and precision of growth estimates from a math CAT. A progress monitoring dataset of 746 Grade 4, 664 Grade 5, and 400 Grade 6 students from 40 schools in the upper Midwest was used to generate model parameters. Across grades, 53% of students were female and 53% were White. Grade level was not as influential as the duration and frequency of data collection on the technical adequacy of growth estimates. Low-stakes decisions were possible after 14-18 weeks when data were collected weekly (420-540 min of assessment), 20-24 weeks when collected every other week (300-360 min of assessment), and 20-28 weeks (150-210 min of assessment) when data were collected once a month, depending on student grade level. The validity and precision of growth estimates improved when the duration and frequency of progress monitoring increased. Given the amount of time required to obtain technically adequate growth estimates in the present study, results highlight the importance of weighing the potential costs of missed instructional time relative to other types of assessments, such as curriculum-based measures. Implications for practice, research, as well as future directions are also discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  6. Technical Adequacy of Growth Estimates from a Computer Adaptive Test: Implications for Progress Monitoring

    ERIC Educational Resources Information Center

    Van Norman, Ethan R.; Nelson, Peter M.; Parker, David C.

    2017-01-01

    Computer adaptive tests (CATs) hold promise to monitor student progress within multitiered systems of support. However, the relationship between how long and how often data are collected and the technical adequacy of growth estimates from CATs has not been explored. Given CAT administration times, it is important to identify optimal data…

  7. Molecule nanoweaver

    DOEpatents

    Gerald, II; Rex, E [Brookfield, IL; Klingler, Robert J [Glenview, IL; Rathke, Jerome W [Homer Glen, IL; Diaz, Rocio [Chicago, IL; Vukovic, Lela [Westchester, IL

    2009-03-10

    A method, apparatus, and system for constructing uniform macroscopic films with tailored geometric assemblies of molecules on the nanometer scale. The method, apparatus, and system include providing starting molecules of selected character, applying one or more force fields to the molecules to cause them to order and condense with NMR spectra and images being used to monitor progress in creating the desired geometrical assembly and functionality of molecules that comprise the films.

  8. Technical Adequacy and Acceptability of Curriculum-Based Measurement and the Measures of Academic Progress

    ERIC Educational Resources Information Center

    January, Stacy-Ann A.; Ardoin, Scott P.

    2015-01-01

    Curriculum-based measurement in reading (CBM-R) and the Measures of Academic Progress (MAP) are assessment tools widely employed for universal screening in schools. Although a large body of research supports the validity of CBM-R, limited empirical evidence exists supporting the technical adequacy of MAP or the acceptability of either measure for…

  9. Generation and focusing of pulsed intense ion beams. Technical progress report, 1 October 1982 - 30 September, 1983

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

    Hammer, D.A.; Kusse, B.R.; Sudan, R.N.

    1983-07-01

    The progress on this contract is described in three parts. The first deals with the technical operation of the LION accelerator. The second and third parts are concerned with the experimental results.

  10. Modeling the impacts of climate change and technical progress on the wheat yield in inland China: An autoregressive distributed lag approach.

    PubMed

    Zhai, Shiyan; Song, Genxin; Qin, Yaochen; Ye, Xinyue; Lee, Jay

    2017-01-01

    This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June) led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention.

  11. Modeling the impacts of climate change and technical progress on the wheat yield in inland China: An autoregressive distributed lag approach

    PubMed Central

    Qin, Yaochen; Lee, Jay

    2017-01-01

    This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June) led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention. PMID:28950027

  12. Inhibition of androgen receptor by decoy molecules delays progression to castration-recurrent prostate cancer.

    PubMed

    Myung, Jae-Kyung; Wang, Gang; Chiu, Helen H L; Wang, Jun; Mawji, Nasrin R; Sadar, Marianne D

    2017-01-01

    Androgen receptor (AR) is a member of the steroid receptor family and a therapeutic target for all stages of prostate cancer. AR is activated by ligand binding within its C-terminus ligand-binding domain (LBD). Here we show that overexpression of the AR NTD to generate decoy molecules inhibited both the growth and progression of prostate cancer in castrated hosts. Specifically, it was shown that lentivirus delivery of decoys delayed hormonal progression in castrated hosts as indicated by increased doubling time of tumor volume, prolonged time to achieve pre-castrate levels of serum prostate-specific antigen (PSA) and PSA nadir. These clinical parameters are indicative of delayed hormonal progression and improved therapeutic response and prognosis. Decoys reduced the expression of androgen-regulated genes that correlated with reduced in situ interaction of the AR with androgen response elements. Decoys did not reduce levels of AR protein or prevent nuclear localization of the AR. Nor did decoys interact directly with the AR. Thus decoys did not inhibit AR transactivation by a dominant negative mechanism. This work provides evidence that the AR NTD plays an important role in the hormonal progression of prostate cancer and supports the development of AR antagonists that target the AR NTD.

  13. Inhibition of androgen receptor by decoy molecules delays progression to castration-recurrent prostate cancer

    PubMed Central

    Myung, Jae-Kyung; Wang, Gang; Chiu, Helen H. L.; Wang, Jun; Mawji, Nasrin R.; Sadar, Marianne D.

    2017-01-01

    Androgen receptor (AR) is a member of the steroid receptor family and a therapeutic target for all stages of prostate cancer. AR is activated by ligand binding within its C-terminus ligand-binding domain (LBD). Here we show that overexpression of the AR NTD to generate decoy molecules inhibited both the growth and progression of prostate cancer in castrated hosts. Specifically, it was shown that lentivirus delivery of decoys delayed hormonal progression in castrated hosts as indicated by increased doubling time of tumor volume, prolonged time to achieve pre-castrate levels of serum prostate-specific antigen (PSA) and PSA nadir. These clinical parameters are indicative of delayed hormonal progression and improved therapeutic response and prognosis. Decoys reduced the expression of androgen-regulated genes that correlated with reduced in situ interaction of the AR with androgen response elements. Decoys did not reduce levels of AR protein or prevent nuclear localization of the AR. Nor did decoys interact directly with the AR. Thus decoys did not inhibit AR transactivation by a dominant negative mechanism. This work provides evidence that the AR NTD plays an important role in the hormonal progression of prostate cancer and supports the development of AR antagonists that target the AR NTD. PMID:28306720

  14. Endothelial activation biomarkers increase after HIV-1 acquisition: plasma vascular cell adhesion molecule-1 predicts disease progression.

    PubMed

    Graham, Susan M; Rajwans, Nimerta; Jaoko, Walter; Estambale, Benson B A; McClelland, R Scott; Overbaugh, Julie; Liles, W Conrad

    2013-07-17

    We aimed to determine whether endothelial activation biomarkers increase after HIV-1 acquisition, and whether biomarker levels measured in chronic infection would predict disease progression and death in HIV-1 seroconverters. HIV-1-seronegative Kenyan women were monitored monthly for seroconversion, and followed prospectively after HIV-1 acquisition. Plasma levels of angiopoietin-1 and angiopoietin-2 (ANG-1, ANG-2) and soluble vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin were tested in stored samples from pre-infection, acute infection, and two chronic infection time points. We used nonparametric tests to compare biomarkers before and after HIV-1 acquisition, and Cox proportional-hazards regression to analyze associations with disease progression (CD4 < 200 cells/μl, stage IV disease, or antiretroviral therapy initiation) or death. Soluble ICAM-1 and VCAM-1 were elevated relative to baseline in all postinfection periods assessed (P < 0.0001). Soluble E-selectin and the ANG-2:ANG-1 ratio increased in acute infection (P = 0.0001), and ANG-1 decreased in chronic infection (P = 0.0004). Among 228 participants followed over 1028 person-years, 115 experienced disease progression or death. Plasma VCAM-1 levels measured during chronic infection were independently associated with time to HIV progression or death (adjusted hazard ratio 5.36, 95% confidence interval 1.99-14.44 per log10 increase), after adjustment for set point plasma viral load, age at infection, and soluble ICAM-1 levels. HIV-1 acquisition was associated with endothelial activation, with sustained elevations of soluble ICAM-1 and VCAM-1 postinfection. Soluble VCAM-1 may be an informative biomarker for predicting the risk of HIV-1 disease progression, morbidity, and mortality.

  15. Technical progress in silicon sheet growth under DOE/JPL FSA program, 1975-1986

    NASA Technical Reports Server (NTRS)

    Kalejs, J. P.

    1986-01-01

    The technical progress made in the Silicon Sheet Growth Program during its 11 years was reviewed. At present, in 1986, only two of the original 9 techniques have survived to the start-up, pilot-plant stage in industry. These two techniques are the edge-defined, film-fed growth (EFG) technique that produces closed shape polygons, and the WEB dendritic technique that produces single ribbons. Both the status and future concerns of the EFG and WEB techniques were discussed.

  16. Progress in Small Molecule Therapeutics for the Treatment of Retinoblastoma

    PubMed Central

    Pritchard, Eleanor M.; Dyer, Michael A.; Guy, R. Kiplin

    2017-01-01

    While mortality is low for intraocular retinoblastoma patients in the developed world who receive aggressive multimodal therapy, partial or full loss of vision occurs in approximately 50% of patients with advanced bilateral retinoblastoma. Therapies that preserve vision and reduce late effects are needed. Because clinical trials for retinoblastoma are difficult due to the young age of the patient population and relative rarity of the disease, robust preclinical testing of new therapies is critical. The last decade has seen advances towards identifying new therapies including the development of animal models of retinoblastoma for preclinical testing, progress in local drug delivery to reach intraocular targets, and improved understanding of the underlying biological mechanisms that give rise to retinoblastoma. This review discusses advances in these areas, with a focus on discovery and development of small molecules for the treatment of retinoblastoma, including novel targeted therapeutics such as inhibitors of the MDMX-p53 interaction (nutlin-3a), histone deacetylase (HDAC) inhibitors, and spleen tyrosine kinase (SYK) inhibitors. PMID:26202204

  17. Progress in Small Molecule Therapeutics for the Treatment of Retinoblastoma.

    PubMed

    Pritchard, Eleanor M; Dyer, Michael A; Guy, R Kiplin

    2016-01-01

    While mortality is low for intraocular retinoblastoma patients in the developed world who receive aggressive multimodal therapy, partial or full loss of vision occurs in approximately 50% of patients with advanced bilateral retinoblastoma. Therapies that preserve vision and reduce late effects are needed. Because clinical trials for retinoblastoma are difficult due to the young age of the patient population and relative rarity of the disease, robust preclinical testing of new therapies is critical. The last decade has seen advances towards identifying new therapies including the development of animal models of retinoblastoma for preclinical testing, progress in local drug delivery to reach intraocular targets, and improved understanding of the underlying biological mechanisms that give rise to retinoblastoma. This review discusses advances in these areas, with a focus on discovery and development of small molecules for the treatment of retinoblastoma, including novel targeted therapeutics such as inhibitors of the MDMX-p53 interaction (nutlin-3a), histone deacetylase (HDAC) inhibitors, and spleen tyrosine kinase (SYK) inhibitors.

  18. The role of MicroRNA molecules and MicroRNA-regulating machinery in the pathogenesis and progression of epithelial ovarian cancer.

    PubMed

    Wang, Xiyin; Ivan, Mircea; Hawkins, Shannon M

    2017-11-01

    MicroRNA molecules are small, single-stranded RNA molecules that function to regulate networks of genes. They play important roles in normal female reproductive tract biology, as well as in the pathogenesis and progression of epithelial ovarian cancer. DROSHA, DICER, and Argonaute proteins are components of the microRNA-regulatory machinery and mediate microRNA production and function. This review discusses aberrant expression of microRNA molecules and microRNA-regulating machinery associated with clinical features of epithelial ovarian cancer. Understanding the regulation of microRNA molecule production and function may facilitate the development of novel diagnostic and therapeutic strategies to improve the prognosis of women with epithelial ovarian cancer. Additionally, understanding microRNA molecules and microRNA-regulatory machinery associations with clinical features may influence prevention and early detection efforts. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. The small molecule AUTEN-99 (autophagy enhancer-99) prevents the progression of neurodegenerative symptoms

    PubMed Central

    Kovács, Tibor; Billes, Viktor; Komlós, Marcell; Hotzi, Bernadette; Manzéger, Anna; Tarnóci, Anna; Papp, Diána; Szikszai, Fanni; Szinyákovics, Janka; Rácz, Ákos; Noszál, Béla; Veszelka, Szilvia; Walter, Fruzsina R.; Deli, Mária A.; Hackler, Laszlo; Alfoldi, Robert; Huzian, Orsolya; Puskas, Laszlo G.; Liliom, Hanna; Tárnok, Krisztián; Schlett, Katalin; Borsy, Adrienn; Welker, Ervin; Kovács, Attila L.; Pádár, Zsolt; Erdős, Attila; Legradi, Adam; Bjelik, Annamaria; Gulya, Károly; Gulyás, Balázs; Vellai, Tibor

    2017-01-01

    Autophagy functions as a main route for the degradation of superfluous and damaged constituents of the cytoplasm. Defects in autophagy are implicated in the development of various age-dependent degenerative disorders such as cancer, neurodegeneration and tissue atrophy, and in accelerated aging. To promote basal levels of the process in pathological settings, we previously screened a small molecule library for novel autophagy-enhancing factors that inhibit the myotubularin-related phosphatase MTMR14/Jumpy, a negative regulator of autophagic membrane formation. Here we identify AUTEN-99 (autophagy enhancer-99), which activates autophagy in cell cultures and animal models. AUTEN-99 appears to effectively penetrate through the blood-brain barrier, and impedes the progression of neurodegenerative symptoms in Drosophila models of Parkinson’s and Huntington’s diseases. Furthermore, the molecule increases the survival of isolated neurons under normal and oxidative stress-induced conditions. Thus, AUTEN-99 serves as a potent neuroprotective drug candidate for preventing and treating diverse neurodegenerative pathologies, and may promote healthy aging. PMID:28205624

  20. The small molecule AUTEN-99 (autophagy enhancer-99) prevents the progression of neurodegenerative symptoms.

    PubMed

    Kovács, Tibor; Billes, Viktor; Komlós, Marcell; Hotzi, Bernadette; Manzéger, Anna; Tarnóci, Anna; Papp, Diána; Szikszai, Fanni; Szinyákovics, Janka; Rácz, Ákos; Noszál, Béla; Veszelka, Szilvia; Walter, Fruzsina R; Deli, Mária A; Hackler, Laszlo; Alfoldi, Robert; Huzian, Orsolya; Puskas, Laszlo G; Liliom, Hanna; Tárnok, Krisztián; Schlett, Katalin; Borsy, Adrienn; Welker, Ervin; Kovács, Attila L; Pádár, Zsolt; Erdős, Attila; Legradi, Adam; Bjelik, Annamaria; Gulya, Károly; Gulyás, Balázs; Vellai, Tibor

    2017-02-16

    Autophagy functions as a main route for the degradation of superfluous and damaged constituents of the cytoplasm. Defects in autophagy are implicated in the development of various age-dependent degenerative disorders such as cancer, neurodegeneration and tissue atrophy, and in accelerated aging. To promote basal levels of the process in pathological settings, we previously screened a small molecule library for novel autophagy-enhancing factors that inhibit the myotubularin-related phosphatase MTMR14/Jumpy, a negative regulator of autophagic membrane formation. Here we identify AUTEN-99 (autophagy enhancer-99), which activates autophagy in cell cultures and animal models. AUTEN-99 appears to effectively penetrate through the blood-brain barrier, and impedes the progression of neurodegenerative symptoms in Drosophila models of Parkinson's and Huntington's diseases. Furthermore, the molecule increases the survival of isolated neurons under normal and oxidative stress-induced conditions. Thus, AUTEN-99 serves as a potent neuroprotective drug candidate for preventing and treating diverse neurodegenerative pathologies, and may promote healthy aging.

  1. Surgical resident technical skill self-evaluation: increased precision with training progression.

    PubMed

    Quick, Jacob A; Kudav, Vishal; Doty, Jennifer; Crane, Megan; Bukoski, Alex D; Bennett, Bethany J; Barnes, Stephen L

    2017-10-01

    Surgical resident ability to accurately evaluate one's own skill level is an important part of educational growth. We aimed to determine if differences exist between self and observer technical skill evaluation of surgical residents performing a single procedure. We prospectively enrolled 14 categorical general surgery residents (six post-graduate year [PGY] 1-2, three PGY 3, and five PGY 4-5). Over a 6-month period, following each laparoscopic cholecystectomy, residents and seven faculty each completed the Objective Structured Assessment of Technical Skills (OSATS). Spearman's coefficient was calculated for three groups: senior (PGY 4-5), PGY3, and junior (PGY 1-2). Rho (ρ) values greater than 0.8 were considered well correlated. Of the 125 paired assessments (resident-faculty each evaluating the same case), 58 were completed for senior residents, 54 for PGY3 residents, and 13 for junior residents. Using the mean from all OSATS categories, trainee self-evaluations correlated well to faculty (senior ρ 0.97, PGY3 ρ 0.9, junior ρ 0.9). When specific OSATS categories were analyzed, junior residents exhibited poor correlation in categories of respect for tissue (ρ -0.5), instrument handling (ρ 0.71), operative flow (ρ 0.41), use of assistants (ρ 0.05), procedural knowledge (ρ 0.32), and overall comfort with the procedure (ρ 0.73). PGY3 residents lacked correlation in two OSATS categories, operative flow (ρ 0.7) and procedural knowledge (ρ 0.2). Senior resident self-evaluations exhibited strong correlations to observers in all areas. Surgical residents improve technical skill self-awareness with progressive training. Less-experienced trainees have a tendency to over-or-underestimate technical skill. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Exotic Molecules in Space: A Coordinated Astronomical, Laboratory, and Theoretical Study

    NASA Technical Reports Server (NTRS)

    Thaddeus, Patrick

    1997-01-01

    The past year has been a period of spectacular progress in our investigation of exotic molecules of astrophysical interest. During this period an entirely new spectrometer for the investigation of reactive molecules was finished: a Fourier-transform microwave spectrometer with a supersonic molecular beam. The instrument is operating almost flawlessly, and during the above period of less than two years has discovered the 23 new carbon chain and ring-chain molecules. Seventeen research papers, nearly all in leading refereed journals such as the Astrophysical Journal and the Journal of Chemical Physics have been published. At least five more papers are being prepared for publication. Already four of our new molecules have been detected in space with large radio telescopes. In many ways the most interesting of these is HC(11)N, which now ranks as the largest molecule definitely identified beyond the solar system. Nearly all the other new molecules are candidates for astronomical detection, and we will be disappointed if a number of them are not found as more sensitive receivers and larger telescopes are constructed. During the next year we expect this wave of discovery to continue, and to insure rapid progress we have designed an even more sensitive spectrometer which will operate at the temperature of liquid helium. The goal of this system is to enhance the sensitivity of Fourier-transform spectroscopy by a further factor of 20 to 50, achieving this by reducing the amplifier and thermal noise to levels routinely achieved in radio astronomy. This new instrument offers a number of technical challenges in cryogenic and microwave engineering, but none of these appears to be insurmountable, and our current schedule is to have the helium cooled system operating within the next six months. A number of investigations continued with our conventional free space spectrometer, which remains a powerful complement to our new FTM instrument.

  3. Laser Slowing of CaF Molecules and Progress towards a Dual-MOT for Li and CaF

    NASA Astrophysics Data System (ADS)

    Chae, Eunmi

    significant progress toward manipulation and control of molecules similar to what has been achieved with atoms and what is necessary for searches for new physics with ultracold molecules.

  4. Measurement of solids motion in gas-fluidized beds. Technical progress report, 1 October 1982-31 December 1982

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

    Chen, M.M.; Chao, B.T.

    This technical progress report covers the progress made during the fifth quarter of the project entitled Measurements of Solids Motion in Gas Fluidized Beds under Grant No. DOE-F22-81PC40804 during the period 1 October through 31 December 1982. The research concerns the measurement of solids particle velocity distribution and residence time distribution using the Computer-Aided Particle Tracking Facility (CAPTF) at the University of Illinois at Urbana-Champaign. The experimental equipment and measuring methods used to determine particle size distribution and particle motion and the results obtained are presented.

  5. Development of new photon-counting detectors for single-molecule fluorescence microscopy.

    PubMed

    Michalet, X; Colyer, R A; Scalia, G; Ingargiola, A; Lin, R; Millaud, J E; Weiss, S; Siegmund, Oswald H W; Tremsin, Anton S; Vallerga, John V; Cheng, A; Levi, M; Aharoni, D; Arisaka, K; Villa, F; Guerrieri, F; Panzeri, F; Rech, I; Gulinatti, A; Zappa, F; Ghioni, M; Cova, S

    2013-02-05

    Two optical configurations are commonly used in single-molecule fluorescence microscopy: point-like excitation and detection to study freely diffusing molecules, and wide field illumination and detection to study surface immobilized or slowly diffusing molecules. Both approaches have common features, but also differ in significant aspects. In particular, they use different detectors, which share some requirements but also have major technical differences. Currently, two types of detectors best fulfil the needs of each approach: single-photon-counting avalanche diodes (SPADs) for point-like detection, and electron-multiplying charge-coupled devices (EMCCDs) for wide field detection. However, there is room for improvements in both cases. The first configuration suffers from low throughput owing to the analysis of data from a single location. The second, on the other hand, is limited to relatively low frame rates and loses the benefit of single-photon-counting approaches. During the past few years, new developments in point-like and wide field detectors have started addressing some of these issues. Here, we describe our recent progresses towards increasing the throughput of single-molecule fluorescence spectroscopy in solution using parallel arrays of SPADs. We also discuss our development of large area photon-counting cameras achieving subnanosecond resolution for fluorescence lifetime imaging applications at the single-molecule level.

  6. Development of new photon-counting detectors for single-molecule fluorescence microscopy

    PubMed Central

    Michalet, X.; Colyer, R. A.; Scalia, G.; Ingargiola, A.; Lin, R.; Millaud, J. E.; Weiss, S.; Siegmund, Oswald H. W.; Tremsin, Anton S.; Vallerga, John V.; Cheng, A.; Levi, M.; Aharoni, D.; Arisaka, K.; Villa, F.; Guerrieri, F.; Panzeri, F.; Rech, I.; Gulinatti, A.; Zappa, F.; Ghioni, M.; Cova, S.

    2013-01-01

    Two optical configurations are commonly used in single-molecule fluorescence microscopy: point-like excitation and detection to study freely diffusing molecules, and wide field illumination and detection to study surface immobilized or slowly diffusing molecules. Both approaches have common features, but also differ in significant aspects. In particular, they use different detectors, which share some requirements but also have major technical differences. Currently, two types of detectors best fulfil the needs of each approach: single-photon-counting avalanche diodes (SPADs) for point-like detection, and electron-multiplying charge-coupled devices (EMCCDs) for wide field detection. However, there is room for improvements in both cases. The first configuration suffers from low throughput owing to the analysis of data from a single location. The second, on the other hand, is limited to relatively low frame rates and loses the benefit of single-photon-counting approaches. During the past few years, new developments in point-like and wide field detectors have started addressing some of these issues. Here, we describe our recent progresses towards increasing the throughput of single-molecule fluorescence spectroscopy in solution using parallel arrays of SPADs. We also discuss our development of large area photon-counting cameras achieving subnanosecond resolution for fluorescence lifetime imaging applications at the single-molecule level. PMID:23267185

  7. 76 FR 64083 - Reliability Technical Conference; Notice of Technical Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-17

    ... Technical Conference; Notice of Technical Conference Take notice that the Federal Energy Regulatory Commission will hold a Technical Conference on Tuesday, November 29, 2011, from 1 p.m. to 5 p.m. and... System. The conference will explore the progress made on the priorities for addressing risks to...

  8. Final Technical Progress Report: Development of Low-Cost Suspension Heliostat; December 7, 2011 - December 6, 2012

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

    Bender, W.

    2013-01-01

    Final technical progress report of SunShot Incubator Solaflect Energy. The project succeeded in demonstrating that the Solaflect Suspension Heliostat design is viable for large-scale CSP installations. Canting accuracy is acceptable and is continually improving as Solaflect improves its understanding of this design. Cost reduction initiatives were successful, and there are still many opportunities for further development and further cost reduction.

  9. Active colloidal molecules

    NASA Astrophysics Data System (ADS)

    Löwen, Hartmut

    2018-03-01

    Like ordinary molecules are composed of atoms, colloidal molecules consist of several species of colloidal particles tightly bound together. If one of these components is self-propelled or swimming, novel “active colloidal molecules” emerge. Active colloidal molecules exist on various levels such as “homonuclear”, “heteronuclear” and “polymeric” and possess a dynamical function moving as propellers, spinners or rotors. Self-assembly of such active complexes has been studied a lot recently and this perspective article summarizes recent progress and gives an outlook to future developments in the rapidly expanding field of active colloidal molecules.

  10. Generation and focusing of pulsed intense ion beams. Technical progress report, 20 August 1981-30 September 1982

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

    Hammer, D.A.; Kusse, B.R.; Sudan, R.N.

    1983-07-01

    The progress on this contract is described in two parts. The first deals with the technical operation of the LION accelerator which is the exact equivalent to one line of PBFA-I. The second part is concerned with the experimental results on the ion diode mounted at the front end of the LION accelerator.

  11. Spray forming -- Aluminum: Third annual report (Phase 2). Technical progress -- Summary

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

    Kozarek, R.L.

    1998-04-20

    Commercial production of aluminum sheet and plate by spray atomization and deposition is a potentially attractive manufacturing alternative to conventional ingot metallurgy/hot-milling and to continuous casting processes because of reduced energy requirements and reduced cost. To realize the full potential of the technology, the Aluminum Company of America (Alcoa), under contract by the US Department of Energy, is investigating currently available state-of-the-art atomization devices to develop nozzle design concepts whose spray characteristics are tailored for continuous sheet production. This third technical progress report will summarize research and development work conducted during the period 1997 October through 1998 March. Included aremore » the latest optimization work on the Alcoa III nozzle, results of spray forming runs with 6111 aluminum alloy and preliminary rolling trials of 6111 deposits.« less

  12. Regulated necrosis-related molecule mRNA expression in humans and mice and in murine acute tissue injury and systemic autoimmunity leading to progressive organ damage, and progressive fibrosis.

    PubMed

    Honarpisheh, Mohsen; Desai, Jyaysi; Marschner, Julian A; Weidenbusch, Marc; Lech, Maciej; Vielhauer, Volker; Anders, Hans-Joachim; Mulay, Shrikant R

    2016-12-01

    The species-specific, as well as organ-specific expression of regulated necrosis (RN)-related molecules, is not known. We determined the expression levels of tumour necrosis factor receptor-1 (TNFR1), receptor activated protein kinase (RIPK)1, RIPK3, mixed lineage kinase domain-like (MLKL), CASP8, Fas-associated protein with death domain (FADD), cellular inhibitor of apoptosis protein (CIAP)1, CIAP2, glutathione peroxidase-4 (GPX4), cyclophilin D (CYPD), CASP1, NLRP3 and poly(ADP-ribose) polymerase-1 (PARP1) in human and mouse solid organs. We observed significant differences in expression of these molecules between human and mice. In addition, we characterized their expression profiles in acute as well as persistent tissue injury and chronic tissue remodelling using acute and chronic kidney injury models. We observed that the degree and pattern of induction of RN-related molecules were highly dependent on the trigger and disease pathogenesis. Furthermore, we studied their expression patterns in mice with lupus-like systemic autoimmunity, which revealed that the expression of MLKL, GPX4 and PARP1 significantly increased in the spleen along disease progression and CASP1, RIPK1, RIPK3 and CYPD were higher at the earlier stages but were significantly decreased in the later stages. In contrast, in the kidney, the expression of genes involved in pyroptosis, e.g. NLRP3 and CASP1 were significantly increased and TNFR1, RIPK1, RIPK3, CIAP1/2 and GPX4 were significantly decreased along the progression of lupus nephritis (LN). Thus, the organ- and species-specific expression of RN-related molecules should be considered during designing experiments, interpreting the results as well as extrapolating the conclusions from one species or organ to another species or organ respectively. © 2016 The Author(s).

  13. Regulated necrosis-related molecule mRNA expression in humans and mice and in murine acute tissue injury and systemic autoimmunity leading to progressive organ damage, and progressive fibrosis

    PubMed Central

    Honarpisheh, Mohsen; Desai, Jyaysi; Marschner, Julian A.; Weidenbusch, Marc; Lech, Maciej; Vielhauer, Volker; Anders, Hans-Joachim; Mulay, Shrikant R.

    2016-01-01

    The species-specific, as well as organ-specific expression of regulated necrosis (RN)-related molecules, is not known. We determined the expression levels of tumour necrosis factor receptor-1 (TNFR1), receptor activated protein kinase (RIPK)1, RIPK3, mixed lineage kinase domain-like (MLKL), CASP8, Fas-associated protein with death domain (FADD), cellular inhibitor of apoptosis protein (CIAP)1, CIAP2, glutathione peroxidase-4 (GPX4), cyclophilin D (CYPD), CASP1, NLRP3 and poly(ADP-ribose) polymerase-1 (PARP1) in human and mouse solid organs. We observed significant differences in expression of these molecules between human and mice. In addition, we characterized their expression profiles in acute as well as persistent tissue injury and chronic tissue remodelling using acute and chronic kidney injury models. We observed that the degree and pattern of induction of RN-related molecules were highly dependent on the trigger and disease pathogenesis. Furthermore, we studied their expression patterns in mice with lupus-like systemic autoimmunity, which revealed that the expression of MLKL, GPX4 and PARP1 significantly increased in the spleen along disease progression and CASP1, RIPK1, RIPK3 and CYPD were higher at the earlier stages but were significantly decreased in the later stages. In contrast, in the kidney, the expression of genes involved in pyroptosis, e.g. NLRP3 and CASP1 were significantly increased and TNFR1, RIPK1, RIPK3, CIAP1/2 and GPX4 were significantly decreased along the progression of lupus nephritis (LN). Thus, the organ- and species-specific expression of RN-related molecules should be considered during designing experiments, interpreting the results as well as extrapolating the conclusions from one species or organ to another species or organ respectively. PMID:27811014

  14. Project LIFE--Language Improvement to Facilitate Education. (Technical Progress Report; Third Quarter; March 1, 1974-May 31, 1974).

    ERIC Educational Resources Information Center

    National Foundation for the Improvement of Education, Washington, DC.

    Reported is the third quarter, fiscal year 1974 (March 1, 1974-May 31, 1974) technical progress of Project LIFE (Language Improvement to Facilitate Education), toward developing an instructional system in which filmstrips in the areas of perceptual training, perceptual thinking, and language/reading are used to assist hearing impaired children in…

  15. The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Kindergarten. Technical Report # 0921

    ERIC Educational Resources Information Center

    Alonzo, Julie; Tindal, Gerald

    2009-01-01

    In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in kindergarten. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2008 and administered to approximately 2800 students from…

  16. Molecule by molecule, the physics and chemistry of life: SMB 2007.

    PubMed

    Block, Steven M; Larson, Matthew H; Greenleaf, William J; Herbert, Kristina M; Guydosh, Nicholas R; Anthony, Peter C

    2007-04-01

    Interdisciplinary work in the life sciences at the boundaries of biology, chemistry and physics is making enormous strides. This progress was showcased at the recent Single Molecule Biophysics conference.

  17. Emmprin (basigin/CD147): matrix metalloproteinase modulator and multifunctional cell recognition molecule that plays a critical role in cancer progression.

    PubMed

    Nabeshima, Kazuki; Iwasaki, Hiroshi; Koga, Kaori; Hojo, Hironobu; Suzumiya, Junji; Kikuchi, Masahiro

    2006-07-01

    Emmprin (basigin, CD147) is a cell surface glycoprotein that belongs to the immunoglobulin superfamily. It is highly expressed on the surface of tumor cells and stimulates adjacent fibroblasts or tumor cells to produce matrix metalloproteinases. Moreover, it has recently been shown that emmprin also stimulates expression of vascular endothelial growth factor and hyaluronan, which leads to angiogenesis and anchorage-independent growth/multidrug resistance, respectively. These findings have made emmprin an important molecule in tumor progression and, thus, more attractive as a target for antitumor treatment. However, other functions of emmprin, including as an activator of T cells, a chaperone for monocarboxylate transporters, a receptor for cyclophilin A and a neural recognition molecule, are also being identified in physiological and pathological conditions. Therefore, it is essential to develop specific means to control particular functions of emmprin, for which elucidation of each mechanism is crucial. This review will discuss the role of emmprin in tumor progression and recent advances in the molecular mechanisms of diverse phenomena regulated by emmprin.

  18. Molecule by molecule, the physics and chemistry of life: SMB 2007

    PubMed Central

    Block, Steven M; Larson, Matthew H; Greenleaf, William J; Herbert, Kristina M; Guydosh, Nicholas R; Anthony, Peter C

    2007-01-01

    Interdisciplinary work in the life sciences at the boundaries of biology, chemistry and physics is making enormous strides. This progress was showcased at the recent Single Molecule Biophysics conference. PMID:17372599

  19. Statin and rottlerin small-molecule inhibitors restrict colon cancer progression and metastasis via MACC1.

    PubMed

    Juneja, Manisha; Kobelt, Dennis; Walther, Wolfgang; Voss, Cynthia; Smith, Janice; Specker, Edgar; Neuenschwander, Martin; Gohlke, Björn-Oliver; Dahlmann, Mathias; Radetzki, Silke; Preissner, Robert; von Kries, Jens Peter; Schlag, Peter Michael; Stein, Ulrike

    2017-06-01

    MACC1 (Metastasis Associated in Colon Cancer 1) is a key driver and prognostic biomarker for cancer progression and metastasis in a large variety of solid tumor types, particularly colorectal cancer (CRC). However, no MACC1 inhibitors have been identified yet. Therefore, we aimed to target MACC1 expression using a luciferase reporter-based high-throughput screening with the ChemBioNet library of more than 30,000 compounds. The small molecules lovastatin and rottlerin emerged as the most potent MACC1 transcriptional inhibitors. They remarkably inhibited MACC1 promoter activity and expression, resulting in reduced cell motility. Lovastatin impaired the binding of the transcription factors c-Jun and Sp1 to the MACC1 promoter, thereby inhibiting MACC1 transcription. Most importantly, in CRC-xenografted mice, lovastatin and rottlerin restricted MACC1 expression and liver metastasis. This is-to the best of our knowledge-the first identification of inhibitors restricting cancer progression and metastasis via the novel target MACC1. This drug repositioning might be of therapeutic value for CRC patients.

  20. The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 1. Technical Report # 0919

    ERIC Educational Resources Information Center

    Alonzo, Julie; Tindal, Gerald

    2009-01-01

    In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grade 1. These measures, available as part of easyCBM [TM], an online progress monitoring assessment system, were developed in 2008 and administered to approximately 2800 students from schools…

  1. The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 2. Technical Report # 0920

    ERIC Educational Resources Information Center

    Alonzo, Julie; Lai, Cheng Fei; Tindal, Gerald

    2009-01-01

    In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

  2. The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 7. Technical Report 0908

    ERIC Educational Resources Information Center

    Lai, Cheng Fei; Alonzo, Julie; Tindal, Gerald

    2009-01-01

    In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

  3. Annual progress report : for the period of January 2001 through December 2001 : Florida Transit Training Program (2001) : Florida Technical Assistance Program (2001)

    DOT National Transportation Integrated Search

    2001-01-01

    The following progress report is intended to highlight the significant activities of the Florida Transit Training Program and Florida Technical Assistant Program for the 2001 year. Activities of the Florida Statewide Transit Training Program are pres...

  4. The structure and function of cell membranes examined by atomic force microscopy and single-molecule force spectroscopy.

    PubMed

    Shan, Yuping; Wang, Hongda

    2015-06-07

    The cell membrane is one of the most complicated biological complexes, and long-term fierce debates regarding the cell membrane persist because of technical hurdles. With the rapid development of nanotechnology and single-molecule techniques, our understanding of cell membranes has substantially increased. Atomic force microscopy (AFM) has provided several unprecedented advances (e.g., high resolution, three-dimensional and in situ measurements) in the study of cell membranes and has been used to systematically dissect the membrane structure in situ from both sides of membranes; as a result, novel models of cell membranes have recently been proposed. This review summarizes the new progress regarding membrane structure using in situ AFM and single-molecule force spectroscopy (SMFS), which may shed light on the study of the structure and functions of cell membranes.

  5. The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 3. Technical Report # 09-02

    ERIC Educational Resources Information Center

    Alonzo, Julie; Lai, Cheng Fei; Tindal, Gerald

    2009-01-01

    In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

  6. The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 5. Technical Report # 09-01

    ERIC Educational Resources Information Center

    Lai, Cheng Fei; Alonzo, Julie; Tindal, Gerald

    2009-01-01

    In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

  7. The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 4. Technical Report # 09-03

    ERIC Educational Resources Information Center

    Alonzo, Julie; Lai, Cheng Fei; Tindal, Gerald

    2009-01-01

    In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

  8. The Development of K-8 Progress Monitoring Measures in Mathematics for Use with the 2% and General Education Populations: Grade 8. Technical Report # 09-04

    ERIC Educational Resources Information Center

    Lai, Cheng Fei; Alonzo, Julie; Tindal, Gerald

    2009-01-01

    In this technical report, we describe the development and piloting of a series of mathematics progress monitoring measures intended for use with students in grades kindergarten through eighth grade. These measures, available as part of easyCBM[TM], an online progress monitoring assessment system, were developed in 2007 and 2008 and administered to…

  9. Index to Nuclear Safety: a technical progress review by chronology, permuted title, and author, Volume 18 (1) through Volume 22 (6)

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

    Cottrell, W.B.; Passiakos, M.

    This index to Nuclear Safety covers articles published in Nuclear Safety, Volume 18, Number 1 (January-February 1977) through Volume 22, Number 6 (November-December 1981). The index is divided into three section: a chronological list of articles (including abstracts), a permuted-title (KWIC) index, and an author index. Nuclear Safety, a bimonthly technical progress review prepared by the Nuclear Safety Information Center, covers all safety aspects of nuclear power reactors and associated facilities. Over 300 technical articles published in Nuclear Safety in the last 5 years are listed in this index.

  10. Influence of vehicles used for oral dosing of test molecules on the progression of Mycobacterium tuberculosis infection in mice.

    PubMed

    Singh, Shubhra; Dwivedi, Richa; Chaturvedi, Vinita

    2012-11-01

    Preclinical evaluation of drug-like molecules requires their oral administration to experimental animals using suitable vehicles. We studied the effect of oral dosing with corn oil, carboxymethyl cellulose, dimethyl sulfoxide, and polysorbate-80 on the progression of Mycobacterium tuberculosis infection in mice. Infection was monitored by physical (survival time and body weight) and bacteriological (viable counts in lungs) parameters. Compared with water, corn oil significantly improved both sets of parameters, whereas the other vehicles affected only physical parameters.

  11. Index to Nuclear Safety. A technical progress review by chronology, permuted title, and author. Vol. 11, No. 1--Vol. 17, No. 6

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

    Cottrell, W.B.; Klein, A.

    1977-02-23

    This index to Nuclear Safety covers articles in Nuclear Safety Vol. 11, No. 1 (Jan.-Feb. 1970), through Vol. 17, No. 6 (Nov.-Dec. 1976). The index includes a chronological list of articles (including abstract) followed by KWIC and Author Indexes. Nuclear Safety, a bimonthly technical progress review prepared by the Nuclear Safety Information Center, covers all safety aspects of nuclear power reactors and associated facilities. The index lists over 350 technical articles in the last six years of publication.

  12. Soluble adhesion molecules in human cancers: sources and fates.

    PubMed

    van Kilsdonk, Jeroen W J; van Kempen, Léon C L T; van Muijen, Goos N P; Ruiter, Dirk J; Swart, Guido W M

    2010-06-01

    Adhesion molecules endow tumor cells with the necessary cell-cell contacts and cell-matrix interactions. As such, adhesion molecules are involved in cell signalling, proliferation and tumor growth. Rearrangements in the adhesion repertoire allow tumor cells to migrate, invade and form metastases. Besides these membrane-bound adhesion molecules several soluble adhesion molecules are detected in the supernatant of tumor cell lines and patient body fluids. Truncated soluble adhesion molecules can be generated by several conventional mechanisms, including alternative splicing of mRNA transcripts, chromosomal translocation, and extracellular proteolytic ectodomain shedding. Secretion of vesicles (ectosomes and exosomes) is an alternative mechanism mediating the release of full-length adhesion molecules. Soluble adhesion molecules function as modulators of cell adhesion, induce proteolytic activity and facilitate cell signalling. Additionally, adhesion molecules present on secreted vesicles might be involved in the vesicle-target cell interaction. Based on currently available data, released soluble adhesion molecules contribute to cancer progression and therefore should not be regarded as unrelated and non-functional side products of tumor progression. 2010 Elsevier GmbH. All rights reserved.

  13. Influence of Vehicles Used for Oral Dosing of Test Molecules on the Progression of Mycobacterium tuberculosis Infection in Mice

    PubMed Central

    Singh, Shubhra; Dwivedi, Richa

    2012-01-01

    Preclinical evaluation of drug-like molecules requires their oral administration to experimental animals using suitable vehicles. We studied the effect of oral dosing with corn oil, carboxymethyl cellulose, dimethyl sulfoxide, and polysorbate-80 on the progression of Mycobacterium tuberculosis infection in mice. Infection was monitored by physical (survival time and body weight) and bacteriological (viable counts in lungs) parameters. Compared with water, corn oil significantly improved both sets of parameters, whereas the other vehicles affected only physical parameters. PMID:22926571

  14. Single-Molecule Analysis of Pre-mRNA Splicing with Colocalization Single-Molecule Spectroscopy (CoSMoS).

    PubMed

    Braun, Joerg E; Serebrov, Victor

    2017-01-01

    Recent development of single-molecule techniques to study pre-mRNA splicing has provided insights into the dynamic nature of the spliceosome. Colocalization single-molecule spectroscopy (CoSMoS) allows following spliceosome assembly in real time at single-molecule resolution in the full complexity of cellular extracts. A detailed protocol of CoSMoS has been published previously (Anderson and Hoskins, Methods Mol Biol 1126:217-241, 2014). Here, we provide an update on the technical advances since the first CoSMoS studies including slide surface treatment, data processing, and representation. We describe various labeling strategies to generate RNA reporters with multiple dyes (or other moieties) at specific locations.

  15. West Hackberry Tertiary Project. Quarterly technical progress report, July 1--September 30, 1995

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

    NONE

    The goal of the West Hackberry Tertiary Project is to demonstrate the technical and economic feasibility of combining air injection with the Double Displacement Process for tertiary oil recovery. The Double Displacement Process is the gas displacement of a water invaded oil column for the purpose of recovering oil through gravity drainage. The novel aspect of this project is the use of air as the injection fluid. The target reservoir for the project is the Camerina C-1,2,3 Sand located on the West Flank of West Hackberry Field in Cameron Parish, Louisiana. If successful, this project will demonstrate that the usemore » of air injection in the Double Displacement Process can economically recover oil in reservoirs where tertiary oil recovery is presented uneconomic. During this quarter, the West Hackberry Tertiary Project completed the first ten months of air injection operations. Plots of air injection rates and cumulative air injected are included in this report as attachments. The following events are reviewed in this quarter`s technical progress report: (1) successful workovers on the Gulf Land D Nos. 44, 45 and 51 and the Watkins No. 3; (2) the unsuccessful repair attempt on the Watkins No. 16; (3) gathering of additional bottom hole pressure data; (4) air compressor operations and repairs; and (5) technology transfer activities.« less

  16. Single Molecule Electronics and Devices

    PubMed Central

    Tsutsui, Makusu; Taniguchi, Masateru

    2012-01-01

    The manufacture of integrated circuits with single-molecule building blocks is a goal of molecular electronics. While research in the past has been limited to bulk experiments on self-assembled monolayers, advances in technology have now enabled us to fabricate single-molecule junctions. This has led to significant progress in understanding electron transport in molecular systems at the single-molecule level and the concomitant emergence of new device concepts. Here, we review recent developments in this field. We summarize the methods currently used to form metal-molecule-metal structures and some single-molecule techniques essential for characterizing molecular junctions such as inelastic electron tunnelling spectroscopy. We then highlight several important achievements, including demonstration of single-molecule diodes, transistors, and switches that make use of electrical, photo, and mechanical stimulation to control the electron transport. We also discuss intriguing issues to be addressed further in the future such as heat and thermoelectric transport in an individual molecule. PMID:22969345

  17. Molecular Rotation Signals: Molecule Chemistry and Particle Physics

    NASA Astrophysics Data System (ADS)

    Grabow, Jens-Uwe

    2015-06-01

    Molecules - large or small - are attractive academic resources, with numerous questions on their chemical behaviour as well as problems in fundamental physics now (or still) waiting to be answered: Targeted by high-resolution spectroscopy, a rotating molecular top can turn into a laboratory for molecule chemistry or a laboratory for particle physics. Once successfully entrained (many species - depending on size and chemical composition - have insufficient vapour pressures or are of transient nature, such that specifically designed pulsed-jet sources are required for their transfer into the gas phase or in-situ generation) into the collision-free environment of a supersonic-jet expansion, each molecular top comes with its own set of challenges, theoretically and experimentally: Multiple internal interactions are causing complicated energy level schemes and the resulting spectra will be rather difficult to predict theoretically. Experimentally, these spectra are difficult to assess and assign. With today's broad-banded chirp microwave techniques, finding and identifying such spectral features have lost their major drawback of being very time consuming for many molecules. For other molecules, the unrivalled resolution and sensitivity of the narrow-banded impulse microwave techniques provide a window to tackle - at the highest precision available to date - fundamental questions in physics, even particle physics - potentially beyond the standard model. Molecular charge distribution, properties of the chemical bond, details on internal dynamics and intermolecular interaction, the (stereo-chemical) molecular structure (including the possibility of their spatial separation) as well as potential evidence for tiny yet significant interactions encode their signature in pure molecular rotation subjected to time-domain microwave spectroscopic techniques. Ongoing exciting technical developments promise rapid progress. We present recent examples from Hannover, new directions, and

  18. THE DEVELOPMENT OF PRE-VOCATIONAL EDUCATION LITERACY COURSES FOR USE WITH COMPUTER ASSISTED INSTRUCTION OF DISADVANTAGED YOUTH AND ADULTS. TECHNICAL PROGRESS REPORT.

    ERIC Educational Resources Information Center

    HANKIN, EDWARD K.; AND OTHERS

    THIS TECHNICAL PROGRESS REPORT COVERS THE FIRST THREE MONTHS OF A PROJECT TO DEVELOP COMPUTER ASSISTED PREVOCATIONAL READING AND ARITHMETIC COURSES FOR DISADVANTAGED YOUTHS AND ADULTS. DURING THE FIRST MONTH OF OPERATION, PROJECT PERSONNEL CONCENTRATED ON SUCH ADMINISTRATIVE MATTERS AS TRAINING STAFF AND PREPARING FACILITIES. AN ARITHMETIC PROGRAM…

  19. A systematic assessment of the state of hazardous waste clean-up technologies. Quarterly technical progress report, April 1--June 30, 1993

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

    Berg, M.T.; Reed, B.E.; Gabr, M.

    1993-07-01

    West Virginia University (WVU) and the US DOE Morgantown Energy Technology Center (METC) entered into a Cooperative Agreement on August 29, 1992 entitled ``Decontamination Systems Information and Research Programs.`` Stipulated within the Agreement is the requirement that WVU submit to METC a series of Technical Progress Report for Year 1 of the Agreement. This report reflects the progress and/or efforts performed on the following nine technical projects encompassed by the Year 1 Agreement for the period of April 1 through June 30, 1993: Systematic assessment of the state of hazardous waste clean-up technologies; site remediation technologies -- drain-enhanced soil flushingmore » (DESF) for organic contaminants removal; site remediation technologies -- in situ bioremediation of organic contaminants; excavation systems for hazardous waste sites; chemical destruction of polychlorinated biphenyls; development of organic sensors -- monolayer and multilayer self-assembled films for chemical sensors; Winfield lock and dam remediation; Assessments of Technologies for hazardous waste site remediation -- non-treatment technologies and pilot scale test facility implementation; and remediation of hazardous sites with stream reforming.« less

  20. In situ click chemistry: from small molecule discovery to synthetic antibodies

    PubMed Central

    Agnew, Heather D.; Lai, Bert; Lee, Su Seong; Lim, Jaehong; Nag, Arundhati; Pitram, Suresh; Rohde, Rosemary; Heath, James R.

    2013-01-01

    Advances in the fields of proteomics, molecular imaging, and therapeutics are closely linked to the availability of affinity reagents that selectively recognize their biological targets. Here we present a review of Iterative Peptide In Situ Click Chemistry (IPISC), a novel screening technology for designing peptide multiligands with high affinity and specificity. This technology builds upon in situ click chemistry, a kinetic target-guided synthesis approach where the protein target catalyzes the conjugation of two small molecules, typically through the azide–alkyne Huisgen cycloaddition. Integrating this methodology with solid phase peptide libraries enables the assembly of linear and branched peptide multiligands we refer to as Protein Catalyzed Capture Agents (PCC Agents). The resulting structures can be thought of as analogous to the antigen recognition site of antibodies and serve as antibody replacements in biochemical and cell-based applications. In this review, we discuss the recent progress in ligand design through IPISC and related approaches, focusing on the improvements in affinity and specificity as multiligands are assembled by target-catalyzed peptide conjugation. We compare the IPISC process to small molecule in situ click chemistry with particular emphasis on the advantages and technical challenges of constructing antibody-like PCC Agents. PMID:22836343

  1. Urology technical and non-technical skills development: the emerging role of simulation.

    PubMed

    Rashid, Prem; Gianduzzo, Troy R J

    2016-04-01

    To review the emerging role of technical and non-technical simulation in urological education and training. A review was conducted to examine the current role of simulation in urology training. A PUBMED search of the terms 'urology training', 'urology simulation' and 'urology education' revealed 11,504 titles. Three hundred and fifty-seven abstracts were identified as English language, peer reviewed papers pertaining to the role of simulation in urology and related topics. Key papers were used to explore themes. Some cross-referenced papers were also included. There is an ongoing need to ensure that training time is efficiently utilised while ensuring that optimal technical and non-technical skills are achieved. Changing working conditions and the need to minimise patient harm by inadvertent errors must be taken into account. Simulation models for specific technical aspects have been the mainstay of graduated step-wise low and high fidelity training. Whole scenario environments as well as non-technical aspects can be slowly incorporated into the curriculum. Doing so should also help define what have been challenging competencies to teach and evaluate. Dedicated time, resources and trainer up-skilling are important. Concurrent studies are needed to help evaluate the effectiveness of introducing step-wise simulation for technical and non-technical competencies. Simulation based learning remains the best avenue of progressing surgical education. Technical and non-technical simulation could be used in the selection process. There are good economic, logistic and safety reasons to pursue the process of ongoing development of simulation co-curricula. While the role of simulation is assured, its progress will depend on a structured program that takes advantage of what can be delivered via this medium. Overall, simulation can be developed further for urological training programs to encompass technical and non-technical skill development at all stages, including

  2. The 1996 NAEP Technical Report.

    ERIC Educational Resources Information Center

    Allen, Nancy L.; Carlson, James E.; Zelenak, Christine A.

    This report documents the design, administration, and data analysis procedure of the National Assessment of Education Progress (NAEP) for 1996. It indicates the technical decisions that were made and the rationale behind them. Detailed substantive findings are not presented in this report. These chapters provide technical information about the…

  3. 48 CFR 742.1170-4 - Progress reporting requirements and contract clause.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... progress. (b) Because the cognizant technical officer is the individual most familiar with the contractor's performance, the contractor must submit the progress reports directly to the cognizant technical officer. The cognizant technical officer must review the reports and advise the contracting officer, in writing, of any...

  4. Development and Validation of a Novel Scoring System for Predicting Technical Success of Chronic Total Occlusion Percutaneous Coronary Interventions: The PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) Score.

    PubMed

    Christopoulos, Georgios; Kandzari, David E; Yeh, Robert W; Jaffer, Farouc A; Karmpaliotis, Dimitri; Wyman, Michael R; Alaswad, Khaldoon; Lombardi, William; Grantham, J Aaron; Moses, Jeffrey; Christakopoulos, Georgios; Tarar, Muhammad Nauman J; Rangan, Bavana V; Lembo, Nicholas; Garcia, Santiago; Cipher, Daisha; Thompson, Craig A; Banerjee, Subhash; Brilakis, Emmanouil S

    2016-01-11

    This study sought to develop a novel parsimonious score for predicting technical success of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) performed using the hybrid approach. Predicting technical success of CTO PCI can facilitate clinical decision making and procedural planning. We analyzed clinical and angiographic parameters from 781 CTO PCIs included in PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) using a derivation and validation cohort (2:1 sampling ratio). Variables with strong association with technical success in multivariable analysis were assigned 1 point, and a 4-point score was developed from summing all points. The PROGRESS CTO score was subsequently compared with the J-CTO (Multicenter Chronic Total Occlusion Registry in Japan) score in the validation cohort. Technical success was 92.9%. On multivariable analysis, factors associated with technical success included proximal cap ambiguity (beta coefficient [b] = 0.88), moderate/severe tortuosity (b = 1.18), circumflex artery CTO (b = 0.99), and absence of "interventional" collaterals (b = 0.88). The resulting score demonstrated good calibration and discriminatory capacity in the derivation (Hosmer-Lemeshow chi-square = 2.633; p = 0.268, and receiver-operator characteristic [ROC] area = 0.778) and validation (Hosmer-Lemeshow chi-square = 5.333; p = 0.070, and ROC area = 0.720) subset. In the validation cohort, the PROGRESS CTO and J-CTO scores performed similarly in predicting technical success (ROC area 0.720 vs. 0.746, area under the curve difference = 0.026, 95% confidence interval = -0.093 to 0.144). The PROGRESS CTO score is a novel useful tool for estimating technical success in CTO PCI performed using the hybrid approach. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. A Small Molecule Polyamine Oxidase Inhibitor Blocks Androgen-Induced Oxidative Stress and Delays Prostate Cancer Progression in the TRAMP Mouse Model

    PubMed Central

    Basu, Hirak S.; Thompson, Todd A.; Church, Dawn R.; Clower, Cynthia C.; Mehraein-Ghomi, Farideh; Amlong, Corey A.; Martin, Christopher T.; Woster, Patrick M.; Lindstrom, Mary J.; Wilding, George

    2009-01-01

    High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiological factor in prostate cancer (CaP) occurrence, recurrence and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase (SSAT), the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data demonstrate that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays prostate cancer progression. PMID:19773450

  6. Progressive Stereo Locking (PSL): A Residual Dipolar Coupling Based Force Field Method for Determining the Relative Configuration of Natural Products and Other Small Molecules.

    PubMed

    Cornilescu, Gabriel; Ramos Alvarenga, René F; Wyche, Thomas P; Bugni, Tim S; Gil, Roberto R; Cornilescu, Claudia C; Westler, William M; Markley, John L; Schwieters, Charles D

    2017-08-18

    Establishing the relative configuration of a bioactive natural product represents the most challenging part in determining its structure. Residual dipolar couplings (RDCs) are sensitive probes of the relative spatial orientation of internuclear vectors. We adapted a force field structure calculation methodology to allow free sampling of both R and S configurations of the stereocenters of interest. The algorithm uses a floating alignment tensor in a simulated annealing protocol to identify the conformations and configurations that best fit experimental RDC and distance restraints (from NOE and J-coupling data). A unique configuration (for rigid molecules) or a very small number of configurations (for less rigid molecules) of the structural models having the lowest chiral angle energies and reasonable magnitudes of the alignment tensor are provided as the best predictions of the unknown configuration. For highly flexible molecules, the progressive locking of their stereocenters into their statistically dominant R or S state dramatically reduces the number of possible relative configurations. The result is verified by checking that the same configuration is obtained by initiating the locking from different regions of the molecule. For all molecules tested having known configurations (with conformations ranging from mostly rigid to highly flexible), the method accurately determined the correct configuration.

  7. 48 CFR 2052.211-70 - Preparation of technical reports.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ....211-70 Preparation of technical reports. As prescribed at 2011.104-70(a), the contracting officer... Reports (JAN 1993) All technical reports required by Section C and all Technical Progress Reports required... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Preparation of technical...

  8. 48 CFR 2052.211-70 - Preparation of technical reports.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ....211-70 Preparation of technical reports. As prescribed at 2011.104-70(a), the contracting officer... Reports (JAN 1993) All technical reports required by Section C and all Technical Progress Reports required... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Preparation of technical...

  9. 48 CFR 2052.211-70 - Preparation of technical reports.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....211-70 Preparation of technical reports. As prescribed at 2011.104-70(a), the contracting officer... Reports (JAN 1993) All technical reports required by Section C and all Technical Progress Reports required... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Preparation of technical...

  10. 48 CFR 2052.211-70 - Preparation of technical reports.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ....211-70 Preparation of technical reports. As prescribed at 2011.104-70(a), the contracting officer... Reports (JAN 1993) All technical reports required by Section C and all Technical Progress Reports required... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Preparation of technical...

  11. 48 CFR 2052.211-70 - Preparation of technical reports.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ....211-70 Preparation of technical reports. As prescribed at 2011.104-70(a), the contracting officer... Reports (JAN 1993) All technical reports required by Section C and all Technical Progress Reports required... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Preparation of technical...

