46 CFR 160.133-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 6 2013-10-01 2013-10-01 false Production inspections, tests, quality control, and..., tests, quality control, and conformance of release mechanisms. (a) Unless the Commandant directs.... The Commandant may prescribe additional production tests and inspections necessary to maintain quality...

46 CFR 160.170-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 6 2014-10-01 2014-10-01 false Production inspections, tests, quality control, and..., quality control, and conformance of release mechanisms. (a) Unless the Commandant directs otherwise, an... prescribe additional production tests and inspections necessary to maintain quality control and to monitor...

46 CFR 160.170-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 6 2012-10-01 2012-10-01 false Production inspections, tests, quality control, and..., quality control, and conformance of release mechanisms. (a) Unless the Commandant directs otherwise, an... prescribe additional production tests and inspections necessary to maintain quality control and to monitor...

46 CFR 160.133-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 6 2014-10-01 2014-10-01 false Production inspections, tests, quality control, and..., quality control, and conformance of release mechanisms. (a) Unless the Commandant directs otherwise, an... prescribe additional production tests and inspections necessary to maintain quality control and to monitor...

46 CFR 160.170-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 6 2013-10-01 2013-10-01 false Production inspections, tests, quality control, and..., quality control, and conformance of release mechanisms. (a) Unless the Commandant directs otherwise, an... prescribe additional production tests and inspections necessary to maintain quality control and to monitor...

46 CFR 160.135-15 - Production inspections, tests, quality control, and conformance of lifeboats.

Code of Federal Regulations, 2013 CFR

2013-10-01

... materials are as per the plans approved under § 160.135-13(h) of this subpart. (2) Post assembly tests and... 46 Shipping 6 2013-10-01 2013-10-01 false Production inspections, tests, quality control, and... Lifeboats (SOLAS) § 160.135-15 Production inspections, tests, quality control, and conformance of lifeboats...

46 CFR 160.135-15 - Production inspections, tests, quality control, and conformance of lifeboats.

Code of Federal Regulations, 2012 CFR

2012-10-01

... materials are as per the plans approved under § 160.135-13(h) of this subpart. (2) Post assembly tests and... 46 Shipping 6 2012-10-01 2012-10-01 false Production inspections, tests, quality control, and... Lifeboats (SOLAS) § 160.135-15 Production inspections, tests, quality control, and conformance of lifeboats...

Driving photomask supplier quality through automation

NASA Astrophysics Data System (ADS)

Russell, Drew; Espenscheid, Andrew

2007-10-01

In 2005, Freescale Semiconductor's newly centralized mask data prep organization (MSO) initiated a project to develop an automated global quality validation system for photomasks delivered to Freescale Semiconductor fabs. The system handles Certificate of Conformance (CofC) quality metric collection, validation, reporting and an alert system for all photomasks shipped to Freescale fabs from all qualified global suppliers. The completed system automatically collects 30+ quality metrics for each photomask shipped. Other quality metrics are generated from the collected data and quality metric conformance is automatically validated to specifications or control limits with failure alerts emailed to fab photomask and mask data prep engineering. A quality data warehouse stores the data for future analysis, which is performed quarterly. The improved access to data provided by the system has improved Freescale engineers' ability to spot trends and opportunities for improvement with our suppliers' processes. This paper will review each phase of the project, current system capabilities and quality system benefits for both our photomask suppliers and Freescale.

Conformal Infinity.

PubMed

Frauendiener, Jörg

2000-01-01

The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, "conformal infinity" is related with almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved out of physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation and how it lends itself very naturally to solve radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

Conformal Infinity.

PubMed

Frauendiener, Jörg

2004-01-01

The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, "conformal infinity" is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation, and how it lends itself very naturally to the solution of radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

Parental Qualities as Predictors of Adolescent Conformity: Perceptions from Adolescents, Mothers, and Fathers.

ERIC Educational Resources Information Center

Henry, Carolyn S.; Peterson, Gary W.

The purpose of this study was to examine how adolescent and parental perceptions of selected parental qualities predicted adolescent conformity to parental expectations, using symbolic interaction as a conceptual foundation. Self-report questionnaire data were collected from a sample of 326 families with adolescents. Four separate multiple…

Fake conformal symmetry in unimodular gravity

NASA Astrophysics Data System (ADS)

Oda, Ichiro

2016-08-01

We study Weyl symmetry (local conformal symmetry) in unimodular gravity. It is shown that the Noether currents for both Weyl symmetry and global scale symmetry vanish exactly as in conformally invariant scalar-tensor gravity. We clearly explain why in the class of conformally invariant gravitational theories, the Noether currents vanish by starting with conformally invariant scalar-tensor gravity. Moreover, we comment on both classical and quantum-mechanical equivalences in Einstein's general relativity, conformally invariant scalar-tensor gravity, and the Weyl-transverse gravity. Finally, we discuss the Weyl current in the conformally invariant scalar action and see that it is also vanishing.

Global Conformational Selection and Local Induced Fit for the Recognition between Intrinsic Disordered p53 and CBP

PubMed Central

Yu, Qingfen; Ye, Wei; Wang, Wei; Chen, Hai-Feng

2013-01-01

The transactivation domain (TAD) of tumor suppressor p53 can bind with the nuclear coactivator binding domain (NCBD) of cyclic-AMP response element binding protein (CBP) and activate transcription. NMR experiments demonstrate that both apo-NCBD and TAD are intrinsic disordered and bound NCBD/TAD undergoes a transition to well folded. The recognition mechanism between intrinsic disordered proteins is still hotly debated. Molecular dynamics (MD) simulations in explicit solvent are used to study the recognition mechanism between intrinsic disordered TAD and NCBD. The average RMSD values between bound and corresponding apo states and Kolmogorov-Smirnov P test analysis indicate that TAD and NCBD may follow an induced fit mechanism. Quantitative analysis indicates there is also a global conformational selection. In summary, the recognition of TAD and NCBD might obey a local induced fit and global conformational selection. These conclusions are further supported by high-temperature unbinding kinetics and room temperature landscape analysis. These methods can be used to study the recognition mechanism of other intrinsic disordered proteins. PMID:23555731

Conformal geodesics in spherically symmetric vacuum spacetimes with cosmological constant

NASA Astrophysics Data System (ADS)

García-Parrado Gómez-Lobo, A.; Gasperín, E.; Valiente Kroon, J. A.

2018-02-01

An analysis of conformal geodesics in the Schwarzschild–de Sitter and Schwarzschild–anti-de Sitter families of spacetimes is given. For both families of spacetimes we show that initial data on a spacelike hypersurface can be given such that the congruence of conformal geodesics arising from this data cover the whole maximal extension of canonical conformal representations of the spacetimes without forming caustic points. For the Schwarzschild–de Sitter family, the resulting congruence can be used to obtain global conformal Gaussian systems of coordinates of the conformal representation. In the case of the Schwarzschild–anti-de Sitter family, the natural parameter of the curves only covers a restricted time span so that these global conformal Gaussian systems do not exist.

Quality improvement and emerging global health priorities

PubMed Central

Mensah Abrampah, Nana; Syed, Shamsuzzoha Babar; Hirschhorn, Lisa R; Nambiar, Bejoy; Iqbal, Usman; Garcia-Elorrio, Ezequiel; Chattu, Vijay Kumar; Devnani, Mahesh; Kelley, Edward

2018-01-01

Abstract Quality improvement approaches can strengthen action on a range of global health priorities. Quality improvement efforts are uniquely placed to reorient care delivery systems towards integrated people-centred health services and strengthen health systems to achieve Universal Health Coverage (UHC). This article makes the case for addressing shortfalls of previous agendas by articulating the critical role of quality improvement in the Sustainable Development Goal era. Quality improvement can stimulate convergence between health security and health systems; address global health security priorities through participatory quality improvement approaches; and improve health outcomes at all levels of the health system. Entry points for action include the linkage with antimicrobial resistance and the contentious issue of the health of migrants. The work required includes focussed attention on the continuum of national quality policy formulation, implementation and learning; alongside strengthening the measurement-improvement linkage. Quality improvement plays a key role in strengthening health systems to achieve UHC. PMID:29873793

General Conformity

EPA Pesticide Factsheets

The General Conformity requirements ensure that the actions taken by federal agencies in nonattainment and maintenance areas do not interfere with a state’s plans to meet national standards for air quality.

Conformal Dimensions via Large Charge Expansion

NASA Astrophysics Data System (ADS)

Banerjee, Debasish; Chandrasekharan, Shailesh; Orlando, Domenico

2018-02-01

We construct an efficient Monte Carlo algorithm that overcomes the severe signal-to-noise ratio problems and helps us to accurately compute the conformal dimensions of large-Q fields at the Wilson-Fisher fixed point in the O (2 ) universality class. Using it, we verify a recent proposal that conformal dimensions of strongly coupled conformal field theories with a global U (1 ) charge can be obtained via a series expansion in the inverse charge 1 /Q . We find that the conformal dimensions of the lowest operator with a fixed charge Q are almost entirely determined by the first few terms in the series.

Overview of NASA's Observations for Global Air Quality

NASA Astrophysics Data System (ADS)

Kaye, J. A.

2015-12-01

Observations of pollutants are central to the study of air quality. Much focus has been placed on local-scale observations that can help specific geographic areas document their air quality issues, plan abatement strategies, and understand potential impacts. In addition, long-range atmospheric transport of pollutants can cause downwind regions to not meet attainment standards. Satellite observations have shed significant light on air quality from local to regional to global scales, especially for pollutants such as ozone, aerosols, carbon monoxide, sulfur dioxide, and nitrogen dioxide. These observations have made use of multiple techniques and in some cases multiple satellite sensors. The satellite observations are complemented by surface observations, as well as atmospheric (in situ) observations typically made as part of focused airborne field campaigns. The synergy between satellite observations and field campaigns has been an important theme for recent and upcoming activities and plans. In this talk, a review of NASA's investments in observations relevant to global air quality will be presented, with examples given for a range of pollutants and measurement approaches covering the last twenty-five years. These investments have helped build national and international collaborations such that the global satellite community is now preparing to deploy a constellation of satellites that together will provide fundamental advances in global observations for air quality.

Exploring global recognition of quality midwifery education: Vision or fiction?

PubMed

Luyben, Ans; Barger, Mary; Avery, Melissa; Bharj, Kuldip Kaur; O'Connell, Rhona; Fleming, Valerie; Thompson, Joyce; Sherratt, Della

2017-06-01

Midwifery education is the foundation for preparing competent midwives to provide a high standard of safe, evidence-based care for women and their newborns. Global competencies and standards for midwifery education have been defined as benchmarks for establishing quality midwifery education and practice worldwide. However, wide variations in type and nature of midwifery education programs exist. To explore and discuss the opportunities and challenges of a global quality assurance process as a strategy to promote quality midwifery education. Accreditation and recognition as two examples of quality assurance processes in education are discussed. A global recognition process, with its opportunities and challenges, is explored from the perspective of four illustrative case studies from Ireland, Kosovo, Latin America and Bangladesh. The discussion highlights that the establishment of a global recognition process may assist in promoting quality of midwifery education programs world-wide, but cannot take the place of formal national accreditation. In addition, a recognition process will not be feasible for many institutions without additional resources, such as financial support or competent evaluators. In order to achieve quality midwifery education through a global recognition process the authors present 5 Essential Challenges for Quality Midwifery Education. Quality midwifery education is vital for establishing a competent workforce, and improving maternal and newborn health. Defining a global recognition process could be instrumental in moving toward this goal, but dealing with the identified challenges will be essential. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Conformational Analysis of Free and Bound Retinoic Acid

PubMed Central

Fu, Zheng; Li, Xue; Merz, Kenneth M.

2012-01-01

The conformational profiles of unbound all-trans and 9-cis retinoic acid (RA) have been determined using classical and quantum mechanical calculations. Sixty-six all-trans-RA (ATRA) and forty-eight 9-cis-RA energy minimum conformers were identified via HF/6-31G* geometry optimizations in vacuo. Their relative conformational energies were estimated utilizing the M06, M06-2x and MP2 methods combined with the 6-311+G(d,p), aug-cc-pVDZ and aug-cc-pVTZ basis sets, as well as complete basis set MP2 extrapolations using the latter two basis sets. Single-point energy calculations performed with the M06-2x density functional were found to yield similar results to MP2/CBS for the low-energy retinoic acid conformations. Not unexpectedly, the conformational propensities of retinoic acid were governed by the orientation and arrangement of the torsion angles associated with the polyene tail. We also used previously reported QM/MM X-ray refinement results on four ATRA-protein crystal structures plus one newly refined 9-cis-RA complex (PDB ID 1XDK) in order to investigate the conformational preferences of bound retinoic acid. In the re-refined RA conformers the conjugated double bonds are nearly coplanar, which is consistent with the global minimum identified by the Omega/QM method rather than the corresponding crystallographically determined conformations given in the PDB. Consequently, a 91.3% average reduction of the local strain energy in the gas phase, as well as 92.1% in PCM solvent, was observed using the QM/MM refined structures versus the PDB deposited RA conformations. These results thus demonstrate that our QM/MM X-ray refinement approach can significantly enhance the quality of X-ray crystal structures refined by conventional refinement protocols, thereby providing reliable drug-target structural information for use in structure-based drug discovery applications. PMID:22844234

1994 Transportation/ Air Quality Conformity Finding

DOT National Transportation Integrated Search

1993-10-01

The purpose of this report is to document the finding that the transportation : plans and programs for the Albuquerque Metropolitan Planning Area (AMPA) are in : conformity with the applicable Clean Air Act implementation plans for the : nonattainmen...

Conformal Dimensions via Large Charge Expansion.

PubMed

Banerjee, Debasish; Chandrasekharan, Shailesh; Orlando, Domenico

2018-02-09

We construct an efficient Monte Carlo algorithm that overcomes the severe signal-to-noise ratio problems and helps us to accurately compute the conformal dimensions of large-Q fields at the Wilson-Fisher fixed point in the O(2) universality class. Using it, we verify a recent proposal that conformal dimensions of strongly coupled conformal field theories with a global U(1) charge can be obtained via a series expansion in the inverse charge 1/Q. We find that the conformal dimensions of the lowest operator with a fixed charge Q are almost entirely determined by the first few terms in the series.

On the use of Schwarz-Christoffel conformal mappings to the grid generation for global ocean models

NASA Astrophysics Data System (ADS)

Xu, S.; Wang, B.; Liu, J.

2015-02-01

In this article we propose two conformal mapping based grid generation algorithms for global ocean general circulation models (OGCMs). Contrary to conventional, analytical forms based dipolar or tripolar grids, the new algorithms are based on Schwarz-Christoffel (SC) conformal mapping with prescribed boundary information. While dealing with the basic grid design problem of pole relocation, these new algorithms also address more advanced issues such as smoothed scaling factor, or the new requirements on OGCM grids arisen from the recent trend of high-resolution and multi-scale modeling. The proposed grid generation algorithm could potentially achieve the alignment of grid lines to coastlines, enhanced spatial resolution in coastal regions, and easier computational load balance. Since the generated grids are still orthogonal curvilinear, they can be readily utilized in existing Bryan-Cox-Semtner type ocean models. The proposed methodology can also be applied to the grid generation task for regional ocean modeling where complex land-ocean distribution is present.

46 CFR 160.156-15 - Production inspections, tests, quality control, and conformance of rescue boats and fast rescue...

Code of Federal Regulations, 2012 CFR

2012-10-01

... materials are as per the plans approved under § 160.156-13(h) of this subpart. (2) Post assembly tests and... 46 Shipping 6 2012-10-01 2012-10-01 false Production inspections, tests, quality control, and... inspections, tests, quality control, and conformance of rescue boats and fast rescue boats. (a) Unless the...

46 CFR 160.156-15 - Production inspections, tests, quality control, and conformance of rescue boats and fast rescue...

Code of Federal Regulations, 2013 CFR

2013-10-01

... materials are as per the plans approved under § 160.156-13(h) of this subpart. (2) Post assembly tests and... 46 Shipping 6 2013-10-01 2013-10-01 false Production inspections, tests, quality control, and... inspections, tests, quality control, and conformance of rescue boats and fast rescue boats. (a) Unless the...

3D QSAR studies on protein tyrosine phosphatase 1B inhibitors: comparison of the quality and predictivity among 3D QSAR models obtained from different conformer-based alignments.

PubMed

Pandey, Gyanendra; Saxena, Anil K

2006-01-01

A set of 65 flexible peptidomimetic competitive inhibitors (52 in the training set and 13 in the test set) of protein tyrosine phosphatase 1B (PTP1B) has been used to compare the quality and predictive power of 3D quantitative structure-activity relationship (QSAR) comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models for the three most commonly used conformer-based alignments, namely, cocrystallized conformer-based alignment (CCBA), docked conformer-based alignment (DCBA), and global minima energy conformer-based alignment (GMCBA). These three conformers of 5-[(2S)-2-({(2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoyl}amino)3-oxo-3-pentylamino)propyl]-2-(carboxymethoxy)benzoic acid (compound number 66) were obtained from the X-ray structure of its cocrystallized complex with PTP1B (PDB ID: 1JF7), its docking studies, and its global minima by simulated annealing. Among the 3D QSAR models developed using the above three alignments, the CCBA provided the optimal predictive CoMFA model for the training set with cross-validated r2 (q2)=0.708, non-cross-validated r2=0.902, standard error of estimate (s)=0.165, and F=202.553 and the optimal CoMSIA model with q2=0.440, r2=0.799, s=0.192, and F=117.782. These models also showed the best test set prediction for the 13 compounds with predictive r2 values of 0.706 and 0.683, respectively. Though the QSAR models derived using the other two alignments also produced statistically acceptable models in the order DCBA>GMCBA in terms of the values of q2, r2, and predictive r2, they were inferior to the corresponding models derived using CCBA. Thus, the order of preference for the alignment selection for 3D QSAR model development may be CCBA>DCBA>GMCBA, and the information obtained from the CoMFA and CoMSIA contour maps may be useful in designing specific PTP1B inhibitors.

Evaluation of the sustainability of contrasted pig farming systems: development of a market conformity tool for pork products based on technological quality traits.

PubMed

Gonzàlez, J; Gispert, M; Gil, M; Hviid, M; Dourmad, J Y; de Greef, K H; Zimmer, C; Fàbrega, E

2014-12-01

A market conformity tool, based on technological meat quality parameters, was developed within the Q-PorkChains project, to be included in a global sustainability evaluation of pig farming systems. The specific objective of the market conformity tool was to define a scoring system based on the suitability of meat to elaborate the main pork products, according to their market shares based on industry requirements, in different pig farming systems. The tool was based on carcass and meat quality parameters that are commonly used for the assessment of technological quality, which provide representative and repeatable data and are easily measurable. They were the following: cold carcass weight; lean meat percentage; minimum subcutaneous back fat depth at m. gluteus medius level, 45 postmortem and ultimate pH (measured at 24-h postmortem) in m. longissimus lumborum and semimembranosus; meat colour; drip losses and intramuscular fat content in a m. longissimus sample. Five categories of pork products produced at large scale in Europe were considered in the study: fresh meat, cooked products, dry products, specialties and other meat products. For each of the studied farming systems, the technological meat quality requirements, as well as the market shares for each product category within farming system, were obtained from the literature and personal communications from experts. The tool resulted in an overall conformity score that enabled to discriminate among systems according to the degree of matching of the achieved carcass and meat quality with the requirements of the targeted market. In order to improve feasibility, the tool was simplified by selecting ultimate pH at m. longissimus or semimembranosus, minimum fat thickness measured at the left half carcass over m. gluteus medius and intramuscular fat content in a m. longissimus sample as iceberg indicators. The overall suitability scores calculated by using both the complete and the reduced tools presented good

Global trends in milk quality: implications for the Irish dairy industry

PubMed Central

2009-01-01

The quality of Irish agricultural product will become increasingly important with the ongoing liberalisation of international trade. This paper presents a review of the global and Irish dairy industries; considers the impact of milk quality on farm profitability, food processing and human health, examines global trends in quality; and explores several models that are successfully being used to tackle milk quality concerns. There is a growing global demand for dairy products, fuelled in part by growing consumer wealth in developing countries. Global dairy trade represents only 6.2% of global production and demand currently outstrips supply. Although the Irish dairy industry is small by global standards, approximately 85% of annual production is exported annually. It is also the world's largest producer of powdered infant formula. Milk quality has an impact on human health, milk processing and on-farm profitability. Somatic cell count (SCC) is a key measure of milk quality, with a SCC not exceeding 400,000 cells/ml (the EU milk quality standard) generally accepted as the international export standard. There have been ongoing improvements in milk quality among both established and emerging international suppliers. A number of countries have developed successful industry-led models to tackle milk quality concerns. Based on international experiences, it is likely that problems with effective translation of knowledge to practice, rather than incomplete knowledge per se, are the more important constraints to national progress towards improved milk quality. PMID:22081986

48 CFR 46.504 - Certificate of conformance.

Code of Federal Regulations, 2014 CFR

2014-10-01

... MANAGEMENT QUALITY ASSURANCE Acceptance 46.504 Certificate of conformance. A certificate of conformance (see... acceptable and any defective work would be replaced, corrected, or repaired without contest. In no case shall...

Schwarz-Christoffel Conformal Mapping based Grid Generation for Global Oceanic Circulation Models

NASA Astrophysics Data System (ADS)

Xu, Shiming

2015-04-01

We propose new grid generation algorithms for global ocean general circulation models (OGCMs). Contrary to conventional, analytical forms based dipolar or tripolar grids, the new algorithm are based on Schwarz-Christoffel (SC) conformal mapping with prescribed boundary information. While dealing with the conventional grid design problem of pole relocation, it also addresses more advanced issues of computational efficiency and the new requirements on OGCM grids arisen from the recent trend of high-resolution and multi-scale modeling. The proposed grid generation algorithm could potentially achieve the alignment of grid lines to coastlines, enhanced spatial resolution in coastal regions, and easier computational load balance. Since the generated grids are still orthogonal curvilinear, they can be readily 10 utilized in existing Bryan-Cox-Semtner type ocean models. The proposed methodology can also be applied to the grid generation task for regional ocean modeling when complex land-ocean distribution is present.

Entanglement evolution across a conformal interface

NASA Astrophysics Data System (ADS)

Wen, Xueda; Wang, Yuxuan; Ryu, Shinsei

2018-05-01

For two-dimensional conformal field theories (CFTs) in the ground state, it is known that a conformal interface along the entanglement cut can suppress the entanglement entropy from to , where L is the length of the subsystem A, and is the effective central charge which depends on the transmission property of the conformal interface. In this work, by making use of conformal mappings, we show that a conformal interface has the same effect on entanglement evolution in non-equilibrium cases, including global, local and certain inhomogeneous quantum quenches. I.e. a conformal interface suppresses the time evolution of entanglement entropy by effectively replacing the central charge c with , where is exactly the same as that in the ground state case. We confirm this conclusion by a numerical study on a critical fermion chain. Furthermore, based on the quasi-particle picture, we conjecture that this conclusion holds for an arbitrary quantum quench in CFTs, as long as the initial state can be described by a regularized conformal boundary state.

Quality end-of-life care: A global perspective

PubMed Central

Singer, Peter A; Bowman, Kerry W

2002-01-01

Background Quality end-of-life care has emerged as an important concept in industrialized countries. Discussion We argue quality end-of-life care should be seen as a global public health and health systems problem. It is a global problem because 85 % of the 56 million deaths worldwide that occur annually are in developing countries. It is a public health problem because of the number of people it affects, directly and indirectly, in terms of the well being of loved ones, and the large-scale, population based nature of some possible interventions. It is a health systems problem because one of its main features is the need for better information on quality end-of-life care. We examine the context of end-of-life care, including the epidemiology of death and cross-cultural considerations. Although there are examples of success, we could not identify systematic data on capacity for delivering quality end-of-life care in developing countries. We also address a possible objection to improving end-of-life care in developing countries; many deaths are preventable and reduction of avoidable deaths should be the focus of attention. Conclusions We make three recommendations: (1) reinforce the recasting of quality end-of-life care as a global public health and health systems problem; (2) strengthen capacity to deliver quality end-of-life care; and (3) develop improved strategies to acquire information about the quality of end-of-life care. PMID:12139768

Are Educational Governance Reforms in a Post-Conflict Society Conforming to Global Standards? Examining the Application of Education Convergence Theory in an Internationally Supervised and Politicized Context

ERIC Educational Resources Information Center

Komatsu, Taro

2016-01-01

This article examines whether and to what extent educational reforms in a post-conflict society conform to "global (regional) standards," and explores the meaning of inconsistencies observed in the process of global reform transfer. Among the nations of the world, nowhere is the influence of external forces on educational reforms more…

Cyclo-biphenalenyl biradicaloid molecular materials: conformation, tautomerization, magnetism, and thermochromism

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

Huang, Jingsong; Sumpter, Bobby G; Meunier, Vincent

2011-01-01

Phenalenyl and its derivatives have recently attracted a great deal of interest as a result of a 2-electron multicenter (2e/mc) covalent pi-pi bonding between two pi-stacked phenalenyl units. The 2e/mc bonded pi-dimers are close in energy to the sigma-dimers of phenalenyl and therefore fickle properties may emerge from bond fluctuation, yielding smart pi-functional materials. Here we examine the valence tautomerization of two cyclo-biphenalenyl biradicaloid molecular materials with chair- and boat-conformations by spin-restricted (R) and unrestricted (U) DFT using the M06 and B3LYP functionals. We found that the chair-conformation involves a 2e/4c pi-pi bonded structure while the boat-conformation involves a 2e/12cmore » pi-pi bonded structure on their potential energy surfaces. The global minimum for the chair-conformation is the sigma-bonded structure while it is the pi-pi bonded structure for the boat-conformation. The chair-conformation exhibits a stepwise [3,3]-sigmatropic rearrangement, and calculations predict a negligible paramagnetic susceptibility near room temperature. In comparison, the paramagnetism of the boat-conformation should be observable by SQUID and/or ESR. According to the difference of the global minima of the two conformations and the parameterized UV-Vis calculations, the color of the chair-conformation is expected to become darker while that of the boat-conformation become lighter with increasing temperature.« less

48 CFR 46.315 - Certificate of conformance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Certificate of conformance. 46.315 Section 46.315 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT QUALITY ASSURANCE Contract Clauses 46.315 Certificate of conformance. The contracting officer...

48 CFR 246.504 - Certificate of conformance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Certificate of conformance. 246.504 Section 246.504 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT QUALITY ASSURANCE Acceptance 246.504 Certificate of conformance...

Potential Energy Surface-Based Automatic Deduction of Conformational Transition Networks and Its Application on Quantum Mechanical Landscapes of d-Glucose Conformers.

PubMed

Satoh, Hiroko; Oda, Tomohiro; Nakakoji, Kumiyo; Uno, Takeaki; Tanaka, Hiroaki; Iwata, Satoru; Ohno, Koichi

2016-11-08

This paper describes our approach that is built upon the potential energy surface (PES)-based conformational analysis. This approach automatically deduces a conformational transition network, called a conformational reaction route map (r-map), by using the Scaled Hypersphere Search of the Anharmonic Downward Distortion Following method (SHS-ADDF). The PES-based conformational search has been achieved by using large ADDF, which makes it possible to trace only low transition state (TS) barriers while restraining bond lengths and structures with high free energy. It automatically performs sampling the minima and TS structures by simply taking into account the mathematical feature of PES without requiring any a priori specification of variable internal coordinates. An obtained r-map is composed of equilibrium (EQ) conformers connected by reaction routes via TS conformers, where all of the reaction routes are already confirmed during the process of the deduction using the intrinsic reaction coordinate (IRC) method. The postcalculation analysis of the deduced r-map is interactively carried out using the RMapViewer software we have developed. This paper presents computational details of the PES-based conformational analysis and its application to d-glucose. The calculations have been performed for an isolated glucose molecule in the gas phase at the RHF/6-31G level. The obtained conformational r-map for α-d-glucose is composed of 201 EQ and 435 TS conformers and that for β-d-glucose is composed of 202 EQ and 371 TS conformers. For the postcalculation analysis of the conformational r-maps by using the RMapViewer software program we have found multiple minimum energy paths (MEPs) between global minima of 1 C 4 and 4 C 1 chair conformations. The analysis using RMapViewer allows us to confirm the thermodynamic and kinetic predominance of 4 C 1 conformations; that is, the potential energy of the global minimum of 4 C 1 is lower than that of 1 C 4 (thermodynamic predominance

Infectious Disinfection: "Exploring Global Water Quality"

ERIC Educational Resources Information Center

Mahaya, Evans; Tippins, Deborah J.; Mueller, Michael P.; Thomson, Norman

2009-01-01

Learning about the water situation in other regions of the world and the devastating effects of floods on drinking water helps students study science while learning about global water quality. This article provides science activities focused on developing cultural awareness and understanding how local water resources are integrally linked to the…

Conformal Nets II: Conformal Blocks

NASA Astrophysics Data System (ADS)

Bartels, Arthur; Douglas, Christopher L.; Henriques, André

2017-08-01

Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

Global sleep quality as a moderator of alcohol consumption and consequences in college students.

PubMed

Kenney, Shannon R; LaBrie, Joseph W; Hummer, Justin F; Pham, Andy T

2012-04-01

The authors examined the relationship between global sleep quality and alcohol risk, including the extent to which global sleep quality moderated the relationship between alcohol use and drinking-related consequences. Global sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) and alcohol-related consequences were assessed using the Rutgers Alcohol Problem Index (RAPI). The sample consisted of 261 college students (61.3% female, 58.2% Caucasian) who completed online surveys. Using a four-step hierarchical multiple regression model, global sleep quality was found to predict alcohol consequences, over and above assessed covariates (demographics and weekly drinking). Further, global sleep quality emerged as a strong moderator in the drinking-consequences relationship such that among heavier drinkers, those with poorer global sleep quality experienced significantly greater alcohol-related harm. Campus health education and alcohol interventions may be adapted to address the importance of maintaining a healthy lifestyle, both in terms of healthful sleeping and drinking behaviors, which appear to play a strong synergistic role in alcohol-related risk. Copyright © 2012 Elsevier Ltd. All rights reserved.

Benchmarking Commercial Conformer Ensemble Generators.

PubMed

Friedrich, Nils-Ole; de Bruyn Kops, Christina; Flachsenberg, Florian; Sommer, Kai; Rarey, Matthias; Kirchmair, Johannes

2017-11-27

We assess and compare the performance of eight commercial conformer ensemble generators (ConfGen, ConfGenX, cxcalc, iCon, MOE LowModeMD, MOE Stochastic, MOE Conformation Import, and OMEGA) and one leading free algorithm, the distance geometry algorithm implemented in RDKit. The comparative study is based on a new version of the Platinum Diverse Dataset, a high-quality benchmarking dataset of 2859 protein-bound ligand conformations extracted from the PDB. Differences in the performance of commercial algorithms are much smaller than those observed for free algorithms in our previous study (J. Chem. Inf. 2017, 57, 529-539). For commercial algorithms, the median minimum root-mean-square deviations measured between protein-bound ligand conformations and ensembles of a maximum of 250 conformers are between 0.46 and 0.61 Å. Commercial conformer ensemble generators are characterized by their high robustness, with at least 99% of all input molecules successfully processed and few or even no substantial geometrical errors detectable in their output conformations. The RDKit distance geometry algorithm (with minimization enabled) appears to be a good free alternative since its performance is comparable to that of the midranked commercial algorithms. Based on a statistical analysis, we elaborate on which algorithms to use and how to parametrize them for best performance in different application scenarios.

Rigidity in vacuum under conformal symmetry

NASA Astrophysics Data System (ADS)

Galloway, Gregory J.; Vega, Carlos

2018-04-01

Motivated in part by Eardley et al. (Commun Math Phys 106(1):137-158, 1986), in this note we obtain a rigidity result for globally hyperbolic vacuum spacetimes in arbitrary dimension that admit a timelike conformal Killing vector field. Specifically, we show that if M is a Ricci flat, timelike geodesically complete spacetime with compact Cauchy surfaces that admits a timelike conformal Killing field X, then M must split as a metric product, and X must be Killing. This gives a partial proof of the Bartnik splitting conjecture in the vacuum setting.

Prescribed curvature tensor in locally conformally flat manifolds

NASA Astrophysics Data System (ADS)

Pina, Romildo; Pieterzack, Mauricio

2018-01-01

A global existence theorem for the prescribed curvature tensor problem in locally conformally flat manifolds is proved for a special class of tensors R. Necessary and sufficient conditions for the existence of a metric g ¯ , conformal to Euclidean g, are determined such that R ¯ = R, where R ¯ is the Riemannian curvature tensor of the metric g ¯ . The solution to this problem is given explicitly for special cases of the tensor R, including the case where the metric g ¯ is complete on Rn. Similar problems are considered for locally conformally flat manifolds.

Global quality imaging: improvement actions.

PubMed

Lau, Lawrence S; Pérez, Maria R; Applegate, Kimberly E; Rehani, Madan M; Ringertz, Hans G; George, Robert

2011-05-01

Workforce shortage, workload increase, workplace changes, and budget challenges are emerging issues around the world, which could place quality imaging at risk. It is important for imaging stakeholders to collaborate, ensure patient safety, improve the quality of care, and address these issues. There is no single panacea. A range of improvement measures, strategies, and actions are required. Examples of improvement actions supporting the 3 quality measures are described under 5 strategies: conducting research, promoting awareness, providing education and training, strengthening infrastructure, and implementing policies. The challenge is to develop long-term, cost-effective, system-based improvement actions that will bring better outcomes and underpin a sustainable future for quality imaging. In an imaging practice, these actions will result in selecting the right procedure (justification), using the right dose (optimization), and preventing errors along the patient journey. To realize this vision and implement these improvement actions, a range of expertise and adequate resources are required. Stakeholders should collaborate and work together. In today's globalized environment, collaboration is strength and provides synergy to achieve better outcomes and greater success. Copyright © 2011 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Conformity and statistical tolerancing

NASA Astrophysics Data System (ADS)

Leblond, Laurent; Pillet, Maurice

2018-02-01

Statistical tolerancing was first proposed by Shewhart (Economic Control of Quality of Manufactured Product, (1931) reprinted 1980 by ASQC), in spite of this long history, its use remains moderate. One of the probable reasons for this low utilization is undoubtedly the difficulty for designers to anticipate the risks of this approach. The arithmetic tolerance (worst case) allows a simple interpretation: conformity is defined by the presence of the characteristic in an interval. Statistical tolerancing is more complex in its definition. An interval is not sufficient to define the conformance. To justify the statistical tolerancing formula used by designers, a tolerance interval should be interpreted as the interval where most of the parts produced should probably be located. This tolerance is justified by considering a conformity criterion of the parts guaranteeing low offsets on the latter characteristics. Unlike traditional arithmetic tolerancing, statistical tolerancing requires a sustained exchange of information between design and manufacture to be used safely. This paper proposes a formal definition of the conformity, which we apply successively to the quadratic and arithmetic tolerancing. We introduce a concept of concavity, which helps us to demonstrate the link between tolerancing approach and conformity. We use this concept to demonstrate the various acceptable propositions of statistical tolerancing (in the space decentring, dispersion).

Global quality imaging: emerging issues.

PubMed

Lau, Lawrence S; Pérez, Maria R; Applegate, Kimberly E; Rehani, Madan M; Ringertz, Hans G; George, Robert

2011-07-01

Quality imaging may be described as "a timely access to and delivery of integrated and appropriate procedures, in a safe and responsive practice, and a prompt delivery of an accurately interpreted report by capable personnel in an efficient, effective, and sustainable manner." For this article, radiation safety is considered as one of the key quality elements. The stakeholders are the drivers of quality imaging. These include those that directly provide or use imaging procedures and others indirectly supporting the system. Imaging is indispensable in health care, and its use has greatly expanded worldwide. Globalization, consumer sophistication, communication and technological advances, corporatization, rationalization, service outsourcing, teleradiology, workflow modularization, and commoditization are reshaping practice. This article defines the emerging issues; an earlier article in the May 2011 issue described possible improvement actions. The issues that could threaten the quality use of imaging for all countries include workforce shortage; increased utilization, population radiation exposure, and cost; practice changes; and efficiency drive and budget constraints. In response to these issues, a range of quality improvement measures, strategies, and actions are used to maximize the benefits and minimize the risks. The 3 measures are procedure justification, optimization of image quality and radiation protection, and error prevention. The development and successful implementation of such improvement actions require leadership, collaboration, and the active participation of all stakeholders to achieve the best outcomes that we all advocate. Copyright © 2011 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Global Measurement of the Quality of Education: A Help to Developing Countries?

ERIC Educational Resources Information Center

Vedder, Paul

1994-01-01

Addresses the involvement of international interest groups in defining and determining educational quality in developing countries, suggesting that global measures of quality damage the educational systems of developing countries by creating feelings of isolation and inferiority. Suggests alternative measures which meet global standards and may be…

Conformity Adequacy Review: Region 5

EPA Pesticide Factsheets

Resources are for air quality and transportation government and community leaders. Information on the conformity SIP adequacy/inadequacy of state implementation plans (SIPs) in EPA Region 5 (IL, IN, MI, OH, WI) is provided here.

Strategies for ensuring global consistency/comparability of water-quality data

USGS Publications Warehouse

Klein, J.M.

1999-01-01

In the past 20 years the water quality of the United States has improved remarkably-the waters are safer for drinking, swimming, and fishing. However, despite many accomplishments, it is still difficult to answer such basic questions as: 'How clean is the water?' and 'How is it changing over time?' These same questions exist on a global scale as well. In order to focus water-data issues in the United States, a national Intergovernmental Task Force on Monitoring Water Quality (ITFM) was initiated for public and private organizations, whereby key elements involved in data collection, analysis, storage, and management could be made consistent and comparable. The ITFM recommended and its members are implementing a nationwide strategy to improve water-quality monitoring, assessment, and reporting activities. The intent of this paper is to suggest that a voluntary effort be initiated to ensure the comparability and utility of hydrological data on a global basis. Consistent, long-term data sets that are comparable are necessary in order to formulate ideas regarding regional and global trends in water quantity and quality. The author recommends that a voluntary effort similar to the ITFM effort be utilized. The strategy proposed would involve voluntary representation from countries and international organizations (e.g. World Health Organization) involved in drinking-water assessments and/or ambient water-quality monitoring. Voluntary partnerships such as this will improve curability to reduce health risks and achieve a better return on public and private investments in monitoring, environmental protection, and natural resource management, and result in a collaborative process that will save millions of dollars.In this work it is suggested that a voluntary effort be initiated to ensure the comparability and utility of hydrological data on a global basis. The strategy proposed would involve voluntary representation from countries and international organizations involved in

Conformal and Nearly Conformal Theories at Large N

NASA Astrophysics Data System (ADS)

Tarnoplskiy, Grigory M.

In this thesis we present new results in conformal and nearly conformal field theories in various dimensions. In chapter two, we study different properties of the conformal Quantum Electrodynamics (QED) in continuous dimension d. At first we study conformal QED using large Nf methods, where Nf is the number of massless fermions. We compute its sphere free energy as a function of d, ignoring the terms of order 1/Nf and higher. For finite Nf we use the epsilon-expansion. Next we use a large Nf diagrammatic approach to calculate the leading corrections to CT, the coefficient of the two-point function of the stress-energy tensor, and CJ, the coefficient of the two-point function of the global symmetry current. We present explicit formulae as a function of d and check them versus the expectations in 2 and 4 - epsilon dimensions. In chapter three, we discuss vacuum stability in 1 + 1 dimensional conformal field theories with external background fields. We show that the vacuum decay rate is given by a non-local two-form. This two-form is a boundary term that must be added to the effective in/out Lagrangian. The two-form is expressed in terms of a Riemann-Hilbert decomposition for background gauge fields, and is given by its novel "functional'' version in the gravitational case. In chapter four, we explore Tensor models. Such models possess the large N limit dominated by the melon diagrams. The quantum mechanics of a real anti-commuting rank-3 tensor has a large N limit similar to the Sachdev-Ye-Kitaev (SYK) model. We also discuss the quantum mechanics of a complex 3-index anti-commuting tensor and argue that it is equivalent in the large N limit to a version of SYK model with complex fermions. Finally, we discuss models of a commuting tensor in dimension d. We study the spectrum of the large N quantum field theory of bosonic rank-3 tensors using the Schwinger-Dyson equations. We compare some of these results with the 4 - epsilon expansion, finding perfect agreement. We

The Functional Quality of Soluble Recombinant Polypeptides Produced in Escherichia coli Is Defined by a Wide Conformational Spectrum▿

PubMed Central

Martínez-Alonso, Mónica; González-Montalbán, Nuria; García-Fruitós, Elena; Villaverde, Antonio

2008-01-01

We have observed that a soluble recombinant green fluorescent protein produced in Escherichia coli occurs in a wide conformational spectrum. This results in differently fluorescent protein fractions in which morphologically diverse soluble aggregates abound. Therefore, the functional quality of soluble versions of aggregation-prone recombinant proteins is defined statistically rather than by the prevalence of a canonical native structure. PMID:18836021

"Power quality system," a new system of quality management for globalization: towards innovation and competitive advantages.

PubMed

Abdul-Rahman, H; Berawi, M A

Knowledge Management (KM) addresses the critical issues of organizational adoption, survival and competence in the face of an increasingly changing environment. KM embodies organizational processes that seek a synergistic combination of the data and information processing capabilities of information and communication technologies (ICT), and the creative and innovative capacity of human beings to improve ICT In that role, knowledge management will improve quality management and avoid or minimize losses and weakness that usually come from poor performance as well as increase the competitive level of the company and its ability to survive in the global marketplace. To achieve quality, all parties including the clients, company consultants, contractors, entrepreneurs, suppliers, and the governing bodies (i.e., all involved stake-holders) need to collaborate and commit to achieving quality. The design based organizations in major business and construction companies have to be quality driven to support healthy growth in today's competitive market. In the march towards vision 2020 and globalization (i.e., the one world community) of many companies, their design based organizations need to have superior quality management and knowledge management to anticipate changes. The implementation of a quality system such as the ISO 9000 Standards, Total Quality Management, or Quality Function Deployment (QFD) focuses the company's resources towards achieving faster and better results in the global market with less cost. To anticipate the needs of the marketplace and clients as the world and technology change, a new system, which we call Power Quality System (PQS), has been designed. PQS is a combination of information and communication technologies (ICT) and the creative and innovative capacity of human beings to meet the challenges of the new world business and to develop high quality products.

Retrospective evaluation of dosimetric quality for prostate carcinomas treated with 3D conformal, intensity modulated and volumetric modulated arc radiotherapy

PubMed Central

Crowe, Scott B; Kairn, Tanya; Middlebrook, Nigel; Hill, Brendan; Christie, David R H; Knight, Richard T; Kenny, John; Langton, Christian M; Trapp, Jamie V

2013-01-01

Introduction This study examines and compares the dosimetric quality of radiotherapy treatment plans for prostate carcinoma across a cohort of 163 patients treated across five centres: 83 treated with three-dimensional conformal radiotherapy (3DCRT), 33 treated with intensity modulated radiotherapy (IMRT) and 47 treated with volumetric modulated arc therapy (VMAT). Methods Treatment plan quality was evaluated in terms of target dose homogeneity and organs at risk (OAR), through the use of a set of dose metrics. These included the mean, maximum and minimum doses; the homogeneity and conformity indices for the target volumes; and a selection of dose coverage values that were relevant to each OAR. Statistical significance was evaluated using two-tailed Welch's T-tests. The Monte Carlo DICOM ToolKit software was adapted to permit the evaluation of dose metrics from DICOM data exported from a commercial radiotherapy treatment planning system. Results The 3DCRT treatment plans offered greater planning target volume dose homogeneity than the other two treatment modalities. The IMRT and VMAT plans offered greater dose reduction in the OAR: with increased compliance with recommended OAR dose constraints, compared to conventional 3DCRT treatments. When compared to each other, IMRT and VMAT did not provide significantly different treatment plan quality for like-sized tumour volumes. Conclusions This study indicates that IMRT and VMAT have provided similar dosimetric quality, which is superior to the dosimetric quality achieved with 3DCRT. PMID:26229621

The 'Alternative Quality Contract,' based on a global budget, lowered medical spending and improved quality.

PubMed

Song, Zirui; Safran, Dana Gelb; Landon, Bruce E; Landrum, Mary Beth; He, Yulei; Mechanic, Robert E; Day, Matthew P; Chernew, Michael E

2012-08-01

Seven provider organizations in Massachusetts entered the Blue Cross Blue Shield Alternative Quality Contract in 2009, followed by four more organizations in 2010. This contract, based on a global budget and pay-for-performance for achieving certain quality benchmarks, places providers at risk for excessive spending and rewards them for quality, similar to the new Pioneer Accountable Care Organizations in Medicare. We analyzed changes in spending and quality associated with the Alternative Quality Contract and found that the rate of increase in spending slowed compared to control groups, more so in the second year than in the first. Overall, participation in the contract over two years led to savings of 2.8 percent (1.9 percent in year 1 and 3.3 percent in year 2) compared to spending in nonparticipating groups. Savings were accounted for by lower prices achieved through shifting procedures, imaging, and tests to facilities with lower fees, as well as reduced utilization among some groups. Quality of care also improved compared to control organizations, with chronic care management, adult preventive care, and pediatric care within the contracting groups improving more in year 2 than in year 1. These results suggest that global budgets with pay-for-performance can begin to slow underlying growth in medical spending while improving quality of care.

Cyclo-biphenalenyl biradicaloid molecular materials: conformation, rearrangement, magnetism, and thermochromism

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

Huang, Jingsong; Sumpter, Bobby G; Meunier, Vincent

2010-01-01

Cyclo-biphenalenyl biradicaloid molecular materials with chair- and boat-conformations are studied by restricted and broken-symmetry DFT using the M06 family of meta-GGA functionals. The global minima of these molecular materials are magnetically silent due to the sigma-bond connecting the two phenalenyls, while the sigma-bond may undergo low-barrier sigmatropic rearrangements via pi-pi bonded paramagnetic intermediates. The validation of theory is performed for the chair-conformation by comparing the sigma-bonded structures and the rearrangement barriers with experimental data. The boat-conformation is then studied using the validated functional. The electronic spectra of both chair- and boat-conformations are calculated and their applications in thermochromism are discussed.

Conformational switching upon phosphorylation: a predictive framework based on energy landscape principles.

PubMed

Lätzer, Joachim; Shen, Tongye; Wolynes, Peter G

2008-02-19

We investigate how post-translational phosphorylation modifies the global conformation of a protein by changing its free energy landscape using two test proteins, cystatin and NtrC. We first examine the changes in a free energy landscape caused by phosphorylation using a model containing information about both structural forms. For cystatin the free energy cost is fairly large indicating a low probability of sampling the phosphorylated conformation in a perfectly funneled landscape. The predicted barrier for NtrC conformational transition is several times larger than the barrier for cystatin, indicating that the switch protein NtrC most probably follows a partial unfolding mechanism to move from one basin to the other. Principal component analysis and linear response theory show how the naturally occurring conformational changes in unmodified proteins are captured and stabilized by the change of interaction potential. We also develop a partially guided structure prediction Hamiltonian which is capable of predicting the global structure of a phosphorylated protein using only knowledge of the structure of the unphosphorylated protein or vice versa. This algorithm makes use of a generic transferable long-range residue contact potential along with details of structure short range in sequence. By comparing the results obtained with this guided transferable potential to those from the native-only, perfectly funneled Hamiltonians, we show that the transferable Hamiltonian correctly captures the nature of the global conformational changes induced by phosphorylation and can sample substantially correct structures for the modified protein with high probability.

An Introduction to School Leadership for Quality Global Learning in Initial Teacher Education

ERIC Educational Resources Information Center

Serf, Jeff; Sinclair, Scott; Wooldridge, Julie

2009-01-01

This article introduces a project, School Leadership for Quality Global Learning, which focuses on the relationship between leadership at different levels within educational institutions and quality global learning. The article outlines briefly the changing societal context within which education is operating currently before exploring key ideas,…

Renewing focus on family planning service quality globally.

PubMed

Hancock, Nancy L; Stuart, Gretchen S; Tang, Jennifer H; Chibwesha, Carla J; Stringer, Jeffrey S A; Chi, Benjamin H

2016-01-01

Reducing the global unmet need for contraception is currently a priority for many governments, multi-lateral initiatives, non-governmental organizations, and donors. Evidence strongly suggests that the provision of quality family planning services can increase uptake, prevalence, and continuation of contraception. While an accepted framework to define the components of family planning service quality exists, translating this framework into assessment tools that are accessible, easily utilized, and valid for service providers has remained a challenge. We propose new approaches to improve the standardization and accessibility of family planning service quality assessment tools to simplify family planning service quality evaluation. With easier approaches to program evaluation, quality improvements can be performed more swiftly to help increase uptake and continuation of contraception to improve the health of women and their families.

Satellite global monitoring of environmental quality

NASA Technical Reports Server (NTRS)

Schiffer, R. A.

1975-01-01

The missions of two NASA satellites for the monitoring of environmental quality are described: Nimbus G, the Air Pollution and Oceanographic Observing Satellite, and the Applications Explorer Mission (AEM) satellite to be used in the Stratospheric Aerosol and Gas Experiment (SAGE). The scientific payload of Nimbus G is described in detail with a discussion of limb infrared monitoring of the stratosphere, the stratospheric and mesospheric sounder, stratospheric aerosol measurement, the solar and backscatter UV spectrometer for ozone mapping, the earth radiation budget experiment, the scanning multichannel microwave radiometer, the coastal zone color scanner and the temperature-humidity infrared radiometer. A brief description is given of the SAGE program and future NASA plans relating to the global monitoring of environmental quality are outlined.

Hierarchical Biomolecular Dynamics: Picosecond Hydrogen Bonding Regulates Microsecond Conformational Transitions.

PubMed

Buchenberg, Sebastian; Schaudinnus, Norbert; Stock, Gerhard

2015-03-10

Biomolecules exhibit structural dynamics on a number of time scales, including picosecond (ps) motions of a few atoms, nanosecond (ns) local conformational transitions, and microsecond (μs) global conformational rearrangements. Despite this substantial separation of time scales, fast and slow degrees of freedom appear to be coupled in a nonlinear manner; for example, there is theoretical and experimental evidence that fast structural fluctuations are required for slow functional motion to happen. To elucidate a microscopic mechanism of this multiscale behavior, Aib peptide is adopted as a simple model system. Combining extensive molecular dynamics simulations with principal component analysis techniques, a hierarchy of (at least) three tiers of the molecule's free energy landscape is discovered. They correspond to chiral left- to right-handed transitions of the entire peptide that happen on a μs time scale, conformational transitions of individual residues that take about 1 ns, and the opening and closing of structure-stabilizing hydrogen bonds that occur within tens of ps and are triggered by sub-ps structural fluctuations. Providing a simple mechanism of hierarchical dynamics, fast hydrogen bond dynamics is found to be a prerequisite for the ns local conformational transitions, which in turn are a prerequisite for the slow global conformational rearrangement of the peptide. As a consequence of the hierarchical coupling, the various processes exhibit a similar temperature behavior which may be interpreted as a dynamic transition.

Conformational Dynamics of Thermus aquaticus DNA Polymerase I during Catalysis

PubMed Central

Suo, Zucai

2014-01-01

Despite the fact that DNA polymerases have been investigated for many years and are commonly used as tools in a number of molecular biology assays, many details of the kinetic mechanism they use to catalyze DNA synthesis remain unclear. Structural and kinetic studies have characterized a rapid, pre-catalytic open-to-close conformational change of the Finger domain during nucleotide binding for many DNA polymerases including Thermus aquaticus DNA polymerase I (Taq Pol), a thermostable enzyme commonly used for DNA amplification in PCR. However, little has been done to characterize the motions of other structural domains of Taq Pol or any other DNA polymerase during catalysis. Here, we used stopped-flow Förster resonance energy transfer (FRET) to investigate the conformational dynamics of all five structural domains of the full-length Taq Pol relative to the DNA substrate during nucleotide binding and incorporation. Our study provides evidence for a rapid conformational change step induced by dNTP binding and a subsequent global conformational transition involving all domains of Taq Pol during catalysis. Additionally, our study shows that the rate of the global transition was greatly increased with the truncated form of Taq Pol lacking the N-terminal domain. Finally, we utilized a mutant of Taq Pol containing a de novo disulfide bond to demonstrate that limiting protein conformational flexibility greatly reduced the polymerization activity of Taq Pol. PMID:24931550

The Impact of Globalization on a Country's Quality of Life: Toward an Integrated Model

ERIC Educational Resources Information Center

Sirgy, M. Joseph; Lee, Dong-Jin; Miller, Chad; Littlefield, James E.

2004-01-01

The purpose of the paper is to develop a set of theoretical propositions to explain the impact of globalization on a country's quality of life (QOL). In this paper, we describe how globalization impacts the quality of life of residents of a country by first articulating the globalization construct (in terms of inflows and outflows of goods,…

AIR QUALITY AND GLOBAL CLIMATE CHANGE (PHASE 1)

EPA Science Inventory

Predicted changes in the global climate over the coming decades could alter weather patterns and, thus, impact land use, source emissions, and tropospheric air quality. The United States has a series of standards for criteria air pollutants and other air pollutants in place to s...

Globalization and the Preparation of Quality Teachers: Rethinking Knowledge Domains for Teaching

ERIC Educational Resources Information Center

Goodwin, A. Lin

2010-01-01

Preparing quality teachers has become a global concern as all nations strive for excellence at all levels. Yet, there is little consensus around what constitutes quality and how quality teachers might best be attained. This article takes up the issue of quality teacher preparation by exploring several pivotal questions: What might quality teaching…

Air Quality Conformity Determination Of the Constrained Long Range Plan And The FY99-2004 Transportation Improvement Program For The Washington Metropolitan Region

DOT National Transportation Integrated Search

1998-07-15

This report documents the assessment of the Constrained Long Range Plan (CLRP) and the FY99-2004 Transportation Improvement Program (TIP) with respect to air quality conformity requirements under the 1990 Clean Air Act Amendments. The assessment used...

Picosecond to nanosecond dynamics provide a source of conformational entropy for protein folding.

PubMed

Stadler, Andreas M; Demmel, Franz; Ollivier, Jacques; Seydel, Tilo

2016-08-03

Myoglobin can be trapped in fully folded structures, partially folded molten globules, and unfolded states under stable equilibrium conditions. Here, we report an experimental study on the conformational dynamics of different folded conformational states of apo- and holomyoglobin in solution. Global protein diffusion and internal molecular motions were probed by neutron time-of-flight and neutron backscattering spectroscopy on the picosecond and nanosecond time scales. Global protein diffusion was found to depend on the α-helical content of the protein suggesting that charges on the macromolecule increase the short-time diffusion of protein. With regard to the molten globules, a gel-like phase due to protein entanglement and interactions with neighbouring macromolecules was visible due to a reduction of the global diffusion coefficients on the nanosecond time scale. Diffusion coefficients, residence and relaxation times of internal protein dynamics and root mean square displacements of localised internal motions were determined for the investigated structural states. The difference in conformational entropy ΔSconf of the protein between the unfolded and the partially or fully folded conformations was extracted from the measured root mean square displacements. Using thermodynamic parameters from the literature and the experimentally determined ΔSconf values we could identify the entropic contribution of the hydration shell ΔShydr of the different folded states. Our results point out the relevance of conformational entropy of the protein and the hydration shell for stability and folding of myoglobin.