  12. Single-Molecule Electronics: Chemical and Analytical Perspectives.

    PubMed

    Nichols, Richard J; Higgins, Simon J

    2015-01-01

    It is now possible to measure the electrical properties of single molecules using a variety of techniques including scanning probe microcopies and mechanically controlled break junctions. Such measurements can be made across a wide range of environments including ambient conditions, organic liquids, ionic liquids, aqueous solutions, electrolytes, and ultra high vacuum. This has given new insights into charge transport across molecule electrical junctions, and these experimental methods have been complemented with increasingly sophisticated theory. This article reviews progress in single-molecule electronics from a chemical perspective and discusses topics such as the molecule-surface coupling in electrical junctions, chemical control, and supramolecular interactions in junctions and gating charge transport. The article concludes with an outlook regarding chemical analysis based on single-molecule conductance.

  13. Responsive copolymers for enhanced petroleum recovery. Quarterly technical progress report, June 23--September 21, 1994

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

    McCormick, C.; Hester, R.

    Summaries are given on the technical progress on three tasks of this project. Monomer and polymer synthesis discusses the preparation of 1(7-aminoheptyloxymethyl)naphthalene and poly(maleic anhydride-alt-ethyl vinyl ether). Task 2, Characterization of molecular structure, discusses terpolymer solution preparation, UV analysis, fluorescence analysis, low angle laser light scattering, and viscometry. The paper discusses the effects of hydrophobic groups, the effect of pH, the effect of electrolyte addition, and photophysical studies. Task 3, Solution properties, describes the factorial experimental design for characterizing polymer solutions by light scattering, the light scattering test model, orthogonal factorial test design, linear regression in coded space, confidence levelmore » for coded space test mode coefficients, coefficients of the real space test model, and surface analysis of the model equations.« less

  14. Microenvironment Influences Interaction of Signaling Molecules | Center for Cancer Research

    Cancer.gov

    Tumor progression depends not only on events that occur within cancer cells but also on the interaction of cancer cells with their environment, which can regulate tumor growth and metastasis and modulate the formation of new blood vessels to nourish the tumor. All cells communicate with other cells around them, including endothelial cells (the cells that make up blood vessels). They also interact with the extracellular matrix (ECM), a network of sugars and proteins that supports cells. Communication between neighboring cells and molecules often occurs through interaction among and between molecules on the cell surface and molecules of the ECM. Defining these interactions should facilitate the development of novel approaches to limit tumor progression.

  15. Binding configurations and intramolecular strain in single-molecule devices.

    PubMed

    Rascón-Ramos, Habid; Artés, Juan Manuel; Li, Yuanhui; Hihath, Joshua

    2015-05-01

    The development of molecular-scale electronic devices has made considerable progress over the past decade, and single-molecule transistors, diodes and wires have all been demonstrated. Despite this remarkable progress, the agreement between theoretically predicted conductance values and those measured experimentally remains limited. One of the primary reasons for these discrepancies lies in the difficulty to experimentally determine the contact geometry and binding configuration of a single-molecule junction. In this Article, we apply a small-amplitude, high-frequency, sinusoidal mechanical signal to a series of single-molecule devices during junction formation and breakdown. By measuring the current response at this frequency, it is possible to determine the most probable binding and contact configurations for the molecular junction at room temperature in solution, and to obtain information about how an applied strain is distributed within the molecular junction. These results provide insight into the complex configuration of single-molecule devices, and are in excellent agreement with previous predictions from theoretical models.

  16. Increased plasma Kidney Injury Molecule-1 suggests early progressive renal decline in non-proteinuric patients with Type 1 diabetes

    PubMed Central

    Nowak, Natalia; Skupien, Jan; Niewczas, Monika A.; Yamanouchi, Masayuki; Major, Melissa; Croall, Stephanie; Smiles, Adam; Warram, James H.; Bonventre, Joseph V.; Krolewski, Andrzej S.

    2015-01-01

    Progressively decreasing glomerular filtration rate (GFR), or renal decline, is seen in patients with type 1 diabetes (T1D) and normoalbuminuria or microalbuminuria. Here we examined the associations of kidney injury molecule-1 (KIM-1) in plasma and urine with the risk of renal decline and determine whether those associations are independent of markers of glomerular damage. The study group comprised patients with T1D from the 2nd Joslin Kidney Study of which 259 had normoalbuminuria and 203 had microalbuminuria. Serial measurements over 4 to 10 years of follow-up (median 8 years) of serum creatinine and cystatin C were used jointly to estimate eGFRcr-cys slopes and time of onset of CKD stage 3 or higher. Baseline urinary excretion of IgG2 and albumin were used as markers of glomerular damage, and urinary excretion of KIM-1 and its plasma concentration were used as markers of proximal tubular damage. All patients had normal renal function at baseline. During follow-up, renal decline (eGFRcr-cys loss 3.3% or more per year) developed in 96 patients and 62 progressed to CKD stage 3. For both outcomes, the risk rose with increasing baseline levels of plasma KIM-1. In multivariable models, elevated baseline plasma KIM-1 was strongly associated with risk of early progressive renal decline, regardless of baseline clinical characteristics, serum TNFR1 or markers of glomerular damage. Thus, damage to proximal tubules may play an independent role in the development of early progressive renal decline in non-proteinuric patients with T1D. PMID:26509588

  17. Individual Magnetic Molecules on Ultrathin Insulating Surfaces

    NASA Astrophysics Data System (ADS)

    El Hallak, Fadi; Warner, Ben; Hirjibehedin, Cyrus

    2012-02-01

    Single molecule magnets have attracted ample interest because of their exciting magnetic and quantum properties. Recent studies have demonstrated that some of these molecules can be evaporated on surfaces without losing their magnetic properties [M. Mannini et al., Nature 468, 417, (2010)]. This remarkable progress enhances the chances of real world applications for these molecules. We present STM imaging and spectroscopy data on iron phthalocyanine molecules deposited on Cu(100) and on a Cu2N ultrathin insulating surface. These molecules have been shown to display a large magnetic anisotropy on another thin insulating surface, oxidized Cu(110) [N. Tsukahara et al., Phys. Rev. Lett. 102, 167203 (2009)]. By using a combination of elastic and inelastic electron tunnelling spectroscopy, we investigate the binding of the molecules to the surface and the impact that the surface has on their electronic and magnetic properties.

  18. Cold molecules: Progress in quantum engineering of chemistry and quantum matter

    NASA Astrophysics Data System (ADS)

    Bohn, John L.; Rey, Ana Maria; Ye, Jun

    2017-09-01

    Cooling atoms to ultralow temperatures has produced a wealth of opportunities in fundamental physics, precision metrology, and quantum science. The more recent application of sophisticated cooling techniques to molecules, which has been more challenging to implement owing to the complexity of molecular structures, has now opened the door to the longstanding goal of precisely controlling molecular internal and external degrees of freedom and the resulting interaction processes. This line of research can leverage fundamental insights into how molecules interact and evolve to enable the control of reaction chemistry and the design and realization of a range of advanced quantum materials.

  19. PFBC HGCU Test Facility. Technical progress report No. 24, Third quarter, CY 1995

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

    NONE

    This is the twenty-fourth and final Technical Progress Report submitted to the Department of Energy (DOE) in connection with the cooperative agreement between the DOE and Ohio Power Company for the Tidd PFBC Hot Gas Clean Up Test Facility. This report covers the work completed during the Third Quarter of CY 1995. All activity this quarter was directed toward the completion of the program final report. A draft copy of the final report was forwarded to DOE during this quarter, and DOE submitted their comments on the report to AEPSC. DOE requested that Westinghouse write an appendix to the reportmore » covering the performance of the fail-safe regenerator devices during Tad operation, and Westinghouse subsequently prepared the appendix. Additional DOE comments were incorporated into the report, and it will be issued in camera-ready form by the end of October, 1995, which is the program end date. Appendix 1 presents the results of filter candle posttest examination by Westinghouse performed on selected filter candles following final shutdown of the system.« less

  20. Research Results Ultra-fast Energy Transfer from Monomer to Dimer within a Trimeric Molecule New Progress in Heterogeneous Catalysis Research Key Progress in Research on Terrestrial Carbon Cycle in China A New Progress in Research on the Mechanism of Bio-Invasion New Findings in Anti-viral infection and Control of Inflammation Major Headway in Avian Origin Research New Progress in Gold-Nanoparticle-Based Biochips Topological Insulator Research Made Important Progress Major Progress in Biodiversity Achieved New Developments of Direct Methods in Protein Crystallography Major Progress in China-UK Collaboration on the Causal Relationship between Volcanic Activity and Biological Distinction News in Brief: NSFC set up "Research Fund for Young Foreign Scholars" How Often Does Human DNA Mutate? Research Progress on Colossal Anisotropic Magneto Resistive Effect

    NASA Astrophysics Data System (ADS)

    2009-01-01

    Ultra-fast Energy Transfer from Monomer to Dimer within a Trimeric Molecule New Progress in Heterogeneous Catalysis Research Key Progress in Research on Terrestrial Carbon Cycle in China A New Progress in Research on the Mechanism of Bio-Invasion New Findings in Anti-viral infection and Control of Inflammation Major Headway in Avian Origin Research New Progress in Gold-Nanoparticle-Based Biochips Topological Insulator Research Made Important Progress Major Progress in Biodiversity Achieved New Developments of Direct Methods in Protein Crystallography Major Progress in China-UK Collaboration on the Causal Relationship between Volcanic Activity and Biological Distinction News in Brief: NSFC set up "Research Fund for Young Foreign Scholars" How Often Does Human DNA Mutate? Research Progress on Colossal Anisotropic Magneto Resistive Effect

  1. [Chemical risk in operating rooms and technical progress: the obligations and responsibilities of law].

    PubMed

    Oddo, Antonio

    2013-01-01

    We are going to consider the specific applications of the new legal system and of the most recent body of laws to those work environments of particular risk, such as healthcare facilities and in particular operating rooms. In such environments, volatile chemicals classified as "dangerous" are used with consequent exposure to "chemical risk", both of those persons professionally involved, depending on the type of activity, and of the patients to whom such activities are addressed in the same environment. Once the chemical risk is framed in the existing regulatory system, it must be specifically evaluated the application of the same principle to the particular chemical risk arising from the use of anesthetic agents in the operating room, for example sevoflurane and desflurane, being careful to test wether and how much this risk can be eliminated or reduced to minimum in relation to the new achievements of the technical progress. So, as soon as the quality of "dangerous chemical agent" of the "volatile chemicals" and of the "volatile liquid anesthetic" (sevoflurane and desflurane) as well--which are characterized by a lower degree of toxicity and for this reason are mostly used in current chemical practice, preferable to some anesthetic gases such as nitrous oxide--is legally verified, it is necessary to relate the scientific and technical data which result from the current "state of art" also to the other binding regulations that are imposed for the "prevention and protection from chemical agents", according to the relative Title IX of the TUSL (Unique text for Safety and Health at Work).

  2. Taking the ruler to the jungle: single-molecule FRET for understanding biomolecular structure and dynamics in live cells.

    PubMed

    Sustarsic, Marko; Kapanidis, Achillefs N

    2015-10-01

    Single-molecule Förster resonance energy transfer (smFRET) serves as a molecular ruler that is ideally posed to study static and dynamic heterogeneity in living cells. Observing smFRET in cells requires appropriately integrated labeling, internalization and imaging strategies, and significant progress has been made towards that goal. Pioneering studies have demonstrated smFRET detection in both prokaryotic and eukaryotic systems, using both wide-field and confocal microscopies, and have started to answer exciting biological questions. We anticipate that future technical developments will open the door to smFRET for the study of structure, conformational changes and kinetics of biomolecules in living cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Assessment Program Technical Progress Report, 1997-1998.

    ERIC Educational Resources Information Center

    Eickmeyer, Barbara; Hill, Stephen

    This Assessment Program Progress Report (APPR) records the institutional activities that have taken place at Coconino Community College (CCC) during the 1997-98 academic year. It presents models, timelines, accomplishments, and opportunities for improvement in the assessment practices at CCC. Implementation and outcomes information is included for…

  4. Photodynamic therapy for treatment of solid tumors – potential and technical challenges

    PubMed Central

    Huang, Zheng; Xu, Heping; Meyers, Arlen D.; Musani, Ali I.; Wang, Luowei; Tagg, Randall; Barqawi, Al B.; Chen, Yang K.

    2008-01-01

    Photodynamic therapy (PDT) involves the administration of photosensitizer followed by local illumination with visible light of specific wavelength(s). In the presence of oxygen molecules, the light illumination of photosensitizer can lead to a series of photochemical reactions and consequently the generation of cytotoxic species. The quantity and location of PDT-induced cytotoxic species determine the nature and consequence of PDT. Much progress has been seen in both basic research and clinical application in recent years. Although the majority of approved PDT clinical protocols have primarily been used for the treatment of superficial lesions of both malignant and non-malignant diseases, interstitial PDT for the ablation of deep-seated solid tumors are now being investigated worldwide. The complexity of the geometry and non-homogeneity of solid tumor pose a great challenge on the implementation of minimally invasive interstitial PDT and the estimation of PDT dosimetry. This review will discuss the recent progress and technical challenges of various forms of interstitial PDT for the treatment of parenchymal and/or stromal tissues of solid tumors. PMID:18642969

  5. Repurposing a Benchtop Centrifuge for High-Throughput Single-Molecule Force Spectroscopy.

    PubMed

    Yang, Darren; Wong, Wesley P

    2018-01-01

    We present high-throughput single-molecule manipulation using a benchtop centrifuge, overcoming limitations common in other single-molecule approaches such as high cost, low throughput, technical difficulty, and strict infrastructure requirements. An inexpensive and compact Centrifuge Force Microscope (CFM) adapted to a commercial centrifuge enables use by nonspecialists, and integration with DNA nanoswitches facilitates both reliable measurements and repeated molecular interrogation. Here, we provide detailed protocols for constructing the CFM, creating DNA nanoswitch samples, and carrying out single-molecule force measurements.

  6. Single molecule tools for enzymology, structural biology, systems biology and nanotechnology: an update

    PubMed Central

    Widom, Julia R.; Dhakal, Soma; Heinicke, Laurie A.; Walter, Nils G.

    2015-01-01

    Toxicology is the highly interdisciplinary field studying the adverse effects of chemicals on living organisms. It requires sensitive tools to detect such effects. After their initial implementation during the 1990s, single-molecule fluorescence detection tools were quickly recognized for their potential to contribute greatly to many different areas of scientific inquiry. In the intervening time, technical advances in the field have generated ever-improving spatial and temporal resolution, and have enabled the application of single-molecule fluorescence to increasingly complex systems, such as live cells. In this review, we give an overview of the optical components necessary to implement the most common versions of single-molecule fluorescence detection. We then discuss current applications to enzymology and structural studies, systems biology, and nanotechnology, presenting the technical considerations that are unique to each area of study, along with noteworthy recent results. We also highlight future directions that have the potential to revolutionize these areas of study by further exploiting the capabilities of single-molecule fluorescence microscopy. PMID:25212907

  7. The Atom in a Molecule: Implications for Molecular Structure and Properties

    DTIC Science & Technology

    2016-05-23

    unlimited. PA Clearance #16075.” Atomic- Product Representations of Molecules Employ “van der Waals” products of atomic states to represent molecules...representation the electrons “stay home” with each nucleus. Atomic fragment operators are well-defined over product representations. Expectation values of...release; distribution unlimited. PA Clearance #16075.” Hamiltonian Matrix in the Atomic- Product Basis Technical Questions Addressed: J. Chem. Phys

  8. Single molecule techniques in DNA repair: A primer

    PubMed Central

    Hughes, Craig D.; Simons, Michelle; Mackenzie, Cassidy E.; Van Houten, Bennett; Kad, Neil M.

    2016-01-01

    A powerful new approach has become much more widespread and offers insights into aspects of DNA repair unattainable with billions of molecules. Single molecule techniques can be used to image, manipulate or characterize the action of a single repair protein on a single strand of DNA. This allows search mechanisms to be probed, and the effects of force to be understood. These physical aspects can dominate a biochemical reaction, where at the ensemble level their nuances are obscured. In this paper we discuss some of the many technical advances that permit study at the single molecule level. We focus on DNA repair to which these techniques are actively being applied. DNA repair is also a process that encompasses so much of what single molecule studies benefit – searching for targets, complex formation, sequential biochemical reactions and substrate hand-off to name just a few. We discuss how single molecule biophysics is poised to transform our understanding of biological systems, in particular DNA repair. PMID:24819596

  9. ISABELLE: a progress report

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

    Hahn, H

    This paper discusses the ISABELLE project, which has the objective of constructing a high-energy proton colliding beam facility at Brookhaven National Laboratory. The major technical features of the intersecting storage accelerators with their projected performance are described. Application of over 1000 superconducting magnets in the two rings represents the salient characteristic of the machine. The status of the entire project, the technical progress made so far, and difficulties encountered are reviewed.

  10. 25 CFR 30.111 - When should the tribal governing body or school board request technical assistance?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... request technical assistance? 30.111 Section 30.111 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION ADEQUATE YEARLY PROGRESS Defining Adequate Yearly Progress Technical Assistance § 30.111 When should the tribal governing body or school board request technical assistance? In order to...

  11. Neural cell adhesion molecule-deficient beta-cell tumorigenesis results in diminished extracellular matrix molecule expression and tumour cell-matrix adhesion.

    PubMed

    Håkansson, Joakim; Xian, Xiaojie; He, Liqun; Ståhlberg, Anders; Nelander, Sven; Samuelsson, Tore; Kubista, Mikael; Semb, Henrik

    2005-01-01

    To understand by which mechanism neural cell adhesion molecule (N-CAM) limits beta tumour cell disaggregation and dissemination, we searched for potential downstream genes of N-CAM during beta tumour cell progression by gene expression profiling. Here, we show that N-CAM-deficient beta-cell tumorigenesis is associated with changes in the expression of genes involved in cell-matrix adhesion and cytoskeletal dynamics, biological processes known to affect the invasive and metastatic behaviour of tumour cells. The extracellular matrix (ECM) molecules emerged as the primary target, i.e. N-CAM deficiency resulted in down-regulated mRNA expression of a broad range of ECM molecules. Consistent with this result, deficient deposition of major ECM stromal components, such as fibronectin, laminin 1 and collagen IV, was observed. Moreover, N-CAM-deficient tumour cells displayed defective matrix adhesion. These results offer a potential mechanism for tumour cell disaggregation during N-CAM-deficient beta tumour cell progression. Prospective consequences of these findings for the role of N-CAM in beta tumour cell dissemination are discussed.

  12. Data-driven high-throughput prediction of the 3-D structure of small molecules: review and progress. A response to the letter by the Cambridge Crystallographic Data Centre.

    PubMed

    Baldi, Pierre

    2011-12-27

    A response is presented to sentiments expressed in "Data-Driven High-Throughput Prediction of the 3-D Structure of Small Molecules: Review and Progress. A Response from The Cambridge Crystallographic Data Centre", recently published in the Journal of Chemical Information and Modeling, (1) which may give readers a misleading impression regarding significant impediments to scientific research posed by the CCDC.

  13. Molecular spintronics using single-molecule magnets

    NASA Astrophysics Data System (ADS)

    Bogani, Lapo; Wernsdorfer, Wolfgang

    2008-03-01

    A revolution in electronics is in view, with the contemporary evolution of the two novel disciplines of spintronics and molecular electronics. A fundamental link between these two fields can be established using molecular magnetic materials and, in particular, single-molecule magnets. Here, we review the first progress in the resulting field, molecular spintronics, which will enable the manipulation of spin and charges in electronic devices containing one or more molecules. We discuss the advantages over more conventional materials, and the potential applications in information storage and processing. We also outline current challenges in the field, and propose convenient schemes to overcome them.

  14. Toward Triplet Ground State NaLi Molecules

    NASA Astrophysics Data System (ADS)

    Ebadi, Sepehr; Jamison, Alan; Rvachov, Timur; Jing, Li; Son, Hyungmok; Jiang, Yijun; Zwierlein, Martin; Ketterle, Wolfgang

    2016-05-01

    The NaLi molecule is expected to have a long lifetime in the triplet ground-state due to its fermionic nature, large rotational constant, and weak spin-orbit coupling. The triplet state has both electric and magnetic dipole moments, affording unique opportunities in quantum simulation and ultracold chemistry. We have mapped the excited state NaLi triplet potential by means of photoassociation spectroscopy. We report on this and our further progress toward the creation of the triplet ground-state molecules using STIRAP. NSF, ARO-MURI, Samsung, NSERC.

  15. Black River Technical College, Exploring America's Communities. Progress Report.

    ERIC Educational Resources Information Center

    Black River Vocational-Technical School, Pocahontas, AR.

    In 1996, Arkansas's Black River Technical College (BRTC) participated in the American Association of Community Colleges' Exploring America's Communities project, which worked to strengthen the teaching and learning of American history, literature, and culture at U.S. community colleges. The proposed centerpiece of BRTC's program is called the…

  16. Nanodevices for Single Molecule Studies

    NASA Astrophysics Data System (ADS)

    Craighead, H. G.; Stavis, S. M.; Samiee, K. T.

    During the last two decades, biotechnology research has resulted in progress in fields as diverse as the life sciences, agriculture and healthcare. While existing technology enables the analysis of a variety of biological systems, new tools are needed for increasing the efficiency of current methods, and for developing new ones altogether. Interest has grown in single molecule analysis for these reasons.

  17. 32 CFR 203.17 - Technical assistance provider reporting requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Technical assistance provider reporting requirements. 203.17 Section 203.17 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY... technical assistance provider shall submit progress reports, financial status reports, materials prepared...

  18. 32 CFR 203.17 - Technical assistance provider reporting requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Technical assistance provider reporting requirements. 203.17 Section 203.17 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY... technical assistance provider shall submit progress reports, financial status reports, materials prepared...

  19. 32 CFR 203.17 - Technical assistance provider reporting requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Technical assistance provider reporting requirements. 203.17 Section 203.17 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY... technical assistance provider shall submit progress reports, financial status reports, materials prepared...

  20. 32 CFR 203.17 - Technical assistance provider reporting requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Technical assistance provider reporting requirements. 203.17 Section 203.17 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY... technical assistance provider shall submit progress reports, financial status reports, materials prepared...

  1. 32 CFR 203.17 - Technical assistance provider reporting requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Technical assistance provider reporting requirements. 203.17 Section 203.17 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY... technical assistance provider shall submit progress reports, financial status reports, materials prepared...

  2. Molecules on si: electronics with chemistry.

    PubMed

    Vilan, Ayelet; Yaffe, Omer; Biller, Ariel; Salomon, Adi; Kahn, Antoine; Cahen, David

    2010-01-12

    Basic scientific interest in using a semiconducting electrode in molecule-based electronics arises from the rich electrostatic landscape presented by semiconductor interfaces. Technological interest rests on the promise that combining existing semiconductor (primarily Si) electronics with (mostly organic) molecules will result in a whole that is larger than the sum of its parts. Such a hybrid approach appears presently particularly relevant for sensors and photovoltaics. Semiconductors, especially Si, present an important experimental test-bed for assessing electronic transport behavior of molecules, because they allow varying the critical interface energetics without, to a first approximation, altering the interfacial chemistry. To investigate semiconductor-molecule electronics we need reproducible, high-yield preparations of samples that allow reliable and reproducible data collection. Only in that way can we explore how the molecule/electrode interfaces affect or even dictate charge transport, which may then provide a basis for models with predictive power.To consider these issues and questions we will, in this Progress Report, review junctions based on direct bonding of molecules to oxide-free Si.describe the possible charge transport mechanisms across such interfaces and evaluate in how far they can be quantified.investigate to what extent imperfections in the monolayer are important for transport across the monolayer.revisit the concept of energy levels in such hybrid systems.

  3. Toward Small-Molecule Inhibition of Protein-Protein Interactions: General Aspects and Recent Progress in Targeting Costimulatory and Coinhibitory (Immune Checkpoint) Interactions.

    PubMed

    Bojadzic, Damir; Buchwald, Peter

    2018-05-30

    Protein-protein interactions (PPIs) that are part of the costimulatory and coinhibitory (immune checkpoint) signaling are critical for adequate T cell response and are important therapeutic targets for immunomodulation. Biologics targeting them have already achieved considerable clinical success in the treatment of autoimmune diseases or transplant recipients (e.g., abatacept, belatacept, and belimumab) as well as cancer (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab). In view of such progress, there have been only relatively limited efforts toward developing small-molecule PPI inhibitors (SMPPIIs) targeting these cosignaling interactions, possibly because they, as all other PPIs, are difficult to target by small molecules and were not considered druggable. Nevertheless, substantial progress has been achieved during the last decade. SMPPIIs proving the feasibility of such approaches have been identified through various strategies for a number of cosignaling interactions including CD40-CD40L, OX40-OX40L, BAFFR-BAFF, CD80-CD28, and PD-1-PD-L1s. Here, after an overview of the general aspects and challenges of SMPPII-focused drug discovery, we review them briefly together with relevant structural, immune-signaling, physicochemical, and medicinal chemistry aspects. While so far only a few of these SMPPIIs have shown activity in animal models (DRI-C21045 for CD40-D40L, KR33426 for BAFFR-BAFF) or reached clinical development (RhuDex for CD80-CD28, CA-170 for PD-1-PD-L1), there is proof-of-principle evidence for the feasibility of such approaches in immunomodulation. They can result in products that are easier to develop/manufacture and are less likely to be immunogenic or encounter postmarket safety events than corresponding biologics, and, contrary to them, can even become orally bioavailable. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Small molecule chemical probes of microRNA function.

    PubMed

    Velagapudi, Sai Pradeep; Vummidi, Balayeshwanth R; Disney, Matthew D

    2015-02-01

    MicroRNAs (miRNAs) are small, non-coding RNAs that control protein expression. Aberrant miRNA expression has been linked to various human diseases, and thus miRNAs have been explored as diagnostic markers and therapeutic targets. Although it is challenging to target RNA with small molecules in general, there have been successful campaigns that have identified small molecule modulators of miRNA function by targeting various pathways. For example, small molecules that modulate transcription and target nuclease processing sites in miRNA precursors have been identified. Herein, we describe challenges in developing chemical probes that target miRNAs and highlight aspects of miRNA cellular biology elucidated by using small molecule chemical probes. We expect that this area will expand dramatically in the near future as progress is made in understanding small molecule recognition of RNA. Copyright © 2014. Published by Elsevier Ltd.

  5. Controlling spin flips of molecules in an electromagnetic trap

    NASA Astrophysics Data System (ADS)

    Reens, David; Wu, Hao; Langen, Tim; Ye, Jun

    2017-12-01

    Doubly dipolar molecules exhibit complex internal spin dynamics when electric and magnetic fields are both applied. Near magnetic trap minima, these spin dynamics lead to enhancements in Majorana spin-flip transitions by many orders of magnitude relative to atoms and are thus an important obstacle for progress in molecule trapping and cooling. We conclusively demonstrate and address this with OH molecules in a trap geometry where spin-flip losses can be tuned from over 200 s-1 to below our 2 s-1 vacuum-limited loss rate with only a simple external bias coil and with minimal impact on trap depth and gradient.

  6. A small molecule polyamine oxidase inhibitor blocks androgen-induced oxidative stress and delays prostate cancer progression in the transgenic adenocarcinoma of the mouse prostate model.

    PubMed

    Basu, Hirak S; Thompson, Todd A; Church, Dawn R; Clower, Cynthia C; Mehraein-Ghomi, Farideh; Amlong, Corey A; Martin, Christopher T; Woster, Patrick M; Lindstrom, Mary J; Wilding, George

    2009-10-01

    High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiologic factor in prostate cancer (CaP) occurrence, recurrence, and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells, as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data show that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays CaP progression.

  7. Quarterly technical progress report, April-June 1982

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

    None

    1984-04-01

    Progress reports are presented for the following tasks: (1) preparation of low-rank coals; application of liquefaction processes to low-rank coals; (2) slagging fixed-bed gasification; (3) atmospheric fluidized-bed combustion of low-rank coal; (4) ash fouling and combustion modification for low-rank coal; (5) combined flue gas cleanup/simultaneous SO/sub x/-NO/sub x/ control; (6) particulate control and hydrocarbons and trace element emissions from low-rank coals; (7) waste characterization and disposal; and (9) exploratory research.

  8. Toward Generalization of Iterative Small Molecule Synthesis

    PubMed Central

    Lehmann, Jonathan W.; Blair, Daniel J.; Burke, Martin D.

    2018-01-01

    Small molecules have extensive untapped potential to benefit society, but access to this potential is too often restricted by limitations inherent to the customized approach currently used to synthesize this class of chemical matter. In contrast, the “building block approach”, i.e., generalized iterative assembly of interchangeable parts, has now proven to be a highly efficient and flexible way to construct things ranging all the way from skyscrapers to macromolecules to artificial intelligence algorithms. The structural redundancy found in many small molecules suggests that they possess a similar capacity for generalized building block-based construction. It is also encouraging that many customized iterative synthesis methods have been developed that improve access to specific classes of small molecules. There has also been substantial recent progress toward the iterative assembly of many different types of small molecules, including complex natural products, pharmaceuticals, biological probes, and materials, using common building blocks and coupling chemistry. Collectively, these advances suggest that a generalized building block approach for small molecule synthesis may be within reach. PMID:29696152

  9. Advanced coal conversion process demonstration. Technical progress report for the period July 1, 1995--September 30, 1995

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

    NONE

    1997-05-01

    This report describes the technical progress made on the Advanced Coal Conversion Process (ACCP) Demonstration Project from July 1, 1995 through September 30, 1995. The ACCP Demonstration Project is a US Department of Energy (DOE) Clean Coal Technology Project. This project demonstrates an advanced, thermal, coal upgrading process, coupled with physical cleaning techniques, that is designed to upgrade high-moisture, low-rank coals to a high-quality, low-sulfur fuel, registered as the SynCoal process. The coal is processed through three stages (two heating stages followed by an inert cooling stage) of vibrating fluidized bed reactors that remove chemically bound water, carboxyl groups, andmore » volatile sulfur compounds. After thermal upgrading, the cola is put through a deep-bed stratifier cleaning process to separate the pyrite-rich ash from the coal.« less

  10. Advances in magnetic tweezers for single molecule and cell biophysics.

    PubMed

    Kilinc, Devrim; Lee, Gil U

    2014-01-01

    Magnetic tweezers (MTW) enable highly accurate forces to be transduced to molecules to study mechanotransduction at the molecular or cellular level. We review recent MTW studies in single molecule and cell biophysics that demonstrate the flexibility of this technique. We also discuss technical advances in the method on several fronts, i.e., from novel approaches for the measurement of torque to multiplexed biophysical assays. Finally, we describe multi-component nanorods with enhanced optical and magnetic properties and discuss their potential as future MTW probes.

  11. Experimental demonstration of a single-molecule electric motor.

    PubMed

    Tierney, Heather L; Murphy, Colin J; Jewell, April D; Baber, Ashleigh E; Iski, Erin V; Khodaverdian, Harout Y; McGuire, Allister F; Klebanov, Nikolai; Sykes, E Charles H

    2011-09-04

    For molecules to be used as components in molecular machines, methods that couple individual molecules to external energy sources and that selectively excite motion in a given direction are required. Significant progress has been made in the construction of molecular motors powered by light and by chemical reactions, but electrically driven motors have not yet been built, despite several theoretical proposals for such motors. Here we report that a butyl methyl sulphide molecule adsorbed on a copper surface can be operated as a single-molecule electric motor. Electrons from a scanning tunnelling microscope are used to drive the directional motion of the molecule in a two-terminal setup. Moreover, the temperature and electron flux can be adjusted to allow each rotational event to be monitored at the molecular scale in real time. The direction and rate of the rotation are related to the chiralities of both the molecule and the tip of the microscope (which serves as the electrode), illustrating the importance of the symmetry of the metal contacts in atomic-scale electrical devices.

  12. Soluble Forms of Intercellular and Vascular Cell Adhesion Molecules Independently Predict Progression to Type 2 Diabetes in Mexican American Families

    PubMed Central

    Kulkarni, Hemant; Mamtani, Manju; Peralta, Juan; Almeida, Marcio; Dyer, Thomas D.; Goring, Harald H.; Johnson, Matthew P.; Duggirala, Ravindranath; Mahaney, Michael C.; Olvera, Rene L.; Almasy, Laura; Glahn, David C.; Williams-Blangero, Sarah; Curran, Joanne E.; Blangero, John

    2016-01-01

    Objective While the role of type 2 diabetes (T2D) in inducing endothelial dysfunction is fairly well-established the etiological role of endothelial dysfunction in the onset of T2D is still a matter of debate. In the light of conflicting evidence in this regard, we conducted a prospective study to determine the association of circulating levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vessel cell adhesion molecule 1 (sVCAM-1) with incident T2D. Methods Data from this study came from 1,269 Mexican Americans of whom 821 initially T2D-free individuals were longitudinally followed up in the San Antonio Family Heart Study. These individuals were followed for 9752.95 person-years for development of T2D. Prospective association of sICAM-1 and sVCAM-1 with incident T2D was studied using Kaplan-Meier survival plots and mixed effects Cox proportional hazards modeling to account for relatedness among study participants. Incremental value of adhesion molecule biomarkers was studied using integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indexes. Results Decreasing median values for serum concentrations of sICAM-1 and sVCAM-1 were observed in the following groups in this order: individuals with T2D at baseline, individuals who developed T2D during follow-up, individuals with prediabetes at baseline and normal glucose tolerant (NGT) individuals who remained T2D-free during follow-up. Top quartiles for sICAM-1 and sVCAM-1 were strongly and significantly associated with homeostatic model of assessment—insulin resistance (HOMA-IR). Mixed effects Cox proportional hazards modeling revealed that after correcting for important clinical confounders, high sICAM-1 and sVCAM-1 concentrations were associated with 2.52 and 1.99 times faster progression to T2D as compared to low concentrations, respectively. Individuals with high concentrations for both sICAM-1 and sVCAM-1 progressed to T2D 3.42 times faster than those with low

  13. 25 CFR 30.110 - What is the process for requesting technical assistance to develop an alternative definition of AYP?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., DEPARTMENT OF THE INTERIOR EDUCATION ADEQUATE YEARLY PROGRESS Defining Adequate Yearly Progress Technical Assistance § 30.110 What is the process for requesting technical assistance to develop an alternative... 25 Indians 1 2011-04-01 2011-04-01 false What is the process for requesting technical assistance...

  14. 25 CFR 30.110 - What is the process for requesting technical assistance to develop an alternative definition of AYP?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false What is the process for requesting technical assistance..., DEPARTMENT OF THE INTERIOR EDUCATION ADEQUATE YEARLY PROGRESS Defining Adequate Yearly Progress Technical Assistance § 30.110 What is the process for requesting technical assistance to develop an alternative...

  15. Technical Progress Report on Application and Development of Appropriate Tools and Technologies for Cost-Effective Carbon Sequestration

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

    Bill Stanley; Patrick Gonzalez; Sandra Brown

    2006-06-30

    The Nature Conservancy is participating in a Cooperative Agreement with the Department of Energy (DOE) National Energy Technology Laboratory (NETL) to explore the compatibility of carbon sequestration in terrestrial ecosystems and the conservation of biodiversity. The title of the research project is ''Application and Development of Appropriate Tools and Technologies for Cost-Effective Carbon Sequestration''. The objectives of the project are to: (1) improve carbon offset estimates produced in both the planning and implementation phases of projects; (2) build valid and standardized approaches to estimate project carbon benefits at a reasonable cost; and (3) lay the groundwork for implementing cost-effective projects,more » providing new testing ground for biodiversity protection and restoration projects that store additional atmospheric carbon. This Technical Progress Report discusses preliminary results of the six specific tasks that The Nature Conservancy is undertaking to answer research needs while facilitating the development of real projects with measurable greenhouse gas reductions. The research described in this report occurred between April 1st and July 30th 2006. The specific tasks discussed include: Task 1: carbon inventory advancements; Task 2: emerging technologies for remote sensing of terrestrial carbon; Task 3: baseline method development; Task 4: third-party technical advisory panel meetings; Task 5: new project feasibility studies; and Task 6: development of new project software screening tool. Work is being carried out in Brazil, Belize, Chile, Peru and the USA.« less

  16. Hybrid antibiotics - clinical progress and novel designs.

    PubMed

    Parkes, Alastair L; Yule, Ian A

    2016-07-01

    There is a growing need for new antibacterial agents, but success in development of antibiotics in recent years has been limited. This has led researchers to investigate novel approaches to finding compounds that are effective against multi-drug resistant bacteria, and that delay onset of resistance. One such strategy has been to link antibiotics to produce hybrids designed to overcome resistance mechanisms. The concept of dual-acting hybrid antibiotics was introduced and reviewed in this journal in 2010. In the present review the authors sought to discover how clinical candidates described had progressed, and to examine how the field has developed. In three sections the authors cover the clinical progress of hybrid antibiotics, novel agents produced from hybridisation of two or more small-molecule antibiotics, and novel agents produced from hybridisation of antibiotics with small-molecules that have complementary activity. Many key questions regarding dual-acting hybrid antibiotics remain to be answered, and the proposed benefits of this approach are yet to be demonstrated. While Cadazolid in particular continues to progress in the clinic, suggesting that there is promise in hybridisation through covalent linkage, it may be that properties other than antibacterial activity are key when choosing a partner molecule.

  17. Molecules as Drives and Witnesses of Star Formation

    NASA Astrophysics Data System (ADS)

    Shustov, B. M.

    2017-07-01

    The progress in understanding the role of molecules in star formation is discussed. After very brief introduction which we note in that no star formation would be possible without molecules at the dawn of the Universe and that molecules are important drivers and witnesses of star formation in the current epoch, we consider observational technologies and emphasize the prospective role of UV observations. Special attention is paid to possibilities of UV spectroscopy with coming space observatory Spektr-UF (World Space Observatory - Ultraviolet; WSO-UV). Only one example (observations of CO-dark clouds) from vast scientific program of the WSO-UV is mentioned. Also very briefly disclosed is a model approach to study complex evolution of very young (prestellar) object focusing on chemical (molecular) evolution.

  18. Ascorbic acid derivatives as a new class of antiproliferative molecules.

    PubMed

    Bordignon, Benoit; Chiron, Julien; Fontés, Michel

    2013-09-28

    Ascorbic acid (AA) has long been described as an antiproliferative agent. However, the molecule has to be used at a very high concentrations, which necessitates i.v. injection, and the tight regulation of in-blood and in-cell AA concentrations making it impossible to hold very high concentrations for any substantial length of time. Here we report evidence that AA derivates are antiproliferative and cytotoxic molecules at an IC50 lower than AA itself. Among these new molecules, we selected K873 that has cytotoxic and antiproliferative effects on different human tumor cells at tenth micromolar concentration. In a further step, we demonstrated that K873 selectively to kills only cancer cells without being toxic for normal non-dividing (or poorly dividing) cells. Finally, we tested the effect of treatment with K873 (5-10 mg/kg/d by i.p. route) on tumor progression in xenografted immunodeficient mice (BALB/c Nude). Our data suggest that K873 administration strongly inhibits tumor progression. In a previous study using microarrays, we demonstrated that AA decreases the expression of two genes families involved in cell cycle progression, i.e. initiation factor of translation and tRNA synthetases. Here we show that K873 treatment also decreases the expression of four of these genes in xenografted tumors, in proportions similar to that previously observed with AA. Taken together, our data suggest that AA and K873 share similar action. Our findings suggest that AA derivatives could be a promising new class of anti-cancer drugs, either alone or in combination with other molecules. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Bone Conduction Communication: Research Progress and Directions

    DTIC Science & Technology

    2017-08-16

    ARL-TR-8096 ● AUG 2017 US Army Research Laboratory Bone Conduction Communication: Research Progress and Directions by Maranda...this report when it is no longer needed. Do not return it to the originator. ARL-TR-8096 ● AUG 2017 US Army Research Laboratory...Bone Conduction Communication: Research Progress and Directions by Maranda McBride North Carolina Agricultural and Technical State University

  20. DNA-Based Single-Molecule Electronics: From Concept to Function.

    PubMed

    Wang, Kun

    2018-01-17

    Beyond being the repository of genetic information, DNA is playing an increasingly important role as a building block for molecular electronics. Its inherent structural and molecular recognition properties render it a leading candidate for molecular electronics applications. The structural stability, diversity and programmability of DNA provide overwhelming freedom for the design and fabrication of molecular-scale devices. In the past two decades DNA has therefore attracted inordinate amounts of attention in molecular electronics. This review gives a brief survey of recent experimental progress in DNA-based single-molecule electronics with special focus on single-molecule conductance and I-V characteristics of individual DNA molecules. Existing challenges and exciting future opportunities are also discussed.

  1. DNA-Based Single-Molecule Electronics: From Concept to Function

    PubMed Central

    2018-01-01

    Beyond being the repository of genetic information, DNA is playing an increasingly important role as a building block for molecular electronics. Its inherent structural and molecular recognition properties render it a leading candidate for molecular electronics applications. The structural stability, diversity and programmability of DNA provide overwhelming freedom for the design and fabrication of molecular-scale devices. In the past two decades DNA has therefore attracted inordinate amounts of attention in molecular electronics. This review gives a brief survey of recent experimental progress in DNA-based single-molecule electronics with special focus on single-molecule conductance and I–V characteristics of individual DNA molecules. Existing challenges and exciting future opportunities are also discussed. PMID:29342091

  2. Enhanced oil recovery utilizing high-angle wells in the Frontier Formation, Badger Basin Field, Park County, Wyoming. Quarterly technical progress report, 1 March 1993--30 June 1993

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

    Fortmann, R.G.; Walker, J.P.

    1993-07-10

    Sierra Energy Company`s targeted goals during the third quarter of this Cooperative Agreement included the following objectives from the Statement of Work: in Phase 2A, completion of subtask 2.1.2--acquire best possible field data in the 3-D seismic program; and initiation of Subtask 2.1.3--process acquired 3-D seismic data. Technical progress is described for these tasks.

  3. 20 CFR 411.180 - What is timely progress toward self-supporting employment?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... certificate or vocational or technical training that will enhance your ability to return to work. In addition...-secondary education requirement or vocational or technical training requirement in the applicable progress... this 12-month period; or (iv) You must have been enrolled in a vocational or technical training program...

  4. Cell Adhesion Molecules and Ubiquitination—Functions and Significance

    PubMed Central

    Homrich, Mirka; Gotthard, Ingo; Wobst, Hilke; Diestel, Simone

    2015-01-01

    Cell adhesion molecules of the immunoglobulin (Ig) superfamily represent the biggest group of cell adhesion molecules. They have been analyzed since approximately 40 years ago and most of them have been shown to play a role in tumor progression and in the nervous system. All members of the Ig superfamily are intensively posttranslationally modified. However, many aspects of their cellular functions are not yet known. Since a few years ago it is known that some of the Ig superfamily members are modified by ubiquitin. Ubiquitination has classically been described as a proteasomal degradation signal but during the last years it became obvious that it can regulate many other processes including internalization of cell surface molecules and lysosomal sorting. The purpose of this review is to summarize the current knowledge about the ubiquitination of cell adhesion molecules of the Ig superfamily and to discuss its potential physiological roles in tumorigenesis and in the nervous system. PMID:26703751

  5. Developments in Technical Education in the British Caribbean, 1940-60.

    ERIC Educational Resources Information Center

    Pemberton, S. Macpherson

    The paper discusses developments in technical education in the British West Indies from 1940-1960 emphasizing the relation between education and economic development. The objective is to analyze the economic basis of progress in technical education. The document is presented in four chapters. Chapter I summarizes historical background prior to…

  6. Self-Assembly of Optical Molecules with Supramolecular Concepts

    PubMed Central

    Okamoto, Ken; Chithra, Parayalil; Richards, Gary J.; Hill, Jonathan P.; Ariga, Katsuhiko

    2009-01-01

    Fabrication of nano-sized objects is one of the most important issues in nanoscience and nanotechnology. Soft nanomaterials with flexible properties have been given much attention and can be obtained through bottom-up processing from functional molecules, where self-assembly based on supramolecular chemistry and designed assembly have become crucial processes and techniques. Among the various functional molecules, dyes have become important materials in certain areas of nanotechnology and their self-assembling behaviors have been actively researched. In this short review, we briefly introduce recent progress in self-assembly of optical molecules and dyes, based mainly on supramolecular concepts. The introduced examples are classified into four categories: self-assembly of (i) low-molecular-weight dyes and (ii) polymeric dyes and dye self-assembly (iii) in nanoscale architectures and (iv) at surfaces. PMID:19564931

  7. Programs of Study: Year 2 Joint Technical Report. Research Snapshot

    ERIC Educational Resources Information Center

    National Research Center for Career and Technical Education, 2010

    2010-01-01

    In January 2010, the National Research Center for Career and Technical Education (NRCCTE) issued a progress report on three studies being conducted by the Center that examine the implementation and outcomes of Programs of Study (POS), which were required in the 2006 reauthorization of the federal legislation for career and technical education…

  8. The Submillimeter-wave Rotational Spectra of Interstellar Molecules

    NASA Technical Reports Server (NTRS)

    Herbst, Eric; DeLucia, Frank C.; Butler, R. A. H.; Winnewisser, M.; Winnewisser, G.; Fuchs, U.; Groner, P.; Sastry, K. V. L. N.

    2002-01-01

    We discuss past and recent progress in our long-term laboratory program concerning the submillimeter-wave rotational spectroscopy of known and likely interstellar molecules, especially those associated with regions of high-mass star formation. Our program on the use of spectroscopy to study rotationally inelastic collisions of interstellar interest is also briefly mentioned.

  9. Kinematic cooling of molecules in a magneto-optical trap

    NASA Astrophysics Data System (ADS)

    Takase, Ken; Chandler, David W.; Strecker, Kevin E.

    2008-05-01

    We will present our current progress on a new experimental technique aimed at slowing and cooling hot molecules using a single collision with magneto-optically trapped atoms. Kinematic cooling, unlike buffer gas and sympathetic cooling, relies only on a single collision between the molecule and atom to stop the molecule in the laboratory frame. This technique has recently been demonstrated in a crossed atomic and molecular beam machine to produce 35mK samples of nitric oxide via a single collision with argon [1]. In this technique we replace the atomic beam with a sample magneto-optically trapped atoms. We are currently designing and building a new apparatus to attempt these experiments. [1] Kevin E. Strecker and David W. Chandler (to be published)

  10. A-D-A small molecules for solution-processed organic photovoltaic cells.

    PubMed

    Ni, Wang; Wan, Xiangjian; Li, Miaomiao; Wang, Yunchuang; Chen, Yongsheng

    2015-03-25

    A-D-A small molecules have drawn more and more attention in solution-processed organic solar cells due to the advantages of a diversity of structures, easy control of energy levels, etc. Recently, a power conversion efficiency of nearly 10% has been achieved through careful material design and device optimization. This feature article reviews recent representative progress in the design and application of A-D-A small molecules in organic photovoltaic cells.

  11. 7 CFR 3402.23 - Documentation of progress on funded projects.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

  12. 7 CFR 3402.23 - Documentation of progress on funded projects.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

  13. 7 CFR 3402.23 - Documentation of progress on funded projects.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

  14. 7 CFR 3402.23 - Documentation of progress on funded projects.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

  15. The Molecular Industrial Revolution: Automated Synthesis of Small Molecules.

    PubMed

    Trobe, Melanie; Burke, Martin D

    2018-04-09

    Today we are poised for a transition from the highly customized crafting of specific molecular targets by hand to the increasingly general and automated assembly of different types of molecules with the push of a button. Creating machines that are capable of making many different types of small molecules on demand, akin to that which has been achieved on the macroscale with 3D printers, is challenging. Yet important progress is being made toward this objective with two complementary approaches: 1) Automation of customized synthesis routes to different targets by machines that enable the use of many reactions and starting materials, and 2) automation of generalized platforms that make many different targets using common coupling chemistry and building blocks. Continued progress in these directions has the potential to shift the bottleneck in molecular innovation from synthesis to imagination, and thereby help drive a new industrial revolution on the molecular scale. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Site-Selection in Single-Molecule Junction for Highly Reproducible Molecular Electronics.

    PubMed

    Kaneko, Satoshi; Murai, Daigo; Marqués-González, Santiago; Nakamura, Hisao; Komoto, Yuki; Fujii, Shintaro; Nishino, Tomoaki; Ikeda, Katsuyoshi; Tsukagoshi, Kazuhito; Kiguchi, Manabu

    2016-02-03

    Adsorption sites of molecules critically determine the electric/photonic properties and the stability of heterogeneous molecule-metal interfaces. Then, selectivity of adsorption site is essential for development of the fields including organic electronics, catalysis, and biology. However, due to current technical limitations, site-selectivity, i.e., precise determination of the molecular adsorption site, remains a major challenge because of difficulty in precise selection of meaningful one among the sites. We have succeeded the single site-selection at a single-molecule junction by performing newly developed hybrid technique: simultaneous characterization of surface enhanced Raman scattering (SERS) and current-voltage (I-V) measurements. The I-V response of 1,4-benzenedithiol junctions reveals the existence of three metastable states arising from different adsorption sites. Notably, correlated SERS measurements show selectivity toward one of the adsorption sites: "bridge sites". This site-selectivity represents an essential step toward the reliable integration of individual molecules on metallic surfaces. Furthermore, the hybrid spectro-electric technique reveals the dependence of the SERS intensity on the strength of the molecule-metal interaction, showing the interdependence between the optical and electronic properties in single-molecule junctions.

  17. Supramolecular Systems and Chemical Reactions in Single-Molecule Break Junctions.

    PubMed

    Li, Xiaohui; Hu, Duan; Tan, Zhibing; Bai, Jie; Xiao, Zongyuan; Yang, Yang; Shi, Jia; Hong, Wenjing

    2017-04-01

    The major challenges of molecular electronics are the understanding and manipulation of the electron transport through the single-molecule junction. With the single-molecule break junction techniques, including scanning tunneling microscope break junction technique and mechanically controllable break junction technique, the charge transport through various single-molecule and supramolecular junctions has been studied during the dynamic fabrication and continuous characterization of molecular junctions. This review starts from the charge transport characterization of supramolecular junctions through a variety of noncovalent interactions, such as hydrogen bond, π-π interaction, and electrostatic force. We further review the recent progress in constructing highly conductive molecular junctions via chemical reactions, the response of molecular junctions to external stimuli, as well as the application of break junction techniques in controlling and monitoring chemical reactions in situ. We suggest that beyond the measurement of single molecular conductance, the single-molecule break junction techniques provide a promising access to study molecular assembly and chemical reactions at the single-molecule scale.

  18. Data-Driven High-Throughput Prediction of the 3D Structure of Small Molecules: Review and Progress

    PubMed Central

    Andronico, Alessio; Randall, Arlo; Benz, Ryan W.; Baldi, Pierre

    2011-01-01

    Accurate prediction of the 3D structure of small molecules is essential in order to understand their physical, chemical, and biological properties including how they interact with other molecules. Here we survey the field of high-throughput methods for 3D structure prediction and set up new target specifications for the next generation of methods. We then introduce COSMOS, a novel data-driven prediction method that utilizes libraries of fragment and torsion angle parameters. We illustrate COSMOS using parameters extracted from the Cambridge Structural Database (CSD) by analyzing their distribution and then evaluating the system’s performance in terms of speed, coverage, and accuracy. Results show that COSMOS represents a significant improvement when compared to the state-of-the-art, particularly in terms of coverage of complex molecular structures, including metal-organics. COSMOS can predict structures for 96.4% of the molecules in the CSD [99.6% organic, 94.6% metal-organic] whereas the widely used commercial method CORINA predicts structures for 68.5% [98.5% organic, 51.6% metal-organic]. On the common subset of molecules predicted by both methods COSMOS makes predictions with an average speed per molecule of 0.15s [0.10s organic, 0.21s metal-organic], and an average RMSD of 1.57Å [1.26Å organic, 1.90Å metal-organic], and CORINA makes predictions with an average speed per molecule of 0.13s [0.18s organic, 0.08s metal-organic], and an average RMSD of 1.60Å [1.13Å organic, 2.11Å metal-organic]. COSMOS is available through the ChemDB chemoinformatics web portal at: http://cdb.ics.uci.edu/. PMID:21417267

  19. An epigenetic signature of adhesion molecules predicts poor prognosis of ovarian cancer patients

    PubMed Central

    Chang, Ping-Ying; Liao, Yu-Ping; Wang, Hui-Chen; Chen, Yu-Chih; Huang, Rui-Lan; Wang, Yu-Chi; Yuan, Chiou-Chung; Lai, Hung-Cheng

    2017-01-01

    DNA methylation is a promising biomarker for cancer. The epigenetic effects of cell adhesion molecules may affect the therapeutic outcome and the present study examined their effects on survival in ovarian cancer. We integrated methylomics and genomics datasets in The Cancer Genome Atlas (n = 391) and identified 106 highly methylated adhesion-related genes in ovarian cancer tissues. Univariate analysis revealed the methylation status of eight genes related to progression-free survival. In multivariate Cox regression analysis, four highly methylated genes (CD97, CTNNA1, DLC1, HAPLN2) and three genes (LAMA4, LPP, MFAP4) with low methylation were significantly associated with poor progression-free survival. Low methylation of VTN was an independent poor prognostic factor for overall survival after adjustment for age and stage. Patients who carried any two of CTNNA1, DLC1 or MFAP4 were significantly associated with poor progression-free survival (hazard ratio: 1.59; 95% confidence interval: 1.23, 2.05). This prognostic methylation signature was validated in a methylomics dataset generated in our lab (n = 37, hazard ratio: 16.64; 95% confidence interval: 2.68, 103.14) and in another from the Australian Ovarian Cancer Study (n = 91, hazard ratio: 2.43; 95% confidence interval: 1.11, 5.36). Epigenetics of cell adhesion molecules is related to ovarian cancer prognosis. A more comprehensive methylomics of cell adhesion molecules is needed and may advance personalized treatment with adhesion molecule-related drugs. PMID:28881822

  20. From single-molecule spectroscopy to super-resolution imaging of the neuron: a review

    PubMed Central

    Laine, Romain F; Kaminski Schierle, Gabriele S; van de Linde, Sebastian; Kaminski, Clemens F

    2016-01-01

    Abstract For more than 20 years, single-molecule spectroscopy has been providing invaluable insights into nature at the molecular level. The field has received a powerful boost with the development of the technique into super-resolution imaging methods, ca. 10 years ago, which overcome the limitations imposed by optical diffraction. Today, single molecule super-resolution imaging is routinely used in the study of macromolecular function and structure in the cell. Concomitantly, computational methods have been developed that provide information on numbers and positions of molecules at the nanometer-scale. In this overview, we outline the technical developments that have led to the emergence of localization microscopy techniques from single-molecule spectroscopy. We then provide a comprehensive review on the application of the technique in the field of neuroscience research. PMID:28809165

  1. Professional technical standards in colleges and schools of pharmacy.

    PubMed

    Berry, Tricia M; Chichester, Clinton O; Lundquist, Lisa M; Sanoski, Cynthia A; Woodward, Donald A; Worley, Marcia M; Early, Johnnie L

    2011-04-11

    To determine the prevalence, characteristics, and use of professional technical standards among colleges and schools of pharmacy accredited by the Accreditation Council for Pharmacy Education (ACPE). The Web site of every college and school of pharmacy accredited by ACPE was searched to identify information regarding the availability, content, and use of technical standards and to obtain demographic information. Information was obtained from all of the 114 colleges and schools of pharmacy and 67 (59%) had technical standards in place. Common themes for technical standards were: observation; communication; motor; intellectual, conceptual, integrative and quantitative abilities; and behavioral and social attributes. Of those colleges and schools with technical standards, 61 (91%) had standards that addressed all 5 of these themes and 34 (51%) specified that the technical standards were used in their admission, progression, and graduation procedures. More than half of the colleges and schools of pharmacy examined in this study have technical standards; however, 41% have yet to develop and implement them. Colleges and schools of pharmacy looking for guidance in technical standards development could use the technical standards themes identified in this study.

  2. Molecular targets for small-molecule modulators of circadian clocks

    PubMed Central

    He, Baokun; Chen, Zheng

    2016-01-01

    Background Circadian clocks are endogenous timing systems that regulate various aspects of mammalian metabolism, physiology and behavior. Traditional chronotherapy refers to the administration of drugs in a defined circadian time window to achieve optimal pharmacokinetic and therapeutic efficacies. In recent years, substantial efforts have been dedicated to developing novel small-molecule modulators of circadian clocks. Methods Here, we review the recent progress in the identification of molecular targets of small-molecule clock modulators and their efficacies in clock-related disorders. Specifically, we examine the clock components and regulatory factors as possible molecular targets of small molecules, and we review several key clock-related disorders as promising venues for testing the preventive/therapeutic efficacies of these small molecules. Finally, we also discuss circadian regulation of drug metabolism. Results Small molecules can modulate the period, phase and/or amplitude of the circadian cycle. Core clock proteins, nuclear hormone receptors, and clock-related kinases and other epigenetic regulators are promising molecular targets for small molecules. Through these targets small molecules exert protective effects against clock-related disorders including the metabolic syndrome, immune disorders, sleep disorders and cancer. Small molecules can also modulate circadian drug metabolism and response to existing therapeutics. Conclusion Small-molecule clock modulators target clock components or diverse cellular pathways that functionally impinge upon the clock. Target identification of new small-molecule modulators will deepen our understanding of key regulatory nodes in the circadian network. Studies of clock modulators will facilitate their therapeutic applications, alone or in combination, for clock-related diseases. PMID:26750111

  3. Single Molecule and Collective Dynamics of Motor Protein Coupled with Mechano-Sensitive Chemical Reaction

    NASA Astrophysics Data System (ADS)

    Iwaki, Mitsuhiro; Marcucci, Lorenzo; Togashi, Yuichi; Yanagida, Toshio

    2013-12-01

    Motor proteins such as myosin and kinesin hydrolyze ATP into ADP and Pi to convert chemical energy into mechanical work. This resultsin various motile processes like muscle contraction, vesicle transport and cell division. Recent single molecule experiments have revealed that external load applied to these motor proteins perturb not only the mechanical motion, but the ATP hydrolysis cycle as well, making these molecules mechano-enzymes. Here, we describe our single molecule detection techniques to reveal the mechano-enzymatic properties of myosin and introduce recent progress from both experimental and theoretical approaches at the single- and multiple-molecule level.

  4. Progress in overcoming the chain association issue in bispecific heterodimeric IgG antibodies

    PubMed Central

    Klein, Christian; Sustmann, Claudio; Thomas, Markus; Stubenrauch, Kay; Croasdale, Rebecca; Schanzer, Jürgen; Brinkmann, Ulrich; Kettenberger, Hubert; Regula, Jörg T.; Schaefer, Wolfgang

    2012-01-01

    The development of bispecific antibodies has attracted substantial interest, and many different formats have been described. Those specifically containing an Fc part are mostly tetravalent, such as stabilized IgG-scFv fusions or dual-variable domain (DVD) IgGs. However, although they exhibit IgG-like properties and technical developability, these formats differ in size and geometry from classical IgG antibodies. Thus, considerable efforts focus on bispecific heterodimeric IgG antibodies that more closely mimic natural IgG molecules. The inherent chain association problem encountered when producing bispecific heterodimeric IgG antibodies can be overcome by several methods. While technologies like knobs-into-holes (KiH) combined with a common light chain or the CrossMab technology enforce the correct chain association, other approaches, e.g., the dual-acting Fab (DAF) IgGs, do not rely on a heterodimeric Fc part. This review discusses the state of the art in bispecific heterodimeric IgG antibodies, with an emphasis on recent progress. PMID:22925968

  5. Microsecond Resolution of Single-Molecule Rotation Catalyzed by Molecular Motors

    PubMed Central

    Hornung, Tassilo; Martin, James; Spetzler, David; Ishmukhametov, Robert; Frasch, Wayne D.

    2017-01-01

    Single-molecule measurements of rotation catalyzed by the F1-ATPase or the FoF1 ATP synthase have provided new insights into the molecular mechanisms of the F1 and Fo molecular motors. We recently developed a method to record ATPase-driven rotation of F1 or FoF1 in a manner that solves several technical limitations of earlier approaches that were significantly hampered by time and angular resolution, and restricted the duration of data collection. With our approach it is possible to collect data for hours and obtain statistically significant quantities of data on each molecule examined with a time resolution of up to 5 μs at unprecedented signal-to-noise. PMID:21809213

  6. N-acteyl-ß-D-glucosaminidase and kidney injury molecule-1: New predictors for long-term progression of chronic kidney disease in patients with heart failure.

    PubMed

    Jungbauer, Carsten G; Uecer, Ekrem; Stadler, Stefan; Birner, Christoph; Buchner, Stefan; Maier, Lars S; Luchner, Andreas

    2016-06-01

    Patients with chronic heart failure (CHF) are often characterized by the cardiorenal syndrome (CRS). The aim of the present study was to assess whether novel markers of kidney injury are able to predict progression of chronic kidney disease (CKD) in patients with CHF. New renal biomarkers, N-acteyl-ß-D-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1) and Neutrophil Gelatinase-Associated Lipocalin (NGAL), were assessed from urine samples of 149 patients with chronic heart failure. During a 5-year-follow-up, renal function was assessed by creatinine and estimated glomerular filtration rate (eGFR CKD EPI) and was available for 138 patients. Further, data regarding all-cause mortality was obtained. Twenty-six patients (18.8%) developed a progression of CKD during the follow-up period, as defined by decline in eGFR category accompanied by a ≥25% drop in eGFR form baseline. No difference regarding age, sex, body mass index, hypertension, diabetes or EF was present between patients with and without CKD progression (each P = n.s.). At baseline, creatinine concentrations and eGFR were significantly different between both groups (sCr: 1.50 ± 0.67 vs 1.04 ± 0.37, P = < 0.001; eGFR: 47.8 ± 12.3 vs. 77.3 ± 23.5 mL/min per 1.73m(2) , each P < 0.001). In a Kaplan-Meier-analysis, KIM-1 and NAG were significant predictors for CKD progression (both P < 0.05). In Cox regression analysis, NAG > median (OR 3.25,P = 0.013), initial eGFR (OR 0.94, P < 0.001) and diuretic use (OR 3.92, P = 0.001) were independent predictors of CKD progression. Further, KIM-1 and NAG were also independent predictors of a combined endpoint of CKD progression and all-cause mortality by Cox regression analysis (each P < 0.05). The combination of both markers showed additive value regarding both endpoints. NGAL showed no association with CKD progression. During long-term follow-up chronic heart failure patients with CKD show a relevant disease progression. The

  7. Toll-Like Receptor and Accessory Molecule mRNA Expression in Humans and Mice as Well as in Murine Autoimmunity, Transient Inflammation, and Progressive Fibrosis

    PubMed Central

    Ramaiah, Santhosh Kumar Vankayala; Günthner, Roman; Lech, Maciej; Anders, Hans-Joachim

    2013-01-01

    The cell type-, organ-, and species-specific expression of the Toll-like receptors (TLRs) are well described, but little is known about the respective expression profiles of their accessory molecules. We therefore determined the mRNA expression levels of LBP, MD2, CD36, CD14, granulin, HMGB1, LL37, GRP94, UNC93b1, TRIL, PRAT4A, AP3B1, AEP and the respective TLRs in human and mouse solid organs. Humans and mice displayed significant differences between their respective mRNA expression patterns of these factors. In addition, the expression profiles in transient tissue inflammation upon renal ischemia-reperfusion injury, in spleens and kidneys from mice with lupus-like systemic autoimmunity, and in progressive tissue fibrosis upon unilateral ureteral obstruction were studied. Several TLR co-factors were specifically regulated during the different phases of these disease entities, suggesting a functional involvement in the disease process. Thus, the organ- and species-specific expression patterns need to be considered in the design and interpretation of studies related to TLR-mediated innate immunity, which seems to be involved in the tissue injury phase, in the phase of tissue regeneration, and in progressive tissue remodelling. PMID:23803655

  8. Olfactory perception of chemically diverse molecules.

    PubMed

    Keller, Andreas; Vosshall, Leslie B

    2016-08-08

    Understanding the relationship between a stimulus and how it is perceived reveals fundamental principles about the mechanisms of sensory perception. While this stimulus-percept problem is mostly understood for color vision and tone perception, it is not currently possible to predict how a given molecule smells. While there has been some progress in predicting the pleasantness and intensity of an odorant, perceptual data for a larger number of diverse molecules are needed to improve current predictions. Towards this goal, we tested the olfactory perception of 480 structurally and perceptually diverse molecules at two concentrations using a panel of 55 healthy human subjects. For each stimulus, we collected data on perceived intensity, pleasantness, and familiarity. In addition, subjects were asked to apply 20 semantic odor quality descriptors to these stimuli, and were offered the option to describe the smell in their own words. Using this dataset, we replicated several previous correlations between molecular features of the stimulus and olfactory perception. The number of sulfur atoms in a molecule was correlated with the odor quality descriptors "garlic," "fish," and "decayed," and large and structurally complex molecules were perceived to be more pleasant. We discovered a number of correlations in intensity perception between molecules. We show that familiarity had a strong effect on the ability of subjects to describe a smell. Many subjects used commercial products to describe familiar odorants, highlighting the role of prior experience in verbal reports of olfactory perception. Nonspecific descriptors like "chemical" were applied frequently to unfamiliar odorants, and unfamiliar odorants were generally rated as neither pleasant nor unpleasant. We present a very large psychophysical dataset and use this to correlate molecular features of a stimulus to olfactory percept. Our work reveals robust correlations between molecular features and perceptual qualities, and

  9. Meeting report: SMART timing--principles of single molecule techniques course at the University of Michigan 2014.

    PubMed

    Bartke, Rebecca M; Cameron, Elizabeth L; Cristie-David, Ajitha S; Custer, Thomas C; Denies, Maxwell S; Daher, May; Dhakal, Soma; Ghosh, Soumi; Heinicke, Laurie A; Hoff, J Damon; Hou, Qian; Kahlscheuer, Matthew L; Karslake, Joshua; Krieger, Adam G; Li, Jieming; Li, Xiang; Lund, Paul E; Vo, Nguyen N; Park, Jun; Pitchiaya, Sethuramasundaram; Rai, Victoria; Smith, David J; Suddala, Krishna C; Wang, Jiarui; Widom, Julia R; Walter, Nils G

    2015-05-01

    Four days after the announcement of the 2014 Nobel Prize in Chemistry for "the development of super-resolved fluorescence microscopy" based on single molecule detection, the Single Molecule Analysis in Real-Time (SMART) Center at the University of Michigan hosted a "Principles of Single Molecule Techniques 2014" course. Through a combination of plenary lectures and an Open House at the SMART Center, the course took a snapshot of a technology with an especially broad and rapidly expanding range of applications in the biomedical and materials sciences. Highlighting the continued rapid emergence of technical and scientific advances, the course underscored just how brightly the future of the single molecule field shines. © 2014 Wiley Periodicals, Inc.

  10. A small molecule inhibitor of NFκB blocks ER stress and the NLRP3 inflammasome and prevents progression of pancreatitis.

    PubMed

    Kanak, Mazhar A; Shahbazov, Rauf; Yoshimatsu, Gumpei; Levy, Marlon F; Lawrence, Michael C; Naziruddin, Bashoo

    2017-03-01

    The underlying molecular mechanism that leads to development of chronic pancreatitis remains elusive. The aim of this study is to understand the downstream inflammatory signaling involved in progression of chronic pancreatitis, and to use withaferin A (WA), a small molecule inhibitor of nuclear factor κB (NFκB), to prevent progression of chronic pancreatitis. Two different protocols were used to induce pancreatitis in mice: standard and stringent administration of cerulein. The severity of pancreatitis was assessed by means of pancreatic histology and serum amylase levels. Immunohistochemistry and flow-cytometric analysis was performed to visualize immune cell infiltration into the pancreas. Real-time PCR and Western blot were used to analyze the downstream signaling mechanism involved in the development of chronic pancreatitis. The severity of cerulein-induced pancreatitis was reduced significantly by WA, used as either preventive or curative treatment. Immune cell infiltration into the pancreas and acinar cell death were efficiently reduced by WA treatment. Expression of proinflammatory and proapoptotic genes regulated by NFκB activation was increased by cerulein treatment, and WA suppressed these genes significantly. Sustained endoplasmic reticulum stress activation by cerulein administration was reduced. NLRP3 inflammasome activation in cerulein-induced pancreatitis was identified, and this was also potently blocked by WA. The human pancreatitis tissue gene signature correlated with the mouse model. Our data provide evidence for the role of NFκB in the pathogenesis of chronic pancreatitis, and strongly suggest that WA could be used as a potential therapeutic drug to alleviate some forms of chronic pancreatitis.

  11. Solar hot water space heating system. Technical progress report

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

    Van Dam, T

    1979-08-13

    A retrofit solar heating system was installed on Madison Hall at Jordan College, Cedar Springs, Michigan. The system provides heating and domestic water preheating for a campus dormitory. Freeze protection is provided by a draindown system. The building and solar system, construction progress, and design changes are described. Included in appendices are: condensate trap design, structural analysis, pictures of installation, operating instructions, maintenance instructions, and as-built drawings. (MHR)

  12. The Molecular Industrial Revolution: Automated Synthesis of Small Molecules

    PubMed Central

    Trobe, Melanie; Burke, Martin D.

    2018-01-01

    The eighteenth and nineteenth centuries marked a sweeping transition from manual to automated manufacturing on the macroscopic scale. This enabled an unmatched period of human innovation that helped drive the Industrial Revolution. The impact on society was transformative, ultimately yielding substantial improvements in living conditions and lifespan in many parts of the world. During the same time period, the first manual syntheses of organic molecules was achieved. Now, two centuries later, we are poised for an analogous transition from highly customized crafting of specific molecular targets by hand to the increasingly general and automated assembly of many different types of molecules with the push of a button. Automation of customized small molecule synthesis pathways is already enabling safer, more reproducible, and readily scalable production of specific targets, and general machines now exist for the synthesis of a wide range of different peptides, oligonucleotides, and oligosaccharides. Creating general machines that are similarly capable of making many different types of small molecules on-demand, akin to that which has been achieved on the macroscopic scale with 3D printers, has proven to be substantially more challenging. Yet important progress is being made toward this potentially transformative objective with two complementary approaches: (1) automation of customized synthesis routes to different targets via machines that enable use of many different reactions and starting materials, and (2) automation of generalized platforms that make many different targets using common coupling chemistry and building blocks. Continued progress in these exciting directions has the potential to shift the bottleneck in molecular innovation from synthesis to imagination, and thereby help drive a new industrial revolution on the molecular scale. PMID:29513400

  13. Mechanically adjustable single-molecule transistors and stencil mask nanofabrication of high-resolution scanning probes

    NASA Astrophysics Data System (ADS)

    Champagne, Alexandre

    This dissertation presents the development of two original experimental techniques to probe nanoscale objects. The first one studies electronic transport in single organic molecule transistors in which the source-drain electrode spacing is mechanically adjustable. The second involves the fabrication of high-resolution scanning probe microscopy sensors using a stencil mask lithography technique. We describe the fabrication of transistors in which a single organic molecule can be incorporated. The source and drain leads of these transistors are freely suspended above a flexible substrate, and their spacing can be adjusted by bending the substrate. We detail the technology developed to carry out measurements on these samples. We study electronic transport in single C60 molecules at low temperature. We observe Coulomb blockaded transport and can resolve the discrete energy spectrum of the molecule. We are able to mechanically tune the spacing between the electrodes (over a range of 5 A) to modulate the lead-molecule coupling, and can electrostatically tune the energy levels on the molecule by up to 160 meV using a gate electrode. Initial progress in studying different transport regimes in other molecules is also discussed. We present a lithographic process that allows the deposition of metal nanostructures with a resolution down to 10 nm directly onto atomic force microscope (AFM) tips. We show that multiple layers of lithography can be deposited and aligned. We fabricate high-resolution magnetic force microscopy (MFM) probes using this method and discuss progress to fabricate other scanning probe microscopy (SPM) sensors.

  14. Professional Technical Standards in Colleges and Schools of Pharmacy

    PubMed Central

    Berry, Tricia M.; Chichester, Clinton O.; Sanoski, Cynthia A.; Woodward, Donald A.; Worley, Marcia M.; Early, Johnnie L.

    2011-01-01

    Objective To determine the prevalence, characteristics, and use of professional technical standards among colleges and schools of pharmacy accredited by the Accreditation Council for Pharmacy Education (ACPE). Methods The Web site of every college and school of pharmacy accredited by ACPE was searched to identify information regarding the availability, content, and use of technical standards and to obtain demographic information. Results Information was obtained from all of the 114 colleges and schools of pharmacy and 67 (59%) had technical standards in place. Common themes for technical standards were: observation; communication; motor; intellectual, conceptual, integrative and quantitative abilities; and behavioral and social attributes. Of those colleges and schools with technical standards, 61 (91%) had standards that addressed all 5 of these themes and 34 (51%) specified that the technical standards were used in their admission, progression, and graduation procedures. Conclusion More than half of the colleges and schools of pharmacy examined in this study have technical standards; however, 41% have yet to develop and implement them. Colleges and schools of pharmacy looking for guidance in technical standards development could use the technical standards themes identified in this study. PMID:21655404

  15. Xenon Feed System Progress

    DTIC Science & Technology

    2006-01-01

    From - To) 13-06-2006 Technical Paper 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER F04611-00-C-0055 Xenon Feed System Progress (Preprint) 5b. GRANT...propulsion xenon feed system for a flight technology demonstration program. Major accomplishments include: 1) Utilization of the Moog...successfully fed xenon to a 200 watt Hall Effect Thruster in a Technology Demonstration Program. The feed system has demonstrated throttling of xenon

  16. A Liquid Array Platform For the Multiplexed Analysis of Synthetic Molecule-Protein Interactions

    PubMed Central

    Doran, Todd M.; Kodadek, Thomas

    2014-01-01

    Synthetic molecule microarrays, consisting of many different compounds spotted onto a planar surface such as modified glass or cellulose, have proven to be useful tools for the multiplexed analysis of small molecule- and peptide-protein interactions. However, these arrays are technically difficult to manufacture and use with high reproducibility and require specialized equipment. Here we report a more convenient alternative comprised of color-encoded beads that display a small molecule protein ligand on the surface. Quantitative, multiplexed assay of protein binding to up to 24 different ligands can be achieved using a common flow cytometer for the readout. This technology should be useful for evaluating hits from library screening efforts, the determination of structure activity relationships and for certain types of serological analyses. PMID:24245981

  17. Lincoln County nuclear waste project. Quarterly progress report, October 1, 1991--December 31, 1991

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

    NONE

    1996-03-01

    This document included the following three progress reports to the Yucca Mountain Project Office on radioactive waste storage in Lincoln County, Nevada: financial status report; federal cash transactions report; and technical progress report.

  18. Lincoln County nuclear waste project. Quarterly progress report, January 1, 1992--March 31, 1992

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

    NONE

    1996-03-01

    This document included the following three progress reports to the Yucca Mountain Project Office on radioactive waste storage in Lincoln County, Nevada: financial status report; federal cash transactions report; and technical progress report.

  19. Lincoln County nuclear waste project quarterly progress report, April 1, 1992--June 30, 1992

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

    NONE

    1996-03-01

    This document included the following three progress reports to the Yucca Mountain Project Office on radioactive waste storage in Lincoln County, Nevada: financial status report; federal cash transactions report; and technical progress report.

  20. Quarterly technical progress report, February 1, 1996--April 30, 1996

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

    NONE

    This report from the Amarillo National REsource Center for PLutonium provides research highlights and provides information regarding the public dissemination of information. The center is a a scientific resource for information regarding the issues of the storage, disposition, potential utilization and transport of plutonium, high explosives, and other hazardous materials generated from nuclear weapons dismantlement. The center responds to informational needs and interpretation of technical and scientific data raised by interested parties and advisory groups. Also, research efforts are carried out on remedial action programs and biological/agricultural studies.

  1. Proceedings: Computer Science and Data Systems Technical Symposium, volume 1

    NASA Technical Reports Server (NTRS)

    Larsen, Ronald L.; Wallgren, Kenneth

    1985-01-01

    Progress reports and technical updates of programs being performed by NASA centers are covered. Presentations in viewgraph form are included for topics in three categories: computer science, data systems and space station applications.

  2. Elucidating Turnover Pathways of Bioactive Small Molecules by Isotopomer Analysis: The Persistent Organic Pollutant DDT

    PubMed Central

    Ehlers, Ina; Betson, Tatiana R.; Vetter, Walter; Schleucher, Jürgen

    2014-01-01

    The persistent organic pollutant DDT (1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane) is still indispensable in the fight against malaria, although DDT and related compounds pose toxicological hazards. Technical DDT contains the dichloro congener DDD (1-chloro-4-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene) as by-product, but DDD is also formed by reductive degradation of DDT in the environment. To differentiate between DDD formation pathways, we applied deuterium NMR spectroscopy to measure intramolecular deuterium distributions (2H isotopomer abundances) of DDT and DDD. DDD formed in the technical DDT synthesis was strongly deuterium-enriched at one intramolecular position, which we traced back to 2H/1H fractionation of a chlorination step in the technical synthesis. In contrast, DDD formed by reductive degradation was strongly depleted at the same position, which was due to the incorporation of 2H-depleted hydride equivalents during reductive degradation. Thus, intramolecular isotope distributions give mechanistic information on reaction pathways, and explain a puzzling difference in the whole-molecule 2H/1H ratio between DDT and DDD. In general, our results highlight that intramolecular isotope distributions are essential to interpret whole-molecule isotope ratios. Intramolecular isotope information allows distinguishing pathways of DDD formation, which is important to identify polluters or to assess DDT turnover in the environment. Because intramolecular isotope data directly reflect isotope fractionation of individual chemical reactions, they are broadly applicable to elucidate transformation pathways of small bioactive molecules in chemistry, physiology and environmental science. PMID:25350380

  3. Method for preparation and readout of polyatomic molecules in single quantum states

    NASA Astrophysics Data System (ADS)

    Patterson, David

    2018-03-01

    Polyatomic molecular ions contain many desirable attributes of a useful quantum system, including rich internal degrees of freedom and highly controllable coupling to the environment. To date, the vast majority of state-specific experimental work on molecular ions has concentrated on diatomic species. The ability to prepare and read out polyatomic molecules in single quantum states would enable diverse experimental avenues not available with diatomics, including new applications in precision measurement, sensitive chemical and chiral analysis at the single-molecule level, and precise studies of Hz-level molecular tunneling dynamics. While cooling the motional state of a polyatomic ion via sympathetic cooling with a laser-cooled atomic ion is straightforward, coupling this motional state to the internal state of the molecule has proven challenging. Here we propose a method for readout and projective measurement of the internal state of a trapped polyatomic ion. The method exploits the rich manifold of technically accessible rotational states in the molecule to realize robust state preparation and readout with far less stringent engineering than quantum logic methods recently demonstrated on diatomic molecules. The method can be applied to any reasonably small (≲10 atoms) polyatomic ion with an anisotropic polarizability.

  4. Profiles of equilibrium constants for self-association of aromatic molecules

    NASA Astrophysics Data System (ADS)

    Beshnova, Daria A.; Lantushenko, Anastasia O.; Davies, David B.; Evstigneev, Maxim P.

    2009-04-01

    Analysis of the noncovalent, noncooperative self-association of identical aromatic molecules assumes that the equilibrium self-association constants are either independent of the number of molecules (the EK-model) or change progressively with increasing aggregation (the AK-model). The dependence of the self-association constant on the number of molecules in the aggregate (i.e., the profile of the equilibrium constant) was empirically derived in the AK-model but, in order to provide some physical understanding of the profile, it is proposed that the sources for attenuation of the equilibrium constant are the loss of translational and rotational degrees of freedom, the ordering of molecules in the aggregates and the electrostatic contribution (for charged units). Expressions are derived for the profiles of the equilibrium constants for both neutral and charged molecules. Although the EK-model has been widely used in the analysis of experimental data, it is shown in this work that the derived equilibrium constant, KEK, depends on the concentration range used and hence, on the experimental method employed. The relationship has also been demonstrated between the equilibrium constant KEK and the real dimerization constant, KD, which shows that the value of KEK is always lower than KD.

  5. Ongoing Progress in Spacecraft Controls

    NASA Technical Reports Server (NTRS)

    Ghosh, Dave (Editor)

    1992-01-01

    This publication is a collection of papers presented at the Mars Mission Research Center workshop on Ongoing Progress in Spacecraft Controls. The technical program addressed additional Mars mission control problems that currently exist in robotic missions in addition to human missions. Topics include control systems design in the presence of large time delays, fuel-optimal propulsive control, and adaptive control to handle a variety of unknown conditions.

  6. Development of novel small molecules for imaging and drug release

    NASA Astrophysics Data System (ADS)

    Cao, Yanting

    Small organic molecules, including small molecule based fluorescent probes, small molecule based drugs or prodrugs, and smart multifunctional fluorescent drug delivery systems play important roles in biological research, drug discovery, and clinical practices. Despite the significant progress made in these fields, the development of novel and diverse small molecules is needed to meet various demands for research and clinical applications. My Ph.D study focuses on the development of novel functional molecules for recognition, imaging and drug release. In the first part, a turn-on fluorescent probe is developed for the detection of intracellular adenosine-5'-triphosphate (ATP) levels based on multiplexing recognitions. Considering the unique and complicated structure of ATP molecules, a fluorescent probe has been implemented with improved sensitivity and selectivity due to two synergistic binding recognitions by incorporating of 2, 2'-dipicolylamine (Dpa)-Zn(II) for targeting of phospho anions and phenylboronic acid group for cis-diol moiety. The novel probe is able to detect intracellular ATP levels in SH-SY5Y cells. Meanwhile, the advantages of multiplexing recognition design concept have been demonstrated using two control molecules. In the second part, a prodrug system is developed to deliver multiple drugs within one small molecule entity. The prodrug is designed by using 1-(2-nitrophenyl)ethyl (NPE) as phototrigger, and biphenol biquaternary ammonium as the prodrug. With controlled photo activation, both DNA cross-linking agents mechlorethamine and o-quinone methide are delivered and released at the preferred site, leading to efficient DNA cross-links formation and cell death. The prodrug shows negligible cytotoxicity towards normal skin cells (Hekn cells) with and without UV activation, but displays potent activity towards cancer cells (HeLa cells) upon UV activation. The multiple drug release system may hold a great potential for practical application. In the

  7. Bioethics for Technical Experts

    NASA Astrophysics Data System (ADS)

    Asano, Shigetaka

    Along with rapidly expanding applications of life science and technology, technical experts have been implicated more and more often with ethical, social, and legal problems than before. It should be noted that in this background there are scientific and social uncertainty elements which are inevitable during the progress of life science in addition to the historically-established social unreliability to scientists and engineers. In order to solve these problems, therefore, we should establish the social governance with ‘relief’ and ‘reliance’ which enables for both citizens and engineers to share the awareness of the issues, to design social orders and criterions based on hypothetical sense of values for bioethics, to carry out practical use management of each subject carefully, and to improve the sense of values from hypothetical to universal. Concerning these measures, the technical experts can learn many things from the present performance in the medical field.

  8. Technical parameters for specifying imagery requirements

    NASA Technical Reports Server (NTRS)

    Coan, Paul P.; Dunnette, Sheri J.

    1994-01-01

    Providing visual information acquired from remote events to various operators, researchers, and practitioners has become progressively more important as the application of special skills in alien or hazardous situations increases. To provide an understanding of the technical parameters required to specify imagery, we have identified, defined, and discussed seven salient characteristics of images: spatial resolution, linearity, luminance resolution, spectral discrimination, temporal discrimination, edge definition, and signal-to-noise ratio. We then describe a generalizing imaging system and identified how various parts of the system affect the image data. To emphasize the different applications of imagery, we have constrasted the common television system with the significant parameters of a televisual imaging system for technical applications. Finally, we have established a method by which the required visual information can be specified by describing certain technical parameters which are directly related to the information content of the imagery. This method requires the user to complete a form listing all pertinent data requirements for the imagery.

  9. Pre-clinical evaluation of small molecule LOXL2 inhibitors in breast cancer

    PubMed Central

    Chang, Joan; Lucas, Morghan C.; Leonte, Lidia E.; Garcia-Montolio, Marc; Singh, Lukram Babloo; Findlay, Alison D.; Deodhar, Mandar; Foot, Jonathan S.; Jarolimek, Wolfgang; Timpson, Paul; Erler, Janine T.; Cox, Thomas R.

    2017-01-01

    Lysyl Oxidase-like 2 (LOXL2), a member of the lysyl oxidase family of amine oxidases is known to be important in normal tissue development and homeostasis, as well as the onset and progression of solid tumors. Here we tested the anti-tumor properties of two generations of novel small molecule LOXL2 inhibitor in the MDA-MB-231 human model of breast cancer. We confirmed a functional role for LOXL2 activity in the progression of primary breast cancer. Inhibition of LOXL2 activity inhibited the growth of primary tumors and reduced primary tumor angiogenesis. Dual inhibition of LOXL2 and LOX showed a greater effect and also led to a lower overall metastatic burden in the lung and liver. Our data provides the first evidence to support a role for LOXL2 specific small molecule inhibitors as a potential therapy in breast cancer. PMID:28199967

  10. Progress 42 re-entry

    NASA Image and Video Library

    2011-10-29

    ISS029-E-034092 (29 Oct. 2011) --- This unusual photograph, captured by one of the Expedition 29 crew members aboard the International Space Station, highlights the reentry plasma trail (center) of Progress 42P (M-10M) supply vehicle. Progress 42P docked at the space station on April 29, 2011, and was undocked and de-orbited approximately 183 days later on Oct. 29, 2011. The ISS was located over the southern Pacific Ocean when this image was taken. Light from the rising sun illuminates the curvature of the Earth limb (horizon line) at top, but does not completely overwhelm the airglow visible at image top left. Airglow is caused by light emitted at specific wavelengths by atoms and molecules excited by ultraviolet radiation in the upper atmosphere.

  11. Proceedings: Computer Science and Data Systems Technical Symposium, volume 2

    NASA Technical Reports Server (NTRS)

    Larsen, Ronald L.; Wallgren, Kenneth

    1985-01-01

    Progress reports and technical updates of programs being performed by NASA centers are covered. Presentations in viewgraph form, along with abstracts, are included for topics in three catagories: computer science, data systems, and space station applications.

  12. [A technical modification of the use of Dwyer's equipment].

    PubMed

    Carlioz, H; Damsin, J P

    1991-01-01

    Dwyer's technique for correction and anterior fusion of the spine was improved by using lockers at the level of each screw. So, like with the Zielke's technic this procedure allowed a global progressive and controllable correction and a real derotation of the spine.

  13. Experimentation with Computer-Assisted Instruction in Technical Education. Semi-Annual Progress Report.

    ERIC Educational Resources Information Center

    Mitzel, Harold E.; Brandon, George L.

    A series of five reports is presented which describes the activities carried out by the Pennsylvania State University group engaged in research in computer-assisted instruction (CAI) in vocational-technical education. The reports cover the period January 1968-June 1968 and deal with: 1) prior knowledge and individualized instruction; 2) numerical…

  14. Case Study on Technical and Vocational Education in Japan. Case Studies on Technical and Vocational Education in Asia and the Pacific.

    ERIC Educational Resources Information Center

    Iwamoto, Muneharu

    In the course of Japan's economic progress, remarkable changes have occurred in the structure of industry and employment. Workers are in extremely short supply in such occupations as mining, manufacturing and construction, services, transportation and communication, sales, and professional and technical. On the basis of recommendations of the…

  15. Synthetic Small Molecule Inhibitors of Hh Signaling As Anti-Cancer Chemotherapeutics

    PubMed Central

    Maschinot, C.A.; Pace, J.R.; Hadden, M.K.

    2016-01-01

    The hedgehog (Hh) pathway is a developmental signaling pathway that is essential to the proper embryonic development of many vertebrate systems. Dysregulation of Hh signaling has been implicated as a causative factor in the development and progression of several forms of human cancer. As such, the development of small molecule inhibitors of Hh signaling as potential anti-cancer chemotherapeutics has been a major area of research interest in both academics and industry over the past ten years. Through these efforts, synthetic small molecules that target multiple components of the Hh pathway have been identified and advanced to preclinical or clinical development. The goal of this review is to provide an update on the current status of several synthetic small molecule Hh pathway inhibitors and explore the potential of several recently disclosed inhibitory scaffolds. PMID:26310919

  16. Multi-Scale Modeling to Improve Single-Molecule, Single-Cell Experiments

    NASA Astrophysics Data System (ADS)

    Munsky, Brian; Shepherd, Douglas

    2014-03-01

    Single-cell, single-molecule experiments are producing an unprecedented amount of data to capture the dynamics of biological systems. When integrated with computational models, observations of spatial, temporal and stochastic fluctuations can yield powerful quantitative insight. We concentrate on experiments that localize and count individual molecules of mRNA. These high precision experiments have large imaging and computational processing costs, and we explore how improved computational analyses can dramatically reduce overall data requirements. In particular, we show how analyses of spatial, temporal and stochastic fluctuations can significantly enhance parameter estimation results for small, noisy data sets. We also show how full probability distribution analyses can constrain parameters with far less data than bulk analyses or statistical moment closures. Finally, we discuss how a systematic modeling progression from simple to more complex analyses can reduce total computational costs by orders of magnitude. We illustrate our approach using single-molecule, spatial mRNA measurements of Interleukin 1-alpha mRNA induction in human THP1 cells following stimulation. Our approach could improve the effectiveness of single-molecule gene regulation analyses for many other process.

  17. Physics with Cold Molecules Using Buffer Gas Cooling: Precision Measurement, Collisions, and Laser Cooling

    NASA Astrophysics Data System (ADS)

    Hutzler, Nicholas R.; Doyle, John M.

    2014-06-01

    Cryogenic buffer gas cooled beams and cells can be used to study many species, from atoms and polar molecules to biomolecules. We report on recent applications of this technique to improve the limit on the electron electric dipole moment [1], load polar molecules into a magnetic trap through optical pumping [2], perform chirally sensitive microwave spectroscopy on polyatomic molecules [3], progress towards magneto-optical trapping of polar molecules [4], and studies of atom-molecule sticking [5]. [1] The ACME Collaboration: J. Baron et al., Science 343, p. 269 (2014) [2] B. Hemmerling et al., arXiv:1310.2669, to appear in Phys. Rev. Lett. [3] D. Patterson, M. Schnell, & J. M. Doyle, Nature 497, p. 475 (2013) [4] H. Lu et al., arXiv:1310.3239, to appear in New. J. Phys. [5] J. Piskorski et al., under preparation

  18. The GABA system in schizophrenia: cells, molecules and microcircuitry.

    PubMed

    Benes, Francine M

    2015-09-01

    This is an overview of several papers that have been published in the Special Issue of Schizophrenia Research entitled The GABA System in Schizophrenia: Cells, Molecules and Microcircuitry. This issue presents a broad range of original reports and scholarly reviews regarding recent progress in studies of neural circuitry in corticolimbic brain regions in patients with schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1

    NASA Astrophysics Data System (ADS)

    Koch, Alisa E.; Halloran, Margaret M.; Haskell, Catherine J.; Shah, Manisha R.; Polverini, Peter J.

    1995-08-01

    ENDOTHELIAL adhesion molecules facilitate the entry of leukocytes into inflamed tissues. This in turn promotes neovascularization, a process central to the progression of rheumatoid arthritis, tumour growth and wound repair1. Here we test the hypothesis that soluble endothelial adhesion molecules promote angiogenesis2á¤-4. Human recombinant soluble E-selectin and soluble vascular cell adhesion molecule-1 induced chemotaxis of human endothelial cells in vitro and were angiogenic in rat cornea. Soluble E-selectin acted on endothelial cells in part through a sialyl Lewis-X-dependent mechanism, while soluble vascular cell adhesion molecule-1 acted on endothelial cells in part through a very late antigen (VLA)-4 dependent mechanism. The chemotactic activity of rheumatoid synovial fluid for endothelial cells, and also its angiogenic activity, were blocked by antibodies to either soluble E-selectin or soluble vascular cell adhesion molecule-1. These results suggest a novel function for soluble endothelial adhesion molecules as mediators of angiogenesis.

  20. The Progression of Podcasting/Vodcasting in a Technical Physics Class

    NASA Astrophysics Data System (ADS)

    Glanville, Y. J.

    2010-11-01

    Technology such as Microsoft PowerPoint presentations, clickers, podcasting, and learning management suites is becoming prevalent in classrooms. Instructors are using these media in both large lecture hall settings and small classrooms with just a handful of students. Traditionally, each of these media is instructor driven. For instance, podcasting (audio recordings) provided my technical physics course with supplemental notes to accompany a traditional algebra-based physics lecture. Podcasting is an ideal tool for this mode of instruction, but podcasting/vodcasting is also an ideal technique for student projects and student-driven learning. I present here the various podcasting/vodcasting projects my students and I have undertaken over the last few years.

  1. Technical Feasibility Aspects of the Geothermal Resource Reporting Methodology (GRRM)

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

    Badgett, Alex; Young, Katherine R; Dobson, Patrick F.

    This paper reviews the technical assessment of the Geothermal Research Reporting Methodology (GRRM, http://en.openei.org/wiki/GRRM) being developed for reporting geothermal resources and project progress. The goal of the methodology is to provide the U.S. Department of Energy's Geothermal Technologies Office (GTO) with a consistent and comprehensible means of evaluating the impacts of its funding programs. The GRRM is designed to provide uniform assessment criteria for geothermal resource grades and developmental phases of geothermal resource exploration and development. This resource grade system provides information on twelve attributes of geothermal resource locations (e.g., temperature, permeability, land access) to indicate potential for geothermal development.more » The GTO plans to use these Protocols to help quantitatively identify the greatest barriers to geothermal development, develop measureable program goals that will have the greatest impact to geothermal deployment, objectively evaluate proposals based (in part) on a project's ability to contribute to program goals, monitor project progress, and report on GTO portfolio performance. The GRRM assesses three areas of geothermal potential: geological, socio-economic, and technical. Previous work and publications have discussed the work done on the geological aspects of this methodology (Young et al. 2015c); this paper details the development of the technical assessment of the GRRM. Technical development attributes considered include: reservoir management, drilling, logistics, and power conversion.« less

  2. Technical Status and Progress of Lead Recycling of Battery

    NASA Astrophysics Data System (ADS)

    Li, Wei-feng; Jiang, Li-hua; Zhan, Jing; Zhang, Chuan-fu

    The characteristics of various components in waste lead acid battery are analyzed in this paper. The present status and the study progress situation in industry production and research field of recycling of waste lead acid battery and lead paste used broken-separation technology are introduced. The comparison of advantages and disadvantages in different industry processes is carried. The advantages of redox bath smelting of lead concentrate and lead paste are analyzed. The method of redox bath smelting will be a low-carbon, environmentally friendly and efficient processes of secondary lead production and can be intensive to desulfurize for high temperature pool.

  3. Technical writing versus technical writing

    NASA Technical Reports Server (NTRS)

    Dillingham, J. W.

    1981-01-01

    Two terms, two job categories, 'technical writer' and 'technical author' are discussed in terms of industrial and business requirements and standards. A distinction between 'technical writing' and technical 'writing' is made. The term 'technical editor' is also considered. Problems inherent in the design of programs to prepare and train students for these jobs are discussed. A closer alliance between industry and academia is suggested as a means of preparing students with competent technical communication skills (especially writing and editing skills) and good technical skills.

  4. Homebuilt single-molecule scanning confocal fluorescence microscope studies of single DNA/protein interactions.

    PubMed

    Zheng, Haocheng; Goldner, Lori S; Leuba, Sanford H

    2007-03-01

    Many technical improvements in fluorescence microscopy over the years have focused on decreasing background and increasing the signal to noise ratio (SNR). The scanning confocal fluorescence microscope (SCFM) represented a major improvement in these efforts. The SCFM acquires signal from a thin layer of a thick sample, rejecting light whose origin is not in the focal plane thereby dramatically decreasing the background signal. A second major innovation was the advent of high quantum-yield, low noise, single-photon counting detectors. The superior background rejection of SCFM combined with low-noise, high-yield detectors makes it possible to detect the fluorescence from single-dye molecules. By labeling a DNA molecule or a DNA/protein complex with a donor/acceptor dye pair, fluorescence resonance energy transfer (FRET) can be used to track conformational changes in the molecule/complex itself, on a single molecule/complex basis. In this methods paper, we describe the core concepts of SCFM in the context of a study that uses FRET to reveal conformational fluctuations in individual Holliday junction DNA molecules and nucleosomal particles. We also discuss data processing methods for SCFM.

  5. A Portfolio Analysis Tool for Measuring NASAs Aeronautics Research Progress toward Planned Strategic Outcomes

    NASA Technical Reports Server (NTRS)

    Tahmasebi, Farhad; Pearce, Robert

    2016-01-01

    Description of a tool for portfolio analysis of NASA's Aeronautics research progress toward planned community strategic Outcomes is presented. The strategic planning process for determining the community Outcomes is also briefly described. Stakeholder buy-in, partnership performance, progress of supporting Technical Challenges, and enablement forecast are used as the criteria for evaluating progress toward Outcomes. A few illustrative examples are also presented.

  6. Silicon photon-counting avalanche diodes for single-molecule fluorescence spectroscopy

    PubMed Central

    Michalet, Xavier; Ingargiola, Antonino; Colyer, Ryan A.; Scalia, Giuseppe; Weiss, Shimon; Maccagnani, Piera; Gulinatti, Angelo; Rech, Ivan; Ghioni, Massimo

    2014-01-01

    Solution-based single-molecule fluorescence spectroscopy is a powerful experimental tool with applications in cell biology, biochemistry and biophysics. The basic feature of this technique is to excite and collect light from a very small volume and work in a low concentration regime resulting in rare burst-like events corresponding to the transit of a single molecule. Detecting photon bursts is a challenging task: the small number of emitted photons in each burst calls for high detector sensitivity. Bursts are very brief, requiring detectors with fast response time and capable of sustaining high count rates. Finally, many bursts need to be accumulated to achieve proper statistical accuracy, resulting in long measurement time unless parallelization strategies are implemented to speed up data acquisition. In this paper we will show that silicon single-photon avalanche diodes (SPADs) best meet the needs of single-molecule detection. We will review the key SPAD parameters and highlight the issues to be addressed in their design, fabrication and operation. After surveying the state-of-the-art SPAD technologies, we will describe our recent progress towards increasing the throughput of single-molecule fluorescence spectroscopy in solution using parallel arrays of SPADs. The potential of this approach is illustrated with single-molecule Förster resonance energy transfer measurements. PMID:25309114

  7. Progression of symptomatic intracranial large artery atherosclerosis is associated with a proinflammatory state and impaired fibrinolysis.

    PubMed

    Arenillas, Juan F; Alvarez-Sabín, José; Molina, Carlos A; Chacón, Pilar; Fernández-Cadenas, Israel; Ribó, Marc; Delgado, Pilar; Rubiera, Marta; Penalba, Anna; Rovira, Alex; Montaner, Joan

    2008-05-01

    The molecular pathways involved in the progression of intracranial large artery atherosclerosis (ILA) are largely unknown. Our objective was to prospectively study the relationship between circulating levels of inflammatory markers and fibrinolysis inhibitors, and the risk of progression of symptomatic ILA. Seventy-five consecutive patients with first-ever symptomatic intracranial atherostenosis were studied. Blood levels of C-reactive protein (CRP), E-selectin, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, matrix metalloproteinases 1, 2, 3, 8, 9, 10, and 13, plasminogen activator inhibitor-1 (PAI-1), and lipoprotein(a) were measured 3 months after the qualifying stroke or transient ischemic attack. Thereafter, patients underwent long-term transcranial Doppler follow-up to detect progression of ILA. During a median follow-up time of 23 months, 25 (33%) patients showed ILA progression. Multivariable adjusted Cox regression models and Kaplan-Meier curves showed that high baseline level of CRP, E-selectin, intercellular adhesion molecule-1, matrix metalloproteinase 9, PAI-1, and lipoprotein(a) predicted ILA progression independently of vascular risk factors. Of them, only CRP (CRP>5.5 mg/L; HR, 5.4 [2.3 to 12.7]; P=0.0001) and PAI-1 (PAI-1>23.1 ng/mL; HR, 2.4 [1.0 to 5.8]; P=0.05) predicted ILA progression also independently of the other studied molecules. Progression of symptomatic ILA is associated with a proinflammatory state, as reflected by high levels of inflammatory markers, and with defective fibrinolysis, as indicated by raised concentrations of endogenous fibrinolysis inhibitors.

  8. Progression of 3D Protein Structure and Dynamics Measurements

    NASA Astrophysics Data System (ADS)

    Sato-Tomita, Ayana; Sekiguchi, Hiroshi; Sasaki, Yuji C.

    2018-06-01

    New measurement methodologies have begun to be proposed with the recent progress in the life sciences. Here, we introduce two new methodologies, X-ray fluorescence holography for protein structural analysis and diffracted X-ray tracking (DXT), to observe the dynamic behaviors of individual single molecules.

  9. Heterodyne Receiver for Laboratory Spectrosocpy of Molecules of Astrophysical Importance

    NASA Astrophysics Data System (ADS)

    Wehres, Nadine; Lewen, Frank; Endres, Christian; Hermanns, Marius; Schlemmer, Stephan

    2016-06-01

    We present first results of a heterodyne receiver built for high-resolution emission laboratory spectroscopy of molecules of astrophysical interest. The room-temperature receiver operates at frequencies between 80 and 110 GHz, consistent with ALMA band 3. Many molecules have been identified in the interstellar and circumstellar medium at exactly these frequencies by comparing emission spectra obtained from telescopes to high-resolution laboratory absorption spectra. Taking advantage of the recent progresses in the field of mm/submm technology in the astronomy community, we have built a room-temperature emission spectrometer making use of heterodyne receiver technology at an instantaneous bandwidth of currently 2.5 GHz. The system performance, in particular the noise temperature and systematic errors, is presented. The proof-of-concept is demonstrated by comparing the emission spectrum of methyl cyanide to respective absorption spectra and to the literature. Future prospects as well as limitations of the new laboratory receiver for the spectroscopy of complex organic molecules or transient species in discharges will be discussed.

  10. Embedding of polyaniline molecules on adhesive tape using successive ionic layer adsorption and reaction (SILAR) technique

    NASA Astrophysics Data System (ADS)

    Pamatmat, J. K.; Gillado, A. V.; Herrera, M. U.

    2017-05-01

    Polyaniline molecules are embedded on adhesive tape using successive ionic layer adsorption and reaction (SILAR) technique. The infrared spectrum shows the existence of molecular vibrational modes associated with the presence of polyaniline molecules on the sample. With the addition of polyaniline molecules, the conductivity of adhesive tape increases. Surface conductivity increases with number of dipping cycle until it reaches a certain value. Beyond this value, surface conductivity begins to decrease. The surface conductivity of the sample is associated with the connectivity of the embedded polyaniline molecules. The connectivity increases as the number of dipping cycle progresses. Meanwhile, the decrease in surface conductivity is attributed to the eroding of existing embedded structure at higher number of dipping cycle.

  11. Electron scattering on molecules: search for semi-empirical indications

    NASA Astrophysics Data System (ADS)

    Fedus, Kamil; Karwasz, Grzegorz P.

    2017-06-01

    Reliable cross-sections for electron-molecule collisions are urgently needed for numerical modeling of various processes important from technological point of view. Unfortunately, a significant progress in theory and experiment over the last decade is not usually accompanied by the convergence of cross-sections measured at different laboratories and calculated with different methods. Moreover the most advanced contemporary theories involve such large basis sets and complicated equations that they are not easily applied to each specific molecule for which data are needed. For these reasons the search for semi-empirical indications in angular and energy dependencies of scattering cross-section becomes important. In this paper we make a brief review of the applicability of the Born-dipole approximation for elastic, rotational, vibrational and ionization processes that can occur during electron-molecule collisions. We take into account the most recent experimental findings as the reference points. Contribution to the Topical Issue "Atomic and Molecular Data and Their Applications", edited by Gordon W.F. Drake, Jung-Sik Yoon, Daiji Kato, and Grzegorz Karwasz.

  12. Molecules Without Atoms

    NASA Astrophysics Data System (ADS)

    Ruth, Anthony; Collins, Laura; Gomes, Kenjiro; Janko, Boldizsar

    We present a real-space representation of molecules which results in the normal bonding rules and electronic structure of chemistry without atom-centered coulomb potentials. Using a simple mapping, we can generate atomless molecules from the structure of real molecules. Additionally, molecules without atoms show similar covalent bonding energies and transfer of charge in ionic bonds as real molecules. The atomless molecules contain only the valence and conduction electronic structure of the real molecule. Using the framework of the Atoms in Molecules (AIM) theory of Bader, we prove that the topological features of the valence charge distribution of molecules without atoms are identical to that of real molecules. In particular, the charge basins of atomless molecules show identical location and quantities of representative charge. We compare the accuracy, computational cost, and intuition gained from electronic structure calculations of molecules without atoms with the use of pseudopotentials to represent atomic cores in density functional theory. A. R. acknowledges support from a NASA Space Technology Research Fellowship.

  13. Reconstructing Folding Energy Landscapes by Single-Molecule Force Spectroscopy

    PubMed Central

    Woodside, Michael T.; Block, Steven M.

    2015-01-01

    Folding may be described conceptually in terms of trajectories over a landscape of free energies corresponding to different molecular configurations. In practice, energy landscapes can be difficult to measure. Single-molecule force spectroscopy (SMFS), whereby structural changes are monitored in molecules subjected to controlled forces, has emerged as a powerful tool for probing energy landscapes. We summarize methods for reconstructing landscapes from force spectroscopy measurements under both equilibrium and nonequilibrium conditions. Other complementary, but technically less demanding, methods provide a model-dependent characterization of key features of the landscape. Once reconstructed, energy landscapes can be used to study critical folding parameters, such as the characteristic transition times required for structural changes and the effective diffusion coefficient setting the timescale for motions over the landscape. We also discuss issues that complicate measurement and interpretation, including the possibility of multiple states or pathways and the effects of projecting multiple dimensions onto a single coordinate. PMID:24895850

  14. Towards a space-borne quantum gravity gradiometer: progress in laboratory demonstration

    NASA Technical Reports Server (NTRS)

    Yu, Nan; Kohel, James M.; Kellogg, James R.; Maleki, Lute

    2005-01-01

    This paper describes the working principles and technical benefits of atom-wave interferometer-based inertial sensors, and gives a progress report on the development of a quantum gravity gradiometer for space applications at JPL.

  15. High precision optical spectroscopy and quantum state selected photodissociation of ultracold 88Sr2 molecules in an optical lattice

    NASA Astrophysics Data System (ADS)

    McDonald, Mickey

    2017-04-01

    Over the past several decades, rapid progress has been made toward the accurate characterization and control of atoms, epitomized by the ever-increasing accuracy and precision of optical atomic lattice clocks. Extending this progress to molecules will have exciting implications for chemistry, condensed matter physics, and precision tests of physics beyond the Standard Model. My thesis describes work performed over the past six years to establish the state of the art in manipulation and quantum control of ultracold molecules. We describe a thorough set of measurements characterizing the rovibrational structure of weakly bound 88Sr2 molecules from several different perspectives, including determinations of binding energies; linear, quadratic, and higher order Zeeman shifts; transition strengths between bound states; and lifetimes of narrow subradiant states. Finally, we discuss measurements of photofragment angular distributions produced by photodissociation of molecules in single quantum states, leading to an exploration of quantum-state-resolved ultracold chemistry. The images of exploding photofragments produced in these studies exhibit dramatic interference effects and strongly violate semiclassical predictions, instead requiring a fully quantum mechanical description.

  16. The physics of life: one molecule at a time

    PubMed Central

    Leake, Mark C.

    2013-01-01

    The esteemed physicist Erwin Schrödinger, whose name is associated with the most notorious equation of quantum mechanics, also wrote a brief essay entitled ‘What is Life?’, asking: ‘How can the events in space and time which take place within the spatial boundary of a living organism be accounted for by physics and chemistry?’ The 60+ years following this seminal work have seen enormous developments in our understanding of biology on the molecular scale, with physics playing a key role in solving many central problems through the development and application of new physical science techniques, biophysical analysis and rigorous intellectual insight. The early days of single-molecule biophysics research was centred around molecular motors and biopolymers, largely divorced from a real physiological context. The new generation of single-molecule bioscience investigations has much greater scope, involving robust methods for understanding molecular-level details of the most fundamental biological processes in far more realistic, and technically challenging, physiological contexts, emerging into a new field of ‘single-molecule cellular biophysics’. Here, I outline how this new field has evolved, discuss the key active areas of current research and speculate on where this may all lead in the near future. PMID:23267186

  17. Department of Clinical Investigation Annual Research Progress Report, Fiscal Year 1984. Volume 1,

    DTIC Science & Technology

    1984-10-01

    on a low dosage of medication . Technical Approach: None. Progress: The placebo has not been received from the company. Since the drug company...determine the effect of high dose Ar-C intensification therapy on the -. incidence of CNS relapse. - Technical Approach: All patients with a new...Enrolled to Date: 7 Date of Periodic Review Results Objective(s): To determine the incidence of

  18. NAEP 1999 Long-Term Trend Technical Analysis Report: Three Decades of Student Performance. NCES 2005-484

    ERIC Educational Resources Information Center

    Allen, Nancy L.; McClellan, Catherine A.; Stoeckel, Joan J.

    2005-01-01

    This report provides an update to the technical analysis procedures documenting the 1996 National Assessment of Educational Progress (NAEP) as presented in "The NAEP 1996 Technical Report" (Allen, Carlson, and Zelenak, 1999). It describes how the 1999 long-term trend data were incorporated into the trend analyses. Since no national main…

  19. Clinicopathologic significance of HLA-G and HLA-E molecules in Tunisian patients with ovarian carcinoma.

    PubMed

    Babay, Wafa; Ben Yahia, Hamza; Boujelbene, Nadia; Zidi, Nour; Laaribi, Ahmed Baligh; Kacem, Dhikra; Ben Ghorbel, Radhia; Boudabous, Abdellatif; Ouzari, Hadda-Imene; Rizzo, Roberta; Rebmann, Vera; Mrad, Karima; Zidi, Inès

    2018-06-01

    The human leukocyte antigen (HLA)-G and HLA-E, non classical HLA class I molecules, have been highly implicated in immune tolerance. HLA-G and HLA-E molecules were proposed as putative markers of several advanced cancers. As a step towards a better understanding of ovarian carcinoma, we evaluated the expression of both HLA-G and HLA-E molecules and explored their prognostic implication. HLA-G and HLA-E expression were studied by immunohistochemistry on ovarian carcinoma tissues. This expression was semi-quantitatively scored into four expression groups and correlated to clinicopathological parameters and patients' survival. HLA-G and HLA-E have been found to be highly expressed in ovarian carcinoma tissues (Respectively, 72.4% and 96.8%). They are frequently co-expressed. Univariate and multivariate analysis revealed that a positive HLA-G expression status in tumor tissue is a promising candidate parameter to predict disease recurrence in addition to the disease status in Tunisian patients with ovarian carcinoma. Moreover, the elevated HLA-E expression was associated with serous ovarian carcinoma subtype as well as with advanced stages of ovarian carcinoma. HLA-G and HLA-E are highly represented in ovarian carcinoma suggesting a potential association with progressive disease mechanism. HLA-G and HLA-E molecules might be new candidates' markers for ovarian carcinoma progression. Copyright © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  20. Complex organic molecules toward low-mass and high-mass star forming regions

    NASA Astrophysics Data System (ADS)

    Favre, C.; Ceccarelli, C.; Lefloch, B.; Bergin, E.; Carvajal, M.; Brouillet, N.; Despois, D.; Jørgensen, J.; Kleiner, I.

    2016-12-01

    One of the most important questions in molecular astrophysics is how, when, and where complex organic molecules, COMs (≥ 6 atoms) are formed. In the Interstellar-Earth connection context, could this have a bearing on the origin of life on Earth? Formation mechanisms of COMs, which include potentially prebiotic molecules, are still debated and may include grain-mantle and/or gas-phase chemistry. Understanding the mechanisms that lead to the interstellar molecular complexification, along with the involved physicochemical processes, is mandatory to answer the above questions. In that context, active researches are ongoing in theory, laboratory experiment, chemical modeling and observations. Thanks to recent progress in radioastronomy instrumentation for both single-dish and millimeter array (e.g. Herschel, NOEMA, ALMA), new results have been obtained. I will review some notable results on the detection of COMs, including prebiotic molecules, towards star forming regions.

  1. Progress Monitoring in Middle School Mathematics: Options and Issues

    ERIC Educational Resources Information Center

    Foegen, Anne

    2008-01-01

    This study investigated the technical features of six potential progress-monitoring measures in mathematics appropriate for use at the middle school level, including two commercially available measures for sixth-grade mathematics, two measures used in previous middle school studies, and two new measures of numeracy concepts. Five hundred…

  2. A potentiometric titration method for the crystallization of drug-like organic molecules.

    PubMed

    Du-Cuny, Lei; Huwyler, Jörg; Fischer, Holger; Kansy, Manfred

    2007-09-05

    It is generally accepted, that crystalline solids representing a low energy polymorph should be selected for development of oral dosage forms. As a consequence, efficient and robust procedures are needed at an early stage during drug discovery to prepare crystals from drug-like organic molecules. In contrast to the use of supersaturated solutions, we present a potentiometric crystallization procedure where saturated solutions are prepared in a controlled manner by pH-titration. Crystallization is carried out under defined conditions using the sample concentration and experimental pK(a) values as input parameters. Crystals of high quality were obtained for 11 drugs selected to demonstrate the efficiency and applicability of the new method. Technical improvements are suggested to overcome practical limitations and to enhance the possibility of obtaining crystals from molecules in their uncharged form.

  3. Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

    PubMed

    Kim, Jin Hyoung; Hossain, Ferdaus Mohd Altaf; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Park, Sang-Youel; Lee, John-Hwa; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

    2016-10-01

    Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Strategies for Detecting Biological Molecules on Titan.