Cyclo-biphenalenyl Biradicaloid Molecular Materials: Conformation, Tautomerization, Magnetism, and Thermochromism

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

Huang, Jingsong; Meunier, Vincent; Tian, Yong-Hui

2010-01-01

Phenalenyl and its derivatives have recently attracted a great deal of interest as a result of a two-electron multicenter (2e/mc) - bonding between two -stacked phenalenyl units. The 2e/mc bonded -dimers are close in energy to the -dimers of phenalenyl and therefore fickle properties may emerge from bond fluctuation, yielding smart -functional materials. Here, we examine the valence tautomerization of two cyclo-biphenalenyl biradicaloid molecular materials with chair and boat conformations by spin-restricted (R) and unrestricted (U) DFT using the M06 and B3LYP functionals. We found that the chair conformation involves a 2e/4c - bonded structure, whereas the boat conformation involvesmore » a 2e/12c - bonded structure on their potential energy surfaces. The global minimum for the chair conformation is the -bonded structure, whereas it is the - bonded structure for the boat conformation. The chair conformation exhibits a stepwise [3,3]-sigmatropic rearrangement, and calculations predict a negligible paramagnetic susceptibility near room temperature. In comparison, the paramagnetism of the boat conformation should be observable by SQUID and ESR. According to the energy differences of the respective - and -dimers of the two conformations and the UV-vis calculations, the color of the chair conformation is expected to become darker, whereas that of the boat conformation should become lighter with increasing temperature.« less

Qualities Required from Engineers of the Global Times

NASA Astrophysics Data System (ADS)

Senuma, Takehide

In this paper, the qualities and characteristics required from an engineer who works globally are discussed based on my own experience of a joint research project with a European company. The most important qualities and characteristics are integrity, one‧s own initiative, basic and expert knowledge, creativity, communicative skills and broad world view. Having initiative seems to be especially significant but is a weak point of young engineers in Japan at present. Ways to develop students‧ initiative are discussed in detail from a view point of the engineering education.

Project-Level Conformity and Hot-Spot Analyses

EPA Pesticide Factsheets

This page contains policy guidance issued by EPA and/or the U.S. Department of Transportation to assist state and local transportation and air quality agencies implement the transportation conformity program.

Recent progress in irrational conformal field theory

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

Halpern, M.B.

1993-09-01

In this talk, I will review the foundations of irrational conformal field theory (ICFT), which includes rational conformal field theory as a small subspace. Highlights of the review include the Virasoro master equation, the Ward identities for the correlators of ICFT and solutions of the Ward identities. In particular, I will discuss the solutions for the correlators of the g/h coset construction and the correlators of the affine-Sugawara nests on g {contains} h{sub 1} {contains} {hor_ellipsis} {contains} h{sub n}. Finally, I will discuss the recent global solution for the correlators of all the ICFT`s in the master equation.

A Global Observatory of Lake Water Quality

NASA Astrophysics Data System (ADS)

Tyler, Andrew N.; Hunter, Peter D.; Spyrakos, Evangelos; Neil, Claire; Simis, Stephen; Groom, Steve; Merchant, Chris J.; Miller, Claire A.; O'Donnell, Ruth; Scott, E. Marian

2017-04-01

Our planet's surface waters are a fundamental resource encompassing a broad range of ecosystems that are core to global biogeochemical cycling, biodiversity and food and energy security. Despite this, these same waters are impacted by multiple natural and anthropogenic pressures and drivers of environmental change. The complex interaction between physical, chemical and biological processes in surface waters poses significant challenges for in situ monitoring and assessment and this often limits our ability to adequately capture the dynamics of aquatic systems and our understanding of their status, functioning and response to pressures. Recent developments in the availability of satellite platforms for Earth observation (including ESA's Copernicus Programme) offers an unprecedented opportunity to deliver measures of water quality at a global scale. The UK NERC-funded GloboLakes project is a five-year research programme investigating the state of lakes and their response to climatic and other environmental drivers of change through the realization of a near-real time satellite based observatory (Sentinel-3) and archive data processing (MERIS, SeaWiFS) to produce a 20-year time-series of observed ecological parameters and lake temperature for more than 1000 lakes globally. However, the diverse and complex optical properties of lakes mean that algorithm performance often varies markedly between different water types. The GloboLakes project is overcoming this challenge by developing a processing chain whereby algorithms are dynamically selected according to the optical properties of the lake under observation. The development and validation of the GloboLakes processing chain has been supported by access to extensive in situ data from more than thirty partners around the world that are now held in the LIMNADES community-owned data repository developed under the auspices of GloboLakes. This approach has resulted in a step-change in our ability to produce regional and

New potentials for conformal mechanics

NASA Astrophysics Data System (ADS)

Papadopoulos, G.

2013-04-01

We find under some mild assumptions that the most general potential of one-dimensional conformal systems with time-independent couplings is expressed as V = V0 + V1, where V0 is a homogeneous function with respect to a homothetic motion in configuration space and V1 is determined from an equation with source a homothetic potential. Such systems admit at most an SL(2,{R}) conformal symmetry which, depending on the couplings, is embedded in {Diff}({R}) in three different ways. In one case, SL(2,{R}) is also embedded in Diff(S1). Examples of such models include those with potential V = αx2 + βx-2 for arbitrary couplings α and β, the Calogero models with harmonic oscillator couplings and nonlinear models with suitable metrics and potentials. In addition, we give the conditions on the couplings for a class of gauge theories to admit a SL(2,{R}) conformal symmetry. We present examples of such systems with general gauge groups and global symmetries that include the isometries of AdS2 × S3 and AdS2 × S3 × S3 which arise as backgrounds in AdS2/CFT1.

Relative electronic and free energies of octane's unique conformations

NASA Astrophysics Data System (ADS)

Kirschner, Karl N.; Heiden, Wolfgang; Reith, Dirk

2017-06-01

This study reports the geometries and electronic energies of n-octane's unique conformations using perturbation methods that best mimic CCSD(T) results. In total, the fully optimised minima of n-butane (2 conformations), n-pentane (4 conformations), n-hexane (12 conformations) and n-octane (96 conformations) were investigated at several different theory levels and basis sets. We find that DF-MP2.5/aug-cc-pVTZ is in very good agreement with the more expensive CCSD(T) results. At this level, we can clearly confirm the 96 stable minima which were previously found using a reparameterised density functional theory (DFT). Excellent agreement was found between their DFT results and our DF-MP2.5 perturbation results. Subsequent Gibbs free energy calculations, using scaled MP2/aug-cc-pVTZ zero-point vibrational energy and frequencies, indicate a significant temperature dependency of the relative energies, with a change in the predicted global minimum. The results of this work will be important for future computational investigations of fuel-related octane reactions and for optimisation of molecular force fields (e.g. lipids).

The detection of conformational disorder by thermal analysis

NASA Astrophysics Data System (ADS)

Wunderlich, B.

Conformational disorder in crystals is found in many molecules that possess a plurality of conformational isomers. Typical examples are linear macromolecules such as polyethylene, polytetrafluoroethylene and trans-1,4-polybutadiene; and small molecules such as paraffins, cycloparaffins, soaps, lipids and many liquid-crystal forming molecules. Conformational motion is often coupled with the cooperative creation of disorder. In this case a heat and entropy of transition is observed by thermal analysis. Levels of transition entropies can be estimated, assuming most of the disorder can be traced to conformational isomerism. In case there is conformational disorder frozen-in at low temperature, thermal analysis can be used to find the glass transition of a condis crystal. An Advanced Thermal Analysis System has been developed, and will be described that permits a detailed interpretation of the thermal analysis traces. It rests with the establishment of high quality heat capacity for the rigid solid state (vibration only) and the mobile liquid state (vibrations and large amplitude cooperative motion).

Conformational Analysis of Retinoic Acids: Effects of Steric Interactions on Nonplanar Conjugated Polyenes.

PubMed

Cox, Bryan D; Muccio, Donald D; Hamilton, Tracy P

2013-05-01

Retinoic acids and other vitamin A analogs contain a trimethylcyclohexenyl ring in conjugation with a polyene chain joined at carbon-6 (C6) and carbon-7 (C7). A MP2-SCS/cc-pVDZ// B3LYP/6-31G(d) 2-D potential energy surface was computed for all- trans retinoic acid, which had 6 minima (3 enantiomeric pairs). The global minima were distorted s-gauche enantiomers ( 6-7 = 53°) with half-chair conformations of the ring. Distorted s-gauche enantiomers ( 6-7 = 55°) with inverted half-chair ring conformations were 1.7 kJ/mol above the global minima. The s-trans enantiomers ( 6-7 = 164°) were 11.3 kJ/mol above the global minima. Steric energies were computed by the method of Guo and Karplus to identify key structural elements in retinoic acids which determines their conformation. Small molecule crystal structures in the CCDC database with trimethylcyclohexenyl ring and exocyclic double bonds have ring-chain geometries near to one of the 6 energy minima of retinoic acids, except for retinaldehyde iminium cations.

Rotational Spectroscopy and Conformational Studies of 4-PENTYNENITRILE, 4-PENTENENITRILE, and Glutaronitrile

NASA Astrophysics Data System (ADS)

Hays, Brian M.; Mehta-Hurt, Deepali; Jawad, Khadija M.; Hernandez-Castillo, Alicia O.; Abeysekera, Chamara; Zhang, Di; Zwier, Timothy S.

2017-06-01

The pure rotational spectra of 4-pentynenitrile, 4-pentenenitrile, and glutaronitrile were acquired using chirped pulse Fouirer transform microwave spectroscopy. 4-pentynenitrile and 4-pentenenitrile are the recombination products of two resonance stabilized radicals, propargyl + cyanomethyl or allyl + cyanomethyl, respectively, and are thus anticipated to be significant among the more complex nitriles in Titan's atmosphere. Indeed, these partially unsaturated alkyl cyanides have been found in laboratory analogs of tholins and are also expected to have interesting photochemistry. The optimized structures of all conformers below predicted energies of 500 \\wn were calculated for each molecule. Both of the conformers, trans and gauche, for 4-pentynenitrile have been identified and assigned. Five conformers were assigned in 4-pentenenitrile. The eclipsed conformers, with respect to the vinyl group, dominate the spectrum but some population was found in the syn conformers including the syn-gauche conformer, calculated to be 324 \\wn above the global minimum. The glutaronitrile spectrum contained only the two conformers below 500 \\wn, with reduced amount of the gauche trans conformer. The assigned spectra and structural assignments will be presented.

76 FR 55060 - Aquatic Ecosystems, Water Quality, and Global Change: Challenges of Conducting Multi-Stressor...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-06

... ENVIRONMENTAL PROTECTION AGENCY [FRL-9459-7] Aquatic Ecosystems, Water Quality, and Global Change... entitled, Aquatic Ecosystems, Water Quality, and Global Change: Challenges of Conducting Multi- stressor... Environmental Assessment (NCEA) within EPA's Office of Research and Development. This report investigates the...

Quantifying polypeptide conformational space: sensitivity to conformation and ensemble definition.

PubMed

Sullivan, David C; Lim, Carmay

2006-08-24

Quantifying the density of conformations over phase space (the conformational distribution) is needed to model important macromolecular processes such as protein folding. In this work, we quantify the conformational distribution for a simple polypeptide (N-mer polyalanine) using the cumulative distribution function (CDF), which gives the probability that two randomly selected conformations are separated by less than a "conformational" distance and whose inverse gives conformation counts as a function of conformational radius. An important finding is that the conformation counts obtained by the CDF inverse depend critically on the assignment of a conformation's distance span and the ensemble (e.g., unfolded state model): varying ensemble and conformation definition (1 --> 2 A) varies the CDF-based conformation counts for Ala(50) from 10(11) to 10(69). In particular, relatively short molecular dynamics (MD) relaxation of Ala(50)'s random-walk ensemble reduces the number of conformers from 10(55) to 10(14) (using a 1 A root-mean-square-deviation radius conformation definition) pointing to potential disconnections in comparing the results from simplified models of unfolded proteins with those from all-atom MD simulations. Explicit waters are found to roughen the landscape considerably. Under some common conformation definitions, the results herein provide (i) an upper limit to the number of accessible conformations that compose unfolded states of proteins, (ii) the optimal clustering radius/conformation radius for counting conformations for a given energy and solvent model, (iii) a means of comparing various studies, and (iv) an assessment of the applicability of random search in protein folding.

Conformal structure of massless scalar amplitudes beyond tree level

NASA Astrophysics Data System (ADS)

Banerjee, Nabamita; Banerjee, Shamik; Bhatkar, Sayali Atul; Jain, Sachin

2018-04-01

We show that the one-loop on-shell four-point scattering amplitude of massless ϕ 4 scalar field theory in 4D Minkowski space time, when Mellin transformed to the Celestial sphere at infinity, transforms covariantly under the global conformal group (SL(2, ℂ)) on the sphere. The unitarity of the four-point scalar amplitudes is recast into this Mellin basis. We show that the same conformal structure also appears for the two-loop Mellin amplitude. Finally we comment on some universal structure for all loop four-point Mellin amplitudes specific to this theory.

Quality Indicators for Global Benchmarking of Localized Prostate Cancer Management.

PubMed

Sampurno, Fanny; Zheng, Jia; Di Stefano, Lydia; Millar, Jeremy L; Foster, Claire; Fuedea, Ferran; Higano, Celestia; Hulan, Hartwig; Mark, Stephen; Moore, Caroline; Richardson, Alison; Sullivan, Frank; Wenger, Neil S; Wittmann, Daniela; Evans, Sue

2018-03-01

We sought to develop a core set of clinical indicators to enable international benchmarking of localized prostate cancer management using data available in the TrueNTH (True North) Global Registry. An international expert panel completed an online survey and participated in a face to face meeting. Participants included 3 urologists, 3 radiation oncologists, 2 psychologists, 1 medical oncologist, 1 nurse and 1 epidemiologist with prostate cancer expertise from a total of 7 countries. Current guidelines on prostate cancer treatment and potential quality indicators were identified from a literature review. These potential indicators were refined and developed through a modified Delphi process during which each panelist independently and repeatedly rated each indicator based on importance (satisfying the indicator demonstrated a provision of high quality care) and feasibility (the likelihood that data used to construct the indicator could be collected at a population level). The main outcome measure was items with panel agreement indicted by a disagreement index less 1, median importance 8.5 or greater and median feasibility 9 or greater. The expert panel endorsed 33 indicators. Seven of these 33 prostate cancer quality indicators assessed care relating to diagnosis, 7 assessed primary treatment, 1 assessed salvage treatment and 18 assessed health outcomes. We developed a set of quality indicators to measure prostate cancer care using numerous international evidence-based clinical guidelines. These indicators will be pilot tested in the TrueNTH Global Registry. Reports comparing indicator performance will subsequently be distributed to groups at participating sites with the purpose of improving the consistency and quality of prostate cancer management on a global basis. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Implementation of Quality Systems in Nuclear Medicine: Why It Matters. An Outcome Analysis (Quality Management Audits in Nuclear Medicine Part III).

PubMed

Dondi, Maurizio; Paez, Diana; Torres, Leonel; Marengo, Mario; Delaloye, Angelika Bischof; Solanki, Kishor; Van Zyl Ellmann, Annare; Lobato, Enrique Estrada; Miller, Rodolfo Nunez; Giammarile, Francesco; Pascual, Thomas

2018-05-01

The International Atomic Energy Agency (IAEA) developed a comprehensive program-Quality Management Audits in Nuclear Medicine (QUANUM). This program covers all aspects of nuclear medicine practices including, but not limited to, clinical practice, management, operations, and services. The QUANUM program, which includes quality standards detailed in relevant checklists, aims at introducing a culture of comprehensive quality audit processes that are patient oriented, systematic, and outcome based. This paper will focus on the impact of the implementation of QUANUM on daily routine practices in audited centers. Thirty-seven centers, which had been externally audited by experts under IAEA auspices at least 1 year earlier, were invited to run an internal audit using the QUANUM checklists. The external audits also served as training in quality management and the use of QUANUM for the local teams, which were responsible of conducting the internal audits. Twenty-five out of the 37 centers provided their internal audit report, which was compared with the previous external audit. The program requires that auditors score each requirement within the QUANUM checklists on a scale of 0-4, where 0-2 means nonconformance and 3-4 means conformance to international regulations and standards on which QUANUM is based. Our analysis covering both general and clinical areas assessed changes on the conformance status on a binary manner and the level of conformance scores. Statistical analysis was performed using nonparametric statistical tests. The evaluation of the general checklists showed a global improvement on both the status and the levels of conformances (P < 0.01). The evaluation of the requirements by checklist also showed a significant improvement in all, with the exception of Hormones and Tumor marker determinations, where changes were not significant. Of the 25 evaluated institutions, 88% (22 of 25) and 92% (23 of 25) improved their status and levels of conformance

Conformance Testing: Measurement Decision Rules

NASA Technical Reports Server (NTRS)

Mimbs, Scott M.

2010-01-01

The goal of a Quality Management System (QMS) as specified in ISO 9001 and AS9100 is to provide assurance to the customer that end products meet specifications. Measuring devices, often called measuring and test equipment (MTE), are used to provide the evidence of product conformity to specified requirements. Unfortunately, processes that employ MTE can become a weak link to the overall QMS if proper attention is not given to the measurement process design, capability, and implementation. Documented "decision rules" establish the requirements to ensure measurement processes provide the measurement data that supports the needs of the QMS. Measurement data are used to make the decisions that impact all areas of technology. Whether measurements support research, design, production, or maintenance, ensuring the data supports the decision is crucial. Measurement data quality can be critical to the resulting consequences of measurement-based decisions. Historically, most industries required simplistic, one-size-fits-all decision rules for measurements. One-size-fits-all rules in some cases are not rigorous enough to provide adequate measurement results, while in other cases are overly conservative and too costly to implement. Ideally, decision rules should be rigorous enough to match the criticality of the parameter being measured, while being flexible enough to be cost effective. The goal of a decision rule is to ensure that measurement processes provide data with a sufficient level of quality to support the decisions being made - no more, no less. This paper discusses the basic concepts of providing measurement-based evidence that end products meet specifications. Although relevant to all measurement-based conformance tests, the target audience is the MTE end-user, which is anyone using MTE other than calibration service providers. Topics include measurement fundamentals, the associated decision risks, verifying conformance to specifications, and basic measurement

The ‘Alternative Quality Contract’ in Massachusetts, Based on Global Budgets, Lowered Medical Spending and Improved Quality

PubMed Central

Song, Zirui; Safran, Dana Gelb; Landon, Bruce E.; Landrum, Mary Beth; He, Yulei; Mechanic, Robert E.; Day, Matthew P.; Chernew, Michael E.

2012-01-01

Seven provider organizations in Massachusetts entered the Blue Cross Blue Shield Alternative Quality Contract in 2009, followed by four more organizations in 2010. This contract, based on a global budget and pay-for-performance for achieving certain quality benchmarks, places providers at risk for excessive spending and rewards them for quality, similar to the new Pioneer Accountable Care Organizations in Medicare. We analyzed changes in spending and quality associated with the Alternative Quality Contract and found that the rate of increase in spending slowed compared to control groups. Overall, participation in the contract over two years led to a savings of 3.3% (1.9% in year-1, 3.3% in year-2) compared to spending in groups not participating in the contract. The savings were even higher for groups whose previous experience had been only in fee-for-service contracting. Such groups’ quarterly savings over two years averaged 8.2% (6.3% in year-1, 9.9% in year-2). Quality of care also improved within organizations participating in the Alternative Quality Contract compared to control organizations in both years. Chronic care management, adult preventive care, and pediatric care improved from year 1 to year 2 within the contracting groups. These results suggest that global budgets coupled with pay-for-performance can begin to slow the underlying growth in medical spending while improving quality. PMID:22786651

Automatic design of conformal cooling channels in injection molding tooling

NASA Astrophysics Data System (ADS)

Zhang, Yingming; Hou, Binkui; Wang, Qian; Li, Yang; Huang, Zhigao

2018-02-01

The generation of cooling system plays an important role in injection molding design. A conformal cooling system can effectively improve molding efficiency and product quality. This paper provides a generic approach for building conformal cooling channels. The centrelines of these channels are generated in two steps. First, we extract conformal loops based on geometric information of product. Second, centrelines in spiral shape are built by blending these loops. We devise algorithms to implement the entire design process. A case study verifies the feasibility of this approach.

Improving the Quality of Health Care Services for Adolescents, Globally: A Standards-Driven Approach

PubMed Central

Nair, Manisha; Baltag, Valentina; Bose, Krishna; Boschi-Pinto, Cynthia; Lambrechts, Thierry; Mathai, Matthews

2015-01-01

Purpose The World Health Organization (WHO) undertook an extensive and elaborate process to develop eight Global Standards to improve quality of health care services for adolescents. The objectives of this article are to present the Global Standards and their method of development. Methods The Global Standards were developed through a four-stage process: (1) conducting needs assessment; (2) developing the Global Standards and their criteria; (3) expert consultations; and (4) assessing their usability. Needs assessment involved conducting a meta-review of systematic reviews and two online global surveys in 2013, one with primary health care providers and another with adolescents. The Global Standards were developed based on the needs assessment in conjunction with analysis of 26 national standards from 25 countries. The final document was reviewed by experts from the World Health Organization regional and country offices, governments, academia, nongovernmental organizations, and development partners. The standards were subsequently tested in Benin and in a regional expert consultation of Latin America and Caribbean countries for their usability. Results The process resulted in the development of eight Global Standards and 79 criteria for measuring them: (1) adolescents' health literacy; (2) community support; (3) appropriate package of services; (4) providers' competencies; (5) facility characteristics; (6) equity and nondiscrimination; (7) data and quality improvement; and (8) adolescents' participation. Conclusions The eight standards are intended to act as benchmarks against which quality of health care provided to adolescents could be compared. Health care services can use the standards as part of their internal quality assurance mechanisms or as part of an external accreditation process. PMID:26299556

40 CFR 89.511 - Suspension and revocation of certificates of conformity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... ENGINES Selective Enforcement Auditing § 89.511 Suspension and revocation of certificates of conformity... proposed quality control and/or quality assurance measures to be taken by the manufacturer to prevent...

40 CFR 90.511 - Suspension and revocation of certificates of conformity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... KILOWATTS Selective Enforcement Auditing § 90.511 Suspension and revocation of certificates of conformity... proposed quality control and/or quality assurance measures to be taken by the manufacturer to prevent...

The detection of conformational disorder by thermal analysis

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

Wunderlich, B.

1988-01-01

Conformational disorder in crystals is found in many molecules that possess a plurality of conformational isomers. Typical examples are linear macromolecules such as polyethylene, polytetrafluoroethylene and trans-1,4-polybutadiene; and small molecules such as paraffins, cycloparaffins, soaps, lipids and many liquid-crystal forming molecules. Conformational motion is often coupled with the cooperative creation of disorder. In this case a heat and entropy of transition is observed by thermal analysis. Levels of transition entropies can be estimated, assuming most of the disorder can be traced to conformational isomerism. In case there is conformational disorder frozen-in at low temperature, thermal analysis can be used tomore » find the glass transition of a condis crystal. An Advanced Thermal Analysis System has been developed, and will be described that permits a detailed interpretation of the thermal analysis traces. It rests with the establishment of high quality heat capacity for the rigid solid state (vibration only) and the mobile liquid state (vibrations and large amplitude cooperative motion). 36 refs., 3 figs.« less

Affective mediators of the association between pleasant events and global sleep quality in community-dwelling adults.

PubMed

Tighe, Caitlan A; Shoji, Kristy D; Dautovich, Natalie D; Lichstein, Kenneth L; Scogin, Forrest

2016-02-01

This study explored the association of engagement in pleasant events and global sleep quality, as well as examined the intermediary roles of positive affect and depressive symptoms in this association. Data were derived from the Midlife in the United States-II study. The sample consisted of 1054 community-dwelling adults. Participants completed the Pittsburgh Sleep Quality Index and indicated the frequency and enjoyableness of experiences on a positive events scale. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Positive affect was measured using the Mood and Symptoms Questionnaire. Regression analyses indicated more frequent engagement in pleasant events was associated with better global sleep quality. Depressive symptoms, but not positive affect, partially mediated the association between pleasant events and global sleep quality. The findings suggest that behavioral engagement in pleasant events may be related to global sleep quality via depressive symptoms, but not positive affect. These findings highlight the potential for engagement in pleasant activities to influence both mood and sleep.

Conformal Yano-Killing Tensors for Space-times with Cosmological Constant

NASA Astrophysics Data System (ADS)

Czajka, P.; Jezierski, J.

We present a new method for constructing conformal Yano-Killing tensors in five-di\\-men\\-sio\\-nal Anti-de Sitter space-time. The found tensors are represented in two different coordinate systems. We also discuss, in terms of CYK tensors, global charges which are well defined for asymptotically (five-dimensional) Anti-de Sitter space-time. Additionally in Appendix we present our own derivation of conformal Killing one-forms in four-dimensional Anti-de Sitter space-time as an application of the Theorem presented in the paper.

Conformational diversity analysis reveals three functional mechanisms in proteins

PubMed Central

Fornasari, María Silvina

2017-01-01

Protein motions are a key feature to understand biological function. Recently, a large-scale analysis of protein conformational diversity showed a positively skewed distribution with a peak at 0.5 Å C-alpha root-mean-square-deviation (RMSD). To understand this distribution in terms of structure-function relationships, we studied a well curated and large dataset of ~5,000 proteins with experimentally determined conformational diversity. We searched for global behaviour patterns studying how structure-based features change among the available conformer population for each protein. This procedure allowed us to describe the RMSD distribution in terms of three main protein classes sharing given properties. The largest of these protein subsets (~60%), which we call “rigid” (average RMSD = 0.83 Å), has no disordered regions, shows low conformational diversity, the largest tunnels and smaller and buried cavities. The two additional subsets contain disordered regions, but with differential sequence composition and behaviour. Partially disordered proteins have on average 67% of their conformers with disordered regions, average RMSD = 1.1 Å, the highest number of hinges and the longest disordered regions. In contrast, malleable proteins have on average only 25% of disordered conformers and average RMSD = 1.3 Å, flexible cavities affected in size by the presence of disordered regions and show the highest diversity of cognate ligands. Proteins in each set are mostly non-homologous to each other, share no given fold class, nor functional similarity but do share features derived from their conformer population. These shared features could represent conformational mechanisms related with biological functions. PMID:28192432

Conformational Analysis of Retinoic Acids: Effects of Steric Interactions on Nonplanar Conjugated Polyenes

PubMed Central

Cox, Bryan D.; Muccio, Donald D.; Hamilton, Tracy P.

2013-01-01

Retinoic acids and other vitamin A analogs contain a trimethylcyclohexenyl ring in conjugation with a polyene chain joined at carbon-6 (C6) and carbon-7 (C7). A MP2-SCS/cc-pVDZ// B3LYP/6-31G(d) 2-D potential energy surface was computed for all-trans retinoic acid, which had 6 minima (3 enantiomeric pairs). The global minima were distorted s-gauche enantiomers (6–7 = 53°) with half-chair conformations of the ring. Distorted s-gauche enantiomers (6–7 = 55°) with inverted half-chair ring conformations were 1.7 kJ/mol above the global minima. The s-trans enantiomers (6–7 = 164°) were 11.3 kJ/mol above the global minima. Steric energies were computed by the method of Guo and Karplus to identify key structural elements in retinoic acids which determines their conformation. Small molecule crystal structures in the CCDC database with trimethylcyclohexenyl ring and exocyclic double bonds have ring-chain geometries near to one of the 6 energy minima of retinoic acids, except for retinaldehyde iminium cations. PMID:25798372

Proceedings from the first Global Summit on Radiological Quality and Safety.

PubMed

Stern, Eric J; Adam, E Jane; Bettman, Michael A; Brink, James A; Dreyer, Keith J; Frija, Guy; Keefer, Raina; Mildenberger, Peter; Remedios, Denis; Vock, Peter

2014-10-01

The ACR, the European Society of Radiology, and the International Society of Radiology held the first joint Global Summit on Radiological Quality and Safety in May 2013. The program was divided into 3 day-long themes: appropriateness of imaging, radiation protection/infrastructure, and quality and safety. Participants came from global organizations, including the International Atomic Energy Agency, the World Health Organization, and other institutions; industry and patient advocacy groups with an interest in imaging were also represented. The goal was to exchange ideas and solutions and share concerns to arrive at a better and more uniform approach to quality and safety. Participants were asked to use the information presented to develop strategies and tactics to harmonize and promote best practices worldwide. These strategies were summarized at the conclusion of the meeting. Copyright © 2014 American College of Radiology. Published by Elsevier Inc. All rights reserved.

How Diverse are the Protein-Bound Conformations of Small-Molecule Drugs and Cofactors?

NASA Astrophysics Data System (ADS)

Friedrich, Nils-Ole; Simsir, Méliné; Kirchmair, Johannes

2018-03-01

Knowledge of the bioactive conformations of small molecules or the ability to predict them with theoretical methods is of key importance to the design of bioactive compounds such as drugs, agrochemicals and cosmetics. Using an elaborate cheminformatics pipeline, which also evaluates the support of individual atom coordinates by the measured electron density, we compiled a complete set (“Sperrylite Dataset”) of high-quality structures of protein-bound ligand conformations from the PDB. The Sperrylite Dataset consists of a total of 10,936 high-quality structures of 4548 unique ligands. Based on this dataset, we assessed the variability of the bioactive conformations of 91 small molecules—each represented by a minimum of ten structures—and found it to be largely independent of the number of rotatable bonds. Sixty-nine molecules had at least two distinct conformations (defined by an RMSD greater than 1 Å). For a representative subset of 17 approved drugs and cofactors we observed a clear trend for the formation of few clusters of highly similar conformers. Even for proteins that share a very low sequence identity, ligands were regularly found to adopt similar conformations. For cofactors, a clear trend for extended conformations was measured, although in few cases also coiled conformers were observed. The Sperrylite Dataset is available for download from http://www.zbh.uni-hamburg.de/sperrylite_dataset.

The human qualities needed to complete the global eradication of polio

PubMed Central

2013-01-01

Abstract Although the 99% decrease seen in global polio incidence between 1988 and 2000 represented remarkable progress towards polio eradication, tackling the last 1% of polio has proved tantalizingly difficult. Pockets of endemic transmission currently persist both on the border between Afghanistan and Pakistan and in northern Nigeria. These pockets have permitted the reinfection of countries that were previously polio-free. Global strategic plans for polio eradication set out the activities, resources and financing needed to overcome the managerial, technical and security challenges faced by those tasked with the interruption of poliovirus transmission. However, polio eradication also depends on the less tangible but equally important human qualities of energy, realism, articulacy, determination, imagination, collaboration, adaptability, tactical awareness, innovation, openness and nimbleness (the initial letters of which give the acronym “ERADICATION”). By paying attention to these human qualities, the stakeholders involved may be more likely to achieve global polio eradication. PMID:23599552

Global Air Quality and Climate

NASA Technical Reports Server (NTRS)

Fiore, Arlene M.; Naik, Vaishali; Steiner, Allison; Unger, Nadine; Bergmann, Dan; Prather, Michael; Righi, Mattia; Rumbold, Steven T.; Shindell, Drew T.; Skeie, Ragnhild B.;

Global air quality and climate.

PubMed

Fiore, Arlene M; Naik, Vaishali; Spracklen, Dominick V; Steiner, Allison; Unger, Nadine; Prather, Michael; Bergmann, Dan; Cameron-Smith, Philip J; Cionni, Irene; Collins, William J; Dalsøren, Stig; Eyring, Veronika; Folberth, Gerd A; Ginoux, Paul; Horowitz, Larry W; Josse, Béatrice; Lamarque, Jean-François; MacKenzie, Ian A; Nagashima, Tatsuya; O'Connor, Fiona M; Righi, Mattia; Rumbold, Steven T; Shindell, Drew T; Skeie, Ragnhild B; Sudo, Kengo; Szopa, Sophie; Takemura, Toshihiko; Zeng, Guang

2012-10-07

Emissions of air pollutants and their precursors determine regional air quality and can alter climate. Climate change can perturb the long-range transport, chemical processing, and local meteorology that influence air pollution. We review the implications of projected changes in methane (CH(4)), ozone precursors (O(3)), and aerosols for climate (expressed in terms of the radiative forcing metric or changes in global surface temperature) and hemispheric-to-continental scale air quality. Reducing the O(3) precursor CH(4) would slow near-term warming by decreasing both CH(4) and tropospheric O(3). Uncertainty remains as to the net climate forcing from anthropogenic nitrogen oxide (NO(x)) emissions, which increase tropospheric O(3) (warming) but also increase aerosols and decrease CH(4) (both cooling). Anthropogenic emissions of carbon monoxide (CO) and non-CH(4) volatile organic compounds (NMVOC) warm by increasing both O(3) and CH(4). Radiative impacts from secondary organic aerosols (SOA) are poorly understood. Black carbon emission controls, by reducing the absorption of sunlight in the atmosphere and on snow and ice, have the potential to slow near-term warming, but uncertainties in coincident emissions of reflective (cooling) aerosols and poorly constrained cloud indirect effects confound robust estimates of net climate impacts. Reducing sulfate and nitrate aerosols would improve air quality and lessen interference with the hydrologic cycle, but lead to warming. A holistic and balanced view is thus needed to assess how air pollution controls influence climate; a first step towards this goal involves estimating net climate impacts from individual emission sectors. Modeling and observational analyses suggest a warming climate degrades air quality (increasing surface O(3) and particulate matter) in many populated regions, including during pollution episodes. Prior Intergovernmental Panel on Climate Change (IPCC) scenarios (SRES) allowed unconstrained growth, whereas

Global Pressures on Education Research: Quality, Utility, and Infrastructure

ERIC Educational Resources Information Center

Herrington, Carolyn D.; Summers, Katherine P.

2014-01-01

This article provides an overview of issues likely to drive educational research globally over the next decade, and it examines the "Asia Pacific Education Review" ("APER")'s role in responding to these issues, shaping research agendas, and delivering high-quality research. We also look at the implications of these…

Co-benefits of mitigating global greenhouse gas emissions for future air quality and human health

NASA Astrophysics Data System (ADS)

West, J. Jason; Smith, Steven J.; Silva, Raquel A.; Naik, Vaishali; Zhang, Yuqiang; Adelman, Zachariah; Fry, Meridith M.; Anenberg, Susan; Horowitz, Larry W.; Lamarque, Jean-Francois

2013-10-01

Actions to reduce greenhouse gas (GHG) emissions often reduce co-emitted air pollutants, bringing co-benefits for air quality and human health. Past studies typically evaluated near-term and local co-benefits, neglecting the long-range transport of air pollutants, long-term demographic changes, and the influence of climate change on air quality. Here we simulate the co-benefits of global GHG reductions on air quality and human health using a global atmospheric model and consistent future scenarios, via two mechanisms: reducing co-emitted air pollutants, and slowing climate change and its effect on air quality. We use new relationships between chronic mortality and exposure to fine particulate matter and ozone, global modelling methods and new future scenarios. Relative to a reference scenario, global GHG mitigation avoids 0.5+/-0.2, 1.3+/-0.5 and 2.2+/-0.8 million premature deaths in 2030, 2050 and 2100. Global average marginal co-benefits of avoided mortality are US$50-380 per tonne of CO2, which exceed previous estimates, exceed marginal abatement costs in 2030 and 2050, and are within the low range of costs in 2100. East Asian co-benefits are 10-70 times the marginal cost in 2030. Air quality and health co-benefits, especially as they are mainly local and near-term, provide strong additional motivation for transitioning to a low-carbon future.

Conformation of ionizable poly Para phenylene ethynylene in dilute solutions

DOE PAGES

Wijesinghe, Sidath; Maskey, Sabina; Perahia, Dvora; ...

2015-11-03

The conformation of dinonyl poly para phenylene ethynylenes (PPEs) with carboxylate side chains, equilibrated in solvents of different quality is studied using molecular dynamics simulations. PPEs are of interest because of their tunable electro-optical properties, chemical diversity, and functionality which are essential in wide range of applications. The polymer conformation determines the conjugation length and their assembly mode and affects electro-optical properties which are critical in their current and potential uses. The current study investigates the effect of carboxylate fraction on PPEs side chains on the conformation of chains in the dilute limit, in solvents of different quality. The dinonylmore » PPE chains are modeled atomistically, where the solvents are modeled both implicitly and explicitly. Dinonyl PPEs maintained a stretched out conformation up to a carboxylate fraction f of 0.7 in all solvents studied. The nonyl side chains are extended and oriented away from the PPE backbone in toluene and in implicit good solvent whereas in water and implicit poor solvent, the nonyl side chains are collapsed towards the PPE backbone. Thus, rotation around the aromatic ring is fast and no long range correlations are seen within the backbone.« less

Conformation of ionizable poly Para phenylene ethynylene in dilute solutions

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

Wijesinghe, Sidath; Maskey, Sabina; Perahia, Dvora

The conformation of dinonyl poly para phenylene ethynylenes (PPEs) with carboxylate side chains, equilibrated in solvents of different quality is studied using molecular dynamics simulations. PPEs are of interest because of their tunable electro-optical properties, chemical diversity, and functionality which are essential in wide range of applications. The polymer conformation determines the conjugation length and their assembly mode and affects electro-optical properties which are critical in their current and potential uses. The current study investigates the effect of carboxylate fraction on PPEs side chains on the conformation of chains in the dilute limit, in solvents of different quality. The dinonylmore » PPE chains are modeled atomistically, where the solvents are modeled both implicitly and explicitly. Dinonyl PPEs maintained a stretched out conformation up to a carboxylate fraction f of 0.7 in all solvents studied. The nonyl side chains are extended and oriented away from the PPE backbone in toluene and in implicit good solvent whereas in water and implicit poor solvent, the nonyl side chains are collapsed towards the PPE backbone. Thus, rotation around the aromatic ring is fast and no long range correlations are seen within the backbone.« less

PubChem3D: conformer ensemble accuracy

PubMed Central

2013-01-01

Background PubChem is a free and publicly available resource containing substance descriptions and their associated biological activity information. PubChem3D is an extension to PubChem containing computationally-derived three-dimensional (3-D) structures of small molecules. All the tools and services that are a part of PubChem3D rely upon the quality of the 3-D conformer models. Construction of the conformer models currently available in PubChem3D involves a clustering stage to sample the conformational space spanned by the molecule. While this stage allows one to downsize the conformer models to more manageable size, it may result in a loss of the ability to reproduce experimentally determined “bioactive” conformations, for example, found for PDB ligands. This study examines the extent of this accuracy loss and considers its effect on the 3-D similarity analysis of molecules. Results The conformer models consisting of up to 100,000 conformers per compound were generated for 47,123 small molecules whose structures were experimentally determined, and the conformers in each conformer model were clustered to reduce the size of the conformer model to a maximum of 500 conformers per molecule. The accuracy of the conformer models before and after clustering was evaluated using five different measures: root-mean-square distance (RMSD), shape-optimized shape-Tanimoto (STST-opt) and combo-Tanimoto (ComboTST-opt), and color-optimized color-Tanimoto (CTCT-opt) and combo-Tanimoto (ComboTCT-opt). On average, the effect of clustering decreased the conformer model accuracy, increasing the conformer ensemble’s RMSD to the bioactive conformer (by 0.18 ± 0.12 Å), and decreasing the STST-opt, ComboTST-opt, CTCT-opt, and ComboTCT-opt scores (by 0.04 ± 0.03, 0.16 ± 0.09, 0.09 ± 0.05, and 0.15 ± 0.09, respectively). Conclusion This study shows the RMSD accuracy performance of the PubChem3D conformer models is operating as designed. In addition, the effect of PubChem3D

Conformational analysis and circular dichroism of bilirubin, the yellow pigment of jaundice

NASA Astrophysics Data System (ADS)

Lightner, David A.; Person, Richard; Peterson, Blake; Puzicha, Gisbert; Pu, Yu-Ming; Bojadziev, Stefan

1991-06-01

Conformational analysis of (4Z, 15Z)-bilirubin-IX(alpha) by molecular mechanics computations reveals a global energy minimum folded conformation. Powerful added stabilization is achieved through intramolecular hydrogen bonding. Theoretical treatment of bilirubin as a molecular exciton predicts an intense bisignate circular dichroism spectrum for the folded conformation: (Delta) (epsilon) is congruent to 270 L (DOT) mole-1 (DOT) cm-1 for the $OM450 nm electronic transition(s). Synthesis of bilirubin analogs with propionic acid groups methylated at the (alpha) or (beta) position introduces an allosteric effect that allows for an optical resolution of the pigments, with enantiomers exhibiting the theoretically predicted circular dichroism.

The Copernicus Atmosphere Monitoring Service: facilitating the prediction of air quality from global to local scales

NASA Astrophysics Data System (ADS)

Engelen, R. J.; Peuch, V. H.

2017-12-01

The European Copernicus Atmosphere Monitoring Service (CAMS) operationally provides daily forecasts of global atmospheric composition and regional air quality. The global forecasting system is using ECMWF's Integrated Forecasting System (IFS), which is used for numerical weather prediction and which has been extended with modules for atmospheric chemistry, aerosols and greenhouse gases. The regional forecasts are produced by an ensemble of seven operational European air quality models that take their boundary conditions from the global system and provide an ensemble median with ensemble spread as their main output. Both the global and regional forecasting systems are feeding their output into air quality models on a variety of scales in various parts of the world. We will introduce the CAMS service chain and provide illustrations of its use in downstream applications. Both the usage of the daily forecasts and the usage of global and regional reanalyses will be addressed.

Conformations of n-butyl imidazole: matrix isolation infrared and DFT studies.

PubMed

Ramanathan, N; Sundararajan, K; Sankaran, K

2015-03-15

Conformations of n-butyl imidazole (B-IMID) were studied using matrix isolation infrared spectroscopy by trapping in argon, xenon and nitrogen matrixes using an effusive nozzle source. The experimental studies were supported by DFT computations performed at the B3LYP/6-311++G(d,p) level. Computations identified nine unique minima for B-IMID, corresponding to conformers with tg(±)tt, tg(±)g(∓)t, tg(±)g(±)t, tg(±)tg(±), tg(±)tg(∓), tg(±)g(∓)g(∓), tg(±)g(±)g(±), tg(±)g(∓)g(±) and tg(±)g(±)g(∓) structures, given in order of increasing energy. Computations of the transition state structures connecting the higher energy conformers to the global minimum, tg(±)tt structure were carried out. The barriers for the conformer inter-conversion were found to be ∼2 kcal/mol. Natural Bond Orbital (NBO) analysis was performed to understand the reasons for conformational preferences in B-IMID. Copyright © 2014 Elsevier B.V. All rights reserved.

Conformational space annealing scheme in the inverse design of functional materials

NASA Astrophysics Data System (ADS)

Kim, Sunghyun; Lee, In-Ho; Lee, Jooyoung; Oh, Young Jun; Chang, Kee Joo

2015-03-01

Recently, the so-called inverse method has drawn much attention, in which specific electronic properties are initially assigned and target materials are subsequently searched. In this work, we develop a new scheme for the inverse design of functional materials, in which the conformational space annealing (CSA) algorithm for global optimization is combined with first-principles density functional calculations. To implement the CSA, we need a series of ingredients, (i) an objective function to minimize, (ii) a 'distance' measure between two conformations, (iii) a local enthalpy minimizer of a given conformation, (iv) ways to combine two parent conformations to generate a daughter one, (v) a special conformation update scheme, and (vi) an annealing method in the 'distance' parameter axis. We show the results of applications for searching for Si crystals with direct band gaps and the lowest-enthalpy phase of boron at a finite pressure and discuss the efficiency of the present scheme. This work is supported by the National Research Foundation of Korea (NRF) under Grant No. NRF-2005-0093845 and by Samsung Science and Technology Foundation under Grant No. SSTFBA1401-08.

A Satellite-Based Multi-Pollutant Index of Global Air Quality

NASA Technical Reports Server (NTRS)

Cooper, Mathew J.; Martin, Randall V.; vanDonkelaar, Aaron; Lamsal, Lok; Brauer, Michael; Brook, Jeffrey R.

2012-01-01

Air pollution is a major health hazard that is responsible formillions of annual excess deaths worldwide. Simpleindicators are useful for comparative studies and to asses strends over time. The development of global indicators hasbeen impeded by the lack of ground-based observations in vast regions of the world. Recognition is growing of the need for amultipollutant approach to air quality to better represent human exposure. Here we introduce the prospect of amultipollutant air quality indicator based on observations from satellite remote sensing.

PDB ligand conformational energies calculated quantum-mechanically.

PubMed

Sitzmann, Markus; Weidlich, Iwona E; Filippov, Igor V; Liao, Chenzhong; Peach, Megan L; Ihlenfeldt, Wolf-Dietrich; Karki, Rajeshri G; Borodina, Yulia V; Cachau, Raul E; Nicklaus, Marc C

2012-03-26

We present here a greatly updated version of an earlier study on the conformational energies of protein-ligand complexes in the Protein Data Bank (PDB) [Nicklaus et al. Bioorg. Med. Chem. 1995, 3, 411-428], with the goal of improving on all possible aspects such as number and selection of ligand instances, energy calculations performed, and additional analyses conducted. Starting from about 357,000 ligand instances deposited in the 2008 version of the Ligand Expo database of the experimental 3D coordinates of all small-molecule instances in the PDB, we created a "high-quality" subset of ligand instances by various filtering steps including application of crystallographic quality criteria and structural unambiguousness. Submission of 640 Gaussian 03 jobs yielded a set of about 415 successfully concluded runs. We used a stepwise optimization of internal degrees of freedom at the DFT level of theory with the B3LYP/6-31G(d) basis set and a single-point energy calculation at B3LYP/6-311++G(3df,2p) after each round of (partial) optimization to separate energy changes due to bond length stretches vs bond angle changes vs torsion changes. Even for the most "conservative" choice of all the possible conformational energies-the energy difference between the conformation in which all internal degrees of freedom except torsions have been optimized and the fully optimized conformer-significant energy values were found. The range of 0 to ~25 kcal/mol was populated quite evenly and independently of the crystallographic resolution. A smaller number of "outliers" of yet higher energies were seen only at resolutions above 1.3 Å. The energies showed some correlation with molecular size and flexibility but not with crystallographic quality metrics such as the Cruickshank diffraction-component precision index (DPI) and R(free)-R, or with the ligand instance-specific metrics such as occupancy-weighted B-factor (OWAB), real-space R factor (RSR), and real-space correlation coefficient

Linking Global and Regional Models to Simulate U.S. Air Quality in the Year 2050

EPA Science Inventory

The potential impact of global climate change on future air quality in the United States is investigated with global and regional-scale models. Regional climate model scenarios are developed by dynamically downscaling the outputs from a global chemistry and climate model and are...

Theoretical study of large conformational transitions in DNA: the B↔A conformational change in water and ethanol/water

PubMed Central

Noy, Agnes; Pérez, Alberto; Laughton, Charles A.; Orozco, Modesto

2007-01-01

We explore here the possibility of determining theoretically the free energy change associated with large conformational transitions in DNA, like the solvent-induced B⇔A conformational change. We find that a combination of targeted molecular dynamics (tMD) and the weighted histogram analysis method (WHAM) can be used to trace this transition in both water and ethanol/water mixture. The pathway of the transition in the A→B direction mirrors the B→A pathway, and is dominated by two processes that occur somewhat independently: local changes in sugar puckering and global rearrangements (particularly twist and roll) in the structure. The B→A transition is found to be a quasi-harmonic process, which follows closely the first spontaneous deformation mode of B-DNA, showing that a physiologically-relevant deformation is in coded in the flexibility pattern of DNA. PMID:17459891

21 CFR 26.70 - Conformity assessment bodies.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Conformity assessment bodies. 26.70 Section 26.70 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS...

Conformational flexibility of two RNA trimers explored by computational tools and database search.

PubMed

Fadrná, Eva; Koca, Jaroslav

2003-04-01

Two RNA sequences, AAA and AUG, were studied by the conformational search program CICADA and by molecular dynamics (MD) in the framework of the AMBER force field, and also via thorough PDB database search. CICADA was used to provide detailed information about conformers and conformational interconversions on the energy surfaces of the above molecules. Several conformational families were found for both sequences. Analysis of the results shows differences, especially between the energy of the single families, and also in flexibility and concerted conformational movement. Therefore, several MD trajectories (altogether 16 ns) were run to obtain more details about both the stability of conformers belonging to different conformational families and about the dynamics of the two systems. Results show that the trajectories strongly depend on the starting structure. When the MD start from the global minimum found by CICADA, they provide a stable run, while MD starting from another conformational family generates a trajectory where several different conformational families are visited. The results obtained by theoretical methods are compared with the thorough database search data. It is concluded that all except for the highest energy conformational families found in theoretical result also appear in experimental data. Registry numbers: adenylyl-(3' --> 5')-adenylyl-(3' --> 5')-adenosine [917-44-2] adenylyl-(3' --> 5')-uridylyl-(3' --> 5')-guanosine [3494-35-7].

Co-benefits of mitigating global greenhouse gas emissions for future air quality and human health

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

West, Jason; Smith, Steven J.; Silva, Raquel

2013-10-01

Reducing greenhouse gas (GHG) emissions also influences air quality. We simulate the co-benefits of global GHG reductions on air quality and human health via two mechanisms: a) reducing co-emitted air pollutants, and b) slowing climate change and its effect on air quality. Relative to a reference scenario, global GHG mitigation in the RCP4.5 scenario avoids 0.5±0.2, 1.3±0.6, and 2.2±1.6 million premature deaths in 2030, 2050, and 2100, from changes in fine particulate matter and ozone. Global average marginal co-benefits of avoided mortality are $40-400 (ton CO2)-1, exceeding marginal abatement costs in 2030 and 2050, and within the low range ofmore » costs in 2100. East Asian co-benefits are 10-80 times the marginal cost in 2030. These results indicate that transitioning to a low-carbon future might be justified by air quality and health co-benefits.« less

Prediction of protein loop conformations using multiscale modeling methods with physical energy scoring functions.

PubMed

Olson, Mark A; Feig, Michael; Brooks, Charles L

2008-04-15

This article examines ab initio methods for the prediction of protein loops by a computational strategy of multiscale conformational sampling and physical energy scoring functions. Our approach consists of initial sampling of loop conformations from lattice-based low-resolution models followed by refinement using all-atom simulations. To allow enhanced conformational sampling, the replica exchange method was implemented. Physical energy functions based on CHARMM19 and CHARMM22 parameterizations with generalized Born (GB) solvent models were applied in scoring loop conformations extracted from the lattice simulations and, in the case of all-atom simulations, the ensemble of conformations were generated and scored with these models. Predictions are reported for 25 loop segments, each eight residues long and taken from a diverse set of 22 protein structures. We find that the simulations generally sampled conformations with low global root-mean-square-deviation (RMSD) for loop backbone coordinates from the known structures, whereas clustering conformations in RMSD space and scoring detected less favorable loop structures. Specifically, the lattice simulations sampled basins that exhibited an average global RMSD of 2.21 +/- 1.42 A, whereas clustering and scoring the loop conformations determined an RMSD of 3.72 +/- 1.91 A. Using CHARMM19/GB to refine the lattice conformations improved the sampling RMSD to 1.57 +/- 0.98 A and detection to 2.58 +/- 1.48 A. We found that further improvement could be gained from extending the upper temperature in the all-atom refinement from 400 to 800 K, where the results typically yield a reduction of approximately 1 A or greater in the RMSD of the detected loop. Overall, CHARMM19 with a simple pairwise GB solvent model is more efficient at sampling low-RMSD loop basins than CHARMM22 with a higher-resolution modified analytical GB model; however, the latter simulation method provides a more accurate description of the all-atom energy

Conformally Invariant Powers of the Laplacian, Q-Curvature, and Tractor Calculus

NASA Astrophysics Data System (ADS)

Gover, A. Rod; Peterson, Lawrence J.

We describe an elementary algorithm for expressing, as explicit formulae in tractor calculus, the conformally invariant GJMS operators due to C.R. Graham et alia. These differential operators have leading part a power of the Laplacian. Conformal tractor calculus is the natural induced bundle calculus associated to the conformal Cartan connection. Applications discussed include standard formulae for these operators in terms of the Levi-Civita connection and its curvature and a direct definition and formula for T. Branson's so-called Q-curvature (which integrates to a global conformal invariant) as well as generalisations of the operators and the Q-curvature. Among examples, the operators of order 4, 6 and 8 and the related Q-curvatures are treated explicitly. The algorithm exploits the ambient metric construction of Fefferman and Graham and includes a procedure for converting the ambient curvature and its covariant derivatives into tractor calculus expressions. This is partly based on [12], where the relationship of the normal standard tractor bundle to the ambient construction is described.

Global Influences on National Definitions of Quality Education: Examples from Spain and Italy

ERIC Educational Resources Information Center

Engel, Laura C.; Rutkowski, David

2014-01-01

There is increasing attention worldwide to advancing quality education. Beyond a rhetorical aim, many international organizations and national education systems have articulated a commitment to promoting measures of quality education through the development of educational indicators. This article broadly explores the global influences on national…

Transport of Aerosols: Regional and Global Implications for Climate, Weather, and Air Quality

NASA Technical Reports Server (NTRS)

Chin, Mian; Diehl, Thomas; Yu, Hongbin; Bian, Huisheng; Remer, Lorraine; Kahn, Ralph

2008-01-01

Long-range transport of atmospheric aerosols can have a significant impact on global climate, regional weather, and local air quality. In this study, we use a global model GOCART together with satellite data and ground-based measurements to assess the emission and transport of pollution, dust, biomass burning, and volcanic aerosols and their implications. In particular, we will show the impact of emissions and long-range transport of aerosols from major pollution and dust source regions to (1) the surface air quality, (2) the atmospheric heating rates, and (3) surface radiation change near the source and downwind regions.

Requirements for conformal coating and staking of printed wiring boards and electronic assemblies

NASA Technical Reports Server (NTRS)

1985-01-01

In order to maintain the high standards of the NASA conformal coating and staking program, this publication: prescribes NASA's requirements for assuring reliable conformal coating and staking for printed wiring boards and electronic assemblies; describes and incorporates basic considerations necessary to assure reliable conformal coating and staking; establishes the supplier's responsibility to train and certify personnel; provides for supplier documentation of the fabrication and inspection procedures to be used for NASA work, including supplier innovations and changes in technology; and provides visual workmanship standards to aid those responsible for determining quality conformance to the established requirements.

The Water Quality in Rio Highlights the Global Public Health ...

EPA Pesticide Factsheets

Water quality issues in Rio have been widely publicized because of the 2016 Olympics. Recent concerns about polluted waters that athletes may be exposed to highlights the conditions that more than a billion people globally are exposed to daily. Despite these unhealthy conditions, much is unknown about the risks and exposure pathways associated with bathing in or drinking untreated or partially treated sewage. Beyond acute illness, we are learning more about the chronic sequelae that arise from repeated exposure to pathogens found in sewage. Additionally, we do not know enough about how to measure water quality, especially in developing countries. A consequence of these knowledge gaps is that data from developed countries are used to guide public health approaches in low· and middle-income settings. More data that are locally specific are needed to inform guidelines for improving sanitation and water quality in Rio and other cities in developing countries. Recent media reports of high levels of sewage contamination have caused wide-ranging concerns about the safety of sailing, rowing, and other open water events at the upcoming Olympics. This commentary discusses the global public health problem of exposures to untreated sewage and describes the need for context specific solutions to monitoring and communication and risk assessment.

Quality in Family Child Care Settings: The Relationship between Provider Educational Experiences and Global Quality Scores in a Statewide Quality Rating and Improvement System

ERIC Educational Resources Information Center

Hallam, Rena A.; Bargreen, Kaitlin N.; Ridgley, Robyn

2013-01-01

This study is a secondary analysis of a statewide sample of licensed family child care providers in the Tennessee Child Care Evaluation and Report Card Program ("N"?=?1,145) that describes the general quality of family child care programs in the state and examines the relationships between provider education and global quality. Study…

The effects of global change upon United States air quality

NASA Astrophysics Data System (ADS)

Gonzalez-Abraham, R.; Chung, S. H.; Avise, J.; Lamb, B.; Salathé, E. P., Jr.; Nolte, C. G.; Loughlin, D.; Guenther, A.; Wiedinmyer, C.; Duhl, T.; Zhang, Y.; Streets, D. G.

2015-11-01

To understand more fully the effects of global changes on ambient concentrations of ozone and particulate matter with aerodynamic diameter smaller than 2.5 μm (PM2.5) in the United States (US), we conducted a comprehensive modeling effort to evaluate explicitly the effects of changes in climate, biogenic emissions, land use and global/regional anthropogenic emissions on ozone and PM2.5 concentrations and composition. Results from the ECHAM5 global climate model driven with the A1B emission scenario from the Intergovernmental Panel on Climate Change (IPCC) were downscaled using the Weather Research and Forecasting (WRF) model to provide regional meteorological fields. We developed air quality simulations using the Community Multiscale Air Quality Model (CMAQ) chemical transport model for two nested domains with 220 and 36 km horizontal grid cell resolution for a semi-hemispheric domain and a continental United States (US) domain, respectively. The semi-hemispheric domain was used to evaluate the impact of projected global emissions changes on US air quality. WRF meteorological fields were used to calculate current (2000s) and future (2050s) biogenic emissions using the Model of Emissions of Gases and Aerosols from Nature (MEGAN). For the semi-hemispheric domain CMAQ simulations, present-day global emissions inventories were used and projected to the 2050s based on the IPCC A1B scenario. Regional anthropogenic emissions were obtained from the US Environmental Protection Agency National Emission Inventory 2002 (EPA NEI2002) and projected to the future using the MARKet ALlocation (MARKAL) energy system model assuming a business as usual scenario that extends current decade emission regulations through 2050. Our results suggest that daily maximum 8 h average ozone (DM8O) concentrations will increase in a range between 2 to 12 parts per billion (ppb) across most of the continental US. The highest increase occurs in the South, Central and Midwest regions of the US due to

To conform or not to conform: spontaneous conformity diminishes the sensitivity to monetary outcomes.

PubMed

Yu, Rongjun; Sun, Sai

2013-01-01

When people have different opinions in a group, they often adjust their own attitudes and behaviors to match the group opinion, known as social conformity. The affiliation account of normative conformity states that people conform to norms in order to 'fit in', whereas the accuracy account of informative conformity posits that the motive to learn from others produces herding. Here, we test another possibility that following the crowd reduces the experienced negative emotion when the group decision turns out to be a bad one. Using event related potential (ERP) combined with a novel group gambling task, we found that participants were more likely to choose the option that was predominately chosen by other players in previous trials, although there was little explicit normative pressure at the decision stage and group choices were not informative. When individuals' choices were different from others, the feedback related negativity (FRN), an ERP component sensitive to losses and errors, was enhanced, suggesting that being independent is aversive. At the outcome stage, the losses minus wins FRN effect was significantly reduced following conformity choices than following independent choices. Analyses of the P300 revealed similar patterns both in the response and outcome period. Our study suggests that social conformity serves as an emotional buffer that protects individuals from experiencing strong negative emotion when the outcomes are bad.

[Non-conformities management in laboratory of medical biology: application to non-conformities of biological samples during 2009].

PubMed

Annaix, Véronique; Rogowski, Julien; Joyau, Mireille; Jaouën, Edtih

2011-01-01

The non-conformity management is required for the ISO 15189 standard. The laboratory of medical biology has to carry out suitable acts and procedures to exploit different indicators through the framework of continuous improvement. We particularly study the indicator of biological samples nonconformities and we report 2009 results to the nurses' team managers to find solutions for quality of care to the patient.

Using a biocultural approach to examine migration/globalization, diet quality, and energy balance.

PubMed

Himmelgreen, David A; Cantor, Allison; Arias, Sara; Romero Daza, Nancy

2014-07-01

The aim of this paper is to examine the role and impact that globalization and migration (e.g., intra-/intercontinental, urban/rural, and circular) have had on diet patterns, diet quality, and energy balance as reported on in the literature during the last 20 years. Published literature from the fields of anthropology, public health, nutrition, and other disciplines (e.g., economics) was collected and reviewed. In addition, case studies from the authors' own research are presented in order to elaborate on key points and dietary trends identified in the literature. While this review is not intended to be comprehensive, the findings suggest that the effects of migration and globalization on diet quality and energy balance are neither lineal nor direct, and that the role of social and physical environments, culture, social organization, and technology must be taken into account to better understand this relationship. Moreover, concepts such as acculturation and the nutrition transition do not necessarily explain or adequately describe all of the global processes that shape diet quality and energy balance. Theories from nutritional anthropology and critical bio-cultural medical anthropology are used to tease out some of these complex interrelationships. Copyright © 2014. Published by Elsevier Inc.

On the use of Schwarz-Christoffel conformal mappings to the grid generation for global ocean models

NASA Astrophysics Data System (ADS)

Xu, S.; Wang, B.; Liu, J.

2015-10-01

In this article we propose two grid generation methods for global ocean general circulation models. Contrary to conventional dipolar or tripolar grids, the proposed methods are based on Schwarz-Christoffel conformal mappings that map areas with user-prescribed, irregular boundaries to those with regular boundaries (i.e., disks, slits, etc.). The first method aims at improving existing dipolar grids. Compared with existing grids, the sample grid achieves a better trade-off between the enlargement of the latitudinal-longitudinal portion and the overall smooth grid cell size transition. The second method addresses more modern and advanced grid design requirements arising from high-resolution and multi-scale ocean modeling. The generated grids could potentially achieve the alignment of grid lines to the large-scale coastlines, enhanced spatial resolution in coastal regions, and easier computational load balance. Since the grids are orthogonal curvilinear, they can be easily utilized by the majority of ocean general circulation models that are based on finite difference and require grid orthogonality. The proposed grid generation algorithms can also be applied to the grid generation for regional ocean modeling where complex land-sea distribution is present.

Conformance testing strategies for DICOM protocols in a heterogenous communications system

NASA Astrophysics Data System (ADS)

Meyer, Ralph; Hewett, Andrew J.; Cordonnier, Emmanuel; Piqueras, Joachim; Jensch, Peter F.

1995-05-01

The goal of the DICOM standard is to define a standard network interface and data model for imaging devices from various vendors. It shall facilitate the development and integration of information systems and picture archiving and communication systems (PACS) in a networked environment. Current activities in Oldenburg, Germany include projects to establish cooperative work applications for radiological purposes, comprising (joined) text, data, signal and image communications, based on narrowband ISDN and ATM communication for regional and Pan European applications. In such a growing and constantly changing environment it is vital to have a solid and implementable plan to bring standards in operation. A communication standard alone cannot ensure interoperability between different vendor implementations. Even DICOM does not specify implementation-specific requirements nor does it specify a testing procedure to assess an implementation's conformance to the standard. The conformance statements defined in the DICOM standard only allow a user to determine which optional components are supported by the implementation. The goal of our work is to build a conformance test suite for DICOM. Conformance testing can aid to simplify and solve problems with multivendor systems. It will check a vendor's implementation against the DICOM standard and state the found subset of functionality. The test suite will be built in respect to the ISO 9646 Standard (OSI-Conformance Testing Methodology and Framework) which is a standard devoted to the subject of conformance testing implementations of Open Systems Interconnection (OSI) standards. For our heterogeneous communication environments we must also consider ISO 9000 - 9004 (quality management and quality assurance) to give the users the confidence in evolving applications.

Effects of future anthropogenic pollution emissions on global air quality

NASA Astrophysics Data System (ADS)

Pozzer, A.; Zimmermann, P.; Doering, U.; van Aardenne, J.; Dentener, F.; Lelieveld, J.

2012-04-01

The atmospheric chemistry general circulation model EMAC is used to estimate the impact of anthropogenic emission changes on global and regional air quality in recent and future years (2005, 2010, 2025 and 2050). The emission scenario assumes that population and economic growth largely determine energy consumption and consequent pollution sources ("business as usual"). By comparing with recent observations, it is shown that the model reproduces the main features of regional air pollution distributions though with some imprecision inherent to the coarse horizontal resolution (around 100 km). To identify possible future hot spots of poor air quality, a multi pollutant index (MPI) has been applied. It appears that East and South Asia and the Arabian Gulf regions represent such hotspots due to very high pollutant concentrations. In East Asia a range of pollutant gases and particulate matter (PM2.5) are projected to reach very high levels from 2005 onward, while in South Asia air pollution, including ozone, will grow rapidly towards the middle of the century. Around the Arabian Gulf, where natural PM2.5 concentrations are already high (desert dust), ozone levels will increase strongly. By extending the MPI definition, we calculated a Per Capita MPI (PCMPI) in which we combined population projections with those of pollution emissions. It thus appears that a rapidly increasing number of people worldwide will experience reduced air quality during the first half of the 21st century. It is projected that air quality for the global average citizen in 2050 will be comparable to the average in East Asia in the year 2005.

Regional cancer centre demonstrates voluntary conformity with the national Radiation Oncology Practice Standards

PubMed Central

Manley, Stephen; Last, Andrew; Fu, Kenneth; Greenham, Stuart; Kovendy, Andrew; Shakespeare, Thomas P

2015-01-01

Radiation Oncology Practice Standards have been developed over the last 10 years and were published for use in Australia in 2011. Although the majority of the radiation oncology community supports the implementation of the standards, there has been no mechanism for uniform assessment or governance. North Coast Cancer Institute's public radiation oncology service is provided across three main service centres on the north coast of NSW. With a strong focus on quality management, we embraced the opportunity to demonstrate conformity with the Radiation Oncology Practice Standards. The Local Health District's Clinical Governance units were engaged to perform assessments of our conformity with the standards and this was signed off as complete on 16 December 2013. The process of demonstrating conformity with the Radiation Oncology Practice Standards has enhanced the culture of quality in our centres. We have demonstrated that self-assessment utilising trained auditors is a viable method for centres to demonstrate conformity. National implementation of the Radiation Oncology Practice Standards will benefit individual centres and the broader radiation oncology community to improve the service delivered to our patients. PMID:26229680

Regional cancer centre demonstrates voluntary conformity with the national Radiation Oncology Practice Standards.

PubMed

Manley, Stephen; Last, Andrew; Fu, Kenneth; Greenham, Stuart; Kovendy, Andrew; Shakespeare, Thomas P

2015-06-01

Radiation Oncology Practice Standards have been developed over the last 10 years and were published for use in Australia in 2011. Although the majority of the radiation oncology community supports the implementation of the standards, there has been no mechanism for uniform assessment or governance. North Coast Cancer Institute's public radiation oncology service is provided across three main service centres on the north coast of NSW. With a strong focus on quality management, we embraced the opportunity to demonstrate conformity with the Radiation Oncology Practice Standards. The Local Health District's Clinical Governance units were engaged to perform assessments of our conformity with the standards and this was signed off as complete on 16 December 2013. The process of demonstrating conformity with the Radiation Oncology Practice Standards has enhanced the culture of quality in our centres. We have demonstrated that self-assessment utilising trained auditors is a viable method for centres to demonstrate conformity. National implementation of the Radiation Oncology Practice Standards will benefit individual centres and the broader radiation oncology community to improve the service delivered to our patients.

Dispositional Optimism and Terminal Decline in Global Quality of Life

ERIC Educational Resources Information Center

Zaslavsky, Oleg; Palgi, Yuval; Rillamas-Sun, Eileen; LaCroix, Andrea Z.; Schnall, Eliezer; Woods, Nancy F.; Cochrane, Barbara B.; Garcia, Lorena; Hingle, Melanie; Post, Stephen; Seguin, Rebecca; Tindle, Hilary; Shrira, Amit

2015-01-01

We examined whether dispositional optimism relates to change in global quality of life (QOL) as a function of either chronological age or years to impending death. We used a sample of 2,096 deceased postmenopausal women from the Women's Health Initiative clinical trials who were enrolled in the 2005-2010 Extension Study and for whom at least 1…

A conformal approach for the analysis of the non-linear stability of radiation cosmologies

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

Luebbe, Christian, E-mail: c.luebbe@ucl.ac.uk; Department of Mathematics, University of Leicester, University Road, LE1 8RH; Valiente Kroon, Juan Antonio, E-mail: j.a.valiente-kroon@qmul.ac.uk

2013-01-15

The conformal Einstein equations for a trace-free (radiation) perfect fluid are derived in terms of the Levi-Civita connection of a conformally rescaled metric. These equations are used to provide a non-linear stability result for de Sitter-like trace-free (radiation) perfect fluid Friedman-Lemaitre-Robertson-Walker cosmological models. The solutions thus obtained exist globally towards the future and are future geodesically complete. - Highlights: Black-Right-Pointing-Pointer We study the Einstein-Euler system in General Relativity using conformal methods. Black-Right-Pointing-Pointer We analyze the structural properties of the associated evolution equations. Black-Right-Pointing-Pointer We establish the non-linear stability of pure radiation cosmological models.

Generative Topographic Mapping of Conformational Space.

PubMed

Horvath, Dragos; Baskin, Igor; Marcou, Gilles; Varnek, Alexandre

2017-10-01

Herein, Generative Topographic Mapping (GTM) was challenged to produce planar projections of the high-dimensional conformational space of complex molecules (the 1LE1 peptide). GTM is a probability-based mapping strategy, and its capacity to support property prediction models serves to objectively assess map quality (in terms of regression statistics). The properties to predict were total, non-bonded and contact energies, surface area and fingerprint darkness. Map building and selection was controlled by a previously introduced evolutionary strategy allowed to choose the best-suited conformational descriptors, options including classical terms and novel atom-centric autocorrellograms. The latter condensate interatomic distance patterns into descriptors of rather low dimensionality, yet precise enough to differentiate between close favorable contacts and atom clashes. A subset of 20 K conformers of the 1LE1 peptide, randomly selected from a pool of 2 M geometries (generated by the S4MPLE tool) was employed for map building and cross-validation of property regression models. The GTM build-up challenge reached robust three-fold cross-validated determination coefficients of Q 2 =0.7…0.8, for all modeled properties. Mapping of the full 2 M conformer set produced intuitive and information-rich property landscapes. Functional and folding subspaces appear as well-separated zones, even though RMSD with respect to the PDB structure was never used as a selection criterion of the maps. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

ConformRank: A conformity-based rank for finding top-k influential users

NASA Astrophysics Data System (ADS)

Wang, Qiyao; Jin, Yuehui; Cheng, Shiduan; Yang, Tan

2017-05-01

Finding influential users is a hot topic in social networks. For example, advertisers identify influential users to make a successful campaign. Retweeters forward messages from original users, who originally publish messages. This action is referred to as retweeting. Retweeting behaviors generate influence. Original users have influence on retweeters. Whether retweeters keep the same sentiment as original users is taken into consideration in this study. Influence is calculated based on conformity from emotional perspective after retweeting. A conformity-based algorithm, called ConformRank, is proposed to find top-k influential users, who make the most users keep the same sentiment after retweeting messages. Emotional conformity is introduced to denote how users conform to original users from the emotional perspective. Conforming weights are introduced to denote how two users keep the same sentiment after retweeting messages. Emotional conformity is applied for users and conforming weights are used for relations. Experiments were conducted on Sina Weibo. Experimental results show that users have larger influence when they publish positive messages.

A multi-model assessment of the co-benefits of climate mitigation for global air quality

NASA Astrophysics Data System (ADS)

Rao, Shilpa; Klimont, Zbigniew; Leitao, Joana; Riahi, Keywan; van Dingenen, Rita; Aleluia Reis, Lara; Calvin, Katherine; Dentener, Frank; Drouet, Laurent; Fujimori, Shinichiro; Harmsen, Mathijs; Luderer, Gunnar; Heyes, Chris; Strefler, Jessica; Tavoni, Massimo; van Vuuren, Detlef P.

2016-12-01

We present a model comparison study that combines multiple integrated assessment models with a reduced-form global air quality model to assess the potential co-benefits of global climate mitigation policies in relation to the World Health Organization (WHO) goals on air quality and health. We include in our assessment, a range of alternative assumptions on the implementation of current and planned pollution control policies. The resulting air pollution emission ranges significantly extend those in the Representative Concentration Pathways. Climate mitigation policies complement current efforts on air pollution control through technology and fuel transformations in the energy system. A combination of stringent policies on air pollution control and climate change mitigation results in 40% of the global population exposed to PM levels below the WHO air quality guideline; with the largest improvements estimated for India, China, and Middle East. Our results stress the importance of integrated multisector policy approaches to achieve the Sustainable Development Goals.

Protein Loop Structure Prediction Using Conformational Space Annealing.

PubMed

Heo, Seungryong; Lee, Juyong; Joo, Keehyoung; Shin, Hang-Cheol; Lee, Jooyoung

2017-05-22

We have developed a protein loop structure prediction method by combining a new energy function, which we call E PLM (energy for protein loop modeling), with the conformational space annealing (CSA) global optimization algorithm. The energy function includes stereochemistry, dynamic fragment assembly, distance-scaled finite ideal gas reference (DFIRE), and generalized orientation- and distance-dependent terms. For the conformational search of loop structures, we used the CSA algorithm, which has been quite successful in dealing with various hard global optimization problems. We assessed the performance of E PLM with two widely used loop-decoy sets, Jacobson and RAPPER, and compared the results against the DFIRE potential. The accuracy of model selection from a pool of loop decoys as well as de novo loop modeling starting from randomly generated structures was examined separately. For the selection of a nativelike structure from a decoy set, E PLM was more accurate than DFIRE in the case of the Jacobson set and had similar accuracy in the case of the RAPPER set. In terms of sampling more nativelike loop structures, E PLM outperformed E DFIRE for both decoy sets. This new approach equipped with E PLM and CSA can serve as the state-of-the-art de novo loop modeling method.

Designing and evaluating the MULTICOM protein local and global model quality prediction methods in the CASP10 experiment

PubMed Central

2014-01-01

Background Protein model quality assessment is an essential component of generating and using protein structural models. During the Tenth Critical Assessment of Techniques for Protein Structure Prediction (CASP10), we developed and tested four automated methods (MULTICOM-REFINE, MULTICOM-CLUSTER, MULTICOM-NOVEL, and MULTICOM-CONSTRUCT) that predicted both local and global quality of protein structural models. Results MULTICOM-REFINE was a clustering approach that used the average pairwise structural similarity between models to measure the global quality and the average Euclidean distance between a model and several top ranked models to measure the local quality. MULTICOM-CLUSTER and MULTICOM-NOVEL were two new support vector machine-based methods of predicting both the local and global quality of a single protein model. MULTICOM-CONSTRUCT was a new weighted pairwise model comparison (clustering) method that used the weighted average similarity between models in a pool to measure the global model quality. Our experiments showed that the pairwise model assessment methods worked better when a large portion of models in the pool were of good quality, whereas single-model quality assessment methods performed better on some hard targets when only a small portion of models in the pool were of reasonable quality. Conclusions Since digging out a few good models from a large pool of low-quality models is a major challenge in protein structure prediction, single model quality assessment methods appear to be poised to make important contributions to protein structure modeling. The other interesting finding was that single-model quality assessment scores could be used to weight the models by the consensus pairwise model comparison method to improve its accuracy. PMID:24731387

Designing and evaluating the MULTICOM protein local and global model quality prediction methods in the CASP10 experiment.

PubMed

Cao, Renzhi; Wang, Zheng; Cheng, Jianlin

2014-04-15

Protein model quality assessment is an essential component of generating and using protein structural models. During the Tenth Critical Assessment of Techniques for Protein Structure Prediction (CASP10), we developed and tested four automated methods (MULTICOM-REFINE, MULTICOM-CLUSTER, MULTICOM-NOVEL, and MULTICOM-CONSTRUCT) that predicted both local and global quality of protein structural models. MULTICOM-REFINE was a clustering approach that used the average pairwise structural similarity between models to measure the global quality and the average Euclidean distance between a model and several top ranked models to measure the local quality. MULTICOM-CLUSTER and MULTICOM-NOVEL were two new support vector machine-based methods of predicting both the local and global quality of a single protein model. MULTICOM-CONSTRUCT was a new weighted pairwise model comparison (clustering) method that used the weighted average similarity between models in a pool to measure the global model quality. Our experiments showed that the pairwise model assessment methods worked better when a large portion of models in the pool were of good quality, whereas single-model quality assessment methods performed better on some hard targets when only a small portion of models in the pool were of reasonable quality. Since digging out a few good models from a large pool of low-quality models is a major challenge in protein structure prediction, single model quality assessment methods appear to be poised to make important contributions to protein structure modeling. The other interesting finding was that single-model quality assessment scores could be used to weight the models by the consensus pairwise model comparison method to improve its accuracy.

Co-benefits of global and regional greenhouse gas mitigation for US air quality in 2050

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

Zhang, Yuqiang; Bowden, Jared H.; Adelman, Zachariah

Policies to mitigate greenhouse gas (GHG) emissions will not only slow climate change but can also have ancillary benefits of improved air quality. Here we examine the co-benefits of both global and regional GHG mitigation for US air quality in 2050 at fine resolution, using dynamical downscaling methods, building on a previous global co-benefits study (West et al., 2013). The co-benefits for US air quality are quantified via two mechanisms: through reductions in co-emitted air pollutants from the same sources and by slowing climate change and its influence on air quality, following West et al. (2013). Additionally, we separate the totalmore » co-benefits into contributions from domestic GHG mitigation vs. mitigation in foreign countries. We use the Weather Research and Forecasting (WRF) model to dynamically downscale future global climate to the regional scale and the Sparse Matrix Operator Kernel Emissions (SMOKE) program to directly process global anthropogenic emissions to the regional domain, and we provide dynamical boundary conditions from global simulations to the regional Community Multi-scale Air Quality (CMAQ) model. The total co-benefits of global GHG mitigation from the RCP4.5 scenario compared with its reference are estimated to be higher in the eastern US (ranging from 0.6 to 1.0 µg m -3) than the west (0–0.4 µg m -3) for fine particulate matter (PM 2.5), with an average of 0.47 µg m -3 over the US; for O 3, the total co-benefits are more uniform at 2–5 ppb, with a US average of 3.55 ppb. Comparing the two mechanisms of co-benefits, we find that reductions in co-emitted air pollutants have a much greater influence on both PM 2.5 (96 % of the total co-benefits) and O 3 (89 % of the total) than the second co-benefits mechanism via slowing climate change, consistent with West et al. (2013). GHG mitigation from foreign countries contributes more to the US O 3 reduction (76 % of the total) than that from domestic GHG mitigation only (24

C-metric solution for conformal gravity with a conformally coupled scalar field

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

Meng, Kun, E-mail: mengkun@tjpu.edu.cn; Zhao, Liu, E-mail: lzhao@nankai.edu.cn

The C-metric solution of conformal gravity with a conformally coupled scalar field is presented. The solution belongs to the class of Petrov type D spacetimes and is conformal to the standard AdS C-metric appeared in vacuum Einstein gravity. For all parameter ranges, we identify some of the physically interesting static regions and the corresponding coordinate ranges. The solution may contain a black hole event horizon, an acceleration horizon, either of which may be cut by the conformal infinity or be hidden behind the conformal infinity. Since the model is conformally invariant, we also discussed the possible effects of the conformalmore » gauge choices on the structure of the spacetime.« less

Maintaining and Enhancing Diversity of Sampled Protein Conformations in Robotics-Inspired Methods.

PubMed

Abella, Jayvee R; Moll, Mark; Kavraki, Lydia E

2018-01-01

The ability to efficiently sample structurally diverse protein conformations allows one to gain a high-level view of a protein's energy landscape. Algorithms from robot motion planning have been used for conformational sampling, and several of these algorithms promote diversity by keeping track of "coverage" in conformational space based on the local sampling density. However, large proteins present special challenges. In particular, larger systems require running many concurrent instances of these algorithms, but these algorithms can quickly become memory intensive because they typically keep previously sampled conformations in memory to maintain coverage estimates. In addition, robotics-inspired algorithms depend on defining useful perturbation strategies for exploring the conformational space, which is a difficult task for large proteins because such systems are typically more constrained and exhibit complex motions. In this article, we introduce two methodologies for maintaining and enhancing diversity in robotics-inspired conformational sampling. The first method addresses algorithms based on coverage estimates and leverages the use of a low-dimensional projection to define a global coverage grid that maintains coverage across concurrent runs of sampling. The second method is an automatic definition of a perturbation strategy through readily available flexibility information derived from B-factors, secondary structure, and rigidity analysis. Our results show a significant increase in the diversity of the conformations sampled for proteins consisting of up to 500 residues when applied to a specific robotics-inspired algorithm for conformational sampling. The methodologies presented in this article may be vital components for the scalability of robotics-inspired approaches.

Prediction of global and local model quality in CASP8 using the ModFOLD server.

PubMed

McGuffin, Liam J

2009-01-01

The development of effective methods for predicting the quality of three-dimensional (3D) models is fundamentally important for the success of tertiary structure (TS) prediction strategies. Since CASP7, the Quality Assessment (QA) category has existed to gauge the ability of various model quality assessment programs (MQAPs) at predicting the relative quality of individual 3D models. For the CASP8 experiment, automated predictions were submitted in the QA category using two methods from the ModFOLD server-ModFOLD version 1.1 and ModFOLDclust. ModFOLD version 1.1 is a single-model machine learning based method, which was used for automated predictions of global model quality (QMODE1). ModFOLDclust is a simple clustering based method, which was used for automated predictions of both global and local quality (QMODE2). In addition, manual predictions of model quality were made using ModFOLD version 2.0--an experimental method that combines the scores from ModFOLDclust and ModFOLD v1.1. Predictions from the ModFOLDclust method were the most successful of the three in terms of the global model quality, whilst the ModFOLD v1.1 method was comparable in performance to other single-model based methods. In addition, the ModFOLDclust method performed well at predicting the per-residue, or local, model quality scores. Predictions of the per-residue errors in our own 3D models, selected using the ModFOLD v2.0 method, were also the most accurate compared with those from other methods. All of the MQAPs described are publicly accessible via the ModFOLD server at: http://www.reading.ac.uk/bioinf/ModFOLD/. The methods are also freely available to download from: http://www.reading.ac.uk/bioinf/downloads/. Copyright 2009 Wiley-Liss, Inc.

Regional cancer centre demonstrates voluntary conformity with the national Radiation Oncology Practice Standards

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

Manley, Stephen, E-mail: stephen.manley@ncahs.health.nsw.gov.au; Last, Andrew; Fu, Kenneth

Radiation Oncology Practice Standards have been developed over the last 10 years and were published for use in Australia in 2011. Although the majority of the radiation oncology community supports the implementation of the standards, there has been no mechanism for uniform assessment or governance. North Coast Cancer Institute's public radiation oncology service is provided across three main service centres on the north coast of NSW. With a strong focus on quality management, we embraced the opportunity to demonstrate conformity with the Radiation Oncology Practice Standards. The Local Health District's Clinical Governance units were engaged to perform assessments of ourmore » conformity with the standards and this was signed off as complete on 16 December 2013. The process of demonstrating conformity with the Radiation Oncology Practice Standards has enhanced the culture of quality in our centres. We have demonstrated that self-assessment utilising trained auditors is a viable method for centres to demonstrate conformity. National implementation of the Radiation Oncology Practice Standards will benefit individual centres and the broader radiation oncology community to improve the service delivered to our patients.« less

76 FR 10892 - Aquatic Ecosystems, Water Quality, and Global Change: Challenges of Conducting Multi-Stressor...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-28

... Ecosystems, Water Quality, and Global Change: Challenges of Conducting Multi-Stressor Vulnerability...: EPA is announcing the release of the draft report titled, ``Aquatic Ecosystems, Water Quality, and... for Environmental Assessment within EPA's Office of Research and Development. This draft report...

Childhood socioeconomic status and risk in early family environments: predictors of global sleep quality in college students.

PubMed

Counts, Cory J; Grubin, Fiona C; John-Henderson, Neha A

2018-06-01

Low socioeconomic status (SES) in childhood associates with poor sleep quality in adulthood. Separately, childhood family environments shape health into adulthood. Here, we investigated whether these early life factors independently or interactively inform global sleep quality in college students. Cross-sectional. College students at a state university (N = 391). As a measure of childhood SES, we asked participants to consider their families' socioeconomic standing relative to the rest of the society during their childhood. We used the Risky Family questionnaire to measure adversity and the presence of warmth and affection in the family environment during childhood, and the Pittsburgh Sleep Quality Index as a measure of current global sleep quality. We used linear regressions adjusting for age and sex to examine relationships between childhood SES, risk in childhood family environments, and global sleep quality. Lower childhood SES and greater risk in childhood family environments independently predicted poor sleep quality. Importantly, in low-risk family environments, there was no significant difference in sleep quality as a function of childhood SES. However, students who were from low childhood SES backgrounds who also reported high levels of risk in their early family environments had the worst sleep quality. Findings highlight the importance of considering socioeconomic and family environments in childhood as informants of sleep quality across the lifespan. Compromised sleep quality in college students could affect academic performance and health over time. Copyright © 2018 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.

Developing Information Services and Tools to Access and Evaluate Data Quality in Global Satellite-based Precipitation Products

NASA Astrophysics Data System (ADS)

Liu, Z.; Shie, C. L.; Meyer, D. J.

2017-12-01

Global satellite-based precipitation products have been widely used in research and applications around the world. Compared to ground-based observations, satellite-based measurements provide precipitation data on a global scale, especially in remote continents and over oceans. Over the years, satellite-based precipitation products have evolved from single sensor and single algorithm to multi-sensors and multi-algorithms. As a result, many satellite-based precipitation products have been enhanced such as spatial and temporal coverages. With inclusion of ground-based measurements, biases of satellite-based precipitation products have been significantly reduced. However, data quality issues still exist and can be caused by many factors such as observations, satellite platform anomaly, algorithms, production, calibration, validation, data services, etc. The NASA Goddard Earth Sciences (GES) Data and Information Services Center (DISC) is home to NASA global precipitation product archives including the Tropical Rainfall Measuring Mission (TRMM), the Global Precipitation Measurement (GPM), as well as other global and regional precipitation products. Precipitation is one of the top downloaded and accessed parameters in the GES DISC data archive. Meanwhile, users want to easily locate and obtain data quality information at regional and global scales to better understand how precipitation products perform and how reliable they are. As data service providers, it is necessary to provide an easy access to data quality information, however, such information normally is not available, and when it is available, it is not in one place and difficult to locate. In this presentation, we will present challenges and activities at the GES DISC to address precipitation data quality issues.

Changes in Health Care Spending and Quality 4 Years into Global Payment

PubMed Central

Song, Zirui; Rose, Sherri; Safran, Dana G.; Landon, Bruce E.; Day, Matthew P.; Chernew, Michael E.

2014-01-01

BACKGROUND Spending and quality under global budgets remain unknown beyond 2 years. We evaluated spending and quality measures during the first 4 years of the Blue Cross Blue Shield of Massachusetts Alternative Quality Contract (AQC). METHODS We compared spending and quality among enrollees whose physician organizations entered the AQC from 2009 through 2012 with those among persons in control states. We studied spending changes according to year, category of service, site of care, experience managing risk contracts, and price versus utilization. We evaluated process and outcome quality. RESULTS In the 2009 AQC cohort, medical spending on claims grew an average of $62.21 per enrollee per quarter less than it did in the control cohort over the 4-year period (P<0.001). This amount is equivalent to a 6.8% savings when calculated as a proportion of the average post-AQC spending level in the 2009 AQC cohort. Analogously, the 2010, 2011, and 2012 cohorts had average savings of 8.8% (P<0.001), 9.1% (P<0.001), and 5.8% (P = 0.04), respectively, by the end of 2012. Claims savings were concentrated in the outpatient-facility setting and in procedures, imaging, and tests, explained by both reduced prices and reduced utilization. Claims savings were exceeded by incentive payments to providers during the period from 2009 through 2011 but exceeded incentive payments in 2012, generating net savings. Improvements in quality among AQC cohorts generally exceeded those seen elsewhere in New England and nationally. CONCLUSIONS As compared with similar populations in other states, Massachusetts AQC enrollees had lower spending growth and generally greater quality improvements after 4 years. Although other factors in Massachusetts may have contributed, particularly in the later part of the study period, global budget contracts with quality incentives may encourage changes in practice patterns that help reduce spending and improve quality. (Funded by the Commonwealth Fund and others

Structure and conformational dynamics of scaffolded DNA origami nanoparticles

DTIC Science & Technology

2017-05-08

all-atom molecular dynamics and coarse-grained finite element modeling to DX-based nanoparticles to elucidate their fine-scale and global conforma... finite element (FE) modeling approach CanDo is also routinely used to predict the 3D equilibrium conformation of programmed DNA assemblies based on a...model with both experimental cryo-electron microscopy (cryo-EM) data and all-atom modeling. MATERIALS AND METHODS Lattice-free finite element model

Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection

PubMed Central

Maciag, Joseph J.; Mackenzie, Sarah H.; Tucker, Matthew B.; Schipper, Joshua L.; Swartz, Paul; Clark, A. Clay

2016-01-01

The native ensemble of caspases is described globally by a complex energy landscape where the binding of substrate selects for the active conformation, whereas targeting an allosteric site in the dimer interface selects an inactive conformation that contains disordered active-site loops. Mutations and posttranslational modifications stabilize high-energy inactive conformations, with mostly formed, but distorted, active sites. To examine the interconversion of active and inactive states in the ensemble, we used detection of related solvent positions to analyze 4,995 waters in 15 high-resolution (<2.0 Å) structures of wild-type caspase-3, resulting in 450 clusters with the most highly conserved set containing 145 water molecules. The data show that regions of the protein that contact the conserved waters also correspond to sites of posttranslational modifications, suggesting that the conserved waters are an integral part of allosteric mechanisms. To test this hypothesis, we created a library of 19 caspase-3 variants through saturation mutagenesis in a single position of the allosteric site of the dimer interface, and we show that the enzyme activity varies by more than four orders of magnitude. Altogether, our database consists of 37 high-resolution structures of caspase-3 variants, and we demonstrate that the decrease in activity correlates with a loss of conserved water molecules. The data show that the activity of caspase-3 can be fine-tuned through globally desolvating the active conformation within the native ensemble, providing a mechanism for cells to repartition the ensemble and thus fine-tune activity through conformational selection. PMID:27681633

Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection.

PubMed

Maciag, Joseph J; Mackenzie, Sarah H; Tucker, Matthew B; Schipper, Joshua L; Swartz, Paul; Clark, A Clay

2016-10-11

The native ensemble of caspases is described globally by a complex energy landscape where the binding of substrate selects for the active conformation, whereas targeting an allosteric site in the dimer interface selects an inactive conformation that contains disordered active-site loops. Mutations and posttranslational modifications stabilize high-energy inactive conformations, with mostly formed, but distorted, active sites. To examine the interconversion of active and inactive states in the ensemble, we used detection of related solvent positions to analyze 4,995 waters in 15 high-resolution (<2.0 Å) structures of wild-type caspase-3, resulting in 450 clusters with the most highly conserved set containing 145 water molecules. The data show that regions of the protein that contact the conserved waters also correspond to sites of posttranslational modifications, suggesting that the conserved waters are an integral part of allosteric mechanisms. To test this hypothesis, we created a library of 19 caspase-3 variants through saturation mutagenesis in a single position of the allosteric site of the dimer interface, and we show that the enzyme activity varies by more than four orders of magnitude. Altogether, our database consists of 37 high-resolution structures of caspase-3 variants, and we demonstrate that the decrease in activity correlates with a loss of conserved water molecules. The data show that the activity of caspase-3 can be fine-tuned through globally desolvating the active conformation within the native ensemble, providing a mechanism for cells to repartition the ensemble and thus fine-tune activity through conformational selection.

The Co-Benefits of Global and Regional Greenhouse Gas Mitigation on US Air Quality at Fine Resolution

NASA Astrophysics Data System (ADS)

Zhang, Y.; Bowden, J. H.; Adelman, Z.; Naik, V.; Horowitz, L. W.; Smith, S.; West, J. J.

2014-12-01

Reducing greenhouse gases (GHGs) not only slows climate change, but can also have co-benefits for improved air quality. In this study, we examine the co-benefits of global and regional GHG mitigation on US air quality at fine resolution through dynamical downscaling, using the latest Community Multi-scale Air Quality (CMAQ) model. We will investigate the co-benefits on US air quality due to domestic GHG mitigation alone, and due to mitigation outside of the US. We also quantity the co-benefits resulting from reductions in co-emitted air pollutants versus slowing climate change and its effects on air quality. Projected climate in the 2050s from the IPCC RCP4.5 and RCP8.5 scenarios is dynamically downscaled with the Weather Research and Forecasting model (WRF). Anthropogenic emissions projections from the RCP4.5 scenario and its reference (REF), are directly processed in SMOKE to provide temporally- and spatially-resolved CMAQ emission input files. Chemical boundary conditions (BCs) are obtained from West et al. (2013), who studied the co-benefits of global GHG reductions on global air quality and human health. Our preliminary results show that the global GHG reduction (RCP4.5 relative to REF) reduces the 1hr daily maximum ozone by 3.3 ppbv annually over entire US, as high as 6 ppbv in September. The west coast of California and the Northeast US are the regions that benefit most. By comparing different scenarios, we find that foreign countries' GHGs mitigation has a larger influence on the US ozone decreases (accounting for 77% of the total decrease), compared with 23% from domestic GHG mitigation only, highlighting the importance of methane reductions and the intercontinental transport of air pollutants. The reduction of global co-emitted air pollutants has a more pronounced effect on ozone decreasing, relative to the effect from slowing climate and its effects on air quality. We also plan to report co-benefits for PM2.5 in the US.

Deciphering the shape and deformation of secondary structures through local conformation analysis

PubMed Central

2011-01-01

Background Protein deformation has been extensively analysed through global methods based on RMSD, torsion angles and Principal Components Analysis calculations. Here we use a local approach, able to distinguish among the different backbone conformations within loops, α-helices and β-strands, to address the question of secondary structures' shape variation within proteins and deformation at interface upon complexation. Results Using a structural alphabet, we translated the 3 D structures of large sets of protein-protein complexes into sequences of structural letters. The shape of the secondary structures can be assessed by the structural letters that modeled them in the structural sequences. The distribution analysis of the structural letters in the three protein compartments (surface, core and interface) reveals that secondary structures tend to adopt preferential conformations that differ among the compartments. The local description of secondary structures highlights that curved conformations are preferred on the surface while straight ones are preferred in the core. Interfaces display a mixture of local conformations either preferred in core or surface. The analysis of the structural letters transition occurring between protein-bound and unbound conformations shows that the deformation of secondary structure is tightly linked to the compartment preference of the local conformations. Conclusion The conformation of secondary structures can be further analysed and detailed thanks to a structural alphabet which allows a better description of protein surface, core and interface in terms of secondary structures' shape and deformation. Induced-fit modification tendencies described here should be valuable information to identify and characterize regions under strong structural constraints for functional reasons. PMID:21284872

Deciphering the shape and deformation of secondary structures through local conformation analysis.

PubMed

Baussand, Julie; Camproux, Anne-Claude

2011-02-01

Protein deformation has been extensively analysed through global methods based on RMSD, torsion angles and Principal Components Analysis calculations. Here we use a local approach, able to distinguish among the different backbone conformations within loops, α-helices and β-strands, to address the question of secondary structures' shape variation within proteins and deformation at interface upon complexation. Using a structural alphabet, we translated the 3 D structures of large sets of protein-protein complexes into sequences of structural letters. The shape of the secondary structures can be assessed by the structural letters that modeled them in the structural sequences. The distribution analysis of the structural letters in the three protein compartments (surface, core and interface) reveals that secondary structures tend to adopt preferential conformations that differ among the compartments. The local description of secondary structures highlights that curved conformations are preferred on the surface while straight ones are preferred in the core. Interfaces display a mixture of local conformations either preferred in core or surface. The analysis of the structural letters transition occurring between protein-bound and unbound conformations shows that the deformation of secondary structure is tightly linked to the compartment preference of the local conformations. The conformation of secondary structures can be further analysed and detailed thanks to a structural alphabet which allows a better description of protein surface, core and interface in terms of secondary structures' shape and deformation. Induced-fit modification tendencies described here should be valuable information to identify and characterize regions under strong structural constraints for functional reasons.

Online tools for uncovering data quality issues in satellite-based global precipitation products

NASA Astrophysics Data System (ADS)

Liu, Z.; Heo, G.

2015-12-01

Accurate and timely available global precipitation products are important to many applications such as flood forecasting, hydrological modeling, vector-borne disease research, crop yield estimates, etc. However, data quality issues such as biases and uncertainties are common in satellite-based precipitation products and it is important to understand these issues in applications. In recent years, algorithms using multi-satellites and multi-sensors for satellite-based precipitation estimates have become popular, such as the TRMM (Tropical Rainfall Measuring Mission) Multi-satellite Precipitation Analysis (TMPA) and the latest Integrated Multi-satellitE Retrievals for GPM (IMERG). Studies show that data quality issues for multi-satellite and multi-sensor products can vary with space and time and can be difficult to summarize. Online tools can provide customized results for a given area of interest, allowing customized investigation or comparison on several precipitation products. Because downloading data and software is not required, online tools can facilitate precipitation product evaluation and comparison. In this presentation, we will present online tools to uncover data quality issues in satellite-based global precipitation products. Examples will be presented as well.

Conceptualising Education Quality in Zambia: A Comparative Analysis across the Local, National and Global Discourses

ERIC Educational Resources Information Center

Lee, Jeongmin; Zuilkowski, Stephanie Simmons

2017-01-01

Building on the Education for All movement, the 2030 Agenda for Sustainable Development re-emphasises quality education as a discrete goal. Contextualising the discussion surrounding this goal in Zambia, this study examines how education quality is conceptualised by educational stakeholders at local, national, and global levels. Triangulating…

Virasoro conformal blocks and thermality from classical background fields

DOE PAGES

Fitzpatrick, A. Liam; Kaplan, Jared; Walters, Matthew T.

2015-11-30

We show that in 2d CFTs at large central charge, the coupling of the stress tensor to heavy operators can be re-absorbed by placing the CFT in a non-trivial background metric. This leads to a more precise computation of the Virasoro conformal blocks between heavy and light operators, which are shown to be equivalent to global conformal blocks evaluated in the new background. We also generalize to the case where the operators carry U(1) charges. The refined Virasoro blocks can be used as the seed for a new Virasoro block recursion relation expanded in the heavy-light limit. Furthermore, we commentmore » on the implications of our results for the universality of black hole thermality in AdS 3 , or equivalently, the eigenstate thermalization hypothesis for CFT 2 at large central charge.« less

A new clustering of antibody CDR loop conformations

PubMed Central

North, Benjamin; Lehmann, Andreas; Dunbrack, Roland L.

2010-01-01

Previous analyses of the complementarity determining regions (CDRs) of antibodies have focused on a small number of “canonical” conformations for each loop. This is primarily the result of the work of Chothia and colleagues, most recently in 1997. Because of the widespread utility of antibodies, we have revisited the clustering of conformations of the six CDR loops with the much larger amount of structural information currently available. In this work, we were careful to use a high-quality data set by eliminating low-resolution structures and CDRs with high B-factors or high conformational energies. We used a distance function based on directional statistics and an effective clustering algorithm using affinity propagation. With this data set of over 300 non-redundant antibody structures, we were able to cover 28 CDR-length combinations (e.g., L1 length 11, or “L1-11” in our nomenclature) for L1, L2, L3, H1 and H2. The Chothia analysis covered only 20 CDR-lengths. Only four of these had more than one conformational cluster, of which two could easily be distinguished by gene source (mouse/human; κ/λ) and one purely by the presence and positions of Pro residues (L3-9). Thus using the Chothia analysis does not require the complicated set of “structure-determining residues” that is often assumed. Of our 28 CDR-lengths, 15 of them have multiple conformational clusters including ten for which Chothia had only one canonical class. We have a total of 72 clusters for the non-H3 CDRs; approximately 85% of the non-H3 sequences can be assigned to a conformational cluster based on gene source and/or sequence. We found that earlier predictions of “bulged” vs. “non-bulged” conformations based on the presence or absence of anchor residues Arg/Lys94 and Asp101 of H3 have not held up, since all four combinations lead to a majority of conformations that are bulged. Thus the earlier analyses have been significantly enhanced by the increased data. We believe the

Fluorescent Protein-Based Ca2+ Sensor Reveals Global, Divalent Cation-Dependent Conformational Changes in Cardiac Troponin C.

PubMed

Badr, Myriam A; Pinto, Jose R; Davidson, Michael W; Chase, P Bryant

2016-01-01

Cardiac troponin C (cTnC) is a key effector in cardiac muscle excitation-contraction coupling as the Ca2+ sensing subunit responsible for controlling contraction. In this study, we generated several FRET sensors for divalent cations based on cTnC flanked by a donor fluorescent protein (CFP) and an acceptor fluorescent protein (YFP). The sensors report Ca2+ and Mg2+ binding, and relay global structural information about the structural relationship between cTnC's N- and C-domains. The sensors were first characterized using end point titrations to decipher the response to Ca2+ binding in the presence or absence of Mg2+. The sensor that exhibited the largest responses in end point titrations, CTV-TnC, (Cerulean, TnC, and Venus) was characterized more extensively. Most of the divalent cation-dependent FRET signal originates from the high affinity C-terminal EF hands. CTV-TnC reconstitutes into skinned fiber preparations indicating proper assembly of troponin complex, with only ~0.2 pCa unit rightward shift of Ca2+-sensitive force development compared to WT-cTnC. Affinity of CTV-TnC for divalent cations is in agreement with known values for WT-cTnC. Analytical ultracentrifugation indicates that CTV-TnC undergoes compaction as divalent cations bind. C-terminal sites induce ion-specific (Ca2+ versus Mg2+) conformational changes in cTnC. Our data also provide support for the presence of additional, non-EF-hand sites on cTnC for Mg2+ binding. In conclusion, we successfully generated a novel FRET-Ca2+ sensor based on full length cTnC with a variety of cellular applications. Our sensor reveals global structural information about cTnC upon divalent cation binding.

The effects of global change upon United States air quality

NASA Astrophysics Data System (ADS)

Gonzalez-Abraham, R.; Avise, J.; Chung, S. H.; Lamb, B.; Salathé, E. P., Jr.; Nolte, C. G.; Loughlin, D.; Guenther, A.; Wiedinmyer, C.; Duhl, T.; Zhang, Y.; Streets, D. G.

2014-12-01

To understand more fully the effects of global changes on ambient concentrations of ozone and particulate matter with aerodynamic diameter smaller than 2.5 μm (PM2.5) in the US, we conducted a comprehensive modeling effort to evaluate explicitly the effects of changes in climate, biogenic emissions, land use, and global/regional anthropogenic emissions on ozone and PM2.5 concentrations and composition. Results from the ECHAM5 global climate model driven with the A1B emission scenario from the Intergovernmental Panel on Climate Change (IPCC) were downscaled using the Weather Research and Forecasting (WRF) model to provide regional meteorological fields. We developed air quality simulations using the Community Multiscale Air Quality Model (CMAQ) chemical transport model for two nested domains with 220 and 36 km horizontal grid cell resolution for a semi-hemispheric domain and a continental United States (US) domain, respectively. The semi-hemispheric domain was used to evaluate the impact of projected Asian emissions changes on US air quality. WRF meteorological fields were used to calculate current (2000s) and future (2050s) biogenic emissions using the Model of Emissions of Gases and Aerosols from Nature (MEGAN). For the semi-hemispheric domain CMAQ simulations, present-day global emissions inventories were used and projected to the 2050s based on the IPCC A1B scenario. Regional anthropogenic emissions were obtained from the US Environmental Protection Agency National Emission Inventory 2002 (EPA NEI2002) and projected to the future using the MARKet ALlocation (MARKAL) energy system model assuming a business as usual scenario that extends current decade emission regulations through 2050. Our results suggest that daily maximum 8 h average ozone (DM8O) concentrations will increase in a range between 2 to 12 ppb across most of the continental US, with the highest increase in the South, Central, and Midwest regions of the US, due to increases in temperature, enhanced

Conformational analysis by intersection: CONAN.

PubMed

Smellie, Andrew; Stanton, Robert; Henne, Randy; Teig, Steve

2003-01-15

As high throughput techniques in chemical synthesis and screening improve, more demands are placed on computer assisted design and virtual screening. Many of these computational methods require one or more three-dimensional conformations for molecules, creating a demand for a conformational analysis tool that can rapidly and robustly cover the low-energy conformational spaces of small molecules. A new algorithm of intersection is presented here, which quickly generates (on average <0.5 seconds/stereoisomer) a complete description of the low energy conformational space of a small molecule. The molecule is first decomposed into nonoverlapping nodes N (usually rings) and overlapping paths P with conformations (N and P) generated in an offline process. In a second step the node and path data are combined to form distinct conformers of the molecule. Finally, heuristics are applied after intersection to generate a small representative collection of conformations that span the conformational space. In a study of approximately 97,000 randomly selected molecules from the MDDR, results are presented that explore these conformations and their ability to cover low-energy conformational space. Copyright 2002 Wiley Periodicals, Inc. J Comput Chem 24: 10-20, 2003

Conformal standard model with an extended scalar sector

NASA Astrophysics Data System (ADS)

Latosinski, Adam; Lewandowski, Adrian; Meissner, Krzysztof A.; Nicolai, Hermann

2015-10-01

We present an extended version of the Conformal Standard Model (characterized by the absence of any new intermediate scales between the electroweak scale and the Planck scale) with an enlarged scalar sector coupling to right-chiral neutrinos. The scalar potential and the Yukawa couplings involving only right-chiral neutrinos are invariant under a new global symmetry SU(3) N that complements the standard U(1) B-L symmetry, and is broken explicitly only by the Yukawa interaction, of order O (10-6), coupling right-chiral neutrinos and the electroweak lepton doublets. We point out four main advantages of this enlargement, namely: (1) the economy of the (non-supersymmetric) Standard Model, and thus its observational success, is preserved; (2) thanks to the enlarged scalar sector the RG improved one-loop effective potential is everywhere positive with a stable global minimum, thereby avoiding the notorious instability of the Standard Model vacuum; (3) the pseudo-Goldstone bosons resulting from spontaneous breaking of the SU(3) N symmetry are natural Dark Matter candidates with calculable small masses and couplings; and (4) the Majorana Yukawa coupling matrix acquires a form naturally adapted to leptogenesis. The model is made perturbatively consistent up to the Planck scale by imposing the vanishing of quadratic divergences at the Planck scale (`softly broken conformal symmetry'). Observable consequences of the model occur mainly via the mixing of the new scalars and the standard model Higgs boson.

Conformal expansions and renormalons

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

Rathsman, J.

2000-02-07

The coefficients in perturbative expansions in gauge theories are factorially increasing, predominantly due to renormalons. This type of factorial increase is not expected in conformal theories. In QCD conformal relations between observables can be defined in the presence of a perturbative infrared fixed-point. Using the Banks-Zaks expansion the authors study the effect of the large-order behavior of the perturbative series on the conformal coefficients. The authors find that in general these coefficients become factorially increasing. However, when the factorial behavior genuinely originates in a renormalon integral, as implied by a postulated skeleton expansion, it does not affect the conformal coefficients.more » As a consequence, the conformal coefficients will indeed be free of renormalon divergence, in accordance with previous observations concerning the smallness of these coefficients for specific observables. The authors further show that the correspondence of the BLM method with the skeleton expansion implies a unique scale-setting procedure. The BLM coefficients can be interpreted as the conformal coefficients in the series relating the fixed-point value of the observable with that of the skeleton effective charge. Through the skeleton expansion the relevance of renormalon-free conformal coefficients extends to real-world QCD.« less

Evaluating which plan quality metrics are appropriate for use in lung SBRT.

PubMed

Yaparpalvi, Ravindra; Garg, Madhur K; Shen, Jin; Bodner, William R; Mynampati, Dinesh K; Gafar, Aleiya; Kuo, Hsiang-Chi; Basavatia, Amar K; Ohri, Nitin; Hong, Linda X; Kalnicki, Shalom; Tome, Wolfgang A

2018-02-01

Several dose metrics in the categories-homogeneity, coverage, conformity and gradient have been proposed in literature for evaluating treatment plan quality. In this study, we applied these metrics to characterize and identify the plan quality metrics that would merit plan quality assessment in lung stereotactic body radiation therapy (SBRT) dose distributions. Treatment plans of 90 lung SBRT patients, comprising 91 targets, treated in our institution were retrospectively reviewed. Dose calculations were performed using anisotropic analytical algorithm (AAA) with heterogeneity correction. A literature review on published plan quality metrics in the categories-coverage, homogeneity, conformity and gradient was performed. For each patient, using dose-volume histogram data, plan quality metric values were quantified and analysed. For the study, the radiation therapy oncology group (RTOG) defined plan quality metrics were: coverage (0.90 ± 0.08); homogeneity (1.27 ± 0.07); conformity (1.03 ± 0.07) and gradient (4.40 ± 0.80). Geometric conformity strongly correlated with conformity index (p < 0.0001). Gradient measures strongly correlated with target volume (p < 0.0001). The RTOG lung SBRT protocol advocated conformity guidelines for prescribed dose in all categories were met in ≥94% of cases. The proportion of total lung volume receiving doses of 20 Gy and 5 Gy (V 20 and V 5 ) were mean 4.8% (±3.2) and 16.4% (±9.2), respectively. Based on our study analyses, we recommend the following metrics as appropriate surrogates for establishing SBRT lung plan quality guidelines-coverage % (ICRU 62), conformity (CN or CI Paddick ) and gradient (R 50% ). Furthermore, we strongly recommend that RTOG lung SBRT protocols adopt either CN or CI Padddick in place of prescription isodose to target volume ratio for conformity index evaluation. Advances in knowledge: Our study metrics are valuable tools for establishing lung SBRT plan quality guidelines.

Evaluation of global water quality - the potential of a data- and model-driven analysis

NASA Astrophysics Data System (ADS)

Bärlund, Ilona; Flörke, Martina; Alcamo, Joseph; Völker, Jeanette; Malsy, Marcus; Kaus, Andrew; Reder, Klara; Büttner, Olaf; Katterfeld, Christiane; Dietrich, Désirée; Borchardt, Dietrich

2016-04-01

The ongoing socio-economic development presents a new challenge for water quality worldwide, especially in developing and emerging countries. It is estimated that due to population growth and the extension of water supply networks, the amount of waste water will rise sharply. This can lead to an increased risk of surface water quality degradation, if the wastewater is not sufficiently treated. This development has impacts on ecosystems and human health, as well as food security. The United Nations Member States have adopted targets for sustainable development. They include, inter alia, sustainable protection of water quality and sustainable use of water resources. To achieve these goals, appropriate monitoring strategies and the development of indicators for water quality are required. Within the pre-study for a 'World Water Quality Assessment' (WWQA) led by United Nations Environment Programme (UNEP), a methodology for assessing water quality, taking into account the above-mentioned objectives has been developed. The novelty of this methodology is the linked model- and data-driven approach. The focus is on parameters reflecting the key water quality issues, such as increased waste water pollution, salinization or eutrophication. The results from the pre-study show, for example, that already about one seventh of all watercourses in Latin America, Africa and Asia show high organic pollution. This is of central importance for inland fisheries and associated food security. In addition, it could be demonstrated that global water quality databases have large gaps. These must be closed in the future in order to obtain an overall picture of global water quality and to target measures more efficiently. The aim of this presentation is to introduce the methodology developed within the WWQA pre-study and to show selected examples of application in Latin America, Africa and Asia.