    PubMed

    Neish, Catherine D; Lorenz, Ralph D; Turtle, Elizabeth P; Barnes, Jason W; Trainer, Melissa G; Stiles, Bryan; Kirk, Randolph; Hibbitts, Charles A; Malaska, Michael J

    2018-05-02

    Saturn's moon Titan has all the ingredients needed to produce "life as we know it." When exposed to liquid water, organic molecules analogous to those found on Titan produce a range of biomolecules such as amino acids. Titan thus provides a natural laboratory for studying the products of prebiotic chemistry. In this work, we examine the ideal locales to search for evidence of, or progression toward, life on Titan. We determine that the best sites to identify biological molecules are deposits of impact melt on the floors of large, fresh impact craters, specifically Sinlap, Selk, and Menrva craters. We find that it is not possible to identify biomolecules on Titan through remote sensing, but rather through in situ measurements capable of identifying a wide range of biological molecules. Given the nonuniformity of impact melt exposures on the floor of a weathered impact crater, the ideal lander would be capable of precision targeting. This would allow it to identify the locations of fresh impact melt deposits, and/or sites where the melt deposits have been exposed through erosion or mass wasting. Determining the extent of prebiotic chemistry within these melt deposits would help us to understand how life could originate on a world very different from Earth. Key Words: Titan-Prebiotic chemistry-Solar system exploration-Impact processes-Volcanism. Astrobiology xx, xxx-xxx.

  5. [Research progress of the molecule mechanisms of Ebola virus infection of cells].

    PubMed

    Shi, Ming; Shen, Yu-Qing

    2013-01-01

    Ebola virus can cause severe Ebola hemorrhagic fever. The mortality rate is 90 percent. Up till now, there is no effective vaccine or treatment of Ebola virus infection. Relaed researches on Ebola virus have become a hot topic in virology. The understanding of molecular mechanisms of Ebola virus infection of cells are important for the development of vaccine and anti-virus drugs. Therefore, this review summarized the recent research progress on the mechanisms of Ebola virus infection.

  6. Solar-powered irrigation systems. Technical progress report, July 1977--January 1978

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

    None

    1978-02-28

    Dispersed solar thermal power systems applied to farm irrigation energy needs are analyzed. The 17 western states, containing 84% of nationwide irrigated croplands and consuming 93% of nationwide irrigation energy, have been selected to determine were solar irrigation systems can compete most favorably with conventional energy sources. Financial analysis of farms, according to size and ownership, was accomplished to permit realistic comparative analyses of system lifetime costs. Market potential of optimized systems has been estimated for the 17-state region for near-term (1985) and intermediate-term (2000) applications. Technical, economic, and institutional factors bearing on penetration and capture of this market aremore » being identified.« less

  7. Technical efficiency and productivity of Chinese county hospitals: an exploratory study in Henan province, China

    PubMed Central

    Cheng, Zhaohui; Tao, Hongbing; Cai, Miao; Lin, Haifeng; Lin, Xiaojun; Shu, Qin; Zhang, Ru-ning

    2015-01-01

    Objectives Chinese county hospitals have been excessively enlarging their scale during the healthcare reform since 2009. The purpose of this paper is to examine the technical efficiency and productivity of county hospitals during the reform process, and to determine whether, and how, efficiency is affected by various factors. Setting and participants 114 sample county hospitals were selected from Henan province, China, from 2010 to 2012. Outcome measures Data envelopment analysis was employed to estimate the technical and scale efficiency of sample hospitals. The Malmquist index was used to calculate productivity changes over time. Tobit regression was used to regress against 4 environmental factors and 5 institutional factors that affected the technical efficiency. Results (1) 112 (98.2%), 112 (98.2%) and 104 (91.2%) of the 114 sample hospitals ran inefficiently in 2010, 2011 and 2012, with average technical efficiency of 0.697, 0.748 and 0.790, respectively. (2) On average, during 2010–2012, productivity of sample county hospitals increased by 7.8%, which was produced by the progress in technical efficiency changes and technological changes of 0.9% and 6.8%, respectively. (3) Tobit regression analysis indicated that government subsidy, hospital size with above 618 beds and average length of stay assumed a negative sign with technical efficiency; bed occupancy rate, ratio of beds to nurses and ratio of nurses to physicians assumed a positive sign with technical efficiency. Conclusions There was considerable space for technical efficiency improvement in Henan county hospitals. During 2010–2012, sample hospitals experienced productivity progress; however, the adverse change in pure technical efficiency should be emphasised. Moreover, according to the Tobit results, policy interventions that strictly supervise hospital bed scale, shorten the average length of stay and coordinate the proportion among physicians, nurses and beds, would benefit hospital efficiency

  8. Progress, innovation and regulatory science in drug development: the politics of international standard-setting.

    PubMed

    Abraham, John; Reed, Tim

    2002-06-01

    This paper examines international standard-setting in the toxicology of pharmaceuticals during the 1990s, which has involved both the pharmaceutical industry and regulatory agencies in an organization known as the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The analysis shows that the relationships between innovation, regulatory science and 'progress' may be more complex and controversial than is often assumed. An assessment of the ICH's claims about the implications of 'technical' harmonization of drug-testing standards for the maintenance of drug safety, via toxicological testing, and the delivery of therapeutic progress, via innovation, is presented. By demonstrating that there is not a technoscientific validity for these claims, it is argued that, within the ICH, a discourse of technological innovation and scientific progress has been used by regulatory agencies and prominent parts of the transnational pharmaceutical industry to legitimize the lowering and loosening of toxicological standards for drug testing. The mobilization and acceptance of this discourse are shown to be pivotal to the ICH's transformation of reductions in safety standards, which are apparently against the interests of patients and public health, into supposed therapeutic benefits derived from promises of greater access to more innovative drug products. The evidence suggests that it is highly implausible that these reductions in the standards of regulatory toxicology are consistent with therapeutic progress for patients, and highlights a worrying aspect embedded in the 'technical trajectories' of regulatory science.

  9. Signaling lymphocytic activation molecules Slam and cancers: friends or foes?

    PubMed

    Fouquet, Gregory; Marcq, Ingrid; Debuysscher, Véronique; Bayry, Jagadeesh; Rabbind Singh, Amrathlal; Bengrine, Abderrahmane; Nguyen-Khac, Eric; Naassila, Mickael; Bouhlal, Hicham

    2018-03-23

    Signaling Lymphocytic Activation Molecules (SLAM) family receptors are initially described in immune cells. These receptors recruit both activating and inhibitory SH2 domain containing proteins through their Immunoreceptor Tyrosine based Switch Motifs (ITSMs). Accumulating evidence suggest that the members of this family are intimately involved in different physiological and pathophysiological events such as regulation of immune responses and entry pathways of certain viruses. Recently, other functions of SLAM, principally in the pathophysiology of neoplastic transformations have also been deciphered. These new findings may prompt SLAM to be considered as new tumor markers, diagnostic tools or potential therapeutic targets for controlling the tumor progression. In this review, we summarize the major observations describing the implications and features of SLAM in oncology and discuss the therapeutic potential attributed to these molecules.

  10. Single-molecule spectroscopy for plastic electronics: materials analysis from the bottom-up.

    PubMed

    Lupton, John M

    2010-04-18

    pi-conjugated polymers find a range of applications in electronic devices. These materials are generally highly disordered in terms of chain length and chain conformation, besides being influenced by a variety of chemical and physical defects. Although this characteristic can be of benefit in certain device applications, disorder severely complicates materials analysis. Accurate analytical techniques are, however, crucial to optimising synthetic procedures and assessing overall material purity. Fortunately, single-molecule spectroscopic techniques have emerged as an unlikely but uniquely powerful approach to unraveling intrinsic material properties from the bottom up. Building on the success of such techniques in the life sciences, single-molecule spectroscopy is finding increasing applicability in materials science, effectively enabling the dissection of the bulk down to the level of the individual molecular constituent. This article reviews recent progress in single molecule spectroscopy of conjugated polymers as used in organic electronics.

  11. Growth cones are actively influenced by substrate-bound adhesion molecules.

    PubMed

    Burden-Gulley, S M; Payne, H R; Lemmon, V

    1995-06-01

    As axons advance to appropriate target tissues during development, their growth cones encounter a variety of cell adhesion molecules (CAMs) and extracellular matrix molecules (ECM molecules). Purified CAMs and ECM molecules influence neurite outgrowth in vitro and are thought to have a similar function in vivo. For example, when retinal ganglion cell (RGC) neurons are grown on different CAM and ECM molecule substrates in vitro, their growth cones display distinctive morphologies (Payne et al., 1992). Similarly, RGC growth cones in vivo have distinctive shapes at different points in the pathway from the eye to the tectum, suggesting the presence of localized cues that determine growth cone behaviors such as pathway selection at choice points. In this report, time-lapse video microscopy was utilized to examine dynamic transformations of RGC growth cones as they progressed from L1/8D9, N-cadherin, or laminin onto a different substrate. Contact made by the leading edge of a growth cone with a new substrate resulted in a rapid and dramatic alteration in growth cone morphology. In some cases, the changes encompassed the entire growth cone including those regions not in direct contact with the new substrate. In addition, the growth cones displayed a variety of behavioral responses that were dependent upon the order of substrate contact. These studies demonstrate that growth cones are actively affected by the substrate, and suggest that abrupt changes in the molecular composition of the growth cone environment are influential during axonal pathfinding.

  12. Identifying Organic Molecules in Space: The AstroBiology Explorer (ABE) MIDEX Mission Concept

    NASA Technical Reports Server (NTRS)

    Sandford, Scott A.; Allamandola, Louis; Bregman, Jesse; Ennico, Kimberly; Greene, Thomas; Hudgins, Douglas; Strecker, Donald; DeVincenzi, Donald (Technical Monitor)

    2001-01-01

    Infrared spectroscopy in the 2.5-16 micron range is a principle means by which organic compounds are detected and identified in space. Ground-based, airborne, and spaceborne IR spectral studies have already demonstrated that a significant fraction of the carbon in the interstellar medium (ISM) resides in the form of complex organic molecular species. Unfortunately, neither the distribution of these materials nor their genetic and evolutionary relationships with each other or their environments are well understood. The Astrobiology Explorer (ABE) is a MIDEX mission concept currently under study at NASA's Ames Research Center in collaboration with Ball Aerospace and Technologies Corporation. ABE will conduct IR spectroscopic observations to address outstanding important problems in astrobiology, astrochemistry, and astrophysics. The core observational program would make fundamental scientific progress in understanding (1) the evolution of ices and organic matter in dense molecular clouds and young forming stellar systems, (2) the chemical evolution of organic molecules in the ISM as they transition from AGB outflows to planetary nebulae to the general diffuse ISM to H II regions and dense clouds, (3) the distribution of organics in the diffuse ISM, (4) the nature of organics in the Solar System (in comets, asteroids, satellites), and (5) the nature and distribution of organics in local galaxies. The technical considerations of achieving these science objectives in a MIDEX-sized mission will be described.

  13. Ultracold molecules for the masses: Evaporative cooling and magneto-optical trapping

    NASA Astrophysics Data System (ADS)

    Stuhl, B. K.

    While cold molecule experiments are rapidly moving towards their promised benefits of precision spectroscopy, controllable chemistry, and novel condensed phases, heretofore the field has been greatly limited by a lack of methods to cool and compress chemically diverse species to temperatures below ten millikelvin. While in atomic physics these needs are fulfilled by laser cooling, magneto-optical trapping, and evaporative cooling, until now none of these techniques have been applicable to molecules. In this thesis, two major breakthroughs are reported. The first is the observation of evaporative cooling in magnetically trapped hydroxyl (OH) radicals, which potentially opens a path all the way to Bose-Einstein condensation of dipolar radicals, as well as allowing cold- and ultracold-chemistry studies of fundamental reaction mechanisms. Through the combination of an extremely high gradient magnetic quadrupole trap and the use of the OH Λ-doublet transition to enable highly selective forced evaporation, cooling by an order of magnitude in temperature was achieved and yielded a final temperature no higher than 5mK. The second breakthrough is the successful application of laser cooling and magneto-optical trapping to molecules. Motivated by a proposal in this thesis, laser cooling of molecules is now known to be technically feasible in a select but substantial pool of diatomic molecules. The demonstration of not only Doppler cooling but also two-dimensional magneto-optical trapping in yttrium (II) oxide, YO, is expected to enable rapid growth in the availability of ultracold molecules—just as the invention of the atomic magneto-optical trap stimulated atomic physics twenty-five years ago.

  14. Nuclear waste management. Semiannual progress report, October 1982-March 1983

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

    Chikalla, T.D.; Powell, J.A.

    1983-06-01

    This document is one of a series of technical progress reports designed to report radioactive waste management programs at the Pacific Northwest Laboratory. Accomplishments in the following programs are reported: waste stabilization; Materials Characterization Center; waste isolation; low-level waste management; remedial action; and supporting studies.

  15. Single molecule transcription factor dynamics in the syncytial Drosophila embryo

    NASA Astrophysics Data System (ADS)

    Darzacq, Xavier

    During early development in the Drosophila embryo, cell fates are determined over the course of just 2 hours with exquisite spatio-temoral precision. One of the key regulators of this process is the transcription factor Bicoid which forms a concentration gradient across the long axis of the embryo. Although Bicoids' primary role is activation at the anterior, where concentrations are highest, it is also known to play a role in the posterior where there are only 100s of molecules per nucleus. Understanding how Bicoid can find its target at such low concentrations has remained intractable, largely due to the inability to perform single molecule imaging in the context of the developing embryo. Here we use lattice light sheet microscopy to overcome the technical barriers of sample thickness and auto-fluorescence to characterize the single molecule dynamics of Bicoid. We find that off-rates do not vary across the embryo and that instead the on-rates are modulated through the formation of clusters that enrich local concentration. This data is contrary to the current concentration dependent model of Bicoid function since local concentration within the nucleus is now a regulated parameter and suggests a previously unknown mechanism for regulation at extremely low concentrations.

  16. Technical and Vocational Education in Cameroon and Critical Avenues for Development

    ERIC Educational Resources Information Center

    Che, S. Megan

    2007-01-01

    Technical and vocational education (TVE) can influence development and economic progress for post-colonial societies. Some newly independent sub-Saharan African countries attempted curricular transformation that might produce a skilled workforce through widespread access to versions of TVE. In Cameroon, no such post-colonial curricular revolution…

  17. Progress in the Correlative Atomic Force Microscopy and Optical Microscopy

    PubMed Central

    Zhou, Lulu; Cai, Mingjun; Tong, Ti; Wang, Hongda

    2017-01-01

    Atomic force microscopy (AFM) has evolved from the originally morphological imaging technique to a powerful and multifunctional technique for manipulating and detecting the interactions between molecules at nanometer resolution. However, AFM cannot provide the precise information of synchronized molecular groups and has many shortcomings in the aspects of determining the mechanism of the interactions and the elaborate structure due to the limitations of the technology, itself, such as non-specificity and low imaging speed. To overcome the technical limitations, it is necessary to combine AFM with other complementary techniques, such as fluorescence microscopy. The combination of several complementary techniques in one instrument has increasingly become a vital approach to investigate the details of the interactions among molecules and molecular dynamics. In this review, we reported the principles of AFM and optical microscopy, such as confocal microscopy and single-molecule localization microscopy, and focused on the development and use of correlative AFM and optical microscopy. PMID:28441775

  18. Single Molecule and Single Cell Epigenomics

    PubMed Central

    Hyun, Byung-Ryool; McElwee, John L.; Soloway, Paul D.

    2014-01-01

    Dynamically regulated changes in chromatin states are vital for normal development and can produce disease when they go awry. Accordingly, much effort has been devoted to characterizing these states under normal and pathological conditions. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is the most widely used method to characterize where in the genome transcription factors, modified histones, modified nucleotides and chromatin binding proteins are found; bisulfite sequencing (BS-seq) and its variants are commonly used to characterize the locations of DNA modifications. Though very powerful, these methods are not without limitations. Notably, they are best at characterizing one chromatin feature at a time, yet chromatin features arise and function in combination. Investigators commonly superimpose separate ChIP-seq or BS-seq datasets, and then infer where chromatin features are found together. While these inferences might be correct, they can be misleading when the chromatin source has distinct cell types, or when a given cell type exhibits any cell to cell variation in chromatin state. These ambiguities can be eliminated by robust methods that directly characterize the existence and genomic locations of combinations of chromatin features in very small inputs of cells or ideally, single cells. Here we review single molecule epigenomic methods under development to overcome these limitations, the technical challenges associated with single molecule methods and their potential application to single cells. PMID:25204781

  19. A Tool for Measuring NASA's Aeronautics Research Progress Toward Planned Strategic Community Outcomes

    NASA Technical Reports Server (NTRS)

    Tahmasebi, Farhad; Pearce, Robert

    2016-01-01

    Description of a tool for portfolio analysis of NASA's Aeronautics research progress toward planned community strategic Outcomes is presented. For efficiency and speed, the tool takes advantage of a function developed in Excels Visual Basic for Applications. The strategic planning process for determining the community Outcomes is also briefly discussed. Stakeholder buy-in, partnership performance, progress of supporting Technical Challenges, and enablement forecast are used as the criteria for evaluating progress toward Outcomes. A few illustrative examples of using the tool are also presented.

  20. USAARL Annual Progress Report Fiscal Year 2012

    DTIC Science & Technology

    2013-04-01

    analyzed. A technical report is currently in progress. A research project entitled “Clinical Assessment of the Noise Immune Stethoscope ” evaluated the...noise immune stethoscope (NIS), a dual mode electronic and Doppler device, at Madigan Army Medical Center. Insight from the evaluations, data...Immune Stethoscope aboard a U.S. Navy Carrier. (Report No. 2012-02). Fort Rucker, AL: U.S. Army Aeromedical Research Laboratory. Gordon, E., & Reeves

  1. The Adaptor Molecule Signaling Lymphocytic Activation Molecule (SLAM)-associated Protein (SAP) Is Essential in Mechanisms Involving the Fyn Tyrosine Kinase for Induction and Progression of Collagen-induced Arthritis

    PubMed Central

    Zhong, Ming-Chao; Veillette, André

    2013-01-01

    Signaling lymphocytic activation molecule-associated protein (SAP) is an Src homology 2 domain-only adaptor involved in multiple immune cell functions. It has also been linked to immunodeficiencies and autoimmune diseases, such as systemic lupus erythematosus. Here, we examined the role and mechanism of action of SAP in autoimmunity using a mouse model of autoimmune arthritis, collagen-induced arthritis (CIA). We found that SAP was essential for development of CIA in response to collagen immunization. It was also required for production of collagen-specific antibodies, which play a key role in disease pathogenesis. These effects required SAP expression in T cells, not in B cells. In mice immunized with a high dose of collagen, the activity of SAP was nearly independent of its ability to bind the protein tyrosine kinase Fyn and correlated with the capacity of SAP to promote full differentiation of follicular T helper (TFH) cells. However, with a lower dose of collagen, the role of SAP was more dependent on Fyn binding, suggesting that additional mechanisms other than TFH cell differentiation were involved. Further studies suggested that this might be due to a role of the SAP-Fyn interaction in natural killer T cell development through the ability of SAP-Fyn to promote Vav-1 activation. We also found that removal of SAP expression during progression of CIA attenuated disease severity. However, it had no effect on disease when CIA was clinically established. Together, these results indicate that SAP plays an essential role in CIA because of Fyn-independent and Fyn-dependent effects on TFH cells and, possibly, other T cell types. PMID:24045941

  2. The adaptor molecule signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is essential in mechanisms involving the Fyn tyrosine kinase for induction and progression of collagen-induced arthritis.

    PubMed

    Zhong, Ming-Chao; Veillette, André

    2013-11-01

    Signaling lymphocytic activation molecule-associated protein (SAP) is an Src homology 2 domain-only adaptor involved in multiple immune cell functions. It has also been linked to immunodeficiencies and autoimmune diseases, such as systemic lupus erythematosus. Here, we examined the role and mechanism of action of SAP in autoimmunity using a mouse model of autoimmune arthritis, collagen-induced arthritis (CIA). We found that SAP was essential for development of CIA in response to collagen immunization. It was also required for production of collagen-specific antibodies, which play a key role in disease pathogenesis. These effects required SAP expression in T cells, not in B cells. In mice immunized with a high dose of collagen, the activity of SAP was nearly independent of its ability to bind the protein tyrosine kinase Fyn and correlated with the capacity of SAP to promote full differentiation of follicular T helper (TFH) cells. However, with a lower dose of collagen, the role of SAP was more dependent on Fyn binding, suggesting that additional mechanisms other than TFH cell differentiation were involved. Further studies suggested that this might be due to a role of the SAP-Fyn interaction in natural killer T cell development through the ability of SAP-Fyn to promote Vav-1 activation. We also found that removal of SAP expression during progression of CIA attenuated disease severity. However, it had no effect on disease when CIA was clinically established. Together, these results indicate that SAP plays an essential role in CIA because of Fyn-independent and Fyn-dependent effects on TFH cells and, possibly, other T cell types.

  3. FY2017 Electrification Annual Progress Report

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

    None

    During fiscal year 2017 (FY 2017), the U.S. Department of Energy (DOE) Vehicle Technologies Office (VTO) funded early stage research & development (R&D) projects that address Batteries and Electrification of the U.S. transportation sector. The VTO Electrification Sub-Program is composed of Electric Drive Technologies, and Grid Integration activities. The Electric Drive Technologies group conducts R&D projects that advance Electric Motors and Power Electronics technologies. The Grid and Charging Infrastructure group conducts R&D projects that advance Grid Modernization and Electric Vehicle Charging technologies. This document presents a brief overview of the Electrification Sub-Program and progress reports for its R&D projects. Eachmore » of the progress reports provide a project overview and highlights of the technical results that were accomplished in FY 2017.« less

  4. Hydrogel Droplet Microfluidics for High-Throughput Single Molecule/Cell Analysis.

    PubMed

    Zhu, Zhi; Yang, Chaoyong James

    2017-01-17

    molecule/cell analysis. The hydrogel can act as a 3D cell culture matrix to mimic the extracellular environment for long-term single cell culture, which allows further heterogeneity study in proliferation, drug screening, and metastasis at the single-cell level. The sol-gel transition allows reactions in solution to be performed rapidly and efficiently with product storage in the gel for flexible downstream manipulation and analysis. More importantly, controllable sol-gel regulation provides a new way to maintain phenotype-genotype linkages in the hydrogel matrix for high throughput molecular evolution. In this Account, we will review the hydrogel droplet generation on microfluidics, single molecule/cell encapsulation in hydrogel droplets, as well as the progress made by our group and others in the application of hydrogel droplet microfluidics for single molecule/cell analysis, including single cell culture, single molecule/cell detection, single cell sequencing, and molecular evolution.

  5. Psychosocial influences on HIV-1 disease progression: neural, endocrine, and virologic mechanisms.

    PubMed

    Cole, Steve W

    2008-06-01

    This review surveys empirical research pertinent to the hypothesis that activity of the hypothalamus-pituitary-adrenal (HPA) axis and/or the sympathetic nervous system (SNS) might mediate biobehavioral influences on HIV-1 pathogenesis and disease progression. Data are considered based on causal effects of neuroeffector molecules on HIV-1 replication, prospective relationships between neural/endocrine parameters and HIV-relevant biological or clinical markers, and correlational data consistent with in vivo neural/endocrine mediation in human or animal studies. Results show that HPA and SNS effector molecules can enhance HIV-1 replication in cellular models via effects on viral infectivity, viral gene expression, and the innate immune response to infection. Animal models and human clinical studies both provide evidence consistent with SNS regulation of viral replication, but data on HPA mediation are less clear. Regulation of leukocyte biology by neuroeffector molecules provides a plausible biological mechanism by which psychosocial factors might influence HIV-1 pathogenesis, even in the era of effective antiretroviral therapy. As such, neural and endocrine parameters might provide useful biomarkers for gauging the promise of behavioral interventions and suggest novel adjunctive strategies for controlling HIV-1 disease progression.

  6. Watching single molecules dance

    NASA Astrophysics Data System (ADS)

    Mehta, Amit Dinesh

    Molecular motors convert chemical energy, from ATP hydrolysis or ion flow, into mechanical motion. A variety of increasingly precise mechanical probes have been developed to monitor and perturb these motors at the single molecule level. Several outstanding questions can be best approached at the single molecule level. These include: how far does a motor progress per energy quanta consumed? how does its reaction cycle respond to load? how many productive catalytic cycles can it undergo per diffusional encounter with its track? and what is the mechanical stiffness of a single molecule connection? A dual beam optical trap, in conjunction with in vitro ensemble motility assays, has been used to characterize two members of the myosin superfamily: muscle myosin II and chick brain myosin V. Both move the helical polymer actin, but myosin II acts in large ensembles to drive muscle contraction or cytokinesis, while myosin V acts in small numbers to transport vesicles. An optical trapping apparatus was rendered sufficiently precise to identify a myosin working stroke with 1nm or so, barring systematic errors such as those perhaps due to random protein orientations. This and other light microscopic motility assays were used to characterize myosin V: unlike myosin II this vesicle transport protein moves through many increments of travel while remaining strongly bound to a single actin filament. The step size, stall force, and travel distance of myosin V reveal a remarkably efficient motor capable of moving along a helical track for over a micrometer without significantly spiraling around it. Such properties are fully consistent with the putative role of an organelle transport motor, present in small numbers to maintain movement over long ranges relative to cellular size scales. The contrast between myosin II and myosin V resembles that between a human running on the moon and one walking on earth, where the former allows for faster motion when in larger ensembles but for less

  7. Resolving metal-molecule interfaces at single-molecule junctions

    NASA Astrophysics Data System (ADS)

    Komoto, Yuki; Fujii, Shintaro; Nakamura, Hisao; Tada, Tomofumi; Nishino, Tomoaki; Kiguchi, Manabu

    2016-05-01

    Electronic and structural detail at the electrode-molecule interface have a significant influence on charge transport across molecular junctions. Despite the decisive role of the metal-molecule interface, a complete electronic and structural characterization of the interface remains a challenge. This is in no small part due to current experimental limitations. Here, we present a comprehensive approach to obtain a detailed description of the metal-molecule interface in single-molecule junctions, based on current-voltage (I-V) measurements. Contrary to conventional conductance studies, this I-V approach provides a correlated statistical description of both, the degree of electronic coupling across the metal-molecule interface, and the energy alignment between the conduction orbital and the Fermi level of the electrode. This exhaustive statistical approach was employed to study single-molecule junctions of 1,4-benzenediamine (BDA), 1,4-butanediamine (C4DA), and 1,4-benzenedithiol (BDT). A single interfacial configuration was observed for both BDA and C4DA junctions, while three different interfacial arrangements were resolved for BDT. This multiplicity is due to different molecular adsorption sites on the Au surface namely on-top, hollow, and bridge. Furthermore, C4DA junctions present a fluctuating I-V curve arising from the greater conformational freedom of the saturated alkyl chain, in sharp contrast with the rigid aromatic backbone of both BDA and BDT.

  8. The versatile role of exosomes in cancer progression: diagnostic and therapeutic implications.

    PubMed

    Sundararajan, Vignesh; Sarkar, Fazlul H; Ramasamy, Thamil Selvee

    2018-06-01

    Recent advances in cancer biology have highlighted the relevance of exosomes and nanovesicles as carriers of genetic and biological messages between cancer cells and their immediate and/or distant environments. It has been found that these molecular cues may play significant roles in cancer progression and metastasis. Cancer cells secrete exosomes containing diverse molecules that can be transferred to recipient cells and/or vice versa to induce a plethora of biological processes, including angiogenesis, metastasis formation, therapeutic resistance, epithelial-mesenchymal transition and epigenetic/stemness (re)programming. While exosomes interact with cells within the tumour microenvironment to promote tumour growth, these vesicles can also facilitate the process of distant metastasis by mediating the formation of pre-metastatic niches. Next to their tumour promoting effects, exosomes have been found to serve as potential tools for cancer diagnosis and therapy. The ease of isolating exosomes and their content from different body fluids has led to the identification of diagnostic and prognostic biomarker signatures, as well as to predictive biomarker signatures for therapeutic responses. Exosomes can also be used as cargos to deliver therapeutic anti-cancer drugs, and they can be engineered to serve as vaccines for immunotherapy. Additionally, it has been found that inhibition of exosome secretion, and thus the transfer of oncogenic molecules, holds promise for inhibiting tumour growth. Here we provide recent information on the diverse roles of exosomes in various cellular and systemic processes governing cancer progression, and discuss novel strategies to halt this progression using exosome-based targeted therapies and methods to inhibit exosome secretion and the transfer of pro-tumorigenic molecules. This review highlights the important role of exosomes in cancer progression and its implications for (non-invasive) diagnostics and the development of novel

  9. Making More-Complex Molecules Using Superthermal Atom/Molecule Collisions

    NASA Technical Reports Server (NTRS)

    Shortt, Brian; Chutjian, Ara; Orient, Otto

    2008-01-01

    A method of making more-complex molecules from simpler ones has emerged as a by-product of an experimental study in outer-space atom/surface collision physics. The subject of the study was the formation of CO2 molecules as a result of impingement of O atoms at controlled kinetic energies upon cold surfaces onto which CO molecules had been adsorbed. In this study, the O/CO system served as a laboratory model, not only for the formation of CO2 but also for the formation of other compounds through impingement of rapidly moving atoms upon molecules adsorbed on such cold interstellar surfaces as those of dust grains or comets. By contributing to the formation of increasingly complex molecules, including organic ones, this study and related other studies may eventually contribute to understanding of the origins of life.

  10. Advancing Stage 2 Research on Measures for Monitoring Kindergarten Reading Progress

    ERIC Educational Resources Information Center

    Clemens, Nathan H.; Soohoo, Michelle M.; Wiley, Colby P.; Hsiao, Yu-Yu; Estrella, Ivonne; Allee-Smith, Paula J.; Yoon, Myeongsun

    2018-01-01

    Although several measures exist for frequently monitoring early reading progress, little research has specifically investigated their technical properties when administered on a frequent basis with kindergarten students. In this study, kindergarten students (N = 137) of whom the majority was receiving supplemental intervention for reading skills…

  11. Global Issues in Career and Technical Fields: Internationalizing the Community College Curriculum.

    ERIC Educational Resources Information Center

    Peck, Shirley S.

    1991-01-01

    Presents a rationale for incorporating international content in both general education and career/technical fields, providing a status report on progress to date. Describes four modules prepared by Catonsville Community College (Maryland) instructors for inclusion in criminal justice, air transportation, automotive service, and electronics…

  12. Addressing tomorrow's DMO technical challenges today

    NASA Astrophysics Data System (ADS)

    Milligan, James R.

    2009-05-01

    Distributed Mission Operations (DMO) is essentially a type of networked training that pulls in participants from all the armed services and, increasingly, allies to permit them to "game" and rehearse highly complex campaigns, using a mix of local, distant, and virtual players. The United States Air Force Research Laboratory (AFRL) is pursuing Science and Technology (S&T) solutions to address technical challenges associated with distributed communications and information management as DMO continues to progressively scale up the number, diversity, and geographic dispersal of participants in training and rehearsal exercises.

  13. Diagnostic Efficiency of easyCBM[R] Math: Oregon. Technical Report #1009

    ERIC Educational Resources Information Center

    Anderson, Daniel; Alonzo, Julie; Tindal, Gerald

    2010-01-01

    The easyCBM[R] assessment system is an online benchmark and progress monitoring assessment system designed for use within a response to intervention framework. Educators using easyCBM[R] are often interested in using the results to predict students' state test performance. In the following technical document, we report diagnostic efficiency…

  14. Physics of Molecules

    NASA Astrophysics Data System (ADS)

    Williams, D.; Murdin, P.

    2000-11-01

    Many varieties of molecule have been detected in the Milky Way and in other galaxies. The processes by which these molecules are formed and destroyed are now broadly understood (see INTERSTELLAR CHEMISTRY). These molecules are important components of galaxies in two ways. Firstly, radiation emitted by molecules enables us to trace the presence of diffuse gas, to infer its physical properties and ...

  15. Bleaching/blinking assisted localization microscopy for superresolution imaging using standard fluorescent molecules.

    PubMed

    Burnette, Dylan T; Sengupta, Prabuddha; Dai, Yuhai; Lippincott-Schwartz, Jennifer; Kachar, Bechara

    2011-12-27

    Superresolution imaging techniques based on the precise localization of single molecules, such as photoactivated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM), achieve high resolution by fitting images of single fluorescent molecules with a theoretical Gaussian to localize them with a precision on the order of tens of nanometers. PALM/STORM rely on photoactivated proteins or photoswitching dyes, respectively, which makes them technically challenging. We present a simple and practical way of producing point localization-based superresolution images that does not require photoactivatable or photoswitching probes. Called bleaching/blinking assisted localization microscopy (BaLM), the technique relies on the intrinsic bleaching and blinking behaviors characteristic of all commonly used fluorescent probes. To detect single fluorophores, we simply acquire a stream of fluorescence images. Fluorophore bleach or blink-off events are detected by subtracting from each image of the series the subsequent image. Similarly, blink-on events are detected by subtracting from each frame the previous one. After image subtractions, fluorescence emission signals from single fluorophores are identified and the localizations are determined by fitting the fluorescence intensity distribution with a theoretical Gaussian. We also show that BaLM works with a spectrum of fluorescent molecules in the same sample. Thus, BaLM extends single molecule-based superresolution localization to samples labeled with multiple conventional fluorescent probes.

  16. Intercellular adhesion molecules (ICAMs) and spermatogenesis

    PubMed Central

    Xiao, Xiang; Mruk, Dolores D.; Cheng, C. Yan

    2013-01-01

    BACKGROUND During the seminiferous epithelial cycle, restructuring takes places at the Sertoli–Sertoli and Sertoli–germ cell interface to accommodate spermatogonia/spermatogonial stem cell renewal via mitosis, cell cycle progression and meiosis, spermiogenesis and spermiation since developing germ cells, in particular spermatids, move ‘up and down’ the seminiferous epithelium. Furthermore, preleptotene spermatocytes differentiated from type B spermatogonia residing at the basal compartment must traverse the blood–testis barrier (BTB) to enter the adluminal compartment to prepare for meiosis at Stage VIII of the epithelial cycle, a process also accompanied by the release of sperm at spermiation. These cellular events that take place at the opposite ends of the epithelium are co-ordinated by a functional axis designated the apical ectoplasmic specialization (ES)—BTB—basement membrane. However, the regulatory molecules that co-ordinate cellular events in this axis are not known. METHODS Literature was searched at http://www.pubmed.org and http://scholar.google.com to identify published findings regarding intercellular adhesion molecules (ICAMs) and the regulation of this axis. RESULTS Members of the ICAM family, namely ICAM-1 and ICAM-2, and the biologically active soluble ICAM-1 (sICAM-1) are the likely regulatory molecules that co-ordinate these events. sICAM-1 and ICAM-1 have antagonistic effects on the Sertoli cell tight junction-permeability barrier, involved in Sertoli cell BTB restructuring, whereas ICAM-2 is restricted to the apical ES, regulating spermatid adhesion during the epithelial cycle. Studies in other epithelia/endothelia on the role of the ICAM family in regulating cell movement are discussed and this information has been evaluated and integrated into studies of these proteins in the testis to create a hypothetical model, depicting how ICAMs regulate junction restructuring events during spermatogenesis. CONCLUSIONS ICAMs are crucial

  17. Potential Roles of Protease Inhibitors in Cancer Progression.

    PubMed

    Yang, Peng; Li, Zhuo-Yu; Li, Han-Qing

    2015-01-01

    Proteases are important molecules that are involved in many key physiological processes. Protease signaling pathways are strictly controlled, and disorders in protease activity can result in pathological changes such as cardiovascular and inflammatory diseases, cancer and neurological disorders. Many proteases have been associated with increasing tumor metastasis in various human cancers, suggesting important functional roles in the metastatic process because of their ability to degrade the extracellular matrix barrier. Proteases are also capable of cleaving non-extracellular matrix molecules. Inhibitors of proteases to some extent can reduce invasion and metastasis of cancer cells, and slow down cancer progression. In this review, we focus on the role of a few proteases and their inhibitors in tumors as a basis for cancer prognostication and therapy.

  18. Cold Rydberg molecules

    NASA Astrophysics Data System (ADS)

    Raithel, Georg; Zhao, Jianming

    2017-04-01

    Cold atomic systems have opened new frontiers at the interface of atomic and molecular physics. These include research on novel types of Rydberg molecules. Three types of molecules will be reviewed. Long-range, homonuclear Rydberg molecules, first predicted in [1] and observed in [2], are formed via low-energy electron scattering of the Rydberg electron from a ground-state atom within the Rydberg atom's volume. The binding mostly arises from S- and P-wave triplet scattering. We use a Fermi model that includes S-wave and P-wave singlet and triplet scattering, the fine structure coupling of the Rydberg atom and the hyperfine structure coupling of the 5S1/2 atom (in rubidium [3]). The hyperfine structure gives rise to mixed singlet-triplet potentials for both low-L and high-L Rydberg molecules [3]. A classification into Hund's cases [3, 4, 5] will be discussed. The talk further includes results on adiabatic potentials and adiabatic states of Rydberg-Rydberg molecules in Rb and Cs. These molecules, which have even larger bonding length than Rydberg-ground molecules, are formed via electrostatic multipole interactions. The leading interaction term of neutral Rydberg-Rydberg molecules is between two dipoles, while for ionic Rydberg molecules it is between a dipole and a monopole. NSF (PHY-1506093), NNSF of China (61475123).

  19. THE DEVELOPMENT OF ACHIEVEMENT MEASURES FOR TRADE AND TECHNICAL EDUCATION. PROGRESS REPORT NUMBER THREE.

    ERIC Educational Resources Information Center

    BALDWIN, THOMAS S.

    DURING THIS PERIOD FROM SEPTEMBER 1 THROUGH NOVEMBER 30, 1966, 35 FIELD CONSULTANTS COMPLETED ANALYSIS OF THEIR INDIVIDUAL TRADE AND TECHNICAL CURRICULUMS. THESE ANALYSES WERE DEVELOPED INTO AN OUTLINE TO SERVE AS A GUIDE FOR DEVELOPING ACHIEVEMENT TESTS. THE FINAL OUTLINE WAS DIVIDED INTO AS MANY DIFFERENT AREAS AS THE CONSULTANTS FELT NECESSARY…

  20. Molecules that target nucleophosmin for cancer treatment: an update

    PubMed Central

    Di Matteo, Adele; Franceschini, Mimma; Chiarella, Sara; Rocchio, Serena; Travaglini-Allocatelli, Carlo; Federici, Luca

    2016-01-01

    Nucleophosmin is a highly and ubiquitously expressed protein, mainly localized in nucleoli but able to shuttle between nucleus and cytoplasm. Nucleophosmin plays crucial roles in ribosome maturation and export, centrosome duplication, cell cycle progression, histone assembly and response to a variety of stress stimuli. Much interest in this protein has arisen in the past ten years, since the discovery of heterozygous mutations in the terminal exon of the NPM1 gene, which are the most frequent genetic alteration in acute myeloid leukemia. Nucleophosmin is also frequently overexpressed in solid tumours and, in many cases, its overexpression correlates with mitotic index and metastatization. Therefore it is considered as a promising target for the treatment of both haematologic and solid malignancies. NPM1 targeting molecules may suppress different functions of the protein, interfere with its subcellular localization, with its oligomerization properties or drive its degradation. In the recent years, several such molecules have been described and here we review what is currently known about them, their interaction with nucleophosmin and the mechanistic basis of their toxicity. Collectively, these molecules exemplify a number of different strategies that can be adopted to target nucleophosmin and we summarize them at the end of the review. PMID:27058426

  1. Genome-Scale Architecture of Small Molecule Regulatory Networks and the Fundamental Trade-Off between Regulation and Enzymatic Activity

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

    Reznik, Ed; Christodoulou, Dimitris; Goldford, Joshua E.

    Metabolic flux is in part regulated by endogenous small molecules that modulate the catalytic activity of an enzyme, e.g., allosteric inhibition. In contrast to transcriptional regulation of enzymes, technical limitations have hindered the production of a genome-scale atlas of small molecule-enzyme regulatory interactions. Here, we develop a framework leveraging the vast, but fragmented, biochemical literature to reconstruct and analyze the small molecule regulatory network (SMRN) of the model organism Escherichia coli, including the primary metabolite regulators and enzyme targets. Using metabolic control analysis, we prove a fundamental trade-off between regulation and enzymatic activity, and we combine it with metabolomic measurementsmore » and the SMRN to make inferences on the sensitivity of enzymes to their regulators. By generalizing the analysis to other organisms, we identify highly conserved regulatory interactions across evolutionarily divergent species, further emphasizing a critical role for small molecule interactions in the maintenance of metabolic homeostasis.« less

  2. Genome-Scale Architecture of Small Molecule Regulatory Networks and the Fundamental Trade-Off between Regulation and Enzymatic Activity

    DOE PAGES

    Reznik, Ed; Christodoulou, Dimitris; Goldford, Joshua E.; ...

    2017-09-12

    Metabolic flux is in part regulated by endogenous small molecules that modulate the catalytic activity of an enzyme, e.g., allosteric inhibition. In contrast to transcriptional regulation of enzymes, technical limitations have hindered the production of a genome-scale atlas of small molecule-enzyme regulatory interactions. Here, we develop a framework leveraging the vast, but fragmented, biochemical literature to reconstruct and analyze the small molecule regulatory network (SMRN) of the model organism Escherichia coli, including the primary metabolite regulators and enzyme targets. Using metabolic control analysis, we prove a fundamental trade-off between regulation and enzymatic activity, and we combine it with metabolomic measurementsmore » and the SMRN to make inferences on the sensitivity of enzymes to their regulators. By generalizing the analysis to other organisms, we identify highly conserved regulatory interactions across evolutionarily divergent species, further emphasizing a critical role for small molecule interactions in the maintenance of metabolic homeostasis.« less

  3. Drug and bioactive molecule screening based on a bioelectrical impedance cell culture platform

    PubMed Central

    Ramasamy, Sakthivel; Bennet, Devasier; Kim, Sanghyo

    2014-01-01

    This review will present a brief discussion on the recent advancements of bioelectrical impedance cell-based biosensors, especially the electric cell-substrate impedance sensing (ECIS) system for screening of various bioactive molecules. The different technical integrations of various chip types, working principles, measurement systems, and applications for drug targeting of molecules in cells are highlighted in this paper. Screening of bioactive molecules based on electric cell-substrate impedance sensing is a trial-and-error process toward the development of therapeutically active agents for drug discovery and therapeutics. In general, bioactive molecule screening can be used to identify active molecular targets for various diseases and toxicity at the cellular level with nanoscale resolution. In the innovation and screening of new drugs or bioactive molecules, the activeness, the efficacy of the compound, and safety in biological systems are the main concerns on which determination of drug candidates is based. Further, drug discovery and screening of compounds are often performed in cell-based test systems in order to reduce costs and save time. Moreover, this system can provide more relevant results in in vivo studies, as well as high-throughput drug screening for various diseases during the early stages of drug discovery. Recently, MEMS technologies and integration with image detection techniques have been employed successfully. These new technologies and their possible ongoing transformations are addressed. Select reports are outlined, and not all the work that has been performed in the field of drug screening and development is covered. PMID:25525360

  4. Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding

    PubMed Central

    Chappell, Paul E; Meziane, El Kahina; Harrison, Michael; Magiera, Łukasz; Hermann, Clemens; Mears, Laura; Wrobel, Antoni G; Durant, Charlotte; Nielsen, Lise Lotte; Buus, Søren; Ternette, Nicola; Mwangi, William; Butter, Colin; Nair, Venugopal; Ahyee, Trudy; Duggleby, Richard; Madrigal, Alejandro; Roversi, Pietro; Lea, Susan M; Kaufman, Jim

    2015-01-01

    Highly polymorphic major histocompatibility complex (MHC) molecules are at the heart of adaptive immune responses, playing crucial roles in many kinds of disease and in vaccination. We report that breadth of peptide presentation and level of cell surface expression of class I molecules are inversely correlated in both chickens and humans. This relationship correlates with protective responses against infectious pathogens including Marek's disease virus leading to lethal tumours in chickens and human immunodeficiency virus infection progressing to AIDS in humans. We propose that differences in peptide binding repertoire define two groups of MHC class I molecules strategically evolved as generalists and specialists for different modes of pathogen resistance. We suggest that differences in cell surface expression level ensure the development of optimal peripheral T cell responses. The inverse relationship of peptide repertoire and expression is evidently a fundamental property of MHC molecules, with ramifications extending beyond immunology and medicine to evolutionary biology and conservation. DOI: http://dx.doi.org/10.7554/eLife.05345.001 PMID:25860507

  5. MHC2NNZ: A novel peptide binding prediction approach for HLA DQ molecules

    NASA Astrophysics Data System (ADS)

    Xie, Jiang; Zeng, Xu; Lu, Dongfang; Liu, Zhixiang; Wang, Jiao

    2017-07-01

    The major histocompatibility complex class II (MHC-II) molecule plays a crucial role in immunology. Computational prediction of MHC-II binding peptides can help researchers understand the mechanism of immune systems and design vaccines. Most of the prediction algorithms for MHC-II to date have made large efforts in human leukocyte antigen (HLA, the name of MHC in Human) molecules encoded in the DR locus. However, HLA DQ molecules are equally important and have only been made less progress because it is more difficult to handle them experimentally. In this study, we propose an artificial neural network-based approach called MHC2NNZ to predict peptides binding to HLA DQ molecules. Unlike previous artificial neural network-based methods, MHC2NNZ not only considers sequence similarity features but also captures the chemical and physical properties, and a novel method incorporating these properties is proposed to represent peptide flanking regions (PFR). Furthermore, MHC2NNZ improves the prediction accuracy by combining with amino acid preference at more specific positions of the peptides binding core. By evaluating on 3549 peptides binding to six most frequent HLA DQ molecules, MHC2NNZ is demonstrated to outperform other state-of-the-art MHC-II prediction methods.

  6. Single-molecule conductance studies of photo-active and photochromic molecules

    NASA Astrophysics Data System (ADS)

    Tam, E. S.; Parks, J. J.; Santiago-Berrios, M. B.; Zhong, Y.-W.; Abruna, H. D.; Ralph, D. C.

    2010-03-01

    We perform statistical measurements of single molecule conductance in repeatedly-formed metal-molecule-metal junctions at room temperature. Our results on diaminoalkanes are consistent with those reported by the Venkataraman group. We focus on photo-active and photochromic molecules, including a series of transition-metal complexes with different metal centers and endgroups. We compare the trend in conductance across the family of complexes with that expected from electrochemical measurements. We will also report initial results on the voltage dependence of single-molecule conductances and the effects of optical excitations.

  7. Cold Rydberg molecules

    NASA Astrophysics Data System (ADS)

    Raithel, Georg

    2017-04-01

    Cold atomic systems have opened new frontiers in atomic and molecular physics, including several types of Rydberg molecules. Three types will be reviewed. Long-range Rydberg-ground molecules, first predicted in and observed in, are formed via low-energy electron scattering of the Rydberg electron from a ground-state atom within the Rydberg atom's volume. The binding mostly arises from S- and P-wave triplet scattering. We use a Fermi model that includes S-wave and P-wave singlet and triplet scattering, the fine structure coupling of the Rydberg atom and the hyperfine structure coupling of the 5S1/2 atom (in rubidium). The hyperfine structure gives rise to mixed singlet-triplet potentials for both low-L and high-L Rydberg molecules. A classification into Hund's cases will be discussed. The talk further includes results on adiabatic potentials and adiabatic states of Rydberg-Rydberg molecules in Rb and Cs. These molecules, which have even larger bonding length than Rydberg-ground molecules, are formed via electrostatic multipole interactions. The leading interaction of neutral Rydberg-Rydberg molecules is dipole-dipole, while for ionic Rydberg molecules it is dipole-monopole. Higher-order terms are discussed. FUNDING: NSF (PHY-1506093), NNSF of China (61475123).

  8. Technical efficiency and productivity of Chinese county hospitals: an exploratory study in Henan province, China.

    PubMed

    Cheng, Zhaohui; Tao, Hongbing; Cai, Miao; Lin, Haifeng; Lin, Xiaojun; Shu, Qin; Zhang, Ru-Ning

    2015-09-09

    Chinese county hospitals have been excessively enlarging their scale during the healthcare reform since 2009. The purpose of this paper is to examine the technical efficiency and productivity of county hospitals during the reform process, and to determine whether, and how, efficiency is affected by various factors. 114 sample county hospitals were selected from Henan province, China, from 2010 to 2012. Data envelopment analysis was employed to estimate the technical and scale efficiency of sample hospitals. The Malmquist index was used to calculate productivity changes over time. Tobit regression was used to regress against 4 environmental factors and 5 institutional factors that affected the technical efficiency. (1) 112 (98.2%), 112 (98.2%) and 104 (91.2%) of the 114 sample hospitals ran inefficiently in 2010, 2011 and 2012, with average technical efficiency of 0.697, 0.748 and 0.790, respectively. (2) On average, during 2010-2012, productivity of sample county hospitals increased by 7.8%, which was produced by the progress in technical efficiency changes and technological changes of 0.9% and 6.8%, respectively. (3) Tobit regression analysis indicated that government subsidy, hospital size with above 618 beds and average length of stay assumed a negative sign with technical efficiency; bed occupancy rate, ratio of beds to nurses and ratio of nurses to physicians assumed a positive sign with technical efficiency. There was considerable space for technical efficiency improvement in Henan county hospitals. During 2010-2012, sample hospitals experienced productivity progress; however, the adverse change in pure technical efficiency should be emphasised. Moreover, according to the Tobit results, policy interventions that strictly supervise hospital bed scale, shorten the average length of stay and coordinate the proportion among physicians, nurses and beds, would benefit hospital efficiency. Published by the BMJ Publishing Group Limited. For permission to use (where

  9. Experimental Program Final Technical Progress Report: 15 February 2007 to 30 September 2012

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

    Kinney, Edward R.

    2014-09-12

    This is the final technical report of the grant DE-FG02-04ER41301 to the University of Colorado at Boulder entitled "Intermediate Energy Nuclear Physics" and describes the results of our funded activities during the period 15 February 2007 to 30 September 2012. These activities were primarily carried out at Fermilab, RHIC, and the German lab DESY. Significant advances in these experiments were carried out by members of the Colorado group and are described in detail.

  10. Localization of single biological molecules out of the focal plane

    NASA Astrophysics Data System (ADS)

    Gardini, L.; Capitanio, M.; Pavone, F. S.

    2014-03-01

    Since the behaviour of proteins and biological molecules is tightly related to the cell's environment, more and more microscopy techniques are moving from in vitro to in living cells experiments. Looking at both diffusion and active transportation processes inside a cell requires three-dimensional localization over a few microns range, high SNR images and high temporal resolution (ms order of magnitude). We developed an apparatus that combines different microscopy techniques to satisfy all the technical requirements for 3D tracking of single fluorescent molecules inside living cells with nanometer accuracy. To account for the optical sectioning of thick samples we built up a HILO (Highly Inclined and Laminated Optical sheet) microscopy system through which we can excite the sample in a widefield (WF) configuration by a thin sheet of light that can follow the molecule up and down along the z axis spanning the entire thickness of the cell with a SNR much higher than traditional WF microscopy. Since protein dynamics inside a cell involve all three dimensions, we included a method to measure the x, y, and z coordinates with nanometer accuracy, exploiting the properties of the point-spread-function of out-of-focus quantum dots bound to the protein of interest. Finally, a feedback system stabilizes the microscope from thermal drifts, assuring accurate localization during the entire duration of the experiment.

  11. Single molecule and single cell epigenomics.

    PubMed

    Hyun, Byung-Ryool; McElwee, John L; Soloway, Paul D

    2015-01-15

    Dynamically regulated changes in chromatin states are vital for normal development and can produce disease when they go awry. Accordingly, much effort has been devoted to characterizing these states under normal and pathological conditions. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is the most widely used method to characterize where in the genome transcription factors, modified histones, modified nucleotides and chromatin binding proteins are found; bisulfite sequencing (BS-seq) and its variants are commonly used to characterize the locations of DNA modifications. Though very powerful, these methods are not without limitations. Notably, they are best at characterizing one chromatin feature at a time, yet chromatin features arise and function in combination. Investigators commonly superimpose separate ChIP-seq or BS-seq datasets, and then infer where chromatin features are found together. While these inferences might be correct, they can be misleading when the chromatin source has distinct cell types, or when a given cell type exhibits any cell to cell variation in chromatin state. These ambiguities can be eliminated by robust methods that directly characterize the existence and genomic locations of combinations of chromatin features in very small inputs of cells or ideally, single cells. Here we review single molecule epigenomic methods under development to overcome these limitations, the technical challenges associated with single molecule methods and their potential application to single cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Hadronic molecules

    NASA Astrophysics Data System (ADS)

    Guo, Feng-Kun; Hanhart, Christoph; Meißner, Ulf-G.; Wang, Qian; Zhao, Qiang; Zou, Bing-Song

    2018-01-01

    A large number of experimental discoveries especially in the heavy quarkonium sector that did not meet the expectations of the until then very successful quark model led to a renaissance of hadron spectroscopy. Among various explanations of the internal structure of these excitations, hadronic molecules, being analogs of light nuclei, play a unique role since for those predictions can be made with controlled uncertainty. Experimental evidence of various candidates of hadronic molecules and methods of identifying such structures are reviewed. Nonrelativistic effective field theories are the suitable framework for studying hadronic molecules and are discussed in both the continuum and finite volumes. Also pertinent lattice QCD results are presented. Further, the production mechanisms and decays of hadronic molecules are discussed and comments are given on the reliability of certain assertions often made in the literature.

  13. High precision optical spectroscopy and quantum state selected photodissociation of ultracold 88Sr2 molecules in an optical lattice

    NASA Astrophysics Data System (ADS)

    McDonald, Mickey Patrick

    Over the past several decades, rapid progress has been made toward the accurate characterization and control of atoms, made possible largely by the development of narrow-linewidth lasers and techniques for trapping and cooling at ultracold temperatures. Extending this progress to molecules will have exciting implications for chemistry, condensed matter physics, and precision tests of physics beyond the Standard Model. These possibilities are all consequences of the richness of molecular structure, which is governed by physics substantially different from that characterizing atomic structure. This same richness of structure, however, increases the complexity of any molecular experiment manyfold over its atomic counterpart, magnifying the difficulty of everything from trapping and cooling to the comparison of theory with experiment. This thesis describes work performed over the past six years to establish the state of the art in manipulation and quantum control of ultracold molecules. Our molecules are produced via photoassociation of ultracold strontium atoms followed by spontaneous decay to a stable ground state. We describe a thorough set of measurements characterizing the rovibrational structure of very weakly bound (and therefore very large) 88Sr2 molecules from several different perspectives, including determinations of binding energies; linear, quadratic, and higher order Zeeman shifts; transition strengths between bound states; and lifetimes of narrow subradiant states. The physical intuition gained in these experiments applies generally to weakly bound diatomic molecules, and suggests extensive applications in precision measurement and metrology. In addition, we present a detailed analysis of the thermally broadened spectroscopic lineshape of molecules in a non-magic optical lattice trap, showing how such lineshapes can be used to directly determine the temperature of atoms or molecules in situ, addressing a long-standing problem in ultracold physics

  14. The Development of CBM Vocabulary Measures: Grade 4. Technical Report #1211

    ERIC Educational Resources Information Center

    Alonzo, Julie; Anderson, Daniel; Park, Bitnara Jasmine; Tindal, Gerald

    2012-01-01

    In this technical report, we describe the development and piloting of a series of vocabulary assessments intended for use with students in grades two through eight. These measures, available as part of easyCBM[TM], an online progress monitoring and benchmark/screening assessment system, were developed in 2010 and administered to approximately 1200…

  15. The Development of CBM Vocabulary Measures: Grade 7. Technical Report #1214

    ERIC Educational Resources Information Center

    Alonzo, Julie; Anderson, Daniel; Park, Bitnara Jasmine; Tindal, Gerald

    2012-01-01

    In this technical report, we describe the development and piloting of a series of vocabulary assessments intended for use with students in grades two through eight. These measures, available as part of easyCBM[TM], an online progress monitoring and benchmark/screening assessment system, were developed in 2010 and administered to approximately 1200…

  16. The Development of CBM Vocabulary Measures: Grade 5. Technical Report #1212

    ERIC Educational Resources Information Center

    Alonzo, Julie; Anderson, Daniel; Park, Bitnara Jasmine; Tindal, Gerald

    2012-01-01

    In this technical report, we describe the development and piloting of a series of vocabulary assessments intended for use with students in grades two through eight. These measures, available as part of easyCBM[TM], an online progress monitoring and benchmark/screening assessment system, were developed in 2010 and administered to approximately 1200…

  17. The Development of CBM Vocabulary Measures: Grade 8. Technical Report #1215

    ERIC Educational Resources Information Center

    Alonzo, Julie; Anderson, Daniel; Park, Bitnara Jasmine; Tindal, Gerald

    2012-01-01

    In this technical report, we describe the development and piloting of a series of vocabulary assessments intended for use with students in grades two through eight. These measures, available as part of easyCBM[TM], an online progress monitoring and benchmark/screening assessment system, were developed in 2010 and administered to approximately 1200…

  18. The Development of CBM Vocabulary Measures: Grade 2. Technical Report #1209

    ERIC Educational Resources Information Center

    Alonzo, Julie; Anderson, Daniel; Park, Bitnara Jasmine; Tindal, Gerald

    2012-01-01

    In this technical report, we describe the development and piloting of a series of vocabulary assessments intended for use with students in grades two through eight. These measures, available as part of easyCBM[TM], an online progress monitoring and benchmark/screening assessment system, were developed in 2010 and administered to approximately 1200…

  19. The Development of CBM Vocabulary Measures: Grade 3. Technical Report #1210

    ERIC Educational Resources Information Center

    Alonzo, Julie; Anderson, Daniel; Park, Bitnara Jasmine; Tindal, Gerald

    2012-01-01

    In this technical report, we describe the development and piloting of a series of vocabulary assessments intended for use with students in grades two through eight. These measures, available as part of easyCBM[TM], an online progress monitoring and benchmark/screening assessment system, were developed in 2010 and administered to approximately 1200…

  20. The Development of CBM Vocabulary Measures: Grade 6. Technical Report # 1213

    ERIC Educational Resources Information Center

    Alonzo, Julie; Anderson, Daniel; Park, Bitnara Jasmine; Tindal, Gerald

    2012-01-01

    In this technical report, we describe the development and piloting of a series of vocabulary assessments intended for use with students in grades two through eight. These measures, available as part of easyCBM[TM], an online progress monitoring and benchmark/screening assessment system, were developed in 2010 and administered to approximately 1200…

  1. Nuclear Technology Division annual progress report for period ending June 30, 1972

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

    None

    1972-10-01

    This document is a report of progress on technical programs of the Nuclear Technology,Division of Aerojet Nuclear Company for FY 72 ending June 30, 1972. It contains abstracts or expansions of abstracts of papers which have been published within the year. In these cases, preprints or reprints of the articles available. Results of work in progress are also reported; since this work is of a preliminary nature, the authors should be contacted before including any reference to these works in other publications.

  2. The adaptor molecule RIAM integrates signaling events critical for integrin-mediated control of immune function and cancer progression.

    PubMed

    Patsoukis, Nikolaos; Bardhan, Kankana; Weaver, Jessica D; Sari, Duygu; Torres-Gomez, Alvaro; Li, Lequn; Strauss, Laura; Lafuente, Esther M; Boussiotis, Vassiliki A

    2017-08-22

    Lymphocyte activation requires adhesion to antigen-presenting cells. This is a critical event linking innate and adaptive immunity. Lymphocyte adhesion is accomplished through LFA-1, which must be activated by a process referred to as inside-out integrin signaling. Among the few signaling molecules that have been implicated in inside-out integrin activation in hematopoietic cells are the small guanosine triphosphatase (GTPase) Rap1 and its downstream effector Rap1-interacting molecule (RIAM), a multidomain protein that defined the Mig10-RIAM-lamellipodin (MRL) class of adaptor molecules. Through its various domains, RIAM is a critical node of signal integration for activation of T cells, recruits monomeric and polymerized actin to drive actin remodeling and cytoskeletal reorganization, and promotes inside-out integrin signaling in T cells. As a regulator of inside-out integrin activation, RIAM affects multiple functions of innate and adaptive immunity. The effects of RIAM on cytoskeletal reorganization and integrin activation have implications in cell migration and trafficking of cancer cells. We provide an overview of the structure and interactions of RIAM, and we discuss the implications of RIAM functions in innate and adaptive immunity and cancer. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  3. U.C. Davis high energy particle physics research: Technical progress report -- 1990

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

    NONE

    Summaries of progress made for this period is given for each of the following areas: (1) Task A--Experiment, H1 detector at DESY; (2) Task C--Experiment, AMY detector at KEK; (3) Task D--Experiment, fixed target detectors at Fermilab; (4) Task F--Experiment, PEP detector at SLAC and pixel detector; (5) Task B--Theory, particle physics; and (6) Task E--Theory, particle physics.

  4. Spectroscopy of LiCa and RbSr Molecules on Helium Nanodroplets

    NASA Astrophysics Data System (ADS)

    Lackner, Florian; Krois, Gunter; Ernst, Wolfgang E.

    2013-06-01

    We report on the investigation of mixed alkali metal (Ak) - alkaline earth metal (Ake) molecules on the surface of helium nanodroplets (He_{N}). These molecules have recently attracted considerable attention as candidates for the formation of ultracold molecules with a magnetic and an electronic dipole moment. In our experiments, LiCa and RbSr molecules are formed in a sequential pick-up process in their X^{2}Σ^{+} ground state and cool down rapidly to the droplet temperature of 0.38 K. Excitation spectra of LiCa and RbSr were recorded by using resonance enhanced multi-photon ionization time-of-flight (REMPI-TOF) spectroscopy and laser induced fluorescence (LIF) spectroscopy. On the helium droplet, vibronic transitions in Ak-Ake molecules are broadened and show a characteristic asymmetric peak form, which is caused by the interaction between the molecule and the superfluid He_{N} environment. For the lower electronic transitions in LiCa and RbSr progressions of vibrational bands excited from the X^{2}Σ^{+} (ν'' = 0) state are observed. The LiCa spectra can be compared to molecular beam experiments, which enables the assignment of three band systems near 15260 cm^{-1}, 19300 cm^{-1} and 22120 cm^{-1} as ^{2}Σ^{+}, ^{2}Π_{Ω} and ^{2}Π band, respectively. In the RbSr excitation spectrum we observe a vibrationally resolved band system near 14020 cm^{-1}. Upon electronic excitation, a fraction of the molecules desorb from the droplet surface and dispersed fluorescence spectra allow to study the X^{2}Σ^{+} ground state and excited states of free Ak-Ake molecules. H. Hara, Y. Takasu, Y. Yamaoka, J.M. Doyle, Y. Takahashi, Phys. Rev. Lett. 106, 205304 (2011) C. Callegari and W. E. Ernst, Helium Droplets as Nanocryostats for Molecular Spectroscopy - from the Vacuum Ultraviolet to the Microwave Regime, in: Handbook of High-Resolution Spectroscopy, eds. M. Quack and F. Merkt, John Wiley & Sons, Chichester, (2011) L. M. Russon, G. K. Rothschopf, M. D. Morse, A. I

  5. Virtual reality visual feedback for hand-controlled scanning probe microscopy manipulation of single molecules.

    PubMed

    Leinen, Philipp; Green, Matthew F B; Esat, Taner; Wagner, Christian; Tautz, F Stefan; Temirov, Ruslan

    2015-01-01

    Controlled manipulation of single molecules is an important step towards the fabrication of single molecule devices and nanoscale molecular machines. Currently, scanning probe microscopy (SPM) is the only technique that facilitates direct imaging and manipulations of nanometer-sized molecular compounds on surfaces. The technique of hand-controlled manipulation (HCM) introduced recently in Beilstein J. Nanotechnol. 2014, 5, 1926-1932 simplifies the identification of successful manipulation protocols in situations when the interaction pattern of the manipulated molecule with its environment is not fully known. Here we present a further technical development that substantially improves the effectiveness of HCM. By adding Oculus Rift virtual reality goggles to our HCM set-up we provide the experimentalist with 3D visual feedback that displays the currently executed trajectory and the position of the SPM tip during manipulation in real time, while simultaneously plotting the experimentally measured frequency shift (Δf) of the non-contact atomic force microscope (NC-AFM) tuning fork sensor as well as the magnitude of the electric current (I) flowing between the tip and the surface. The advantages of the set-up are demonstrated by applying it to the model problem of the extraction of an individual PTCDA molecule from its hydrogen-bonded monolayer grown on Ag(111) surface.

  6. Attomole-level Genomics with Single-molecule Direct DNA, cDNA and RNA Sequencing Technologies.

    PubMed

    Ozsolak, Fatih

    2016-01-01

    With the introduction of next-generation sequencing (NGS) technologies in 2005, the domination of microarrays in genomics quickly came to an end due to NGS's superior technical performance and cost advantages. By enabling genetic analysis capabilities that were not possible previously, NGS technologies have started to play an integral role in all areas of biomedical research. This chapter outlines the low-quantity DNA and cDNA sequencing capabilities and applications developed with the Helicos single molecule DNA sequencing technology.

  7. Scientific and Technical Information Transfer for Education (STITE). Research Report No. 2.

    ERIC Educational Resources Information Center

    Zunde, Pranas

    STITE (Scientific and Technical Information Transfer for Education) is basically a system to interface between science information and the science learner. As such STITE acts as a link between STIC (Science and Technology Infromation Centers) and LIS (Learning Information Systems). In this second progress report the internal knowledge of STITE is…

  8. A new semiquantitative method for evaluation of metastasis progression.

    PubMed

    Volarevic, A; Ljujic, B; Volarevic, V; Milovanovic, M; Kanjevac, T; Lukic, A; Arsenijevic, N

    2012-01-01

    Although recent technical advancements are directed toward developing novel assays and methods for detection of micro and macro metastasis, there are still no reports of reliable, simple to use imaging software that could be used for the detection and quantification of metastasis in tissue sections. We herein report a new semiquantitative method for evaluation of metastasis progression in a well established 4T1 orthotopic mouse model of breast cancer metastasis. The new semiquantitative method presented here was implemented by using the Autodesk AutoCAD 2012 program, a computer-aided design program used primarily for preparing technical drawings in 2 dimensions. By using the Autodesk AutoCAD 2012 software- aided graphical evaluation we managed to detect each metastatic lesion and we precisely calculated the average percentage of lung and liver tissue parenchyma with metastasis in 4T1 tumor-bearing mice. The data were highly specific and relevant to descriptive histological analysis, confirming reliability and accuracy of the AutoCAD 2012 software as new method for quantification of metastatic lesions. The new semiquantitative method using AutoCAD 2012 software provides a novel approach for the estimation of metastatic progression in histological tissue sections.

  9. Along the Central Dogma-Controlling Gene Expression with Small Molecules.

    PubMed

    Schneider-Poetsch, Tilman; Yoshida, Minoru

    2018-05-04

    The central dogma of molecular biology, that DNA is transcribed into RNA and RNA translated into protein, was coined in the early days of modern biology. Back in the 1950s and 1960s, bacterial genetics first opened the way toward understanding life as the genetically encoded interaction of macromolecules. As molecular biology progressed and our knowledge of gene control deepened, it became increasingly clear that expression relied on many more levels of regulation. In the process of dissecting mechanisms of gene expression, specific small-molecule inhibitors played an important role and became valuable tools of investigation. Small molecules offer significant advantages over genetic tools, as they allow inhibiting a process at any desired time point, whereas mutating or altering the gene of an important regulator would likely result in a dead organism. With the advent of modern sequencing technology, it has become possible to monitor global cellular effects of small-molecule treatment and thereby overcome the limitations of classical biochemistry, which usually looks at a biological system in isolation. This review focuses on several molecules, especially natural products, that have played an important role in dissecting gene expression and have opened up new fields of investigation as well as clinical venues for disease treatment. Expected final online publication date for the Annual Review of Biochemistry Volume 87 is June 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  10. [Biophysics of single molecules].

    PubMed

    Serdiuk, I N; Deriusheva, E I

    2011-01-01

    The modern methods of research of biological molecules whose application led to the development of a new field of science, biophysics of single molecules, are reviewed. The measurement of the characteristics of single molecules enables one to reveal their individual features, and it is just for this reason that much more information can be obtained from one molecule than from the entire ensample of molecules. The high sensitivity of the methods considered in detail makes it possible to come close to the solution of the basic problem of practical importance, namely, the determination of the nucleotide sequence of a single DNA molecule.

  11. Modeling Molecules

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The molecule modeling method known as Multibody Order (N) Dynamics, or MBO(N)D, was developed by Moldyn, Inc. at Goddard Space Flight Center through funding provided by the SBIR program. The software can model the dynamics of molecules through technology which stimulates low-frequency molecular motions and properties, such as movements among a molecule's constituent parts. With MBO(N)D, a molecule is substructured into a set of interconnected rigid and flexible bodies. These bodies replace the computation burden of mapping individual atoms. Moldyn's technology cuts computation time while increasing accuracy. The MBO(N)D technology is available as Insight II 97.0 from Molecular Simulations, Inc. Currently the technology is used to account for forces on spacecraft parts and to perform molecular analyses for pharmaceutical purposes. It permits the solution of molecular dynamics problems on a moderate workstation, as opposed to on a supercomputer.

  12. Recent progresses on AI-2 bacterial quorum sensing inhibitors.

    PubMed

    Zhu, Peng; Li, Minyong

    2012-01-01

    Quorum sensing (QS) is a communication procedure that predominates gene expression in response to cell density and fluctuations in the neighboring environment as a result of discerning molecules termed autoinducers (AIs). It has been embroiled that QS can govern bacterial behaviors such as the secretion of virulence factors, biofilm formation, bioluminescence production, conjugation, sporulation and swarming motility. Autoinducer 2 (AI-2), a QS signaling molecule brought up to be involved in interspecies communication, exists in both gram-negative and -positive bacteria. Therefore, novel approaches to interrupt AI-2 quorum sensing are being recognized as next generation antimicrobials. In the present review article, we summarized recent progresses on AI-2 bacterial quorum sensing inhibitors and discussed their potential as the antibacterial agents.

  13. Combining single-molecule manipulation and single-molecule detection.

    PubMed

    Cordova, Juan Carlos; Das, Dibyendu Kumar; Manning, Harris W; Lang, Matthew J

    2014-10-01

    Single molecule force manipulation combined with fluorescence techniques offers much promise in revealing mechanistic details of biomolecular machinery. Here, we review force-fluorescence microscopy, which combines the best features of manipulation and detection techniques. Three of the mainstay manipulation methods (optical traps, magnetic traps and atomic force microscopy) are discussed with respect to milestones in combination developments, in addition to highlight recent contributions to the field. An overview of additional strategies is discussed, including fluorescence based force sensors for force measurement in vivo. Armed with recent exciting demonstrations of this technology, the field of combined single-molecule manipulation and single-molecule detection is poised to provide unprecedented views of molecular machinery. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Progress and Prospect: A Report Submitted to the Governing Board of the Maricopa County Community College District.

    ERIC Educational Resources Information Center

    Maricopa Technical Community Coll., Phoenix, AZ.

    This two-part report seeks to outline the progress made to date by Maricopa Technical Community College (MTCC) through its first eight years of operation, and to recommend specific actions which might be taken in the future by the college to insure its continued progress and response to community needs in light of constraints on funding and…

  15. Monitoring Student Progress and Publicising the Results. Information Bank Number 1270.

    ERIC Educational Resources Information Center

    Jones, D. T. L.

    Arguing that assessments of student progress describe the consequences of the interaction of the multitude of elements that make up the educational system, this paper examines the three-tiered assessment system used at Redhill Technical College (RTC), in Surrey, England, to fulfill diagnostic and motivational functions for the college as a whole.…

  16. Diagnostic Efficiency of easyCBM[R] Math: Washington State. Technical Report #1008

    ERIC Educational Resources Information Center

    Anderson, Daniel; Alonzo, Julie; Tindal, Gerald

    2010-01-01

    easyCBM[R] is an online benchmark and progress monitoring assessment system designed for use within a response to intervention framework. Educators using easyCBM[R] are often interested in using the results to predict students' state test performance. In the following technical document, we report diagnostic efficiency statistics using a sample…

  17. FY2013 Energy Storage R&D Progress Report

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

    none,

    2014-02-01

    The FY 2013 Progress Report for Energy Storage R&D focuses on advancing the development of batteries to enable a large market penetration of hybrid and electric vehicles. Program targets focus on overcoming technical barriers to enable market success including: (1) significantly reducing battery cost, (2) increasing battery performance (power, energy, durability), (3) reducing battery weight & volume, and (4) increasing battery tolerance to abusive conditions such as short circuit, overcharge, and crush.

  18. Final report : for the period of December 1999 through November 30, 2000 : Florida Transit Training Program (1999/2000) : Florida Technical Assistance Program (1999/2000)

    DOT National Transportation Integrated Search

    2000-01-01

    The following progress report is intended to highlight the significant activities of the Florida Transit Training Program and Florida Technical Assistant Program. The following progress report is intended to highlight the significant activities of th...

  19. The Independent Technical Analysis Process Final Report 2006-2007.

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

    Duberstein, Corey; Ham, Kenneth; Dauble, Dennis

    2007-03-01

    The Bonneville Power Administration (BPA) contracted with the Pacific Northwest National Laboratory (PNNL) to provide technical analytical support for system-wide fish passage information (BPA Project No. 2006-010-00). The goal of this project was to produce rigorous technical analysis products using independent analysts and anonymous peer reviewers. This project provided an independent technical source for non-routine fish passage analyses while allowing routine support functions to be performed by other well-qualified entities. The Independent Technical Analysis Process (ITAP) was created to provide non-routine analysis for fish and wildlife agencies and tribes in particular and the public in general on matters related tomore » juvenile and adult salmon and steelhead passage through the mainstem hydrosystem. The process was designed to maintain the independence of analysts and reviewers from parties requesting analyses, to avoid potential bias in technical products. The objectives identified for this project were to administer a rigorous, transparent process to deliver unbiased technical assistance necessary to coordinate recommendations for storage reservoir and river operations that avoid potential conflicts between anadromous and resident fish. Seven work elements, designated by numbered categories in the Pisces project tracking system, were created to define and accomplish project goals as follows: (1) 118 Coordination - Coordinate technical analysis and review process: (a) Retain expertise for analyst/reviewer roles. (b) Draft research directives. (c) Send directive to the analyst. (d) Coordinate two independent reviews of the draft report. (e) Ensure reviewer comments are addressed within the final report. (2) 162 Analyze/Interpret Data - Implement the independent aspects of the project. (3) 122 Provide Technical Review - Implement the review process for the analysts. (4) 132 Produce Annual Report - FY06 annual progress report with Pisces Disseminate (5

  20. Mathematics Technical Report: Exercise Volume. National Assessment of Educational Progress. Report No. 04-MA-20.

    ERIC Educational Resources Information Center

    Education Commission of the States, Denver, CO. National Assessment of Educational Progress.

    Included in Chapter 1 of this report are background information on the 1972-73 mathematics assessment; details of the computational formulas used in reporting results; and explanations of the technical documentation, exercise presentation, documentation pages, scoring guides, and data tables for released and unreleased exercises. The remainder of…

  1. Nanoparticle assisted laser desorption/ionization mass spectrometry for small molecule analytes.

    PubMed

    Abdelhamid, Hani Nasser

    2018-03-01

    Nanoparticle assisted laser desorption/ionization mass spectrometry (NPs-ALDI-MS) shows remarkable characteristics and has a promising future in terms of real sample analysis. The incorporation of NPs can advance several methods including surface assisted LDI-MS, and surface enhanced LDI-MS. These methods have advanced the detection of many thermally labile and nonvolatile biomolecules. Nanoparticles circumvent the drawbacks of conventional organic matrices for the analysis of small molecules. In most cases, NPs offer a clear background without interfering peaks, absence of fragmentation of thermally labile molecules, and allow the ionization of species with weak noncovalent interactions. Furthermore, an enhancement in sensitivity and selectivity can be achieved. NPs enable straightforward analysis of target species in a complex sample. This review (with 239 refs.) covers the progress made in laser-based mass spectrometry in combination with the use of metallic NPs (such as AuNPs, AgNPs, PtNPs, and PdNPs), NPs consisting of oxides and chalcogenides, silicon-based NPs, carbon-based nanomaterials, quantum dots, and metal-organic frameworks. Graphical abstract An overview is given on nanomaterials for use in surface-assisted laser desorption/ionization mass spectrometry of small molecules.

  2. Advances in treating psoriasis in the elderly with small molecule inhibitors.

    PubMed

    Cline, Abigail; Cardwell, Leah A; Feldman, Steven R

    2017-12-01

    Due to the chronic nature of psoriasis, the population of elderly psoriasis patients is increasing. However, many elderly psoriatic patients are not adequately treated because management is challenging as a result of comorbidities, polypharmacy, and progressive impairment of organ systems. Physicians may hesitate to use systemic or biologic agents in elderly psoriasis patients because of an increased risk of adverse events in this patient population. Small molecule medications are emerging as promising options for elderly patients with psoriasis and other inflammatory conditions. Areas covered: Here we review the efficacy, safety and tolerability of small molecule inhibitors apremilast, tofacitinib, ruxolitinib, baricitinib, and peficitinib in the treatment of psoriasis, with focus on their use in the elderly population. Expert opinion: Although small molecule inhibitors demonstrate efficacy in elderly patients with psoriasis, they will require larger head-to-head studies and post-marketing registries to evaluate their effectiveness and safety in specific patient populations. Apremilast, ruxolitinib, and peficitinib are effective agents with favorable side effect profiles; however, physicians should exercise caution when prescribing tofacitinib or baricitinib in elderly populations due to adverse events. The high cost of these drugs in the U.S. is likely to limit their use.

  3. Small-molecule ligand docking into comparative models with Rosetta

    PubMed Central

    Combs, Steven A; DeLuca, Samuel L; DeLuca, Stephanie H; Lemmon, Gordon H; Nannemann, David P; Nguyen, Elizabeth D; Willis, Jordan R; Sheehan, Jonathan H; Meiler, Jens

    2017-01-01

    Structure-based drug design is frequently used to accelerate the development of small-molecule therapeutics. Although substantial progress has been made in X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, the availability of high-resolution structures is limited owing to the frequent inability to crystallize or obtain sufficient NMR restraints for large or flexible proteins. Computational methods can be used to both predict unknown protein structures and model ligand interactions when experimental data are unavailable. This paper describes a comprehensive and detailed protocol using the Rosetta modeling suite to dock small-molecule ligands into comparative models. In the protocol presented here, we review the comparative modeling process, including sequence alignment, threading and loop building. Next, we cover docking a small-molecule ligand into the protein comparative model. In addition, we discuss criteria that can improve ligand docking into comparative models. Finally, and importantly, we present a strategy for assessing model quality. The entire protocol is presented on a single example selected solely for didactic purposes. The results are therefore not representative and do not replace benchmarks published elsewhere. We also provide an additional tutorial so that the user can gain hands-on experience in using Rosetta. The protocol should take 5–7 h, with additional time allocated for computer generation of models. PMID:23744289

  4. Investigation on Large Molecule Permeation through Liposome Lipid Bilayer Induced by Microplasma Irradiation

    NASA Astrophysics Data System (ADS)

    Nagaiwa, Hidenori; Aibara, Daijiro; Ikeda, Yoshihisa; Motomura, Hideki; Kido, Yugo; Satoh, Susumu; Tachibana, Kunihide; Jinno, Masahumi

    2015-09-01

    The authors have been developing a novel gene transfection method using microplasma irradiation. In order to clarify the mechanism of large molecule permeation process through the lipid bilayer, plasma induced outflow of hydrophilic fluorescent dye molecules, which were encapsulated in the liposome, was observed. By microplasma irradiation on the liposome suspension, the dyes flowed out from the inside of the liposomes. The outflow of the dyes was enhanced by longer plasma irradiation time. Investigation of the outflow mechanism, i.e. permeation enhancement of the lipid bilayer or burst of the liposome, is under progress. This work was partly supported by JSPS KAKENHI Grant-in-Aid for Scientific Research on Innovative Areas (Number 25108509,15H00896) and a grant from Ehime University.

  5. Technical change in US industry: A cross-industry analysis

    NASA Technical Reports Server (NTRS)

    Nelson, R. R. (Editor)

    1981-01-01

    The nature of the public policies which have influenced the pace and pattern of technical progress in a number of American industries is studied with the view of assessing the broad effects of these policies. The industries studied are agriculture, pharmaceuticals, semiconductors, computers, civil aircraft, automobiles and residential construction. The policies considered include research and development funding as well as government procurement, education, information dissemination, patent protection, licensing, regulations, and anti-trust policies.

  6. Novel dual small-molecule HIV inhibitors: scaffolds and discovery strategies.

    PubMed

    Song, Anran; Yu, Haiqing; Wang, Changyuan; Zhu, Xingqi; Liu, Kexin; Ma, Xiaodong

    2015-01-01

    Searching for safe and effective treatments for HIV infection is still a great challenge worldwide in spite of the 27 marketed anti-HIV drugs and the powerful highly active antiretroviral therapy (HAART). As a promising prospect for generation of new HIV therapy drugs, multiple ligands (MDLs) were greatly focused on recently due to their lower toxicity, simplified dosing and patient adherence than single-target drugs. Till now, by disrupting two active sites or steps of HIV replications, a number of HIV dual inhibitors, such as CD4-gssucap120 inhibitors, CXCR4-gp20 inhibitors, RT-CXCR4 inhibitors, RT-protease inhibitors, RT-integrase inhibitors, and RTassociated functions inhibitors have been identified. Generally, these dual inhibitors were discovered mainly through screening approaches and design strategies. Of these compounds, the molecules bearing small skeletons exhibited strong anti-HIV activity and aroused great attention recently. Reviewing the progress of the dual small-molecule HIV inhibitors from the point of view of their scaffolds and discovery strategies will provide valuable information for producing more effective anti-HIV drugs. In this regard, novel dual small-molecule HIV inhibitors were illustrated, and their discovery paradigms as the major contents were also summarized in this manuscript.

  7. Recent Progress in SERS Biosensing

    PubMed Central

    Bantz, Kyle C.; Meyer, Audrey F.; Wittenberg, Nathan J.; Im, Hyungsoon; Kurtuluş, Özge; Lee, Si Hoon; Lindquist, Nathan C.

    2011-01-01

    This perspective gives an overview of recent developments in surface-enhanced Raman scattering (SERS) for biosensing. We focus this review on SERS papers published in the last 10 years and to specific applications of detecting biological analytes. Both intrinsic and extrinsic SERS biosensing schemes have been employed to detect and identify small molecules, nucleic acids, lipids, peptides, and proteins, as well as for in vivo and cellular sensing. Current SERS substrate technologies along with a series of advancements in surface chemistry, sample preparation, intrinsic/extrinsic signal transduction schemes, and tip-enhanced Raman spectroscopy are discussed. The progress covered herein shows great promise for widespread adoption of SERS biosensing. PMID:21509385

  8. Technical Advances in Intracellular Detection Using Immuno-Gold Particles: Simple Cryofixation with Metal Contact Quick Freezing.

    PubMed

    Song, Chihong; Lee, Ju Huck; Jun, Sangmi; Chung, Jeong Min; Hyun, Jaekyung; Jung, Hyun Suk

    2016-05-01

    The preparation of biological specimens using cryofixation techniques ensures excellent visibility of intracellular structures and preserves the antigenic sites of subcellular molecules. Hence, cryofixation is an effective method of preparing samples for analyses using antibodies conjugated to gold nanoparticles that are designed to detect the localization of specific target molecules within cells. However, cryofixation cannot be utilized easily because it requires expensive equipment and skilled technologists, resulting in a high level of expense for researchers. Here, we describe a simple technical approach to cryofixation that uses metal contact quick freezing followed by a modified freeze substitution technique and immuno-gold labeling electron microscopy. Micrograph images of cells prepared using this modified cryofixation method demonstrated its superiority over chemical fixation for high contrast visualization of the morphologies of cellular components and preservation of antigenicity for immuno-gold labeling. This report provides valuable technical information related to the advancement of metal contact quick freezing techniques, which can be used to visualize biomedical events of interest in an easy, simple, and rapid manner.

  9. Developing Technical Writing Skills in the Physical Chemistry Laboratory: A Progressive Approach Employing Peer Review

    ERIC Educational Resources Information Center

    Gragson, Derek E.; Hagen, John P.

    2010-01-01

    Writing formal "journal-style" lab reports is often one of the requirements chemistry and biochemistry students encounter in the physical chemistry laboratory. Helping students improve their technical writing skills is the primary reason this type of writing is a requirement in the physical chemistry laboratory. Developing these skills is an…

  10. 41. Photocopy of progress photograph ca. 1974, photographer unknown. Original ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    41. Photocopy of progress photograph ca. 1974, photographer unknown. Original photograph Property of United States Air Force, 21" Space Command. This is the source for views 41 to 47. CAPE COD AIR STATION PAVE PAWS FACILITY - SHOWING BUILDING "RED IRON" STEEL STRUCTURE NEARING COMPLETION. - Cape Cod Air Station, Technical Facility-Scanner Building & Power Plant, Massachusetts Military Reservation, Sandwich, Barnstable County, MA

  11. Micromanipulation by laser microbeam and optical tweezers: from plant cells to single molecules.

    PubMed

    Greulich, K O; Pilarczyk, G; Hoffmann, A; Meyer Zu Hörste, G; Schäfer, B; Uhl, V; Monajembashi, S

    2000-06-01

    Complete manipulation by laser light allows precise and gentle treatment of plant cells, subcellular structures, and even individual DNA molecules. Recently, affordable lasers have become available for the construction of microbeams as well as for optical tweezers. This may generate new interest in these tools for plant biologists. Early experiments, reviewed in this journal, showed that laser supported microinjection of material into plant cells or tissues circumvents mechanical problems encountered in microinjection by fragile glass capillaries. Plant protoplasts could be fused with each other when under microscopical observation, and it was no major problem to generate a triple or quadruple fusion product. In the present paper we review experiments where membrane material was prepared from root hair tips and microgravity was simulated in algae. As many plant cells are transparent, it is possible to work inside living, intact cells. New experiments show that it is possible to release by optical micromanipulation, with high spatial resolutions, intracellular calcium from caged compounds and to study calcium oscillations. An example for avian cardiac tissue is given, but the technique is also suitable for plant cell research. As a more technical tool, optical tweezers can be used to spatially fix subcellular structures otherwise moving inside a cell and thus make them available for investigation with a confocal microscope even when the time for image formation is extended (for example at low fluorescence emission). A molecular biological example is the handling of chromosomes and isolated individual DNA molecules by laser microtools. For example, chromosomes can be cut along complex trajectories, not only perpendicular to their long axis. Single DNA molecules are cut by the laser microbeam and, after coupling such a molecule to a polystrene microbead, are handled in complex geometries. Here, the individual DNA molecules are made visible with a conventional

  12. Effect of pulsed progressive fluoroscopy on reduction of radiation dose in the cardiac catheterization laboratory

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

    Holmes, D.R. Jr.; Wondrow, M.A.; Gray, J.E.

    1990-01-01

    The increased application of therapeutic interventional cardiology procedures is associated with increased radiation exposure to physicians, patients and technical personnel. New advances in imaging techniques have the potential for reducing radiation exposure. A progressive scanning video system with a standard vascular phantom has been shown to decrease entrance radiation exposure. The effect of this system on reducing actual radiation exposure to physicians and technicians was assessed from 1984 through 1987. During this time, progressive fluoroscopy was added sequentially to all four adult catheterization laboratories; no changes in shielding procedures were made. During this time, the case load per physician increasedmore » by 63% and the number of percutaneous transluminal coronary angioplasty procedures (a high radiation procedure) increased by 244%. Despite these increases in both case load and higher radiation procedures, the average radiation exposure per physician declined by 37%. During the same time, the radiation exposure for technicians decreased by 35%. Pulsed progressive fluoroscopy is effective for reducing radiation exposure to catheterization laboratory physicians and technical staff.« less

  13. Cytokine and adhesion molecule expression evolves between the neutrophilic and lymphocytic phases of viral meningitis.

    PubMed

    Makis, Alexandros; Shipway, David; Hatzimichael, Eleftheria; Galanakis, Emmanouil; Pshezhetskiy, Dmitry; Chaliasos, Nikolaos; Stebbing, Justin; Siamopoulou, Antigone

    2010-09-01

    Viral meningitis is characterized by cerebrospinal fluid (CSF) lymphocyte pleocytosis, although neutrophils may predominate in the early phase. The T helper 1 (Th1)/Th2 cytokine balance and expression of adhesion molecules seem to be involved in the CSF chemotaxis. We aimed to determine expression of cytokines and adhesion molecules in enteroviral meningitis. We investigated the serum and CSF levels of adhesion molecules (E-selectin, L-selectin, vascular cell adhesion molecule-1 [VCAM-1], and intracellular adhesion molecule-1 [ICAM-1]) and cytokines (interleukin-12 [IL-12] and IL-4) in 105 children during an outbreak of enteroviral meningitis. Diagnosis was confirmed with positive polymerase chain reaction (PCR) and/or serology for echovirus or Coxsackie virus, and matched with control subjects for clinical features but with negative PCR and/or serology. Apart from VCAM-1, the CSF levels of all investigated inflammatory molecules were significantly increased. In serum, sL-selectin and ICAM-1 levels were significantly higher than control subjects. Serum and CSF L-selectin, serum VCAM-1, and CSF IL-12 were all observed to be expressed in significantly higher levels in the neutrophil-dominant subgroup (72% had duration of symptoms <24 h) than in the lymphocyte-dominant group (87.5% had duration of symptoms >24 h). Serum and CSF ICAM-1 was found at significantly higher levels in the latter group. Evolving expression of adhesion molecules and cytokines indicates a shift from Th1 to Th2 immune responses as infection progresses.

  14. Strategy to discover diverse optimal molecules in the small molecule universe.

    PubMed

    Rupakheti, Chetan; Virshup, Aaron; Yang, Weitao; Beratan, David N

    2015-03-23

    The small molecule universe (SMU) is defined as a set of over 10(60) synthetically feasible organic molecules with molecular weight less than ∼500 Da. Exhaustive enumerations and evaluation of all SMU molecules for the purpose of discovering favorable structures is impossible. We take a stochastic approach and extend the ACSESS framework ( Virshup et al. J. Am. Chem. Soc. 2013 , 135 , 7296 - 7303 ) to develop diversity oriented molecular libraries that can generate a set of compounds that is representative of the small molecule universe and that also biases the library toward favorable physical property values. We show that the approach is efficient compared to exhaustive enumeration and to existing evolutionary algorithms for generating such libraries by testing in the NKp fitness landscape model and in the fully enumerated GDB-9 chemical universe containing 3 × 10(5) molecules.

  15. Strategy To Discover Diverse Optimal Molecules in the Small Molecule Universe

    PubMed Central

    2015-01-01

    The small molecule universe (SMU) is defined as a set of over 1060 synthetically feasible organic molecules with molecular weight less than ∼500 Da. Exhaustive enumerations and evaluation of all SMU molecules for the purpose of discovering favorable structures is impossible. We take a stochastic approach and extend the ACSESS framework (Virshup et al. J. Am. Chem. Soc.2013, 135, 7296–730323548177) to develop diversity oriented molecular libraries that can generate a set of compounds that is representative of the small molecule universe and that also biases the library toward favorable physical property values. We show that the approach is efficient compared to exhaustive enumeration and to existing evolutionary algorithms for generating such libraries by testing in the NKp fitness landscape model and in the fully enumerated GDB-9 chemical universe containing 3 × 105 molecules. PMID:25594586

  16. Exotic Molecules in Space: A Coordinated Astronomical Laboratory and Theoretical Study

    NASA Technical Reports Server (NTRS)

    Thaddeus, Patrick

    1999-01-01

    The past three years have been a period of great progress in our laboratory investigation of molecules of astrophysical interest-the most productive by far in the 20-year history of a research program which has led to the discovery of over 20% of the 123 known interstellar and circumstellar molecules. Most of the discoveries made during this period have been the result of the construction in late 1995 and early 1996 of a Fourier transform microwave spectrometer working in the centimeter-wave band. The sensitivity of this instrument from the moment that it was turned on has exceeded our expectations by an order of magnitude. The Table below shows the 46 new molecules which have been discovered. Most are carbon chains, the dominant type of molecule which has been found in space. Several comments with respect to these molecules should be made: 1. There are probably no mistakes in any of the identifications, since these have been confirmed by the standard, powerful assays and tests used to check spectroscopic identifications: isotopic substitution, quantum calculations of the expected molecular structures, detection of hyperfine structure, Zeeman effect, etc. 2. The radio laboratory astrophysics of the entire set is complete for the time being, in the sense that essentially all the astronomically interesting radio transitions (including hfs when present) are either directly measured or can now be calculated from the derived spectroscopic constants to better than 1 part per million (or 0.3 km s-1 in radial velocity, and often much better than that). 3. Six of the forty six new molecules have already been identified in space, in every case but one on the basis of our laboratory measurements. 4. Sensitive as they are, our laboratory techniques are far from fundamental limits on sensitivity, and 5. One of the principal motivations of our research is to close the fairly small mass and size gap, now only a factor of a few, between the smallest postulated interstellar grains

  17. The Kinetic Mechanism for DNA Unwinding by Multiple Molecules of Dda Helicase Aligned on DNA†

    PubMed Central

    Eoff, Robert L.; Raney, Kevin D.

    2010-01-01

    Helicases catalyze the separation of double-stranded nucleic acids to form single-stranded intermediates. Using transient state kinetic methods we have determined the kinetic properties of DNA unwinding under conditions that favor a monomeric form of the Dda helicase as well as conditions that allow multiple molecules to function on the same substrate. Multiple helicase molecules can align like a train on the DNA track. The number of base pairs unwound in a single binding event for Dda is increased from ~19 bp for the monomeric form to ~64 bp when as many as four Dda molecules are aligned on the same substrate, while the kinetic step-size (3.2 ± 0.7 bp) and unwinding rate (242 ± 25 bp s−1) appear to be independent of the number of Dda molecules present on a given substrate. The data support a model in which the helicase molecules bound to the same substrate move along the DNA track independently during DNA unwinding. The observed increase in processivity arises from the increased probability that at least one of the helicases will completely unwind the DNA prior to dissociation. These results are in contrast to previous reports in which multiple Dda molecules on the same track greatly enhanced the rate and amplitude for displacement of protein blocks on the track. Therefore, only when the progress of the lead molecule in the train is impeded by some type of block, such as a protein bound to DNA, do the trailing molecules interact with the lead molecule in order to overcome the block. The fact that trailing helicase molecules have little impact on the lead molecule in the train during routine DNA unwinding suggests that the trailing molecules are moving at similar rates as the lead molecule. This result implicates a step in the translocation mechanism as contributing greatly to the overall rate-limiting step for unwinding of duplex DNA. PMID:20408588

  18. Annual Progress Report (17th) and 1992-97 Renewal Proposal Interactive Graphics for Molecular Studies

    DTIC Science & Technology

    1991-01-24

    Molecular Graphics, vol. 6, No. 4 (Dec. 1988), p. 223. Turk, Greg, "Interactive Collision Detection for Molecular Graphics," M.S. thesis , UNC-Chapel Hill...Problem," Master’s thesis , UNC Department of Computer Science Technical Report #TR87-013, May 1987. Pique, ME., "Technical Trends in Molecular Graphics...AD-A236 598 Seventeenth Annual Progress Report and 1992-97 Renewal Proposal Interactive Graphics for Molecular Studies TR91-020 January 24, 1991 red

  19. Advanced light source: Compendium of user abstracts and technical reports,1993-1996

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

    None, None

    1997-04-01

    This compendium contains abstracts written by users summarizing research completed or in progress from 1993-1996, ALS technical reports describing ongoing efforts related to improvement in machine operations and research and development projects, and information on ALS beamlines planned through 1998. Two tables of contents organize the user abstracts by beamline and by area of research, and an author index makes abstracts accessible by author and by principal investigator. Technical details for each beamline including whom to contact for additional information can be found in the beamline information section. Separate abstracts have been indexed into the database for contributions to thismore » compendium.« less

  20. Seizing the Future: How Ohio's Career-Technical Education Programs Fuse Academic Rigor and Real-World Experiences to Prepare Students for College and Careers

    ERIC Educational Resources Information Center

    Guarino, Heidi; Yoder, Shaun

    2015-01-01

    "Seizing the Future: How Ohio's Career and Technical Education Programs Fuse Academic Rigor and Real-World Experiences to Prepare Students for College and Work," demonstrates Ohio's progress in developing strong policies for career and technical education (CTE) programs to promote rigor, including college- and career-ready graduation…

  1. An approach to knowledge structuring for advanced phases of the Technical and Management Information System (TMIS)

    NASA Technical Reports Server (NTRS)

    Goranson, H. T.

    1986-01-01

    The Technical and Management Information System (TMIS) must employ on enlightened approach to its object structure, but basic issues in conceptual structuring remain to be resolved. Sirius outlines the necessary agenda and reports on progress toward solutions.

  2. INDOT Technical Training Plan : [Technical Summary

    DOT National Transportation Integrated Search

    2012-01-01

    A wide range of job classifications, increasing technical : performance expectations, licensing and certification requirements, : budget restrictions and frequent department : reorganization has made technical training of employees : more difficult, ...

  3. The Gap That Can't Go Away: The Catch-22 of Reclassification in Monitoring the Progress of English Learners

    ERIC Educational Resources Information Center

    Saunders, William M.; Marcelletti, David J.

    2013-01-01

    When English Learners (ELs) demonstrate English language proficiency, they are reclassified as Fluent English Proficient (RFEP). Subsequently they are often left out of the analysis of EL progress because they are, technically, no longer ELs. This article examines the effects of including and excluding RFEPs from the analysis of EL progress. Based…

  4. 2D nanomaterials assembled from sequence-defined molecules

    DOE PAGES

    Mu, Peng; Zhou, Guangwen; Chen, Chun-Long

    2017-10-21

    Two dimensional (2D) nanomaterials have attracted broad interest owing to their unique physical and chemical properties with potential applications in electronics, chemistry, biology, medicine and pharmaceutics. Due to the current limitations of traditional 2D nanomaterials (e.g., graphene and graphene oxide) in tuning surface chemistry and compositions, 2D nanomaterials assembled from sequence-defined molecules (e.g., DNAs, proteins, peptides and peptoids) have recently been developed. They represent an emerging class of 2D nanomaterials with attractive physical and chemical properties. Here, we summarize the recent progress in the synthesis and applications of this type of sequence-defined 2D nanomaterials. We also discuss the challenges andmore » opportunities in this new field.« less

  5. 2D nanomaterials assembled from sequence-defined molecules

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

    Mu, Peng; Zhou, Guangwen; Chen, Chun-Long

    Two dimensional (2D) nanomaterials have attracted broad interest owing to their unique physical and chemical properties with potential applications in electronics, chemistry, biology, medicine and pharmaceutics. Due to the current limitations of traditional 2D nanomaterials (e.g., graphene and graphene oxide) in tuning surface chemistry and compositions, 2D nanomaterials assembled from sequence-defined molecules (e.g., DNAs, proteins, peptides and peptoids) have recently been developed. They represent an emerging class of 2D nanomaterials with attractive physical and chemical properties. Here, we summarize the recent progress in the synthesis and applications of this type of sequence-defined 2D nanomaterials. We also discuss the challenges andmore » opportunities in this new field.« less

  6. Recent progress on the structure separation of single-wall carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Cui, Jiaming; Yang, Dehua; Zeng, Xiang; Zhou, Naigen; Liu, Huaping

    2017-11-01

    The mass production of single-structure, single-wall carbon nanotubes (SWCNTs) with identical properties is critical for their basic research and technical applications in the fields of electronics, optics and optoelectronics. Great efforts have been made to control the structures of SWCNTs since their discovery. Recently, the structure separation of SWCNTs has been making great progress. Various solution-sorting methods have been developed to achieve not only the separation of metallic and semiconducting species, but also the sorting of distinct (n, m) single-chirality species and even their enantiomers. This progress would dramatically accelerate the application of SWCNTs in the next-generation electronic devices. Here, we review the recent progress in the structure sorting of SWCNTs and outline the challenges and prospects of the structure separation of SWCNTs.

  7. Spectroscopy, Manipulation and Trapping of Neutral Atoms, Molecules, and Other Particles Using Optical Nanofibers: A Review

    PubMed Central

    Morrissey, Michael J.; Deasy, Kieran; Frawley, Mary; Kumar, Ravi; Prel, Eugen; Russell, Laura; Truong, Viet Giang; Chormaic, Síle Nic

    2013-01-01

    The use of tapered optical fibers, i.e., optical nanofibers, for spectroscopy and the detection of small numbers of particles, such as neutral atoms or molecules, has been gaining interest in recent years. In this review, we briefly introduce the optical nanofiber, its fabrication, and optical mode propagation within. We discuss recent progress on the integration of optical nanofibers into laser-cooled atom and vapor systems, paying particular attention to spectroscopy, cold atom cloud characterization, and optical trapping schemes. Next, a natural extension of this work to molecules is introduced. Finally, we consider several alternatives to optical nanofibers that display some advantages for specific applications. PMID:23945738

  8. Examining the Technical Adequacy of Progress Monitoring Using Early Writing Curriculum-Based Measures

    ERIC Educational Resources Information Center

    Hampton, David D.; Lembke, Erica S.

    2016-01-01

    The purpose of this study was to examine 4 early writing measures used to monitor the early writing progress of 1st-grade students. We administered the measures to 23 1st-grade students biweekly for a total of 16 weeks. We obtained 3-min samples and conducted analyses for each 1-min increment. We scored samples using 2 different methods: correct…

  9. High beta and second stability region transport and stability analysis: Technical progress report

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

    Hughes, M.H.; Phillips, M.W.

    1995-03-01

    This report summarizes MHD equilibrium and stability studies carried out at Northrop Grumman`s Advanced Technology and Development Center during the 12 month period starting March 1, 1994. Progress is reported in both ideal and resistive MHD modeling of TFTR plasmas. The development of codes to calculate the significant effects of highly anisotropic pressure distributions is discussed along with results from this model.

  10. Single molecule dynamics at a mechanically controllable break junction in solution at room temperature.

    PubMed

    Konishi, Tatsuya; Kiguchi, Manabu; Takase, Mai; Nagasawa, Fumika; Nabika, Hideki; Ikeda, Katsuyoshi; Uosaki, Kohei; Ueno, Kosei; Misawa, Hiroaki; Murakoshi, Kei

    2013-01-23

    The in situ observation of geometrical and electronic structural dynamics of a single molecule junction is critically important in order to further progress in molecular electronics. Observations of single molecular junctions are difficult, however, because of sensitivity limits. Here, we report surface-enhanced Raman scattering (SERS) of a single 4,4'-bipyridine molecule under conditions of in situ current flow in a nanogap, by using nano-fabricated, mechanically controllable break junction (MCBJ) electrodes. When adsorbed at room temperature on metal nanoelectrodes in solution to form a single molecule junction, statistical analysis showed that nontotally symmetric b(1) and b(2) modes of 4,4'-bipyridine were strongly enhanced relative to observations of the same modes in solid or aqueous solutions. Significant changes in SERS intensity, energy (wavenumber), and selectivity of Raman vibrational bands that are coincident with current fluctuations provide information on distinct states of electronic and geometrical structure of the single molecule junction, even under large thermal fluctuations occurring at room temperature. We observed the dynamics of 4,4'-bipyridine motion between vertical and tilting configurations in the Au nanogap via b(1) and b(2) mode switching. A slight increase in the tilting angle of the molecule was also observed by noting the increase in the energies of Raman modes and the decrease in conductance of the molecular junction.

  11. The Molecule Pages database

    PubMed Central

    Saunders, Brian; Lyon, Stephen; Day, Matthew; Riley, Brenda; Chenette, Emily; Subramaniam, Shankar

    2008-01-01

    The UCSD-Nature Signaling Gateway Molecule Pages (http://www.signaling-gateway.org/molecule) provides essential information on more than 3800 mammalian proteins involved in cellular signaling. The Molecule Pages contain expert-authored and peer-reviewed information based on the published literature, complemented by regularly updated information derived from public data source references and sequence analysis. The expert-authored data includes both a full-text review about the molecule, with citations, and highly structured data for bioinformatics interrogation, including information on protein interactions and states, transitions between states and protein function. The expert-authored pages are anonymously peer reviewed by the Nature Publishing Group. The Molecule Pages data is present in an object-relational database format and is freely accessible to the authors, the reviewers and the public from a web browser that serves as a presentation layer. The Molecule Pages are supported by several applications that along with the database and the interfaces form a multi-tier architecture. The Molecule Pages and the Signaling Gateway are routinely accessed by a very large research community. PMID:17965093

  12. The Molecule Pages database.

    PubMed

    Saunders, Brian; Lyon, Stephen; Day, Matthew; Riley, Brenda; Chenette, Emily; Subramaniam, Shankar; Vadivelu, Ilango

    2008-01-01

    The UCSD-Nature Signaling Gateway Molecule Pages (http://www.signaling-gateway.org/molecule) provides essential information on more than 3800 mammalian proteins involved in cellular signaling. The Molecule Pages contain expert-authored and peer-reviewed information based on the published literature, complemented by regularly updated information derived from public data source references and sequence analysis. The expert-authored data includes both a full-text review about the molecule, with citations, and highly structured data for bioinformatics interrogation, including information on protein interactions and states, transitions between states and protein function. The expert-authored pages are anonymously peer reviewed by the Nature Publishing Group. The Molecule Pages data is present in an object-relational database format and is freely accessible to the authors, the reviewers and the public from a web browser that serves as a presentation layer. The Molecule Pages are supported by several applications that along with the database and the interfaces form a multi-tier architecture. The Molecule Pages and the Signaling Gateway are routinely accessed by a very large research community.

  13. Robust nonparametric quantification of clustering density of molecules in single-molecule localization microscopy

    PubMed Central

    Jiang, Shenghang; Park, Seongjin; Challapalli, Sai Divya; Fei, Jingyi; Wang, Yong

    2017-01-01

    We report a robust nonparametric descriptor, J′(r), for quantifying the density of clustering molecules in single-molecule localization microscopy. J′(r), based on nearest neighbor distribution functions, does not require any parameter as an input for analyzing point patterns. We show that J′(r) displays a valley shape in the presence of clusters of molecules, and the characteristics of the valley reliably report the clustering features in the data. Most importantly, the position of the J′(r) valley (rJm′) depends exclusively on the density of clustering molecules (ρc). Therefore, it is ideal for direct estimation of the clustering density of molecules in single-molecule localization microscopy. As an example, this descriptor was applied to estimate the clustering density of ptsG mRNA in E. coli bacteria. PMID:28636661

  14. Involvement of HLA class I molecules in the immune escape of urologic tumors.

    PubMed

    Carretero, R; Gil-Julio, H; Vázquez-Alonso, F; Garrido, F; Castiñeiras, J; Cózar, J M

    2014-04-01

    To analyze the influence of different alterations in human leukocyte antigen class I molecules (HLA I) in renal cell carcinoma, as well as in bladder and prostate cancer. We also study the correlation between HLA I expression and the progression of the disease and the response after immunotherapy protocols. It has been shown, experimentally, that the immune system can recognize and kill neoplastic cells. By analyzing the expression of HLA I molecules on the surface of cancer cells, we were able to study the tumor escape mechanisms against the immune system. Alteration or irreversible damage in HLA I molecules is used by the neoplastic cells to escape the immune system. The function of these molecules is to recognize endogenous peptides and present them to T cells of the immune system. There is a clear relationship between HLA I reversible alterations and success of therapy. Irreversible lesions also imply a lack of response to treatment. The immune system activation can reverse HLA I molecules expression in tumors with reversible lesions, whereas tumors with irreversible ones do not respond to such activation. Determine the type of altered HLA I molecules in tumors is of paramount importance when choosing the type of treatment to keep looking for therapeutic success. Those tumors with reversible lesions can be treated with traditional immunotherapy; however, tumour with irreversible alterations should follow alternative protocols, such as the use of viral vectors carrying the HLA genes to achieve damaged re-expression of the protein. From studies in urologic tumors, we can conclude that the HLA I molecules play a key role in these tumors escape to the immune system. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  15. Dietary Selenium Supplementation Modulates Growth of Brain Metastatic Tumors and Changes the Expression of Adhesion Molecules in Brain Microvessels.

    PubMed

    Wrobel, Jagoda K; Wolff, Gretchen; Xiao, Rijin; Power, Ronan F; Toborek, Michal

    2016-08-01

    Various dietary agents can modulate tumor invasiveness. The current study explored whether selenoglycoproteins (SeGPs) extracted from selenium-enriched yeast affect tumor cell homing and growth in the brain. Mice were fed diets enriched with specific SeGPs (SeGP40 or SeGP65, 1 mg/kg Se each), glycoproteins (GP40 or GP65, 0.2-0.3 mg/kg Se each) or a control diet (0.2-0.3 mg/kg Se) for 12 weeks. Then, murine Lewis lung carcinoma cells were infused into the brain circulation. Analyses were performed at early (48 h) and late stages (3 weeks) post tumor cell infusion. Imaging of tumor progression in the brain revealed that mice fed SeGP65-enriched diet displayed diminished metastatic tumor growth, fewer extravasating tumor cells and smaller metastatic lesions. While administration of tumor cells resulted in a significant upregulation of adhesion molecules in the early stage of tumor progression, overexpression of VCAM-1 (vascular call adhesion molecule-1) and ALCAM (activated leukocyte cell adhesion molecule) messenger RNA (mRNA) was diminished in SeGP65 supplemented mice. Additionally, mice fed SeGP65 showed decreased expression of acetylated NF-κB p65, 48 h post tumor cell infusion. The results indicate that tumor progression in the brain can be modulated by specific SeGPs. Selenium-containing compounds were more effective than their glycoprotein controls, implicating selenium as a potential negative regulator of metastatic process.

  16. Small-Molecule Modulators of Methyl-Lysine Binding for the CBX7 Chromodomain

    DOE PAGES

    Ren, Chunyan; Morohashi, Keita; Plotnikov, Alexander N.; ...

    2015-02-05

    Chromobox homolog 7 (CBX7) plays an important role in gene transcription in a wide array of cellular processes, ranging from stem cell self-renewal and differentiation to tumor progression. CBX7 functions through its N-terminal chromodomain (ChD), which recognizes tri-methylated lysine 27 of histone 3 (H3K27me3), a conserved epigenetic mark that signifies gene transcriptional repression. Here in this study, we report discovery of small molecules that inhibit CBX7ChD binding to H3K27me3. Our crystal structures reveal the binding modes of these molecules that compete against H3K27me3 binding through interactions with key residues in the methyl-lysine binding pocket of CBX7ChD. We further show thatmore » a lead compound MS37452, derepresses transcription of Polycomb repressive complex target gene p16/CDKN2A by displacing CBX7 binding to the INK4A/ARF locus in prostate cancer cells. Ultimately, these small molecules have the potential to be developed into high-potency chemical modulators that target CBX7 functions in gene transcription in different disease pathways.« less

  17. Technical Summary for 1993 Fall MRS Symposium O, ’Complex Fluids’

    DTIC Science & Technology

    1994-08-19

    specific "lock-and-key" bine’ A ’ protein receptor and ligand molecules. Philippe Richetti [CRPP, BordeaL c .•c ,. d surface forces apparatus...Cameron Staticon Alexandria, Virginia 22304-6145 Plese find enclosed a copy of the Technical Summary for Symposium 0, "Complex Fluids", of the Fall...well as by Exxon Research and Engineering and Exxon Chemical Company. Sincerely, ,J kZ PhL \\PIC Scott Milner SM:pk Enc. c. D . J. Gillespie 0819940I.STM

  18. Quality and Quality Assurance in Technical and Vocational Education and Training. Thematic Studies

    ERIC Educational Resources Information Center

    Seyfried, Erwin

    2008-01-01

    In many countries in both the Mediterranean region and the European Union (EU), interest in the quality of, and improvements to, technical and vocational education and training (TVET) systems has increased progressively in recent years. The main reason underlying this interest is a growing awareness of the key role played by education and training…

  19. Manipulating TRPV1 antagonists: how to cool down a hot molecule?

    PubMed

    Islas, Leon; Szallasi, Arpad

    2018-05-05

    TRPV1 is a promising pain target. Although a number of small molecule TRPV1 antagonists have been advanced into clinical trials, thus far none has progressed beyond Phase II due to on-target side-effects such as a febrile reaction. In this issue of Acta Physiologica, Romanovsky and colleagues report two TRPV1 antagonists that paradoxically induce hypothermia in experimental animals, potentially opening a new avenue for drug development. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. Site Operator technical report. Final report (1992--1996)

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

    NONE

    1996-12-01

    The Southern California Edison Company (SCE) and the US Department of Energy (DOE) entered into cooperative agreement No. DE-FC07-91ID13077 on August 23, 1991, which expired on August 3, 1996. This cooperative agreement provided SCE with DOE cofunding for participation in the DOE`s Electric and Hybrid Vehicle Site Operator Program. In return, SCE provided the DOE with quarterly progress reports which include operating and maintenance data for the electric (EVs) vehicles in SCE`s fleet. Herein is SCE`s final report for the 1992 to 1996 agreement period. As of September 1, 1996 the SCE fleet had 65 electric vehicles in service. Amore » total of 578,200 miles had been logged. During the agreement period, SCE sent the DOE a total of 19 technical reports (Appendix B). This report summarizes the technical achievements which took place during a long, productive and rewarding, relationship with the DOE.« less

  1. HIGH RESOLUTION SPECTROSCOPY IN THE GAS PHASE: Even Large Molecules Have Well-Defined Shapes

    NASA Astrophysics Data System (ADS)

    Pratt, David W.

    1998-10-01

    A review of recent high-resolution microwave, infrared, and optical spectroscopy experiments demonstrates that remarkable progress has been made in the past 20 years in determining the equilibrium geometries of large polyatomic molecules and their clusters in the gas phase, and how these geometries change when the photon is absorbed. A special focus is on the dynamical information that can be obtained from such studies, particularly of electronically excited states.

  2. A gene-signature progression approach to identifying candidate small-molecule cancer therapeutics with connectivity mapping.