Global Quality of Life Among WHI Women Aged 80 Years and Older

PubMed Central

Brunner, Robert L.; Hogan, Patricia E.; Danhauer, Suzanne C.; Brenes, Gretchen A.; Bowen, Deborah J.; Snively, Beverly M.; Goveas, Joseph S.; Saquib, Nazmus; Zaslavsky, Oleg; Shumaker, Sally A.

2016-01-01

Abstract Background. The number of older adults living to age 80 and older is increasing rapidly, particularly among women. Correlates of quality of life (QOL) in very advanced ages are not known. We examined the association of demographic, social-psychological, lifestyle, and physical health variables with global QOL in a Women’s Health Initiative (WHI) cohort of women aged 80 and older. Methods. 26,299 WHI participants, who had completed a recent psychosocial and medical update, were included in these analyses. Global QOL was assessed by a single item, asking the women to rate their overall QOL on a scale from 0 to 10. Characteristics of the women were examined by the level of their transformed global QOL scores (≤50, 50–70, ≥70), and multiple regression was used to examine which demographic, social-psychological, lifestyle and health variables were independently associated with higher global QOL. Results. Social-psychological and current health variables were more strongly associated with global QOL than a history of selected comorbid conditions. In particular, higher self-rated health and fewer depressive symptoms were the most strongly associated with better global QOL in WHI women ≥80 years. Conclusions. Interventions to reduce depressive symptoms and improve health may lead to better self-reported health and global QOL among older women. Physical and mental health screenings followed by evidence-based interventions are imperative in geriatric care. PMID:26858327

Global impacts of conversions from natural to agricultural ecosystems on water resources: Quantity versus quality

NASA Astrophysics Data System (ADS)

Scanlon, Bridget R.; Jolly, Ian; Sophocleous, Marios; Zhang, Lu

2007-03-01

Past land use changes have greatly impacted global water resources, with often opposing effects on water quantity and quality. Increases in rain-fed cropland (460%) and pastureland (560%) during the past 300 years from forest and grasslands decreased evapotranspiration and increased recharge (two orders of magnitude) and streamflow (one order of magnitude). However, increased water quantity degraded water quality by mobilization of salts, salinization caused by shallow water tables, and fertilizer leaching into underlying aquifers that discharge to streams. Since the 1950s, irrigated agriculture has expanded globally by 174%, accounting for ˜90% of global freshwater consumption. Irrigation based on surface water reduced streamflow and raised water tables resulting in waterlogging in many areas (China, India, and United States). Marked increases in groundwater-fed irrigation in the last few decades in these areas has lowered water tables (≤1 m/yr) and reduced streamflow. Degradation of water quality in irrigated areas has resulted from processes similar to those in rain-fed agriculture: salt mobilization, salinization in waterlogged areas, and fertilizer leaching. Strategies for remediating water resource problems related to agriculture often have opposing effects on water quantity and quality. Long time lags (decades to centuries) between land use changes and system response (e.g., recharge, streamflow, and water quality), particularly in semiarid regions, mean that the full impact of land use changes has not been realized in many areas and remediation to reverse impacts will also take a long time. Future land use changes should consider potential impacts on water resources, particularly trade-offs between water, salt, and nutrient balances, to develop sustainable water resources to meet human and ecosystem needs.

Global impacts of conversions from natural to agricultural ecosystems on water resources: Quantity versus quality

USGS Publications Warehouse

Scanlon, Bridget R.; Jolly, Ian; Sophocleous, Marios; Zhang, Lu

2007-01-01

Past land use changes have greatly impacted global water resources, with often opposing effects on water quantity and quality. Increases in rain‐fed cropland (460%) and pastureland (560%) during the past 300 years from forest and grasslands decreased evapotranspiration and increased recharge (two orders of magnitude) and streamflow (one order of magnitude). However, increased water quantity degraded water quality by mobilization of salts, salinization caused by shallow water tables, and fertilizer leaching into underlying aquifers that discharge to streams. Since the 1950s, irrigated agriculture has expanded globally by 174%, accounting for ∼90% of global freshwater consumption. Irrigation based on surface water reduced streamflow and raised water tables resulting in waterlogging in many areas (China, India, and United States). Marked increases in groundwater‐fed irrigation in the last few decades in these areas has lowered water tables (≤1 m/yr) and reduced streamflow. Degradation of water quality in irrigated areas has resulted from processes similar to those in rain‐fed agriculture: salt mobilization, salinization in waterlogged areas, and fertilizer leaching. Strategies for remediating water resource problems related to agriculture often have opposing effects on water quantity and quality. Long time lags (decades to centuries) between land use changes and system response (e.g., recharge, streamflow, and water quality), particularly in semiarid regions, mean that the full impact of land use changes has not been realized in many areas and remediation to reverse impacts will also take a long time. Future land use changes should consider potential impacts on water resources, particularly trade‐offs between water, salt, and nutrient balances, to develop sustainable water resources to meet human and ecosystem needs.

Is non-conformity WEIRD? Cultural variation in adults' beliefs about children's competency and conformity.

PubMed

Clegg, Jennifer M; Wen, Nicole J; Legare, Cristine H

2017-03-01

Cross-cultural comparisons provide critical insight into variation in reasoning about intelligence. In two studies, the authors used a novel methodology based on multivocal ethnography to assess the role of conformity in U.S. and Ni-Vanuatu adults' judgments of children's intelligence and, as a comparison trait, good behavior. In Study 1, there were cultural differences in the impact of conformity on U.S. and Ni-Vanuatu adults' judgments of children's intelligence and good behavior. When evaluating U.S. children only, U.S. adults were less likely to endorse high conformity children as intelligent, often citing creativity as a justification for their judgments. In contrast, Ni-Vanuatu adults were more likely to endorse Ni-Vanuatu high conformity children as intelligent. Ni-Vanuatu adults were also more likely to endorse high conformity children as well-behaved than U.S. adults. In Study 2, there were no effects of socioeconomic status on U.S. adults' evaluations of conformity. U.S. adults were less likely to endorse high conformity children as intelligent than Ni-Vanuatu adults. Taken together, the data demonstrate that beliefs about the relations between intelligence, conformity, and creativity vary within and across cultures. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Using the ACEI Global Guidelines Assessment to Evaluate the Quality of Early Child Care in Greek Settings

ERIC Educational Resources Information Center

Rentzou, Konstantina

2010-01-01

In recent years, there has been a significant growth of interest in ensuring that child care provision for children is of a high quality. This interest has been stimulated by research evidence according to which good quality child care has a positive influence on children's overall development. The global quality in Greek preschool and…

INTERIM GUIDANCE FOR DEVELOPING GLOBAL POSITIONING SYSTEM DATA COLLECTION STANDARD OPERATING PROCEDURES AND QUALITY ASSURANCE PROJECT PLANS

EPA Science Inventory

The United States Environmental Protection Agency Geospatial Quality Council developed this document to harmonize the process of collecting, editing, and exporting spatial data of known quality using the Global Positioning System (GPS). Each organizational entity may adopt this d...

MQAPRank: improved global protein model quality assessment by learning-to-rank.

PubMed

Jing, Xiaoyang; Dong, Qiwen

2017-05-25

Protein structure prediction has achieved a lot of progress during the last few decades and a greater number of models for a certain sequence can be predicted. Consequently, assessing the qualities of predicted protein models in perspective is one of the key components of successful protein structure prediction. Over the past years, a number of methods have been developed to address this issue, which could be roughly divided into three categories: single methods, quasi-single methods and clustering (or consensus) methods. Although these methods achieve much success at different levels, accurate protein model quality assessment is still an open problem. Here, we present the MQAPRank, a global protein model quality assessment program based on learning-to-rank. The MQAPRank first sorts the decoy models by using single method based on learning-to-rank algorithm to indicate their relative qualities for the target protein. And then it takes the first five models as references to predict the qualities of other models by using average GDT_TS scores between reference models and other models. Benchmarked on CASP11 and 3DRobot datasets, the MQAPRank achieved better performances than other leading protein model quality assessment methods. Recently, the MQAPRank participated in the CASP12 under the group name FDUBio and achieved the state-of-the-art performances. The MQAPRank provides a convenient and powerful tool for protein model quality assessment with the state-of-the-art performances, it is useful for protein structure prediction and model quality assessment usages.

Chinese vaccine products go global: vaccine development and quality control.

PubMed

Xu, Miao; Liang, Zhenglun; Xu, Yinghua; Wang, Junzhi

2015-05-01

Through the continuous efforts of several generations, China has become one of the few countries in the world that is capable of independently addressing all the requirements by the Expanded Program on Immunization. Regulatory science is applied to continuously improve the vaccine regulatory system. Passing the prequalification by WHO has allowed Chinese vaccine products to go global. Chinese vaccine products not only secure disease prevention and control domestically but also serve the needs for international public health. This article describes the history of Chinese vaccine development, the current situation of Chinese vaccine industry and its contribution to the prevention and control of infectious diseases. We also share our experience of national quality control and vaccine regulation during the past decades. China's experience in vaccine development and quality control can benefit other countries and regions worldwide, including the developing countries.

Reducing greenhouse gas emissions and improving air quality: Two global challenges.

PubMed

Erickson, Larry E

2017-07-01

There are many good reasons to promote sustainable development and reduce greenhouse gas emissions and other combustion emissions. The air quality in many urban environments is causing many premature deaths because of asthma, cardiovascular disease, chronic obstructive pulmonary disease, lung cancer, and dementia associated with combustion emissions. The global social cost of air pollution is at least $3 trillion/year; particulates, nitrogen oxides and ozone associated with combustion emissions are very costly pollutants. Better air quality in urban environments is one of the reasons for countries to work together to reduce greenhouse gas emissions through the Paris Agreement on Climate Change. There are many potential benefits associated with limiting climate change. In the recent past, the concentrations of greenhouse gases in the atmosphere have been increasing and the number of weather and climate disasters with costs over $1 billion has been increasing. The average global temperature set new record highs in 2014, 2015, and 2016. To reduce greenhouse gas emissions, the transition to electric vehicles and electricity generation using renewable energy must take place in accord with the goals of the Paris Agreement on Climate Change. This work reviews progress and identifies some of the health benefits associated with reducing combustion emissions. © 2017 American Institute of Chemical Engineers Environ Prog, 36: 982-988, 2017.

Conformal superalgebras via tractor calculus

NASA Astrophysics Data System (ADS)

Lischewski, Andree

2015-01-01

We use the manifestly conformally invariant description of a Lorentzian conformal structure in terms of a parabolic Cartan geometry in order to introduce a superalgebra structure on the space of twistor spinors and normal conformal vector fields formulated in purely algebraic terms on parallel sections in tractor bundles. Via a fixed metric in the conformal class, one reproduces a conformal superalgebra structure that has been considered in the literature before. The tractor approach, however, makes clear that the failure of this object to be a Lie superalgebra in certain cases is due to purely algebraic identities on the spinor module and to special properties of the conformal holonomy representation. Moreover, it naturally generalizes to higher signatures. This yields new formulas for constructing new twistor spinors and higher order normal conformal Killing forms out of existing ones, generalizing the well-known spinorial Lie derivative. Moreover, we derive restrictions on the possible dimension of the space of twistor spinors in any metric signature.

Protonation-dependent conformational dynamics of the multidrug transporter EmrE

PubMed Central

Dastvan, Reza; Mishra, Smriti; Meiler, Jens; Mchaourab, Hassane S.

2016-01-01

The small multidrug transporter from Escherichia coli, EmrE, couples the energetically uphill extrusion of hydrophobic cations out of the cell to the transport of two protons down their electrochemical gradient. Although principal mechanistic elements of proton/substrate antiport have been described, the structural record is limited to the conformation of the substrate-bound state, which has been shown to undergo isoenergetic alternating access. A central but missing link in the structure/mechanism relationship is a description of the proton-bound state, which is an obligatory intermediate in the transport cycle. Here we report a systematic spin labeling and double electron electron resonance (DEER) study that uncovers the conformational changes of EmrE subsequent to protonation of critical acidic residues in the context of a global description of ligand-induced structural rearrangements. We find that protonation of E14 leads to extensive rotation and tilt of transmembrane helices 1–3 in conjunction with repacking of loops, conformational changes that alter the coordination of the bound substrate and modulate its access to the binding site from the lipid bilayer. The transport model that emerges from our data posits a proton-bound, but occluded, resting state. Substrate binding from the inner leaflet of the bilayer releases the protons and triggers alternating access between inward- and outward-facing conformations of the substrate-loaded transporter, thus enabling antiport without dissipation of the proton gradient. PMID:26787875

An Acrobatic Substrate Metamorphosis Reveals a Requirement for Substrate Conformational Dynamics in Trypsin Proteolysis*

PubMed Central

Kayode, Olumide; Wang, Ruiying; Pendlebury, Devon F.; Cohen, Itay; Henin, Rachel D.; Hockla, Alexandra; Soares, Alexei S.; Papo, Niv; Caulfield, Thomas R.; Radisky, Evette S.

2016-01-01

The molecular basis of enzyme catalytic power and specificity derives from dynamic interactions between enzyme and substrate during catalysis. Although considerable effort has been devoted to understanding how conformational dynamics within enzymes affect catalysis, the role of conformational dynamics within protein substrates has not been addressed. Here, we examine the importance of substrate dynamics in the cleavage of Kunitz-bovine pancreatic trypsin inhibitor protease inhibitors by mesotrypsin, finding that the varied conformational dynamics of structurally similar substrates can profoundly impact the rate of catalysis. A 1.4-Å crystal structure of a mesotrypsin-product complex formed with a rapidly cleaved substrate reveals a dramatic conformational change in the substrate upon proteolysis. By using long all-atom molecular dynamics simulations of acyl-enzyme intermediates with proteolysis rates spanning 3 orders of magnitude, we identify global and local dynamic features of substrates on the nanosecond-microsecond time scale that correlate with enzymatic rates and explain differential susceptibility to proteolysis. By integrating multiple enhanced sampling methods for molecular dynamics, we model a viable conformational pathway between substrate-like and product-like states, linking substrate dynamics on the nanosecond-microsecond time scale with large collective substrate motions on the much slower time scale of catalysis. Our findings implicate substrate flexibility as a critical determinant of catalysis. PMID:27810896

An Acrobatic Substrate Metamorphosis Reveals a Requirement for Substrate Conformational Dynamics in Trypsin Proteolysis

DOE PAGES

Kayode, Olumide; Wang, Ruiying; Pendlebury, Devon F.; ...

2016-11-03

The molecular basis of enzyme catalytic power and specificity derives from dynamic interactions between enzyme and substrate during catalysis. While considerable effort has been devoted to understanding how conformational dynamics within enzymes affect catalysis, the role of conformational dynamics within protein substrates has not been addressed. Here in this paper, we examine the importance of substrate dynamics in the cleavage of Kunitz-BPTI protease inhibitors by mesotrypsin, finding that the varied conformational dynamics of structurally similar substrates can profoundly impact the rate of catalysis. A 1.4 Å crystal structure of a mesotrypsin-product complex formed with a rapidly cleaved substrate reveals amore » dramatic conformational change in the substrate upon proteolysis. Using long all-atom molecular dynamics simulations of acyl-enzyme intermediates with proteolysis rates spanning three orders of magnitude, we identify global and local dynamic features of substrates on the ns-μs timescale that correlate with enzymatic rates and explain differential susceptibility to proteolysis. By integrating multiple enhanced sampling methods for molecular dynamics, we model a viable conformational pathway between substratelike and product-like states, linking substrate dynamics on the ns-μs timescale with large collective substrate motions on the much slower timescale of catalysis. Our findings implicate substrate flexibility as a critical determinant of catalysis.« less

Implementation of three dimensional conformal radiation therapy: prospects, opportunities, and challenges.

PubMed

Vijayakumar, S; Chen, G T

1995-12-01

To briefly review scientific rationale of 3D conformal radiation therapy (3DCRT) and discuss the prospects, opportunities, and challenges in the implementation of 3DCRT. Some of these ideas were discussed during a workshop on "Implementation of Three-Dimensional Conformal Radiation Therapy" in April 1994 at Bethesda, MD, and others have been discussed elsewhere in the literature. Local-regional control of cancer is an important component in the overall treatment strategy in any patient with cancer. It has been shown that failure to achieve local-regional control can lead to (a) an increase in chances of distant metastases, and (b) a decrease in the survival. In many disease sites, the doses delivered currently are inadequate to achieve satisfactory local tumor control rates; this is because in many sites, only limited doses of radiotherapy can be delivered due to the proximity of cancer to radiosensitive normal tissues. By conforming the radiotherapy beams to the tumor, doses to the tumors can be enhanced and doses to the normal tissues can be reduced. With the advances in 3DCRT, such conformation is possible now and is the rationale for using 3DCRT. However, a number of questions do remain that are not limited to the following: (a) What are the implications in terms of target volume definitions when implementing 3DCRT? (b) Are there some sites where research efforts can be focused to document the efficacy and cost effectiveness of 3DCRT? (c) How do we implement day-to-day 3DCRT treatment efficiently? (d) How do we transfer the technology from the university centers to the community without compromising quality? (e) What are all the quality assurance/quality improvement questions that need to be addressed and how do we ascertain quality assurance of 3DCRT? (f) Have we looked at cost-benefit ratios and quality of life (QOL) issues closely? There is a need for defining multiple target volumes: gross tumor volume, clinical target volume(s), and planning target volume

Fabrication challenges associated with conformal optics

NASA Astrophysics Data System (ADS)

Schaefer, John; Eichholtz, Richard A.; Sulzbach, Frank C.

2001-09-01

A conformal optic is typically an optical window that conforms smoothly to the external shape of a system platform to improve aerodynamics. Conformal optics can be on-axis, such as an ogive missile dome, or off-axis, such as in a free form airplane wing. A common example of conformal optics is the automotive head light window that conforms to the body of the car aerodynamics and aesthetics. The unusual shape of conformal optics creates tremendous challenges for design, manufacturing, and testing. This paper will discuss fabrication methods that have been successfully demonstrated to produce conformal missile domes and associated wavefront corrector elements. It will identify challenges foreseen with more complex free-form configurations. Work presented in this paper was directed by the Precision Conformal Optics Consortium (PCOT). PCOT is comprised of both industrial and academic members who teamed to develop and demonstrate conformal optical systems suitable for insertion into future military programs. The consortium was funded under DARPA agreement number MDA972-96-9-08000.

Reactions driving conformational movements (molecular motors) in gels: conformational and structural chemical kinetics.

PubMed

Otero, Toribio F

2017-01-18

In this perspective the empirical kinetics of conducting polymers exchanging anions and solvent during electrochemical reactions to get dense reactive gels is reviewed. The reaction drives conformational movements of the chains (molecular motors), exchange of ions and solvent with the electrolyte and structural (relaxation, swelling, shrinking and compaction) gel changes. Reaction-driven structural changes are identified and quantified from electrochemical responses. The empirical reaction activation energy (E a ), the reaction coefficient (k) and the reaction orders (α and β) change as a function of the conformational energy variation during the reaction. This conformational energy becomes an empirical magnitude. E a , k, α and β include and provide quantitative conformational and structural information. The chemical kinetics becomes structural chemical kinetics (SCK) for reactions driving conformational movements of the reactants. The electrochemically stimulated conformational relaxation model describes empirical results and some results from the literature for biochemical reactions. In parallel the development of an emerging technological world of soft, wet, multifunctional and biomimetic tools and anthropomorphic robots driven by reactions of the constitutive material, as in biological organs, can be now envisaged being theoretically supported by the kinetic model.

Fermion-scalar conformal blocks

DOE PAGES

Iliesiu, Luca; Kos, Filip; Poland, David; ...

2016-04-13

In this study, we compute the conformal blocks associated with scalar-scalar-fermionfermion 4-point functions in 3D CFTs. Together with the known scalar conformal blocks, our result completes the task of determining the so-called ‘seed blocks’ in three dimensions. In addition, conformal blocks associated with 4-point functions of operators with arbitrary spins can now be determined from these seed blocks by using known differential operators.

OSI Conformance Testing for Bibliographic Applications.

ERIC Educational Resources Information Center

Arbez, Gilbert; Swain, Leigh

1990-01-01

Describes the development of Open Systems Interconnection (OSI) conformance testing sites, conformance testing tools, and conformance testing services. Discusses related topics such as interoperability testing, arbitration testing, and international harmonization of conformance testing. A glossary is included. (24 references) (SD)

Tired telomeres: Poor global sleep quality, perceived stress, and telomere length in immune cell subsets in obese men and women.

PubMed

Prather, Aric A; Gurfein, Blake; Moran, Patricia; Daubenmier, Jennifer; Acree, Michael; Bacchetti, Peter; Sinclair, Elizabeth; Lin, Jue; Blackburn, Elizabeth; Hecht, Frederick M; Epel, Elissa S

2015-07-01

Poor sleep quality and short sleep duration are associated with increased incidence and progression of a number of chronic health conditions observed at greater frequency among the obese and those experiencing high levels of stress. Accelerated cellular aging, as indexed by telomere attrition in immune cells, is a plausible pathway linking sleep and disease risk. Prior studies linking sleep and telomere length are mixed. One factor may be reliance on leukocytes, which are composed of varied immune cell types, as the sole measure of telomere length. To better clarify these associations, we investigated the relationships of global sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI), and diary-reported sleep duration with telomere length in different immune cell subsets, including granulocytes, peripheral blood mononuclear cells (PBMCs), CD8+ and CD4+ T lymphocytes, and B lymphocytes in a sample of 87 obese men and women (BMI mean=35.4, SD=3.6; 81.6% women; 62.8% Caucasian). Multiple linear regression analyses were performed adjusting for age, gender, race, education, BMI, sleep apnea risk, and perceived stress. Poorer PSQI global sleep quality was associated with statistically significantly shorter telomere length in lymphocytes but not granulocytes and in particular CD8+ T cells (b=-56.8 base pairs per one point increase in PSQI, SE=20.4, p=0.007) and CD4+ T cells (b=-37.2, SE=15.9, p=0.022). Among separate aspects of global sleep quality, low perceived sleep quality and decrements in daytime function were most related to shorter telomeres. In addition, perceived stress moderated the sleep-CD8+ telomere association. Poorer global sleep quality predicted shorter telomere length in CD8+ T cells among those with high perceived stress but not in low stress participants. These findings provide preliminary evidence that poorer global sleep quality is related to telomere length in several immune cell types, which may serve as a pathway linking sleep and

PubChem3D: Conformer generation

PubMed Central

2011-01-01

Background PubChem, an open archive for the biological activities of small molecules, provides search and analysis tools to assist users in locating desired information. Many of these tools focus on the notion of chemical structure similarity at some level. PubChem3D enables similarity of chemical structure 3-D conformers to augment the existing similarity of 2-D chemical structure graphs. It is also desirable to relate theoretical 3-D descriptions of chemical structures to experimental biological activity. As such, it is important to be assured that the theoretical conformer models can reproduce experimentally determined bioactive conformations. In the present study, we investigate the effects of three primary conformer generation parameters (the fragment sampling rate, the energy window size, and force field variant) upon the accuracy of theoretical conformer models, and determined optimal settings for PubChem3D conformer model generation and conformer sampling. Results Using the software package OMEGA from OpenEye Scientific Software, Inc., theoretical 3-D conformer models were generated for 25,972 small-molecule ligands, whose 3-D structures were experimentally determined. Different values for primary conformer generation parameters were systematically tested to find optimal settings. Employing a greater fragment sampling rate than the default did not improve the accuracy of the theoretical conformer model ensembles. An ever increasing energy window did increase the overall average accuracy, with rapid convergence observed at 10 kcal/mol and 15 kcal/mol for model building and torsion search, respectively; however, subsequent study showed that an energy threshold of 25 kcal/mol for torsion search resulted in slightly improved results for larger and more flexible structures. Exclusion of coulomb terms from the 94s variant of the Merck molecular force field (MMFF94s) in the torsion search stage gave more accurate conformer models at lower energy windows. Overall

The Global Streamflow Indices and Metadata Archive (GSIM) - Part 2: Quality control, time-series indices and homogeneity assessment

NASA Astrophysics Data System (ADS)

Gudmundsson, Lukas; Do, Hong Xuan; Leonard, Michael; Westra, Seth

2018-04-01

This is Part 2 of a two-paper series presenting the Global Streamflow Indices and Metadata Archive (GSIM), which is a collection of daily streamflow observations at more than 30 000 stations around the world. While Part 1 (Do et al., 2018a) describes the data collection process as well as the generation of auxiliary catchment data (e.g. catchment boundary, land cover, mean climate), Part 2 introduces a set of quality controlled time-series indices representing (i) the water balance, (ii) the seasonal cycle, (iii) low flows and (iv) floods. To this end we first consider the quality of individual daily records using a combination of quality flags from data providers and automated screening methods. Subsequently, streamflow time-series indices are computed for yearly, seasonal and monthly resolution. The paper provides a generalized assessment of the homogeneity of all generated streamflow time-series indices, which can be used to select time series that are suitable for a specific task. The newly generated global set of streamflow time-series indices is made freely available with an digital object identifier at https://doi.pangaea.de/10.1594/PANGAEA.887470 and is expected to foster global freshwater research, by acting as a ground truth for model validation or as a basis for assessing the role of human impacts on the terrestrial water cycle. It is hoped that a renewed interest in streamflow data at the global scale will foster efforts in the systematic assessment of data quality and provide momentum to overcome administrative barriers that lead to inconsistencies in global collections of relevant hydrological observations.

Global chain properties of an all l-α-eicosapeptide with a secondary α-helix and its all retro d-inverso-α-eicosapeptide estimated through the modeling of their CZE-determined electrophoretic mobilities.

PubMed

Deiber, Julio A; Piaggio, Maria V; Peirotti, Marta B

2014-03-01

Several global chain properties of relatively long peptides composed of 20 amino acid residues are estimated through the modeling of their experimental effective electrophoretic mobilities determined by CZE for 2 < pH < 6. In this regard, an all l-α-eicosapeptide, including a secondary α-helix (Peptide 1) and its all retro d-inverso-α-eicosapeptide (Peptide 2), are considered. Despite Peptides 1 and 2 are isomeric chains, they do not present similar global conformations in the whole range of pH studied. These peptides may also differ in the quality of BGE components chain interactions depending on the pH value. Three Peptide 1 fragments (Peptides 3, 4, and 5) are also analyzed in this framework with the following purposes: (i) visualization of the effects of initial and final strands at each side of the α-helix on the global chain conformations of Peptide 1 at different pHs and (ii) analysis of global chain conformations of Peptides 1 and 2, and Peptide 1 fragments in relation to their pI values. Also, the peptide maximum and minimum hydrations predicted by the model, compatible with experimental effective electrophoretic mobilities at different pHs, are quantified and discussed, and needs for further research concerning chain hydration are proposed. It is shown that CZE is a useful analytical tool for peptidomimetic designs and purposes. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Social Factors in Aesthetics: Social Conformity Pressure and a Sense of Being Watched Affect Aesthetic Judgments

PubMed Central

Carbon, Claus-Christian; Hecht, Heiko

2017-01-01

The present study is a first attempt to experimentally test the impact of two specific social factors, namely social conformity pressure and a sense of being watched, on participants’ judgments of the artistic quality of aesthetic objects. We manipulated conformity pressure with a test form in which a photograph of each stimulus was presented together with unanimously low (downward pressure) or high quality ratings (upward pressure) of three would-be previous raters. Participants’ sense of being watched was manipulated by testing each of them in two settings, one of which contained an eyespots stimulus. Both social factors significantly affected the participants’ judgments—unexpectedly, however, with conformity pressure only working in the downward direction and eyespots leading to an overall downward shift in participants’ judgments. Our findings indicate the relevance of including explicit and implicit social factors in aesthetics research, thus also reminding us of the limitations of overly reductionist approaches to investigating aesthetic perception and experience. PMID:29201336

Social Factors in Aesthetics: Social Conformity Pressure and a Sense of Being Watched Affect Aesthetic Judgments.

PubMed

Hesslinger, Vera M; Carbon, Claus-Christian; Hecht, Heiko

2017-01-01

The present study is a first attempt to experimentally test the impact of two specific social factors, namely social conformity pressure and a sense of being watched, on participants' judgments of the artistic quality of aesthetic objects. We manipulated conformity pressure with a test form in which a photograph of each stimulus was presented together with unanimously low (downward pressure) or high quality ratings (upward pressure) of three would-be previous raters. Participants' sense of being watched was manipulated by testing each of them in two settings, one of which contained an eyespots stimulus. Both social factors significantly affected the participants' judgments-unexpectedly, however, with conformity pressure only working in the downward direction and eyespots leading to an overall downward shift in participants' judgments. Our findings indicate the relevance of including explicit and implicit social factors in aesthetics research, thus also reminding us of the limitations of overly reductionist approaches to investigating aesthetic perception and experience.

Diagnostic Accuracy of Global Pharma Health Fund Minilab™ in Assessing Pharmacopoeial Quality of Antimicrobials.

PubMed

Pan, Hui; Ba-Thein, William

2018-01-01

Global Pharma Health Fund (GPHF) Minilab™, a semi-quantitative thin-layer chromatography (TLC)-based commercially available test kit, is widely used in drug quality surveillance globally, but its diagnostic accuracy is unclear. We investigated the diagnostic accuracy of Minilab system for antimicrobials, using high-performance liquid chromatography (HPLC) as reference standard. Following the Minilab protocols and the Pharmacopoeia of the People's Republic of China protocols, Minilab-TLC and HPLC were used to test five common antimicrobials (506 batches) for relative concentration of active pharmaceutical ingredients. The prevalence of poor-quality antimicrobials determined, respectively, by Minilab TLC and HPLC was amoxicillin (0% versus 14.9%), azithromycin (0% versus 17.4%), cefuroxime axetil (14.3% versus 0%), levofloxacin (0% versus 3.0%), and metronidazole (0% versus 38.0%). The Minilab TLC had false-positive and false-negative detection rates of 2.6% (13/506) and 15.2% (77/506) accordingly, resulting in the following test characteristics: sensitivity 0%, specificity 97.0%, positive predictive value 0, negative predictive value 0.8, positive likelihood ratio 0, negative likelihood ratio 1.0, diagnostic odds ratio 0, and adjusted diagnostic odds ratio 0.2. This study demonstrates unsatisfying diagnostic accuracy of Minilab system in screening poor-quality antimicrobials of common use. Using Minilab as a stand-alone system for monitoring drug quality should be reconsidered.

Dynamic and Progressive Control of DNA Origami Conformation by Modulating DNA Helicity with Chemical Adducts.

PubMed

Chen, Haorong; Zhang, Hanyu; Pan, Jing; Cha, Tae-Gon; Li, Shiming; Andréasson, Joakim; Choi, Jong Hyun

2016-05-24

DNA origami has received enormous attention for its ability to program complex nanostructures with a few nanometer precision. Dynamic origami structures that change conformation in response to environmental cues or external signals hold great promises in sensing and actuation at the nanoscale. The reconfiguration mechanism of existing dynamic origami structures is mostly limited to single-stranded hinges and relies almost exclusively on DNA hybridization or strand displacement. Here, we show an alternative approach by demonstrating on-demand conformation changes with DNA-binding molecules, which intercalate between base pairs and unwind DNA double helices. The unwinding effect modulates the helicity mismatch in DNA origami, which significantly influences the internal stress and the global conformation of the origami structure. We demonstrate the switching of a polymerized origami nanoribbon between different twisting states and a well-constrained torsional deformation in a monomeric origami shaft. The structural transformation is shown to be reversible, and binding isotherms confirm the reconfiguration mechanism. This approach provides a rapid and reversible means to change DNA origami conformation, which can be used for dynamic and progressive control at the nanoscale.

Quality of Life Theory I. The IQOL Theory: An Integrative Theory of the Global Quality of Life Concept

PubMed Central

Ventegodt, Soren; Merrick, Joav; Andersen, Niels Jorgen

2003-01-01

Quality of life (QOL) means a good life and we believe that a good life is the same as living a life with a high quality. This paper presents the theoretical and philosophical framework of the Danish Quality of Life Survey, and of the SEQOL, QOL5, and QOL1 questionnaires.The notion of a good life can be observed from subjective to the objective, where this spectrum incorporates a number of existing quality of life theories. We call this spectrum the integrative quality-of-life (IQOL) theory and discuss the following aspects in this paper: well being, satisfaction with life, happiness, meaning in life, the biological information system (“balance”), realizing life potential, fulfillment of needs, and objective factors.The philosophy of life outlined in this paper tries to measure the global quality of life with questions derived from the integrative theory of the quality of life. The IQOL theory is an overall theory or meta-theory encompassing eight more factual theories in a subjective-existential-objective spectrum. Other philosophies of life can stress other aspects of life, but by this notion of introducing such an existential depth into the health and social sciences, we believe to have taken a necessary step towards a new humility and respect for the richness and complexity of life. PMID:14570993

Preparing the Model for Prediction Across Scales (MPAS) for global retrospective air quality modeling

EPA Science Inventory

The US EPA has a plan to leverage recent advances in meteorological modeling to develop a "Next-Generation" air quality modeling system that will allow consistent modeling of problems from global to local scale. The meteorological model of choice is the Model for Predic...

Reducing greenhouse gas emissions and improving air quality: Two global challenges

PubMed Central

2017-01-01

There are many good reasons to promote sustainable development and reduce greenhouse gas emissions and other combustion emissions. The air quality in many urban environments is causing many premature deaths because of asthma, cardiovascular disease, chronic obstructive pulmonary disease, lung cancer, and dementia associated with combustion emissions. The global social cost of air pollution is at least $3 trillion/year; particulates, nitrogen oxides and ozone associated with combustion emissions are very costly pollutants. Better air quality in urban environments is one of the reasons for countries to work together to reduce greenhouse gas emissions through the Paris Agreement on Climate Change. There are many potential benefits associated with limiting climate change. In the recent past, the concentrations of greenhouse gases in the atmosphere have been increasing and the number of weather and climate disasters with costs over $1 billion has been increasing. The average global temperature set new record highs in 2014, 2015, and 2016. To reduce greenhouse gas emissions, the transition to electric vehicles and electricity generation using renewable energy must take place in accord with the goals of the Paris Agreement on Climate Change. This work reviews progress and identifies some of the health benefits associated with reducing combustion emissions. © 2017 American Institute of Chemical Engineers Environ Prog, 36: 982–988, 2017 PMID:29238442

The conformal characters

NASA Astrophysics Data System (ADS)

Bourget, Antoine; Troost, Jan

2018-04-01

We revisit the study of the multiplets of the conformal algebra in any dimension. The theory of highest weight representations is reviewed in the context of the Bernstein-Gelfand-Gelfand category of modules. The Kazhdan-Lusztig polynomials code the relation between the Verma modules and the irreducible modules in the category and are the key to the characters of the conformal multiplets (whether finite dimensional, infinite dimensional, unitary or non-unitary). We discuss the representation theory and review in full generality which representations are unitarizable. The mathematical theory that allows for both the general treatment of characters and the full analysis of unitarity is made accessible. A good understanding of the mathematics of conformal multiplets renders the treatment of all highest weight representations in any dimension uniform, and provides an overarching comprehension of case-by-case results. Unitary highest weight representations and their characters are classified and computed in terms of data associated to cosets of the Weyl group of the conformal algebra. An executive summary is provided, as well as look-up tables up to and including rank four.

Predictors of health-related and global quality of life among young adults with difficult-to-treat epilepsy and mild intellectual disability.

PubMed

Endermann, Michael

2013-02-01

This study evaluated predictors of health-related quality of life (HRQOL) and global quality of life (QOL) among young adults with difficult-to-treat epilepsy and mild intellectual disability. One hundred and forty-two persons with epilepsy and cognitive problems were routinely screened on HRQOL, global QOL, and psychological distress four weeks after admission to a time-limited residential rehabilitation unit. The PESOS scales (PE = PErformance, SO = SOciodemographic aspects, S = Subjective evaluation/estimation) on epilepsy-specific problems were administered as measures of HRQOL; a questionnaire on life satisfaction and an item on overall QOL were used as measures of global QOL. Psychological distress was captured with the Symptom Checklist 90-R. Further data were gained from medical files. Quality-of- life predictors were identified using univariate methods and stepwise regression analyses. Psychological distress was the only predictor of all HRQOL and global QOL parameters. Seizure frequency was a predictor of most HRQOL variables. Other epilepsy variables affected only some HRQOL variables but were not associated with global QOL. Health-related quality of life did not seem to be strongly impaired. Only low correlations were found between HRQOL and global QOL. The notion of psychological distress as the most influential predictor of all QOL measures is in line with most findings on QOL in epilepsy. Former observations of weak associations between HRQOL and global QOL among patients with epilepsy and mild intellectual disability are supported. Thus, interventions to reduce psychological distress, besides epilepsy treatment, seem to be of great importance to improve QOL. Copyright © 2012 Elsevier Inc. All rights reserved.

An Acrobatic Substrate Metamorphosis Reveals a Requirement for Substrate Conformational Dynamics in Trypsin Proteolysis.

PubMed

Kayode, Olumide; Wang, Ruiying; Pendlebury, Devon F; Cohen, Itay; Henin, Rachel D; Hockla, Alexandra; Soares, Alexei S; Papo, Niv; Caulfield, Thomas R; Radisky, Evette S

2016-12-16

The molecular basis of enzyme catalytic power and specificity derives from dynamic interactions between enzyme and substrate during catalysis. Although considerable effort has been devoted to understanding how conformational dynamics within enzymes affect catalysis, the role of conformational dynamics within protein substrates has not been addressed. Here, we examine the importance of substrate dynamics in the cleavage of Kunitz-bovine pancreatic trypsin inhibitor protease inhibitors by mesotrypsin, finding that the varied conformational dynamics of structurally similar substrates can profoundly impact the rate of catalysis. A 1.4-Å crystal structure of a mesotrypsin-product complex formed with a rapidly cleaved substrate reveals a dramatic conformational change in the substrate upon proteolysis. By using long all-atom molecular dynamics simulations of acyl-enzyme intermediates with proteolysis rates spanning 3 orders of magnitude, we identify global and local dynamic features of substrates on the nanosecond-microsecond time scale that correlate with enzymatic rates and explain differential susceptibility to proteolysis. By integrating multiple enhanced sampling methods for molecular dynamics, we model a viable conformational pathway between substrate-like and product-like states, linking substrate dynamics on the nanosecond-microsecond time scale with large collective substrate motions on the much slower time scale of catalysis. Our findings implicate substrate flexibility as a critical determinant of catalysis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Finding the global minimum: a fuzzy end elimination implementation

NASA Technical Reports Server (NTRS)

Keller, D. A.; Shibata, M.; Marcus, E.; Ornstein, R. L.; Rein, R.

1995-01-01

The 'fuzzy end elimination theorem' (FEE) is a mathematically proven theorem that identifies rotameric states in proteins which are incompatible with the global minimum energy conformation. While implementing the FEE we noticed two different aspects that directly affected the final results at convergence. First, the identification of a single dead-ending rotameric state can trigger a 'domino effect' that initiates the identification of additional rotameric states which become dead-ending. A recursive check for dead-ending rotameric states is therefore necessary every time a dead-ending rotameric state is identified. It is shown that, if the recursive check is omitted, it is possible to miss the identification of some dead-ending rotameric states causing a premature termination of the elimination process. Second, we examined the effects of removing dead-ending rotameric states from further considerations at different moments of time. Two different methods of rotameric state removal were examined for an order dependence. In one case, each rotamer found to be incompatible with the global minimum energy conformation was removed immediately following its identification. In the other, dead-ending rotamers were marked for deletion but retained during the search, so that they influenced the evaluation of other rotameric states. When the search was completed, all marked rotamers were removed simultaneously. In addition, to expand further the usefulness of the FEE, a novel method is presented that allows for further reduction in the remaining set of conformations at the FEE convergence. In this method, called a tree-based search, each dead-ending pair of rotamers which does not lead to the direct removal of either rotameric state is used to reduce significantly the number of remaining conformations. In the future this method can also be expanded to triplet and quadruplet sets of rotameric states. We tested our implementation of the FEE by exhaustively searching ten protein

Static models with conformal symmetry

NASA Astrophysics Data System (ADS)

Manjonjo, A. M.; Maharaj, S. D.; Moopanar, S.

2018-02-01

We study static spherically symmetric spacetimes with a spherical conformal symmetry and a nonstatic conformal factor associated with the conformal Killing field. With these assumptions we find an explicit relationship relating two metric components of the metric tensor field. This leads to the general solution of the Einstein field equations with a conformal symmetry in a static spherically symmetric spacetime. For perfect fluids we can find all metrics explicitly and show that the models always admit a barotropic equation of state. Contained within this class of spacetimes are the well known metrics of (interior) Schwarzschild, Tolman, Kuchowicz, Korkina and Orlyanskii, Patwardhan and Vaidya, and Buchdahl and Land. The isothermal metric of Saslaw et al also admits a conformal symmetry. For imperfect fluids an infinite family of exact solutions to the field equations can be generated.

Connecting global change science with communities: About the conformation of a social network for early warnings in Colombia

NASA Astrophysics Data System (ADS)

Arias, P. A.; Vidal, L. M.; Serna, A. M.; Vieira, C.; Machado, J.; Cadavid, C. A.

2014-12-01

The risk associated with natural and social phenomena has notably increased in modern societies. On the other hand, socio-natural hazards have increased and diversified, in association with economic development. During 2010 and 2011, Colombia faced one of the most severe wet seasons in decades. One of the most significant impacts of this flood emergency was the demonstration of poor preparedness of communities, local authorities, and regional and national authorities to confront situations of large coverage. The emergencies occurred during 2010 and 2011, induced in association with a strong La Niña event, immediately demanded environmental and risk management authorities to provide communities with basic tools to understand the dynamics associated with excesses of rainfall and mitigate the possible impacts in their populations. For this reason, the Regional Autonomous Corporation of Central Antioquia, Colombia (CORANTIOQUIA) funded a project aimed to the design and conformation of a social network for early warnings of events associated to floods, torrential floods, and mass movements in 80 municipalities of the department of Antioquia, Colombia. For the execution of this project, the Corporation invited the Faculty of Engineering of the University of Antioquia. This talk aims to socialize this inititative that looked for integrating scientific and technical knowledge with popular knowledge in order to provide Latin American communities with tools to mitigate the possible impacts of global change.

Conformational selection in protein binding and function

PubMed Central

Weikl, Thomas R; Paul, Fabian

2014-01-01

Protein binding and function often involves conformational changes. Advanced nuclear magnetic resonance (NMR) experiments indicate that these conformational changes can occur in the absence of ligand molecules (or with bound ligands), and that the ligands may “select” protein conformations for binding (or unbinding). In this review, we argue that this conformational selection requires transition times for ligand binding and unbinding that are small compared to the dwell times of proteins in different conformations, which is plausible for small ligand molecules. Such a separation of timescales leads to a decoupling and temporal ordering of binding/unbinding events and conformational changes. We propose that conformational-selection and induced-change processes (such as induced fit) are two sides of the same coin, because the temporal ordering is reversed in binding and unbinding direction. Conformational-selection processes can be characterized by a conformational excitation that occurs prior to a binding or unbinding event, while induced-change processes exhibit a characteristic conformational relaxation that occurs after a binding or unbinding event. We discuss how the ordering of events can be determined from relaxation rates and effective on- and off-rates determined in mixing experiments, and from the conformational exchange rates measured in advanced NMR or single-molecule fluorescence resonance energy transfer experiments. For larger ligand molecules such as peptides, conformational changes and binding events can be intricately coupled and exhibit aspects of conformational-selection and induced-change processes in both binding and unbinding direction. PMID:25155241

Accounting for a mirror-image conformation as a subtle effect in protein folding.

PubMed

Kachlishvili, Khatuna; Maisuradze, Gia G; Martin, Osvaldo A; Liwo, Adam; Vila, Jorge A; Scheraga, Harold A

2014-06-10

By using local (free-energy profiles along the amino acid sequence and (13)C(α) chemical shifts) and global (principal component) analyses to examine the molecular dynamics of protein-folding trajectories, generated with the coarse-grained united-residue force field, for the B domain of staphylococcal protein A, we are able to (i) provide the main reason for formation of the mirror-image conformation of this protein, namely, a slow formation of the second loop and part of the third helix (Asp29-Asn35), caused by the presence of multiple local conformational states in this portion of the protein; (ii) show that formation of the mirror-image topology is a subtle effect resulting from local interactions; (iii) provide a mechanism for how protein A overcomes the barrier between the metastable mirror-image state and the native state; and (iv) offer a plausible reason to explain why protein A does not remain in the metastable mirror-image state even though the mirror-image and native conformations are at least energetically compatible.

Accounting for a mirror-image conformation as a subtle effect in protein folding

PubMed Central

Kachlishvili, Khatuna; Maisuradze, Gia G.; Martin, Osvaldo A.; Liwo, Adam; Vila, Jorge A.; Scheraga, Harold A.

2014-01-01

By using local (free-energy profiles along the amino acid sequence and 13Cα chemical shifts) and global (principal component) analyses to examine the molecular dynamics of protein-folding trajectories, generated with the coarse-grained united-residue force field, for the B domain of staphylococcal protein A, we are able to (i) provide the main reason for formation of the mirror-image conformation of this protein, namely, a slow formation of the second loop and part of the third helix (Asp29–Asn35), caused by the presence of multiple local conformational states in this portion of the protein; (ii) show that formation of the mirror-image topology is a subtle effect resulting from local interactions; (iii) provide a mechanism for how protein A overcomes the barrier between the metastable mirror-image state and the native state; and (iv) offer a plausible reason to explain why protein A does not remain in the metastable mirror-image state even though the mirror-image and native conformations are at least energetically compatible. PMID:24912167

An Investigation of Conformal Field Theory: Understanding the Conformal and Weyl Symmetries and Constraining Theories with Energy Conditions

NASA Astrophysics Data System (ADS)

Prilepina, Valentina V.

This thesis represents an investigation of topics in conformal field theory (CFT). Here we discuss three new contributions to this area. The first one relates to the famous problem of scale versus conformal invariance in d = 4. We give an argument that rules out a serious loophole present in relevant arguments for the conjecture that scale implies conformal invariance in 4D local unitary quantum field theories, namely that the trace of the energy-momentum tensor T could potentially be a generalized free field. Our argument hinges on the observation that any 4D unitary theory endowed with scale but not conformal invariance necessarily has a non-vanishing anomaly for global scale transformations. We show that this anomaly cannot be reproduced if T is a generalized free field unless a dimension-2 scalar operator is present in the theory. In the case that the theory does contain such an operator, we demonstrate that it can be exploited to redefine or "improve" Tmunu such that there is always at least one possible improvement of T which is not a generalized free field. This argument thus essentially excludes this option in a 4D unitary scale but not conformally invariant theory. Our next contribution relates to using energy positivity conditions to place constraints on conformal field theories. We propose a new special kind of weak energy condition with spacetime averaging over a finite region of length scale L to suppress quantum fluctuations. Our Spacetime Averaged Weak Energy Condition (SAWEC) is a novel completely local inequality closely related to the positivity of total energy. It is a proposed bound on the energy density of the form T00 ≥ -C/L4, where L is the size of the smearing region, and C is a positive theory-dependent constant. We motivate this condition as a fundamental consistency requirement for any 4D quantum field theory. We argue that violation of this statement would have serious undesirable consequences for a theory. In particular, the theory

Exploring the Relationship between Global Quality and Group Engagement in Toddler Child Care Classrooms

ERIC Educational Resources Information Center

Hooper, Alison; Hallam, Rena

2017-01-01

Toddlers' engagement with their social and physical environment is an important aspect of their experience in early care and education programs. The purpose of this research study was to examine how global quality relates to children's engagement in toddler child care classrooms. Additionally, this study explored how toddlers' group engagement…

Reducing the global burden of type 2 diabetes by improving the quality of staple foods: The Global Nutrition and Epidemiologic Transition Initiative.

PubMed

Mattei, Josiemer; Malik, Vasanti; Wedick, Nicole M; Hu, Frank B; Spiegelman, Donna; Willett, Walter C; Campos, Hannia

2015-06-04

The prevalence of type 2 diabetes has been reaching epidemic proportions across the globe, affecting low/middle-income and developed countries. Two main contributors to this burden are the reduction in mortality from infectious conditions and concomitant negative changes in lifestyles, including diet. We aimed to depict the current state of type 2 diabetes worldwide in light of the undergoing epidemiologic and nutrition transition, and to posit that a key factor in the nutrition transition has been the shift in the type and processing of staple foods, from less processed traditional foods to highly refined and processed carbohydrate sources. We showed data from 11 countries participating in the Global Nutrition and Epidemiologic Transition Initiative, a collaborative effort across countries at various stages of the nutrition-epidemiologic transition whose mission is to reduce diabetes by improving the quality of staple foods through culturally-appropriate interventions. We depicted the epidemiologic transition using demographic and mortality data from the World Health Organization, and the nutrition transition using data from the Food and Agriculture Organization food balance sheets. Main staple foods (maize, rice, wheat, pulses, and roots) differed by country, with most countries undergoing a shift in principal contributors to energy consumption from grains in the past 50 years. Notably, rice and wheat products accounted for over half of the contribution to energy consumption from staple grains, while the trends for contribution from roots and pulses generally decreased in most countries. Global Nutrition and Epidemiologic Transition Initiative countries with pilot data have documented key barriers and motivators to increase intake of high-quality staple foods. Global research efforts to identify and promote intake of culturally-acceptable high-quality staple foods could be crucial in preventing diabetes. These efforts may be valuable in shaping future research

Sialyldisaccharide conformations: a molecular dynamics perspective

NASA Astrophysics Data System (ADS)

Selvin, Jeyasigamani F. A.; Priyadarzini, Thanu R. K.; Veluraja, Kasinadar

2012-04-01

Sialyldisaccharides are significant terminal components of glycoconjugates and their negative charge and conformation are extensively utilized in molecular recognition processes. The conformation and flexibility of four biologically important sialyldisaccharides [Neu5Acα(2-3)Gal, Neu5Acα(2-6)Gal, Neu5Acα(2-8)Neu5Ac and Neu5Acα(2-9)Neu5Ac] are studied using Molecular Dynamics simulations of 20 ns duration to deduce the conformational preferences of the sialyldisaccharides and the interactions which stabilize the conformations. This study clearly describes the possible conformational models of sialyldisaccharides deduced from 20 ns Molecular Dynamics simulations and our results confirm the role of water in the structural stabilization of sialyldisaccharides. An extensive analysis on the sialyldisaccharide structures available in PDB also confirms the conformational regions found by experiments are detected in MD simulations of 20 ns duration. The three dimensional structural coordinates for all the MD derived sialyldisaccharide conformations are deposited in the 3DSDSCAR database and these conformational models will be useful for glycobiologists and biotechnologists to understand the biological functions of sialic acid containing glycoconjugates.

Dissecting the dynamic conformations of the metamorphic protein lymphotactin.

PubMed

Harvey, Sophie R; Porrini, Massimiliano; Konijnenberg, Albert; Clarke, David J; Tyler, Robert C; Langridge-Smith, Patrick R R; MacPhee, Cait E; Volkman, Brian F; Barran, Perdita E

2014-10-30

A mass spectrometer provides an ideal laboratory to probe the structure and stability of isolated protein ions. Interrogation of each discrete mass/charge-separated species enables the determination of the intrinsic stability of a protein fold, gaining snapshots of unfolding pathways. In solution, the metamorphic protein lymphotactin (Ltn) exists in equilibrium between two distinct conformations, a monomeric (Ltn10) and a dimeric (Ltn40) fold. Here, we use electron capture dissociation (ECD) and drift tube ion mobility-mass spectrometry (DT IM-MS) to analyze both forms and use molecular dynamics (MD) to consider how the solution fold alters in a solvent-free environment. DT IM-MS reveals significant conformational flexibility for the monomer, while the dimer appears more conformationally restricted. These findings are supported by MD calculations, which reveal how salt bridges stabilize the conformers in vacuo. Following ECD experiments, a distinctive fragmentation pattern is obtained for both the monomer and dimer. Monomer fragmentation becomes more pronounced with increasing charge state especially in the disordered regions and C-terminal α-helix in the solution fold. Lower levels of fragmentation are seen in the β-sheet regions and in regions that contain salt bridges, identified by MD simulations. The lowest charge state of the dimer for which we obtain ECD data ([D+9H](9+)) exhibits extensive fragmentation with no relationship to the solution fold and has a smaller collision cross section (CCS) than charge states 10-13+, suggesting a "collapsed" encounter complex. Other charge states of the dimer, as for the monomer, are resistant to fragmentation in regions of β-sheets in the solution fold. This study provides evidence for preservation and loss of global fold and secondary structural elements, providing a tantalizing glimpse into the power of the emerging field of native top-down mass spectrometry.

Shape dynamics and Mach's principles: Gravity from conformal geometrodynamics

NASA Astrophysics Data System (ADS)

Gryb, Sean

2012-04-01

In this PhD thesis, we develop a new approach to classical gravity starting from Mach's principles and the idea that the local shape of spatial configurations is fundamental. This new theory, "shape dynamics", is equivalent to general relativity but differs in an important respect: shape dynamics is a theory of dynamic conformal 3-geometry, not a theory of spacetime. Equivalence is achieved by trading foliation invariance for local conformal invariance (up to a global scale). After the trading, what is left is a gauge theory invariant under 3d diffeomorphisms and conformal transformations that preserve the volume of space. The local canonical constraints are linear and the constraint algebra closes with structure constants. Shape dynamics, thus, provides a novel new starting point for quantum gravity. The procedure for the trading of symmetries was inspired by a technique called "best matching". We explain best matching and its relation to Mach's principles. The key features of best matching are illustrated through finite dimensional toy models. A general picture is then established where relational theories are treated as gauge theories on configuration space. Shape dynamics is then constructed by applying best matching to conformal geometry. We then study shape dynamics in more detail by computing its Hamiltonian and Hamilton-Jacobi functional perturbatively. This thesis is intended as a pedagogical but complete introduction to shape dynamics and the Machian ideas that led to its discovery. The reader is encouraged to start with the introduction, which gives a conceptual outline and links to the relevant sections in the text for a more rigorous exposition. When full rigor is lacking, references to the literature are given. It is hoped that this thesis may provide a starting point for anyone interested in learning about shape dynamics.

Conformations of Substituted Ethanes.

ERIC Educational Resources Information Center

Kingsbury, Charles A.

1979-01-01

Reviews state-of-the-art of conformational analysis and factors which affect it. Emphasizes sp-3 hybridized acrylic molecules. Provides examples on the importance of certain factors in determining conformation. Purpose, is to provide examples for examination questions. (Author/SA)

Towards conformal loop quantum gravity

NASA Astrophysics Data System (ADS)

H-T Wang, Charles

2006-03-01

A discussion is given of recent developments in canonical gravity that assimilates the conformal analysis of gravitational degrees of freedom. The work is motivated by the problem of time in quantum gravity and is carried out at the metric and the triad levels. At the metric level, it is shown that by extending the Arnowitt-Deser-Misner (ADM) phase space of general relativity (GR), a conformal form of geometrodynamics can be constructed. In addition to the Hamiltonian and Diffeomorphism constraints, an extra first class constraint is introduced to generate conformal transformations. This phase space consists of York's mean extrinsic curvature time, conformal three-metric and their momenta. At the triad level, the phase space of GR is further enlarged by incorporating spin-gauge as well as conformal symmetries. This leads to a canonical formulation of GR using a new set of real spin connection variables. The resulting gravitational constraints are first class, consisting of the Hamiltonian constraint and the canonical generators for spin-gauge and conformorphism transformations. The formulation has a remarkable feature of being parameter-free. Indeed, it is shown that a conformal parameter of the Barbero-Immirzi type can be absorbed by the conformal symmetry of the extended phase space. This gives rise to an alternative approach to loop quantum gravity that addresses both the conceptual problem of time and the technical problem of functional calculus in quantum gravity.