    PubMed

    Wen, Qing; Kim, Chang-Sik; Hamilton, Peter W; Zhang, Shu-Dong

    2016-05-11

    Gene expression connectivity mapping has gained much popularity recently with a number of successful applications in biomedical research testifying its utility and promise. Previously methodological research in connectivity mapping mainly focused on two of the key components in the framework, namely, the reference gene expression profiles and the connectivity mapping algorithms. The other key component in this framework, the query gene signature, has been left to users to construct without much consensus on how this should be done, albeit it has been an issue most relevant to end users. As a key input to the connectivity mapping process, gene signature is crucially important in returning biologically meaningful and relevant results. This paper intends to formulate a standardized procedure for constructing high quality gene signatures from a user's perspective. We describe a two-stage process for making quality gene signatures using gene expression data as initial inputs. First, a differential gene expression analysis comparing two distinct biological states; only the genes that have passed stringent statistical criteria are considered in the second stage of the process, which involves ranking genes based on statistical as well as biological significance. We introduce a "gene signature progression" method as a standard procedure in connectivity mapping. Starting from the highest ranked gene, we progressively determine the minimum length of the gene signature that allows connections to the reference profiles (drugs) being established with a preset target false discovery rate. We use a lung cancer dataset and a breast cancer dataset as two case studies to demonstrate how this standardized procedure works, and we show that highly relevant and interesting biological connections are returned. Of particular note is gefitinib, identified as among the candidate therapeutics in our lung cancer case study. Our gene signature was based on gene expression data from Taiwan

  3. Motor-motor interactions in ensembles of muscle myosin: using theory to connect single molecule to ensemble measurements

    NASA Astrophysics Data System (ADS)

    Walcott, Sam

    2013-03-01

    Interactions between the proteins actin and myosin drive muscle contraction. Properties of a single myosin interacting with an actin filament are largely known, but a trillion myosins work together in muscle. We are interested in how single-molecule properties relate to ensemble function. Myosin's reaction rates depend on force, so ensemble models keep track of both molecular state and force on each molecule. These models make subtle predictions, e.g. that myosin, when part of an ensemble, moves actin faster than when isolated. This acceleration arises because forces between molecules speed reaction kinetics. Experiments support this prediction and allow parameter estimates. A model based on this analysis describes experiments from single molecule to ensemble. In vivo, actin is regulated by proteins that, when present, cause the binding of one myosin to speed the binding of its neighbors; binding becomes cooperative. Although such interactions preclude the mean field approximation, a set of linear ODEs describes these ensembles under simplified experimental conditions. In these experiments cooperativity is strong, with the binding of one molecule affecting ten neighbors on either side. We progress toward a description of myosin ensembles under physiological conditions.

  4. Small molecule inhibition of FOXM1: How to bring a novel compound into genomic context.

    PubMed

    Marsico, Giovanni; Gormally, Michael V

    2015-03-01

    Deregulation of transcription factor (TF) networks is emerging as a major pathogenic event in many human cancers (Darnell, 2002 [1]; Libermann and Zerbini, 2006 [2]; Laoukili et al., 2007 [3]). Small molecule intervention is an attractive avenue to understand TF regulatory mechanisms in healthy and disease state, as well as for exploiting these targets therapeutically (Koehler et al., 2003 [4]; Berg, 2008 [5]; Koehler, 2010 [6]). However, because of their physico-chemical properties, TF targeting has been proven to be difficult (Verdine and Walensky, 2007 [7]). The TF FOXM1 is an important mitotic player (Wonsey and Follettie, 2005 [8]; Laoukili et al., 2005 [9]; McDonald, 2005 [10]) also implicated in cancer progression (Laoukili et al., 2007 [3]; Teh, 2011 [11]; Koo, 2012 [12]) and drug resistance development (Kwok et al., 2010 [13]; Carr et al., [14]). Therefore, its inhibition is an attractive goal for cancer therapy. Here, we describe a computational biology approach, by giving detailed insights into methodologies and technical results, which was used to analyze the transcriptional RNA-Seq data presented in our previous work (Gormally et al., 2014 [20]). Our Bioinformatics analysis shed light on the cellular effect of a novel FOXM1 inhibitor (FDI-6) newly identified through a biophysical screen. The data for this report is available at the public GEO repository (accession number http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE58626).

  5. E-cadherin: A determinant molecule associated with ovarian cancer progression, dissemination and aggressiveness

    PubMed Central

    Devis, Laura; Lapyckyj, Lara; Besso, María José; Llauradó, Marta; Abascal, María Florencia; Matos, María Laura; Lanau, Lucia; Castellví, Josep; Sánchez, José Luis; Pérez Benavente, Asunción; Gil-Moreno, Antonio; Reventós, Jaume; Santamaria Margalef, Anna; Rigau, Marina; Vazquez-Levin, Mónica Hebe

    2017-01-01

    Ovarian cancer (OC) is the fifth cancer death cause in women worldwide. The malignant nature of this disease stems from its unique dissemination pattern. Epithelial-to-mesenchymal transition (EMT) has been reported in OC and downregulation of Epithelial cadherin (E-cadherin) is a hallmark of this process. However, findings on the relationship between E-cadherin levels and OC progression, dissemination and aggressiveness are controversial. In this study, the evaluation of E-cadherin expression in an OC tissue microarray revealed its prognostic value to discriminate between advanced- and early-stage tumors, as well as serous tumors from other histologies. Moreover, E-cadherin, Neural cadherin (N-cadherin), cytokeratins and vimentin expression was assessed in TOV-112, SKOV-3, OAW-42 and OV-90 OC cell lines grown in monolayers and under anchorage-independent conditions to mimic ovarian tumor cell dissemination, and results were associated with cell aggressiveness. According to these EMT-related markers, cell lines were classified as mesenchymal (M; TOV-112), intermediate mesenchymal (IM; SKOV-3), intermediate epithelial (IE; OAW-42) and epithelial (E; OV-90). M- and IM-cells depicted the highest migration capacity when grown in monolayers, and aggregates derived from M- and IM-cell lines showed lower cell death, higher adhesion to extracellular matrices and higher invasion capacity than E- and IE-aggregates. The analysis of E-cadherin, N-cadherin, cytokeratin 19 and vimentin mRNA levels in 20 advanced-stage high-grade serous human OC ascites showed an IM phenotype in all cases, characterized by higher proportions of N- to E-cadherin and vimentin to cytokeratin 19. In particular, higher E-cadherin mRNA levels were associated with cancer antigen 125 levels more than 500 U/mL and platinum-free intervals less than 6 months. Altogether, E-cadherin expression levels were found relevant for the assessment of OC progression and aggressiveness. PMID:28934230

  6. Cytoplasmic accumulation of activated leukocyte cell adhesion molecule is a predictor of disease progression and reduced survival in oral cancer patients.

    PubMed

    Sawhney, Meenakshi; Matta, Ajay; Macha, Muzafar A; Kaur, Jatinder; DattaGupta, Siddhartha; Shukla, Nootan K; Ralhan, Ranju

    2009-05-01

    Activated leukocyte cell adhesion molecule (ALCAM) has been proposed to function as a cell surface sensor for cell density, controlling the transition between local cell proliferation and tissue invasion in cancer progression. Herein, we determined ALCAM expression in 107 oral squamous cell carcinomas (OSCCs), 78 oral lesions (58 hyperplasias and 20 dysplasias) and 30 histologically normal oral tissues using immunohistochemistry and correlated with clinicopathological parameters. Significant increase in ALCAM immunopositivity was observed from normal oral mucosa, hyperplasia, dysplasia to OSCCs (p(trend) < 0.001). Increased ALCAM expression was observed in cytoplasm of epithelial cells as early as in hyperplasia (p = 0.001, OR = 3.8). Sixty-five of 107 (61%) OSCCs showed significant overexpression of ALCAM protein in cytoplasm/membrane of tumor cells (p = 0.043; OR = 3.3) in comparison with the normal oral tissues. Among OSCCs, cytoplasmic ALCAM was associated with advanced tumor size, tumor stage and tobacco consumption. Importantly, cytoplasmic ALCAM was an independent predictor of poor prognosis of OSCCs in multivariate analysis (p = 0.012, OR = 6.2). In an attempt to understand the molecular basis of cytoplasmic localization of ALCAM, 14-3-3 zeta and 14-3-3 sigma were identified as its novel binding partners in oral cancer cells. In conclusion, increased expression of ALCAM is an early event in oral tumorigenesis; its cytoplasmic accumulation in tumor cells is a predictor of poor prognosis of OSCCs, underscoring its potential as a candidate prognostic marker for oral cancer. (c) 2008 Wiley-Liss, Inc.

  7. Waste Isolation Safety Assessment Program. Technical progress report for FY-1978

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

    Brandstetter, A.; Harwell, M.A.; Howes, B.W.

    1979-07-01

    Associated with commercial nuclear power production in the United States is the generation of potentially hazardous radioactive wastes. The Department of Energy (DOE) is seeking to develop nuclear waste isolation systems in geologic formations that will preclude contact with the biosphere of waste radionuclides in concentrations which are sufficient to cause deleterious impact on humans or their environments. Comprehensive analyses of specific isolation systems are needed to assess the expectations of meeting that objective. The Waste Isolation Safety Assessment Program (WISAP) has been established at the Pacific Northwest Laboratory (operated by Battelle Memorial Institute) for developing the capability of makingmore » those analyses. Progress on the following tasks is reported: release scenario analysis, waste form release rate analysis, release consequence analysis, sorption-desorption analysis, and societal acceptance analysis. (DC)« less

  8. Internal Consistency of General Outcome Measures in Grades 1-8. Technical Report # 0915

    ERIC Educational Resources Information Center

    Anderson, Daniel; Tindal, Gerald; Alonzo, Julie

    2009-01-01

    We developed alternate forms of a math test for use in both screening students at risk of failure and monitoring their progress over time. In this technical report, we present results of the screener, used in the fall of 2009. The 48-item test was aligned to the National Council of Teachers of Mathematics (NCTM) Curriculum Focal Point Standards…

  9. Computational approach for deriving cancer progression roadmaps from static sample data

    PubMed Central

    Yao, Jin; Yang, Le; Chen, Runpu; Nowak, Norma J.

    2017-01-01

    Abstract As with any biological process, cancer development is inherently dynamic. While major efforts continue to catalog the genomic events associated with human cancer, it remains difficult to interpret and extrapolate the accumulating data to provide insights into the dynamic aspects of the disease. Here, we present a computational strategy that enables the construction of a cancer progression model using static tumor sample data. The developed approach overcame many technical limitations of existing methods. Application of the approach to breast cancer data revealed a linear, branching model with two distinct trajectories for malignant progression. The validity of the constructed model was demonstrated in 27 independent breast cancer data sets, and through visualization of the data in the context of disease progression we were able to identify a number of potentially key molecular events in the advance of breast cancer to malignancy. PMID:28108658

  10. SINGLE MOLECULE APPROACHES TO BIOLOGY, 2010 GORDON RESEARCH CONFERENCE, JUNE 27-JULY 2, 2010, ITALY

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

    Professor William Moerner

    2010-07-09

    The 2010 Gordon Conference on Single-Molecule Approaches to Biology focuses on cutting-edge research in single-molecule science. Tremendous technical developments have made it possible to detect, identify, track, and manipulate single biomolecules in an ambient environment or even in a live cell. Single-molecule approaches have changed the way many biological problems are addressed, and new knowledge derived from these approaches continues to emerge. The ability of single-molecule approaches to avoid ensemble averaging and to capture transient intermediates and heterogeneous behavior renders them particularly powerful in elucidating mechanisms of biomolecular machines: what they do, how they work individually, how they work together,more » and finally, how they work inside live cells. The burgeoning use of single-molecule methods to elucidate biological problems is a highly multidisciplinary pursuit, involving both force- and fluorescence-based methods, the most up-to-date advances in microscopy, innovative biological and chemical approaches, and nanotechnology tools. This conference seeks to bring together top experts in molecular and cell biology with innovators in the measurement and manipulation of single molecules, and will provide opportunities for junior scientists and graduate students to present their work in poster format and to exchange ideas with leaders in the field. A number of excellent poster presenters will be selected for short oral talks. Topics as diverse as single-molecule sequencing, DNA/RNA/protein interactions, folding machines, cellular biophysics, synthetic biology and bioengineering, force spectroscopy, new method developments, superresolution imaging in cells, and novel probes for single-molecule imaging will be on the program. Additionally, the collegial atmosphere of this Conference, with programmed discussion sessions as well as opportunities for informal gatherings in the afternoons and evenings in the beauty of the Il Ciocco site

  11. Predictors of employer satisfaction: technical and non-technical skills.

    PubMed

    Danielson, Jared A; Wu, Tsui-Feng; Fales-Williams, Amanda J; Kirk, Ryan A; Preast, Vanessa A

    2012-01-01

    Employers of 2007-2009 graduates from Iowa State University College of Veterinary Medicine were asked to respond to a survey regarding their overall satisfaction with their new employees as well as their new employees' preparation in several technical and non-technical skill areas. Seventy-five responses contained complete data and were used in the analysis. Four technical skill areas (data collection, data interpretation, planning, and taking action) and five non-technical skill areas (interpersonal skills, ability to deal with legal issues, business skills, making referrals, and problem solving) were identified. All of the skill area subscales listed above had appropriate reliability (Cronbach's alpha>0.70) and were positively and significantly correlated with overall employer satisfaction. Results of two simultaneous regression analyses indicated that of the four technical skill areas, taking action is the most salient predictor of employer satisfaction. Of the five non-technical skill areas, interpersonal skills, business skills, making referrals, and problem solving were the most important skills in predicting employer satisfaction. Hierarchical regression analysis revealed that all technical skills explained 25% of the variation in employer satisfaction; non-technical skills explained an additional 42% of the variation in employer satisfaction.

  12. 2D nanomaterials assembled from sequence-defined molecules

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

    Mu, Peng; Zhou, Guangwen; Chen, Chun-Long

    Two dimensional (2D) nanomaterials have attracted broad interest owing to their unique physical and chemical properties with potential applications in electronics, chemistry, biology, medicine and pharmaceutics. Due to the current limitations of traditional 2D nanomaterials (e.g., graphene and graphene oxide) in tuning surface chemistry and compositions, 2D nanomaterials assembled from sequence-defined molecules (e.g., DNAs, proteins, peptides and peptoids) have recently been developed. They represent an emerging class of 2D nanomaterials with attractive physical and chemical properties. In this mini-review, we summarize the recent progress in the synthesis and applications of this type of sequence-defined 2D nanomaterials. The challenges and opportunitiesmore » in this new field are also discussed.« less

  13. Useful Sensor Web Capabilities to Enable Progressive Mission Autonomy

    NASA Technical Reports Server (NTRS)

    Mandl, Dan

    2007-01-01

    This viewgraph presentation reviews using the Sensor Web capabilities as an enabling technology to allow for progressive autonomy of NASA space missions. The presentation reviews technical challenges for future missions, and some of the capabilities that exist to meet those challenges. To establish the ability of the technology to meet the challenges, experiments were conducted on three missions: Earth Observing 1 (EO-1), Cosmic Hot Interstellar Plasma Spectrometer (CHIPS) and Space Technology 5 (ST-5). These experiments are reviewed.

  14. Combined Secretomics and Transcriptomics Revealed Cancer-Derived GDF15 is Involved in Diffuse-Type Gastric Cancer Progression and Fibroblast Activation.

    PubMed

    Ishige, Takayuki; Nishimura, Motoi; Satoh, Mamoru; Fujimoto, Mai; Fukuyo, Masaki; Semba, Toshihisa; Kado, Sayaka; Tsuchida, Sachio; Sawai, Setsu; Matsushita, Kazuyuki; Togawa, Akira; Matsubara, Hisahiro; Kaneda, Atsushi; Nomura, Fumio

    2016-02-19

    Gastric cancer is classified into two subtypes, diffuse and intestinal. The diffuse-type gastric cancer (DGC) has poorer prognosis, and the molecular pathology is not yet fully understood. The purpose of this study was to identify functional secreted molecules involved in DGC progression. We integrated the secretomics of six gastric cancer cell lines and gene expression analysis of gastric cancer tissues with publicly available microarray data. Hierarchical clustering revealed characteristic gene expression differences between diffuse- and intestinal-types. GDF15 was selected as a functional secreted molecule owing to high expression only in fetal tissues. Protein expression of GDF15 was higher in DGC cell lines and tissues. Serum levels of GDF15 were significant higher in DGC patients as compared with healthy individuals and chronic gastritis patients, and positively correlated with wall invasion and lymph node metastasis. In addition, the stimulation of GDF15 on NIH3T3 fibroblast enhanced proliferation and up-regulated expression of extracellular matrix genes, which were similar to TGF-β stimulation. These results indicate that GDF15 contributes to fibroblast activation. In conclusion, this study revealed that GDF15 may be a novel functional secreted molecule for DGC progression, possibly having important roles for cancer progression via the affecting fibroblast function, as well as TGF-β.

  15. U.S. TIMSS and PIRLS 2011 Technical Report and User's Guide. NCES 2013-046

    ERIC Educational Resources Information Center

    Kastberg, David; Roey, Stephen; Ferraro, David; Lemanski, Nita; Erberber, Ebru

    2013-01-01

    The "U.S. TIMSS and PIRLS 2011 Technical Report and User's Guide" provides an overview of the design and implementation of the Trends in International Mathematics and Science Study (TIMSS) 2011 and the Progress in International Reading Literacy Study (PIRLS) 2011 in the United States and the nine participating benchmarking states:…

  16. The Development of the easyCBM CCSS Reading Assessments: Grade 3. Technical Report #1221

    ERIC Educational Resources Information Center

    Alonzo, Julie; Park, Bitnara Jasmine; Tindal, Gerald

    2012-01-01

    In this technical report, we document the development and piloting of easyCBM reading measures aligned to the Common Core State Standards, designed for use in screening students at risk for reading difficulty and monitoring their progress as they develop reading skills. The measures, which assess students' ability to respond to…

  17. Current progress and technical challenges of flexible liquid crystal displays

    NASA Astrophysics Data System (ADS)

    Fujikake, Hideo; Sato, Hiroto

    2009-02-01

    We focused on several technical approaches to flexible liquid crystal (LC) display in this report. We have been developing flexible displays using plastic film substrates based on polymer-dispersed LC technology with molecular alignment control. In our representative devices, molecular-aligned polymer walls keep plastic-substrate gap constant without LC alignment disorder, and aligned polymer networks create monostable switching of fast-response ferroelectric LC (FLC) for grayscale capability. In the fabrication process, a high-viscosity FLC/monomer solution was printed, sandwiched and pressed between plastic substrates. Then the polymer walls and networks were sequentially formed based on photo-polymerization-induced phase separation in the nematic phase by two exposure processes of patterned and uniform ultraviolet light. The two flexible backlight films of direct illumination and light-guide methods using small three-primary-color light-emitting diodes were fabricated to obtain high-visibility display images. The fabricated flexible FLC panels were driven by external transistor arrays, internal organic thin film transistor (TFT) arrays, and poly-Si TFT arrays. We achieved full-color moving-image displays using the flexible FLC panel and the flexible backlight film based on field-sequential-color driving technique. Otherwise, for backlight-free flexible LC displays, flexible reflective devices of twisted guest-host nematic LC and cholesteric LC were discussed with molecular-aligned polymer walls. Singlesubstrate device structure and fabrication method using self-standing polymer-stabilized nematic LC film and polymer ceiling layer were also proposed for obtaining LC devices with excellent flexibility.

  18. Soluble intercellular adhesion molecule-1 and interleukin-6 levels reflect endothelial dysfunction in patients with primary hypercholesterolaemia treated with atorvastatin.

    PubMed

    Nawawi, H; Osman, N S; Annuar, R; Khalid, B A K; Yusoff, K

    2003-08-01

    Adhesion molecules and cytokines are involved in the pathogenesis of intimal injury in atherosclerosis but their relationship with endothelial function remains unclear. The objectives of this study were to examine the effects of atorvastatin on soluble adhesion molecules, interleukin-6 (IL-6) and brachial artery endothelial-dependent flow mediated dilatation (FMD) in patients with familial (FH) and non-familial hypercholesterolaemia (NFH). A total of 74 patients (27 FH and 47 NFH) were recruited. Fasting lipid profiles, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular-cellular adhesion molecule-1 (sVCAM-1), E-selectin, IL-6 and FMD were measured at baseline, 2 weeks, 3 and 9 months post-atorvastatin treatment (FH--80 mg/day, NFH--10 mg/day). In both groups, compared to baseline, sICAM-1 levels were significantly reduced at 2 weeks, further reduced at 3 months and maintained at 9 months (P<0.0001). The IL-6 levels were significantly reduced at 3 months and 9 months compared to baseline for FH (P<0.005) and NFH (P<0.0001). In both groups, the FMD at 2 weeks was higher than baseline (P<0.005), with progressive improvement up to 9 months. FMD was negatively correlated with sICAM-1 and IL-6. In conclusion, both low and high doses of atorvastatin lead to early progressive improvement in endothelial function in patients with primary hypercholesterolaemia. sICAM-1 and IL-6 levels reflect endothelial dysfunction in these patients.

  19. A Milieu Molecule for TGF-β Required for Microglia Function in the Nervous System.

    PubMed

    Qin, Yan; Garrison, Brian S; Ma, Wenjiang; Wang, Rui; Jiang, Aiping; Li, Jing; Mistry, Meeta; Bronson, Roderick T; Santoro, Daria; Franco, Charlotte; Robinton, Daisy A; Stevens, Beth; Rossi, Derrick J; Lu, Chafen; Springer, Timothy A

    2018-06-12

    Extracellular proTGF-β is covalently linked to "milieu" molecules in the matrix or on cell surfaces and is latent until TGF-β is released by integrins. Here, we show that LRRC33 on the surface of microglia functions as a milieu molecule and enables highly localized, integrin-αVβ8-dependent TGF-β activation. Lrrc33 -/- mice lack CNS vascular abnormalities associated with deficiency in TGF-β-activating integrins but have microglia with a reactive phenotype and after 2 months develop ascending paraparesis with loss of myelinated axons and death by 5 months. Whole bone marrow transplantation results in selective repopulation of Lrrc33 -/- brains with WT microglia and halts disease progression. The phenotypes of WT and Lrrc33 -/- microglia in the same brain suggest that there is little spreading of TGF-β activated from one microglial cell to neighboring microglia. Our results suggest that interactions between integrin-bearing cells and cells bearing milieu molecule-associated TGF-β provide localized and selective activation of TGF-β. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Ion-Molecule Reaction Dynamics

    NASA Astrophysics Data System (ADS)

    Meyer, Jennifer; Wester, Roland

    2017-05-01

    We review the recent advances in the investigation of the dynamics of ion-molecule reactions. During the past decade, the combination of single-collision experiments in crossed ion and neutral beams with the velocity map ion imaging detection technique has enabled a wealth of studies on ion-molecule reactions. These methods, in combination with chemical dynamics simulations, have uncovered new and unexpected reaction mechanisms, such as the roundabout mechanism and the subtle influence of the leaving group in anion-molecule nucleophilic substitution reactions. For this important class of reactions, as well as for many fundamental cation-molecule reactions, the information obtained with crossed-beam imaging is discussed. The first steps toward understanding micro-solvation of ion-molecule reaction dynamics are presented. We conclude with the presentation of several interesting directions for future research.

  1. Negative ions of polyatomic molecules.

    PubMed Central

    Christophorou, L G

    1980-01-01

    In this paper general concepts relating to, and recent advances in, the study of negative ions of polyatomic molecules area discussed with emphasis on halocarbons. The topics dealt with in the paper are as follows: basic electron attachment processes, modes of electron capture by molecules, short-lived transient negative ions, dissociative electron attachment to ground-state molecules and to "hot" molecules (effects of temperature on electron attachment), parent negative ions, effect of density, nature, and state of the medium on electron attachment, electron attachment to electronically excited molecules, the binding of attached electrons to molecules ("electron affinity"), and the basic and the applied significance of negative-ion studies. PMID:7428744

  2. Biomass power for rural development. Technical progress report, January 1--March 31, 1998

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

    Neuhauser, E.

    Brief progress reports are presented on the following tasks: design packages for retrofits at the Dunkirk Station; fuel supply and site development plans; major equipment guarantees and project risk sharing; power production commitment; power plant site plan, construction and environmental permits; and experimental strategies for system evaluation. The paper then discusses in more detail the following: feedstock development efforts; clone-site testing and genetic studies; and efforts at outreach, extension and technology transfer.

  3. Probing Trapped Ion Energies Via Ion-Molecule Reaction Kinetics: Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

    DTIC Science & Technology

    1992-05-28

    ORGANIZATION (if applicable) Office of Naval Research N00014-87- j - 1248 Bc. ADDRESS (City, State, and ZIP Code) 10. SOURCE OF FUNDING NUMBERS 800 N. Quincy St...RESEARCH Grant NOOO14-87- J -1248 R & T Code 4134052 TECHNICAL REPORT NO. 36 Probing Trapped Ion Energies Via Ion-Molecule Reaction Kinetics: Fourier...reactivity (for charge transfer with N2) of the higher energy J =1/2 state is approximately three times that of the J =3/2 state at collision energies

  4. Longitudinal Surveys of Australian Youth (LSAY) 2009 Cohort: Wave 2 (2010)-- Questionnaire. Technical Report 71A

    ERIC Educational Resources Information Center

    National Centre for Vocational Education Research (NCVER), 2012

    2012-01-01

    The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the questionnaire for the LSAY 2009 cohort Wave 2 (2010) data set.

  5. Longitudinal Surveys of Australian Youth (LSAY) 2009 Cohort: Wave 3 (2011)--Questionnaire. Technical Report 72A

    ERIC Educational Resources Information Center

    National Centre for Vocational Education Research (NCVER), 2012

    2012-01-01

    The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the questionnaire for the LSAY 2009 cohort Wave 3 (2011) data set.

  6. Motion of Fullerenes around Topological Defects on Metals: Implications for the Progress of Molecular Scale Devices.

    PubMed

    Nirmalraj, Peter; Daly, Ronan; Martin, Nazario; Thompson, Damien

    2017-03-08

    Research on motion of molecules in the presence of thermal noise is central for progress in two-terminal molecular scale electronic devices. However, it is still unclear what influence imperfections in bottom metal electrode surface can have on molecular motion. Here, we report a two-layer crowding study, detailing the early stages of surface motion of fullerene molecules on Au(111) with nanoscale pores in a n-tetradecane chemical environment. The motion of the fullerenes is directed by crowding of the underlying n-tetradecane molecules around the pore fringes at the liquid-solid interface. We observe in real-space the growth of molecular populations around different pore geometries. Supported by atomic-scale modeling, our findings extend the established picture of molecular crowding by revealing that trapped solvent molecules serve as prime nucleation sites at nanopore fringes.

  7. Measurement and control of detailed electronic properties in a single molecule break junction.

    PubMed

    Wang, Kun; Hamill, Joseph; Zhou, Jianfeng; Guo, Cunlan; Xu, Bingqian

    2014-01-01

    The lack of detailed experimental controls has been one of the major obstacles hindering progress in molecular electronics. While large fluctuations have been occurring in the experimental data, specific details, related mechanisms, and data analysis techniques are in high demand to promote our physical understanding at the single-molecule level. A series of modulations we recently developed, based on traditional scanning probe microscopy break junctions (SPMBJs), have helped to discover significant properties in detail which are hidden in the contact interfaces of a single-molecule break junction (SMBJ). For example, in the past we have shown that the correlated force and conductance changes under the saw tooth modulation and stretch-hold mode of PZT movement revealed inherent differences in the contact geometries of a molecular junction. In this paper, using a bias-modulated SPMBJ and utilizing emerging data analysis techniques, we report on the measurement of the altered alignment of the HOMO of benzene molecules with changing the anchoring group which coupled the molecule to metal electrodes. Further calculations based on Landauer fitting and transition voltage spectroscopy (TVS) demonstrated the effects of modulated bias on the location of the frontier molecular orbitals. Understanding the alignment of the molecular orbitals with the Fermi level of the electrodes is essential for understanding the behaviour of SMBJs and for the future design of more complex devices. With these modulations and analysis techniques, fruitful information has been found about the nature of the metal-molecule junction, providing us insightful clues towards the next step for in-depth study.

  8. Single molecule quantitation and sequencing of rare translocations using microfluidic nested digital PCR.

    PubMed

    Shuga, Joe; Zeng, Yong; Novak, Richard; Lan, Qing; Tang, Xiaojiang; Rothman, Nathaniel; Vermeulen, Roel; Li, Laiyu; Hubbard, Alan; Zhang, Luoping; Mathies, Richard A; Smith, Martyn T

    2013-09-01

    Cancers are heterogeneous and genetically unstable. New methods are needed that provide the sensitivity and specificity to query single cells at the genetic loci that drive cancer progression, thereby enabling researchers to study the progression of individual tumors. Here, we report the development and application of a bead-based hemi-nested microfluidic droplet digital PCR (dPCR) technology to achieve 'quantitative' measurement and single-molecule sequencing of somatically acquired carcinogenic translocations at extremely low levels (<10(-6)) in healthy subjects. We use this technique in our healthy study population to determine the overall concentration of the t(14;18) translocation, which is strongly associated with follicular lymphoma. The nested dPCR approach improves the detection limit to 1×10(-7) or lower while maintaining the analysis efficiency and specificity. Further, the bead-based dPCR enabled us to isolate and quantify the relative amounts of the various clonal forms of t(14;18) translocation in these subjects, and the single-molecule sensitivity and resolution of dPCR led to the discovery of new clonal forms of t(14;18) that were otherwise masked by the conventional quantitative PCR measurements. In this manner, we created a quantitative map for this carcinogenic mutation in this healthy population and identified the positions on chromosomes 14 and 18 where the vast majority of these t(14;18) events occur.

  9. Flat-plate solar array progress and plans

    NASA Technical Reports Server (NTRS)

    Callaghan, W. T.; Henry, P. K.

    1984-01-01

    The Flat-Plate Solar Array Project (FSA), sponsored by the U.S. Department of Energy (DOE) and managed by the Jet Propulsion Laboratory (JPL), has achieved progress in a broad range of technical activities since that reported at the Fourth European Communities Conference. A particularly important analysis has been completed recently which confirms the adoption into practice by the U.S. Photovoltaic (PV Industry, of all the low-cost module technology elements proposed at the 16th Project Integration Meeting for a $2.80/Wp (1980 U.S. Dollars) design approach in the fall of 1980. This work presents along with a projection, using the same techniques, for what is believed to be a very credible ribbon-based module design for less that $0.55/Wp (1980 U.S. Dollars). Other areas to be reported upon include low-cost Si feedstock refinement; ribbon growth; process sequence development for cells; environmental isolation; engineering science investigations; and module testing progress.

  10. Attachment of second harmonic-active moiety to molecules for detection of molecules at interfaces

    DOEpatents

    Salafsky, Joshua S.; Eisenthal, Kenneth B.

    2005-10-11

    This invention provides methods of detecting molecules at an interface, which comprise labeling the molecules with a second harmonic-active moiety and detecting the labeled molecules at the interface using a surface selective technique. The invention also provides methods for detecting a molecule in a medium and for determining the orientation of a molecular species within a planar surface using a second harmonic-active moiety and a surface selective technique.

  11. Rapid parameterization of small molecules using the Force Field Toolkit.

    PubMed

    Mayne, Christopher G; Saam, Jan; Schulten, Klaus; Tajkhorshid, Emad; Gumbart, James C

    2013-12-15

    The inability to rapidly generate accurate and robust parameters for novel chemical matter continues to severely limit the application of molecular dynamics simulations to many biological systems of interest, especially in fields such as drug discovery. Although the release of generalized versions of common classical force fields, for example, General Amber Force Field and CHARMM General Force Field, have posited guidelines for parameterization of small molecules, many technical challenges remain that have hampered their wide-scale extension. The Force Field Toolkit (ffTK), described herein, minimizes common barriers to ligand parameterization through algorithm and method development, automation of tedious and error-prone tasks, and graphical user interface design. Distributed as a VMD plugin, ffTK facilitates the traversal of a clear and organized workflow resulting in a complete set of CHARMM-compatible parameters. A variety of tools are provided to generate quantum mechanical target data, setup multidimensional optimization routines, and analyze parameter performance. Parameters developed for a small test set of molecules using ffTK were comparable to existing CGenFF parameters in their ability to reproduce experimentally measured values for pure-solvent properties (<15% error from experiment) and free energy of solvation (±0.5 kcal/mol from experiment). Copyright © 2013 Wiley Periodicals, Inc.

  12. Theoretical Calculations for Electron Impact Ionization of Atoms and Molecules

    NASA Astrophysics Data System (ADS)

    Amami, Sadek Mohamed Fituri

    In the last twenty years, significant progress has been made for the theoretical treatment of electron impact ionization (e,2e) of atoms and molecules and, for some cases, very nice agreement between experiment and theory has been achieved. In particular, excellent agreement between theory and experiment and theory has been achieved for ionization of hydrogen and helium. However, agreement between experiment and theory is not nearly as good for ionization of larger atoms and molecules. In the first part of this dissertation, different theoretical approaches will be employed to study the triply differential cross section (TDCS) for low and intermediate energy electron-impact ionization of Neon and Argon for different orbital states. There is a very recent interest in studying ionization of Laser aligned atoms in order to get a better understanding about electron impact ionization of molecules. In the next part of this dissertation, results will be presented for electron-impact ionization of three laser aligned atoms, Mg, Ca, and Na. The comparison between the theory and experiment showed that our three body distorted wave (3DW) model gave excellent agreement with experiment in the scattering plane but very poor agreement perpendicular to the scattering plane. An explanation for this poor agreement out of the scattering plane has been provided by comparing our theoretical results with those of the time depended close coupling (TDCC) model and this explanation is also provided in this dissertation. Recently, significant attention has been directed towards obtaining a better under-standing of electron-impact ionization of molecules which are significantly more challenging than atoms. In the last part of this dissertation, results will be presented for electron-impact ionization of three different molecules (N2 , H2O, and CH4) which have been studied comprehensively using different theoretical approximations for different types of geometries. The published papers in

  13. Review of Recent Progress of Plasmonic Materials and Nano-Structures for Surface-Enhanced Raman Scattering

    PubMed Central

    Wang, Alan X.; Kong, Xianming

    2015-01-01

    Surface-enhanced Raman scattering (SERS) has demonstrated single-molecule sensitivity and is becoming intensively investigated due to its significant potential in chemical and biomedical applications. SERS sensing is highly dependent on the substrate, where excitation of the localized surface plasmons (LSPs) enhances the Raman scattering signals of proximate analyte molecules. This paper reviews research progress of SERS substrates based on both plasmonic materials and nano-photonic structures. We first discuss basic plasmonic materials, such as metallic nanoparticles and nano-rods prepared by conventional bottom-up chemical synthesis processes. Then, we review rationally-designed plasmonic nano-structures created by top-down approaches or fine-controlled synthesis with high-density hot-spots to provide large SERS enhancement factors (EFs). Finally, we discuss the research progress of hybrid SERS substrates through the integration of plasmonic nano-structures with other nano-photonic devices, such as photonic crystals, bio-enabled nanomaterials, guided-wave systems, micro-fluidics and graphene. PMID:26900428

  14. Review of Recent Progress of Plasmonic Materials and Nano-Structures for Surface-Enhanced Raman Scattering.

    PubMed

    Wang, Alan X; Kong, Xianming

    2015-06-01

    Surface-enhanced Raman scattering (SERS) has demonstrated single-molecule sensitivity and is becoming intensively investigated due to its significant potential in chemical and biomedical applications. SERS sensing is highly dependent on the substrate, where excitation of the localized surface plasmons (LSPs) enhances the Raman scattering signals of proximate analyte molecules. This paper reviews research progress of SERS substrates based on both plasmonic materials and nano-photonic structures. We first discuss basic plasmonic materials, such as metallic nanoparticles and nano-rods prepared by conventional bottom-up chemical synthesis processes. Then, we review rationally-designed plasmonic nano-structures created by top-down approaches or fine-controlled synthesis with high-density hot-spots to provide large SERS enhancement factors (EFs). Finally, we discuss the research progress of hybrid SERS substrates through the integration of plasmonic nano-structures with other nano-photonic devices, such as photonic crystals, bio-enabled nanomaterials, guided-wave systems, micro-fluidics and graphene.

  15. easyCBM[R] Mathematics Criterion Related Validity Evidence: Oregon State Test. Technical Report #1011

    ERIC Educational Resources Information Center

    Anderson, Daniel; Alonzo, Julie; Tindal, Gerald

    2010-01-01

    In this technical report, we present the results of a study examining the relation between the math measures available on the easyCBM[R] online benchmark and progress monitoring assessment system and the Oregon statewide assessment of mathematics. Designed for use within a response to intervention (RTI) framework, easyCBM[R] is intended to help…

  16. Generation of Gene-Engineered Chimeric DNA Molecules for Specific Therapy of Autoimmune Diseases

    PubMed Central

    Gesheva, Vera; Szekeres, Zsuzsanna; Mihaylova, Nikolina; Dimitrova, Iliyana; Nikolova, Maria; Erdei, Anna; Prechl, Jozsef

    2012-01-01

    Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the development of self-reactive B and T cells and autoantibody production. In particular, double-stranded DNA-specific B cells play an important role in lupus progression, and their selective elimination is a reasonable approach for effective therapy of SLE. DNA-based vaccines aim at the induction of immune response against the vector-encoded antigen. Here, we are exploring, as a new DNA-based therapy of SLE, a chimeric DNA molecule encoding a DNA-mimotope peptide, and the Fv but not the immunogenic Fc fragment of an FcγRIIb-specific monoclonal antibody. This DNA construct was inserted in the expression vector pNut and used as a naked DNA vaccine in a mouse model of lupus. The chimeric DNA molecule can be expressed in eukaryotic cells and cross-links cell surface receptors on DNA-specific B cells, delivering an inhibitory intracellular signal. Intramuscular administration of the recombinant DNA molecule to lupus-prone MRL/lpr mice prevented increase in IgG anti-DNA antibodies and was associated with a low degree of proteinuria, modulation of cytokine profile, and suppression of lupus nephritis. PMID:23075110

  17. High serum level of the soluble form of CD30 molecule in the early phase of HIV-1 infection as an independent predictor of progression to AIDS.

    PubMed

    Pizzolo, G; Vinante, F; Morosato, L; Nadali, G; Chilosi, M; Gandini, G; Sinicco, A; Raiteri, R; Semenzato, G; Stein, H

    1994-06-01

    To determine the serum levels of the soluble form of the CD30 (sCD30) activation molecule in the early phase of HIV-1 infection, and to investigate the possible correlation with evolution to AIDS. sCD30 values were determined by an enzyme-linked immunosorbent assay (ELISA) on serum samples collected at the time of the first evidence of HIV-1 infection in 110 individuals with a median follow-up of 56 months (range, 12-88 months), at the A1 (74 cases) or A2 (36 cases) stages of the 1993 revised Centers for Disease Control and Prevention classification. The data were evaluated using established clinical and immunological parameters, including circulating CD4+ T-cell count. The controls were 110 blood donors and 51 HIV-1-negative subjects belonging to groups at risk for HIV-1 infection. Elevated sCD30 levels (> 20 U/ml) were found in 83.6% of HIV-1-infected cases and in 47% of at-risk seronegatives. Data analysis revealed that HIV-1-infected patients with higher sCD30 levels (> 35 U/ml) experienced faster disease progression (P = 0.0002). This was also the case in patients at the earliest stage (A1) of HIV infection (P = 0.0027). In these latter cases the predictive value of sCD30 was independent of the initial absolute number of circulating CD4+ lymphocytes. Serum levels of sCD30 are increased in the large majority of patients in the early phase of HIV-1 infection and represent an indicator of progression to AIDS independent of other prognostic parameters.

  18. Challenges for single molecule electronic devices with nanographene and organic molecules. Do single molecules offer potential as elements of electronic devices in the next generation?

    NASA Astrophysics Data System (ADS)

    Enoki, Toshiaki; Kiguchi, Manabu

    2018-03-01

    Interest in utilizing organic molecules to fabricate electronic materials has existed ever since organic (molecular) semiconductors were first discovered in the 1950s. Since then, scientists have devoted serious effort to the creation of various molecule-based electronic systems, such as molecular metals and molecular superconductors. Single-molecule electronics and the associated basic science have emerged over the past two decades and provided hope for the development of highly integrated molecule-based electronic devices in the future (after the Si-based technology era has ended). Here, nanographenes (nano-sized graphene) with atomically precise structures are among the most promising molecules that can be utilized for electronic/spintronic devices. To manipulate single small molecules for an electronic device, a single molecular junction has been developed. It is a powerful tool that allows even small molecules to be utilized. External electric, magnetic, chemical, and mechanical perturbations can change the physical and chemical properties of molecules in a way that is different from bulk materials. Therefore, the various functionalities of molecules, along with changes induced by external perturbations, allows us to create electronic devices that we cannot create using current top-down Si-based technology. Future challenges that involve the incorporation of condensed matter physics, quantum chemistry calculations, organic synthetic chemistry, and electronic device engineering are expected to open a new era in single-molecule device electronic technology.

  19. Electron-Molecule Col1isions: Quantitative Approaches, and the Legacy of Aaron Temkin

    NASA Technical Reports Server (NTRS)

    Schneider, B.I.

    2007-01-01

    This article, on electron-molecule collisions, is dedicated to the legacy of my good friend and sometime collaborator, Aaron Temkin on his retirement from the NASA-Goddard Space Flight Center after many years of work at the highest intellectual level in the theoretical treatment of electron-atom and electron-molecule scattering. Aaron's contributions to the manner in which we think about electron-molecule collisions is clear to all of us who have worked in this field. I doubt that the great progress that has occurred in the computational treatment of such complex collision problems could have happened without these contributions. For a brief historical account, see the discussion of Temkin's contribution to electron-molecule scattering in the first article of this volume by Dr. A. K. Bhatia. In this article, I will concentrate on the application of the so called, non-adiabatic R-matrix theory, to vibrational excitation and dissociative attachment, although I will also present some results applying the Linear Algebraic and Kohn-Variational methods to vibrational excitation. As a starting point for almost all computationally effective approaches to electron-molecule collisions, is the fixed nuclei approximation. That is, one recognizes, just as one does with molecular bound states, that there is a separation of electronic(fast) and nuclear(s1ow) degrees of freedom. This separation makes it possible to "freeze" the nuclei in space, calculate the collision parameters for the frozen molecule and then, somehow to add back the vibrations and rotations. The manner in which this is done, depends on the details of the collision problem. It is the work of Aaron and a number of other researchers that has provided the guidance necessary to resolve these issues.

  20. Enzymatic DNA molecules

    NASA Technical Reports Server (NTRS)

    Joyce, Gerald F. (Inventor); Breaker, Ronald R. (Inventor)

    1998-01-01

    The present invention discloses deoxyribonucleic acid enzymes--catalytic or enzymatic DNA molecules--capable of cleaving nucleic acid sequences or molecules, particularly RNA, in a site-specific manner, as well as compositions including same. Methods of making and using the disclosed enzymes and compositions are also disclosed.

  1. Hydrogen Vehicles: Impacts of DOE Technical Targets on Market Acceptance and Societal Benefits

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

    Lin, Zhenhong; Dong, Jing; Greene, David L

    2013-01-01

    Hydrogen vehicles (H2V), including H2 internal combustion engine, fuel cell and fuel cell plugin hybrid, could greatly reduce petroleum consumption and greenhouse gas (GHG) emissions in the transportation sector. The U.S. Department of Energy has adopted targets for vehicle component technologies to address key technical barriers towidespread commercialization of H2Vs. This study estimates the market acceptance of H2Vs and the resulting societal benefits and subsidy in 41 scenarios that reflect a wide range of progress in meeting these technical targets. Important results include: (1) H2Vs could reach 20e70% market shares by 2050, depending on progress in achieving the technical targets.Withmore » a basic hydrogen infrastructure (w5% hydrogen availability), the H2V market share is estimated to be 2e8%. Fuel cell and hydrogen costs are the most important factors affecting the long-term market shares of H2Vs. (2) Meeting all technical targets on time could result in about an 80% cut in petroleumuse and a 62% (or 72% with aggressive electricity de-carbonization) reduction in GHG in 2050. (3) The required hydrogen infrastructure subsidy is estimated to range from $22 to $47 billion and the vehicle subsidy from $4 to $17 billion. (4) Long-term H2V market shares, societal benefits and hydrogen subsidies appear to be highly robust against delay in one target, if all other targets are met on time. R&D diversification could provide insurance for greater societal benefits. (5) Both H2Vs and plug-in electric vehicles could exceed 50% market shares by 2050, if all targets are met on time. The overlapping technology, the fuel cell plug-in hybrid electric vehicle, appears attractive both in the short and long runs, but for different reasons.« less

  2. Preparation of translationally cold neutral molecules.

    PubMed

    Di Domenicantonio, Giulia; Bertsche, Benjamin; Osterwalder, Andreas

    2011-01-01

    Efforts at EPFL to obtain translationally cold neutral molecules are described. Active deceleration of polar molecules is performed by confining the molecules in moving three-dimensional electrostatic traps, and by appropriately choosing the velocity of those traps. Alternatively, cold molecules can be obtained by velocity filtering. Here, the velocity of the molecules is not changed, but instead the cold molecules are extracted from a thermal sample by using the competition between the electrostatic force and the centrifugal force inside a bent electrostatic guide for polar molecules.

  3. Reversible capture of small molecules on bimetallaborane clusters: synthesis, structural characterization, and photophysical aspects.

    PubMed

    Bould, Jonathan; Baše, Tomáš; Londesborough, Michael G S; Oro, Luis A; Macías, Ramón; Kennedy, John D; Kubát, Pavel; Fuciman, Marcel; Polívka, Tomáš; Lang, Kamil

    2011-08-15

    Metallaborane compounds containing two adjacent metal atoms, [(PMe(2)Ph)(4)MM'B(10)H(10)] (where MM' = Pt(2), 1; PtPd, 7; Pd(2), 8), have been synthesized, and their propensity to sequester O(2), CO, and SO(2) and to then release them under pulsed and continuous irradiation are described. Only [(PMe(2)Ph)(4)Pt(2)B(10)H(10)], 1, undergoes reversible binding of O(2) to form [(PMe(2)Ph)(4)(O(2))Pt(2)B(10)H(10)] 3, but solutions of 1, 7, and 8 all quantitatively take up CO across their metal-metal vectors to form [(PMe(2)Ph)(4)(CO)Pt(2)B(10)H(10)] 4, [(PMe(2)Ph)(4)(CO)PtPdB(10)H(10)] 10, and [(PMe(2)Ph)(4)(CO)Pd(2)B(10)H(10)] 11, respectively. Crystallographically determined interatomic M-M distances and infrared CO stretching frequencies show that the CO molecule is bound progressively more weakly in the sequence {PtPt} > {PtPd} > {PdPd}. Similarly, SO(2) forms [(PMe(2)Ph)(4)(SO(2))Pt(2)B(10)H(10)] 5, [(PMe(2)Ph)(4)(SO(2))PtPdB(10)H(10)] 12, and [(PMe(2)Ph)(4)(SO(2))Pd(2)B(10)H(10)] 13 with progressively weaker binding of the SO(2) molecule. The uptake and release of gas molecules are accompanied by changes in their absorption spectra. Nanosecond transient absorption spectroscopy clearly shows that the O(2) and CO molecules are liberated from the bimetallic binding site with high quantum yields of about 0.6. For 3, in addition to dioxygen release in the triplet ground state, singlet oxygen O(2)((1)Δ(g)) was also detected with a quantum yield <0.01. In most cases, the release and rebinding of the gas molecules can be cycled with little photodegradation of the compounds. Femtosecond transient absorption spectroscopy further reveals that the photorelease of the O(2) and CO molecules, from 3 and 4 respectively, is an ultrafast process taking place on a time scale of tens of picoseconds. For SO(2), the release is even faster (<1 ps), but only in the case of mixed metal PtPd adducts, most probably because of the metal-metal bonding asymmetry in the mixed metal clusters

  4. Schrödinger equation solved for the hydrogen molecule with unprecedented accuracy

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

    Pachucki, Krzysztof, E-mail: krp@fuw.edu.pl; Komasa, Jacek, E-mail: komasa@man.poznan.pl

    2016-04-28

    The hydrogen molecule can be used for determination of physical constants, including the proton charge radius, and for improved tests of the hypothetical long range force between hadrons, which require a sufficiently accurate knowledge of the molecular levels. In this work, we perform the first step toward a significant improvement in theoretical predictions of H{sub 2} and solve the nonrelativistic Schrödinger equation to the unprecedented accuracy of 10{sup −12}. We hope that it will inspire a parallel progress in the spectroscopy of the molecular hydrogen.

  5. Mechanisms of small molecule–DNA interactions probed by single-molecule force spectroscopy

    PubMed Central

    Almaqwashi, Ali A.; Paramanathan, Thayaparan; Rouzina, Ioulia; Williams, Mark C.

    2016-01-01

    There is a wide range of applications for non-covalent DNA binding ligands, and optimization of such interactions requires detailed understanding of the binding mechanisms. One important class of these ligands is that of intercalators, which bind DNA by inserting aromatic moieties between adjacent DNA base pairs. Characterizing the dynamic and equilibrium aspects of DNA-intercalator complex assembly may allow optimization of DNA binding for specific functions. Single-molecule force spectroscopy studies have recently revealed new details about the molecular mechanisms governing DNA intercalation. These studies can provide the binding kinetics and affinity as well as determining the magnitude of the double helix structural deformations during the dynamic assembly of DNA–ligand complexes. These results may in turn guide the rational design of intercalators synthesized for DNA-targeted drugs, optical probes, or integrated biological self-assembly processes. Herein, we survey the progress in experimental methods as well as the corresponding analysis framework for understanding single molecule DNA binding mechanisms. We discuss briefly minor and major groove binding ligands, and then focus on intercalators, which have been probed extensively with these methods. Conventional mono-intercalators and bis-intercalators are discussed, followed by unconventional DNA intercalation. We then consider the prospects for using these methods in optimizing conventional and unconventional DNA-intercalating small molecules. PMID:27085806

  6. Metals and Ceramics Division progress report for period ending June 30, 1984

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

    Brogden, I.

    1984-09-01

    This progress report covers the research and development activities of the Metals and Ceramics Division from January 1, 1983, through June 30, 1984. The format of the report follows the organizational structure of the division. Short summaries of technical work in progress in the various experimental groups are presented in six parts. Chapter 1 deals with the research and development activities of the Engineering Materials Section, Chapter 2 with the Processing Science and Technology Section, Chapter 3 with the Materials Science Section, Chapter 4 with Project Activities, Chapter 5 with Specialized Research Facilities and Equipment, and Chapter 6 with Miscellaneousmore » Activities.« less

  7. What is the minimum number of water molecules required to dissolve a potassium chloride molecule?

    PubMed

    Sen, Anik; Ganguly, Bishwajit

    2010-12-01

    This work answers an unsolved question that consists of determining the least number of water molecules necessary to separate a potassium chloride molecule. The answer based on accurate quantum chemical calculations suggests that tetramers are the smallest clusters necessary to dissociate KCl molecules. The study was made with Møller-Plesset second-order perturbation theory modified with the cluster theory having single, double, and perturbative triple excitations. With this extensive study, the dissociation of KCl molecule in different water clusters was evaluated. The calculated results show that four water molecules stabilize a solvent separated K(+)/Cl(-) ion-pair in prismatic structure and with six water molecules further dissociation was observed. Attenuated total reflection infrared spectroscopy of KCl dissolved in water establishes that clusters are made of closely bound ions with a mean of five water molecules per ion-pair [K(+)(H(2)O)(5)Cl(-)]. (Max and Chapados, Appl Spectrosc 1999, 53, 1601; Max and Chapados, J Chem Phys 2001, 115, 2664.) The calculated results tend to support that five water molecules leads toward the formation of contact ion-pair. The structures, energies, and infrared spectra of KCl molecules in different water clusters are also discussed. © 2010 Wiley Periodicals, Inc.

  8. Physics of lateral triple quantum-dot molecules with controlled electron numbers.

    PubMed

    Hsieh, Chang-Yu; Shim, Yun-Pil; Korkusinski, Marek; Hawrylak, Pawel

    2012-11-01

    We review the recent progress in theory and experiments with lateral triple quantum dots with controlled electron numbers down to one electron in each dot. The theory covers electronic and spin properties as a function of topology, number of electrons, gate voltage and external magnetic field. The orbital Hund's rules and Nagaoka ferromagnetism, magnetic frustration and chirality, interplay of quantum interference and electron-electron interactions and geometrical phases are described and related to charging and transport spectroscopy. Fabrication techniques and recent experiments are covered, as well as potential applications of triple quantum-dot molecule in coherent control, spin manipulation and quantum computation.

  9. 77 FR 75441 - Healthy Home and Lead Hazard Control Grant Programs Data Collection; Progress Reporting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-20

    ... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5603-N-93] Healthy Home and Lead Hazard... collection is designed to provide HUD timely information on progress of Healthy Homes Demonstration Program, Healthy Homes Technical Studies Program, Lead Base paint Hazard Control program, Lead Hazard Reduction...

  10. Final Scientific/Technical Report (DE-FG02-05ER46201)

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

    Car, Roberto

    The research supported by this grant focused on the quantum mechanical theory of the electrons in materials and molecules. Progress was made in dealing with electronic correlation effects in the ground state energy of molecular systems, and with topological concepts to classify the electronic state of molecules and materials, including excitation and transport properties. The physical and chemical properties of molecules and materials derive from their electronic structure, but the latter cannot be calculated exactly even with the most powerful computers because the computational cost of solving the exact equations of quantum mechanics increases exponentially with the number of electrons.more » The exponential cost originates from the correlations among the electrons that repel each other via Coulombic forces. In this project we have developed a new functional approximation for the ground state electronic energy that includes explicitly, and in a controllable way, the effects of the interelectronic correlations. In addition we have further developed topological concepts for classifying the electronic states of periodic ring molecules and solids. Topological concepts are very powerful because they allow us to predict subtle properties of materials and molecules using very general geometrical properties of the electron wavefunctions that do not depend on the quantitative details of the electronic interactions, which are very difficult to calculate with high accuracy. The development of a new class of controlled functional approximations for the ground state energy of molecules and materials was the main goal of the project. It has been fulfilled with the formulation of the occupation-probabilities natural orbital functional theory (OP-NOFT). This approach introduces new theoretical concepts but practical application has proved to be harder than anticipated. So far it has been utilized only at its lowest level of approximation in the context of relatively small

  11. Department of Energy: Office of Scientific and Technical Information

    NASA Technical Reports Server (NTRS)

    Grissom, Catherine

    1994-01-01

    The international acquisitions functions and activities of the Office of Scientific and Technical Information (OSTI) are described. There are four mechanisms for obtaining foreign information related to energy and nuclear science: The Energy Technology Data Exchange consisting of 14 member countries and 2 associate members; the International Nuclear Information System consisting of 86 countries and 17 international organizations; the Nuclear Energy Agency's 19 member countries provide reports for departmental scientists' use; bilateral agreements with countries such as Germany, the Nordic Consortium, and Australia result in records of foreign research in progress.

  12. EDITORIAL: Focus on Cold and Ultracold Molecules FOCUS ON COLD AND ULTRACOLD MOLECULES

    NASA Astrophysics Data System (ADS)

    Carr, Lincoln D.; Ye, Jun

    2009-05-01

    Cold and ultracold molecules are the next wave of ultracold physics, giving rise to an exciting array of scientific opportunities, including many body physics for novel quantum phase transitions, new states of matter, and quantum information processing. Precision tests of fundamental physical laws benefit from the existence of molecular internal structure with exquisite control. The study of novel collision and reaction dynamics will open a new chapter of quantum chemistry. Cold molecules bring together researchers from a variety of fields, including atomic, molecular, and optical physics, chemistry and chemical physics, quantum information science and quantum simulations, condensed matter physics, nuclear physics, and astrophysics, a truly remarkable synergy of scientific explorations. For the past decade there have been steady advances in direct cooling techniques, from buffer-gas cooling to cold molecular beams to electro- and magneto-molecular decelerators. These techniques have allowed a large variety of molecules to be cooled for pioneering studies. Recent amazing advances in experimental techniques combining the ultracold and the ultraprecise have furthermore brought molecules to the point of quantum degeneracy. These latter indirect cooling techniques magnetically associate atoms from a Bose-Einstein condensate and/or a quantum degenerate Fermi gas, transferring at 90% efficiency highly excited Fano-Feshbach molecules, which are on the order of 10 000 Bohr radii in size, to absolute ground state molecules just a few Bohr across. It was this latter advance, together with significant breakthroughs in internal state manipulations, which inspired us to coordinate this focus issue now, and is the reason why we say the next wave of ultracold physics has now arrived. Whether directly or indirectly cooled, heteronuclear polar molecules offer distinct new features in comparison to cold atoms, while sharing all of their advantages (purity, high coherence

  13. Optical differential reflectance spectroscopy for photochromic molecules on solid surfaces

    NASA Astrophysics Data System (ADS)

    Nickel, Fabian; Bernien, Matthias; Lipowski, Uwe; Kuch, Wolfgang

    2018-03-01

    Optical reflectance of thin adsorbates on solid surfaces is able to reveal fundamental changes of molecular properties compared to bulk systems. The detection of very small changes in the optical reflectance required several technical improvements in the past decades. We present an experimental setup that is capable of high-quality measurements of submonolayers and ultrathin layers of photochromic molecules on surfaces as well as quantifying their isomerization kinetics. By using photomultipliers as detectors, an enhancement of the signal-to-noise ratio by a factor of three with a total reduction of light exposure on the sample by at least four orders of magnitude is achieved. The potential of the experimental setup is demonstrated by a characterization of the photoswitching and thermal switching of a spirooxazine derivate on a bismuth surface.

  14. Re-Evaluating Progression in an Era of Progress: A Review of First- and Second-Line Treatment Options in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer.

    PubMed

    Castellanos, Emily H; Horn, Leora

    2016-06-01

    : The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer. The development of second-generation ALK inhibitors, starting with the recent U.S. Food and Drug Administration approval of ceritinib, promises to expand the therapeutic landscape for this cohort of patients. With increasing use of molecularly targeted therapy options, it has been observed that disease progression in patients receiving targeted agents has a heterogeneous biology, manifesting as either oligoprogressive or widely progressive disease, which may require development of innovative treatment strategies. This review discusses the first- and second-generation ALK inhibitors approved or in clinical development, as well as the novel challenges and approaches to disease progression in patients on targeted agents. The identification of driver mutations in non-small cell lung cancer (NSCLC), most prominently epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has expanded treatment options for a significant cohort of patients. However, the success of targeted agents has brought new challenges, particularly regarding management of progression. Progression manifests heterogeneously, and management of oligoprogression may differ from diffusely progressive disease. Multiple options for treatment at progression exist, and it is becoming evident that selecting the best avenue of care requires understanding the biology and potential drivers of disease progression. This review discusses the array of treatment options available for patients with ALK-positive NSCLC, as well as evaluation and treatment of progressive disease. ©AlphaMed Press.

  15. Re-Evaluating Progression in an Era of Progress: A Review of First- and Second-Line Treatment Options in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer

    PubMed Central

    Castellanos, Emily H.

    2016-01-01

    The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer. The development of second-generation ALK inhibitors, starting with the recent U.S. Food and Drug Administration approval of ceritinib, promises to expand the therapeutic landscape for this cohort of patients. With increasing use of molecularly targeted therapy options, it has been observed that disease progression in patients receiving targeted agents has a heterogeneous biology, manifesting as either oligoprogressive or widely progressive disease, which may require development of innovative treatment strategies. This review discusses the first- and second-generation ALK inhibitors approved or in clinical development, as well as the novel challenges and approaches to disease progression in patients on targeted agents. Implications for Practice: The identification of driver mutations in non-small cell lung cancer (NSCLC), most prominently epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has expanded treatment options for a significant cohort of patients. However, the success of targeted agents has brought new challenges, particularly regarding management of progression. Progression manifests heterogeneously, and management of oligoprogression may differ from diffusely progressive disease. Multiple options for treatment at progression exist, and it is becoming evident that selecting the best avenue of care requires understanding the biology and potential drivers of disease progression. This review discusses the array of treatment options available for patients with ALK-positive NSCLC, as well as evaluation and treatment of progressive disease. PMID:27053502

  16. Algorithmic methods to infer the evolutionary trajectories in cancer progression

    PubMed Central

    Graudenzi, Alex; Ramazzotti, Daniele; Sanz-Pamplona, Rebeca; De Sano, Luca; Mauri, Giancarlo; Moreno, Victor; Antoniotti, Marco; Mishra, Bud

    2016-01-01

    The genomic evolution inherent to cancer relates directly to a renewed focus on the voluminous next-generation sequencing data and machine learning for the inference of explanatory models of how the (epi)genomic events are choreographed in cancer initiation and development. However, despite the increasing availability of multiple additional -omics data, this quest has been frustrated by various theoretical and technical hurdles, mostly stemming from the dramatic heterogeneity of the disease. In this paper, we build on our recent work on the “selective advantage” relation among driver mutations in cancer progression and investigate its applicability to the modeling problem at the population level. Here, we introduce PiCnIc (Pipeline for Cancer Inference), a versatile, modular, and customizable pipeline to extract ensemble-level progression models from cross-sectional sequenced cancer genomes. The pipeline has many translational implications because it combines state-of-the-art techniques for sample stratification, driver selection, identification of fitness-equivalent exclusive alterations, and progression model inference. We demonstrate PiCnIc’s ability to reproduce much of the current knowledge on colorectal cancer progression as well as to suggest novel experimentally verifiable hypotheses. PMID:27357673

  17. Placing and preserving priorities: projects, productivity, progress and people

    PubMed Central

    Babiak, John

    1998-01-01

    High throughput screening (HTS) involves using automated equipment to test a large number of samples against a defined molecular target to identify a reasonable number of active molecules in a timely fashion. Major factors which can influence priorities for the limited resources of the HTS group are projects, productivity, progress and people. The challenge to the HTS group is to provide excellent and timely screening services, but still devote efforts to new technologies and personnel development. This article explains why these factors are so important. PMID:18924829

  18. The bright future of single-molecule fluorescence imaging

    PubMed Central

    Juette, Manuel F.; Terry, Daniel S.; Wasserman, Michael R.; Zhou, Zhou; Altman, Roger B.; Zheng, Qinsi; Blanchard, Scott C.

    2014-01-01

    Single-molecule Förster resonance energy transfer (smFRET) is an essential and maturing tool to probe biomolecular interactions and conformational dynamics in vitro and, increasingly, in living cells. Multi-color smFRET enables the correlation of multiple such events and the precise dissection of their order and timing. However, the requirements for good spectral separation, high time resolution, and extended observation times place extraordinary demands on the fluorescent labels used in such experiments. Together with advanced experimental designs and data analysis, the development of long-lasting, non-fluctuating fluorophores is therefore proving key to progress in the field. Recently developed strategies for obtaining ultra-stable organic fluorophores spanning the visible spectrum are underway that will enable multi-color smFRET studies to deliver on their promise of previously unachievable biological insights. PMID:24956235

  19. Longitudinal Surveys of Australian Youth (LSAY) 2009 Cohort: Wave 2 (2010)--Frequency Tables. Technical Report 71B

    ERIC Educational Resources Information Center

    National Centre for Vocational Education Research (NCVER), 2012

    2012-01-01

    The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the frequency tables for the LSAY 2009 cohort Wave 2 (2010) data set.

  20. Current Progress of siRNA/shRNA Therapeutics in Clinical Trials

    PubMed Central

    Burnett, John C.; Rossi, John J.; Tiemann, Katrin

    2012-01-01

    Through a mechanism known as RNA interference (RNAi), small interfering RNA (siRNA) molecules can target complementary mRNA strands for degradation, thus specifically inhibiting gene expression. The ability of siRNAs to inhibit gene expression offers a mechanism that can be exploited for novel therapeutics. Indeed, over the past decade, at least 21 siRNA therapeutics have been developed for more than a dozen diseases, including various cancers, viruses, and genetic disorders. Like other biological drugs, RNAi-based therapeutics often require a delivery vehicle to transport them to the targeted cells. Thus, the clinical advancement of numerous siRNA drugs has relied on the development of siRNA carriers including biodegradable nanoparticles, lipids, bacteria, and attenuated viruses. Most therapies permit systemic delivery of the siRNA drug, while others use ex vivo delivery by autologous cell therapy. For some of the drugs, advancements in bioengineering and nanotechnology have led to improved control of delivery and release of the siRNA. Likewise, progress in molecular biology has allowed for improved design of the siRNA molecules. Here, we provide an overview of siRNA therapeutics in clinical trials, including their clinical progress, the challenges they have encountered, and the future they hold in the treatment of human diseases. PMID:21744502

  1. Protease-Activated Receptor-2 Deficiency Attenuates Atherosclerotic Lesion Progression and Instability in Apolipoprotein E-Deficient Mice

    PubMed Central

    Zuo, Pengfei; Zuo, Zhi; Zheng, Yueyue; Wang, Xin; Zhou, Qianxing; Chen, Long; Ma, Genshan

    2017-01-01

    Inflammatory mechanisms are involved in the process of atherosclerotic plaque formation and rupture. Accumulating evidence suggests that protease-activated receptor (PAR)-2 contributes to the pathophysiology of chronic inflammation on the vasculature. To directly examine the role of PAR-2 in atherosclerosis, we generated apolipoprotein E/PAR-2 double-deficient mice. Mice were fed with high-fat diet for 12 weeks starting at ages of 6 weeks. PAR-2 deficiency attenuated atherosclerotic lesion progression with reduced total lesion area, reduced percentage of stenosis and reduced total necrotic core area. PAR-2 deficiency increased fibrous cap thickness and collagen content of plaque. Moreover, PAR-2 deficiency decreased smooth muscle cell content, macrophage accumulation, matrix metallopeptidase-9 expression and neovascularization in plaque. Relative quantitative PCR assay using thoracic aorta revealed that PAR-2 deficiency reduced mRNA expression of inflammatory molecules, such as vascular cell adhesion molecule-1, intercellular adhesion molecule-1, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. In vitro experiment, we found that PAR-2 deficiency reduced mRNA expression of interferon-γ, interleukin-6, TNF-α and MCP-1 in macrophage under unstimulated and lipopolysaccharide-stimulated conditions. These results suggest that PAR-2 deficiency attenuates the progression and instability of atherosclerotic plaque. PMID:28959204

  2. The small molecule CS1 inhibits mitosis and sister chromatid resolution in HeLa cells.

    PubMed

    Wu, Xingkang; Li, Zhenyu; Shen, Yuemao

    2018-05-01

    Mitosis, the most dramatic event in the cell cycle, involves the reorganization of virtually all cellular components. Antimitotic agents are useful for dissecting the mechanism of this reorganization. Previously, we found that the small molecule CS1 accumulates cells in G2/M phase [1], but the mechanism of its action remains unknown. Cell cycle analysis, live cell imaging and nuclear staining were used. Chromosomal morphology was detected by chromosome spreading. The effects of CS1 on microtubules were confirmed by tubulin polymerization, colchicine tubulin-binding, cellular tubulin polymerization and immunofluorescence assays and by analysis of microtubule dynamics and molecular modeling. Histone phosphoproteomics was performed using mass spectrometry. Cell signaling cascades were analyzed using immunofluorescence, immunoprecipitation, immunoblotting, siRNA knockdown and chemical inhibition of specific proteins. The small molecule CS1 was shown to be an antimitotic agent. CS1 potently inhibited microtubule polymerization via interaction with the colchicine-binding pocket of tubulin in vitro and inhibited the formation of the spindle apparatus by reducing the bulk of growing microtubules in HeLa cells, which led to activation of the spindle assembly checkpoint (SAC) and mitotic arrest of HeLa cells. Compared with colchicine, CS1 impaired the progression of sister chromatid resolution independent of cohesin dissociation, and this was reversed by the removal of CS1. Additionally, CS1 induced unique histone phosphorylation patterns distinct from those induced by colchicine. CS1 is a unique antimitotic small molecule and a powerful tool with unprecedented value over colchicine that makes it possible to specifically and conditionally perturb mitotic progression. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Quarterly Technical Progress Report - Investigation of Syngas Interaction in Alcohol Synthesis Catalysts

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

    Murty A. Akundi

    This report presents the work done on " Investigation of Syngas Interaction in Alcohol Synthesis Catalysts" during the last quarter. The major activity during this period is on FTIR absorption studies of Co/Cr catalysts using CO as a probe molecule. Transition metals cobalt and copper play significant roles in the conversion of syngas (CO + H2 ) to liquid fuels. With a view to examine the nature of interaction between CO and metal, the FTIR spectra of CO adsorbed on Co-Cr2 O3 composites were investigated. The results indicate that as cobalt loading increases, the intensity of the CO adsorption bandsmore » increase and several vibrational modes seem to be promoted. Heat treatment of the sample revealed two distinct processes of adsorption. Bands due to physisorption disappeared while bands due to chemisorption not only increased in intensity but persisted even after desorption. It seems that the physisorption process is more active when the catalyst is fresh and is hindered when carbidic/carbonyl formations occur on the metal surfaces.« less

  4. Single-Molecule Bioelectronics

    PubMed Central

    Rosenstein, Jacob K.; Lemay, Serge G.; Shepard, Kenneth L.

    2014-01-01

    Experimental techniques which interface single biomolecules directly with microelectronic systems are increasingly being used in a wide range of powerful applications, from fundamental studies of biomolecules to ultra-sensitive assays. Here we review several technologies which can perform electronic measurements of single molecules in solution: ion channels, nanopore sensors, carbon nanotube field-effect transistors, electron tunneling gaps, and redox cycling. We discuss the shared features among these techniques that enable them to resolve individual molecules, and discuss their limitations. Recordings from each of these methods all rely on similar electronic instrumentation, and we discuss the relevant circuit implementations and potential for scaling these single-molecule bioelectronic interfaces to high-throughput arrayed sensing platforms. PMID:25529538

  5. Progress in satellite quantum key distribution

    NASA Astrophysics Data System (ADS)

    Bedington, Robert; Arrazola, Juan Miguel; Ling, Alexander

    2017-08-01

    Quantum key distribution (QKD) is a family of protocols for growing a private encryption key between two parties. Despite much progress, all ground-based QKD approaches have a distance limit due to atmospheric losses or in-fibre attenuation. These limitations make purely ground-based systems impractical for a global distribution network. However, the range of communication may be extended by employing satellites equipped with high-quality optical links. This manuscript summarizes research and development which is beginning to enable QKD with satellites. It includes a discussion of protocols, infrastructure, and the technical challenges involved with implementing such systems, as well as a top level summary of on-going satellite QKD initiatives around the world.

  6. Trends in Articulation Arrangements for Technical and Vocational Education in the South East Asian Region.

    ERIC Educational Resources Information Center

    Haas, Adrian R.

    Trends in articulation arrangements for technical and vocational education (TVE) in the South East Asia region were studied. A key feature of articulation is the existence of pathways that allow graduates of one course of study to progress to other courses. Effective articulation opens up advancement for individuals and helps to create a flexible…

  7. Single-molecule dynamics in nanofabricated traps

    NASA Astrophysics Data System (ADS)

    Cohen, Adam

    2009-03-01

    The Anti-Brownian Electrokinetic trap (ABEL trap) provides a means to immobilize a single fluorescent molecule in solution, without surface attachment chemistry. The ABEL trap works by tracking the Brownian motion of a single molecule, and applying feedback electric fields to induce an electrokinetic motion that approximately cancels the Brownian motion. We present a new design for the ABEL trap that allows smaller molecules to be trapped and more information to be extracted from the dynamics of a single molecule than was previously possible. In particular, we present strategies for extracting dynamically fluctuating mobilities and diffusion coefficients, as a means to probe dynamic changes in molecular charge and shape. If one trapped molecule is good, many trapped molecules are better. An array of single molecules in solution, each immobilized without surface attachment chemistry, provides an ideal test-bed for single-molecule analyses of intramolecular dynamics and intermolecular interactions. We present a technology for creating such an array, using a fused silica plate with nanofabricated dimples and a removable cover for sealing single molecules within the dimples. With this device one can watch the shape fluctuations of single molecules of DNA or study cooperative interactions in weakly associating protein complexes.

  8. Longitudinal Surveys of Australian Youth (LSAY) 1998 Cohort: Wave 12 (2009)--Questionnaire. Technical Report 58A

    ERIC Educational Resources Information Center

    National Centre for Vocational Education Research (NCVER), 2010

    2010-01-01

    The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the questionnaire for the LSAY 1998 cohort Wave 12 (2009) data set. [For the accompanying frequency tables, "Longitudinal Surveys…

  9. Application of Communications Satellites to Educational Development. Final Technical Report, September 1, 1969-August 31, 1975.

    ERIC Educational Resources Information Center

    Morgan, Robert P.

    Research is summarized in a brief final report built around a four-section bibliography. The first section lists periodic progress reports and articles which provide an overview of the program, including articles which pertain primarily to educational rather than technical aspects of satellite utilization. Theses carried out in the fields of…

  10. Relationship between intraoperative non-technical performance and technical events in bariatric surgery.

    PubMed

    Fecso, A B; Kuzulugil, S S; Babaoglu, C; Bener, A B; Grantcharov, T P

    2018-03-30

    The operating theatre is a unique environment with complex team interactions, where technical and non-technical performance affect patient outcomes. The correlation between technical and non-technical performance, however, remains underinvestigated. The purpose of this study was to explore these interactions in the operating theatre. A prospective single-centre observational study was conducted at a tertiary academic medical centre. One surgeon and three fellows participated as main operators. All patients who underwent a laparoscopic Roux-en-Y gastric bypass and had the procedures captured using the Operating Room Black Box ® platform were included. Technical assessment was performed using the Objective Structured Assessment of Technical Skills and Generic Error Rating Tool instruments. For non-technical assessment, the Non-Technical Skills for Surgeons (NOTSS) and Scrub Practitioners' List of Intraoperative Non-Technical Skills (SPLINTS) tools were used. Spearman rank-order correlation and N-gram statistics were conducted. Fifty-six patients were included in the study and 90 procedural steps (gastrojejunostomy and jejunojejunostomy) were analysed. There was a moderate to strong correlation between technical adverse events (r s  = 0·417-0·687), rectifications (r s  = 0·380-0·768) and non-technical performance of the surgical and nursing teams (NOTSS and SPLINTS). N-gram statistics showed that after technical errors, events and prior rectifications, the staff surgeon and the scrub nurse exhibited the most positive non-technical behaviours, irrespective of operator (staff surgeon or fellow). This study demonstrated that technical and non-technical performances are related, on both an individual and a team level. Valuable data can be obtained around intraoperative errors, events and rectifications. © 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

  11. Small Molecule Anticonvulsant Agents with Potent In Vitro Neuroprotection

    PubMed Central

    Smith, Garry R.; Zhang, Yan; Du, Yanming; Kondaveeti, Sandeep K.; Zdilla, Michael J.; Reitz, Allen B.

    2012-01-01

    Severe seizure activity is associated with recurring cycles of excitotoxicity and oxidative stress that result in progressive neuronal damage and death. Intervention to halt these pathological processes is a compelling disease-modifying strategy for the treatment of seizure disorders. In the present study, a core small molecule with anticonvulsant activity has been structurally optimized for neuroprotection. Phenotypic screening of rat hippocampal cultures with nutrient medium depleted of antioxidants was utilized as a disease model. Increased cell death and decreased neuronal viability produced by acute treatment with glutamate or hydrogen peroxide were prevented by our novel molecules. The neuroprotection associated with this chemical series has marked structure activity relationships that focus on modification of the benzylic position of a 2-phenyl-2-hydroxyethyl sulfamide core structure. Complete separation between anticonvulsant activity and neuroprotective action was dependent on substitution at the benzylic carbon. Chiral selectivity was evident in that the S-enantiomer of the benzylic hydroxy group had neither neuroprotective nor anticonvulsant activity, while the R-enantiomer of the lead compound had full neuroprotective action at ≤40 nM and antiseizure activity in three animal models. These studies indicate that potent, multifunctional neuroprotective anticonvulsants are feasible within a single molecular entity. PMID:22535312

  12. Recent progress in boron nanomaterials

    PubMed Central

    Kondo, Takahiro

    2017-01-01

    Abstract Various types of zero, one, and two-dimensional boron nanomaterials such as nanoclusters, nanowires, nanotubes, nanobelts, nanoribbons, nanosheets, and monolayer crystalline sheets named borophene have been experimentally synthesized and identified in the last 20 years. Owing to their low dimensionality, boron nanomaterials have different bonding configurations from those of three-dimensional bulk boron crystals composed of icosahedra or icosahedral fragments. The resulting intriguing physical and chemical properties of boron nanomaterials are fascinating from the viewpoint of material science. Moreover, the wide variety of boron nanomaterials themselves could be the building blocks for combining with other existing nanomaterials, molecules, atoms, and/or ions to design and create materials with new functionalities and properties. Here, the progress of the boron nanomaterials is reviewed and perspectives and future directions are described. PMID:29152014

  13. Magnetoassociation of KRb Feshbach molecules

    NASA Astrophysics Data System (ADS)

    Cumby, Tyler; Perreault, John; Shewmon, Ruth; Jin, Deborah

    2010-03-01

    I will discuss experiments in which we study the creation of ^40K^87Rb Feshbach molecules via magnetoassociation. We measure the molecule number as a function of the magnetic-field sweep rate through the interspecies Feshbach resonance and explore the dependence of association on the initial atom gas conditions. This study of the Feshbach molecule creation process may be relevant to the production of ultracold polar molecules, where magnetoassociated Feshbach molecules can be a crucial first step [1].[4pt] [1] K.-K. Ni, S. Ospelkaus, M. H. G. de Miranda, A. Peer, B. Neyenhuis, J. J. Zirbel, S. Kotochigova, P. S. Julienne, D. S. Jin, and J. Ye, Science, 2008, 322, 231- 235.

  14. Magnetoassociation of KRb Feshbach molecules

    NASA Astrophysics Data System (ADS)

    Cumby, Tyler; Perreault, John; Shewmon, Ruth; Jin, Deborah

    2010-03-01

    I will discuss experiments in which we study the creation of ^40K^87Rb Feshbach molecules via magnetoassociation. We measure the molecule number as a function of the magnetic-field sweep rate through the interspecies Feshbach resonance and explore the dependence of association on the initial atom gas conditions. This study of the Feshbach molecule creation process may be relevant to the production of ultracold polar molecules, where magnetoassociated Feshbach molecules can be a crucial first step [1].[4pt] [1] K.-K. Ni, S. Ospelkaus, M. H. G. de Miranda, A. Peer, B. Neyenhuis, J. J. Zirbel, S. Kotochigova, P. S. Julienne, D. S. Jin, and J. Ye, Science, 2008, 322, 231-235.

  15. Organizing and addressing magnetic molecules.

    PubMed

    Gatteschi, Dante; Cornia, Andrea; Mannini, Matteo; Sessoli, Roberta

    2009-04-20

    Magnetic molecules ranging from simple organic radicals to single-molecule magnets (SMMs) are intensively investigated for their potential applications in molecule-based information storage and processing. The goal of this Article is to review recent achievements in the organization of magnetic molecules on surfaces and in their individual probing and manipulation. We stress that the inherent fragility and redox sensitivity of most SMM complexes, combined with the noninnocent role played by the substrate, ask for a careful evaluation of the structural and electronic properties of deposited molecules going beyond routine methods for surface analysis. Detailed magnetic information can be directly obtained using X-ray magnetic circular dichroism or newly emerging scanning probe techniques with magnetic detection capabilities.

  16. Ab Initio Calculation of Accurate Vibrational Frequencies for Molecules of Interest in Atmospheric Chemistry

    NASA Technical Reports Server (NTRS)

    Lee, Timothy J.; Langhoff, Stephen R. (Technical Monitor)

    1996-01-01

    Due to advances in quantum mechanical methods over the last few years, it is now possible to determine ab initio potential energy surfaces in which fundamental vibrational frequencies are accurate to within +/- 8 cm(sup -1) on average, and molecular bond distances are accurate to within +/- 0.001-0.003 A, depending on the nature of the bond. That is, the potential energy surfaces have not been scaled or empirically adjusted in any way, showing that theoretical methods have progressed to the point of being useful in analyzing spectra that are not from a tightly controlled laboratory environment, such as rovibrational spectra from the interstellar medium. Some recent examples demonstrating this accuracy win be presented and discussed. These include the HNO, CH4, C2H4, and ClCN molecules. The HNO molecule is interesting due to the very large H-N anharmonicity, while ClCN has a very large Fermi resonance. The ab initio studies for the CH4 and C2H4 molecules present the first accurate full quartic force fields of any kind (i.e., whether theoretical or empirical) for a five-atom and six-atom system, respectively.

  17. Curriculum-Based Measurement in Science Learning: Vocabulary-Matching as an Indicator of Performance and Progress

    ERIC Educational Resources Information Center

    Espin, Christine A.; Busch, Todd W.; Lembke, Erica S.; Hampton, David D.; Seo, Kyounghee; Zukowski, Beth A.

    2013-01-01

    The technical adequacy of curriculum-based measures in the form of short and simple vocabulary-matching probes to predict students' performance and progress in science at the secondary level was investigated. Participants were 198 seventh-grade students from 10 science classrooms. Curriculum-based measurements (CBM) were 5-min vocabulary-matching…

  18. Progress in the First Five Years: An Evaluation of Achieving the Dream Colleges in Washington State

    ERIC Educational Resources Information Center

    Jenkins, Davis; Wachen, John; Kerrigan, Monica Reid; Mayer, Alexander K.

    2012-01-01

    In 2006, six community and technical colleges in Washington State joined the innovative national reform initiative called Achieving the Dream (ATD). This report describes the progress each college made in implementing ATD's "culture of evidence" principles for institutional improvement, examines strategies implemented by the colleges to…

  19. Do failures in non-technical skills contribute to fatal medical accidents in Japan? A review of the 2010-2013 national accident reports.

    PubMed

    Uramatsu, Masashi; Fujisawa, Yoshikazu; Mizuno, Shinya; Souma, Takahiro; Komatsubara, Akinori; Miki, Tamotsu

    2017-02-16

    We sought to clarify how large a proportion of fatal medical accidents can be considered to be caused by poor non-technical skills, and to support development of a policy to reduce number of such accidents by making recommendations about possible training requirements. Summaries of reports of fatal medical accidents, published by the Japan Medical Safety Research Organization, were reviewed individually. Three experienced clinicians and one patient safety expert conducted the reviews to determine the cause of death. Views of the patient safety expert were given additional weight in the overall determination. A total of 73 summary reports of fatal medical accidents were reviewed. These reports had been submitted by healthcare organisations across Japan to the Japan Medical Safety Research Organization between April 2010 and March 2013. The cause of death in fatal medical accidents, categorised into technical skills, non-technical skills and inevitable progress of disease were evaluated. Non-technical skills were further subdivided into situation awareness, decision making, communication, team working, leadership, managing stress and coping with fatigue. Overall, the cause of death was identified as non-technical skills in 34 cases (46.6%), disease progression in 33 cases (45.2%) and technical skills in two cases (5.5%). In two cases, no consensual determination could be achieved. Further categorisation of cases of non-technical skills were identified as 14 cases (41.2%) of problems with situation awareness, eight (23.5%) with team working and three (8.8%) with decision making. These three subcategories, or combinations of them, were identified as the cause of death in 33 cases (97.1%). Poor non-technical skills were considered to be a significant cause of adverse events in nearly half of the fatal medical accidents examined. Improving non-technical skills may be effective for reducing accidents, and training in particular subcategories of non-technical skills may be

  20. Activation of cannabinoid CB2 receptor ameliorates atherosclerosis associated with suppression of adhesion molecules.

    PubMed

    Zhao, Yan; Yuan, Zuyi; Liu, Yan; Xue, Jiahong; Tian, Yuling; Liu, Weimin; Zhang, Weiping; Shen, Yan; Xu, Wei; Liang, Xiao; Chen, Tao

    2010-03-01

    Adhesion molecules have been implicated in the development and progression of atherosclerosis. Cannabinoids have been reported to modulate the migration and adhesion molecules expression of various cell types. Here we examined the effects of WIN55212-2, a cannabinoid receptor 1 (CB1-R)/cannabinoid receptor 2 (CB2-R) agonist on the development of atherosclerotic lesions in apolipoprotein E-deficient (ApoE-/-) mice, which are vulnerable because of their high plasma cholesterol and triacylglycerol levels, focusing on the expression of endothelial adhesion molecules. In the aorta of ApoE-/- mice, WIN55212-2 significantly reduced aortic root plaque area. The mechanism for this seemed to be reduced infiltration of macrophages into the atherosclerotic plaque which was also associated with reduced expression of vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and P-selectin in the aorta. In vitro studies revealed reduced cell adhesion of a monocytic cell line (U937) to human umbilical vein endothelial cells after incubation with WIN55212-2. The reduction in macrophage adhesion also correlated with significant reductions in the expression of VCAM-1, ICAM-1, and P-selectin, indicating that reduced infiltration of macrophages in atherosclerotic plaques may occur as a result of the direct effect of WIN55212-2 on adhesion molecules in macrophages and endothelial cells. In conclusion, WIN55212-2 seems to have direct anti-atherosclerotic effects in an animal model of atherosclerosis. These effects were at least partly due to effects on the expression of VCAM-1, ICAM-1, and P-selectin, which led to reduced macrophage adhesion and infiltration. Furthermore, the protective effects completely blocked by the highly selective CB2 receptor antagonist AM630 suggest that these beneficial effects of WIN55212-2 may be mediated through the CB2 receptor.

  1. Programmable colloidal molecules from sequential capillarity-assisted particle assembly

    PubMed Central

    Ni, Songbo; Leemann, Jessica; Buttinoni, Ivo; Isa, Lucio; Wolf, Heiko

    2016-01-01

    The assembly of artificial nanostructured and microstructured materials which display structures and functionalities that mimic nature’s complexity requires building blocks with specific and directional interactions, analogous to those displayed at the molecular level. Despite remarkable progress in synthesizing “patchy” particles encoding anisotropic interactions, most current methods are restricted to integrating up to two compositional patches on a single “molecule” and to objects with simple shapes. Currently, decoupling functionality and shape to achieve full compositional and geometrical programmability remains an elusive task. We use sequential capillarity-assisted particle assembly which uniquely fulfills the demands described above. This is a new method based on simple, yet essential, adaptations to the well-known capillary assembly of particles over topographical templates. Tuning the depth of the assembly sites (traps) and the surface tension of moving droplets of colloidal suspensions enables controlled stepwise filling of traps to “synthesize” colloidal molecules. After deposition and mechanical linkage, the colloidal molecules can be dispersed in a solvent. The template’s shape solely controls the molecule’s geometry, whereas the filling sequence independently determines its composition. No specific surface chemistry is required, and multifunctional molecules with organic and inorganic moieties can be fabricated. We demonstrate the “synthesis” of a library of structures, ranging from dumbbells and triangles to units resembling bar codes, block copolymers, surfactants, and three-dimensional chiral objects. The full programmability of our approach opens up new directions not only for assembling and studying complex materials with single-particle-level control but also for fabricating new microscale devices for sensing, patterning, and delivery applications. PMID:27051882

  2. Observation of pendular butterfly Rydberg molecules

    PubMed Central

    Niederprüm, Thomas; Thomas, Oliver; Eichert, Tanita; Lippe, Carsten; Pérez-Ríos, Jesús; Greene, Chris H.; Ott, Herwig

    2016-01-01

    Engineering molecules with a tunable bond length and defined quantum states lies at the heart of quantum chemistry. The unconventional binding mechanism of Rydberg molecules makes them a promising candidate to implement such tunable molecules. A very peculiar type of Rydberg molecules are the so-called butterfly molecules, which are bound by a shape resonance in the electron–perturber scattering. Here we report the observation of these exotic molecules and employ their exceptional properties to engineer their bond length, vibrational state, angular momentum and orientation in a small electric field. Combining the variable bond length with their giant dipole moment of several hundred Debye, we observe counter-intuitive molecules which locate the average electron position beyond the internuclear distance. PMID:27703143

  3. Curcumin inhibits cancer progression through regulating expression of microRNAs.

    PubMed

    Zhou, Siying; Zhang, Sijie; Shen, Hongyu; Chen, Wei; Xu, Hanzi; Chen, Xiu; Sun, Dawei; Zhong, Shanliang; Zhao, Jianhua; Tang, Jinhai

    2017-02-01

    Curcumin, a major yellow pigment and spice in turmeric and curry, is a powerful anti-cancer agent. The anti-tumor activities of curcumin include inhibition of tumor proliferation, angiogenesis, invasion and metastasis, induction of tumor apoptosis, increase of chemotherapy sensitivity, and regulation of cell cycle and cancer stem cell, indicating that curcumin maybe a strong therapeutic potential through modulating various cancer progression. It has been reported that microRNAs as small noncoding RNA molecules are related to cancer progression, which can be regulated by curcumin. Dysregulated microRNAs play vital roles in tumor biology via regulating expressions of target genes and then influencing multiple cancer-related signaling pathways. In this review, we focused on the inhibition effect of curcumin on various cancer progression by regulating expression of multiple microRNAs. Curcumin-induced dysregulation of microRNAs may activate or inactivate a set of signaling pathways, such as Akt, Bcl-2, PTEN, p53, Notch, and Erbb signaling pathways. A better understanding of the relation between curcumin and microRNAs may provide a potential therapeutic target for various cancers.

  4. A small molecule mitigates hearing loss in a mouse model of Usher syndrome III.

    PubMed

    Alagramam, Kumar N; Gopal, Suhasini R; Geng, Ruishuang; Chen, Daniel H-C; Nemet, Ina; Lee, Richard; Tian, Guilian; Miyagi, Masaru; Malagu, Karine F; Lock, Christopher J; Esmieu, William R K; Owens, Andrew P; Lindsay, Nicola A; Ouwehand, Krista; Albertus, Faywell; Fischer, David F; Bürli, Roland W; MacLeod, Angus M; Harte, William E; Palczewski, Krzysztof; Imanishi, Yoshikazu

    2016-06-01

    Usher syndrome type III (USH3), characterized by progressive deafness, variable balance disorder and blindness, is caused by destabilizing mutations in the gene encoding the clarin-1 (CLRN1) protein. Here we report a new strategy to mitigate hearing loss associated with a common USH3 mutation CLRN1(N48K) that involves cell-based high-throughput screening of small molecules capable of stabilizing CLRN1(N48K), followed by a secondary screening to eliminate general proteasome inhibitors, and finally an iterative process to optimize structure-activity relationships. This resulted in the identification of BioFocus 844 (BF844). To test the efficacy of BF844, we developed a mouse model that mimicked the progressive hearing loss associated with USH3. BF844 effectively attenuated progressive hearing loss and prevented deafness in this model. Because the CLRN1(N48K) mutation causes both hearing and vision loss, BF844 could in principle prevent both sensory deficiencies in patients with USH3. Moreover, the strategy described here could help identify drugs for other protein-destabilizing monogenic disorders.

  5. Fluorous tagging strategy for solution-phase synthesis of small molecules, peptides and oligosaccharides

    PubMed Central

    Zhang, Wei

    2005-01-01

    The purification of reaction mixtures is a slow process in organic synthesis, especially during the production of large numbers of analogs and compound libraries. Phase-tag methods such as solid-phase synthesis and fluorous synthesis, provide efficient ways of addressing the separation issue. Fluorous synthesis employs functionalized perfluoroalkyl groups attached to substrates or reagents. The separation of the resulting fluorous molecules can be achieved using strong and selective fluorous liquid-liquid extraction, fluorous silica gel-based solid-phase extraction or high-performance liquid chromatography. Fluorous technology is a novel solution-phase method, which has the advantages of fast reaction times in homogeneous environments, being readily adaptable to literature conditions, having easy intermediate analysis, and having flexibility in reaction scale and scope. In principle, any synthetic methods that use a solid-support could be conducted in solution-phase by replacing the polymer linker with a corresponding fluorous tag. This review summarizes the progress of fluorous tags in solution-phase synthesis of small molecules, peptides and oligosaccharides. PMID:15595439

  6. Amarillo National Resource Center for Plutonium. Quarterly technical progress report, May 1, 1997--July 31, 1997

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

    NONE

    Progress summaries are provided from the Amarillo National Center for Plutonium. Programs include the plutonium information resource center, environment, public health, and safety, education and training, nuclear and other material studies.

  7. Longitudinal Surveys of Australian Youth (LSAY) 2003 Cohort: Wave 7 (2009)--Questionnaire. Technical Report 57A

    ERIC Educational Resources Information Center

    National Centre for Vocational Education Research (NCVER), 2010

    2010-01-01

    The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the questionnaire for the LSAY 2003 cohort Wave 7 (2009) data set. [For the related frequency tables, see ED512163.

  8. Longitudinal Surveys of Australian Youth (LSAY): 2006 Cohort Wave 4 (2009)--Questionnaire. Technical Report 56A

    ERIC Educational Resources Information Center

    National Centre for Vocational Education Research (NCVER), 2010

    2010-01-01

    The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the questionnaire for the LSAY 2006 cohort Wave 4 (2009) data set. [For the "Longitudinal Surveys of Australian Youth (LSAY):…

  9. 25 CFR 547.7 - What are the minimum technical hardware standards applicable to Class II gaming systems?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... OF CLASS II GAMES § 547.7 What are the minimum technical hardware standards applicable to Class II... the game, and are specially manufactured or proprietary and not off-the-shelf, shall display a unique... outcome or integrity of any game, progressive award, financial instrument, cashless transaction, voucher...

  10. 25 CFR 547.7 - What are the minimum technical hardware standards applicable to Class II gaming systems?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... OF CLASS II GAMES § 547.7 What are the minimum technical hardware standards applicable to Class II... the game, and are specially manufactured or proprietary and not off-the-shelf, shall display a unique... outcome or integrity of any game, progressive award, financial instrument, cashless transaction, voucher...

  11. 25 CFR 547.7 - What are the minimum technical hardware standards applicable to Class II gaming systems?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... OF CLASS II GAMES § 547.7 What are the minimum technical hardware standards applicable to Class II... the game, and are specially manufactured or proprietary and not off-the-shelf, shall display a unique... outcome or integrity of any game, progressive award, financial instrument, cashless transaction, voucher...

  12. Shape-selective adsorption of aromatic molecules from water by tetramethylammonium-smectite

    USGS Publications Warehouse

    Lee, J.; Mortland, M.M.; Boyd, S.A.; Chiou, C.T.

    1989-01-01

    The adsorption of aromatic compounds by smectite exchanged with tetramethylammonium (TMA) has been studied. Aromatic compounds adsorbed by TMA-smectite are assumed to adopt a tilted orientation in a face-to-face arrangment with the TMA tetrahedra. The sorptive characteristics of TMA-smectite were influenced strongly by the presence of water. The dry TMA-smectite showed little selectivity in the uptake of benzen, toluene and xylene. In the presence of water, TMA-smectite showed a high degree of selectivity based on molecular size/shape, resulting in high uptake of benzene and progressively lower uptake of larger aromatic molecules. This selectivity appeared to result from the shrinkage of interlamellar cavities by water.

  13. Progress in Modeling and Simulation of Batteries

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

    Turner, John A

    2016-01-01

    Modeling and simulation of batteries, in conjunction with theory and experiment, are important research tools that offer opportunities for advancement of technologies that are critical to electric motors. The development of data from the application of these tools can provide the basis for managerial and technical decision-making. Together, these will continue to transform batteries for electric vehicles. This collection of nine papers presents the modeling and simulation of batteries and the continuing contribution being made to this impressive progress, including topics that cover: * Thermal behavior and characteristics * Battery management system design and analysis * Moderately high-fidelity 3D capabilitiesmore » * Optimization Techniques and Durability As electric vehicles continue to gain interest from manufacturers and consumers alike, improvements in economy and affordability, as well as adoption of alternative fuel sources to meet government mandates are driving battery research and development. Progress in modeling and simulation will continue to contribute to battery improvements that deliver increased power, energy storage, and durability to further enhance the appeal of electric vehicles.« less

  14. PATHFINDER ATOMIC POWER PLANT TECHNICAL PROGRESS REPORT FOR JULY 1, 1959- SEPTEMBER 30, 1959

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

    None

    1960-10-31

    ABS>Fuel Element Research and Development. Dynamic and static corrosion tests on 8001 Al were completed. Annealmmmg of 1100 cladding on 5083 and M400 cladding on X2219 were tested at 500 deg C, and investigation continued on producing X8101 Al alloy cladding in tube plates by extrusion. Boiler fuel element capsule irradiation tests and subassembly tests are described Heat transfer loop studies and fuel fabrication for the critical facility are reported. Boiler fuel element mechanical design and testing progress is desc ribed. and the superheater fuel element temperature evaluating routine is discussed. Low- enrichment superheater fuel element development included design studiesmore » and stainless steel powder and UO/sub 2/ powder fabrication studies Reactor Mechanical Studies. Research is reported on vessel and structure design, fabrication, and testing, recirculation system design, steam separator tests, and control rod studies. Nuclear Analysis. Reactor physics studies are reported on nuclear constants, baffle plate analysis, comparison of core representations, delayed neutron fraction. and shielding analysis of the reactor building. Reactor and system dynamics and critical experiments were also studied. Chemistry. Progress is reported on recombiner. radioactive gas removal and storage, ion exchanger and radiochemical processing. (For preceding period see ACNP-5915.) (T.R.H.)« less

  15. DNA nanomapping using CRISPR-Cas9 as a programmable nanoparticle.

    PubMed

    Mikheikin, Andrey; Olsen, Anita; Leslie, Kevin; Russell-Pavier, Freddie; Yacoot, Andrew; Picco, Loren; Payton, Oliver; Toor, Amir; Chesney, Alden; Gimzewski, James K; Mishra, Bud; Reed, Jason

    2017-11-21

    Progress in whole-genome sequencing using short-read (e.g., <150 bp), next-generation sequencing technologies has reinvigorated interest in high-resolution physical mapping to fill technical gaps that are not well addressed by sequencing. Here, we report two technical advances in DNA nanotechnology and single-molecule genomics: (1) we describe a labeling technique (CRISPR-Cas9 nanoparticles) for high-speed AFM-based physical mapping of DNA and (2) the first successful demonstration of using DVD optics to image DNA molecules with high-speed AFM. As a proof of principle, we used this new "nanomapping" method to detect and map precisely BCL2-IGH translocations present in lymph node biopsies of follicular lymphoma patents. This HS-AFM "nanomapping" technique can be complementary to both sequencing and other physical mapping approaches.

  16. Slow Progress In Finalizing Measles And Rubella Elimination In The European Region.

    PubMed

    Biellik, Robin; Davidkin, Iria; Esposito, Susanna; Lobanov, Andrey; Kojouharova, Mira; Pfaff, Günter; Santos, José Ignacio; Simpson, John; Mamou, Myriam Ben; Butler, Robb; Deshevoi, Sergei; Huseynov, Shahin; Jankovic, Dragan; Shefer, Abigail

    2016-02-01

    All countries in the World Health Organization European Region committed to eliminating endemic transmission of measles and rubella by 2015, and disease incidence has decreased dramatically. However, there was little progress between 2012 and 2013, and the goal will likely not be achieved on time. Genuine political commitment, increased technical capacity, and greater public awareness are urgently needed, especially in Western Europe. Project HOPE—The People-to-People Health Foundation, Inc.

  17. Voluntary Medical Male Circumcision Scale-Up in Nyanza, Kenya: Evaluating Technical Efficiency and Productivity of Service Delivery

    PubMed Central

    Omondi Aduda, Dickens S.; Ouma, Collins; Onyango, Rosebella; Onyango, Mathews; Bertrand, Jane

    2015-01-01

    Background Voluntary medical male circumcision (VMMC) service delivery is complex and resource-intensive. In Kenya’s context there is still paucity of information on resource use vis-à-vis outputs as programs scale up. Knowledge of technical efficiency, productivity and potential sources of constraints is desirable to improve decision-making. Objective To evaluate technical efficiency and productivity of VMMC service delivery in Nyanza in 2011/2012 using data envelopment analysis. Design Comparative process evaluation of facilities providing VMMC in Nyanza in 2011/2012 using output orientated data envelopment analysis. Results Twenty one facilities were evaluated. Only 1 of 7 variables considered (total elapsed operation time) significantly improved from 32.8 minutes (SD 8.8) in 2011 to 30 minutes (SD 6.6) in 2012 (95%CI = 0.0350–5.2488; p = 0.047). Mean scale technical efficiency significantly improved from 91% (SD 19.8) in 2011 to 99% (SD 4.0) in 2012 particularly among outreach compared to fixed service delivery facilities (CI -31.47959–4.698508; p = 0.005). Increase in mean VRS technical efficiency from 84% (SD 25.3) in 2011 and 89% (SD 25.1) in 2012 was not statistically significant. Benchmark facilities were #119 and #125 in 2011 and #103 in 2012. Malmquist Productivity Index (MPI) at fixed facilities declined by 2.5% but gained by 4.9% at outreach ones by 2012. Total factor productivity improved by 83% (p = 0.032) in 2012, largely due to progress in technological efficiency by 79% (p = 0.008). Conclusions Significant improvement in scale technical efficiency among outreach facilities in 2012 was attributable to accelerated activities. However, ongoing pure technical inefficiency requires concerted attention. Technological progress was the key driver of service productivity growth in Nyanza. Incorporating service-quality dimensions and using stepwise-multiple criteria in performance evaluation enhances comprehensiveness and validity. These findings

  18. Voluntary medical male circumcision scale-up in Nyanza, Kenya: evaluating technical efficiency and productivity of service delivery.

    PubMed

    Omondi Aduda, Dickens S; Ouma, Collins; Onyango, Rosebella; Onyango, Mathews; Bertrand, Jane

    2015-01-01

    Voluntary medical male circumcision (VMMC) service delivery is complex and resource-intensive. In Kenya's context there is still paucity of information on resource use vis-à-vis outputs as programs scale up. Knowledge of technical efficiency, productivity and potential sources of constraints is desirable to improve decision-making. To evaluate technical efficiency and productivity of VMMC service delivery in Nyanza in 2011/2012 using data envelopment analysis. Comparative process evaluation of facilities providing VMMC in Nyanza in 2011/2012 using output orientated data envelopment analysis. Twenty one facilities were evaluated. Only 1 of 7 variables considered (total elapsed operation time) significantly improved from 32.8 minutes (SD 8.8) in 2011 to 30 minutes (SD 6.6) in 2012 (95%CI = 0.0350-5.2488; p = 0.047). Mean scale technical efficiency significantly improved from 91% (SD 19.8) in 2011 to 99% (SD 4.0) in 2012 particularly among outreach compared to fixed service delivery facilities (CI -31.47959-4.698508; p = 0.005). Increase in mean VRS technical efficiency from 84% (SD 25.3) in 2011 and 89% (SD 25.1) in 2012 was not statistically significant. Benchmark facilities were #119 and #125 in 2011 and #103 in 2012. Malmquist Productivity Index (MPI) at fixed facilities declined by 2.5% but gained by 4.9% at outreach ones by 2012. Total factor productivity improved by 83% (p = 0.032) in 2012, largely due to progress in technological efficiency by 79% (p = 0.008). Significant improvement in scale technical efficiency among outreach facilities in 2012 was attributable to accelerated activities. However, ongoing pure technical inefficiency requires concerted attention. Technological progress was the key driver of service productivity growth in Nyanza. Incorporating service-quality dimensions and using stepwise-multiple criteria in performance evaluation enhances comprehensiveness and validity. These findings highlight site-level resource use and sources of

  19. Molecular physics. Production of trilobite Rydberg molecule dimers with kilo-Debye permanent electric dipole moments.

    PubMed

    Booth, D; Rittenhouse, S T; Yang, J; Sadeghpour, H R; Shaffer, J P

    2015-04-03

    Permanent electric dipole moments are important for understanding symmetry breaking in molecular physics, control of chemical reactions, and realization of strongly correlated many-body quantum systems. However, large molecular permanent electric dipole moments are challenging to realize experimentally. We report the observation of ultralong-range Rydberg molecules with bond lengths of ~100 nanometers and kilo-Debye permanent electric dipole moments that form when an ultracold ground-state cesium (Cs) atom becomes bound within the electronic cloud of an extended Cs electronic orbit. The electronic character of this hybrid class of "trilobite" molecules is dominated by degenerate Rydberg manifolds, making them difficult to produce by conventional photoassociation. We used detailed coupled-channel calculations to reproduce their properties quantitatively. Our findings may lead to progress in ultracold chemistry and strongly correlated many-body physics. Copyright © 2015, American Association for the Advancement of Science.

  20. Water on graphene: review of recent progress

    NASA Astrophysics Data System (ADS)

    Melios, C.; Giusca, C. E.; Panchal, V.; Kazakova, O.

    2018-04-01

    The sensitivity of graphene to the surrounding environment is given by its π electrons, which are directly exposed to molecules in the ambient air. The high sensitivity of graphene to the local environment has shown to be both advantageous and problematic for graphene-based devices, such as transistors and sensors, where the graphene carrier concentration and mobility changes due to ambient humidity variations. In this review, recent progress is presented in understanding the effects of water on different types of graphene: epitaxially grown and quasi-free standing on SiC(0 0 0 1), grown by chemical vapour deposition and transfered on SiO2, and exfoliated flakes. It is demonstrated that water withdraws electrons from graphene, but the graphene-water interaction highly depends on the thickness, layer stacking, underlying substrate and substrate-induced doping. Moreover, we highlight the importance of clear and unambiguous description of the environmental conditions (i.e. relative humidity) whenever a routine characterisation for carrier concentration and mobility is reported (often presented as a simple figure-of-merit), as these electrical characteristics are highly dependent on the adsorbed molecules and the surrounding environment.

  1. Do failures in non-technical skills contribute to fatal medical accidents in Japan? A review of the 2010–2013 national accident reports

    PubMed Central

    Uramatsu, Masashi; Fujisawa, Yoshikazu; Mizuno, Shinya; Souma, Takahiro; Komatsubara, Akinori; Miki, Tamotsu

    2017-01-01

    Objectives We sought to clarify how large a proportion of fatal medical accidents can be considered to be caused by poor non-technical skills, and to support development of a policy to reduce number of such accidents by making recommendations about possible training requirements. Design Summaries of reports of fatal medical accidents, published by the Japan Medical Safety Research Organization, were reviewed individually. Three experienced clinicians and one patient safety expert conducted the reviews to determine the cause of death. Views of the patient safety expert were given additional weight in the overall determination. Setting A total of 73 summary reports of fatal medical accidents were reviewed. These reports had been submitted by healthcare organisations across Japan to the Japan Medical Safety Research Organization between April 2010 and March 2013. Primary and secondary outcome measures The cause of death in fatal medical accidents, categorised into technical skills, non-technical skills and inevitable progress of disease were evaluated. Non-technical skills were further subdivided into situation awareness, decision making, communication, team working, leadership, managing stress and coping with fatigue. Results Overall, the cause of death was identified as non-technical skills in 34 cases (46.6%), disease progression in 33 cases (45.2%) and technical skills in two cases (5.5%). In two cases, no consensual determination could be achieved. Further categorisation of cases of non-technical skills were identified as 14 cases (41.2%) of problems with situation awareness, eight (23.5%) with team working and three (8.8%) with decision making. These three subcategories, or combinations of them, were identified as the cause of death in 33 cases (97.1%). Conclusions Poor non-technical skills were considered to be a significant cause of adverse events in nearly half of the fatal medical accidents examined. Improving non-technical skills may be effective for

  2. The role of damage associated molecular pattern molecules in acetaminophen-induced liver injury in mice.

    PubMed

    Martin-Murphy, Brittany V; Holt, Michael P; Ju, Cynthia

    2010-02-15

    The idiosyncratic nature, severity and poor diagnosis of drug-induced liver injury (DILI) make these reactions a major safety issue during drug development, as well as the most common cause for the withdrawal of drugs from the pharmaceutical market. Elucidation of the underlying mechanism(s) is necessary for identifying predisposing factors and developing strategies in the treatment and prevention of DILI. Acetaminophen (APAP) is a widely used over the counter therapeutic that is known to be effective and safe at therapeutic doses. However, in overdose situations fatal and non-fatal hepatic necrosis can result. Evidence suggests that the chemically reactive metabolite of the drug initiates hepatocyte damage and that inflammatory innate immune responses also occur within the liver, leading to the exacerbation and progression of tissue injury. Here we investigate whether following APAP-induced liver injury (AILI) damaged hepatocytes release "danger" signals or damage associated molecular pattern (DAMP) molecules, which induce pro-inflammatory activation of hepatic macrophages, further contributing to the progression of liver injury. Our study demonstrated a clear activation of Kupffer cells following early exposure to APAP (1h). Activation of a murine macrophage cell line, RAW cells, was also observed following treatment with liver perfusate from APAP-treated mice, or with culture supernatant of APAP-challenged hepatocytes. Moreover, in these media, the DAMP molecules, heat-shock protein-70 (HSP-70) and high mobility group box-1 (HMGB1) were detected. Overall, these findings reveal that DAMP molecules released from damaged and necrotic hepatocytes may serve as a crucial link between the initial hepatocyte damage and the activation of innate immune cells following APAP-exposure, and that DAMPs may represent a potential therapeutic target for AILI. Published by Elsevier Ireland Ltd.

  3. Longitudinal Surveys of Australian Youth (LSAY) 1998 Cohort: Wave 12 (2009)--Frequency Tables. Technical Report 58B

    ERIC Educational Resources Information Center

    National Centre for Vocational Education Research (NCVER), 2010

    2010-01-01

    The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the frequency tables for the LSAY 1998 cohort Wave 12 (2009) data set. [For the accompanying questionnaire, "Longitudinal Surveys…

  4. Review of Web-Based Technical Documentation Processes. FY07 NAEP-QA Special Study Report. TR-08-17

    ERIC Educational Resources Information Center

    Gribben, Monica; Wise, Lauress; Becker, D. E.

    2008-01-01

    Beginning with the 2000 and 2001 National Assessment of Educational Progress (NAEP) assessments, the National Center for Education Statistics (NCES) has made technical documentation available on the worldwide web at http://nces.ed.gov/nationsreportcard/tdw/. The web-based documentation is designed to be less dense and more accessible than prior…

  5. Symptomatic thoracic spinal cord herniation: case series and technical report.

    PubMed

    Hawasli, Ammar H; Ray, Wilson Z; Wright, Neill M

    2014-09-01

    Idiopathic spinal cord herniation (ISCH) is an uncommon condition located predominantly in the thoracic spine and often associated with a remote history of a major traumatic injury. ISCH has an incompletely described presentation and unknown etiology. There is no consensus on the treatment algorithm and surgical technique, and there are few data on clinical outcomes. In this case series and technical report, we describe the atypical myelopathy presentation, remote history of traumatic injury, radiographic progression, treatment, and outcomes of 5 patients treated at Washington University for symptomatic ISCH. A video showing surgical repair is presented. In contrast to classic compressive myelopathy symptomatology, ISCH patients presented with an atypical myelopathy, characterized by asymmetric motor and sensory deficits and early-onset urinary incontinence. Clinical deterioration correlated with progressive spinal cord displacement and herniation observed on yearly spinal imaging in a patient imaged serially because of multiple sclerosis. Finally, compared with compressive myelopathy in the thoracic spine, surgical treatment of ISCH led to rapid improvement despite a long duration of symptoms. Symptomatic ISCH presents with atypical myelopathy and slow temporal progression and can be successfully managed with surgical repair.

  6. Symptomatic Thoracic Spinal Cord Herniation: Case Series and Technical Report

    PubMed Central

    Hawasli, Ammar H.; Ray, Wilson Z.; Wright, Neill M.

    2014-01-01

    Background and Importance Idiopathic spinal cord herniation (ISCH) is an uncommon condition located predominantly in the thoracic spine and often associated with a remote history of a major traumatic injury. ISCH has an incompletely described presentation and unknown etiology. There is no consensus on treatment algorithm and surgical technique, and there is little data on clinical outcomes. Clinical Presentation In this case series and technical report, we describe the atypical myelopathy presentation, remote history of traumatic injury, radiographic progression, treatment, and outcomes of 5 patients treated at Washington University for symptomatic ISCH. A video showing surgical repair is presented. In contrast to classic compressive myelopathy symptomology, ISCH patients presented with an atypical myelopathy, characterized by asymmetric motor and sensory deficits and early-onset urinary incontinence. Clinical deterioration correlated with progressive spinal cord displacement and herniation observed on yearly spinal imaging in a patient imaged serially due to multiple sclerosis. Finally compared to compressive myelopathy in the thoracic spine, surgical treatment of ISH led to rapid improvement despite long duration of symptoms. Conclusion Symptomatic ISCH presents with atypical myelopathy and slow temporal progression and can be successfully managed with surgical repair. PMID:24871148

  7. Crystallography Without Crystals: Determining the Structure of Individual Biological Molecules and Nanoparticles

    ScienceCinema

    Ourmazd, Abbas [University of Wisconsin, Milwaukee, Wisconsin, USA

    2017-12-09

    Ever shattered a valuable vase into 10 to the 6th power pieces and tried to reassemble it under a light providing a mean photon count of 10 minus 2 per detector pixel with shot noise? If you can do that, you can do single-molecule crystallography. This talk will outline how this can be done in principle. In more technical terms, the talk will describe how the combination of scattering physics and Bayesian algorithms can be used to reconstruct the 3-D diffracted intensity distribution from a collection of individual 2-D diffiraction patterns down to a mean photon count of 10 minus 2 per pixel, the signal level anticipated from the Linac Coherent Light Source, and hence determine the structure of individual macromolecules and nanoparticles.

  8. Critical Review of Technical Questions Facing Low Impact Development and Green Infrastructure: A Perspective from the Great Plains.

    PubMed

    Vogel, Jason R; Moore, Trisha L; Coffman, Reid R; Rodie, Steven N; Hutchinson, Stacy L; McDonough, Kelsey R; McLemore, Alex J; McMaine, John T

    2015-09-01

    Since its inception, Low Impact Development (LID) has become part of urban stormwater management across the United States, marking progress in the gradual transition from centralized to distributed runoff management infrastructure. The ultimate goal of LID is full, cost-effective implementation to maximize watershed-scale ecosystem services and enhance resilience. To reach that goal in the Great Plains, the multi-disciplinary author team presents this critical review based on thirteen technical questions within the context of regional climate and socioeconomics across increasing complexities in scale and function. Although some progress has been made, much remains to be done including continued basic and applied research, development of local LID design specifications, local demonstrations, and identifying funding mechanisms for these solutions. Within the Great Plains and beyond, by addressing these technical questions within a local context, the goal of widespread acceptance of LID can be achieved, resulting in more effective and resilient stormwater management.