Enhanced conformational sampling technique provides an energy landscape view of large-scale protein conformational transitions.

PubMed

Shao, Qiang

2016-10-26

Large-scale conformational changes in proteins are important for their functions. Tracking the conformational change in real time at the level of a single protein molecule, however, remains a great challenge. In this article, we present a novel in silico approach with the combination of normal mode analysis and integrated-tempering-sampling molecular simulation (NMA-ITS) to give quantitative data for exploring the conformational transition pathway in multi-dimensional energy landscapes starting only from the knowledge of the two endpoint structures of the protein. The open-to-closed transitions of three proteins, including nCaM, AdK, and HIV-1 PR, were investigated using NMA-ITS simulations. The three proteins have varied structural flexibilities and domain communications in their respective conformational changes. The transition state structure in the conformational change of nCaM and the associated free-energy barrier are in agreement with those measured in a standard explicit-solvent REMD simulation. The experimentally measured transition intermediate structures of the intrinsically flexible AdK are captured by the conformational transition pathway measured here. The dominant transition pathways between the closed and fully open states of HIV-1 PR are very similar to those observed in recent REMD simulations. Finally, the evaluated relaxation times of the conformational transitions of three proteins are roughly at the same level as reported experimental data. Therefore, the NMA-ITS method is applicable for a variety of cases, providing both qualitative and quantitative insights into the conformational changes associated with the real functions of proteins.

[Schools, office buildings, leisure settings: diversity of indoor air quality issues. Global review on indoor air quality in these settings].

PubMed

Mandin, C; Derbez, M; Kirchner, S

2012-07-01

This review provides a global overview of indoor air quality issues in schools, office buildings and recreational settings. It presents the most recent scientific publications and the on-going work conducted in France in the frame of the indoor air quality Observatory. Monitoring campaigns on indoor air quality in schools have been carried out in the recent years in Europe. However, few studies have specifically addressed the role of exposure in these buildings on children's health. Indoor air quality in office buildings has been little studied so far. However, some specificities, such as emissions from electronic devices, frequent cleaning, impossibility to open windows in high-rise buildings, for example, should be examined and their role on the health and comfort studied. Finally, even if the time spent in recreational settings is short, the quality of indoor air should also be considered because of specific pollution. This is the case of indoor swimming pools (exposure to chlorination byproducts) and ice-rinks (exposure to exhaust from machines used to smooth the ice). Copyright © 2012 Elsevier Masson SAS. All rights reserved.

The Water Quality in Rio Highlights the Global Public Health Concern Over Untreated Sewage Disposal

EPA Science Inventory

Water quality issues in Rio have been widely publicized because of the 2016 Olympics. Recent concerns about polluted waters that athletes may be exposed to highlights the conditions that more than a billion people globally are exposed to daily. Despite these unhealthy conditions,...

Conformable derivative approach to anomalous diffusion

NASA Astrophysics Data System (ADS)

Zhou, H. W.; Yang, S.; Zhang, S. Q.

2018-02-01

By using a new derivative with fractional order, referred to conformable derivative, an alternative representation of the diffusion equation is proposed to improve the modeling of anomalous diffusion. The analytical solutions of the conformable derivative model in terms of Gauss kernel and Error function are presented. The power law of the mean square displacement for the conformable diffusion model is studied invoking the time-dependent Gauss kernel. The parameters related to the conformable derivative model are determined by Levenberg-Marquardt method on the basis of the experimental data of chloride ions transportation in reinforced concrete. The data fitting results showed that the conformable derivative model agrees better with the experimental data than the normal diffusion equation. Furthermore, the potential application of the proposed conformable derivative model of water flow in low-permeability media is discussed.

Weight shifting operators and conformal blocks

NASA Astrophysics Data System (ADS)

Karateev, Denis; Kravchuk, Petr; Simmons-Duffin, David

2018-02-01

We introduce a large class of conformally-covariant differential operators and a crossing equation that they obey. Together, these tools dramatically simplify calculations involving operators with spin in conformal field theories. As an application, we derive a formula for a general conformal block (with arbitrary internal and external representations) in terms of derivatives of blocks for external scalars. In particular, our formula gives new expressions for "seed conformal blocks" in 3d and 4d CFTs. We also find simple derivations of identities between external-scalar blocks with different dimensions and internal spins. We comment on additional applications, including deriving recursion relations for general conformal blocks, reducing inversion formulae for spinning operators to inversion formulae for scalars, and deriving identities between general 6 j symbols (Racah-Wigner coefficients/"crossing kernels") of the conformal group.

Stories from OpenAQ, a Global and Grassroots Open Air Quality Community

NASA Astrophysics Data System (ADS)

Hasenkopf, C. A.; Flasher, J. C.; Veerman, O.; Scalamogna, A.; Silva, D.; Salmon, M.; Buuralda, D.; DeWitt, L. H.

2016-12-01

Air pollution, responsible for more deaths each year than HIV/AIDS and malaria, combined, is a global public health crisis. Yet many scientific questions, including those directly relevant for policy, remain unanswered when it comes to the impact of air pollution on health in highly polluted environments. Often, specific solutions to improving air quality are local and sustained through public engagement, policy and monitoring. Both the overarching science of air quality and health and local solutions rely on access to reliable, timely air quality data. Over the past year, the OpenAQ community has opened up existing disparate air quality data in 24 countries through an open source platform (openaq.org) so that communities around the world can use it to advance science, public engagement, and policy. We will share stories of communities, from Delhi to Ulaanbaatar and from scientists to journalists, using open air quality data from our platform to advance their fight against air inequality. We will share recent research we have conducted on best practices for engaging different communities and building tools that enable the public to fully unleash the power of open air quality data to fight air inequality. The subsequent open-source tools (github.com/openaq) we have developed from this research and our entire data-sharing platform may be of interest to other open data communities.

The impact of global budgets on pharmaceutical spending and utilization: early experience from the alternative quality contract.

PubMed

Afendulis, Christopher C; Fendrick, A Mark; Song, Zirui; Landon, Bruce E; Safran, Dana Gelb; Mechanic, Robert E; Chernew, Michael E

2014-01-01

In 2009, Blue Cross Blue Shield of Massachusetts implemented a global budget-based payment system, the Alternative Quality Contract (AQC), in which provider groups assumed accountability for spending. We investigate the impact of global budgets on the utilization of prescription drugs and related expenditures. Our analyses indicate no statistically significant evidence that the AQC reduced the use of drugs. Although the impact may change over time, early evidence suggests that it is premature to conclude that global budget systems may reduce access to medications. © The Author(s) 2014.

Procrustean rotation in concert with principal component analysis of molecular dynamics trajectories: Quantifying global and local differences between conformational samples.

PubMed

Oblinsky, Daniel G; Vanschouwen, Bryan M B; Gordon, Heather L; Rothstein, Stuart M

2009-12-14

Given the principal component analysis (PCA) of a molecular dynamics (MD) conformational trajectory for a model protein, we perform orthogonal Procrustean rotation to "best fit" the PCA squared-loading matrix to that of a target matrix computed for a related but different molecular system. The sum of squared deviations of the elements of the rotated matrix from those of the target, known as the error of fit (EOF), provides a quantitative measure of the dissimilarity between the two conformational samples. To estimate precision of the EOF, we perform bootstrap resampling of the molecular conformations within the trajectories, generating a distribution of EOF values for the system and target. The average EOF per variable is determined and visualized to ascertain where, locally, system and target sample properties differ. We illustrate this approach by analyzing MD trajectories for the wild-type and four selected mutants of the beta1 domain of protein G.

Procrustean rotation in concert with principal component analysis of molecular dynamics trajectories: Quantifying global and local differences between conformational samples

NASA Astrophysics Data System (ADS)

Oblinsky, Daniel G.; VanSchouwen, Bryan M. B.; Gordon, Heather L.; Rothstein, Stuart M.

2009-12-01

Given the principal component analysis (PCA) of a molecular dynamics (MD) conformational trajectory for a model protein, we perform orthogonal Procrustean rotation to "best fit" the PCA squared-loading matrix to that of a target matrix computed for a related but different molecular system. The sum of squared deviations of the elements of the rotated matrix from those of the target, known as the error of fit (EOF), provides a quantitative measure of the dissimilarity between the two conformational samples. To estimate precision of the EOF, we perform bootstrap resampling of the molecular conformations within the trajectories, generating a distribution of EOF values for the system and target. The average EOF per variable is determined and visualized to ascertain where, locally, system and target sample properties differ. We illustrate this approach by analyzing MD trajectories for the wild-type and four selected mutants of the β1 domain of protein G.

Protein Allostery and Conformational Dynamics.

PubMed

Guo, Jingjing; Zhou, Huan-Xiang

2016-06-08

The functions of many proteins are regulated through allostery, whereby effector binding at a distal site changes the functional activity (e.g., substrate binding affinity or catalytic efficiency) at the active site. Most allosteric studies have focused on thermodynamic properties, in particular, substrate binding affinity. Changes in substrate binding affinity by allosteric effectors have generally been thought to be mediated by conformational transitions of the proteins or, alternatively, by changes in the broadness of the free energy basin of the protein conformational state without shifting the basin minimum position. When effector binding changes the free energy landscape of a protein in conformational space, the change affects not only thermodynamic properties but also dynamic properties, including the amplitudes of motions on different time scales and rates of conformational transitions. Here we assess the roles of conformational dynamics in allosteric regulation. Two cases are highlighted where NMR spectroscopy and molecular dynamics simulation have been used as complementary approaches to identify residues possibly involved in allosteric communication. Perspectives on contentious issues, for example, the relationship between picosecond-nanosecond local and microsecond-millisecond conformational exchange dynamics, are presented.

Global Initiatives for Early Childhood Care and Education: Global Guidelines and Global Guidelines Assessment

ERIC Educational Resources Information Center

Trube, Mary Barbara

2015-01-01

This report focuses on the Association for Childhood Education International's (ACEI) Global Guidelines (GG) and Global Guidelines Assessment (GGA), which were developed in response to and in keeping with the prominence that the issue of quality early childhood care, development, and education has reached globally. Further, the paper positions the…

Entropy–enthalpy transduction caused by conformational shifts can obscure the forces driving protein–ligand binding

PubMed Central

Fenley, Andrew T.; Muddana, Hari S.; Gilson, Michael K.

2012-01-01

Molecular dynamics simulations of unprecedented duration now can provide new insights into biomolecular mechanisms. Analysis of a 1-ms molecular dynamics simulation of the small protein bovine pancreatic trypsin inhibitor reveals that its main conformations have different thermodynamic profiles and that perturbation of a single geometric variable, such as a torsion angle or interresidue distance, can select for occupancy of one or another conformational state. These results establish the basis for a mechanism that we term entropy–enthalpy transduction (EET), in which the thermodynamic character of a local perturbation, such as enthalpic binding of a small molecule, is camouflaged by the thermodynamics of a global conformational change induced by the perturbation, such as a switch into a high-entropy conformational state. It is noted that EET could occur in many systems, making measured entropies and enthalpies of folding and binding unreliable indicators of actual thermodynamic driving forces. The same mechanism might also account for the high experimental variance of measured enthalpies and entropies relative to free energies in some calorimetric studies. Finally, EET may be the physical mechanism underlying many cases of entropy–enthalpy compensation. PMID:23150595

Laparoscopic redo fundoplication improves disease-specific and global quality of life following failed laparoscopic or open fundoplication.

PubMed

Del Campo, Sara E Martin; Mansfield, Sara A; Suzo, Andrew J; Hazey, Jeffrey W; Perry, Kyle A

2017-11-01

Laparoscopic fundoplication is associated with failure rates of up to 30% and redo operation rates of 5-8%. Redo fundoplication improves patient symptoms, but its impact on patient quality of life remains unclear. We hypothesized that laparoscopic redo fundoplication improves disease-specific and global quality of life in patients with recurrent symptoms following failed laparoscopic or open fundoplication. Data for all patients undergoing a redo fundoplication between August 2009 and June 2014 were collected prospectively. Reflux symptoms and quality of life were assessed using the Gastroesophageal Reflux Symptom Scale (GERSS), the Gastroesophageal Reflux Disease Health-Related Quality of Life (GERD-HRQL), and the global quality of life Short Form-36 (SF-36) questionnaires obtained at 4 weeks and 16 months post-operatively. Forty-six patients underwent laparoscopic redo fundoplication during the study period for symptomatic hernia (n = 11), GERD (n = 18), or dysphagia (n = 17). GERSS improved from 41 at baseline to 9 at late follow-up (p < 0.001), and GERD-HRQL scores improved from 30 at baseline to 7 at late follow-up (p < 0.001). Median dysphagia scores decreased from 4.5 to 1 (p = 0.035). SF-36 scores demonstrated a significant improvement in general health (p = 0.016) and emotional well-being (p = 0.036) and a trend toward improved physical function (p = 0.068) in the post-operative period, but these improvements were not statistically significant at longer-term follow-up. Overall, 82% of patients reported satisfaction with their operation, and 96% reported that they would have the operation performed again given the benefit of hindsight. While associated with long operative times and significant complications, laparoscopic redo fundoplication produces a durable improvement in reflux symptoms and disease-specific quality of life. These procedures also improve global quality of life in the short term and are associated with high patient

How smoke-free laws improve air quality: a global study of Irish pubs.

PubMed

Connolly, Gregory N; Carpenter, Carrie M; Travers, Mark J; Cummings, K Michael; Hyland, Andrew; Mulcahy, Maurice; Clancy, Luke

2009-06-01

The present study examined indoor air quality in a global sample of smoke-free and smoking-permitted Irish pubs. We hypothesized that levels of respirable suspended particles, an important marker of secondhand smoke, would be significantly lower in smoke-free Irish pubs than in pubs that allowed smoking. Indoor air quality was assessed in 128 Irish pubs in 15 countries between 21 January 2004 and 10 March 2006. Air quality was evaluated using an aerosol monitor, which measures the level of fine particle (PM(2.5)) pollution in the air. A standard measurement protocol was used by data collectors across study sites. Overall, the level of air pollution inside smoke-free Irish pubs was 93% lower than the level found in pubs where smoking was permitted. Levels of indoor air pollution can be massively reduced by enacting and enforcing smoke-free policies.

Dissecting the large-scale galactic conformity

NASA Astrophysics Data System (ADS)

Seo, Seongu

2018-01-01

Galactic conformity is an observed phenomenon that galaxies located in the same region have similar properties such as star formation rate, color, gas fraction, and so on. The conformity was first observed among galaxies within in the same halos (“one-halo conformity”). The one-halo conformity can be readily explained by mutual interactions among galaxies within a halo. Recent observations however further witnessed a puzzling connection among galaxies with no direct interaction. In particular, galaxies located within a sphere of ~5 Mpc radius tend to show similarities, even though the galaxies do not share common halos with each other ("two-halo conformity" or “large-scale conformity”). Using a cosmological hydrodynamic simulation, Illustris, we investigate the physical origin of the two-halo conformity and put forward two scenarios. First, back-splash galaxies are likely responsible for the large-scale conformity. They have evolved into red galaxies due to ram-pressure stripping in a given galaxy cluster and happen to reside now within a ~5 Mpc sphere. Second, galaxies in strong tidal field induced by large-scale structure also seem to give rise to the large-scale conformity. The strong tides suppress star formation in the galaxies. We discuss the importance of the large-scale conformity in the context of galaxy evolution.

Producing a Climate-Quality Database of Global Upper Ocean Profile Temperatures - The IQuOD (International Quality-controlled Ocean Database) Project.

NASA Astrophysics Data System (ADS)

Sprintall, J.; Cowley, R.; Palmer, M. D.; Domingues, C. M.; Suzuki, T.; Ishii, M.; Boyer, T.; Goni, G. J.; Gouretski, V. V.; Macdonald, A. M.; Thresher, A.; Good, S. A.; Diggs, S. C.

2016-02-01

Historical ocean temperature profile observations provide a critical element for a host of ocean and climate research activities. These include providing initial conditions for seasonal-to-decadal prediction systems, evaluating past variations in sea level and Earth's energy imbalance, ocean state estimation for studying variability and change, and climate model evaluation and development. The International Quality controlled Ocean Database (IQuOD) initiative represents a community effort to create the most globally complete temperature profile dataset, with (intelligent) metadata and assigned uncertainties. With an internationally coordinated effort organized by oceanographers, with data and ocean instrumentation expertise, and in close consultation with end users (e.g., climate modelers), the IQuOD initiative will assess and maximize the potential of an irreplaceable collection of ocean temperature observations (tens of millions of profiles collected at a cost of tens of billions of dollars, since 1772) to fulfil the demand for a climate-quality global database that can be used with greater confidence in a vast range of climate change related research and services of societal benefit. Progress towards version 1 of the IQuOD database, ongoing and future work will be presented. More information on IQuOD is available at www.iquod.org.

Conformational Heterogeneity in a Fully Complementary DNA Three-Way Junction with a GC-Rich Branchpoint.

PubMed

Toulmin, Anita; Baltierra-Jasso, Laura E; Morten, Michael J; Sabir, Tara; McGlynn, Peter; Schröder, Gunnar F; Smith, Brian O; Magennis, Steven W

2017-09-19

DNA three-way junctions (3WJs) are branched structures that serve as important biological intermediates and as components in DNA nanostructures. We recently derived the global structure of a fully complementary 3WJ and found that it contained unpaired bases at the branchpoint, which is consistent with previous observations of branch flexibility and branchpoint reactivity. By combining high-resolution single-molecule Förster resonance energy transfer, molecular modeling, time-resolved ensemble fluorescence spectroscopy, and the first 19 F nuclear magnetic resonance observations of fully complementary 3WJs, we now show that the 3WJ structure can adopt multiple distinct conformations depending upon the sequence at the branchpoint. A 3WJ with a GC-rich branchpoint adopts an open conformation with unpaired bases at the branch and at least one additional conformation with an increased number of base interactions at the branchpoint. This structural diversity has implications for branch interactions and processing in vivo and for technological applications.

Implementing clinical protocols in oncology: quality gaps and the learning curve phenomenon.

PubMed

Kedikoglou, Simos; Syrigos, Konstantinos; Skalkidis, Yannis; Ploiarchopoulou, Fani; Dessypris, Nick; Petridou, Eleni

2005-08-01

The quality improvement effort in clinical practice has focused mostly on 'performance quality', i.e. on the development of comprehensive, evidence-based guidelines. This study aimed to assess the 'conformance quality', i.e. the extent to which guidelines once developed are correctly and consistently applied. It also aimed to assess the existence of quality gaps in the treatment of certain patient segments as defined by age or gender and to investigate methods to improve overall conformance quality. A retrospective audit of clinical practice in a well-defined oncology setting was undertaken and the results compared to those obtained from prospectively applying an internally developed clinical protocol in the same setting and using specific tools to increase conformance quality. All indicators showed improvement after the implementation of the protocol that in many cases reached statistical significance, while in the entire cohort advanced age was associated (although not significantly) with sub-optimal delivery of care. A 'learning curve' phenomenon in the implementation of quality initiatives was detected, with all indicators improving substantially in the second part of the prospective study. Clinicians should pay separate attention to the implementation of chosen protocols and employ specific tools to increase conformance quality in patient care.

Peptidic Macrocycles - Conformational Sampling and Thermodynamic Characterization

PubMed Central

2018-01-01

Macrocycles are of considerable interest as highly specific drug candidates, yet they challenge standard conformer generators with their large number of rotatable bonds and conformational restrictions. Here, we present a molecular dynamics-based routine that bypasses current limitations in conformational sampling and extensively profiles the free energy landscape of peptidic macrocycles in solution. We perform accelerated molecular dynamics simulations to capture a diverse conformational ensemble. By applying an energetic cutoff, followed by geometric clustering, we demonstrate the striking robustness and efficiency of the approach in identifying highly populated conformational states of cyclic peptides. The resulting structural and thermodynamic information is benchmarked against interproton distances from NMR experiments and conformational states identified by X-ray crystallography. Using three different model systems of varying size and flexibility, we show that the method reliably reproduces experimentally determined structural ensembles and is capable of identifying key conformational states that include the bioactive conformation. Thus, the described approach is a robust method to generate conformations of peptidic macrocycles and holds promise for structure-based drug design. PMID:29652495

Peptidic Macrocycles - Conformational Sampling and Thermodynamic Characterization.

PubMed

Kamenik, Anna S; Lessel, Uta; Fuchs, Julian E; Fox, Thomas; Liedl, Klaus R

2018-05-29

Macrocycles are of considerable interest as highly specific drug candidates, yet they challenge standard conformer generators with their large number of rotatable bonds and conformational restrictions. Here, we present a molecular dynamics-based routine that bypasses current limitations in conformational sampling and extensively profiles the free energy landscape of peptidic macrocycles in solution. We perform accelerated molecular dynamics simulations to capture a diverse conformational ensemble. By applying an energetic cutoff, followed by geometric clustering, we demonstrate the striking robustness and efficiency of the approach in identifying highly populated conformational states of cyclic peptides. The resulting structural and thermodynamic information is benchmarked against interproton distances from NMR experiments and conformational states identified by X-ray crystallography. Using three different model systems of varying size and flexibility, we show that the method reliably reproduces experimentally determined structural ensembles and is capable of identifying key conformational states that include the bioactive conformation. Thus, the described approach is a robust method to generate conformations of peptidic macrocycles and holds promise for structure-based drug design.

The Conformational Landscape of L-Threonine Matrix Isolation Infrared and {AB-INITIO Studies

NASA Astrophysics Data System (ADS)

Dubey, Pankaj; Mukhopadhyay, Anamika; Viswanathan, K. S.

2017-06-01

Amino acids, containing hydroxy side chains such as L-threonine and tyrosine play an important role in molecular recognition, such as in the docking of propofol, which is a commonly used anaesthetic. A rich conformational landscape of these amino acids makes them interesting candidates in the study of intra and intermolecular interactions. In this work, the conformational landscape of L-threonine was studied, as it can be expected to serve as a basis for understanding structure and functions of polypeptides and other biomolecules. The matrix isolation technique (MI) coupled with a high temperature effusive molecular beam (EMB) nozzle was used to trap conformers of amino acid, which were then characterized using FTIR spectroscopy. The usefulness of MI-EMB-FTIR spectroscopy is that it can trap structures corresponding to the local minima along with the global minimum and hence allows for a better exploration of the potential energy surface. A major challenge in conformational analysis of amino acids using matrix isolation FTIR arises from its non-volatile nature. A home built heating system which was mounted close to the cryotip, was used to evaporate the non-volatile amino acids. Our infrared spectra show that three conformations were trapped in the matrix. Experimental results were supported by {ab-initio calculations performed using the CCSD(T), MP2 and M06-2X methods together with 6-311++G(d,p) and aug/cc-pVDZ basis sets. The side chains of the amino acids appeared to have an influence on the preferential stabilisation of a particular backbone structure of amino acids. Factors such as entropy, anomeric effect and intramolecular H-bonding were also found to play an important role in determining conformal preferences, which will be discussed.

Interplay of charge distribution and conformation in peptides: comparison of theory and experiment.

PubMed

Makowska, Joanna; Bagińska, Katarzyna; Kasprzykowski, F; Vila, Jorge A; Jagielska, Anna; Liwo, Adam; Chmurzyński, Lech; Scheraga, Harold A

2005-01-01

We assessed the correlation between charge distribution and conformation of flexible peptides by comparing the theoretically calculated potentiometric-titration curves of two model peptides, Ac-Lys5-NHMe (a model of poly-L-lysine) and Ac-Lys-Ala11-Lys-Gly2-Tyr-NH2 (P1) in water and methanol, with the experimental curves. The calculation procedure consisted of three steps: (i) global conformational search of the peptide under study using the electrostatically driven Monte Carlo (EDMC) method with the empirical conformational energy program for peptides (ECEPP)/3 force field plus the surface-hydration (SRFOPT) or the generalized Born surface area (GBSA) solvation model as well as a molecular dynamics method with the assisted model building and energy refinement (AMBER)99/GBSA force field; (ii) reevaluation of the energy in the pH range considered by using the modified Poisson-Boltzmann approach and taking into account all possible protonation microstates of each conformation, and (iii) calculation of the average degree of protonation of the peptide at a given pH value by Boltzmann averaging over conformations. For Ac-Lys5-NHMe, the computed titration curve agrees qualitatively with the experimental curve of poly-L-lysine in 95% methanol. The experimental titration curves of peptide P1 in water and methanol indicate a remarkable downshift of the first pK(a) value compared to the values for reference compounds (n-butylamine and phenol, respectively), suggesting the presence of a hydrogen bond between the tyrosine hydroxyl oxygen and the H(epsilon) proton of a protonated lysine side chain. The theoretical titration curves agree well with the experimental curves, if conformations with such hydrogen bonds constitute a significant part of the ensemble; otherwise, the theory predicts too small a downward pH shift. Copyright 2005 Wiley Periodicals, Inc

Honey Bee Deformed Wing Virus Structures Reveal that Conformational Changes Accompany Genome Release.

PubMed

Organtini, Lindsey J; Shingler, Kristin L; Ashley, Robert E; Capaldi, Elizabeth A; Durrani, Kulsoom; Dryden, Kelly A; Makhov, Alexander M; Conway, James F; Pizzorno, Marie C; Hafenstein, Susan

2017-01-15

The picornavirus-like deformed wing virus (DWV) has been directly linked to colony collapse; however, little is known about the mechanisms of host attachment or entry for DWV or its molecular and structural details. Here we report the three-dimensional (3-D) structures of DWV capsids isolated from infected honey bees, including the immature procapsid, the genome-filled virion, the putative entry intermediate (A-particle), and the empty capsid that remains after genome release. The capsids are decorated by large spikes around the 5-fold vertices. The 5-fold spikes had an open flower-like conformation for the procapsid and genome-filled capsids, whereas the putative A-particle and empty capsids that had released the genome had a closed tube-like spike conformation. Between the two conformations, the spikes undergo a significant hinge-like movement that we predicted using a Robetta model of the structure comprising the spike. We conclude that the spike structures likely serve a function during host entry, changing conformation to release the genome, and that the genome may escape from a 5-fold vertex to initiate infection. Finally, the structures illustrate that, similarly to picornaviruses, DWV forms alternate particle conformations implicated in assembly, host attachment, and RNA release. Honey bees are critical for global agriculture, but dramatic losses of entire hives have been reported in numerous countries since 2006. Deformed wing virus (DWV) and infestation with the ectoparasitic mite Varroa destructor have been linked to colony collapse disorder. DWV was purified from infected adult worker bees to pursue biochemical and structural studies that allowed the first glimpse into the conformational changes that may be required during transmission and genome release for DWV. Copyright © 2017 American Society for Microbiology.

Conformer-specific hydrogen atom tunnelling in trifluoromethylhydroxycarbene

NASA Astrophysics Data System (ADS)

Mardyukov, Artur; Quanz, Henrik; Schreiner, Peter R.

2017-01-01

Conformational control of organic reactions is at the heart of the biomolecular sciences. To achieve a particular reactivity, one of many conformers may be selected, for instance, by a (bio)catalyst, as the geometrically most suited and appropriately reactive species. The equilibration of energetically close-lying conformers is typically assumed to be facile and less energetically taxing than the reaction under consideration itself: this is termed the 'Curtin-Hammett principle'. Here, we show that the trans conformer of trifluoromethylhydroxycarbene preferentially rearranges through a facile quantum-mechanical hydrogen tunnelling pathway, while its cis conformer is entirely unreactive. Hence, this presents the first example of a conformer-specific hydrogen tunnelling reaction. The Curtin-Hammett principle is not applicable, due to the high barrier between the two conformers.

Using animation quality metric to improve efficiency of global illumination computation for dynamic environments

NASA Astrophysics Data System (ADS)

Myszkowski, Karol; Tawara, Takehiro; Seidel, Hans-Peter

2002-06-01

In this paper, we consider applications of perception-based video quality metrics to improve the performance of global lighting computations for dynamic environments. For this purpose we extend the Visible Difference Predictor (VDP) developed by Daly to handle computer animations. We incorporate into the VDP the spatio-velocity CSF model developed by Kelly. The CSF model requires data on the velocity of moving patterns across the image plane. We use the 3D image warping technique to compensate for the camera motion, and we conservatively assume that the motion of animated objects (usually strong attractors of the visual attention) is fully compensated by the smooth pursuit eye motion. Our global illumination solution is based on stochastic photon tracing and takes advantage of temporal coherence of lighting distribution, by processing photons both in the spatial and temporal domains. The VDP is used to keep noise inherent in stochastic methods below the sensitivity level of the human observer. As a result a perceptually-consistent quality across all animation frames is obtained.

A comparison between cobalt and linear accelerator-based treatment plans for conformal and intensity-modulated radiotherapy.

PubMed

Adams, E J; Warrington, A P

2008-04-01

The simplicity of cobalt units gives them the advantage of reduced maintenance, running costs and downtime when compared with linear accelerators. However, treatments carried out on such units are typically limited to simple techniques. This study has explored the use of cobalt beams for conformal and intensity-modulated radiotherapy (IMRT). Six patients, covering a range of treatment sites, were planned using both X-ray photons (6/10 MV) and cobalt-60 gamma rays (1.17 and 1.33 MeV). A range of conformal and IMRT techniques were considered, as appropriate. Conformal plans created using cobalt beams for small breast, meningioma and parotid cases were found to compare well with those created using X-ray photons. By using additional fields, acceptable conformal plans were also created for oesophagus and prostate cases. IMRT plans were found to be of comparable quality for meningioma, parotid and thyroid cases on the basis of dose-volume histogram analysis. We conclude that it is possible to plan high-quality radical radiotherapy treatments for cobalt units. A well-designed beam blocking/compensation system would be required to enable a practical and efficient alternative to multileaf collimator (MLC)-based linac treatments to be offered. If cobalt units were to have such features incorporated into them, they could offer considerable benefits to the radiotherapy community.

Refoldable Foldamers: Global Conformational Switching by Deletion or Insertion of a Single Hydrogen Bond

PubMed Central

Le Bailly, Bryden A. F.; Byrne, Liam

2016-01-01

Abstract Small changes in the structure of a foldamer may lead to gross changes in conformational preference. We show that the simple insertion or deletion of a single hydrogen bond by changes in pH or by photochemical deprotection is sufficient to refold a helical oligomer, interconverting M and P screw‐sense preference. As a consequence of the switch, information may be transmitted to a remote catalytic site, selectively directing the formation of either of two enantiomeric products by a reaction involving 1,22‐remote intermolecular asymmetric induction. PMID:26762559

40 CFR 52.799 - Transportation conformity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Transportation conformity. 52.799... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.799 Transportation conformity. On June 4, 2010, Indiana submitted the Transportation Conformity Consultation SIP consisting of...

40 CFR 52.799 - Transportation conformity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Transportation conformity. 52.799... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.799 Transportation conformity. On June 4, 2010, Indiana submitted the Transportation Conformity Consultation SIP consisting of...

40 CFR 52.799 - Transportation conformity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Transportation conformity. 52.799... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.799 Transportation conformity. On June 4, 2010, Indiana submitted the Transportation Conformity Consultation SIP consisting of...

40 CFR 52.799 - Transportation conformity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Transportation conformity. 52.799... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.799 Transportation conformity. On June 4, 2010, Indiana submitted the Transportation Conformity Consultation SIP consisting of...

Lattice Simulations and Infrared Conformality

DOE PAGES

Appelquist, Thomas; Fleming, George T.; Lin, Meifeng; ...

2011-09-01

We examine several recent lattice-simulation data sets, asking whether they are consistent with infrared conformality. We observe, in particular, that for an SU(3) gauge theory with 12 Dirac fermions in the fundamental representation, recent simulation data can be described assuming infrared conformality. Lattice simulations include a fermion mass m which is then extrapolated to zero, and we note that this data can be fit by a small-m expansion, allowing a controlled extrapolation. We also note that the conformal hypothesis does not work well for two theories that are known or expected to be confining and chirally broken, and that itmore » does work well for another theory expected to be infrared conformal.« less

Conformers, infrared spectrum, UV-induced photochemistry, and near-IR-induced generation of two rare conformers of matrix-isolated phenylglycine.

PubMed

Borba, Ana; Gómez-Zavaglia, Andrea; Fausto, Rui

2014-10-21

The conformational space of α-phenylglycine (PG) have been investigated theoretically at both the DFT/B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) levels of approximation. Seventeen different minima were found on the investigated potential energy surfaces, which are characterized by different dominant intramolecular interactions: type I conformers are stabilized by hydrogen bonds of the type N-H···O=C, type II by a strong O-H···N hydrogen bond, type III by weak N-H···O-H hydrogen bonds, and type IV by a C=O···H-C contact. The calculations indicate also that entropic effects are relevant in determining the equilibrium populations of the conformers of PG in the gas phase, in particular in the case of conformers of type II, where the strong intramolecular O-H···N hydrogen bond considerably diminishes entropy by reducing the conformational mobility of the molecule. In consonance with the relative energies of the conformers and barriers for conformational interconversion, only 3 conformers of PG were observed for the compound isolated in cryogenic Ar, Xe, and N2 matrices: the conformational ground state (ICa), and forms ICc and IITa. All other significantly populated conformers existing in the gas phase prior to deposition convert either to conformer ICa or to conformer ICc during matrix deposition. The experimental observation of ICc had never been achieved hitherto. Narrowband near-IR irradiation of the first overtone of νOH vibrational mode of ICa and ICc in nitrogen matrices (at 6910 and 6930 cm(-1), respectively) led to selective generation of two additional conformers of high-energy, ITc and ITa, respectively, which were also observed experimentally for the first time. In addition, these experiments also provided the key information for the detailed vibrational characterization of the 3 conformers initially present in the matrices. On the other hand, UV irradiation (λ = 255 nm) of PG isolated in a xenon matrix revealed that PG undergoes facile

Conformers, infrared spectrum, UV-induced photochemistry, and near-IR-induced generation of two rare conformers of matrix-isolated phenylglycine

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

Borba, Ana, E-mail: anaborba@ci.uc.pt; Fausto, Rui; Gómez-Zavaglia, Andrea

The conformational space of α-phenylglycine (PG) have been investigated theoretically at both the DFT/B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) levels of approximation. Seventeen different minima were found on the investigated potential energy surfaces, which are characterized by different dominant intramolecular interactions: type I conformers are stabilized by hydrogen bonds of the type N–H···O=C, type II by a strong O–H···N hydrogen bond, type III by weak N–H···O–H hydrogen bonds, and type IV by a C=O···H–C contact. The calculations indicate also that entropic effects are relevant in determining the equilibrium populations of the conformers of PG in the gas phase, in particular in the casemore » of conformers of type II, where the strong intramolecular O–H···N hydrogen bond considerably diminishes entropy by reducing the conformational mobility of the molecule. In consonance with the relative energies of the conformers and barriers for conformational interconversion, only 3 conformers of PG were observed for the compound isolated in cryogenic Ar, Xe, and N{sub 2} matrices: the conformational ground state (ICa), and forms ICc and IITa. All other significantly populated conformers existing in the gas phase prior to deposition convert either to conformer ICa or to conformer ICc during matrix deposition. The experimental observation of ICc had never been achieved hitherto. Narrowband near-IR irradiation of the first overtone of νOH vibrational mode of ICa and ICc in nitrogen matrices (at 6910 and 6930 cm{sup −1}, respectively) led to selective generation of two additional conformers of high-energy, ITc and ITa, respectively, which were also observed experimentally for the first time. In addition, these experiments also provided the key information for the detailed vibrational characterization of the 3 conformers initially present in the matrices. On the other hand, UV irradiation (λ = 255 nm) of PG isolated in a xenon matrix

Warpage optimisation on the moulded part with straight-drilled and conformal cooling channels using response surface methodology (RSM) and glowworm swarm optimisation (GSO)

NASA Astrophysics Data System (ADS)

Hazwan, M. H. M.; Shayfull, Z.; Sharif, S.; Nasir, S. M.; Zainal, N.

2017-09-01

In injection moulding process, quality and productivity are notably important and must be controlled for each product type produced. Quality is measured as the extent of warpage of moulded parts while productivity is measured as a duration of moulding cycle time. To control the quality, many researchers have introduced various of optimisation approaches which have been proven enhanced the quality of the moulded part produced. In order to improve the productivity of injection moulding process, some of researches have proposed the application of conformal cooling channels which have been proven reduced the duration of moulding cycle time. Therefore, this paper presents an application of alternative optimisation approach which is Response Surface Methodology (RSM) with Glowworm Swarm Optimisation (GSO) on the moulded part with straight-drilled and conformal cooling channels mould. This study examined the warpage condition of the moulded parts before and after optimisation work applied for both cooling channels. A front panel housing have been selected as a specimen and the performance of proposed optimisation approach have been analysed on the conventional straight-drilled cooling channels compared to the Milled Groove Square Shape (MGSS) conformal cooling channels by simulation analysis using Autodesk Moldflow Insight (AMI) 2013. Based on the results, melt temperature is the most significant factor contribute to the warpage condition and warpage have optimised by 39.1% after optimisation for straight-drilled cooling channels and cooling time is the most significant factor contribute to the warpage condition and warpage have optimised by 38.7% after optimisation for MGSS conformal cooling channels. In addition, the finding shows that the application of optimisation work on the conformal cooling channels offers the better quality and productivity of the moulded part produced.

Grain Boundary Conformed Volumetric Mesh Generation from a Three-Dimensional Voxellated Polycrystalline Microstructure

NASA Astrophysics Data System (ADS)

Lee, Myeong-Jin; Jeon, Young-Ju; Son, Ga-Eun; Sung, Sihwa; Kim, Ju-Young; Han, Heung Nam; Cho, Soo Gyeong; Jung, Sang-Hyun; Lee, Sukbin

2018-03-01

We present a new comprehensive scheme for generating grain boundary conformed, volumetric mesh elements from a three-dimensional voxellated polycrystalline microstructure. From the voxellated image of a polycrystalline microstructure obtained from the Monte Carlo Potts model in the context of isotropic normal grain growth simulation, its grain boundary network is approximated as a curvature-maintained conformal triangular surface mesh using a set of in-house codes. In order to improve the surface mesh quality and to adjust mesh resolution, various re-meshing techniques in a commercial software are applied to the approximated grain boundary mesh. It is found that the aspect ratio, the minimum angle and the Jacobian value of the re-meshed surface triangular mesh are successfully improved. Using such an enhanced surface mesh, conformal volumetric tetrahedral elements of the polycrystalline microstructure are created using a commercial software, again. The resultant mesh seamlessly retains the short- and long-range curvature of grain boundaries and junctions as well as the realistic morphology of the grains inside the polycrystal. It is noted that the proposed scheme is the first to successfully generate three-dimensional mesh elements for polycrystals with high enough quality to be used for the microstructure-based finite element analysis, while the realistic characteristics of grain boundaries and grains are maintained from the corresponding voxellated microstructure image.

Grain Boundary Conformed Volumetric Mesh Generation from a Three-Dimensional Voxellated Polycrystalline Microstructure

NASA Astrophysics Data System (ADS)

Lee, Myeong-Jin; Jeon, Young-Ju; Son, Ga-Eun; Sung, Sihwa; Kim, Ju-Young; Han, Heung Nam; Cho, Soo Gyeong; Jung, Sang-Hyun; Lee, Sukbin

2018-07-01

We present a new comprehensive scheme for generating grain boundary conformed, volumetric mesh elements from a three-dimensional voxellated polycrystalline microstructure. From the voxellated image of a polycrystalline microstructure obtained from the Monte Carlo Potts model in the context of isotropic normal grain growth simulation, its grain boundary network is approximated as a curvature-maintained conformal triangular surface mesh using a set of in-house codes. In order to improve the surface mesh quality and to adjust mesh resolution, various re-meshing techniques in a commercial software are applied to the approximated grain boundary mesh. It is found that the aspect ratio, the minimum angle and the Jacobian value of the re-meshed surface triangular mesh are successfully improved. Using such an enhanced surface mesh, conformal volumetric tetrahedral elements of the polycrystalline microstructure are created using a commercial software, again. The resultant mesh seamlessly retains the short- and long-range curvature of grain boundaries and junctions as well as the realistic morphology of the grains inside the polycrystal. It is noted that the proposed scheme is the first to successfully generate three-dimensional mesh elements for polycrystals with high enough quality to be used for the microstructure-based finite element analysis, while the realistic characteristics of grain boundaries and grains are maintained from the corresponding voxellated microstructure image.

Lie algebra of conformal Killing-Yano forms

NASA Astrophysics Data System (ADS)

Ertem, Ümit

2016-06-01

We provide a generalization of the Lie algebra of conformal Killing vector fields to conformal Killing-Yano forms. A new Lie bracket for conformal Killing-Yano forms that corresponds to slightly modified Schouten-Nijenhuis bracket of differential forms is proposed. We show that conformal Killing-Yano forms satisfy a graded Lie algebra in constant curvature manifolds. It is also proven that normal conformal Killing-Yano forms in Einstein manifolds also satisfy a graded Lie algebra. The constructed graded Lie algebras reduce to the graded Lie algebra of Killing-Yano forms and the Lie algebras of conformal Killing and Killing vector fields in special cases.

Conformational Dynamics of Insulin

PubMed Central

Hua, Qing-Xin; Jia, Wenhua; Weiss, Michael A.

2011-01-01

We have exploited a prandial insulin analog to elucidate the underlying structure and dynamics of insulin as a monomer in solution. A model was provided by insulin lispro (the active component of Humalog®; Eli Lilly and Co.). Whereas NMR-based modeling recapitulated structural relationships of insulin crystals (T-state protomers), dynamic anomalies were revealed by amide-proton exchange kinetics in D2O. Surprisingly, the majority of hydrogen bonds observed in crystal structures are only transiently maintained in solution, including key T-state-specific inter-chain contacts. Long-lived hydrogen bonds (as defined by global exchange kinetics) exist only at a subset of four α-helical sites (two per chain) flanking an internal disulfide bridge (cystine A20–B19); these sites map within the proposed folding nucleus of proinsulin. The anomalous flexibility of insulin otherwise spans its active surface and may facilitate receptor binding. Because conformational fluctuations promote the degradation of pharmaceutical formulations, we envisage that “dynamic re-engineering” of insulin may enable design of ultra-stable formulations for humanitarian use in the developing world. PMID:22649374

How smoke-free laws improve air quality: A global study of Irish pubs

PubMed Central

Carpenter, Carrie M.; Travers, Mark J.; Cummings, K. Michael; Hyland, Andrew; Mulcahy, Maurice; Clancy, Luke

2009-01-01

Introduction The present study examined indoor air quality in a global sample of smoke-free and smoking-permitted Irish pubs. We hypothesized that levels of respirable suspended particles, an important marker of secondhand smoke, would be significantly lower in smoke-free Irish pubs than in pubs that allowed smoking. Methods Indoor air quality was assessed in 128 Irish pubs in 15 countries between 21 January 2004 and 10 March 2006. Air quality was evaluated using an aerosol monitor, which measures the level of fine particle (PM2.5) pollution in the air. A standard measurement protocol was used by data collectors across study sites. Results Overall, the level of air pollution inside smoke-free Irish pubs was 93% lower than the level found in pubs where smoking was permitted. Discussion Levels of indoor air pollution can be massively reduced by enacting and enforcing smoke-free policies. PMID:19380381

Developing Global Standards Framework and Quality Integrated Models for Cooperative and Work-Integrated Education Programs

ERIC Educational Resources Information Center

Khampirat, Buratin; McRae, Norah

2016-01-01

Cooperative and Work-integrated Education (CWIE) programs have been widely accepted as educational programs that can effectively connect what students are learning to the world of work through placements. Because a global quality standards framework could be a very valuable resource and guide to establishing, developing, and accrediting quality…

Subtle Convergence? Locating Similarities between Chinese Educational Reforms and Global Quality Assurance and Evaluation Trends

ERIC Educational Resources Information Center

Suominen, Olli; Rinne, Risto; Kallo, Johanna; Fan, Yihong

2017-01-01

Purpose: Different aspects of the globalisation of Chinese basic education have been examined in recent studies. This paper aims to contribute to this research base by examining the relationship between global quality assurance and evaluation (QAEVAL) trends and reforms in the Chinese basic education system. Design/methodology/approach: Relevant…

Availability and quality of cause-of-death data for estimating the global burden of injuries

PubMed Central

Harrison, James E; Shahraz, Saeid; Fingerhut, Lois A

2010-01-01

Abstract Objective To assess the availability and quality of global death registration data used for estimating injury mortality. Methods The completeness and coverage of recent national death registration data from the World Health Organization mortality database were assessed. The quality of data on a specific cause of injury death was judged high if fewer than 20% of deaths were attributed to any of several partially specified causes of injury, such as “unspecified unintentional injury”. Findings Recent death registration data were available for 83 countries, comprising 28% of the global population. They included most high-income countries, most countries in Latin America and several in central Asia and the Caribbean. Categories commonly used for partially specified external causes of injury resulting in death included “undetermined intent,” “unspecified mechanism of unintentional injury,” “unspecified road injury” and “unspecified mechanism of homicide”. Only 20 countries had high-quality data. Nevertheless, because the partially specified categories do contain some information about injury mechanisms, reliable estimates of deaths due to specific external causes of injury, such as road injury, suicide and homicide, could be derived for many more countries. Conclusion Only 20 countries had high-quality death registration data that could be used for estimating injury mortality because injury deaths were frequently classified using imprecise partially specified categories. Analytical methods that can derive national estimates of injury mortality from alternative data sources are needed for countries without reliable death registration systems. PMID:21076564

Conformational Clusters of Phosphorylated Tyrosine.

PubMed

Abdelrasoul, Maha; Ponniah, Komala; Mao, Alice; Warden, Meghan S; Elhefnawy, Wessam; Li, Yaohang; Pascal, Steven M

2017-12-06

Tyrosine phosphorylation plays an important role in many cellular and intercellular processes including signal transduction, subcellular localization, and regulation of enzymatic activity. In 1999, Blom et al., using the limited number of protein data bank (PDB) structures available at that time, reported that the side chain structures of phosphorylated tyrosine (pY) are partitioned into two conserved conformational clusters ( Blom, N.; Gammeltoft, S.; Brunak, S. J. Mol. Biol. 1999 , 294 , 1351 - 1362 ). We have used the spectral clustering algorithm to cluster the increasingly growing number of protein structures with pY sites, and have found that the pY residues cluster into three distinct side chain conformations. Two of these pY conformational clusters associate strongly with a narrow range of tyrosine backbone conformation. The novel cluster also highly correlates with the identity of the n + 1 residue, and is strongly associated with a sequential pYpY conformation which places two adjacent pY side chains in a specific relative orientation. Further analysis shows that the three pY clusters are associated with distinct distributions of cognate protein kinases.

The Problem and Goals Are Global, the Solutions Are Local: Revisiting Quality Measurements and the Role of the Private Sector in Global Health Professions Education.

PubMed

Hamdy, Hossam

2017-08-01

The shortage of a competent health workforce is a global challenge. However, its manifestations and proposed solutions are very much context related (i.e., local). In addition to the shortage of health professionals, the quality of health professions education programs, institutions, and graduates, and how to measure quality, are also problematic. Commonly used metrics like the Credit Hours System and the European Credit Transfer and Accumulation System have limitations (e.g., being more focused on quantity than quality).In this Invited Commentary, the author discusses the need to revisit quality measurements in health professions education and the issue of whether the private sector has a role to play in narrowing the ever-increasing gap between the demand for health care professionals and the health care workforce shortage.

Thickenings and conformal gravity

NASA Astrophysics Data System (ADS)

Lebrun, Claude

1991-07-01

A twistor correspondence is given for complex conformal space-times with vanishing Bach and Eastwood-Dighton tensors; when the Weyl curvature is algebraically general, these equations are precisely the conformal version of Einstein's vacuum equations with cosmological constant. This gives a fully curved version of the linearized correspondence of Baston and Mason [B-M].

Scale invariance, conformality, and generalized free fields

DOE PAGES

Dymarsky, Anatoly; Farnsworth, Kara; Komargodski, Zohar; ...

2016-02-16

This paper addresses the question of whether there are 4D Lorentz invariant unitary quantum fi eld theories with scale invariance but not conformal invariance. We present an important loophole in the arguments of Luty-Polchinski-Rattazzi and Dymarsky-Komargodski-Schwimmer-Theisen that is the trace of the energy-momentum tensor T could be a generalized free field. In this paper we rule out this possibility. The key ingredient is the observation that a unitary theory with scale but not conformal invariance necessarily has a non-vanishing anomaly for global scale transformations. We show that this anomaly cannot be reproduced if T is a generalized free field unlessmore » the theory also contains a dimension-2 scalar operator. In the special case where such an operator is present it can be used to redefine ("improve") the energy-momentum tensor, and we show that there is at least one energy-momentum tensor that is not a generalized free field. In addition, we emphasize that, in general, large momentum limits of correlation functions cannot be understood from the leading terms of the coordinate space OPE. This invalidates a recent argument by Farnsworth-Luty-Prilepina (FLP). Finally, despite the invalidity of the general argument of FLP, some of the techniques turn out to be useful in the present context.« less

Laboratory evolution of protein conformational dynamics.

PubMed

Campbell, Eleanor C; Correy, Galen J; Mabbitt, Peter D; Buckle, Ashley M; Tokuriki, Nobuhiko; Jackson, Colin J

2017-11-08

This review focuses on recent work that has begun to establish specific functional roles for protein conformational dynamics, specifically how the conformational landscapes that proteins can sample can evolve under laboratory based evolutionary selection. We discuss recent technical advances in computational and biophysical chemistry, which have provided us with new ways to dissect evolutionary processes. Finally, we offer some perspectives on the emerging view of conformational dynamics and evolution, and the challenges that we face in rationally engineering conformational dynamics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Data quality through a web-based QA/QC system: implementation for atmospheric mercury data from the global mercury observation system.

PubMed

D'Amore, Francesco; Bencardino, Mariantonia; Cinnirella, Sergio; Sprovieri, Francesca; Pirrone, Nicola

2015-08-01

The overall goal of the on-going Global Mercury Observation System (GMOS) project is to develop a coordinated global monitoring network for mercury, including ground-based, high altitude and sea level stations. In order to ensure data reliability and comparability, a significant effort has been made to implement a centralized system, which is designed to quality assure and quality control atmospheric mercury datasets. This system, GMOS-Data Quality Management (G-DQM), uses a web-based approach with real-time adaptive monitoring procedures aimed at preventing the production of poor-quality data. G-DQM is plugged on a cyberinfrastructure and deployed as a service. Atmospheric mercury datasets, produced during the first-three years of the GMOS project, are used as the input to demonstrate the application of the G-DQM and how it identifies a number of key issues concerning data quality. The major issues influencing data quality are presented and discussed for the GMOS stations under study. Atmospheric mercury data collected at the Longobucco (Italy) station is used as a detailed case study.

Chemical and Conformational Diversity of Modified Nucleosides Affects tRNA Structure and Function.

PubMed

Väre, Ville Y P; Eruysal, Emily R; Narendran, Amithi; Sarachan, Kathryn L; Agris, Paul F

2017-03-16

RNAs are central to all gene expression through the control of protein synthesis. Four major nucleosides, adenosine, guanosine, cytidine and uridine, compose RNAs and provide sequence variation, but are limited in contributions to structural variation as well as distinct chemical properties. The ability of RNAs to play multiple roles in cellular metabolism is made possible by extensive variation in length, conformational dynamics, and the over 100 post-transcriptional modifications. There are several reviews of the biochemical pathways leading to RNA modification, but the physicochemical nature of modified nucleosides and how they facilitate RNA function is of keen interest, particularly with regard to the contributions of modified nucleosides. Transfer RNAs (tRNAs) are the most extensively modified RNAs. The diversity of modifications provide versatility to the chemical and structural environments. The added chemistry, conformation and dynamics of modified nucleosides occurring at the termini of stems in tRNA's cloverleaf secondary structure affect the global three-dimensional conformation, produce unique recognition determinants for macromolecules to recognize tRNAs, and affect the accurate and efficient decoding ability of tRNAs. This review will discuss the impact of specific chemical moieties on the structure, stability, electrochemical properties, and function of tRNAs.

Transportation Conformity

EPA Pesticide Factsheets

This section provides information on: current laws, regulations and guidance, policy and technical guidance, project-level conformity, general information, contacts and training, adequacy review of SIP submissions

Implementing subgrid-scale cloudiness into the Model for Prediction Across Scales-Atmosphere (MPAS-A) for next generation global air quality modeling

EPA Science Inventory

A next generation air quality modeling system is being developed at the U.S. EPA to enable seamless modeling of air quality from global to regional to (eventually) local scales. State of the science chemistry and aerosol modules from the Community Multiscale Air Quality (CMAQ) mo...

Coexisting stable conformations of gaseous protein ions.

PubMed Central

Suckau, D; Shi, Y; Beu, S C; Senko, M W; Quinn, J P; Wampler, F M; McLafferty, F W

1993-01-01

For further insight into the role of solvent in protein conformer stabilization, the structural and dynamic properties of protein ions in vacuo have been probed by hydrogen-deuterium exchange in a Fourier-transform mass spectrometer. Multiply charged ions generated by electrospray ionization of five proteins show exchange reactions with 2H2O at 10(-7) torr (1 torr = 133.3 Pa) exhibiting pseudo-first-order kinetics. Gas-phase compactness of the S-S cross-linked RNase A relative to denatured S-derivatized RNase A is indicated by exchange of 35 and 135 hydrogen atoms, respectively. For pure cytochrome c ions, the existence of at least three distinct gaseous conformers is indicated by the substantially different values--52, 113, and 74--of reactive H atoms; the observation of these same values for ions of a number--2, 7, and 5, respectively--of different charge states indicates conformational insensitivity to coulombic forces. For each of these conformers, the compactness in vacuo indicated by these values corresponds directly to that of a known conformer structure in the solution from which the conformer ions are produced by electrospray. S-derivatized RNase A ions also exist as at least two gaseous conformers exchanging 50-140 H atoms. Gaseous conformer ions are isometrically stable for hours; removal of solvent greatly increases conformational rigidity. More specific ion-molecule reactions could provide further details of conformer structures. Images PMID:8381533

Global Scenarios of Air Pollution until 2030: Combining Air Quality, Climate Change and Energy Access Policies

NASA Astrophysics Data System (ADS)

Rao, S.; Dentener, F. J.; Klimont, Z.; Riahi, K.

2011-12-01

Outdoor air pollution is increasingly recognized as a significant contributor to global health outcomes. This has led to the implementation of a number of air quality policies worldwide, with total air pollution control costs in 2005 estimated at US$195 billion. More than 80% of the world's population is still found to be exposed to PM2.5 concentrations exceeding WHO air quality guidelines and health impacts resulting from these exposures estimated at around 2-5% of the global disease burden. Key questions to answer are 1) How will pollutant emissions evolve in the future given developments in the energy system and how will energy and environmental policies influence such emission trends. 2) What implications will this have for resulting exposures and related health outcomes. In order to answer these questions, varying levels of stringency of air quality legislation are analyzed in combination with policies on universal access to clean cooking fuels and limiting global temperature change to 2°C in 2100. Bottom-up methodologies using energy emissions modeling are used to derive sector-based pollutant emission trajectories until 2030. Emissions are spatially downscaled and used in combination with a global transport chemistry model to derive ambient concentrations of PM2.5. Health impacts of these exposures are further estimated consistent with WHO data and methodology. The results indicate that currently planned air quality legislation combined with rising energy demand will be insufficient in controlling future emissions growth in developing countries. In order to achieve significant reductions in pollutant emissions of the order of more than 50% from 2005 levels and reduce exposures to levels consistent with WHO standards, it will be necessary to increase the stringency of such legislations and combine them with policies on energy access and climate change. Combined policies also result in reductions in air pollution control costs as compared to those associated

A Novel Method Using Abstract Convex Underestimation in Ab-Initio Protein Structure Prediction for Guiding Search in Conformational Feature Space.

PubMed

Hao, Xiao-Hu; Zhang, Gui-Jun; Zhou, Xiao-Gen; Yu, Xu-Feng

2016-01-01

To address the searching problem of protein conformational space in ab-initio protein structure prediction, a novel method using abstract convex underestimation (ACUE) based on the framework of evolutionary algorithm was proposed. Computing such conformations, essential to associate structural and functional information with gene sequences, is challenging due to the high-dimensionality and rugged energy surface of the protein conformational space. As a consequence, the dimension of protein conformational space should be reduced to a proper level. In this paper, the high-dimensionality original conformational space was converted into feature space whose dimension is considerably reduced by feature extraction technique. And, the underestimate space could be constructed according to abstract convex theory. Thus, the entropy effect caused by searching in the high-dimensionality conformational space could be avoided through such conversion. The tight lower bound estimate information was obtained to guide the searching direction, and the invalid searching area in which the global optimal solution is not located could be eliminated in advance. Moreover, instead of expensively calculating the energy of conformations in the original conformational space, the estimate value is employed to judge if the conformation is worth exploring to reduce the evaluation time, thereby making computational cost lower and the searching process more efficient. Additionally, fragment assembly and the Monte Carlo method are combined to generate a series of metastable conformations by sampling in the conformational space. The proposed method provides a novel technique to solve the searching problem of protein conformational space. Twenty small-to-medium structurally diverse proteins were tested, and the proposed ACUE method was compared with It Fix, HEA, Rosetta and the developed method LEDE without underestimate information. Test results show that the ACUE method can more rapidly and more

Linking transportation and air quality planning : implementation of the transportation conformity regulations in 15 nonattainment areas

DOT National Transportation Integrated Search

1999-07-01

The Clean Air Act Amendments (CAAA) of 1990 require far-reaching efforts under the "transportation conformity" regulations to assure that transportation investments in nonattainment and maintenance areas are consistent with state commitments to meet ...

Impact of Asian Dust on Global Surface Air Quality and Radiation Budget

NASA Technical Reports Server (NTRS)

Chin, Mian; Diehl, Thomas; Yu, Hongbin; Ginoux, Paul

2006-01-01

Dust originating from Asian deserts and desertification areas can be transported regionally and globally to affect surface air quality, visibility, and radiation budget not only at immediate downwind locations (e.g., eastern Asia) but also regions far away from the sources (e.g., North America). Deposition of Asian dust to the North Pacific Ocean basin influences the ocean productivity. In this study, we will use the Goddard Chemistry Aerosol Radiation and Transport (GOCART) model, remote sensing data form satellite and from the ground-based network, and in-situ data from aircraft and surface observations to address the following questions: - What are the effects of Asian dust on the surface air quality and visibility over Asia and North America? - What are the seasonal and spatial variations of dust deposition to the North Pacific Ocean? How does the Asian dust affect surface radiation budget?

Galilean field theories and conformal structure

NASA Astrophysics Data System (ADS)

Bagchi, Arjun; Chakrabortty, Joydeep; Mehra, Aditya

2018-04-01

We perform a detailed analysis of Galilean field theories, starting with free theories and then interacting theories. We consider non-relativistic versions of massless scalar and Dirac field theories before we go on to review our previous construction of Galilean Electrodynamics and Galilean Yang-Mills theory. We show that in all these cases, the field theories exhibit non-relativistic conformal structure (in appropriate dimensions). The surprising aspect of the analysis is that the non-relativistic conformal structure exhibited by these theories, unlike relativistic conformal invariance, becomes infinite dimensional even in spacetime dimensions greater than two. We then couple matter with Galilean gauge theories and show that there is a myriad of different sectors that arise in the non-relativistic limit from the parent relativistic theories. In every case, if the parent relativistic theory exhibited conformal invariance, we find an infinitely enhanced Galilean conformal invariance in the non-relativistic case. This leads us to suggest that infinite enhancement of symmetries in the non-relativistic limit is a generic feature of conformal field theories in any dimension.

Discrepancies on quality perceived by the patients versus professionals on the quality of a nuclear medicine department.

PubMed

Rodrigo-Rincon, I; Goñi-Girones, E; Serra-Arbeloa, P; Martinez-Lozano, M E; Reyes-Pérez, M

2015-01-01

To evaluate the discrepancies between the professionals and outpatients on quality perceived of a Nuclear Medicine Department (NMD). This cross-sectional study has been carried out using two questionnaires: a validated patient experience questionnaire and a quality perception questionnaire for professionals. Both questionnaires use the same 25 categorical items to measure service quality, 2 Likert scale items to measure satisfaction and willingness to recommend the NMD and 1 open-ended question. The patient questionnaire included 6 socio-demographic items and one job-related question (professionals). The categorical items were classified as "conformity" or "non-conformity." The response rate was 36.7% for outpatients and 100% for professionals. Mean value for satisfaction with the NMD was 9 points for patients and 6.9 points for professionals. Mean number of non-conformity items per person was 2.8 for the patient group and 8.7 for the professional group. Cohen's Kappa value was 0.112, indicating poor agreement in the classification of items as strong points and areas for improvement. Of the 25 items, the professionals and patients coincided on 12 (48%). Agreement was low between the quality perception of patients and professionals. The patients scored quality of service higher than the NMD professionals did. These instruments are useful aid to help health organizations detect areas for improvement, and to improve the quality of the service provided to patients. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Transportation Conformity Training and Presentations

EPA Pesticide Factsheets

EPA's OTAQ has provided multiple conformity training sessions in the past to assist state and local governments in implementing conformity requirements. As training information is prepared for other venues, it will be posted on this page.

3D printed conformal microfluidics for isolation and profiling of biomarkers from whole organs.

PubMed

Singh, Manjot; Tong, Yuxin; Webster, Kelly; Cesewski, Ellen; Haring, Alexander P; Laheri, Sahil; Carswell, Bill; O'Brien, Timothy J; Aardema, Charles H; Senger, Ryan S; Robertson, John L; Johnson, Blake N

2017-07-25

The ability to interface microfluidic devices with native complex biological architectures, such as whole organs, has the potential to shift the paradigm for the study and analysis of biological tissue. Here, we show 3D printing can be used to fabricate bio-inspired conformal microfluidic devices that directly interface with the surface of whole organs. Structured-light scanning techniques enabled the 3D topographical matching of microfluidic device geometry to porcine kidney anatomy. Our studies show molecular species are spontaneously transferred from the organ cortex to the conformal microfluidic device in the presence of fluid flow through the organ-conforming microchannel. Large animal studies using porcine kidneys (n = 32 organs) revealed the profile of molecular species in the organ-conforming microfluidic stream was dependent on the organ preservation conditions. Enzyme-linked immunosorbent assay (ELISA) studies revealed conformal microfluidic devices isolate clinically relevant metabolic and pathophysiological biomarkers from whole organs, including heat shock protein 70 (HSP-70) and kidney injury molecule-1 (KIM-1), which were detected in the microfluidic device as high as 409 and 12 pg mL -1 , respectively. Overall, these results show conformal microfluidic devices enable a novel minimally invasive 'microfluidic biopsy' technique for isolation and profiling of biomarkers from whole organs within a clinically relevant interval. This achievement could shift the paradigm for whole organ preservation and assessment, thereby helping to relieve the organ shortage crisis through increased availability and quality of donor organs. Ultimately, this work provides a major advance in microfluidics through the design and manufacturing of organ-conforming microfluidic devices and a novel technique for microfluidic-based analysis of whole organs.

Conformational Switching of a Foldamer in a Multicomponent System by pH-Filtered Selection between Competing Noncovalent Interactions

PubMed Central

2015-01-01

Biomolecular systems are able to respond to their chemical environment through reversible, selective, noncovalent intermolecular interactions. Typically, these interactions induce conformational changes that initiate a signaling cascade, allowing the regulation of biochemical pathways. In this work, we describe an artificial molecular system that mimics this ability to translate selective noncovalent interactions into reversible conformational changes. An achiral but helical foldamer carrying a basic binding site interacts selectively with the most acidic member of a suite of chiral ligands. As a consequence of this noncovalent interaction, a global absolute screw sense preference, detectable by 13C NMR, is induced in the foldamer. Addition of base, or acid, to the mixture of ligands competitively modulates their interaction with the binding site, and reversibly switches the foldamer chain between its left and right-handed conformations. As a result, the foldamer–ligand mixture behaves as a biomimetic chemical system with emergent properties, functioning as a “proton-counting” molecular device capable of providing a tunable, pH-dependent conformational response to its environment. PMID:25915163

Transforming University Education and Quality Assurance for Sustainable Development in Nigeria for a Globalized World

ERIC Educational Resources Information Center

Mamman, F. N.

2013-01-01

Education has been recognized as an important tool for achieving a nation's goals, vision and objectives. The quality of Nigerian universities has been and still is an issue of concern among stakeholders due to the challenges posed by globalization and the need for continued scientific and technological advancement. Over the years, this concern…

Global mapping of DNA conformational flexibility on Saccharomyces cerevisiae.

PubMed

Menconi, Giulia; Bedini, Andrea; Barale, Roberto; Sbrana, Isabella

2015-04-01

In this study we provide the first comprehensive map of DNA conformational flexibility in Saccharomyces cerevisiae complete genome. Flexibility plays a key role in DNA supercoiling and DNA/protein binding, regulating DNA transcription, replication or repair. Specific interest in flexibility analysis concerns its relationship with human genome instability. Enrichment in flexible sequences has been detected in unstable regions of human genome defined fragile sites, where genes map and carry frequent deletions and rearrangements in cancer. Flexible sequences have been suggested to be the determinants of fragile gene proneness to breakage; however, their actual role and properties remain elusive. Our in silico analysis carried out genome-wide via the StabFlex algorithm, shows the conserved presence of highly flexible regions in budding yeast genome as well as in genomes of other Saccharomyces sensu stricto species. Flexibile peaks in S. cerevisiae identify 175 ORFs mapping on their 3'UTR, a region affecting mRNA translation, localization and stability. (TA)n repeats of different extension shape the central structure of peaks and co-localize with polyadenylation efficiency element (EE) signals. ORFs with flexible peaks share common features. Transcripts are characterized by decreased half-life: this is considered peculiar of genes involved in regulatory systems with high turnover; consistently, their function affects biological processes such as cell cycle regulation or stress response. Our findings support the functional importance of flexibility peaks, suggesting that the flexible sequence may be derived by an expansion of canonical TAYRTA polyadenylation efficiency element. The flexible (TA)n repeat amplification could be the outcome of an evolutionary neofunctionalization leading to a differential 3'-end processing and expression regulation in genes with peculiar function. Our study provides a new support to the functional role of flexibility in genomes and a

Global Mapping of DNA Conformational Flexibility on Saccharomyces cerevisiae

PubMed Central

Menconi, Giulia; Bedini, Andrea; Barale, Roberto; Sbrana, Isabella

2015-01-01

In this study we provide the first comprehensive map of DNA conformational flexibility in Saccharomyces cerevisiae complete genome. Flexibility plays a key role in DNA supercoiling and DNA/protein binding, regulating DNA transcription, replication or repair. Specific interest in flexibility analysis concerns its relationship with human genome instability. Enrichment in flexible sequences has been detected in unstable regions of human genome defined fragile sites, where genes map and carry frequent deletions and rearrangements in cancer. Flexible sequences have been suggested to be the determinants of fragile gene proneness to breakage; however, their actual role and properties remain elusive. Our in silico analysis carried out genome-wide via the StabFlex algorithm, shows the conserved presence of highly flexible regions in budding yeast genome as well as in genomes of other Saccharomyces sensu stricto species. Flexibile peaks in S. cerevisiae identify 175 ORFs mapping on their 3’UTR, a region affecting mRNA translation, localization and stability. (TA)n repeats of different extension shape the central structure of peaks and co-localize with polyadenylation efficiency element (EE) signals. ORFs with flexible peaks share common features. Transcripts are characterized by decreased half-life: this is considered peculiar of genes involved in regulatory systems with high turnover; consistently, their function affects biological processes such as cell cycle regulation or stress response. Our findings support the functional importance of flexibility peaks, suggesting that the flexible sequence may be derived by an expansion of canonical TAYRTA polyadenylation efficiency element. The flexible (TA)n repeat amplification could be the outcome of an evolutionary neofunctionalization leading to a differential 3’-end processing and expression regulation in genes with peculiar function. Our study provides a new support to the functional role of flexibility in genomes and a

Intramolecular BSSE and dispersion affect the structure of a dipeptide conformer

NASA Astrophysics Data System (ADS)

Hameed, Rabia; Khan, Afsar; van Mourik, Tanja

2018-05-01

B3LYP and MP2 calculations with the commonly-used 6-31+G(d) basis set predict qualitatively different structures for the Tyr-Gly conformer book1, which is the most stable conformer identified in a previous study. The structures differ mainly in the ψtyr Ramachandran angle (138° in the B3LYP structure and 120° in the MP2 structure). The causes for the discrepant structures are attributed to missing dispersion in the B3LYP calculations and large intramolecular BSSE in the MP2 calculations. The correct ψtyr value is estimated to be 130°. The MP2/6-31+G(d) profile identified an additional conformer, not present on the B3LYP surface, with a ψtyr value of 96° and a more folded structure. This minimum is, however, likely an artefact of large intramolecular BSSE values. We recommend the use of basis sets of at least quadruple-zeta quality in density functional theory (DFT), DFTaugmented with an empirical dispersion term (DFT-D) and second-order Møller-Plesset perturbation theory (MP2 ) calculations in cases where intramolecular BSSE is expected to be large.

Euclidean sections of protein conformation space and their implications in dimensionality reduction

PubMed Central

Duan, Mojie; Li, Minghai; Han, Li; Huo, Shuanghong

2014-01-01

Dimensionality reduction is widely used in searching for the intrinsic reaction coordinates for protein conformational changes. We find the dimensionality–reduction methods using the pairwise root–mean–square deviation as the local distance metric face a challenge. We use Isomap as an example to illustrate the problem. We believe that there is an implied assumption for the dimensionality–reduction approaches that aim to preserve the geometric relations between the objects: both the original space and the reduced space have the same kind of geometry, such as Euclidean geometry vs. Euclidean geometry or spherical geometry vs. spherical geometry. When the protein free energy landscape is mapped onto a 2D plane or 3D space, the reduced space is Euclidean, thus the original space should also be Euclidean. For a protein with N atoms, its conformation space is a subset of the 3N-dimensional Euclidean space R3N. We formally define the protein conformation space as the quotient space of R3N by the equivalence relation of rigid motions. Whether the quotient space is Euclidean or not depends on how it is parameterized. When the pairwise root–mean–square deviation is employed as the local distance metric, implicit representations are used for the protein conformation space, leading to no direct correspondence to a Euclidean set. We have demonstrated that an explicit Euclidean-based representation of protein conformation space and the local distance metric associated to it improve the quality of dimensionality reduction in the tetra-peptide and β–hairpin systems. PMID:24913095

Protein structure modeling for CASP10 by multiple layers of global optimization.

PubMed

Joo, Keehyoung; Lee, Juyong; Sim, Sangjin; Lee, Sun Young; Lee, Kiho; Heo, Seungryong; Lee, In-Ho; Lee, Sung Jong; Lee, Jooyoung

2014-02-01

In the template-based modeling (TBM) category of CASP10 experiment, we introduced a new protocol called protein modeling system (PMS) to generate accurate protein structures in terms of side-chains as well as backbone trace. In the new protocol, a global optimization algorithm, called conformational space annealing (CSA), is applied to the three layers of TBM procedure: multiple sequence-structure alignment, 3D chain building, and side-chain re-modeling. For 3D chain building, we developed a new energy function which includes new distance restraint terms of Lorentzian type (derived from multiple templates), and new energy terms that combine (physical) energy terms such as dynamic fragment assembly (DFA) energy, DFIRE statistical potential energy, hydrogen bonding term, etc. These physical energy terms are expected to guide the structure modeling especially for loop regions where no template structures are available. In addition, we developed a new quality assessment method based on random forest machine learning algorithm to screen templates, multiple alignments, and final models. For TBM targets of CASP10, we find that, due to the combination of three stages of CSA global optimizations and quality assessment, the modeling accuracy of PMS improves at each additional stage of the protocol. It is especially noteworthy that the side-chains of the final PMS models are far more accurate than the models in the intermediate steps. Copyright © 2013 Wiley Periodicals, Inc.

Protein Conformational Populations and Functionally Relevant Sub-states

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

Agarwal, Pratul K; Burger, Virginia; Savol, Andrej

2013-01-01

Functioning proteins do not remain fixed in a unique structure, but instead they sample a range of conformations facilitated by motions within the protein. Even in the native state, a protein exists as a collection of interconverting conformations driven by thermodynamic fluctuations. Motions on the fast time scale allow a protein to sample conformations in the nearby area of its conformational landscape, while motions on slower time scales give it access to conformations in distal areas of the landscape. Emerging evidence indicates that protein landscapes contain conformational substates with dynamic and structural features that support the designated function of themore » protein. Nuclear magnetic resonance (NMR) experiments provide information about conformational ensembles of proteins. X-ray crystallography allows researchers to identify the most populated states along the landscape, and computational simulations give atom-level information about the conformational substates of different proteins. This ability to characterize and obtain quantitative information about the conformational substates and the populations of proteins within them is allowing researchers to better understand the relationship between protein structure and dynamics and the mechanisms of protein function. In this Account, we discuss recent developments and challenges in the characterization of functionally relevant conformational populations and substates of proteins. In some enzymes, the sampling of functionally relevant conformational substates is connected to promoting the overall mechanism of catalysis. For example, the conformational landscape of the enzyme dihydrofolate reductase has multiple substates, which facilitate the binding and the release of the cofactor and substrate and catalyze the hydride transfer. For the enzyme cyclophilin A, computational simulations reveal that the long time scale conformational fluctuations enable the enzyme to access conformational substates that

Harmony of spinning conformal blocks

NASA Astrophysics Data System (ADS)

Schomerus, Volker; Sobko, Evgeny; Isachenkov, Mikhail

2017-03-01

Conformal blocks for correlation functions of tensor operators play an increasingly important role for the conformal bootstrap programme. We develop a universal approach to such spinning blocks through the harmonic analysis of certain bundles over a coset of the conformal group. The resulting Casimir equations are given by a matrix version of the Calogero-Sutherland Hamiltonian that describes the scattering of interacting spinning particles in a 1-dimensional external potential. The approach is illustrated in several examples including fermionic seed blocks in 3D CFT where they take a very simple form.

Conformational Map of Phenolic Acids.

PubMed

Cortijo, Vanessa; Alonso, Elena R; Mata, Santiago; Alonso, José L

2018-01-18

The benefits of vaporization by laser ablation and the high resolution and sensitivity attained by the chirped pulse Fourier transform microwave spectroscopy CP-FTMW have provided the first conformational map of the simplest phenolic acids of trans-cinnamic and p-coumaric. Two conformers of trans-cinnamic acid and four conformers of trans-p-coumaric acid have been characterized under the isolation conditions of a supersonic expansion. The spectroscopic constants derived from the analysis of the rotational spectra compared with those predicted theoretically provide an unmatched means to achieve an unambiguous identification of the observed species.

Conformations of eight-membered cyclosiloxanes

NASA Astrophysics Data System (ADS)

Palyulin, V. A.; Zefirov, N. S.; Shklover, V. E.; Struchkov, Yu. T.

1981-01-01

Using the Cremer—Pople approach the classification and quantitative description of the conformations of eight-membered rings has been accomplished. The conformations of eight-membered cyclosiloxanes are considered and classified on the basis of available X-ray structural data.

Quality of Life and Survival Outcome for Patients With Nasopharyngeal Carcinoma Receiving Three-Dimensional Conformal Radiotherapy vs. Intensity-Modulated Radiotherapy-A Longitudinal Study

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

Fang, F.-M.; Kaohsiung Chang Gung Head and Neck Oncology Group, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung Hsien, Taiwan; Chien, C.-Y.

2008-10-01

Purpose: To investigate the changes of quality of life (QoL) and survival outcomes for patients with nasopharyngeal carcinoma (NPC) treated by three-dimensional conformal radiotherapy (3D-CRT) vs. intensity-modulated radiotherapy (IMRT). Methods and Materials: Two hundred and three newly diagnosed NPC patients, who were curatively treated by 3D-CRT (n = 93) or IMRT (n = 110) between March 2002 and July 2004, were analyzed. The distributions of clinical stage according to American Joint Committee on Cancer 1997 were I: 15 (7.4%), II: 78 (38.4%), III: 74 (36.5%), and IV: 36 (17.7%). QoL was longitudinally assessed by the European Organization for Research andmore » Treatment of Cancer (EORTC) QLQ-C30 and the EORTC QLQ-H and N35 questionnaires at the five time points: before RT, during RT (36 Gy), and 3 months, 12 months, and 24 months after RT. Results: The 3-year locoregional control, metastasis-free survival, and overall survival rates were 84.8%, 76.7%, and 81.7% for the 3D-CRT group, respectively, compared with 84.2%, 82.6%, and 85.4% for the IMRT group (p value > 0.05). A general trend of maximal deterioration in most QoL scales was observed during RT, followed by a gradual recovery thereafter. There was no significant difference in most scales between the two groups at each time point. The exception was that patients treated by IMRT had a both statistically and clinically significant improvement in global QoL, fatigue, taste/smell, dry mouth, and feeling ill at the time point of 3 months after RT. Conclusions: The potential advantage of IMRT over 3D-CRT in treating NPC patients might occur in QoL outcome during the recovery phase of acute toxicity.« less

Commissioning of a conformal irradiation system for heavy-ion radiotherapy using a layer-stacking method.

PubMed

Kanai, Tatsuaki; Kanematsu, Nobuyuki; Minohara, Shinichi; Komori, Masataka; Torikoshi, Masami; Asakura, Hiroshi; Ikeda, Noritoshi; Uno, Takayuki; Takei, Yuka

2006-08-01

The commissioning of conformal radiotherapy system using heavy-ion beams at the Heavy Ion Medical Accelerator in Chiba (HIMAC) is described in detail. The system at HIMAC was upgraded for a clinical trial using a new technique: large spot uniform scanning with conformal layer stacking. The system was developed to localize the irradiation dose to the target volume more effectively than with the old system. With the present passive irradiation method using a ridge filter, a scatterer, a pair of wobbler magnets, and a multileaf collimator, the width of the spread-out Bragg peak (SOBP) in the radiation field could not be changed. With dynamic control of the beam-modifying devices during irradiation, a more conformal radiotherapy could be achieved. In order to safely perform treatments with this conformal therapy, the moving devices should be watched during irradiation and the synchronousness among the devices should be verified. This system, which has to be safe for patient irradiations, was constructed and tested for safety and for the quality of the dose localization realized. Through these commissioning tests, we were successfully able to prepare the conformal technique using layer stacking for patients. Subsequent to commissioning the technique has been applied to patients in clinical trials.

Proper Conformal Killing Vectors in Kantowski-Sachs Metric

NASA Astrophysics Data System (ADS)

Hussain, Tahir; Farhan, Muhammad

2018-04-01

This paper deals with the existence of proper conformal Killing vectors (CKVs) in Kantowski-Sachs metric. Subject to some integrability conditions, the general form of vector filed generating CKVs and the conformal factor is presented. The integrability conditions are solved generally as well as in some particular cases to show that the non-conformally flat Kantowski-Sachs metric admits two proper CKVs, while it admits a 15-dimensional Lie algebra of CKVs in the case when it becomes conformally flat. The inheriting conformal Killing vectors (ICKVs), which map fluid lines conformally, are also investigated.

Measurement of Quality of Life III. From the IQOL Theory to the Global, Generic SEQOL Questionnaire

PubMed Central

Ventegodt, Soren; Merrick, Joav; Andersen, Niels Jorgen

2003-01-01

The Danish Quality of Life Survey is based on the philosophy of life known as the integrative quality-of-life (IQOL) theory. It consists of eight different quality-of-life concepts, ranging from the superficially subjective via the deeply existential to the superficially objective (well being, satisfaction with life, happiness, meaning in life, biological order, realizing life potential, fulfillment of needs, and objective factors [ability of functioning and fulfilling societal norms]).This paper presents the work underlying the formulation of the theories of a good life and how these theories came to be expressed in a comprehensive, multidimensional, generic questionnaire for the evaluation of the global quality of life — SEQOL (self-evaluation of quality of life) — presented in full length in this paper. The instruments and theories on which the Quality of Life Survey was based are constantly being updated. It is an on-going process due to aspects such as human development, language, and culture. We arrived at eight rating scales for the quality of life that, guided by the IQOL theory, were combined into a global and generic quality-of-life rating scale. This was simplified to the validated QOL5 with only five questions, made for use in clinical databases. Unfortunately, the depth of human existence is to some extent lost in QOL5.We continue to aim towards greater simplicity, precision, and depth in the questions in order to explore the depths of human existence. We have not yet found a final form that enables us to fully rate the quality of life in practice. We hope that the several hundred questions we found necessary to adequately implement the theories of the Quality of Life Survey can be replaced by far fewer; ideally, only eight questions representing the eight component theories. These eight ideal questions have not yet been evaluated, and therefore they should not form the basis of a survey. However, the perspective is clear. If eight simple questions

Self-Efficacy, Pulmonary Function, Perceived Health and Global Quality of Life of Cystic Fibrosis Patients

ERIC Educational Resources Information Center

Wahl, Astrid K.; Rustoen ,Tone; Hanestad, Berit R.; Gjengedal, Eva; Moum, Torbjorn

2005-01-01

This study examined the extent that pulmonary function is related to perceived health status and global quality of life in adults suffering from cystic fibrosis, and the extent that self-efficacy modifies these relationships. Our sample comprised 86 adults (48% female; mean age, 29 years; age range, 18-54 years) with cystic fibrosis, recruited…

Perceived neighborhood safety and sleep quality: a global analysis of six countries.

PubMed

Hill, Terrence D; Trinh, Ha Ngoc; Wen, Ming; Hale, Lauren

2016-02-01

Building on previous North American and European studies of neighborhood context and sleep quality, we tested whether several self-reported sleep outcomes (sleep duration, insomnia symptoms, sleepiness, lethargy, and overall sleep quality) vary according to the level of perceived neighborhood safety in six countries: Mexico, Ghana, South Africa, India, China, and Russia. Using data (n = 39,590) from Wave I of the World Health Organization's Longitudinal Study on Global Ageing and Adult Health (2007-2010), we estimated a series of multinomial and binary logistic regression equations to model each sleep outcome within each country. Taken together, our results show that respondents who feel safe from crime and violence in their neighborhoods tend to exhibit more favorable sleep outcomes than respondents who feel less safe. This general pattern is especially pronounced in China and Russia, moderately evident in Mexico, Ghana, and South Africa, and sporadic in India. Perceptions of neighborhood safety are strongly associated with insomnia symptoms and poor sleep quality (past 30 days), moderately associated with sleepiness, lethargy, and poor sleep quality (past 2 days), and inconsistently associated with sleep duration (past two days). We show that perceived neighborhood safety is associated with more favorable self-reported sleep outcomes in six understudied countries. Additional research is needed to replicate our findings using longitudinal data, more reliable neighborhood measures, and more direct measures of sleep quality in these and other regions of the world. Copyright © 2014 Elsevier B.V. All rights reserved.

48 CFR 1646.201 - Contract Quality Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ensure that services acquired under the FEHB contract conform to the contract's quality and audit requirements. (b) OPM will periodically evaluate the contractor's system of internal controls under the quality... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Contract Quality Policy...

40 CFR 52.2682 - Air quality surveillance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Air quality surveillance. 52.2682... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Guam § 52.2682 Air quality... Pollution Control Standards and Regulations” (buffer zones—air quality sampling) are not in conformance with...

40 CFR 52.2682 - Air quality surveillance.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 5 2012-07-01 2012-07-01 false Air quality surveillance. 52.2682... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Guam § 52.2682 Air quality... Pollution Control Standards and Regulations” (buffer zones—air quality sampling) are not in conformance with...

40 CFR 52.2682 - Air quality surveillance.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 5 2013-07-01 2013-07-01 false Air quality surveillance. 52.2682... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Guam § 52.2682 Air quality... Pollution Control Standards and Regulations” (buffer zones—air quality sampling) are not in conformance with...

40 CFR 52.2682 - Air quality surveillance.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 5 2014-07-01 2014-07-01 false Air quality surveillance. 52.2682... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Guam § 52.2682 Air quality... Pollution Control Standards and Regulations” (buffer zones—air quality sampling) are not in conformance with...

40 CFR 52.2682 - Air quality surveillance.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 4 2011-07-01 2011-07-01 false Air quality surveillance. 52.2682... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Guam § 52.2682 Air quality... Pollution Control Standards and Regulations” (buffer zones—air quality sampling) are not in conformance with...

Highly conformationally constrained halogenated 6-spiroepoxypenicillins as probes for the bioactive side-chain conformation of benzylpenicillin

NASA Astrophysics Data System (ADS)

Shute, Richard E.; Jackson, David E.; Bycroft, Barrie W.

1989-06-01

The halogenated 6-spiroepoxypenicillins are a series of novel semisynthetic β-lactam compounds with highly conformationally restricted side chains incorporating an epoxide. Their biological activity profiles depend crucially on the configuration at position C-3 of that epoxide. In derivatives with aromatic-containing side chains, e.g., anilide, the 3 R-compounds possess notable Gram-positive antibacterial activity and potent β-lactamase inhibitory properties. The comparable 3S-compounds are antibacterially inactive, but retain β-lactamase inhibitory activity. Using the molecular simulation programs COSMIC and ASTRAL, we attempted to map a putative, lipophilic accessory binding site on the PBPs that must interact with the side-chain aromatic residue. Comparative computer-assisted modelling of the 3 R, and 3 S-anilides, along with benzylpenicillin, indicated that the available conformational space at room temperature for the side chains of the 3 R and the 3 S-anilides was mutually exclusive. The conformational space for the more flexible benzylpenicillin could accommodate the side chains of both the constrained penicillin derivatives. By a combination of van der Waals surface calculations and a pharmacophoric distance approach, closely coincident conformers of the 3 R-anilide and benzylpenicillin were identified. These conformers must be related to the antibacterial, `bioactive' conformer for the classical β-lactam antibiotics. From these proposed bioactive conformations, a model for the binding of benzylpenicillin to the PBPs relating the three-dimensional arrangement of a putative lipophilic S2-subsite, specific for the side-chain aromatic moiety, and the 3 α-carboxylate functionality is presented.

CCProf: exploring conformational change profile of proteins

PubMed Central

Chang, Che-Wei; Chou, Chai-Wei; Chang, Darby Tien-Hao

2016-01-01

In many biological processes, proteins have important interactions with various molecules such as proteins, ions or ligands. Many proteins undergo conformational changes upon these interactions, where regions with large conformational changes are critical to the interactions. This work presents the CCProf platform, which provides conformational changes of entire proteins, named conformational change profile (CCP) in the context. CCProf aims to be a platform where users can study potential causes of novel conformational changes. It provides 10 biological features, including conformational change, potential binding target site, secondary structure, conservation, disorder propensity, hydropathy propensity, sequence domain, structural domain, phosphorylation site and catalytic site. All these information are integrated into a well-aligned view, so that researchers can capture important relevance between different biological features visually. The CCProf contains 986 187 protein structure pairs for 3123 proteins. In addition, CCProf provides a 3D view in which users can see the protein structures before and after conformational changes as well as binding targets that induce conformational changes. All information (e.g. CCP, binding targets and protein structures) shown in CCProf, including intermediate data are available for download to expedite further analyses. Database URL: http://zoro.ee.ncku.edu.tw/ccprof/ PMID:27016699

A Projective-to-Conformal Fefferman-Type Construction

NASA Astrophysics Data System (ADS)

Hammerl, Matthias; Sagerschnig, Katja; Šilhan, Josef; Taghavi-Chabert, Arman; Zádník, Vojtĕch

2017-10-01

We study a Fefferman-type construction based on the inclusion of Lie groups SL(n+1) into Spin(n+1,n+1). The construction associates a split-signature (n,n)-conformal spin structure to a projective structure of dimension n. We prove the existence of a canonical pure twistor spinor and a light-like conformal Killing field on the constructed conformal space. We obtain a complete characterisation of the constructed conformal spaces in terms of these solutions to overdetermined equations and an integrability condition on the Weyl curvature. The Fefferman-type construction presented here can be understood as an alternative approach to study a conformal version of classical Patterson-Walker metrics as discussed in recent works by Dunajski-Tod and by the authors. The present work therefore gives a complete exposition of conformal Patterson-Walker metrics from the viewpoint of parabolic geometry.

Matching of electron beams for conformal therapy of target volumes at moderate depths.

PubMed

Zackrisson, B; Karlsson, M

1996-06-01

The basic requirements for conformal electron therapy are an accelerator with a wide range of energies and field shapes. The beams should be well characterised in a full 3-D dose planning system which has been verified for the geometries of the current application. Differences in the basic design of treatment units have been shown to have a large influence on beam quality and dosimetry. Modern equipment can deliver electron beams of good quality with a high degree of accuracy. A race-track microtron with minimised electron scattering and a multi-leaf collimator (MLC) for electron collimating will facilitate the isocentric technique as a general treatment technique for electrons. This will improve the possibility of performing combined electron field techniques in order to conform the dose distribution with no or minimal use of a bolus. Furthermore, the isocentric technique will facilitate multiple field arrangements that decrease the problems with distortion of the dose distribution due to inhomogeneities, etc. These situations are demonstrated by clinical examples where isocentric, matched electron fields for treatment of the nose, thyroid and thoracic wall have been used.

Conformational effects in photoelectron circular dichroism

NASA Astrophysics Data System (ADS)

Turchini, S.

2017-12-01

Photoelectron circular dichroism (PECD) is a novel type of spectroscopy, which presents surprising sensitivity to conformational effects in chiral systems. While classical photoelectron spectroscopy mainly responds to conformational effects in terms of energy level shifts, PECD provides a rich and detailed response to tiny changes in electronic and structural properties by means of the intensity dispersion of the circular dichroism as a function of photoelectron kinetic energy. In this work, the basics of PECD will be outlined, emphasizing the role of interference from the l,l+/- 1 outgoing partial wave of the photoelectron in the PECD transition matrix element, which is responsible for the extreme sensitivity to conformational effects. Examples using molecular systems and interfaces will shed light on the powerful application of PECD to classical conformational effects such as group substitution, isomerism, conformer population and clustering. Moreover, the PECD results will be reported in challenging new fields where conformations play a key role, such as vibrational effects, transient chirality and time- resolved experiments. To date, PECD has mostly been based on synchrotron radiation facilities, but it also has a future as a table-top lab experiment by means of multiphoton ionization. An important application of PECD as an analytical tool will be reported. The aim of this review is to illustrate that in PECD, the presence of conformational effects is essential for understanding a wide range of effects from a new perspective, making it different from classical spectroscopy.

14 CFR 21.53 - Statement of conformity.

Code of Federal Regulations, 2011 CFR

2011-01-01

... each aircraft engine and propeller presented to the Administrator for type certification. This statement of conformity must include a statement that the aircraft engine or propeller conforms to the type... aircraft engine or propeller presented for type certification conforms to its type design. ...

Gluon amplitudes as 2 d conformal correlators

NASA Astrophysics Data System (ADS)

Pasterski, Sabrina; Shao, Shu-Heng; Strominger, Andrew

2017-10-01

Recently, spin-one wave functions in four dimensions that are conformal primaries of the Lorentz group S L (2 ,C ) were constructed. We compute low-point, tree-level gluon scattering amplitudes in the space of these conformal primary wave functions. The answers have the same conformal covariance as correlators of spin-one primaries in a 2 d CFT. The Britto-Cachazo-Feng-Witten (BCFW) recursion relation between three- and four-point gluon amplitudes is recast into this conformal basis.

Stabilizing the boat conformation of cyclohexane rings

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

Dasgupta, S.; Goddard, W.A. III; Moldowan, J.M.

1995-06-21

In calculating the energetics for various conformers of the A, B, and C series of hopanoid hydrocarbons present in mature oil reservoirs, we find that the B series prefers the boat conformation (by 1.3-2.5 kcal/mol) for the D cyclohexane ring. We analyze the structural elements responsible for stabilizing this boat conformation, identify the key features, and illustrate how one might stabilize boat conformations of other systems. 5 refs., 3 figs., 2 tabs.

Aquatic Ecosystems, Water Quality, and Global Change: Challenges of conducting Multi-Stressor Vulnerability Assessments (External Review Draft)

EPA Science Inventory

This draft report investigates the issues and challenges associated with identifying, calculating, and mapping indicators of the relative vulnerability of water quality and aquatic ecosystems, across the United States, to the potential impacts of global change. Using a large set...

Air Quality Forecasts Using the NASA GEOS Model: A Unified Tool from Local to Global Scales

NASA Technical Reports Server (NTRS)

Knowland, E. Emma; Keller, Christoph; Nielsen, J. Eric; Orbe, Clara; Ott, Lesley; Pawson, Steven; Saunders, Emily; Duncan, Bryan; Cook, Melanie; Liu, Junhua;

Global / globalizing cities.

PubMed

Yeoh, B S

1999-01-01

Along with the rise in research on globalization, the concept of globalization has become a subject to a more critical scrutiny. While majority agree that it represents a serious challenge to the state-centrist assumptions of most previous social science, doubts about its newness, inevitability and epoch-making qualities are also being raised. Others argue that the globalization literature neglects issues of social regulation by the nation-state, while some critics view it as a discourse drawn upon to legitimize particular political and economic agendas. Debates focus on metropolitan manifestations and impacts. Moving from this background, the paper presents three sociospatial urban configurations that have emerged in the literature. Alongside attempts at identifying globalizing cities and transnational urban networks as new theoretical subjects, another significant vein in the literature focuses on the complex forces of globalization and the production of new urban spaces in these cities. In addition, economic conceptions of globalization is now being pushed beyond adding sociocultural or sociopolitical dimensions and argue instead for the need to theorize globalization as a discursive formation. The global city as a discursive category conjures up imaginary concepts of high modernity, megadevelopment, 21st century urbanity. However, it is noted that the way forward is to focus on the distinctive ways in which urban actors engage in specific processes of economic and social reflexivity. There exists an urgent task for theorizations of the global city, which weave together historical, economic, cultural, sociopolitical and discursive dimensions.

Multichannel conformal blocks for scattering amplitudes

NASA Astrophysics Data System (ADS)

Belitsky, A. V.

2018-05-01

By performing resummation of small fermion-antifermion pairs within the pentagon form factor program to scattering amplitudes in planar N = 4 superYang-Mills theory, we construct multichannel conformal blocks within the flux-tube picture for N-sided NMHV polygons. This procedure is equivalent to summation of descendants of conformal primaries in the OPE framework. The resulting conformal partial waves are determined by multivariable hypergeometric series of Lauricella-Saran type.

Global ozone and air quality: a multi-model assessment of risks to human health and crops

NASA Astrophysics Data System (ADS)

Ellingsen, K.; Gauss, M.; van Dingenen, R.; Dentener, F. J.; Emberson, L.; Fiore, A. M.; Schultz, M. G.; Stevenson, D. S.; Ashmore, M. R.; Atherton, C. S.; Bergmann, D. J.; Bey, I.; Butler, T.; Drevet, J.; Eskes, H.; Hauglustaine, D. A.; Isaksen, I. S. A.; Horowitz, L. W.; Krol, M.; Lamarque, J. F.; Lawrence, M. G.; van Noije, T.; Pyle, J.; Rast, S.; Rodriguez, J.; Savage, N.; Strahan, S.; Sudo, K.; Szopa, S.; Wild, O.

2008-02-01

Within ACCENT, a European Network of Excellence, eighteen atmospheric models from the U.S., Europe, and Japan calculated present (2000) and future (2030) concentrations of ozone at the Earth's surface with hourly temporal resolution. Comparison of model results with surface ozone measurements in 14 world regions indicates that levels and seasonality of surface ozone in North America and Europe are characterized well by global models, with annual average biases typically within 5-10 nmol/mol. However, comparison with rather sparse observations over some regions suggest that most models overestimate annual ozone by 15-20 nmol/mol in some locations. Two scenarios from the International Institute for Applied Systems Analysis (IIASA) and one from the Intergovernmental Panel on Climate Change Special Report on Emissions Scenarios (IPCC SRES) have been implemented in the models. This study focuses on changes in near-surface ozone and their effects on human health and vegetation. Different indices and air quality standards are used to characterise air quality. We show that often the calculated changes in the different indices are closely inter-related. Indices using lower thresholds are more consistent between the models, and are recommended for global model analysis. Our analysis indicates that currently about two-thirds of the regions considered do not meet health air quality standards, whereas only 2-4 regions remain below the threshold. Calculated air quality exceedances show moderate deterioration by 2030 if current emissions legislation is followed and slight improvements if current emissions reduction technology is used optimally. For the "business as usual" scenario severe air quality problems are predicted. We show that model simulations of air quality indices are particularly sensitive to how well ozone is represented, and improved accuracy is needed for future projections. Additional measurements are needed to allow a more quantitative assessment of the risks to

Conformational heterogeneity in closed and open states of the KcsA potassium channel in lipid bicelles

PubMed Central

Kim, Dorothy M.; Dikiy, Igor; Upadhyay, Vikrant; Posson, David J.

2016-01-01

The process of ion channel gating—opening and closing—involves local and global structural changes in the channel in response to external stimuli. Conformational changes depend on the energetic landscape that underlies the transition between closed and open states, which plays a key role in ion channel gating. For the prokaryotic, pH-gated potassium channel KcsA, closed and open states have been extensively studied using structural and functional methods, but the dynamics within each of these functional states as well as the transition between them is not as well understood. In this study, we used solution nuclear magnetic resonance (NMR) spectroscopy to investigate the conformational transitions within specific functional states of KcsA. We incorporated KcsA channels into lipid bicelles and stabilized them into a closed state by using either phosphatidylcholine lipids, known to favor the closed channel, or mutations designed to trap the channel shut by disulfide cross-linking. A distinct state, consistent with an open channel, was uncovered by the addition of cardiolipin lipids. Using selective amino acid labeling at locations within the channel that are known to move during gating, we observed at least two different slowly interconverting conformational states for both closed and open channels. The pH dependence of these conformations and the predictable disruptions to this dependence observed in mutant channels with altered pH sensing highlight the importance of conformational heterogeneity for KcsA gating. PMID:27432996

Rates and equilibrium constants of the ligand-induced conformational transition of an HCN ion channel protein domain determined by DEER spectroscopy.

PubMed

Collauto, Alberto; DeBerg, Hannah A; Kaufmann, Royi; Zagotta, William N; Stoll, Stefan; Goldfarb, Daniella

2017-06-14

Ligand binding can induce significant conformational changes in proteins. The mechanism of this process couples equilibria associated with the ligand binding event and the conformational change. Here we show that by combining the application of W-band double electron-electron resonance (DEER) spectroscopy with microfluidic rapid freeze quench (μRFQ) it is possible to resolve these processes and obtain both equilibrium constants and reaction rates. We studied the conformational transition of the nitroxide labeled, isolated carboxy-terminal cyclic-nucleotide binding domain (CNBD) of the HCN2 ion channel upon binding of the ligand 3',5'-cyclic adenosine monophosphate (cAMP). Using model-based global analysis, the time-resolved data of the μRFQ DEER experiments directly provide fractional populations of the open and closed conformations as a function of time. We modeled the ligand-induced conformational change in the protein using a four-state model: apo/open (AO), apo/closed (AC), bound/open (BO), bound/closed (BC). These species interconvert according to AC + L ⇌ AO + L ⇌ BO ⇌ BC. By analyzing the concentration dependence of the relative contributions of the closed and open conformations at equilibrium, we estimated the equilibrium constants for the two conformational equilibria and the open-state ligand dissociation constant. Analysis of the time-resolved μRFQ DEER data gave estimates for the intrinsic rates of ligand binding and unbinding as well as the rates of the conformational change. This demonstrates that DEER can quantitatively resolve both the thermodynamics and the kinetics of ligand binding and the associated conformational change.

Inverse bootstrapping conformal field theories

NASA Astrophysics Data System (ADS)

Li, Wenliang

2018-01-01

We propose a novel approach to study conformal field theories (CFTs) in general dimensions. In the conformal bootstrap program, one usually searches for consistent CFT data that satisfy crossing symmetry. In the new method, we reverse the logic and interpret manifestly crossing-symmetric functions as generating functions of conformal data. Physical CFTs can be obtained by scanning the space of crossing-symmetric functions. By truncating the fusion rules, we are able to concentrate on the low-lying operators and derive some approximate relations for their conformal data. It turns out that the free scalar theory, the 2d minimal model CFTs, the ϕ 4 Wilson-Fisher CFT, the Lee-Yang CFTs and the Ising CFTs are consistent with the universal relations from the minimal fusion rule ϕ 1 × ϕ 1 = I + ϕ 2 + T , where ϕ 1 , ϕ 2 are scalar operators, I is the identity operator and T is the stress tensor.

Cation-Size-Dependent Conformational Locking of Glutamic Acid by Alkali Ions: Infrared Photodissociation Spectroscopy of Cryogenic Ions.

PubMed

Klyne, Johanna; Bouchet, Aude; Ishiuchi, Shun-Ichi; Fujii, Masaaki; Dopfer, Otto

2018-03-01

Consolidated knowledge of conformation and stability of amino acids and their clusters is required to understand their biochemical recognition. Often, alkali ions interact with amino acids and proteins. Herein, infrared photodissociation (IRPD) spectra of cryogenic metalated glutamic acid ions (GluM + , M = Li-Cs) are systematically analyzed in the isomer-specific fingerprint and XH stretch ranges (1100-1900, 2600-3600 cm -1 ) to provide a direct measure for cation-size-dependent conformational locking. GluM + ions are generated by electrospray ionization and cooled down to 15 K in a cryogenic quadrupole ion trap. The assignment of the IRPD spectra is supported by density functional theory calculations at the dispersion-corrected B3LYP-D3/aug-cc-pVTZ level. In the global minimum of GluM + , the flexibility of Glu is strongly reduced by the formation of rigid ionic CO···M + ···OC metal bridges, corresponding to charge solvation. The M + binding energy decreases monotonically with increasing cation size from D 0 = 314 to 119 kJ/mol for Li-Cs. Whereas for Li and Na only the global minimum of GluM + is observed, for K-Cs at least three isomers exist at cryogenic temperature. The IRPD spectra of cold GluM + ions are compared to IR multiple-photon dissociation spectra measured at room temperature. Furthermore, we elucidate the differences of the impact of protonation and metalation on the structure and conformational locking of Glu.

The quality of rivers: From pristine stage to global pollution

NASA Astrophysics Data System (ADS)

Meybeck, Michel; Helmer, Richard

1989-12-01

River water quality is highly variable by nature due to environmental conditions such as basin lithology, vegetation and climate. In small watersheds spatial variations extend over orders of magnitude for most major elements and nutrients, while this variability is an order of magnitude lower for major basins. A standard river water for use as reference is therefore not applicable. As a consequence natural waters can possibly be unfit for various human uses, even including drinking. The Water Quality (WQ) concept has greatly evolved since the beginning of the century in accordance with expanding water uses and analytical developments. Even in well developed countries the dissolved heavy metal measurements in rivers are not very reliable while dissolved organic micro-pollutants are even rarely analysed routinely. Major WQ problems have been identified according to river basin size, including organic pollution, salinity, total suspended solids, heavy metals, eutrophication, nitrate, organic micro-pollutants, acidification. They generally occurred in this order over a period of about 100 years in the industrialized countries. Historical records of WQ are rare but can be established indirectly through studies of lake sediments. When proper control action is taken at an early stage, numerous examples of WQ recovery have been found in rivers for most of the common pollution problems. Future WQ problems will mostly derive from mine tailings and toxic waste disposal in both developed and developing countries, industrial accidents and organic micropollutants which emerge faster than our analytical capacities. The newly industrializing countries will face all the above-mentioned problems within a very short time period without having the means to cope with them one at a time. River studies point out the global alteration of the biogeochemical cycles of many major elements and nutrients (S, Na, K, N, P). For heavy metals such as lead, present estimates of global river loads

Predicting bioactive conformations and binding modes of macrocycles

NASA Astrophysics Data System (ADS)

Anighoro, Andrew; de la Vega de León, Antonio; Bajorath, Jürgen

2016-10-01

Macrocyclic compounds experience increasing interest in drug discovery. It is often thought that these large and chemically complex molecules provide promising candidates to address difficult targets and interfere with protein-protein interactions. From a computational viewpoint, these molecules are difficult to treat. For example, flexible docking of macrocyclic compounds is hindered by the limited ability of current docking approaches to optimize conformations of extended ring systems for pose prediction. Herein, we report predictions of bioactive conformations of macrocycles using conformational search and binding modes using docking. Conformational ensembles generated using specialized search technique of about 70 % of the tested macrocycles contained accurate bioactive conformations. However, these conformations were difficult to identify on the basis of conformational energies. Moreover, docking calculations with limited ligand flexibility starting from individual low energy conformations rarely yielded highly accurate binding modes. In about 40 % of the test cases, binding modes were approximated with reasonable accuracy. However, when conformational ensembles were subjected to rigid body docking, an increase in meaningful binding mode predictions to more than 50 % of the test cases was observed. Electrostatic effects did not contribute to these predictions in a positive or negative manner. Rather, achieving shape complementarity at macrocycle-target interfaces was a decisive factor. In summary, a combined computational protocol using pre-computed conformational ensembles of macrocycles as a starting point for docking shows promise in modeling binding modes of macrocyclic compounds.

A Network of Conformational Transitions in the Apo Form of NDM-1 Enzyme Revealed by MD Simulation and a Markov State Model.

PubMed

Gao, Kaifu; Zhao, Yunjie

2017-04-13

New Delhi metallo-β-lactamase-1 (NDM-1) is a novel β-lactamase enzyme that confers enteric bacteria with nearly complete resistance to all β-lactam antibiotics, so it raises a formidable and global threat to human health. However, the binding mechanism between apo-NDM-1 and antibiotics as well as related conformational changes remains poorly understood, which largely hinders the overcoming of its antibiotic resistance. In our study, long-time conventional molecular dynamics simulation and Markov state models were applied to reveal both the dynamical and conformational landscape of apo-NDM-1: the MD simulation demonstrates that loop L3, which is responsible for antibiotic binding, is the most flexible and undergoes dramatic conformational changes; moreover, the Markov state model built from the simulation maps four metastable states including open, semiopen, and closed conformations of loop L3 as well as frequent transitions between the states. Our findings propose a possible conformational selection model for the binding mechanism between apo-NDM-1 and antibiotics, which facilitates the design of novel inhibitors and antibiotics.

Spectral analysis and quantum chemical studies of chair and twist-boat conformers of cycloheximide in gas and solution phases

NASA Astrophysics Data System (ADS)

Tokatli, A.; Ucun, F.; Sütçü, K.; Osmanoğlu, Y. E.; Osmanoğlu, Ş.

2018-02-01

In this study the conformational behavior of cycloheximide in the gas and solution (CHCl3) phases has theoretically been investigated by spectroscopic and quantum chemical properties using density functional theory (wB97X-D) method with 6-31++G(d,p) basis set, for the first time. The calculated IR results reveal that in the ground state the molecule exits as a mixture of the chair and twist-boat conformers in the gas phase, while the calculated NMR results reveal that it only exits as the chair conformer in the solution phase. In order to obtain the contributions coming from intramolecular interactions to the stability of the conformers in the gas and solution phases, the quantum theory of atoms in molecules (QTAIM), noncovalent interactions (NCI) method, and natural bond orbital analysis (NBO) have been employed. The QTAIM and NCI methods indicated that by intramolecular interactions with bond critical point (BCP) the twist-boat conformer is more stabilized than the chair conformer, while by steric interactions it is more destabilized. Considering that these interactions balance each other, the stabilities of the conformers are understood to be dictated by the van der Waals interactions. The NBO analyses show that the hyperconjugative and steric effects play an important role in the stabilization in the gas and solution phases. Furthermore, to get a better understanding of the chemical behavior of this important antibiotic drug we have evaluated and, commented the global and local reactivity descriptors of the both conformers. Finally, the EPR analysis of γ-irradiated cycloheximide has been done. The comparison of the experimental and calculated data have showed the inducement of a radical structure of (CH2)2ĊCH2 in the molecule. The experimental EPR spectrum has also confirmed that the molecule simultaneously exists in the chair and twist-boat conformers in the solid phase.

A Unified Conformational Selection and Induced Fit Approach to Protein-Peptide Docking

PubMed Central

Trellet, Mikael; Melquiond, Adrien S. J.; Bonvin, Alexandre M. J. J.

2013-01-01

Protein-peptide interactions are vital for the cell. They mediate, inhibit or serve as structural components in nearly 40% of all macromolecular interactions, and are often associated with diseases, making them interesting leads for protein drug design. In recent years, large-scale technologies have enabled exhaustive studies on the peptide recognition preferences for a number of peptide-binding domain families. Yet, the paucity of data regarding their molecular binding mechanisms together with their inherent flexibility makes the structural prediction of protein-peptide interactions very challenging. This leaves flexible docking as one of the few amenable computational techniques to model these complexes. We present here an ensemble, flexible protein-peptide docking protocol that combines conformational selection and induced fit mechanisms. Starting from an ensemble of three peptide conformations (extended, a-helix, polyproline-II), flexible docking with HADDOCK generates 79.4% of high quality models for bound/unbound and 69.4% for unbound/unbound docking when tested against the largest protein-peptide complexes benchmark dataset available to date. Conformational selection at the rigid-body docking stage successfully recovers the most relevant conformation for a given protein-peptide complex and the subsequent flexible refinement further improves the interface by up to 4.5 Å interface RMSD. Cluster-based scoring of the models results in a selection of near-native solutions in the top three for ∼75% of the successfully predicted cases. This unified conformational selection and induced fit approach to protein-peptide docking should open the route to the modeling of challenging systems such as disorder-order transitions taking place upon binding, significantly expanding the applicability limit of biomolecular interaction modeling by docking. PMID:23516555

A unified conformational selection and induced fit approach to protein-peptide docking.