  9. p54nrb is a new regulator of progression of malignant melanoma.

    PubMed

    Schiffner, Susanne; Zimara, Nicole; Schmid, Rainer; Bosserhoff, Anja-Katrin

    2011-08-01

    Nuclear RNA-binding protein p54(nrb) and its murine homolog NonO are known to be involved in a variety of nuclear processes including transcription and RNA processing. Melanoma inhibitory activity (MIA) has been shown to play an essential role in the progression of malignant melanoma and to influence melanoma-associated molecules and pathways in the early tumor formation steps. Interestingly, recent studies suggest that MIA is a regulator of p54(nrb). Here, we show that p54(nrb) is strongly expressed and localized in the nucleus of both melanoma cell lines and melanoma tissue samples compared with normal human melanocytes or normal skin, respectively. Furthermore, all tested melanoma cell lines revealed strong p54(nrb) promoter activity. Treatment with MIA-specific small interfering RNAs showed an influence of MIA on p54(nrb) expression on both messenger RNA (mRNA) and protein level. Knockdown of p54(nrb) protein in melanoma cell lines led to reduced proliferation rates and to a strong decrease in their migratory potential. In addition, attachment to laminin and poly-l-lysine was significantly increased. We could identify Connexin-43 (Cx-43) as a downstream target molecule of p54(nrb) as knockdown of p54(nrb) resulted in enhanced Cx-43 mRNA and protein levels. As a confirmation of these findings, melanoma cell lines showed very low Cx-43 expression levels compared with melanocytes. Our results demonstrate that p54(nrb) is highly expressed in malignant melanoma and, as a MIA target molecule, it seems to be involved in the development and progression of malignant melanoma.

  10. High-harmonic spectroscopy of aligned molecules

    NASA Astrophysics Data System (ADS)

    Yun, Hyeok; Yun, Sang Jae; Lee, Gae Hwang; Nam, Chang Hee

    2017-01-01

    High harmonics emitted from aligned molecules driven by intense femtosecond laser pulses provide the opportunity to explore the structural information of molecules. The field-free molecular alignment technique is an expedient tool for investigating the structural characteristics of linear molecules. The underlying physics of field-free alignment, showing the characteristic revival structure specific to molecular species, is clearly explained from the quantum-phase analysis of molecular rotational states. The anisotropic nature of molecules is shown from the harmonic polarization measurement performed with spatial interferometry. The multi-orbital characteristics of molecules are investigated using high-harmonic spectroscopy, applied to molecules of N2 and CO2. In the latter case the two-dimensional high-harmonic spectroscopy, implemented using a two-color laser field, is applied to distinguish harmonics from different orbitals. Molecular high-harmonic spectroscopy will open a new route to investigate ultrafast dynamics of molecules.

  11. Adhesion molecules and receptors

    USDA-ARS?s Scientific Manuscript database

    Adhesion molecules are necessary for leukocyte trafficking and differentiation. They serve to initiate cell-cell interactions under conditions of shear, and they sustain the cell-cell and cell-matrix interactions needed for cellular locomotion. They also can serve directly as signaling molecules act...

  12. Current progress of siRNA/shRNA therapeutics in clinical trials.

    PubMed

    Burnett, John C; Rossi, John J; Tiemann, Katrin

    2011-09-01

    Through a mechanism known as RNA interference (RNAi), small interfering RNA (siRNA) molecules can target complementary mRNA strands for degradation, thus specifically inhibiting gene expression. The ability of siRNAs to inhibit gene expression offers a mechanism that can be exploited for novel therapeutics. Indeed, over the past decade, at least 21 siRNA therapeutics have been developed for more than a dozen diseases, including various cancers, viruses, and genetic disorders. Like other biological drugs, RNAi-based therapeutics often require a delivery vehicle to transport them to the targeted cells. Thus, the clinical advancement of numerous siRNA drugs has relied on the development of siRNA carriers, including biodegradable nanoparticles, lipids, bacteria, and attenuated viruses. Most therapies permit systemic delivery of the siRNA drug, while others use ex vivo delivery by autologous cell therapy. Advancements in bioengineering and nanotechnology have led to improved control of delivery and release of some siRNA therapeutics. Likewise, progress in molecular biology has allowed for improved design of the siRNA molecules. Here, we provide an overview of siRNA therapeutics in clinical trials, including their clinical progress, the challenges they have encountered, and the future they hold in the treatment of human diseases. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Chronic epithelial kidney injury molecule-1 expression causes murine kidney fibrosis.

    PubMed

    Humphreys, Benjamin D; Xu, Fengfeng; Sabbisetti, Venkata; Grgic, Ivica; Movahedi Naini, Said; Wang, Ningning; Chen, Guochun; Xiao, Sheng; Patel, Dhruti; Henderson, Joel M; Ichimura, Takaharu; Mou, Shan; Soeung, Savuth; McMahon, Andrew P; Kuchroo, Vijay K; Bonventre, Joseph V

    2013-09-01

    Acute kidney injury predisposes patients to the development of both chronic kidney disease and end-stage renal failure, but the molecular details underlying this important clinical association remain obscure. We report that kidney injury molecule-1 (KIM-1), an epithelial phosphatidylserine receptor expressed transiently after acute injury and chronically in fibrotic renal disease, promotes kidney fibrosis. Conditional expression of KIM-1 in renal epithelial cells (Kim1(RECtg)) in the absence of an injury stimulus resulted in focal epithelial vacuolization at birth, but otherwise normal tubule histology and kidney function. By 4 weeks of age, Kim1(RECtg) mice developed spontaneous and progressive interstitial kidney inflammation with fibrosis, leading to renal failure with anemia, proteinuria, hyperphosphatemia, hypertension, cardiac hypertrophy, and death, analogous to progressive kidney disease in humans. Kim1(RECtg) kidneys had elevated expression of proinflammatory monocyte chemotactic protein-1 (MCP-1) at early time points. Heterologous expression of KIM-1 in an immortalized proximal tubule cell line triggered MCP-1 secretion and increased MCP-1-dependent macrophage chemotaxis. In mice expressing a mutant, truncated KIM-1 polypeptide, experimental kidney fibrosis was ameliorated with reduced levels of MCP-1, consistent with a profibrotic role for native KIM-1. Thus, sustained KIM-1 expression promotes kidney fibrosis and provides a link between acute and recurrent injury with progressive chronic kidney disease.

  14. Quarterly Technical Progress Report

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

    Mary K. Banken

    This project has identified all FDD oil reservoirs in Oklahoma; grouped those reservoirs into plays that have similar depositional origins; collected, organized, and analyzed all available data; conducted characterization and simulation studies on selected reservoirs in each plays; and implemented a technology transfer program targeted to the operators of FDD reservoirs. By fulfilling these objectives, the FDD project has had the goal of helping to sustain the life expectancy of existing wells and provide incentive for development and exploratory wells with the ultimate objective of increasing oil recovery.

  15. TECHNICAL REPORTS DATABASE

    EPA Science Inventory

    The Defense Technical Information Center (DTIC?) is the central facility for the collection and dissemination of scientific and technical information for the Department of Defense (DoD). Much of this information is made available by DTIC in the form of technical reports about com...

  16. Chemistry, manufacturing and control (CMC) and clinical trial technical support for influenza vaccine manufacturers.

    PubMed

    Wahid, Rahnuma; Holt, Renee; Hjorth, Richard; Berlanda Scorza, Francesco

    2016-10-26

    With the support of the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services, PATH has contributed to the World Health Organization's (WHO's) Global Action Plan for Influenza Vaccines (GAP) by providing technical and clinical assistance to several developing country vaccine manufacturers (DCVMs). GAP builds regionally based independent and sustainable influenza vaccine production capacity to mitigate the overall global shortage of influenza vaccines. The program also ensures adequate influenza vaccine manufacturing capacity in the event of an influenza pandemic. Since 2009, PATH has worked closely with two DCVMs in Vietnam: the Institute of Vaccines and Medical Biologicals (IVAC) and VABIOTECH. Beginning in 2013, PATH also began working with Torlak Institute in Serbia; Instituto Butantan in Brazil; Serum Institute of India Private Ltd. in India; and Changchun BCHT Biotechnology Co. (BCHT) in China. The DCVMs supported under the GAP program all had existing influenza vaccine manufacturing capability and required technical support from PATH to improve vaccine yield, process efficiency, and product formulation. PATH has provided customized technical support for the manufacturing process to each DCVM based on their respective requirements. Additionally, PATH, working with BARDA and WHO, supported several DCVMs in the clinical development of influenza vaccine candidates progressing toward national licensure or WHO prequalification. As a result of the activities outlined in this review, several companies were able to make excellent progress in developing state-of-the-art manufacturing processes and completing early phase clinical trials. Licensure trials are currently ongoing or planned for several DCVMs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Progressive learning in endoscopy simulation training improves clinical performance: a blinded randomized trial.

    PubMed

    Grover, Samir C; Scaffidi, Michael A; Khan, Rishad; Garg, Ankit; Al-Mazroui, Ahmed; Alomani, Tareq; Yu, Jeffrey J; Plener, Ian S; Al-Awamy, Mohamed; Yong, Elaine L; Cino, Maria; Ravindran, Nikila C; Zasowski, Mark; Grantcharov, Teodor P; Walsh, Catharine M

    2017-11-01

    A structured comprehensive curriculum (SCC) that uses simulation-based training (SBT) can improve clinical colonoscopy performance. This curriculum may be enhanced through the application of progressive learning, a training strategy centered on incrementally challenging learners. We aimed to determine whether a progressive learning-based curriculum (PLC) would lead to superior clinical performance compared with an SCC. This was a single-blinded randomized controlled trial conducted at a single academic center. Thirty-seven novice endoscopists were recruited and randomized to either a PLC (n = 18) or to an SCC (n = 19). The PLC comprised 6 hours of SBT, which progressed in complexity and difficulty. The SCC included 6 hours of SBT, with cases of random order of difficulty. Both groups received expert feedback and 4 hours of didactic teaching. Participants were assessed at baseline, immediately after training, and 4 to 6 weeks after training. The primary outcome was participants' performance during their first 2 clinical colonoscopies, as assessed by using the Joint Advisory Group Direct Observation of Procedural Skills assessment tool (JAG DOPS). Secondary outcomes were differences in endoscopic knowledge, technical and communication skills, and global performance in the simulated setting. The PLC group outperformed the SCC group during first and second clinical colonoscopies, measured by JAG DOPS (P < .001). Additionally, the PLC group had superior technical and communication skills and global performance in the simulated setting (P < .05). There were no differences between groups in endoscopic knowledge (P > .05). Our findings demonstrate the superiority of a PLC for endoscopic simulation, compared with an SCC. Challenging trainees progressively is a simple, theory-based approach to simulation whereby the performance of clinical colonoscopies can be improved. (Clinical trial registration number: NCT02000180.). Copyright © 2017 American Society for

  18. LINER FOR EXTRUSION BILLET CONTAINERS. Interim Technical Documentary Progress Report, June 5, 1962-September 5, 1962

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

    Spachner, S.A.

    1962-10-31

    A container-sleeve-liner assembly was designed which will provide adequate support for ceramic, ceramic coated metal, or metal liners. The design minimizes mechanical property requirements of liner materials, and permits rapid removal of worn or damaged liners. A high-strength stem was designed and fabricated. Technical literature on high-strength materials was reviewed, and high-strength materials producers were contacted to locate sources and assess applicability of existing materials for refractory metal extrusion liner use. (auth)

  19. Progress in Norwegian-Russian Regulatory Cooperation in Management of the Nuclear Legacy

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

    Sneve, M.K.; Shandala, N.K.; Smith, G.M.

    2008-07-01

    The Norwegian Radiation Protection Authority (NRPA) and the Federal Medical-Biological Agency (FMBA) of the Russian Federation have a collaboration programme which forms part of the Norwegian government's Plan of Action to improve radiation and nuclear safety in northwest Russia. The background to the NRPA-FMBA collaboration programme has been described in previous WM presentations. This paper presents the substantial progress made within that programme, describes ongoing progress within specific projects and sets out the value arising from wider involvement in the programme of other organisations such as NATO and the technical support derived from other national agencies such as the IAEA,more » and regulatory authorities from the USA, the UK and France. The main activities of the cooperation projects are concerned with the management of the nuclear legacy in northwest Russia, in particular the remediation of facilities, and related spent fuel and radioactive waste management, at the former Shore Technical Bases at Andreeva Bay and Gremikha Village. New regulatory guidance documents have been developed, necessary because of the special abnormal situation at these sites, now designated as Sites of Temporary Storage (STS), but also because of the transition from military to civilian regulatory supervision and the evolving regulatory system in the Russian Federation. The work has involved major technical inputs from the Russian Federation Institute of Biophysics, as well as review and advice on international recommendations and good practice in other countries provided by other technical support organisations. Projects on-going in 2007 are described which involve regulatory guidance on very Low-Level Waste management, specifically for the licensing and operation of new VLLW disposal facilities; optimisation of operational radiation protection, particularly in areas of high ambient radiation dose rate as are found in some parts of the STSs; determination of factors

  20. Single-Molecule Interfacial Electron Transfer

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

    Lu, H. Peter

    This project is focused on the use of single-molecule high spatial and temporal resolved techniques to study molecular dynamics in condensed phase and at interfaces, especially, the complex reaction dynamics associated with electron and energy transfer rate processes. The complexity and inhomogeneity of the interfacial ET dynamics often present a major challenge for a molecular level comprehension of the intrinsically complex systems, which calls for both higher spatial and temporal resolutions at ultimate single-molecule and single-particle sensitivities. Combined single-molecule spectroscopy and electrochemical atomic force microscopy approaches are unique for heterogeneous and complex interfacial electron transfer systems because the static andmore » dynamic inhomogeneities can be identified and characterized by studying one molecule at a specific nanoscale surface site at a time. The goal of our project is to integrate and apply these spectroscopic imaging and topographic scanning techniques to measure the energy flow and electron flow between molecules and substrate surfaces as a function of surface site geometry and molecular structure. We have been primarily focusing on studying interfacial electron transfer under ambient condition and electrolyte solution involving both single crystal and colloidal TiO 2 and related substrates. The resulting molecular level understanding of the fundamental interfacial electron transfer processes will be important for developing efficient light harvesting systems and broadly applicable to problems in fundamental chemistry and physics. We have made significant advancement on deciphering the underlying mechanism of the complex and inhomogeneous interfacial electron transfer dynamics in dyesensitized TiO 2 nanoparticle systems that strongly involves with and regulated by molecule-surface interactions. We have studied interfacial electron transfer on TiO 2 nanoparticle surfaces by using ultrafast single-molecule spectroscopy

  1. Electrorheological crystallization of proteins and other molecules

    DOEpatents

    Craig, George D.; Rupp, Bernhard

    1996-01-01

    An electrorheological crystalline mass of a molecule is formed by dispersing the molecule in a dispersion fluid and subjecting the molecule dispersion to a uniform electrical field for a period of time during which time an electrorheological crystalline mass is formed. Molecules that may be used to form an electrorheological crystalline mass include any organic or inorganic molecule which has a permanent dipole and/or which is capable of becoming an induced dipole in the presence of an electric field. The molecules used to form the electrorheological crystalline mass are preferably macromolecules, such as biomolecules, such as proteins, nucleic acids, carbohydrates, lipoproteins and viruses. Molecules are crystallized by a method in which an electric field is maintained for a period of time after the electrorheological crystalline mass has formed during which time at least some of the molecules making up the electrorheological crystalline mass form a crystal lattice. The three dimensional structure of a molecule is determined by a method in which an electrorheological crystalline mass of the molecule is formed, an x-ray diffraction pattern of the electrorheological crystalline mass is obtained and the three dimensional structure of the molecule is calculated from the x-ray diffraction pattern.

  2. Preface: Special Topic on Single-Molecule Biophysics

    NASA Astrophysics Data System (ADS)

    Makarov, Dmitrii E.; Schuler, Benjamin

    2018-03-01

    Single-molecule measurements are now almost routinely used to study biological systems and processes. The scope of this special topic emphasizes the physics side of single-molecule observations, with the goal of highlighting new developments in physical techniques as well as conceptual insights that single-molecule measurements bring to biophysics. This issue also comprises recent advances in theoretical physical models of single-molecule phenomena, interpretation of single-molecule signals, and fundamental areas of statistical mechanics that are related to single-molecule observations. A particular goal is to illustrate the increasing synergy between theory, simulation, and experiment in single-molecule biophysics.

  3. Longitudinal Surveys of Australian Youth (LSAY): 2003 Cohort Wave 7 (2009)--Frequency Tables. Technical Report 57B

    ERIC Educational Resources Information Center

    National Centre for Vocational Education Research (NCVER), 2010

    2010-01-01

    The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the frequency tables for the LSAY 2003 cohort Wave 7 (2009) data set. [For the related questionnaire, see ED512164.

  4. Longitudinal Surveys of Australian Youth (LSAY) 2009 Cohort: Wave 3 (2011)--Frequency Tables. Technical Report 72B

    ERIC Educational Resources Information Center

    National Centre for Vocational Education Research (NCVER), 2012

    2012-01-01

    The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the frequency tables for the LSAY 2009 cohort Wave 3 (2011) data set. [For the related questionnaire, see ED536306.

  5. Loosely-Bound Diatomic Molecules.

    ERIC Educational Resources Information Center

    Balfour, W. J.

    1979-01-01

    Discusses concept of covalent bonding as related to homonuclear diatomic molecules. Article draws attention to the existence of bound rare gas and alkaline earth diatomic molecules. Summarizes their molecular parameters and offers spectroscopic data. Strength and variation with distance of interatomic attractive forces is given. (Author/SA)

  6. Triatomic molecules laser-cooled

    NASA Astrophysics Data System (ADS)

    2017-06-01

    Molecules containing three atoms have been laser-cooled to ultracold temperatures for the first time. John Doyle and colleagues at Harvard University in the US used a technique called Sisyphus cooling to chill an ensemble of about a million strontium-monohydroxide molecules to 750 μK.

  7. Processes of energy deposition by heavy-particle and electron impact. Final progress report

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

    Salop, A.; Smith, F.T.

    1978-04-18

    Progress is reported in three areas of reasearch during the present period: K-shell ionization in high energy collisions of heavy ions with light target atoms using the sudden (Magnus) approximation, K-L level matching phenomena associated with K-shell vacancy production in heavy-ion collisions, and studies of low energy collisions of electrons with molecules using semi-classical perturbation theory. A brief discussion of each of these activities is given.

  8. Productivity and technical efficiency of suckler beef production systems: trends for the period 1990 to 2012.

    PubMed

    Veysset, P; Lherm, M; Roulenc, M; Troquier, C; Bébin, D

    2015-12-01

    Over the past 23 years (1990 to 2012), French beef cattle farms have expanded in size and increased labour productivity by over 60%, chiefly, though not exclusively, through capital intensification (labour-capital substitution) and simplifying herd feeding practices (more concentrates used). The technical efficiency of beef sector production systems, as measured by the ratio of the volume value (in constant euros) of farm output excluding aids to volume of intermediate consumption, has fallen by nearly 20% while income per worker has held stable thanks to subsidies and the labour productivity gains made. This aggregate technical efficiency of beef cattle systems is positively correlated to feed self-sufficiency, which is in turn negatively correlated to farm and herd size. While volume of farm output per hectare of agricultural area has not changed, forage feed self-sufficiency decreased by 6 percentage points. The continual increase in farm size and labour productivity has come at a cost of lower production-system efficiency - a loss of technical efficiency that 20 years of genetic, technical, technological and knowledge-driven progress has barely managed to offset.

  9. The 1990 progress report and future plans

    NASA Technical Reports Server (NTRS)

    Friedland, Peter; Zweben, Monte; Compton, Michael

    1990-01-01

    This document describes the progress and plans of the Artificial Intelligence Research Branch (RIA) at ARC in 1990. Activities span a range from basic scientific research to engineering development and to fielded NASA applications, particularly those applications that are enabled by basic research carried out at RIA. Work is conducted in-house and through collaborative partners in academia and industry. Our major focus is on a limited number of research themes with a dual commitment to technical excellence and proven applicability to NASA short, medium, and long-term problems. RIA acts as the Agency's lead organization for research aspects of artificial intelligence, working closely with a second research laboratory at JPL and AI applications groups at all NASA centers.

  10. FY2017 Technology Integration Annual Progress Report

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

    None

    The 2017 Technology Integration Annual Progress Report covers 27 multi-year projects funded by the Vehicle Technologies Office. The report includes information on 20 competitively awarded projects, ranging from training on alternative fuels and vehicles for first responders, to safety training and design for maintenance facilities housing gaseous fuel vehicles, to electric vehicle community partner programs. It also includes seven projects conducted by several of VTO’s national laboratory partners, Argonne National Laboratory, Oak Ridge National Laboratory and the National Renewable Energy Laboratory. These projects range from a Technical Assistance project for business, industry, government and individuals, to the EcoCar 3 Studentmore » Competition, and the Fuel Economy Information Project.« less

  11. Medical expert system for assessment of coronary heart disease destabilization based on the analysis of the level of soluble vascular adhesion molecules

    NASA Astrophysics Data System (ADS)

    Serkova, Valentina K.; Pavlov, Sergey V.; Romanava, Valentina A.; Monastyrskiy, Yuriy I.; Ziepko, Sergey M.; Kuzminova, Nanaliya V.; Wójcik, Waldemar; DzierŻak, RóŻa; Kalizhanova, Aliya; Kashaganova, Gulzhan

    2017-08-01

    Theoretical and practical substantiation of the possibility of the using the level of soluble vascular adhesion molecules (sVCAM) is performed. Expert system for the assessment of coronary heart disease (CHD) destabilization on the base of the analysis of soluble vascular adhesion molecules level is developed. Correlation between the increase of VCAM level and C-reactive protein (CRP) in patients with different variants of CHD progression is established. Association of chronic nonspecific vascular inflammation activation and CHD destabilization is shown. The expedience of parallel determination of sVCAM and CRP levels for diagnostics of CHD destabilization and forecast elaboration is noted.

  12. Design and Synthesis of Novel Small-molecule Inhibitors of the Hypoxia Inducible Factor Pathway

    PubMed Central

    Mooring, Suazette Reid; Jin, Hui; Devi, Narra S.; Jabbar, Adnan A.; Kaluz, Stefan; Liu, Yuan; Van Meir, Erwin G.; Wang, Binghe

    2012-01-01

    Hypoxia, a reduction in partial oxygen pressure, is a salient property of solid tumors. Hypoxia drives malignant progression and metastasis in tumors and participates in tumor resistance to radio- and chemotherapies. Hypoxia activates the hypoxia-inducible factor (HIF) family of transcription factors, which induce target genes that regulate adaptive biological processes such as anaerobic metabolism, cell motility and angiogenesis. Clinical evidence has demonstrated that expression of HIF-1 is strongly associated with poor patient prognosis and activation of HIF-1 contributes to malignant behavior and therapeutic resistance. Consequently, HIF-1 has become an important therapeutic target for inhibition by small molecules. Herein, we describe the design and synthesis of small molecules that inhibit the HIF-1 signaling pathway. Many of these compounds exhibit inhibitory activity in the nanomolar range. Separate mechanistic studies indicate that these inhibitors do not alter HIF-1 levels, but interfere with the HIF-1α/HIF-1β/p300/CBP complex formation by interacting with p300 and CBP. PMID:22032632

  13. Boron removal and its concentration in aqueous solution through progressive freeze concentration.

    PubMed

    Wang, Li Pang

    2017-09-01

    This study explored the feasibility of progressive freeze concentration in boron removal and its concentration in aqueous solution. The influence of three key parameters in progressive freeze concentration on boron removal and concentration, namely, the advance speed of the ice front, the circumferential velocity of the stirrer, and the initial boron concentration, are investigated by conducting batch experiments. The results show that the effectiveness of boron removal increases with a lower advance speed of the ice front, a higher circumferential velocity of the stirrer, and a lower initial boron concentration. For a model boron solution with an initial concentration of 100 mg/L, the boron concentration in the ice phase after progressive freeze concentration is below 1 mg/L when the advance speed of the ice front is lower than 1 cm/h and the circumferential velocity of the stirrer is higher than 0.12 m/s. In addition, the concentration of boron in the liquid phase occurs simultaneously with progressive freeze concentration. Furthermore, the results also suggest that this method can be applied to the purification and concentration of not only organic molecules but also inorganic ions.

  14. Electron collisions with atoms, ions, molecules, and surfaces: Fundamental science empowering advances in technology

    PubMed Central

    Bartschat, Klaus; Kushner, Mark J.

    2016-01-01

    Electron collisions with atoms, ions, molecules, and surfaces are critically important to the understanding and modeling of low-temperature plasmas (LTPs), and so in the development of technologies based on LTPs. Recent progress in obtaining experimental benchmark data and the development of highly sophisticated computational methods is highlighted. With the cesium-based diode-pumped alkali laser and remote plasma etching of Si3N4 as examples, we demonstrate how accurate and comprehensive datasets for electron collisions enable complex modeling of plasma-using technologies that empower our high-technology–based society. PMID:27317740

  15. Progress towards barium daughter tagging in Xe136 decay using single molecule fluorescence imaging

    NASA Astrophysics Data System (ADS)

    McDonald, Austin; NEXT Collaboration

    2017-09-01

    The existence of Majorana fermions is of great interest as it may be related to the asymmetry between matter and anti-matter particles in the universe. However, the search for them has proven to be a difficult one. Neutrino-less Double Beta decay (NLDB) offers a possible opportunity for direct observation of a Majorana Fermion. The rate for NLDB decay may be as low as 1 count /ton /year if the mass ordering is inverted. Current detector technologies have background rates between 4 to 300 count /ton /year /ROI at the 100kg scale which is much larger than the universal goal of 0.1 count /ton /year /ROI desired for ton-scale detectors. The premise of my research is to develop new detector technologies that will allow for a background-free experiment. My current work is to develop a sensor that will tag the daughter ion Ba++ from the Xe136 decay. The development of a sensor that is sensitive to single barium ion detection based on the single molecule fluorescence imaging technique is the major focus of this work. If successful, this could provide a path to a background-free experiment.

  16. Progress towards barium daughter tagging in Xe136 decay using single molecule fluorescence imaging

    NASA Astrophysics Data System (ADS)

    McDonald, Austin; Jones, Ben; Benson, Jordan; Nygren, David; NEXT Collaboration

    2017-01-01

    The existence of Majorana Fermions has been predicted, and is of great interest as it may be related to the asymmetry between matter and anti-matter particles in the universe. However, the search for them has proven to be a difficult one. Neutrino-less Double Beta decay (NLDB) offers a possible opportunity for direct observation of a Majorana Fermion. The rate for NLDB decay may be as low as 1 count / ton / year . Current detector technologies have background rates between 4 to 300 count / ton / year / ROI which is much larger than the universal goal of 0 . 1 count / ton / year / ROI desired for ton-scale detectors. The premise of my research is to develop new detector technologies that will allow for a background-free experiment. My current work is to develop a sensor that will tag the daughter ion Ba++ from the Xe136 decay. The development of a sensor that is sensitive to single barium ion detection based on the single molecule fluorescence imaging technique is the major focus of this work. If successful, this could provide a path to a background-free experiment.

  17. Electrorheological crystallization of proteins and other molecules

    DOEpatents

    Craig, G.D.; Rupp, B.

    1996-06-11

    An electrorheological crystalline mass of a molecule is formed by dispersing the molecule in a dispersion fluid and subjecting the molecule dispersion to a uniform electrical field for a period of time during which time an electrorheological crystalline mass is formed. Molecules that may be used to form an electrorheological crystalline mass include any organic or inorganic molecule which has a permanent dipole and/or which is capable of becoming an induced dipole in the presence of an electric field. The molecules used to form the electrorheological crystalline mass are preferably macromolecules, such as biomolecules, such as proteins, nucleic acids, carbohydrates, lipoproteins and viruses. Molecules are crystallized by a method in which an electric field is maintained for a period of time after the electrorheological crystalline mass has formed during which time at least some of the molecules making up the electrorheological crystalline mass form a crystal lattice. The three dimensional structure of a molecule is determined by a method in which an electrorheological crystalline mass of the molecule is formed, an X-ray diffraction pattern of the electrorheological crystalline mass is obtained and the three dimensional structure of the molecule is calculated from the X-ray diffraction pattern. 4 figs.

  18. An optical conveyor for molecules.

    PubMed

    Weinert, Franz M; Braun, Dieter

    2009-12-01

    Trapping single ions under vacuum allows for precise spectroscopy in atomic physics. The confinement of biological molecules in bulk water is hindered by the lack of comparably strong forces. Molecules have been immobilized to surfaces, however often with detrimental effects on their function. Here, we optically trap molecules by creating the microscale analogue of a conveyor belt: a bidirectional flow is combined with a perpendicular thermophoretic molecule drift. Arranged in a toroidal geometry, the conveyor accumulates a hundredfold excess of 5-base DNA within seconds. The concentrations of the trapped DNA scale exponentially with length, reaching trapping potential depths of 14 kT for 50 bases. The mechanism does not require microfluidics, electrodes, or surface modifications. As a result, the trap can be dynamically relocated. The optical conveyor can be used to enhance diffusion-limited surface reactions, redirect cellular signaling, observe individual biomolecules over a prolonged time, or approach single-molecule chemistry in bulk water.

  19. Advances in ultrasensitive mass spectrometry of organic molecules.

    PubMed

    Kandiah, Mathivathani; Urban, Pawel L

    2013-06-21

    Ultrasensitive mass spectrometric analysis of organic molecules is important for various branches of chemistry, and other fields including physics, earth and environmental sciences, archaeology, biomedicine, and materials science. It finds applications--as an enabling tool--in systems biology, biological imaging, clinical analysis, and forensics. Although there are a number of technical obstacles associated with the analysis of samples by mass spectrometry at ultratrace level (for example analyte losses during sample preparation, insufficient sensitivity, ion suppression), several noteworthy developments have been made over the years. They include: sensitive ion sources, loss-free interfaces, ion optics components, efficient mass analyzers and detectors, as well as "smart" sample preparation strategies. Some of the mass spectrometric methods published to date can achieve sensitivity which is by several orders of magnitude higher than that of alternative approaches. Femto- and attomole level limits of detection are nowadays common, while zepto- and yoctomole level limits of detection have also been reported. We envision that the ultrasensitive mass spectrometric assays will soon contribute to new discoveries in bioscience and other areas.

  20. Disentangling DNA molecules

    NASA Astrophysics Data System (ADS)

    Vologodskii, Alexander

    2016-09-01

    The widespread circular form of DNA molecules inside cells creates very serious topological problems during replication. Due to the helical structure of the double helix the parental strands of circular DNA form a link of very high order, and yet they have to be unlinked before the cell division. DNA topoisomerases, the enzymes that catalyze passing of one DNA segment through another, solve this problem in principle. However, it is very difficult to remove all entanglements between the replicated DNA molecules due to huge length of DNA comparing to the cell size. One strategy that nature uses to overcome this problem is to create the topoisomerases that can dramatically reduce the fraction of linked circular DNA molecules relative to the corresponding fraction at thermodynamic equilibrium. This striking property of the enzymes means that the enzymes that interact with DNA only locally can access their topology, a global property of circular DNA molecules. This review considers the experimental studies of the phenomenon and analyzes the theoretical models that have been suggested in attempts to explain it. We describe here how various models of enzyme action can be investigated computationally. There is no doubt at the moment that we understand basic principles governing enzyme action. Still, there are essential quantitative discrepancies between the experimental data and the theoretical predictions. We consider how these discrepancies can be overcome.

  1. Exploration of target molecules for molecular imaging of inflammatory bowel disease

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

    Higashikawa, Kei; Akada, Naoki; Yagi, Katsuharu

    2011-07-08

    Highlights: {sup {yields}18}F-FDG PET could discriminate each inflamed area of IBD model mice clearly. {sup {yields}18}F-FDG PET could not discriminate the difference of pathogenic mechanism. {yields} Cytokines and cytokine receptors expression was different by pathogenic mechanism. {yields} Cytokines and cytokine receptors would be new target molecules for IBD imaging. -- Abstract: Molecular imaging technology is a powerful tool for the diagnosis of inflammatory bowel disease (IBD) and the efficacy evaluation of various drug therapies for it. However, it is difficult to elucidate directly the relationships between the responsible molecules and IBD using existing probes. Therefore, the development of an alternativemore » probe that is able to elucidate the pathogenic mechanism and provide information on the appropriate guidelines for treatment is earnestly awaited. In this study, we investigated pathognomonic molecules in the intestines of model mice. The accumulation of fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) in the inflamed area of the intestines of dextran sulfate sodium (DSS)- or indomethacin (IND)-induced IBD model mice was measured by positron emission tomography (PET) and autoradiography to confirm the inflamed area. The results suggested that the inflammation was selectively induced in the colons of mice by the administration of DSS, whereas it was induced mainly in the ilea and the proximal colons of mice by the administration of IND. To explore attractive target molecules for the molecular imaging of IBD, we evaluated the gene expression levels of cytokines and cytokine receptors in the inflamed area of the intestines of both model mice. We found that the expression levels of cytokines and cytokine receptors were significantly increased during the progression of IBD, whereas the expression levels were decreased as the mucosa began to heal. In particular, the expression levels of these molecules had already changed before the symptoms of IBD

  2. Savannah River Ecology Laboratory. Annual technical progress report of ecological research

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

    Smith, M.H.

    1996-07-31

    The Savannah River Ecology Laboratory (SREL) is a research unit of the University of Georgia (UGA). The overall mission of the Laboratory is to acquire and communicate knowledge of ecological processes and principles. SREL conducts basic and applied ecological research, as well as education and outreach programs, under a contract with the U.S. Department of Energy (DOE) at the Savannah River Site (SRS) near Aiken, South Carolina. Significant accomplishments were made during the past year in the areas of research, education and service. The Laboratory`s research mission was fulfilled with the publication of two books and 143 journal articles andmore » book chapters by faculty, technical and students, and visiting scientists. An additional three books and about 80 journal articles currently are in press. Faculty, technician and students presented 193 lectures, scientific presentations, and posters to colleges and universities, including minority institutions. Dr. J Vaun McArthur organized and conducted the Third Annual SREL Symposium on the Environment: New Concepts in Strewn Ecology: An Integrative Approach. Dr. Michael Newman conducted a 5-day course titled Quantitative Methods in Ecotoxicology, and Dr. Brian Teppen of The Advanced Analytical Center for Environmental Sciences (AACES) taught a 3-day short course titled Introduction to Molecular Modeling of Environmental Systems. Dr. I. Lehr Brisbin co-hosted a meeting of the Crocodile Special Interest Group. Dr. Rebecca Sharitz attended four symposia in Japan during May and June 1996 and conducted meetings of the Executive Committee and Board of the International Association for Ecology (ENTECOL).« less

  3. Fourier Transform Microwave Spectroscopy of Multiconformational Molecules and Van Der Waals Complexes.

    NASA Astrophysics Data System (ADS)

    Hight Walker, Angela Renee

    1995-01-01

    With the use of a Fourier transform microwave (FTM) spectrometer, structural determinations of two types of species; multiconformational molecules and van der Waals complexes, have been performed. Presented in this thesis are three sections summarizing this research effort. The first section contains a detailed explanation of the FTM instrument. In Section II, the study of three multiconformational molecules is presented as two chapters. Finally, three chapters in Section III outline the work still in progress on many van der Waals complexes. Section I was written to be a "manual" for the FTM spectrometer and to aid new additions to the group in their understanding of the instrument. An instruction guide is necessary for home-built instruments such as this one due to their unique design and application. Vital techniques and theories are discussed and machine operation is outlined. A brief explanation of general microwave spectroscopy as performed on an FTM spectrometer is also given. Section II is composed of two chapters pertaining to multiconformational molecules. In Chapter 2, a complete structural analysis of dipropyl ether is reported. The only conformer assigned had C_{rm s} symmetry. Many transitions are yet unassigned. Chapter 3 summarizes an investigation of two nitrosamines; methyl ethyl and methyl propyl nitrosamine. Only one conformer was observed for methyl ethyl nitrosamine, but two were assigned to methyl propyl nitrosamine. Nuclear hyperfine structure and internal methyl rotation complicated the spectra. The final section, Section III, contains the ongoing progress on weakly bound van der Waals complexes. The analysis of the OCS--HBr complex identified the structure as quasi-linear with large amplitude bending motions. Five separate isotopomers were assigned. Transitions originating from the HBr--DBr complex were measured and presented in Chapter 5. Although early in the analysis, the structure was determined to be bent and deuterium bonded. The

  4. Longitudinal Surveys of Australian Youth (LSAY): 2006 Cohort Wave 4 (2009)--Frequency Tables. Technical Report 56B

    ERIC Educational Resources Information Center

    National Centre for Vocational Education Research (NCVER), 2010

    2010-01-01

    The Longitudinal Surveys of Australian Youth (LSAY) program studies the progress of several groups of young Australians as they move from school into post-secondary education and work. This technical paper contains the frequency tables for the LSAY 2006 cohort Wave 4 (2009) data set. [For the "Longitudinal Surveys of Australian Youth (LSAY):…

  5. Legitimizing Technical Communication in English Departments: Carolyn Miller's "Humanistic Rationale for Technical Writing"

    ERIC Educational Resources Information Center

    Moore, Patrick

    2006-01-01

    Carolyn Miller's oft-cited "Humanistic Rationale for Technical Writing," published in 1979, tries to give technical communication faculty more cultural capital in English departments controlled by literature professors. Miller replaces a positivistic emphasis in technical communication pedagogy with rhetoric. She shows how technical knowledge is…

  6. Understanding ultracold polar molecules

    NASA Astrophysics Data System (ADS)

    Julienne, Paul

    2009-05-01

    The successful production of a dense sample of ultracold ground state KRb polar molecules [1] opens the door to a new era of research with dipolar gases and lattices of such species. This feat was achieved by first associating a K and a Rb atom to make a weakly bound Feshbach molecule and then coherently transferring the population to the ground vibrational level of the molecule. This talk focuses on theoretical issues associated with making and using ultracold polar molecules, using KRb as an example [2]. Full understanding of this species and the processes by which it is made requires taking advantage of accurate molecular potentials [3], ab initio calculations [4], and the properties of the long-range potential. A highly accurate model is available for KRb for all bound states below the ground state separated atom limit and could be constructed for other species. The next step is to develop an understanding of the interactions between polar molecules, and their control in the ultracold domain. Understanding long-range interactions and threshold resonances will be crucial for future work. [1] K.-K. Ni, et al, Science 322, 231(2008). [2] P. S. Julienne, arXiv:0812:1233. [3] Pashov et al., Phys. Rev. A76, 022511 (2007). [4] S. Kotochigova, et al., arXiv:0901.1486.

  7. Improving single-molecule FRET measurements by confining molecules in nanopipettes

    NASA Astrophysics Data System (ADS)

    Vogelsang, J.; Doose, S.; Sauer, M.; Tinnefeld, P.

    2007-07-01

    In recent years Fluorescence Resonance Energy Transfer (FRET) has been widely used to determine distances, observe distance dynamics, and monitor molecular binding at the single-molecule level. A basic constraint of single-molecule FRET studies is the limited distance resolution owing to low photon statistics. We demonstrate that by confining molecules in nanopipettes (50-100 nm diameter) smFRET can be measured with improved photon statistics reducing the width of FRET proximity ratio distributions (PRD). This increase in distance resolution makes it possible to reveal subpopulations and dynamics in biomolecular complexes. Our data indicate that the width of PRD is not only determined by photon statistics (shot noise) and distance distributions between the chromophores but that photoinduced dark states of the acceptor also contribute to the PRD width. Furthermore, acceptor dark states such as triplet states influence the accuracy of determined mean FRET values. In this context, we present a strategy for the correction of the shift of the mean PR that is related to triplet induced blinking of the acceptor using reference FCS measurements.

  8. Role of epithelial-mesenchymal transition involved molecules in the progression of cutaneous melanoma.

    PubMed

    Murtas, Daniela; Maxia, Cristina; Diana, Andrea; Pilloni, Luca; Corda, Claudia; Minerba, Luigi; Tomei, Sara; Piras, Franca; Ferreli, Caterina; Perra, Maria Teresa

    2017-12-01

    Epithelial-mesenchymal transition (EMT) has been suggested to have a driving role in the acquisition of a metastatic potential by melanoma cells. Important hallmarks of EMT include both E-cadherin downregulation and increased expression of N-cadherin. This switch in distinct classes of adhesion molecules leads melanoma cells to lose contact with adjacent keratinocytes and interact instead with stromal fibroblasts and endothelial cells, thus promoting dermal and vascular melanoma invasion. Consequently, tumor cells migrate to distant host tissues and establish metastases. A key regulator in the induction of EMT in melanoma is the Notch1 signaling pathway that, when activated, is prompt to upregulate N-cadherin expression. By means of this strategy, melanoma cells gain enhanced survival, proliferation and invasion properties, driving the tumor toward a more aggressive phenotype. On the basis of these statements, the present study aimed to investigate the possible association between N-cadherin and Notch1 presence in primary cutaneous melanomas and lymph node metastases. Our results from immunohistochemical analysis confirmed a positive correlation between N-cadherin and Notch1 presence in the same tumor samples. Moreover, this study highlighted that a concomitant high expression of N-cadherin and Notch1, both in primary lesions and in lymph node metastases, predicts an adverse clinical outcome in melanoma patients. Therefore, N-cadherin and Notch1 co-presence can be monitored as a predictive factor in early- and advanced-stage melanomas and open additional therapeutic targets for the restraint of melanoma metastasis.

  9. A general method for controlling and resolving rotational orientation of molecules in molecule-surface collisions

    PubMed Central

    Godsi, Oded; Corem, Gefen; Alkoby, Yosef; Cantin, Joshua T.; Krems, Roman V.; Somers, Mark F.; Meyer, Jörg; Kroes, Geert-Jan; Maniv, Tsofar; Alexandrowicz, Gil

    2017-01-01

    The outcome of molecule–surface collisions can be modified by pre-aligning the molecule; however, experiments accomplishing this are rare because of the difficulty of preparing molecules in aligned quantum states. Here we present a general solution to this problem based on magnetic manipulation of the rotational magnetic moment of the incident molecule. We apply the technique to the scattering of H2 from flat and stepped copper surfaces. We demonstrate control of the molecule's initial quantum state, allowing a direct comparison of differences in the stereodynamic scattering from the two surfaces. Our results show that a stepped surface exhibits a much larger dependence of the corrugation of the interaction on the alignment of the molecule than the low-index surface. We also demonstrate an extension of the technique that transforms the set-up into an interferometer, which is sensitive to molecular quantum states both before and after the scattering event. PMID:28480890

  10. Water Molecule Hops on Ceres

    NASA Image and Video Library

    2016-12-15

    This graphic shows a theoretical path of a water molecule on Ceres. Some water molecules fall into cold, dark craters at high latitudes called "cold traps," where very little of the ice turns into vapor, even over the course of a billion years. Other water molecules that do not land in cold traps are lost to space as they hop around the dwarf planet. http://photojournal.jpl.nasa.gov/catalog/PIA21083

  11. The RERTR Program status and progress

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

    Travelli, A.

    1995-12-01

    The progress of the Reduced Enrichment Research and Test Reactor (RERTR) Program is described. The major events, findings, and activities of 1995 are reviewed after a brief summary of the results which the RERTR Program had achieved by the end of 1994. The revelation that Iraq was on the verge of developing a nuclear weapon at the time of the Gulf War, and that it was planning to do so by extracting HEU from the fuel of its research reactors, has given new impetus and urgency to the RERTR commitment of eliminating HEU use in research and test reactors worldwide.more » Development of advanced LEU research reactor fuels is scheduled to begin in October 1995. The Russian RERTR program, which aims to develop and demonstrate within the next five years the technical means needed to convert Russian-supplied research reactors to LEU fuels, is now in operation. A Statement of Intent was signed by high US and Chinese officials, endorsing cooperative activities between the RERTR program and Chinese laboratories involved in similar activities. Joint studies of LEU technical feasibility were completed for the SAFARI-I reactor in South Africa and for the ANS reactor in the US. A new study has been initiated for the FRM-II reactor in Germany. Significant progress was made on several aspects of producing {sup 99}Mo from fission targets utilizing LEU instead of HEU. A cooperation agreements is in place with the Indonesian BATAN. The first prototypical irradiation of an LEU metal-foil target for {sup 99}Mo production was accomplished in Indonesia. The TR-2 reactor, in Turkey, began conversion. SAPHIR, in Switzerland, was shut down. LEU fuel fabrication has begun for the conversion of two more US reactors. Twelve foreign reactors and nine domestic reactors have been fully converted. Approximately 60 % of the work required to eliminate the use of HEU in US-supplied research reactors has been accomplished.« less

  12. Permeability of uncharged organic molecules in reverse osmosis desalination membranes.

    PubMed

    Dražević, Emil; Košutić, Krešimir; Svalina, Marin; Catalano, Jacopo

    2017-06-01

    Reverse osmosis (RO) membranes are primarily designed for removal of salts i.e. for desalination of brackish and seawater, but they have also found applications in removal of organic molecules. While it is clear that steric exclusion is the dominant removal mechanism, the fundamental explanation for how and why the separation occurs remains elusive. Until recently there was no strong microscopic evidences elucidating the structure of the active polyamide layers of RO membranes, and thus they have been conceived as "black boxes"; or as an array of straight capillaries with a distribution of radii; or as polymers with a small amount of polymer free domains. The knowledge of diffusion and sorption coefficients is a prerequisite for understanding the intrinsic permeability of any organic solute in any polymer. At the same time, it is technically challenging to accurately measure these two fundamental parameters in very thin (20-300 nm) water-swollen active layers. In this work we have measured partition and diffusion coefficients and RO permeabilities of ten organic solutes in water-swollen active layers of two types of RO membranes, low (SWC4+) and high flux (XLE). We deduced from our results and recent microscopic studies that the solute flux of organic molecules in polyamide layer of RO membranes occurs in two domains, dense polymer (the key barrier layer) and the water filled domains. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Spectroscopy and Chemistry of Cold Molecules

    NASA Astrophysics Data System (ADS)

    Momose, Takamasa

    2012-06-01

    Molecules at low temperatures are expected to behave quite differently from those at high temperatures because pronounced quantum effects emerge from thermal averages. Even at 10 K, a significant enhancement of reaction cross section is expected due to tunneling and resonance effects. Chemistry at this temperature is very important in order to understand chemical reactions in interstellar molecular clouds. At temperatures lower than 1 K, collisions and intermolecular interactions become qualitatively different from those at high temperatures because of the large thermal de Broglie wavelength of molecules. Collisions at these temperatures must be treated as the interference of molecular matter waves, but not as hard sphere collisions. A Bose-Einstein condensate is a significant state of matter as a result of coherent matter wave interaction. Especially, dense para-H_2 molecules are predicted to become a condensate even around 1 K. A convenient method to investigate molecules around 1 K is to dope molecules in cold matrices. Among various matrices, quantum hosts such as solid para-H_2 and superfluid He nano-droplets have been proven to be an excellent host for high-resolution spectroscopy. Rovibrational motion of molecules in these quantum hosts is well quantized on account of the weak interactions and the softness of quantum environment. The linewidths of infrared spectra of molecules in the quantum hosts are extremely narrow compared with those in other matrices. The sharp linewidths allow us to resolve fine spectral structures originated in subtle interactions between guest and host molecules. In this talk, I will describe how the splitting and lineshape of high-resolution spectra of molecules in quantum hosts give us new information on the static and dynamical interactions of molecules in quantum medium. The topics include dynamical response of superfluid environment upon rotational excitation, and possible superfluid phase of para-H_2 clusters. I will also

  14. Progress and future direction for the interim safe storage and disposal of Hanford high-level waste

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

    Kinzer, J.E.; Wodrich, D.D.; Bacon, R.F.

    This paper describes the progress made at the largest environmental cleanup program in the United States. Substantial advances in methods to start interim safe storage of Hanford Site high-level wastes, waste characterization to support both safety- and disposal-related information needs, and proceeding with cost-effective disposal by the U.S. Department of Energy (DOE) and its Hanford Site contractors, have been realized. Challenges facing the Tank Waste Remediation System (TWRS) Program, which is charged with the dual and parallel missions of interim safe storage and disposal of the high-level tank waste stored at the Hanford Site, are described. In these times ofmore » budget austerity, implementing an ongoing program that combines technical excellence and cost effectiveness is the near-term challenge. The technical initiatives and progress described in this paper are made more cost effective by DOE`s focus on work force productivity improvement, reduction of overhead costs, and reduction, integration and simplification of DOE regulations and operations requirements to more closely model those used in the private sector.« less

  15. 9.73% Efficiency Nonfullerene All Organic Small Molecule Solar Cells with Absorption-Complementary Donor and Acceptor.

    PubMed

    Bin, Haijun; Yang, Yankang; Zhang, Zhi-Guo; Ye, Long; Ghasemi, Masoud; Chen, Shanshan; Zhang, Yindong; Zhang, Chunfeng; Sun, Chenkai; Xue, Lingwei; Yang, Changduk; Ade, Harald; Li, Yongfang

    2017-03-29

    In the last two years, polymer solar cells (PSCs) developed quickly with n-type organic semiconductor (n-OSs) as acceptor. In contrast, the research progress of nonfullerene organic solar cells (OSCs) with organic small molecule as donor and the n-OS as acceptor lags behind. Here, we synthesized a D-A structured medium bandgap organic small molecule H11 with bithienyl-benzodithiophene (BDTT) as central donor unit and fluorobenzotriazole as acceptor unit, and achieved a power conversion efficiency (PCE) of 9.73% for the all organic small molecules OSCs with H11 as donor and a low bandgap n-OS IDIC as acceptor. A control molecule H12 without thiophene conjugated side chains on the BDT unit was also synthesized for investigating the effect of the thiophene conjugated side chains on the photovoltaic performance of the p-type organic semiconductors (p-OSs). Compared with H12, the 2D-conjugated H11 with thiophene conjugated side chains shows intense absorption, low-lying HOMO energy level, higher hole mobility and ordered bimodal crystallite packing in the blend films. Moreover, a larger interaction parameter (χ) was observed in the H11 blends calculated from Hansen solubility parameters and differential scanning calorimetry measurements. These special features combined with the complementary absorption of H11 donor and IDIC acceptor resulted in the best PCE of 9.73% for nonfullerene all small molecule OSCs up to date. Our results indicate that fluorobenzotriazole based 2D conjugated p-OSs are promising medium bandgap donors in the nonfullerene OSCs.

  16. The symmetry of single-molecule conduction.

    PubMed

    Solomon, Gemma C; Gagliardi, Alessio; Pecchia, Alessandro; Frauenheim, Thomas; Di Carlo, Aldo; Reimers, Jeffrey R; Hush, Noel S

    2006-11-14

    We introduce the conductance point group which defines the symmetry of single-molecule conduction within the nonequilibrium Green's function formalism. It is shown, either rigorously or to within a very good approximation, to correspond to a molecular-conductance point group defined purely in terms of the properties of the conducting molecule. This enables single-molecule conductivity to be described in terms of key qualitative chemical descriptors that are independent of the nature of the molecule-conductor interfaces. We apply this to demonstrate how symmetry controls the conduction through 1,4-benzenedithiol chemisorbed to gold electrodes as an example system, listing also the molecular-conductance point groups for a range of molecules commonly used in molecular electronics research.

  17. Spectroscopic photon localization microscopy: breaking the resolution limit of single molecule localization microscopy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Dong, Biqin; Almassalha, Luay Matthew; Urban, Ben E.; Nguyen, The-Quyen; Khuon, Satya; Chew, Teng-Leong; Backman, Vadim; Sun, Cheng; Zhang, Hao F.

    2017-02-01

    Distinguishing minute differences in spectroscopic signatures is crucial for revealing the fluorescence heterogeneity among fluorophores to achieve a high molecular specificity. Here we report spectroscopic photon localization microscopy (SPLM), a newly developed far-field spectroscopic imaging technique, to achieve nanoscopic resolution based on the principle of single-molecule localization microscopy while simultaneously uncovering the inherent molecular spectroscopic information associated with each stochastic event (Dong et al., Nature Communications 2016, in press). In SPLM, by using a slit-less monochromator, both the zero-order and the first-order diffractions from a grating were recorded simultaneously by an electron multiplying charge-coupled device to reveal the spatial distribution and the associated emission spectra of individual stochastic radiation events, respectively. As a result, the origins of photon emissions from different molecules can be identified according to their spectral differences with sub-nm spectral resolution, even when the molecules are within close proximity. With the newly developed algorithms including background subtraction and spectral overlap unmixing, we established and tested a method which can significantly extend the fundamental spatial resolution limit of single molecule localization microscopy by molecular discrimination through spectral regression. Taking advantage of this unique capability, we demonstrated improvement in spatial resolution of PALM/STORM up to ten fold with selected fluorophores. This technique can be readily adopted by other research groups to greatly enhance the optical resolution of single molecule localization microscopy without the need to modify their existing staining methods and protocols. This new resolving capability can potentially provide new insights into biological phenomena and enable significant research progress to be made in the life sciences.

  18. Progress in bio-manufacture of platelets for transfusion.

    PubMed

    Heazlewood, Shen Y; Nilsson, Susan K; Cartledge, Kellie; Be, Cheang Ly; Vinson, Andrew; Gel, Murat; Haylock, David N

    2017-11-01

    Blood transfusion services face an ever-increasing demand for donor platelets to meet clinical needs. Whilst strategies for increasing platelet storage life and improving the efficiency of donor platelet collection are important, in the longer term, platelets generated by bio-manufacturing processes will be required to meet demands. Production of sufficient numbers of in vitro-derived platelets for transfusion represents a significant bioengineering challenge. In this review, we highlight recent progress in this area of research and outline the main technical and biological obstacles that need to be met before this becomes feasible and economic. A critical consideration is assurance of the functional properties of these cells as compared to their fresh, donor collected, counterparts. We contend that platelet-like particles and in vitro-derived platelets that phenotypically resemble fresh platelets must deliver the same functions as these cells upon transfusion. We also note recent progress with immortalized megakaryocyte progenitor cell lines, molecular strategies for reducing expression of HLA Class I to generate universal donor platelets and the move to early clinical studies with in vitro-derived platelets.

  19. Technical advance: soluble OX40 molecule mimics regulatory T cell modulatory activity on FcεRI-dependent mast cell degranulation.

    PubMed

    Sibilano, Riccardo; Gri, Giorgia; Frossi, Barbara; Tripodo, Claudio; Suzuki, Ryo; Rivera, Juan; MacDonald, Andrew S; Pucillo, Carlo E

    2011-10-01

    Tregs play a central role in modulating FcεRI-dependent MC effector functions in the course of the allergic response. Cellular interaction depends on the constitutive expression of OX40 on Tregs and the OX40L counterpart on MCs. Study of OX40L signaling on MCs is hampered by the need of a highly purified molecule, which triggers OX40L specifically. We now report that sOX40 mimics the physiological activity of Treg interaction by binding to activated MCs. When treated with sOX40, activated MCs showed decreased degranulation and Ca(++) influx, whereas PLC-γ2 phosphorylation remained unaffected. Once injected into experimental animals, sOX40 not only located within the endothelium but also in parenchyma, where it could be found in close proximity and apparently bound to MCs. This soluble molecule triggers MC-OX40L without the requirement of Tregs, thus allowing study of OX40L signaling pathways in MCs and in other OX40L-expressing cell populations. Importantly, as sOX40 inhibits MC degranulation, it may provide an in vivo therapeutic tool in allergic disease.

  20. Technical Advance: Soluble OX40 molecule mimics regulatory T cell modulatory activity on FcεRI-dependent mast cell degranulation

    PubMed Central

    Sibilano, Riccardo; Gri, Giorgia; Frossi, Barbara; Tripodo, Claudio; Suzuki, Ryo; Rivera, Juan; MacDonald, Andrew S.; Pucillo, Carlo E.

    2011-01-01

    Tregs play a central role in modulating FcεRI-dependent MC effector functions in the course of the allergic response. Cellular interaction depends on the constitutive expression of OX40 on Tregs and the OX40L counterpart on MCs. Study of OX40L signaling on MCs is hampered by the need of a highly purified molecule, which triggers OX40L specifically. We now report that sOX40 mimics the physiological activity of Treg interaction by binding to activated MCs. When treated with sOX40, activated MCs showed decreased degranulation and Ca++ influx, whereas PLC-γ2 phosphorylation remained unaffected. Once injected into experimental animals, sOX40 not only located within the endothelium but also in parenchyma, where it could be found in close proximity and apparently bound to MCs. This soluble molecule triggers MC-OX40L without the requirement of Tregs, thus allowing study of OX40L signaling pathways in MCs and in other OX40L-expressing cell populations. Importantly, as sOX40 inhibits MC degranulation, it may provide an in vivo therapeutic tool in allergic disease. PMID:21653238