PubMed

Trellet, Mikael; Melquiond, Adrien S J; Bonvin, Alexandre M J J

2013-01-01

Protein-peptide interactions are vital for the cell. They mediate, inhibit or serve as structural components in nearly 40% of all macromolecular interactions, and are often associated with diseases, making them interesting leads for protein drug design. In recent years, large-scale technologies have enabled exhaustive studies on the peptide recognition preferences for a number of peptide-binding domain families. Yet, the paucity of data regarding their molecular binding mechanisms together with their inherent flexibility makes the structural prediction of protein-peptide interactions very challenging. This leaves flexible docking as one of the few amenable computational techniques to model these complexes. We present here an ensemble, flexible protein-peptide docking protocol that combines conformational selection and induced fit mechanisms. Starting from an ensemble of three peptide conformations (extended, a-helix, polyproline-II), flexible docking with HADDOCK generates 79.4% of high quality models for bound/unbound and 69.4% for unbound/unbound docking when tested against the largest protein-peptide complexes benchmark dataset available to date. Conformational selection at the rigid-body docking stage successfully recovers the most relevant conformation for a given protein-peptide complex and the subsequent flexible refinement further improves the interface by up to 4.5 Å interface RMSD. Cluster-based scoring of the models results in a selection of near-native solutions in the top three for ∼75% of the successfully predicted cases. This unified conformational selection and induced fit approach to protein-peptide docking should open the route to the modeling of challenging systems such as disorder-order transitions taking place upon binding, significantly expanding the applicability limit of biomolecular interaction modeling by docking.

Measuring the mechanical properties of molecular conformers

NASA Astrophysics Data System (ADS)

Jarvis, S. P.; Taylor, S.; Baran, J. D.; Champness, N. R.; Larsson, J. A.; Moriarty, P.

2015-09-01

Scanning probe-actuated single molecule manipulation has proven to be an exceptionally powerful tool for the systematic atomic-scale interrogation of molecular adsorbates. To date, however, the extent to which molecular conformation affects the force required to push or pull a single molecule has not been explored. Here we probe the mechanochemical response of two tetra(4-bromophenyl)porphyrin conformers using non-contact atomic force microscopy where we find a large difference between the lateral forces required for manipulation. Remarkably, despite sharing very similar adsorption characteristics, variations in the potential energy surface are capable of prohibiting probe-induced positioning of one conformer, while simultaneously permitting manipulation of the alternative conformational form. Our results are interpreted in the context of dispersion-corrected density functional theory calculations which reveal significant differences in the diffusion barriers for each conformer. These results demonstrate that conformational variation significantly modifies the mechanical response of even simple porpyhrins, potentially affecting many other flexible molecules.

Modeling Aircraft Emissions for Regional-scale Air Quality: Adapting a New Global Aircraft Emissions Database for the U.S

NASA Astrophysics Data System (ADS)

Arunachalam, S.; Baek, B. H.; Vennam, P. L.; Woody, M. C.; Omary, M.; Binkowski, F.; Fleming, G.

2012-12-01

Commercial aircraft emit substantial amounts of pollutants during their complete activity cycle that ranges from landing-and-takeoff (LTO) at airports to cruising in upper elevations of the atmosphere, and affect both air quality and climate. Since these emissions are not uniformly emitted over the earth, and have substantial temporal and spatial variability, it is vital to accurately evaluate and quantify the relative impacts of aviation emissions on ambient air quality. Regional-scale air quality modeling applications do not routinely include these aircraft emissions from all cycles. Federal Aviation Administration (FAA) has developed the Aviation Environmental Design Tool (AEDT), a software system that dynamically models aircraft performance in space and time to calculate fuel burn and emissions from gate-to-gate for all commercial aviation activity from all airports globally. To process in-flight aircraft emissions and to provide a realistic representation of these for treatment in grid-based air quality models, we have developed an interface processor called AEDTproc that accurately distributes full-flight chorded emissions in time and space to create gridded, hourly model-ready emissions input data. Unlike the traditional emissions modeling approach of treating aviation emissions as ground-level sources or processing emissions only from the LTO cycles in regional-scale air quality studies, AEDTproc distributes chorded inventories of aircraft emissions during LTO cycles and cruise activities into a time-variant 3-D gridded structure. We will present results of processed 2006 global emissions from AEDT over a continental U.S. modeling domain to support a national-scale air quality assessment of the incremental impacts of aircraft emissions on surface air quality. This includes about 13.6 million flights within the U.S. out of 31.2 million flights globally. We will focus on assessing spatio-temporal variability of these commercial aircraft emissions, and

Revealing Hidden Conformational Space of LOV Protein VIVID Through Rigid Residue Scan Simulations

NASA Astrophysics Data System (ADS)

Zhou, Hongyu; Zoltowski, Brian D.; Tao, Peng

2017-04-01

VIVID(VVD) protein is a Light-Oxygen-Voltage(LOV) domain in circadian clock system. Upon blue light activation, a covalent bond is formed between VVD residue Cys108 and its cofactor flavin adenine dinucleotide(FAD), and prompts VVD switching from Dark state to Light state with significant conformational deviation. However, the mechanism of this local environment initiated global protein conformational change remains elusive. We employed a recently developed computational approach, rigid residue scan(RRS), to systematically probe the impact of the internal degrees of freedom in each amino acid residue of VVD on its overall dynamics by applying rigid body constraint on each residue in molecular dynamics simulations. Key residues were identified with distinctive impacts on Dark and Light states, respectively. All the simulations display wide range of distribution on a two-dimensional(2D) plot upon structural root-mean-square deviations(RMSD) from either Dark or Light state. Clustering analysis of the 2D RMSD distribution leads to 15 representative structures with drastically different conformation of N-terminus, which is also a key difference between Dark and Light states of VVD. Further principle component analyses(PCA) of RRS simulations agree with the observation of distinctive impact from individual residues on Dark and Light states.

Revealing Hidden Conformational Space of LOV Protein VIVID Through Rigid Residue Scan Simulations

PubMed Central

Zhou, Hongyu; Zoltowski, Brian D.; Tao, Peng

2017-01-01

VIVID(VVD) protein is a Light-Oxygen-Voltage(LOV) domain in circadian clock system. Upon blue light activation, a covalent bond is formed between VVD residue Cys108 and its cofactor flavin adenine dinucleotide(FAD), and prompts VVD switching from Dark state to Light state with significant conformational deviation. However, the mechanism of this local environment initiated global protein conformational change remains elusive. We employed a recently developed computational approach, rigid residue scan(RRS), to systematically probe the impact of the internal degrees of freedom in each amino acid residue of VVD on its overall dynamics by applying rigid body constraint on each residue in molecular dynamics simulations. Key residues were identified with distinctive impacts on Dark and Light states, respectively. All the simulations display wide range of distribution on a two-dimensional(2D) plot upon structural root-mean-square deviations(RMSD) from either Dark or Light state. Clustering analysis of the 2D RMSD distribution leads to 15 representative structures with drastically different conformation of N-terminus, which is also a key difference between Dark and Light states of VVD. Further principle component analyses(PCA) of RRS simulations agree with the observation of distinctive impact from individual residues on Dark and Light states. PMID:28425502

WATERSHED BOUNDARY CONDITIONS FOR GLOBAL CHANGE IMPACT ANALYSIS

EPA Science Inventory

The US Global Change Research Program (USGCRP) studies (among other issues) the impact of global change on water quality. This field study evaluates the impact of global changes (land-use change and climate change) on source water quality. Changes in source water quality change...

Renormalization, conformal ward identities and the origin of a conformal anomaly pole

NASA Astrophysics Data System (ADS)

Corianò, Claudio; Maglio, Matteo Maria

2018-06-01

We investigate the emergence of a conformal anomaly pole in conformal field theories in the case of the TJJ correlator. We show how it comes to be generated in dimensional renormalization, using a basis of 13 form factors (the F-basis), where only one of them requires renormalization (F13), extending previous studies. We then combine recent results on the structure of the non-perturbative solutions of the conformal Ward identities (CWI's) for the TJJ in momentum space, expressed in terms of a minimal set of 4 form factors (A-basis), with the properties of the F-basis, and show how the singular behaviour of the corresponding form factors in both basis can be related. The result proves the centrality of such massless effective interactions induced by the anomaly, which have recently found realization in solid state, in the theory of topological insulators and of Weyl semimetals. This pattern is confirmed in massless abelian and nonabelian theories (QED and QCD) investigated at one-loop.

Concurrent Increases and Decreases in Local Stability and Conformational Heterogeneity in Cu, Zn Superoxide Dismutase Variants Revealed by Temperature-Dependence of Amide Chemical Shifts.

PubMed

Doyle, Colleen M; Rumfeldt, Jessica A; Broom, Helen R; Sekhar, Ashok; Kay, Lewis E; Meiering, Elizabeth M

2016-03-08

The chemical shifts of backbone amide protons in proteins are sensitive reporters of local structural stability and conformational heterogeneity, which can be determined from their readily measured linear and nonlinear temperature-dependences, respectively. Here we report analyses of amide proton temperature-dependences for native dimeric Cu, Zn superoxide dismutase (holo pWT SOD1) and structurally diverse mutant SOD1s associated with amyotrophic lateral sclerosis (ALS). Holo pWT SOD1 loses structure with temperature first at its periphery and, while having extremely high global stability, nevertheless exhibits extensive conformational heterogeneity, with ∼1 in 5 residues showing evidence for population of low energy alternative states. The holo G93A and E100G ALS mutants have moderately decreased global stability, whereas V148I is slightly stabilized. Comparison of the holo mutants as well as the marginally stable immature monomeric unmetalated and disulfide-reduced (apo(2SH)) pWT with holo pWT shows that changes in the local structural stability of individual amides vary greatly, with average changes corresponding to differences in global protein stability measured by differential scanning calorimetry. Mutants also exhibit altered conformational heterogeneity compared to pWT. Strikingly, substantial increases as well as decreases in local stability and conformational heterogeneity occur, in particular upon maturation and for G93A. Thus, the temperature-dependence of amide shifts for SOD1 variants is a rich source of information on the location and extent of perturbation of structure upon covalent changes and ligand binding. The implications for potential mechanisms of toxic misfolding of SOD1 in disease and for general aspects of protein energetics, including entropy-enthalpy compensation, are discussed.

Direct Determination of Hydroxymethyl Conformations of Plant Cell Wall Cellulose Using 1H Polarization Transfer Solid-State NMR.

PubMed

Phyo, Pyae; Wang, Tuo; Yang, Yu; O'Neill, Hugh; Hong, Mei

2018-05-14

In contrast to the well-studied crystalline cellulose of microbial and animal origins, cellulose in plant cell walls is disordered due to its interactions with matrix polysaccharides. Plant cell wall (PCW) is an undisputed source of sustainable global energy; therefore, it is important to determine the molecular structure of PCW cellulose. The most reactive component of cellulose is the exocyclic hydroxymethyl group: when it adopts the tg conformation, it stabilizes intrachain and interchain hydrogen bonding, while gt and gg conformations destabilize the hydrogen-bonding network. So far, information about the hydroxymethyl conformation in cellulose has been exclusively obtained from 13 C chemical shifts of monosaccharides and oligosaccharides, which do not reflect the environment of cellulose in plant cell walls. Here, we use solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy to measure the hydroxymethyl torsion angle of cellulose in two model plants, by detecting distance-dependent polarization transfer between H4 and H6 protons in 2D 13 C- 13 C correlation spectra. We show that the interior crystalline portion of cellulose microfibrils in Brachypodium and Arabidopsis cell walls exhibits H4-H6 polarization transfer curves that are indicative of a tg conformation, whereas surface cellulose chains exhibit slower H4-H6 polarization transfer that is best fit to the gt conformation. Joint constraints by the H4-H6 polarization transfer curves and 13 C chemical shifts indicate that it is unlikely for interior cellulose to have a significant population of the gt and gg conformation mixed with the tg conformation, while surface cellulose may adopt a small percentage of the gg conformation. These results provide new constraints to the structure and matrix interactions of cellulose in plant cell walls, and represent the first direct determination of a torsion angle in an important noncrystalline carbohydrate polymer.

Conformational dynamics of the molecular chaperone Hsp90

PubMed Central

Krukenberg, Kristin A.; Street, Timothy O.; Lavery, Laura A.; Agard, David A.

2016-01-01

The molecular chaperone Hsp90 is an essential eukaryotic protein that makes up 1–2% of all cytosolic proteins. Hsp90 is vital for the maturation and maintenance of a wide variety of substrate proteins largely involved in signaling and regulatory processes. Many of these substrates have also been implicated in cancer and other diseases making Hsp90 an attractive target for therapeutics. Hsp90 is a highly dynamic and flexible molecule that can adapt its conformation to the wide variety of substrate proteins with which it acts. Large conformational rearrangements are also required for the activation of these client proteins. One driving force for these rearrangements is the intrinsic ATPase activity of Hsp90, as seen with other chaperones. However, unlike other chaperones, studies have shown that the ATPase cycle of Hsp90 is not conformationally deterministic. That is, rather than dictating the conformational state, ATP binding and hydrolysis shifts the equilibrium between a pre-existing set of conformational states in an organism-dependent manner. In vivo Hsp90 functions as part of larger heterocomplexes. The binding partners of Hsp90, co-chaperones, assist in the recruitment and activation of substrates, and many co-chaperones further regulate the conformational dynamics of Hsp90 by shifting the conformational equilibrium towards a particular state. Studies have also suggested alternative mechanisms for the regulation of Hsp90’s conformation. In this review, we discuss the structural and biochemical studies leading to our current understanding of the conformational dynamics of Hsp90 and the role that nucleotide, co-chaperones, post-translational modification and clients play in regulating Hsp90’s conformation. We also discuss the effects of current Hsp90 inhibitors on conformation and the potential for developing small molecules that inhibit Hsp90 by disrupting the conformational dynamics. PMID:21414251

tRNA Shifts the G-quadruplex-Hairpin Conformational Equilibrium in RNA towards the Hairpin Conformer.

PubMed

Rode, Ambadas B; Endoh, Tamaki; Sugimoto, Naoki

2016-11-07

Non-coding RNAs play important roles in cellular homeostasis and are involved in many human diseases including cancer. Intermolecular RNA-RNA interactions are the basis for the diverse functions of many non-coding RNAs. Herein, we show how the presence of tRNA influences the equilibrium between hairpin and G-quadruplex conformations in the 5' untranslated regions of oncogenes and model sequences. Kinetic and equilibrium analyses of the hairpin to G-quadruplex conformational transition of purified RNA as well as during co-transcriptional folding indicate that tRNA significantly shifts the equilibrium toward the hairpin conformer. The enhancement of relative translation efficiency in a reporter gene assay is shown to be due to the tRNA-mediated shift in hairpin-G-quadruplex equilibrium of oncogenic mRNAs. Our findings suggest that tRNA is a possible therapeutic target in diseases in which RNA conformational equilibria is dysregulated. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

14 CFR 21.53 - Statement of conformity.

Code of Federal Regulations, 2010 CFR

2010-01-01

... conformity (FAA Form 317) to the Administrator for each aircraft engine and propeller presented to the... engine or propeller conforms to the type design therefor. (b) Each applicant must submit a statement of... statement that each aircraft engine or propeller presented for type certification conforms to its type...

SCit: web tools for protein side chain conformation analysis.

PubMed

Gautier, R; Camproux, A-C; Tufféry, P

2004-07-01

SCit is a web server providing services for protein side chain conformation analysis and side chain positioning. Specific services use the dependence of the side chain conformations on the local backbone conformation, which is described using a structural alphabet that describes the conformation of fragments of four-residue length in a limited library of structural prototypes. Based on this concept, SCit uses sets of rotameric conformations dependent on the local backbone conformation of each protein for side chain positioning and the identification of side chains with unlikely conformations. The SCit web server is accessible at http://bioserv.rpbs.jussieu.fr/SCit.

SCit: web tools for protein side chain conformation analysis

PubMed Central

Gautier, R.; Camproux, A.-C.; Tufféry, P.

2004-01-01

SCit is a web server providing services for protein side chain conformation analysis and side chain positioning. Specific services use the dependence of the side chain conformations on the local backbone conformation, which is described using a structural alphabet that describes the conformation of fragments of four-residue length in a limited library of structural prototypes. Based on this concept, SCit uses sets of rotameric conformations dependent on the local backbone conformation of each protein for side chain positioning and the identification of side chains with unlikely conformations. The SCit web server is accessible at http://bioserv.rpbs.jussieu.fr/SCit. PMID:15215438

Conformal Killing horizons and their thermodynamics

NASA Astrophysics Data System (ADS)

Nielsen, Alex B.; Shoom, Andrey A.

2018-05-01

Certain dynamical black hole solutions can be mapped to static spacetimes by conformal metric transformations. This mapping provides a physical link between the conformal Killing horizon of the dynamical black hole and the Killing horizon of the static spacetime. Using the Vaidya spacetime as an example, we show how this conformal relation can be used to derive thermodynamic properties of such dynamical black holes. Although these horizons are defined quasi-locally and can be located by local experiments, they are distinct from other popular notions of quasi-local horizons such as apparent horizons. Thus in the dynamical Vaidya spacetime describing constant accretion of null dust, the conformal Killing horizon, which is null by construction, is the natural horizon to describe the black hole.

Molecular dynamics studies of the conformation of sorbitol

PubMed Central

Lerbret, A.; Mason, P.E.; Venable, R.M.; Cesàro, A.; Saboungi, M.-L.; Pastor, R.W.; Brady, J.W.

2009-01-01

Molecular dynamics simulations of a 3 m aqueous solution of D-sorbitol (also called D-glucitol) have been performed at 300 K, as well as at two elevated temperatures to promote conformational transitions. In principle, sorbitol is more flexible than glucose since it does not contain a constraining ring. However, a conformational analysis revealed that the sorbitol chain remains extended in solution, in contrast to the bent conformation found experimentally in the crystalline form. While there are 243 staggered conformations of the backbone possible for this open-chain polyol, only a very limited number were found to be stable in the simulations. Although many conformers were briefly sampled, only eight were significantly populated in the simulation. The carbon backbones of all but two of these eight conformers were completely extended, unlike the bent crystal conformation. These extended conformers were stabilized by a quite persistent intramolecular hydrogen bond between the hydroxyl groups of carbon C-2 and C-4. The conformational populations were found to be in good agreement with the limited available NMR data except for the C-2–C-3 torsion (spanned by the O-2–O-4 hydrogen bond), where the NMR data supports a more bent structure. PMID:19744646

Conformal Robotic Stereolithography

PubMed Central

Stevens, Adam G.; Oliver, C. Ryan; Kirchmeyer, Matthieu; Wu, Jieyuan; Chin, Lillian; Polsen, Erik S.; Archer, Chad; Boyle, Casey; Garber, Jenna

2016-01-01

Abstract Additive manufacturing by layerwise photopolymerization, commonly called stereolithography (SLA), is attractive due to its high resolution and diversity of materials chemistry. However, traditional SLA methods are restricted to planar substrates and planar layers that are perpendicular to a single-axis build direction. Here, we present a robotic system that is capable of maskless layerwise photopolymerization on curved surfaces, enabling production of large-area conformal patterns and the construction of conformal freeform objects. The system comprises an industrial six-axis robot and a custom-built maskless projector end effector. Use of the system involves creating a mesh representation of the freeform substrate, generation of a triangulated toolpath with curved layers that represents the target object to be printed, precision mounting of the substrate in the robot workspace, and robotic photopatterning of the target object by coordinated motion of the robot and substrate. We demonstrate printing of conformal photopatterns on spheres of various sizes, and construction of miniature three-dimensional objects on spheres without requiring support features. Improvement of the motion accuracy and development of freeform toolpaths would enable construction of polymer objects that surpass the size and support structure constraints imparted by traditional SLA systems. PMID:29577062

Operator product expansion for conformal defects

NASA Astrophysics Data System (ADS)

Fukuda, Masayuki; Kobayashi, Nozomu; Nishioka, Tatsuma

2018-01-01

We study the operator product expansion (OPE) for scalar conformal defects of any codimension in CFT. The OPE for defects is decomposed into "defect OPE blocks", the irreducible representations of the conformal group, each of which packages the contribution from a primary operator and its descendants. We use the shadow formalism to deduce an integral representation of the defect OPE blocks. They are shown to obey a set of constraint equations that can be regarded as equations of motion for a scalar field propagating on the moduli space of the defects. By employing the Radon transform between the AdS space and the moduli space, we obtain a formula of constructing an AdS scalar field from the defect OPE block for a conformal defect of any codimension in a scalar representation of the conformal group, which turns out to be the Euclidean version of the HKLL formula. We also introduce a duality between conformal defects of different codimensions and prove the equivalence between the defect OPE block for codimension-two defects and the OPE block for a pair of local operators.

The importance of quality assurance/quality control of diagnostics to increase the confidence in global foot-and-mouth disease control.

PubMed

De Clercq, K; Goris, N; Barnett, P V; MacKay, D K

2008-01-01

The last decade international trade in animals and animal products was liberated and confidence in this global trade can increase only if appropriate control measures are applied. As foot-and-mouth disease (FMD) diagnostics will play an essential role in this respect, the Food and Agriculture Organization European Commission for the Control of Foot-and-Mouth Disease (EUFMD) co-ordinates, in collaboration with the European Commission, several programmes to increase the quality of FMD diagnostics. A quality assurance (QA) system is deemed essential for laboratories involved in certifying absence of FMDV or antibodies against the virus. Therefore, laboratories are encouraged to validate their diagnostic tests fully and to install a continuous quality control (QC) monitoring system. Knowledge of performance characteristics of diagnostics is essential to interpret results correctly and to calculate sample rates in regional surveillance campaigns. Different aspects of QA/QC of classical and new FMD virological and serological diagnostics are discussed in respect to the EU FMD directive (2003/85/EC). We recommended accepting trade certificates only from laboratories participating in international proficiency testing on a regular basis.

40 CFR 51.854 - Conformity analysis.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Federal Government taking an action subject to this subpart must make its own conformity determination... agency or develop its own analysis in order to make its conformity determination. Effective Date Note: At...

21 CFR 26.70 - Conformity assessment bodies.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Conformity assessment bodies. 26.70 Section 26.70...Frameworkâ Provisions § 26.70 Conformity assessment bodies. Each party recognizes that the conformity assessment bodies (CAB's) listed in subpart B of this part fulfill the conditions of eligibility to assess...

Global Atmosphere Watch Workshop on Measurement-Model Fusion for Global Total Atmospheric Deposition (MMF-GTAD)

EPA Science Inventory

The World Meteorological Organization’s (WMO) Global Atmosphere Watch (GAW) Programme coordinates high-quality observations of atmospheric composition from global to local scales with the aim to drive high-quality and high-impact science while co-producing a new generation of pro...

Analytical halo model of galactic conformity

NASA Astrophysics Data System (ADS)

Pahwa, Isha; Paranjape, Aseem

2017-09-01

We present a fully analytical halo model of colour-dependent clustering that incorporates the effects of galactic conformity in a halo occupation distribution framework. The model, based on our previous numerical work, describes conformity through a correlation between the colour of a galaxy and the concentration of its parent halo, leading to a correlation between central and satellite galaxy colours at fixed halo mass. The strength of the correlation is set by a tunable 'group quenching efficiency', and the model can separately describe group-level correlations between galaxy colour (1-halo conformity) and large-scale correlations induced by assembly bias (2-halo conformity). We validate our analytical results using clustering measurements in mock galaxy catalogues, finding that the model is accurate at the 10-20 per cent level for a wide range of luminosities and length-scales. We apply the formalism to interpret the colour-dependent clustering of galaxies in the Sloan Digital Sky Survey (SDSS). We find good overall agreement between the data and a model that has 1-halo conformity at a level consistent with previous results based on an SDSS group catalogue, although the clustering data require satellites to be redder than suggested by the group catalogue. Within our modelling uncertainties, however, we do not find strong evidence of 2-halo conformity driven by assembly bias in SDSS clustering.

Rapid roll inflation with conformal coupling

NASA Astrophysics Data System (ADS)

Kofman, Lev; Mukohyama, Shinji

2008-02-01

Usual inflation is realized with a slow rolling scalar field minimally coupled to gravity. In contrast, we consider dynamics of a scalar with a flat effective potential, conformally coupled to gravity. Surprisingly, it contains an attractor inflationary solution with the rapidly rolling inflaton field. We discuss models with the conformal inflaton with a flat potential (including hybrid inflation). There is no generation of cosmological fluctuations from the conformally coupled inflaton. We consider realizations of modulated (inhomogeneous reheating) or curvaton cosmological fluctuations in these models. We also implement these unusual features for the popular string-theoretic warped inflationary scenario, based on the interacting D3-D¯3 branes. The original warped brane inflation suffers a large inflaton mass due to conformal coupling to 4-dimensional gravity. Instead of considering this as a problem and trying to cure it with extra engineering, we show that warped inflation with the conformally coupled, rapidly rolling inflaton is yet possible with N=37 efoldings, which requires low-energy scales 1 100 TeV of inflation. Coincidentally, the same warping numerology can be responsible for the hierarchy. It is shown that the scalars associated with angular isometries of the warped geometry of compact manifold (e.g. S3 of Klebanov-Strassler (KS) geometry) have solutions identical to conformally coupled modes and also cannot be responsible for cosmological fluctuations. We discuss other possibilities.

Target dose conformity in 3-dimensional conformal radiotherapy and intensity modulated radiotherapy.

PubMed

Wu, Vincent W C; Kwong, Dora L W; Sham, Jonathan S T

2004-05-01

Dose conformity to the planning target volume is an important criterion in radiotherapy treatment planning, for which the conformity index is a useful assessment tool. The purpose of this study is to compare the differences in CI for the treatment planning of four cancers including the nasopharynx, oesophagus, lung and prostate. Seventy patients with cancers of nasopharynx (30), oesophagus (15), lung (15) and prostate (10) were recruited. Each of these patients was planned with three sets of treatment plans using the FOCUS treatment planning system: the forward and inverse 3DCRT plans and the IMRT plan. The CI was generated for each treatment plan. The mean CI from each cancer patient group was calculated and compared with the other three cancer groups. The mean value of CI was also compared among the three planning methods. The oesophageal and lung cancers demonstrated relatively higher overall mean CI values (0.64 and 0.62, respectively), whereas that of the nasopharynx and prostate were lower (0.54 and 0.50, respectively). With regards to the planning method groups, the IMRT plans produced the highest overall mean CI (0.62), while those for the forward and inverse 3DCRT were similar (0.57 and 0.55, respectively). For the four selected cancers, oesophageal and lung cancers were easier to conform than the nasopharyngeal and prostate cancers. The IMRT plans were more effective in achieving better dose conformity than that of the 3DCRT.

Bioactive focus in conformational ensembles: a pluralistic approach

NASA Astrophysics Data System (ADS)

Habgood, Matthew

2017-12-01

Computational generation of conformational ensembles is key to contemporary drug design. Selecting the members of the ensemble that will approximate the conformation most likely to bind to a desired target (the bioactive conformation) is difficult, given that the potential energy usually used to generate and rank the ensemble is a notoriously poor discriminator between bioactive and non-bioactive conformations. In this study an approach to generating a focused ensemble is proposed in which each conformation is assigned multiple rankings based not just on potential energy but also on solvation energy, hydrophobic or hydrophilic interaction energy, radius of gyration, and on a statistical potential derived from Cambridge Structural Database data. The best ranked structures derived from each system are then assembled into a new ensemble that is shown to be better focused on bioactive conformations. This pluralistic approach is tested on ensembles generated by the Molecular Operating Environment's Low Mode Molecular Dynamics module, and by the Cambridge Crystallographic Data Centre's conformation generator software.

Probing RNA Native Conformational Ensembles with Structural Constraints.

PubMed

Fonseca, Rasmus; van den Bedem, Henry; Bernauer, Julie

2016-05-01

Noncoding ribonucleic acids (RNA) play a critical role in a wide variety of cellular processes, ranging from regulating gene expression to post-translational modification and protein synthesis. Their activity is modulated by highly dynamic exchanges between three-dimensional conformational substates, which are difficult to characterize experimentally and computationally. Here, we present an innovative, entirely kinematic computational procedure to efficiently explore the native ensemble of RNA molecules. Our procedure projects degrees of freedom onto a subspace of conformation space defined by distance constraints in the tertiary structure. The dimensionality reduction enables efficient exploration of conformational space. We show that the conformational distributions obtained with our method broadly sample the conformational landscape observed in NMR experiments. Compared to normal mode analysis-based exploration, our procedure diffuses faster through the experimental ensemble while also accessing conformational substates to greater precision. Our results suggest that conformational sampling with a highly reduced but fully atomistic representation of noncoding RNA expresses key features of their dynamic nature.

The research of conformal optical design

NASA Astrophysics Data System (ADS)

Li, Lin; Li, Yan; Huang, Yi-fan; Du, Bao-lin

2009-07-01

Conformal optical domes are characterized as having external more elongated optical surfaces that are optimized to minimize drag, increased missile velocity and extended operational range. The outer surface of the conformal domes typically deviate greatly from spherical surface descriptions, so the inherent asymmetry of conformal surfaces leads to variations in the aberration content presented to the optical sensor as it is gimbaled across the field of regard, which degrades the sensor's ability to properly image targets of interest and then undermine the overall system performance. Consequently, the aerodynamic advantages of conformal domes cannot be realized in practical systems unless the dynamic aberration correction techniques are developed to restore adequate optical imaging capabilities. Up to now, many optical correction solutions have been researched in conformal optical design, including static aberrations corrections and dynamic aberrations corrections. There are three parts in this paper. Firstly, the combination of static and dynamic aberration correction is introduced. A system for correcting optical aberration created by a conformal dome has an outer surface and an inner surface. The optimization of the inner surface is regard as the static aberration correction; moreover, a deformable mirror is placed at the position of the secondary mirror in the two-mirror all reflective imaging system, which is the dynamic aberration correction. Secondly, the using of appropriate surface types is very important in conformal dome design. Better performing optical systems can result from surface types with adequate degrees of freedom to describe the proper corrector shape. Two surface types and the methods of using them are described, including Zernike polynomial surfaces used in correct elements and user-defined surfaces used in deformable mirror (DM). Finally, the Adaptive optics (AO) correction is presented. In order to correct the dynamical residual aberration

New open conformation of SMYD3 implicates conformational selection and allostery

PubMed Central

Spellmon, Nicholas; Sun, Xiaonan; Xue, Wen; Holcomb, Joshua; Chakravarthy, Srinivas; Shang, Weifeng; Edwards, Brian; Sirinupong, Nualpun; Li, Chunying; Yang, Zhe

2016-01-01

SMYD3 plays a key role in cancer cell viability, adhesion, migration and invasion. SMYD3 promotes formation of inducible regulatory T cells and is involved in reducing autoimmunity. However, the nearly “closed” substrate-binding site and poor in vitro H3K4 methyltransferase activity have obscured further understanding of this oncogenically related protein. Here we reveal that SMYD3 can adopt an “open” conformation using molecular dynamics simulation and small-angle X-ray scattering. This ligand-binding-capable open state is related to the crystal structure-like closed state by a striking clamshell-like inter-lobe dynamics. The two states are characterized by many distinct structural and dynamical differences and the conformational transition pathway is mediated by a reversible twisting motion of the C-terminal domain (CTD). The spontaneous transition from the closed to open states suggests two possible, mutually non-exclusive models for SMYD3 functional regulation and the conformational selection mechanism and allostery may regulate the catalytic or ligand binding competence of SMYD3. This study provides an immediate clue to the puzzling role of SMYD3 in epigenetic gene regulation. PMID:28050603

Reciprocity Outperforms Conformity to Promote Cooperation.

PubMed

Romano, Angelo; Balliet, Daniel

2017-10-01

Evolutionary psychologists have proposed two processes that could give rise to the pervasiveness of human cooperation observed among individuals who are not genetically related: reciprocity and conformity. We tested whether reciprocity outperformed conformity in promoting cooperation, especially when these psychological processes would promote a different cooperative or noncooperative response. To do so, across three studies, we observed participants' cooperation with a partner after learning (a) that their partner had behaved cooperatively (or not) on several previous trials and (b) that their group members had behaved cooperatively (or not) on several previous trials with that same partner. Although we found that people both reciprocate and conform, reciprocity has a stronger influence on cooperation. Moreover, we found that conformity can be partly explained by a concern about one's reputation-a finding that supports a reciprocity framework.

Discovering Conformational Sub-States Relevant to Protein Function

PubMed Central

Ramanathan, Arvind; Savol, Andrej J.; Langmead, Christopher J.; Agarwal, Pratul K.; Chennubhotla, Chakra S.

2011-01-01

Background Internal motions enable proteins to explore a range of conformations, even in the vicinity of native state. The role of conformational fluctuations in the designated function of a protein is widely debated. Emerging evidence suggests that sub-groups within the range of conformations (or sub-states) contain properties that may be functionally relevant. However, low populations in these sub-states and the transient nature of conformational transitions between these sub-states present significant challenges for their identification and characterization. Methods and Findings To overcome these challenges we have developed a new computational technique, quasi-anharmonic analysis (QAA). QAA utilizes higher-order statistics of protein motions to identify sub-states in the conformational landscape. Further, the focus on anharmonicity allows identification of conformational fluctuations that enable transitions between sub-states. QAA applied to equilibrium simulations of human ubiquitin and T4 lysozyme reveals functionally relevant sub-states and protein motions involved in molecular recognition. In combination with a reaction pathway sampling method, QAA characterizes conformational sub-states associated with cis/trans peptidyl-prolyl isomerization catalyzed by the enzyme cyclophilin A. In these three proteins, QAA allows identification of conformational sub-states, with critical structural and dynamical features relevant to protein function. Conclusions Overall, QAA provides a novel framework to intuitively understand the biophysical basis of conformational diversity and its relevance to protein function. PMID:21297978

Irreversibility and higher-spin conformal field theory

NASA Astrophysics Data System (ADS)

Anselmi, Damiano

2000-08-01

I discuss the properties of the central charges c and a for higher-derivative and higher-spin theories (spin 2 included). Ordinary gravity does not admit a straightforward identification of c and a in the trace anomaly, because it is not conformal. On the other hand, higher-derivative theories can be conformal, but have negative c and a. A third possibility is to consider higher-spin conformal field theories. They are not unitary, but have a variety of interesting properties. Bosonic conformal tensors have a positive-definite action, equal to the square of a field strength, and a higher-derivative gauge invariance. There exists a conserved spin-2 current (not the canonical stress tensor) defining positive central charges c and a. I calculate the values of c and a and study the operator-product structure. Higher-spin conformal spinors have no gauge invariance, admit a standard definition of c and a and can be coupled to Abelian and non-Abelian gauge fields in a renormalizable way. At the quantum level, they contribute to the one-loop beta function with the same sign as ordinary matter, admit a conformal window and non-trivial interacting fixed points. There are composite operators of high spin and low dimension, which violate the Ferrara-Gatto-Grillo theorem. Finally, other theories, such as conformal antisymmetric tensors, exhibit more severe internal problems. This research is motivated by the idea that fundamental quantum field theories should be renormalization-group (RG) interpolations between ultraviolet and infrared conformal fixed points, and quantum irreversibility should be a general principle of nature.

[Cost-effectiveness analysis and diet quality index applied to the WHO Global Strategy].

PubMed

Machado, Flávia Mori Sarti; Simões, Arlete Naresse

2008-02-01

To test the use of cost-effectiveness analysis as a decision making tool in the production of meals for the inclusion of the recommendations published in the World Health Organization's Global Strategy. Five alternative options for breakfast menu were assessed previously to their adoption in a food service at a university in the state of Sao Paulo, Southeastern Brazil, in 2006. Costs of the different options were based on market prices of food items (direct cost). Health benefits were estimated based on adaptation of the Diet Quality Index (DQI). Cost-effectiveness ratios were estimated by dividing benefits by costs and incremental cost-effectiveness ratios were estimated as cost differential per unit of additional benefit. The meal choice was based on health benefit units associated to direct production cost as well as incremental effectiveness per unit of differential cost. The analysis showed the most simple option with the addition of a fruit (DQI = 64 / cost = R$ 1.58) as the best alternative. Higher effectiveness was seen in the options with a fruit portion (DQI1=64 / DQI3=58 / DQI5=72) compared to the others (DQI2=48 / DQI4=58). The estimate of cost-effectiveness ratio allowed to identifying the best breakfast option based on cost-effectiveness analysis and Diet Quality Index. These instruments allow easy application easiness and objective evaluation which are key to the process of inclusion of public or private institutions under the Global Strategy directives.

Essential role of conformational selection in ligand binding.

PubMed

Vogt, Austin D; Pozzi, Nicola; Chen, Zhiwei; Di Cera, Enrico

2014-02-01

Two competing and mutually exclusive mechanisms of ligand recognition - conformational selection and induced fit - have dominated our interpretation of ligand binding in biological macromolecules for almost six decades. Conformational selection posits the pre-existence of multiple conformations of the macromolecule from which the ligand selects the optimal one. Induced fit, on the other hand, postulates the existence of conformational rearrangements of the original conformation into an optimal one that are induced by binding of the ligand. In the former case, conformational transitions precede the binding event; in the latter, conformational changes follow the binding step. Kineticists have used a facile criterion to distinguish between the two mechanisms based on the dependence of the rate of relaxation to equilibrium, kobs, on the ligand concentration, [L]. A value of kobs decreasing hyperbolically with [L] has been seen as diagnostic of conformational selection, while a value of kobs increasing hyperbolically with [L] has been considered diagnostic of induced fit. However, this simple conclusion is only valid under the rather unrealistic assumption of conformational transitions being much slower than binding and dissociation events. In general, induced fit only produces values of kobs that increase with [L] but conformational selection is more versatile and is associated with values of kobs that increase with, decrease with or are independent of [L]. The richer repertoire of kinetic properties of conformational selection applies to kinetic mechanisms with single or multiple saturable relaxations and explains the behavior of nearly all experimental systems reported in the literature thus far. Conformational selection is always sufficient and often necessary to account for the relaxation kinetics of ligand binding to a biological macromolecule and is therefore an essential component of any binding mechanism. On the other hand, induced fit is never necessary and

Thermodynamic analysis of the disorder-to-α-helical transition of 18.5-kDa myelin basic protein reveals an equilibrium intermediate representing the most compact conformation.

PubMed

Vassall, Kenrick A; Jenkins, Andrew D; Bamm, Vladimir V; Harauz, George

2015-05-22

The intrinsically disordered, 18.5-kDa isoform of myelin basic protein (MBP) is a peripheral membrane protein that is essential to proper myelin formation in the central nervous system. MBP acts in oligodendrocytes both to adjoin membrane leaflets to each other in forming myelin and as a hub in numerous protein-protein and protein-membrane interaction networks. Like many intrinsically disordered proteins (IDPs), MBP multifunctionality arises from its high conformational plasticity and its ability to undergo reversible disorder-to-order transitions. One such transition is the disorder-to-α-helical conformational change that is induced upon MBP-membrane binding. Here, we have investigated the disorder-to-α-helical transition of MBP-derived α-peptides and the full-length 18.5-kDa protein. This transition was induced through titration of the membrane-mimetic solvent trifluoroethanol into both protein and peptide solutions, and conformational change was monitored using circular dichroism spectroscopy, 1-anilinonaphthalene-8-sulfonic acid binding, tryptophan fluorescence quenching, and Förster (fluorescence) resonance energy transfer measurements. The data suggest that the disorder-to-α-helical transition of MBP follows a 3-state model: disordered↔intermediate↔α-helical, with each of the identified equilibrium states likely representing a conformational ensemble. The disordered state is characterized by slight compaction with little regular secondary structure, whereas the intermediate is also disordered but globally more compact. Surprisingly, the α-helical conformation is less compact than the intermediate. This study suggests that multifunctionality in MBP could arise from differences in the population of energetically distinct ensembles under different conditions and also provides an example of an IDP that undergoes cooperative global conformation change. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pilot Non-Conformance to Alerting System Commands

NASA Technical Reports Server (NTRS)

Pritchett, Amy R.; Hansman, R. John

1997-01-01

Instances of pilot non-conformance to alerting system commands have been identified in previous studies. Pilot non-conformance changes the final behavior of the system, and therefore may reduce actual performance from that anticipated. A simulator study has examined pilot non-conformance, using the task of collision avoidance during closely spaced parallel approaches as a case study. Consonance between the display and the alerting system was found to significantly improve subject agreement with automatic alerts. Based on these results, a more general discussion of the factors involved in pilot conformance is given, and design guidelines for alerting systems are given.

Rotational Spectroscopy Unveils Eleven Conformers of Adrenaline

NASA Astrophysics Data System (ADS)

Cabezas, C.; Cortijo, V.; Mata, S.; Lopez, J. C.; Alonso, J. L.

2013-06-01

Recent improvements in our LA-MB-FTMW instrumentation have allowed the characterization of eleven and eight conformers for the neurotransmitters adrenaline and noradrenaline respectively. The observation of this rich conformational behavior is in accordance with the recent observation of seven conformers for dopamine and in sharp contrast with the conformational reduction proposed for catecholamines. C. Cabezas, I. Peña, J. C. López, J. L. Alonso J. Phys. Chem. Lett. 2013, 4, 486. H. Mitsuda, M. Miyazaki, I. B. Nielsen, P. Carcabal,C. Dedonder, C. Jouvet, S. Ishiuchi, M. Fujii J. Phys. Chem. Lett. 2010, 1, 1130.

A Subspace Semi-Definite programming-based Underestimation (SSDU) method for stochastic global optimization in protein docking*

PubMed Central

Nan, Feng; Moghadasi, Mohammad; Vakili, Pirooz; Vajda, Sandor; Kozakov, Dima; Ch. Paschalidis, Ioannis

2015-01-01

We propose a new stochastic global optimization method targeting protein docking problems. The method is based on finding a general convex polynomial underestimator to the binding energy function in a permissive subspace that possesses a funnel-like structure. We use Principal Component Analysis (PCA) to determine such permissive subspaces. The problem of finding the general convex polynomial underestimator is reduced into the problem of ensuring that a certain polynomial is a Sum-of-Squares (SOS), which can be done via semi-definite programming. The underestimator is then used to bias sampling of the energy function in order to recover a deep minimum. We show that the proposed method significantly improves the quality of docked conformations compared to existing methods. PMID:25914440

Impacts of ozone-vegetation coupling and feedbacks on global air quality, ecosystems and food security

NASA Astrophysics Data System (ADS)

Tai, A. P. K.

2016-12-01

Surface ozone is an air pollutant of significant concerns due to its harmful effects on human health, vegetation and crop productivity. Chronic ozone exposure is shown to reduce photosynthesis and interfere with gas exchange in plants, thereby influencing surface energy balance and biogeochemical fluxes with important ramifications for climate and atmospheric composition, including possible feedbacks onto ozone itself that are not well understood. Ozone damage on crops has been well documented, but a mechanistic understanding is not well established. Here we present several results pertaining to the effects of ozone-vegetation coupling on air quality, ecosystems and agriculture. Using the Community Earth System Model (CESM), we find that inclusion of ozone damage on plants reduces the global land carbon sink by up to 5%, while simulated ozone is enhanced by up to 6 ppbv North America, Europe and East Asia. This strong positive feedback on ozone air quality via ozone-vegetation coupling arises mainly from reduced stomatal conductance, which induces two feedback pathways: 1) reduced dry deposition and ozone uptake; and 2) reduced evapotranspiration that enhances vegetation temperature and thus isoprene emission. Using the same ozone-vegetation scheme in a crop model within CESM, we further examine the impacts of historical ozone exposure on global crop production. We contrast our model results with a separate statistical analysis designed to characterize the spatial variability of crop-ozone-temperature relationships and account for the confounding effect of ozone-temperature covariation, using multidecadal global datasets of crop yields, agroclimatic variables and ozone exposures. We find that several crops (especially C4 crops such as maize) exhibit stronger sensitivities to ozone than found by field studies or in CESM simulations. We also find a strong anticorrelation between crop sensitivities and average ozone levels, reflecting biological adaptive ozone

Conformity and Psychopathology: A Comparative Study of Conformity Behaviors in Manic-depressive, Paranoid Schizophrenic and Normal Populations

ERIC Educational Resources Information Center

Marsella, Anthony J.

1975-01-01

The present study investigated the relationship between conformity and psychopathology in male and female manic-depressive (MD), paranoid schizophrenics (PS), and normals (N) on two conformity tasks under conditions of live social pressure. (Author)

A multi-model assessment of the co-benefits of climate mitigation for global air quality

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

Rao, Shilpa; Klimont, Zbigniew; Leitao, Joana

The recent International Panel on Climate change (IPCC) report identifies significant co-benefits from climate policies on near-term ambient air pollution and related human health outcomes [1]. This is increasingly relevant for policy making as the health impacts of air pollution are a major global concern- the Global Burden of Disease (GBD) study identifies outdoor air pollution as the sixth major cause of death globally [2]. Integrated assessment models (IAMs) are an effective tool to evaluate future air pollution outcomes across a wide range of assumptions on socio-economic development and policy regimes. The Representative Concentration Pathways (RCPs) [3] were the firstmore » set of long-term global scenarios developed across multiple integrated assessment models that provided detailed estimates of a number of air pollutants until 2100. However these scenarios were primarily designed to cover a defined range of radiative forcing outcomes and thus did not specifically focus on the interactions of long-term climate goals on near-term air pollution impacts. More recently, [4] used the RCP4.5 scenario to evaluate the co-benefits of global GHG reductions on air quality and human health in 2030. [5-7] have further examined the interactions of more diverse pollution control regimes with climate policies. This paper extends the listed studies in a number of ways. Firstly it uses multiple IAMs to look into the co-benefits of a global climate policy for ambient air pollution under harmonized assumptions on near-term air pollution control. Multi-model frameworks have been extensively used in the analysis of climate change mitigation pathways, and the structural uncertainties regarding the underlying mechanisms (see for example [8-10]. This is to our knowledge the first time that a multi-model evaluation has been specifically designed and applied to analyze the co-benefits of climate change policy on ambient air quality, thus enabling a better understanding of at a

A fluorescent probe-labeled Escherichia coli aspartate transcarbamoylase that monitors the allosteric conformational state.

PubMed

West, Jay M; Tsuruta, Hiro; Kantrowitz, Evan R

2004-01-09

A new system has been developed capable of monitoring conformational changes of the 240s loop of aspartate transcarbamoylase, which are tightly correlated with the quaternary structural transition, with high sensitivity in solution. Pyrene, a fluorescent probe, was conjugated to residue 241 in the 240s loop of aspartate transcarbamoylase to monitor changes in conformation by fluorescence spectroscopy. Pyrene maleimide was conjugated to a cysteine residue on the 240s loop of a previously constructed double catalytic chain mutant version of the enzyme, C47A/A241C. The pyrene-labeled enzyme undergoes the normal T to R structural transition, as demonstrated by small-angle x-ray scattering. Like the wild-type enzyme, the pyrene-labeled enzyme exhibits cooperativity toward aspartate, and is activated by ATP and inhibited by CTP at subsaturating concentrations of aspartate. The binding of the bisubstrate analogue N-(phosphonoacetyl)-l-aspartate (PALA), or the aspartate analogue succinate, in the presence of saturating carbamoyl phosphate, to the pyrenelabeled enzyme caused a sigmoidal change in the fluorescence emission. Saturation with ATP and CTP (in the presence of either subsaturating amounts of PALA or succinate and carbamoyl phosphate) caused a hyperbolic increase and decrease, respectively, in the fluorescence emission. The half-saturation values from the fluorescence saturation curves and kinetic saturation curves were, within error, identical. Fluorescence and small-angle x-ray scattering stopped-flow experiments, using aspartate and carbamoyl phosphate, confirm that the change in excimer fluorescence and the quaternary structure change correlate. These results in conjunction with previous studies suggest that the allosteric transition involves both global and local conformational changes and that the heterotropic effect of the nucleotides may be exerted through local conformational changes in the active site by directly influencing the conformation of the 240s

Spacer conformation in biologically active molecules. Part 1. Structure and conformational preferences of 2-substituted benzoxazoles

NASA Astrophysics Data System (ADS)

Czylkowski, R.; Karolak-Wojciechowska, J.; Mrozek, A.; Yalçin, I.; Aki-Şener, E.

2001-12-01

The mutual position of two pharmacophoric elements in flexible biologically active molecules depends on the spacer conformation. This is true even for a two-atomic chain put to use as a spacer. It was established for 2-substituted-benzoxazoles containing two aromatic centres joined by -CH2-X- (X=S or O). From crystallographic studies of four molecules it was found that the role of heteroatom is essential for the whole molecule conformation. The spacer with X=S adopts the (-)synclinal conformation while for X=O the (+)antiperiplanar one. Such preferences were also found in the statistical data from Cambridge Structural Database (CSD).

Syntaxin1a variants lacking an N-peptide or bearing the LE mutation bind to Munc18a in a closed conformation

DOE PAGES

Colbert, Karen N.; Hattendorf, Douglas A.; Weiss, Thomas M.; ...

2013-07-15

In neurons, soluble N-ethylmaleimide–sensitive factor attachment receptor (SNARE) proteins drive the fusion of synaptic vesicles to the plasma membrane through the formation of a four-helix SNARE complex. Members of the Sec1/Munc18 protein family regulate membrane fusion through interactions with the syntaxin family of SNARE proteins. The neuronal protein Munc18a interacts with a closed conformation of the SNARE protein syntaxin1a (Syx1a) and with an assembled SNARE complex containing Syx1a in an open conformation. The N-peptide of Syx1a (amino acids 1–24) has been implicated in the transition of Munc18a-bound Syx1a to Munc18a-bound SNARE complex, but the underlying mechanism is not understood. Inmore » addition, we report the X-ray crystal structures of Munc18a bound to Syx1a with and without its native N-peptide (Syx1aΔN), along with small-angle X-ray scattering (SAXS) data for Munc18a bound to Syx1a, Syx1aΔN, and Syx1a L165A/E166A (LE), a mutation thought to render Syx1a in a constitutively open conformation. We show that all three complexes adopt the same global structure, in which Munc18a binds a closed conformation of Syx1a. We also identify a possible structural connection between the Syx1a N-peptide and SNARE domain that might be important for the transition of closed-to-open Syx1a in SNARE complex assembly. Although the role of the N-peptide in Munc18a-mediated SNARE complex assembly remains unclear, our results demonstrate that the N-peptide and LE mutation have no effect on the global conformation of the Munc18a–Syx1a complex.« less

A multiscale approach to simulating the conformational properties of unbound multi-C₂H₂ zinc finger proteins.

PubMed

Liu, Lei; Wade, Rebecca C; Heermann, Dieter W

2015-09-01

The conformational properties of unbound multi-Cys2 His2 (mC2H2) zinc finger proteins, in which zinc finger domains are connected by flexible linkers, are studied by a multiscale approach. Three methods on different length scales are utilized. First, atomic detail molecular dynamics simulations of one zinc finger and its adjacent flexible linker confirmed that the zinc finger is more rigid than the flexible linker. Second, the end-to-end distance distributions of mC2H2 zinc finger proteins are computed using an efficient atomistic pivoting algorithm, which only takes excluded volume interactions into consideration. The end-to-end distance distribution gradually changes its profile, from left-tailed to right-tailed, as the number of zinc fingers increases. This is explained by using a worm-like chain model. For proteins of a few zinc fingers, an effective bending constraint favors an extended conformation. Only for proteins containing more than nine zinc fingers, is a somewhat compacted conformation preferred. Third, a mesoscale model is modified to study both the local and the global conformational properties of multi-C2H2 zinc finger proteins. Simulations of the CCCTC-binding factor (CTCF), an important mC2H2 zinc finger protein for genome spatial organization, are presented. © 2015 Wiley Periodicals, Inc.

Unique contributions of dynamic versus global measures of parent-child interaction quality in predicting school adjustment.

PubMed

Bardack, Sarah; Herbers, Janette E; Obradović, Jelena

2017-09-01

This study investigates the unique contribution of microsocial and global measures of parent-child positive coregulation (PCR) in predicting children's behavioral and social adjustment in school. Using a community sample of 102 children, ages 4-6, and their parents, we conducted nested path analytic models to identify the unique effects of 2 measures of PCR on school outcomes. Microsocial PCR independently predicted fewer externalizing and inattention/impulsive behaviors in school. Global PCR did not uniquely relate to children's behavioral and social adjustment outcomes. Household socioeconomic status was related to both microsocial and global measures of PCR, but not directly associated with school outcomes. Findings illustrate the importance of using dynamic measures of PCR based on microsocial coding to further understand how the quality of parent-child interaction is related to children's self-regulatory and social development during school transition. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Galactic conformity measured in semi-analytic models

NASA Astrophysics Data System (ADS)

Lacerna, I.; Contreras, S.; González, R. E.; Padilla, N.; Gonzalez-Perez, V.

2018-03-01

We study the correlation between the specific star formation rate of central galaxies and neighbour galaxies, also known as `galactic conformity', out to 20 h^{-1} {Mpc} using three semi-analytic models (SAMs, one from L-GALAXIES and other two from GALFORM). The aim is to establish whether SAMs are able to show galactic conformity using different models and selection criteria. In all the models, when the selection of primary galaxies is based on an isolation criterion in real space, the mean fraction of quenched (Q) galaxies around Q primary galaxies is higher than that around star-forming primary galaxies of the same stellar mass. The overall signal of conformity decreases when we remove satellites selected as primary galaxies, but the effect is much stronger in GALFORM models compared with the L-GALAXIES model. We find this difference is partially explained by the fact that in GALFORM once a galaxy becomes a satellite remains as such, whereas satellites can become centrals at a later time in L-GALAXIES. The signal of conformity decreases down to 60 per cent in the L-GALAXIES model after removing central galaxies that were ejected from their host halo in the past. Galactic conformity is also influenced by primary galaxies at fixed stellar mass that reside in dark matter haloes of different masses. Finally, we explore a proxy of conformity between distinct haloes. In this case, the conformity is weak beyond ˜3 h^{-1} {Mpc} (<3 per cent in L-GALAXIES, <1-2 per cent in GALFORM models). Therefore, it seems difficult that conformity is directly related with a long-range effect.

Vapor deposition routes to conformal polymer thin films

PubMed Central

Moni, Priya; Al-Obeidi, Ahmed

2017-01-01

Vapor phase syntheses, including parylene chemical vapor deposition (CVD) and initiated CVD, enable the deposition of conformal polymer thin films to benefit a diverse array of applications. This short review for nanotechnologists, including those new to vapor deposition methods, covers the basic theory in designing a conformal polymer film vapor deposition, sample preparation and imaging techniques to assess film conformality, and several applications that have benefited from vapor deposited, conformal polymer thin films. PMID:28487816

Conformational analysis and global warming potentials of 1,1,1,3,3,3-hexafluoro-2-propanol from absorption spectroscopy

NASA Astrophysics Data System (ADS)

Godin, Paul J.; Le Bris, Karine; Strong, Kimberly

2017-12-01

Absorption cross-sections of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) were derived from Fourier transform infrared spectra recorded from 530 to 3400 cm-1 with a resolution of 0.1 cm-1 over a temperature range of 300-362 K. These results were compared to previously published experimental measurements made at room temperature and to a theoretical spectrum from density functional theory (DFT) calculations. Good agreement is found between the experimentally derived results, DFT calculations, and previously published data. The only temperature dependence observed was in the amplitude of some of the absorption peaks due to the changing ratio of the stable conformations of HFIP. This temperature dependence does not result in a significant trend in integrated band strength as a function of temperature. The average value for integrated band strength is found to be (2.649 ± 0.065)x10-16 cm molecule-1 for HFIP over the spectral range of 595 to 3010 cm-1. Radiative efficiency (RE) and the global warming potential (GWP) for HFIP were also derived. A RE of 0.293 ± 0.059 Wm-2ppbv-1 is derived, which leads to a GWP100 of 188 in the range of 530 to 3000 cm-1. The DFT calculation is linearly adjusted to match the experimental spectrum. Using this adjusted DFT spectrum to expand the range below 530 to 0 cm-1 , increases the RE to 0.317 ± 0.063 Wm-2ppbv-1 and the GWP100 to 203.

Finite conformal quantum gravity and spacetime singularities

NASA Astrophysics Data System (ADS)

Modesto, Leonardo; Rachwał, Lesław

2017-12-01

We show that a class of finite quantum non-local gravitational theories is conformally invariant at classical as well as at quantum level. This is actually a range of conformal anomaly-free theories in the spontaneously broken phase of the Weyl symmetry. At classical level we show how the Weyl conformal invariance is able to tame all the spacetime singularities that plague not only Einstein gravity, but also local and weakly non-local higher derivative theories. The latter statement is proved by a singularity theorem that applies to a large class of weakly non-local theories. Therefore, we are entitled to look for a solution of the spacetime singularity puzzle in a missed symmetry of nature, namely the Weyl conformal symmetry. Following the seminal paper by Narlikar and Kembhavi, we provide an explicit construction of singularity-free black hole exact solutions in a class of conformally invariant theories.

The impact of base stacking on the conformations and electrostatics of single-stranded DNA.

PubMed

Plumridge, Alex; Meisburger, Steve P; Andresen, Kurt; Pollack, Lois

2017-04-20

Single-stranded DNA (ssDNA) is notable for its interactions with ssDNA binding proteins (SSBs) during fundamentally important biological processes including DNA repair and replication. Previous work has begun to characterize the conformational and electrostatic properties of ssDNA in association with SSBs. However, the conformational distributions of free ssDNA have been difficult to determine. To capture the vast array of ssDNA conformations in solution, we pair small angle X-ray scattering with novel ensemble fitting methods, obtaining key parameters such as the size, shape and stacking character of strands with different sequences. Complementary ion counting measurements using inductively coupled plasma atomic emission spectroscopy are employed to determine the composition of the ion atmosphere at physiological ionic strength. Applying this combined approach to poly dA and poly dT, we find that the global properties of these sequences are very similar, despite having vastly different propensities for single-stranded helical stacking. These results suggest that a relatively simple mechanism for the binding of ssDNA to non-specific SSBs may be at play, which explains the disparity in binding affinities observed for these systems. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Conformal and projective symmetries in Newtonian cosmology

NASA Astrophysics Data System (ADS)

Duval, C.; Gibbons, G. W.; Horváthy, P. A.

2017-02-01

Definitions of non-relativistic conformal transformations are considered both in the Newton-Cartan and in the Kaluza-Klein-type Eisenhart/Bargmann geometrical frameworks. The symmetry groups that come into play are exemplified by the cosmological, and also the Newton-Hooke solutions of Newton's gravitational field equations. It is shown, in particular, that the maximal symmetry group of the standard cosmological model is isomorphic to the 13-dimensional conformal-Newton-Cartan group whose conformal-Bargmann extension is explicitly worked out. Attention is drawn to the appearance of independent space and time dilations, in contrast with the Schrödinger group or the Conformal Galilei Algebra.

Quality of institution and the FEG (forest, energy intensity, and globalization) -environment relationships in sub-Saharan Africa.

PubMed

Amuakwa-Mensah, Franklin; Adom, Philip Kofi

2017-07-01

The current share of sub-Saharan Africa in global carbon dioxide emissions is negligible compared to major contributors like Asia, Americas, and Europe. This trend is, however, likely to change given that both economic growth and rate of urbanization in the region are projected to be robust in the future. The current study contributes to the literature by examining both the direct and the indirect impacts of quality of institution on the environment. Specifically, we investigate whether the institutional setting in the region provides some sort of a complementary role in the environment-FEG relationships. We use the panel two-step system generalized method of moments (GMM) technique to deal with the simultaneity problem. Data consists of 43 sub-Saharan African countries. The result shows that energy inefficiency compromises environmental standards. However, the quality of the institutional setting helps moderate this negative consequences; countries with good institutions show greater prospects than countries with poor institutions. On the other hand, globalization of the region and increased forest size generate positive environmental outcomes in the region. Their impacts are, however, independent of the quality of institution. Afforestation programs, promotion of other clean energy types, and investment in energy efficiency, basic city infrastructure, and regulatory and institutional structures, are desirable policies to pursue to safeguard the environment.

Modeling the Conformation-Specific Infrared Spectra of N-Alkylbenzenes

NASA Astrophysics Data System (ADS)

Tabor, Daniel P.; Sibert, Edwin; Hewett, Daniel M.; Korn, Joseph A.; Zwier, Timothy S.

2016-06-01

Conformation-specific UV-IR double resonance spectra are presented for n-alkylbenzenes. With the aid of a local mode Hamiltonian that includes the effects of stretch-bend Fermi coupling, the spectra of ethyl, n-propyl, and n-butylbenzene are assigned to individual conformers. These molecules allow for further development of the work on a first principles method for calculating alkyl stretch spectra. Due to the consistency of the anharmonic couplings from conformer to conformer, construction of the model Hamiltonian for a given conformer only requires a harmonic frequency calculation at the conformer's minimum geometry as an input. The model Hamiltonian can be parameterized with either density functional theory or MP2 electronic structure calculations. The relative strengths and weaknesses of these methods are evaluated, including their predictions of the relative energetics of the conformers. Finally, the IR spectra for conformers that have the alkyl chain bend back and interact with the π cloud of the benzene ring are modeled.

Boundary conformal anomalies on hyperbolic spaces and Euclidean balls

NASA Astrophysics Data System (ADS)

Rodriguez-Gomez, Diego; Russo, Jorge G.

2017-12-01

We compute conformal anomalies for conformal field theories with free conformal scalars and massless spin 1/2 fields in hyperbolic space ℍ d and in the ball B^d , for 2≤d≤7. These spaces are related by a conformal transformation. In even dimensional spaces, the conformal anomalies on ℍ2 n and B^{2n} are shown to be identical. In odd dimensional spaces, the conformal anomaly on B^{2n+1} comes from a boundary contribution, which exactly coincides with that of ℍ2 n + 1 provided one identifies the UV short-distance cutoff on B^{2n+1} with the inverse large distance IR cutoff on ℍ2 n + 1, just as prescribed by the conformal map. As an application, we determine, for the first time, the conformal anomaly coefficients multiplying the Euler characteristic of the boundary for scalars and half-spin fields with various boundary conditions in d = 5 and d = 7.

Side-chain conformational space analysis (SCSA): A multi conformation-based QSAR approach for modeling and prediction of protein-peptide binding affinities

NASA Astrophysics Data System (ADS)

Zhou, Peng; Chen, Xiang; Shang, Zhicai

2009-03-01

In this article, the concept of multi conformation-based quantitative structure-activity relationship (MCB-QSAR) is proposed, and based upon that, we describe a new approach called the side-chain conformational space analysis (SCSA) to model and predict protein-peptide binding affinities. In SCSA, multi-conformations (rather than traditional single-conformation) have received much attention, and the statistical average information on multi-conformations of side chains is determined using self-consistent mean field theory based upon side chain rotamer library. Thereby, enthalpy contributions (including electrostatic, steric, hydrophobic interaction and hydrogen bond) and conformational entropy effects to the binding are investigated in terms of occurrence probability of residue rotamers. Then, SCSA was applied into the dataset of 419 HLA-A*0201 binding peptides, and nonbonding contributions of each position in peptide ligands are well determined. For the peptides, the hydrogen bond and electrostatic interactions of the two ends are essential to the binding specificity, van der Waals and hydrophobic interactions of all the positions ensure strong binding affinity, and the loss of conformational entropy at anchor positions partially counteracts other favorable nonbonding effects.

Conformal mapping for multiple terminals

PubMed Central

Wang, Weimin; Ma, Wenying; Wang, Qiang; Ren, Hao

2016-01-01

Conformal mapping is an important mathematical tool that can be used to solve various physical and engineering problems in many fields, including electrostatics, fluid mechanics, classical mechanics, and transformation optics. It is an accurate and convenient way to solve problems involving two terminals. However, when faced with problems involving three or more terminals, which are more common in practical applications, existing conformal mapping methods apply assumptions or approximations. A general exact method does not exist for a structure with an arbitrary number of terminals. This study presents a conformal mapping method for multiple terminals. Through an accurate analysis of boundary conditions, additional terminals or boundaries are folded into the inner part of a mapped region. The method is applied to several typical situations, and the calculation process is described for two examples of an electrostatic actuator with three electrodes and of a light beam splitter with three ports. Compared with previously reported results, the solutions for the two examples based on our method are more precise and general. The proposed method is helpful in promoting the application of conformal mapping in analysis of practical problems. PMID:27830746

Mapping Conformational Dynamics of Proteins Using Torsional Dynamics Simulations

PubMed Central

Gangupomu, Vamshi K.; Wagner, Jeffrey R.; Park, In-Hee; Jain, Abhinandan; Vaidehi, Nagarajan

2013-01-01

All-atom molecular dynamics simulations are widely used to study the flexibility of protein conformations. However, enhanced sampling techniques are required for simulating protein dynamics that occur on the millisecond timescale. In this work, we show that torsional molecular dynamics simulations enhance protein conformational sampling by performing conformational search in the low-frequency torsional degrees of freedom. In this article, we use our recently developed torsional-dynamics method called Generalized Newton-Euler Inverse Mass Operator (GNEIMO) to study the conformational dynamics of four proteins. We investigate the use of the GNEIMO method in simulations of the conformationally flexible proteins fasciculin and calmodulin, as well as the less flexible crambin and bovine pancreatic trypsin inhibitor. For the latter two proteins, the GNEIMO simulations with an implicit-solvent model reproduced the average protein structural fluctuations and sample conformations similar to those from Cartesian simulations with explicit solvent. The application of GNEIMO with replica exchange to the study of fasciculin conformational dynamics produced sampling of two of this protein’s experimentally established conformational substates. Conformational transition of calmodulin from the Ca2+-bound to the Ca2+-free conformation occurred readily with GNEIMO simulations. Moreover, the GNEIMO method generated an ensemble of conformations that satisfy about half of both short- and long-range interresidue distances obtained from NMR structures of holo to apo transitions in calmodulin. Although unconstrained all-atom Cartesian simulations have failed to sample transitions between the substates of fasciculin and calmodulin, GNEIMO simulations show the transitions in both systems. The relatively short simulation times required to capture these long-timescale conformational dynamics indicate that GNEIMO is a promising molecular-dynamics technique for studying domain motion in

Research on conformal dome of Karman-curve shape

NASA Astrophysics Data System (ADS)

Zhang, Yunqiang; Chang, Jun; Niu, Yajun

2018-01-01

Because the conformal optical technology can obviously improve the aerodynamic performance of the infrared guidance missile, it has been studied deeply in recent years. By comparing the performance of the missiles with conformal dome and conventional missiles, the advantages of the conformal optical technology are demonstrated in the maneuverability and stealth of the missile. At present, the study of conformal optical systems focuses on ellipsoid or quadratic curve types. But in actual use, the dome using these curves is not the best choice. In this paper, the influence of different shape of the dome on aerodynamic performance, aerodynamic heating, internal space volume and other properties is discussed. The result shows infrared optical system with conformal dome of Karman-curve shape has a good application prospect, is the future direction of development. Finally, the difficult problems of conformal dome of Karman-curve shape are discussed.

UV conformal window for asymptotic safety

NASA Astrophysics Data System (ADS)

Bond, Andrew D.; Litim, Daniel F.; Vazquez, Gustavo Medina; Steudtner, Tom

2018-02-01

Interacting fixed points in four-dimensional gauge theories coupled to matter are investigated using perturbation theory up to three loop order. It is shown how fixed points, scaling exponents, and anomalous dimensions are obtained as a systematic power series in a small parameter. The underlying ordering principle is explained and contrasted with conventional perturbation theory and Weyl consistency conditions. We then determine the conformal window with asymptotic safety from the complete next-to-next-to-leading order in perturbation theory. Limits for the conformal window arise due to fixed point mergers, the onset of strong coupling, or vacuum instability. A consistent picture is uncovered by comparing various levels of approximation. The theory remains perturbative in the entire conformal window, with vacuum stability dictating the tightest constraints. We also speculate about a secondary conformal window at strong coupling and estimate its lower limit. Implications for model building and cosmology are indicated.

Exercise Improves Clinical Symptoms, Quality of Life, Global Functioning, and Depression in Schizophrenia: A Systematic Review and Meta-analysis

PubMed Central

Dauwan, Meenakshi; Begemann, Marieke J. H.; Heringa, Sophie M.; Sommer, Iris E.

2016-01-01

Background: Physical exercise may be valuable for patients with schizophrenia spectrum disorders as it may have beneficial effect on clinical symptoms, quality of life and cognition. Methods: A systematic search was performed using PubMed (Medline), Embase, PsychInfo, and Cochrane Database of Systematic Reviews. Controlled and uncontrolled studies investigating the effect of any type of physical exercise interventions in schizophrenia spectrum disorders were included. Outcome measures were clinical symptoms, quality of life, global functioning, depression or cognition. Meta-analyses were performed using Comprehensive Meta-Analysis software. A random effects model was used to compute overall weighted effect sizes in Hedges’ g. Results: Twenty-nine studies were included, examining 1109 patients. Exercise was superior to control conditions in improving total symptom severity (k = 14, n = 719: Hedges’ g = .39, P < .001), positive (k = 15, n = 715: Hedges’ g = .32, P < .01), negative (k = 18, n = 854: Hedges’ g = .49, P < .001), and general (k = 10, n = 475: Hedges’ g = .27, P < .05) symptoms, quality of life (k = 11, n = 770: Hedges’ g = .55, P < .001), global functioning (k = 5, n = 342: Hedges’ g = .32, P < .01), and depressive symptoms (k = 7, n = 337: Hedges’ g = .71, P < .001). Yoga, specifically, improved the cognitive subdomain long-term memory (k = 2, n = 184: Hedges’ g = .32, P < .05), while exercise in general or in any other form had no effect on cognition. Conclusion: Physical exercise is a robust add-on treatment for improving clinical symptoms, quality of life, global functioning, and depressive symptoms in patients with schizophrenia. The effect on cognition is not demonstrated, but may be present for yoga. PMID:26547223

Conformation transitions of a single polyelectrolyte chain in a poor solvent: a replica-exchange lattice Monte-Carlo study.

PubMed

Wang, Lang; Wang, Zheng; Jiang, Run; Yin, Yuhua; Li, Baohui

2017-03-15

The thermodynamic behaviors of a strongly charged polyelectrolyte chain in a poor solvent are studied using replica-exchange Monte-Carlo simulations on a lattice model, focusing on the effects of finite chain length and the solvent quality on the chain conformation and conformation transitions. The neutralizing counterions and solvent molecules are considered explicitly. The thermodynamic quantities that vary continuously with temperature over a wide range are computed using the multiple histogram reweighting method. Our results suggest that the strength of the short-range hydrophobic interaction, the chain length, and the temperature of the system, characterized by ε, N, and T, respectively, are important parameters that control the conformations of a charged chain. When ε is moderate, the competition between the electrostatic energy and the short-range hydrophobic interaction leads to rich conformations and conformation transitions for a longer chain with a fixed length. Our results have unambiguously demonstrated the stability of the n-pearl-necklace structures, where n has a maximum value and decreases with decreasing temperature. The maximum n value increases with increasing chain length. Our results have also demonstrated the first-order nature of the conformation transitions between the m-pearl and the (m-1)-pearl necklaces. With the increase of ε, the transition temperature increases and the first-order feature becomes more pronounced. It is deduced that at the thermodynamic limit of infinitely long chain length, the conformational transitions between the m-pearl and the (m-1)-pearl necklaces may remain first order when ε > 0 and m = 2 or 3. Pearl-necklace conformations cannot be observed when either ε is too large or N is too small. To observe a pearl-necklace conformation, the T value needs to be carefully chosen for simulations performed at only a single temperature.

Global Ocean Data Quality Assessment of SARAL/AltiKa GDR products

NASA Astrophysics Data System (ADS)

Picot, Nicolas; Prandi, Pierre; desjonqueres, jean-damien

2015-04-01

The SARAL mission was successfully launched on February, 5th 2013 and cycle 1 started a few days later on March 14th. For more than 2 years, the Ka-band altimeter and dual frequency radiometer on board have been collecting high quality ocean topography measurements. Within the first months of the mission, a first patch (P1) was developed to correct some small anomalies detected in the products and to account for in-flight calibration data. At the beginning of year 2014, a second patch (P2) was produced (applied from cycle 10 pass 407 on OGDR data and from pass 566 on IGDR data) and the all GDR produced before this were reprocessed in order to deliver a consistent dataset to users. This new version of the products provides, among other changes, important improvements regarding radiometer data processing, sea-state bias and wind speed. Since the beginning of the mission, data quality assessment of OGDR, IGDR and GDR data has been routinely performed at CNES and CLS (as part of the CNES SALP project). We will present the main results of the data quality assessment over ocean based on SARAL/AltiKa GDR data reprocessed using the homogeneous P2 version. The main data quality metrics presented will include: Data availability and validity, Monitoring of the main altimeter and radiometer parameters and comparisons to other altimeter missions such as OSTM/Jason-2, Mission performance through mono-mission crossovers analysis, Investigation of inter-mission biases and large-scale regional differences from multi-mission crossovers between SARAL and Jason-2. Monitoring of the global mean SLA and comparison to Jason-2 Finally, we will present the new product version standard that is currently under development on CNES side.

Direct observation of fast protein conformational switching.

PubMed

Ishikawa, Haruto; Kwak, Kyungwon; Chung, Jean K; Kim, Seongheun; Fayer, Michael D

2008-06-24

Folded proteins can exist in multiple conformational substates. Each substate reflects a local minimum on the free-energy landscape with a distinct structure. By using ultrafast 2D-IR vibrational echo chemical-exchange spectroscopy, conformational switching between two well defined substates of a myoglobin mutant is observed on the approximately 50-ps time scale. The conformational dynamics are directly measured through the growth of cross peaks in the 2D-IR spectra of CO bound to the heme active site. The conformational switching involves motion of the distal histidine/E helix that changes the location of the imidazole side group of the histidine. The exchange between substates changes the frequency of the CO, which is detected by the time dependence of the 2D-IR vibrational echo spectrum. These results demonstrate that interconversion between protein conformational substates can occur on very fast time scales. The implications for larger structural changes that occur on much longer time scales are discussed.

Performance of Conformable Ablators in Aerothermal Environments

NASA Technical Reports Server (NTRS)

Thornton, J.; Fan, W.; Skokova, K.; Stackpoole, M.; Beck, R.; Chavez-Garcia, J.

2012-01-01

Conformable Phenolic Impregnated Carbon Ablator, a cousin of Phenolic Impregnated Carbon Ablator (PICA), was developed at NASA Ames Research Center as a lightweight thermal protection system under the Fundamental Aeronautics Program. PICA is made using a brittle carbon substrate, which has a very low strain to failure. Conformable PICA is made using a flexible carbon substrate, a felt in this case. The flexible felt significantly increases the strain to failure of the ablator. PICA is limited by its thermal mechanical properties. Future NASA missions will require heatshields that are more fracture resistant than PICA and, as a result, NASA Ames is working to improve PICAs performance by developing conformable PICA to meet these needs. Research efforts include tailoring the chemistry of conformable PICA with varying amounts of additives to enhance mechanical properties and testing them in aerothermal environments. This poster shows the performance of conformable PICA variants in arc jets tests. Some mechanical and thermal properties will also be presented.

Frequency of Behavior Witnessed and Conformity in an Everyday Social Context

PubMed Central

Claidière, Nicolas; Bowler, Mark; Brookes, Sarah; Brown, Rebecca; Whiten, Andrew

2014-01-01

Conformity is thought to be an important force in human evolution because it has the potential to stabilize cultural homogeneity within groups and cultural diversity between groups. However, the effects of such conformity on cultural and biological evolution will depend much on the particular way in which individuals are influenced by the frequency of alternative behavioral options they witness. In a previous study we found that in a natural situation people displayed a tendency to be ‘linear-conformist’. When visitors to a Zoo exhibit were invited to write or draw answers to questions on cards to win a small prize and we manipulated the proportion of text versus drawings on display, we found a strong and significant effect of the proportion of text displayed on the proportion of text in the answers, a conformist effect that was largely linear with a small non-linear component. However, although this overall effect is important to understand cultural evolution, it might mask a greater diversity of behavioral responses shaped by variables such as age, sex, social environment and attention of the participants. Accordingly we performed a further study explicitly to analyze the effects of these variables, together with the quality of the information participants' responses made available to further visitors. Results again showed a largely linear conformity effect that varied little with the variables analyzed. PMID:24950212

Incompleteness of Bluetooth protocol conformance test cases

NASA Astrophysics Data System (ADS)

Wu, Peng; Gao, Qiang

2001-10-01

This paper describes a formal method to verify the completeness of conformance testing, in which not only Implementation Under Test (IUT) is formalized in SDL, but also conformance tester is described in SDL so that conformance testing can be performed in simulator provided with CASE tool. The protocol set considered is Bluetooth, an open wireless communication technology. Our research results show that Bluetooth conformance test specification is not complete in that it has only limited coverage and many important capabilities defined in Bluetooth core specification are not tested. We also give a detail report on the missing test cases against Bluetooth core specification, and provide a guide on further test case generation in the future.

Mapping conformational dynamics of proteins using torsional dynamics simulations.

PubMed

Gangupomu, Vamshi K; Wagner, Jeffrey R; Park, In-Hee; Jain, Abhinandan; Vaidehi, Nagarajan

2013-05-07

All-atom molecular dynamics simulations are widely used to study the flexibility of protein conformations. However, enhanced sampling techniques are required for simulating protein dynamics that occur on the millisecond timescale. In this work, we show that torsional molecular dynamics simulations enhance protein conformational sampling by performing conformational search in the low-frequency torsional degrees of freedom. In this article, we use our recently developed torsional-dynamics method called Generalized Newton-Euler Inverse Mass Operator (GNEIMO) to study the conformational dynamics of four proteins. We investigate the use of the GNEIMO method in simulations of the conformationally flexible proteins fasciculin and calmodulin, as well as the less flexible crambin and bovine pancreatic trypsin inhibitor. For the latter two proteins, the GNEIMO simulations with an implicit-solvent model reproduced the average protein structural fluctuations and sample conformations similar to those from Cartesian simulations with explicit solvent. The application of GNEIMO with replica exchange to the study of fasciculin conformational dynamics produced sampling of two of this protein's experimentally established conformational substates. Conformational transition of calmodulin from the Ca(2+)-bound to the Ca(2+)-free conformation occurred readily with GNEIMO simulations. Moreover, the GNEIMO method generated an ensemble of conformations that satisfy about half of both short- and long-range interresidue distances obtained from NMR structures of holo to apo transitions in calmodulin. Although unconstrained all-atom Cartesian simulations have failed to sample transitions between the substates of fasciculin and calmodulin, GNEIMO simulations show the transitions in both systems. The relatively short simulation times required to capture these long-timescale conformational dynamics indicate that GNEIMO is a promising molecular-dynamics technique for studying domain motion in

Intrinsic Conformational Preferences of Cα,α-Dibenzylglycine

PubMed Central

Casanovas, Jordi; Nussinov, Ruth; Alemán, Carlos

2009-01-01

The intrinsic conformational preferences of Cα,α-dibenzylglycine, a symmetric α,α-dialkylated amino acid bearing two benzyl substituents on the α-carbon atom, have been determined using quantum chemical calculations at the B3LYP/6-31+G(d,p) level. A total of 46 minimum energy conformations were found for the N-acetyl-N'-methylamide derivative, even though only 9 of them showed a relative energy lower than 5.0 kcal/mol. The latter involves C7, C5 and α' backbone conformations stabilized by intramolecular hydrogen bonds and/or N-H…π interactions. Calculation of the conformational free energies in different environments (gas-phase, carbon tetrachloride, chloroform, methanol and water solutions) indicates that four different minima (two C5 and two C7) are energetically accessible at room temperature in the gas-phase, while in methanol and aqueous solutions one such minimum (C5) becomes the only significant conformation. Comparison with results recently reported for Cα,α-diphenylglycine indicates that substitution of phenyl side groups by benzyl enhances the conformational flexibility leading to (i) a reduction of the strain of the peptide backbone; and (ii) alleviating the repulsive interactions between the π electron density of the phenyl groups and the lone pairs of the carbonyl oxygen atoms. PMID:18465898

Dosimetric Comparison of Helical Tomotherapy and Dynamic Conformal Arc Therapy in Stereotactic Radiosurgery for Vestibular Schwannomas

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

Lee, Tsair-Fwu, E-mail: tflee@cc.kuas.edu.t; Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Chao, Pei-Ju

2011-04-01

The dosimetric results of stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) performed using dynamic conformal arc therapy (DCAT) with the Novalis system and helical TomoTherapy (HT) were compared using plan quality indices. The HT plans were created for 10 consecutive patients with VS previously treated with SRS using the Novalis system. The dosimetric indices used to compare the techniques included the conformity index (CI) and homogeneity index (HI) for the planned target volume (PTV), the comprehensive quality index (CQI) for nine organs at risk (OARs), gradient score index (GSI) for the dose drop-off outside the PTV, and plan quality indexmore » (PQI), which was verified using the plan quality discerning power (PQDP) to incorporate 3 plan indices, to evaluate the rival plans. The PTV ranged from 0.27-19.99 cm{sup 3} (median 3.39 cm{sup 3}), with minimum required PTV prescribed doses of 10-16 Gy (median 12 Gy). Both systems satisfied the minimum required PTV prescription doses. HT conformed better to the PTV (CI: 1.51 {+-} 0.23 vs. 1.94 {+-} 0.34; p < 0.01), but had a worse drop-off outside the PTV (GSI: 40.3 {+-} 10.9 vs. 64.9 {+-} 13.6; p < 0.01) compared with DCAT. No significant difference in PTV homogeneity was observed (HI: 1.08 {+-} 0.03 vs. 1.09 {+-} 0.02; p = 0.20). HT had a significantly lower maximum dose in 4 OARs and significant lower mean dose in 1 OAR; by contrast, DCAT had a significantly lower maximum dose in 1 OAR and significant lower mean dose in 2 OARs, with the CQI of the 9 OARs = 0.92 {+-} 0.45. Plan analysis using PQI (HT 0.37 {+-} 0.12 vs. DCAT 0.65 {+-} 0.08; p < 0.01), and verified using the PQDP, confirmed the dosimetric advantage of HT. However, the HT system had a longer beam-on time (33.2 {+-} 7.4 vs. 4.6 {+-} 0.9 min; p < 0.01) and consumed more monitor units (16772 {+-} 3803 vs. 1776 {+-} 356.3; p < 0.01). HT had a better dose conformity and similar dose homogeneity but worse dose gradient than DCAT. Plan analysis

Satellite Models for Global Environmental Change in the NASA Health and Air Quality Programs

NASA Astrophysics Data System (ADS)

Haynes, J.; Estes, S. M.

2015-12-01

Satellite remote sensing of the environment offers a unique vantage point that can fill in the gaps of environmental, spatial, and temporal data for tracking disease. Health and Air Quality providers and researchers are effective by the global environmental changes that are occurring and they need environmental data to study and understand the geographic, environmental, and meteorological differences in disease. This presentation maintains a diverse constellation of Earth observing research satellites and sponsors research in developing satellite data applications across a wide spectrum of areas including environmental health; infectious disease; air quality standards, policies, and regulations; and the impact of climate change on health and air quality. Successfully providing predictions with the accuracy and specificity required by decision makers will require advancements over current capabilities in a number of interrelated areas. These areas include observations, modeling systems, forecast development, application integration, and the research to operations transition process. This presentation will highlight many projects on which NASA satellites have been a primary partner with local, state, Federal, and international operational agencies over the past twelve years in these areas. Domestic and International officials have increasingly recognized links between environment and health. Health providers and researchers need environmental data to study and understand the geographic, environmental, and meteorological differences in disease. The presentation is directly related to Earth Observing systems and Global Health Surveillance and will present research results of the remote sensing environmental observations of earth and health applications, which can contribute to the health research. As part of NASA approach and methodology they have used Earth Observation Systems and Applications for Health Models to provide a method for bridging gaps of environmental

Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding.

PubMed

Gui, Miao; Song, Wenfei; Zhou, Haixia; Xu, Jingwei; Chen, Silian; Xiang, Ye; Wang, Xinquan

2017-01-01

The global outbreak of SARS in 2002-2003 was caused by the infection of a new human coronavirus SARS-CoV. The infection of SARS-CoV is mediated mainly through the viral surface glycoproteins, which consist of S1 and S2 subunits and form trimer spikes on the envelope of the virions. Here we report the ectodomain structures of the SARS-CoV surface spike trimer in different conformational states determined by single-particle cryo-electron microscopy. The conformation 1 determined at 4.3 Å resolution is three-fold symmetric and has all the three receptor-binding C-terminal domain 1 (CTD1s) of the S1 subunits in "down" positions. The binding of the "down" CTD1s to the SARS-CoV receptor ACE2 is not possible due to steric clashes, suggesting that the conformation 1 represents a receptor-binding inactive state. Conformations 2-4 determined at 7.3, 5.7 and 6.8 Å resolutions are all asymmetric, in which one RBD rotates away from the "down" position by different angles to an "up" position. The "up" CTD1 exposes the receptor-binding site for ACE2 engagement, suggesting that the conformations 2-4 represent a receptor-binding active state. This conformational change is also required for the binding of SARS-CoV neutralizing antibodies targeting the CTD1. This phenomenon could be extended to other betacoronaviruses utilizing CTD1 of the S1 subunit for receptor binding, which provides new insights into the intermediate states of coronavirus pre-fusion spike trimer during infection.

Conformations of organophosphine oxides

DOE PAGES

De Silva, Nuwan; Zahariev, Federico; Hay, Benjamin P.; ...

2015-07-17

The conformations of a series of organophosphine oxides, OP(CH 3) 2R, where R = methyl, ethyl, isopropyl, tert-butyl, vinyl, and phenyl, are predicted using the MP2/cc-pVTZ level of theory. Comparison of potential energy surfaces for rotation about P–C bonds with crystal structure data reveals a strong correlation between predicted location and energetics of minima and histograms of dihedral angle distributions observed in the solid state. In addition, the most stable conformers are those that minimize the extent of steric repulsion between adjacent rotor substituents, and the torsional barriers tend to increase with the steric bulk of the rotating alkyl group.more » MM3 force field parameters were adjusted to fit the MP2 results, providing a fast and accurate model for predicting organophosphine oxides shapes—an essential part of understanding the chemistry of these compounds. As a result, the predictive power of the modified MM3 model was tested against MP2/cc-pVTZ conformations for triethylphosphine oxide, OP(CH 2CH 3) 3, and triphenylphosphine oxide, OP(Ph) 3.« less

Conformal coating of amorphous silicon and germanium by high pressure chemical vapor deposition for photovoltaic fabrics

NASA Astrophysics Data System (ADS)

Ji, Xiaoyu; Cheng, Hiu Yan; Grede, Alex J.; Molina, Alex; Talreja, Disha; Mohney, Suzanne E.; Giebink, Noel C.; Badding, John V.; Gopalan, Venkatraman

2018-04-01

Conformally coating textured, high surface area substrates with high quality semiconductors is challenging. Here, we show that a high pressure chemical vapor deposition process can be employed to conformally coat the individual fibers of several types of flexible fabrics (cotton, carbon, steel) with electronically or optoelectronically active materials. The high pressure (˜30 MPa) significantly increases the deposition rate at low temperatures. As a result, it becomes possible to deposit technologically important hydrogenated amorphous silicon (a-Si:H) from silane by a simple and very practical pyrolysis process without the use of plasma, photochemical, hot-wire, or other forms of activation. By confining gas phase reactions in microscale reactors, we show that the formation of undesired particles is inhibited within the microscale spaces between the individual wires in the fabric structures. Such a conformal coating approach enables the direct fabrication of hydrogenated amorphous silicon-based Schottky junction devices on a stainless steel fabric functioning as a solar fabric.

Nucleotide-induced conformational dynamics in ABC transporters from structure-based coarse grained modelling.

NASA Astrophysics Data System (ADS)

Flechsig, Holger

2016-02-01

ATP-binding cassette (ABC) transporters are integral membrane proteins which mediate the exchange of diverse substrates across membranes powered by ATP molecules. Our understanding of their activity is still hampered since the conformational dynamics underlying the operation of such proteins cannot yet be resolved in detailed molecular dynamics studies. Here a coarse grained model which allows to mimic binding of nucleotides and follow subsequent conformational motions of full-length transporter structures in computer simulations is proposed and implemented. To justify its explanatory quality, the model is first applied to the maltose transporter system for which multiple conformations are known and we find that the model predictions agree remarkably well with the experimental data. For the MalK subunit the switching from open to the closed dimer configuration upon ATP binding is reproduced and, moreover, for the full-length maltose transporter, progression from inward-facing to the outward-facing state is correctly obtained. For the heme transporter HmuUV, for which only the free structure could yet be determined, the model was then applied to predict nucleotide-induced conformational motions. Upon binding of ATP-mimicking ligands the structure changed from a conformation in which the nucleotide-binding domains formed an open shape, to a conformation in which they were found in tight contact, while, at the same time, a pronounced rotation of the transmembrane domains was observed. This finding is supported by normal mode analysis, and, comparison with structural data of the homologous vitamin B12 transporter BtuCD suggests that the observed rotation mechanism may contribute a common functional aspect for this class of ABC transporters. Although in HmuuV noticeable rearrangement of essential transmembrane helices was detected, there are no indications from our simulations that ATP binding alone may facilitate propagation of substrate molecules in this transporter

Conformable apparatus in a drill string

DOEpatents

Hall, David R [Provo, UT; Hall, Jr., H. Tracy; Pixton, David S [Lehi, UT; Fox, Joe [Spanish Fork, UT

2007-08-28

An apparatus in a drill string comprises an internally upset drill pipe. The drill pipe comprises a first end, a second end, and an elongate tube intermediate the first and second ends. The elongate tube and the ends comprising a continuous an inside surface with a plurality of diameters. A conformable metal tube is disposed within the drill pipe intermediate the ends thereof and terminating adjacent to the ends of the drill pipe. The conformable metal tube substantially conforms to the continuous inside surface of the metal tube. The metal tube may comprise a non-uniform section which is expanded to conform to the inside surface of the drill pipe. The non-uniform section may comprise protrusions selected from the group consisting of convolutions, corrugations, flutes, and dimples. The non-uniform section extends generally longitudinally along the length of the tube. The metal tube may be adapted to stretch as the drill pipes stretch.

Conformal Electromagnetic Particle in Cell: A Review

DOE PAGES

Meierbachtol, Collin S.; Greenwood, Andrew D.; Verboncoeur, John P.; ...

2015-10-26

We review conformal (or body-fitted) electromagnetic particle-in-cell (EM-PIC) numerical solution schemes. Included is a chronological history of relevant particle physics algorithms often employed in these conformal simulations. We also provide brief mathematical descriptions of particle-tracking algorithms and current weighting schemes, along with a brief summary of major time-dependent electromagnetic solution methods. Several research areas are also highlighted for recommended future development of new conformal EM-PIC methods.

The novel 2016 WHO Neisseria gonorrhoeae reference strains for global quality assurance of laboratory investigations: phenotypic, genetic and reference genome characterization.

PubMed

Unemo, Magnus; Golparian, Daniel; Sánchez-Busó, Leonor; Grad, Yonatan; Jacobsson, Susanne; Ohnishi, Makoto; Lahra, Monica M; Limnios, Athena; Sikora, Aleksandra E; Wi, Teodora; Harris, Simon R

2016-11-01

Gonorrhoea and MDR Neisseria gonorrhoeae remain public health concerns globally. Enhanced, quality-assured, gonococcal antimicrobial resistance (AMR) surveillance is essential worldwide. The WHO global Gonococcal Antimicrobial Surveillance Programme (GASP) was relaunched in 2009. We describe the phenotypic, genetic and reference genome characteristics of the 2016 WHO gonococcal reference strains intended for quality assurance in the WHO global GASP, other GASPs, diagnostics and research worldwide. The 2016 WHO reference strains (n = 14) constitute the eight 2008 WHO reference strains and six novel strains. The novel strains represent low-level to high-level cephalosporin resistance, high-level azithromycin resistance and a porA mutant. All strains were comprehensively characterized for antibiogram (n = 23), serovar, prolyliminopeptidase, plasmid types, molecular AMR determinants, N. gonorrhoeae multiantigen sequence typing STs and MLST STs. Complete reference genomes were produced using single-molecule PacBio sequencing. The reference strains represented all available phenotypes, susceptible and resistant, to antimicrobials previously and currently used or considered for future use in gonorrhoea treatment. All corresponding resistance genotypes and molecular epidemiological types were described. Fully characterized, annotated and finished references genomes (n = 14) were presented. The 2016 WHO gonococcal reference strains are intended for internal and external quality assurance and quality control in laboratory investigations, particularly in the WHO global GASP and other GASPs, but also in phenotypic (e.g. culture, species determination) and molecular diagnostics, molecular AMR detection, molecular epidemiology and as fully characterized, annotated and finished reference genomes in WGS analysis, transcriptomics, proteomics and other molecular technologies and data analysis. © The Author 2016. Published by Oxford University Press on behalf of the

Linking transportation and air quality planning implementation of the transportation conformity regulations in 15 nonattainment areas : executive summary

DOT National Transportation Integrated Search

1999-03-01

Clean Air Act Amendments (CAAA) of 1980 requires far reaching efforts under the "transportation conformity" regulations to assure that transportation investments in non-attainment and maintenance areas are consistent with state commitments to meet na...

A stochastic algorithm for global optimization and for best populations: A test case of side chains in proteins

PubMed Central

Glick, Meir; Rayan, Anwar; Goldblum, Amiram

2002-01-01

The problem of global optimization is pivotal in a variety of scientific fields. Here, we present a robust stochastic search method that is able to find the global minimum for a given cost function, as well as, in most cases, any number of best solutions for very large combinatorial “explosive” systems. The algorithm iteratively eliminates variable values that contribute consistently to the highest end of a cost function's spectrum of values for the full system. Values that have not been eliminated are retained for a full, exhaustive search, allowing the creation of an ordered population of best solutions, which includes the global minimum. We demonstrate the ability of the algorithm to explore the conformational space of side chains in eight proteins, with 54 to 263 residues, to reproduce a population of their low energy conformations. The 1,000 lowest energy solutions are identical in the stochastic (with two different seed numbers) and full, exhaustive searches for six of eight proteins. The others retain the lowest 141 and 213 (of 1,000) conformations, depending on the seed number, and the maximal difference between stochastic and exhaustive is only about 0.15 Kcal/mol. The energy gap between the lowest and highest of the 1,000 low-energy conformers in eight proteins is between 0.55 and 3.64 Kcal/mol. This algorithm offers real opportunities for solving problems of high complexity in structural biology and in other fields of science and technology. PMID:11792838

A Mediated Moderation Model of Conformative Peer Bullying

ERIC Educational Resources Information Center

Cho, Yoonju; Chung, Ock-Boon

2012-01-01

We investigated the relationship between conformative peer bullying and issues of peer conformity among adolescents. This relationship is examined through the establishment of a mediated moderation model for conformative peer bullying using structural equation modeling in a sample of 391 second-year middle school students in Seoul, South Korea. We…

40 CFR 93.154 - Conformity analysis.

Code of Federal Regulations, 2010 CFR

2010-07-01

... department, agency, or instrumentality of the Federal government taking an action subject to this subpart... conformity determination. Effective Date Note: At 75 FR 17275, Apr. 5, 2010, § 93.154 was revised, effective... government taking an action subject to this subpart must make its own conformity determination consistent...

Tackling the conformational sampling of larger flexible compounds and macrocycles in pharmacology and drug discovery.

PubMed

Chen, I-Jen; Foloppe, Nicolas

2013-12-15

Computational conformational sampling underpins much of molecular modeling and design in pharmaceutical work. The sampling of smaller drug-like compounds has been an active area of research. However, few studies have tested in details the sampling of larger more flexible compounds, which are also relevant to drug discovery, including therapeutic peptides, macrocycles, and inhibitors of protein-protein interactions. Here, we investigate extensively mainstream conformational sampling methods on three carefully curated compound sets, namely the 'Drug-like', larger 'Flexible', and 'Macrocycle' compounds. These test molecules are chemically diverse with reliable X-ray protein-bound bioactive structures. The compared sampling methods include Stochastic Search and the recent LowModeMD from MOE, all the low-mode based approaches from MacroModel, and MD/LLMOD recently developed for macrocycles. In addition to default settings, key parameters of the sampling protocols were explored. The performance of the computational protocols was assessed via (i) the reproduction of the X-ray bioactive structures, (ii) the size, coverage and diversity of the output conformational ensembles, (iii) the compactness/extendedness of the conformers, and (iv) the ability to locate the global energy minimum. The influence of the stochastic nature of the searches on the results was also examined. Much better results were obtained by adopting search parameters enhanced over the default settings, while maintaining computational tractability. In MOE, the recent LowModeMD emerged as the method of choice. Mixed torsional/low-mode from MacroModel performed as well as LowModeMD, and MD/LLMOD performed well for macrocycles. The low-mode based approaches yielded very encouraging results with the flexible and macrocycle sets. Thus, one can productively tackle the computational conformational search of larger flexible compounds for drug discovery, including macrocycles. Copyright © 2013 Elsevier Ltd. All

Non-local Effects of Conformal Anomaly

NASA Astrophysics Data System (ADS)

Meissner, Krzysztof A.; Nicolai, Hermann

2018-03-01

It is shown that the nonlocal anomalous effective actions corresponding to the quantum breaking of the conformal symmetry can lead to observable modifications of Einstein's equations. The fact that Einstein's general relativity is in perfect agreement with all observations including cosmological or recently observed gravitational waves imposes strong restrictions on the field content of possible extensions of Einstein's theory: all viable theories should have vanishing conformal anomalies. It is shown that a complete cancellation of conformal anomalies in D=4 for both the C^2 invariant and the Euler (Gauss-Bonnet) invariant can only be achieved for N-extended supergravity multiplets with N ≥ 5.

Invariant classification of second-order conformally flat superintegrable systems

NASA Astrophysics Data System (ADS)

Capel, J. J.; Kress, J. M.

2014-12-01

In this paper we continue the work of Kalnins et al in classifying all second-order conformally-superintegrable (Laplace-type) systems over conformally flat spaces, using tools from algebraic geometry and classical invariant theory. The results obtained show, through Stäckel equivalence, that the list of known nondegenerate superintegrable systems over three-dimensional conformally flat spaces is complete. In particular, a seven-dimensional manifold is determined such that each point corresponds to a conformal class of superintegrable systems. This manifold is foliated by the nonlinear action of the conformal group in three dimensions. Two systems lie in the same conformal class if and only if they lie in the same leaf of the foliation. This foliation is explicitly described using algebraic varieties formed from representations of the conformal group. The proof of these results rely heavily on Gröbner basis calculations using the computer algebra software packages Maple and Singular.

Optimizing Quality of Care and Patient Safety in Malaysia: The Current Global Initiatives, Gaps and Suggested Solutions.

PubMed

Jarrar, Mu'taman; Abdul Rahman, Hamzah; Don, Mohammad Sobri

2015-10-20

Demand for health care service has significantly increased, while the quality of healthcare and patient safety has become national and international priorities. This paper aims to identify the gaps and the current initiatives for optimizing the quality of care and patient safety in Malaysia. Review of the current literature. Highly cited articles were used as the basis to retrieve and review the current initiatives for optimizing the quality of care and patient safety. The country health plan of Ministry of Health (MOH) Malaysia and the MOH Malaysia Annual Reports were reviewed. The MOH has set four strategies for optimizing quality and sustaining quality of life. The 10th Malaysia Health Plan promotes the theme "1 Care for 1 Malaysia" in order to sustain the quality of care. Despite of these efforts, the total number of complaints received by the medico-legal section of the MOH Malaysia is increasing. The current global initiatives indicted that quality performance generally belong to three main categories: patient; staffing; and working environment related factors. There is no single intervention for optimizing quality of care to maintain patient safety. Multidimensional efforts and interventions are recommended in order to optimize the quality of care and patient safety in Malaysia.

Optimizing Quality of Care and Patient Safety in Malaysia: The Current Global Initiatives, Gaps and Suggested Solutions

PubMed Central

Jarrar, Mu’taman; Rahman, Hamzah Abdul; Don, Mohammad Sobri

2016-01-01

Background and Objective: Demand for health care service has significantly increased, while the quality of healthcare and patient safety has become national and international priorities. This paper aims to identify the gaps and the current initiatives for optimizing the quality of care and patient safety in Malaysia. Design: Review of the current literature. Highly cited articles were used as the basis to retrieve and review the current initiatives for optimizing the quality of care and patient safety. The country health plan of Ministry of Health (MOH) Malaysia and the MOH Malaysia Annual Reports were reviewed. Results: The MOH has set four strategies for optimizing quality and sustaining quality of life. The 10th Malaysia Health Plan promotes the theme “1 Care for 1 Malaysia” in order to sustain the quality of care. Despite of these efforts, the total number of complaints received by the medico-legal section of the MOH Malaysia is increasing. The current global initiatives indicted that quality performance generally belong to three main categories: patient; staffing; and working environment related factors. Conclusions: There is no single intervention for optimizing quality of care to maintain patient safety. Multidimensional efforts and interventions are recommended in order to optimize the quality of care and patient safety in Malaysia. PMID:26755459

The endoscopy Global Rating Scale – Canada: Development and implementation of a quality improvement tool

PubMed Central

MacIntosh, Donald; Dubé, Catherine; Hollingworth, Roger; van Zanten, Sander Veldhuyzen; Daniels, Sandra; Ghattas, George

2013-01-01

BACKGROUND: Increasing use of gastrointestinal endoscopy, particularly for colorectal cancer screening, and increasing emphasis on health care quality highlight the need for endoscopy facilities to review the quality of the service they offer. OBJECTIVE: To adapt the United Kingdom Global Rating Scale (UK-GRS) to develop a web-based and patient-centred tool to assess and improve the quality of endoscopy services provided. METHODS: Based on feedback from 22 sites across Canada that completed the UK endoscopy GRS, and integrating results of the Canadian consensus on safety and quality indicators in endoscopy and other Canadian consensus reports, a working group of endoscopists experienced with the GRS developed the GRS-Canada (GRS-C). RESULTS: The GRS-C mirrors the two dimensions (clinical quality and quality of the patient experience) and 12 patient-centred items of the UK-GRS, but was modified to apply to Canadian health care infrastructure, language and current practice. Each item is assessed by a yes/no response to eight to 12 statements that are divided into levels graded D (basic) through A (advanced). A core team consisting of a booking clerk, charge nurse and the physician responsible for the unit is recommended to complete the GRS-C twice yearly. CONCLUSION: The GRS-C is intended to improve endoscopic services in Canada by providing endoscopy units with a straightforward process to review the quality of the service they provide. PMID:23472242

Generalized conformal structure, dilaton gravity and SYK

NASA Astrophysics Data System (ADS)

Taylor, Marika

2018-01-01

A theory admits generalized conformal structure if the only scale in the quantum theory is set by a dimensionful coupling. SYK is an example of a theory with generalized conformal structure and in this paper we investigate the consequences of this structure for correlation functions and for the holographic realization of SYK. The Ward identities associated with the generalized conformal structure of SYK are implemented holographically in gravity/multiple scalar theories, which always have a parent AdS3 origin. For questions involving only the graviton/running scalar sector, one can always describe the bulk running in terms of a single scalar but multiple running scalars are in general needed once one includes the bulk fields corresponding to all SYK operators. We then explore chaos in holographic theories with generalized conformal structure. The four point function explored by Maldacena, Shenker and Stanford exhibits exactly the same chaotic behaviour in any such theory as in holographic realizations of conformal theories i.e. the dimensionful coupling scale does not affect the chaotic exponential growth.

Conformal collineations and anisotropic fluids in general relativity

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

Duggal, K.L.; Sharma, R.

1986-10-01

Recently, Herrera et al. (L. Herrera, J. Jimenez, L. Leal, J. Ponce de Leon, M. Esculpi, and V. Galino, J. Math. Phys. 25, 3274 (1984)) studied the consequences of the existence of a one-parameter group of conformal motions for anisotropic matter. They concluded that for special conformal motions, the stiff equation of state (p = ..mu..) is singled out in a unique way, provided the generating conformal vector field is orthogonal to the four-velocity. In this paper, the same problem is studied by using conformal collineations (which include conformal motions as subgroups). It is shown that, for a special conformalmore » collineation, the stiff equation of state is not singled out. Non-Einstein Ricci-recurrent spaces are considered as physical models for the fluid matter.« less

Conformational Changes in Orotidine 5-Monophosphate Decarboxylase: "Remote" Residues That Stabilize the Active Conformation

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

Wood, B.; Amyes, T; Fedorov, A

2010-01-01

The structural factors responsible for the extraordinary rate enhancement ({approx}10{sup 17}) of the reaction catalyzed by orotidine 5{prime}-monophosphate decarboxylase (OMPDC) have not been defined. Catalysis requires a conformational change that closes an active site loop and 'clamps' the orotate base proximal to hydrogen-bonded networks that destabilize the substrate and stabilize the intermediate. In the OMPDC from Methanobacter thermoautotrophicus, a 'remote' structurally conserved cluster of hydrophobic residues that includes Val 182 in the active site loop is assembled in the closed, catalytically active conformation. Substitution of these residues with Ala decreases k{sub cat}/K{sub m} with a minimal effect on k{sub cat},more » providing evidence that the cluster stabilizes the closed conformation. The intrinsic binding energies of the 5{prime}-phosphate group of orotidine 5{prime}-monophosphate for the mutant enzymes are similar to that for the wild type, supporting this conclusion.« less

Probing conformational dynamics by photoinduced electron transfer

NASA Astrophysics Data System (ADS)

Neuweiler, Hannes; Herten, Dirk P.; Marme, N.; Knemeyer, J. P.; Piestert, Oliver; Tinnefeld, Philip; Sauer, Marcus

2004-07-01

We demonstrate how photoinduced electron transfer (PET) reactions can be successfully applied to monitor conformational dynamics in individual biopolymers. Single-pair fluorescence resonance energy transfer (FRET) experiments are ideally suited to study conformational dynamics occurring on the nanometer scale, e.g. during protein folding or unfolding. In contrast, conformational dynamics with functional significance, for example occurring in enzymes at work, often appear on much smaller spatial scales of up to several Angströms. Our results demonstrate that selective PET-reactions between fluorophores and amino acids or DNA nucleotides represent a versatile tool to measure small-scale conformational dynamics in biopolymers on a wide range of time scales, extending from nanoseconds to seconds, at the single-molecule level under equilibrium conditions. That is, the monitoring of conformational dynamics of biopolymers with temporal resolutions comparable to those within reach using new techniques of molecular dynamic simulations. We present data about structural changes of single biomolecules like DNA hairpins and peptides by using quenching electron transfer reactions between guanosine or tryptophan residues in close proximity to fluorescent dyes. Furthermore, we demonstrate that the strong distance dependence of charge separation reactions on the sub-nanometer scale can be used to develop conformationally flexible PET-biosensors. These sensors enable the detection of specific target molecules in the sub-picomolar range and allow one to follow their molecular binding dynamics with temporal resolution.

Conformal Symmetry as a Template for QCD

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

Brodsky, S

2004-08-04

Conformal symmetry is broken in physical QCD; nevertheless, one can use conformal symmetry as a template, systematically correcting for its nonzero {beta} function as well as higher-twist effects. For example, commensurate scale relations which relate QCD observables to each other, such as the generalized Crewther relation, have no renormalization scale or scheme ambiguity and retain a convergent perturbative structure which reflects the underlying conformal symmetry of the classical theory. The ''conformal correspondence principle'' also dictates the form of the expansion basis for hadronic distribution amplitudes. The AdS/CFT correspondence connecting superstring theory to superconformal gauge theory has important implications for hadronmore » phenomenology in the conformal limit, including an all-orders demonstration of counting rules for hard exclusive processes as well as determining essential aspects of hadronic light-front wavefunctions. Theoretical and phenomenological evidence is now accumulating that QCD couplings based on physical observables such as {tau} decay become constant at small virtuality; i.e., effective charges develop an infrared fixed point in contradiction to the usual assumption of singular growth in the infrared. The near-constant behavior of effective couplings also suggests that QCD can be approximated as a conformal theory even at relatively small momentum transfer. The importance of using an analytic effective charge such as the pinch scheme for unifying the electroweak and strong couplings and forces is also emphasized.« less

A global assessment of climate-water quality relationships in large rivers: an elasticity perspective.

PubMed

Jiang, Jiping; Sharma, Ashish; Sivakumar, Bellie; Wang, Peng

2014-01-15

To uncover climate-water quality relationships in large rivers on a global scale, the present study investigates the climate elasticity of river water quality (CEWQ) using long-term monthly records observed at 14 large rivers. Temperature and precipitation elasticities of 12 water quality parameters, highlighted by N- and P-nutrients, are assessed. General observations on elasticity values show the usefulness of this approach to describe the magnitude of stream water quality responses to climate change, which improves that of simple statistical correlation. Sensitivity type, intensity and variability rank of CEWQ are reported and specific characteristics and mechanism of elasticity of nutrient parameters are also revealed. Among them, the performance of ammonia, total phosphorus-air temperature models, and nitrite, orthophosphorus-precipitation models are the best. Spatial and temporal assessment shows that precipitation elasticity is more variable in space than temperature elasticity and that seasonal variation is more evident for precipitation elasticity than for temperature elasticity. Moreover, both anthropogenic activities and environmental factors are found to impact CEWQ for select variables. The major relationships that can be inferred include: (1) human population has a strong linear correlation with temperature elasticity of turbidity and total phosphorus; and (2) latitude has a strong linear correlation with precipitation elasticity of turbidity and N nutrients. As this work improves our understanding of the relation between climate factors and surface water quality, it is potentially helpful for investigating the effect of climate change on water quality in large rivers, such as on the long-term change of nutrient concentrations. © 2013.

Estimation of global structural and transport properties of peptides through the modeling of their CZE mobility data.

PubMed

Piaggio, Maria V; Peirotti, Marta B; Deiber, Julio A

2010-08-01

Peptide electrophoretic mobility data are interpreted through a physicochemical CZE model, providing estimates of the equivalent hydrodynamic radius, hydration, effective and total charge numbers, actual ionizing pK, pH-near molecule and electrical permittivity of peptide domain, among other basic properties. In this study, they are used to estimate some peptide global structural properties proposed, providing thus a distinction among different peptides. Therefore, the solvent drag on the peptide is obtained through a characteristic friction power coefficient of the number of amino acid residues, defined from the global chain conformation in solution. As modeling of the effective electrophoretic mobility of peptides is carried out in terms of particle hydrodynamic size and shape coupled to hydration and effective charge, a packing dimension related to chain conformation within the peptide domain may be defined. In addition, the effective and total charge number fractions of peptides provide some clues on the interpretation of chain conformations within the framework of scaling laws. Furthermore, the model estimates transport properties, such as sedimentation, friction and diffusion coefficients. As the relative numbers of ionizing, polar and non-polar amino acid residues vary in peptides, their global structural properties defined here change appreciably. Needs for further research are also discussed.

Network visualization of conformational sampling during molecular dynamics simulation.

PubMed

Ahlstrom, Logan S; Baker, Joseph Lee; Ehrlich, Kent; Campbell, Zachary T; Patel, Sunita; Vorontsov, Ivan I; Tama, Florence; Miyashita, Osamu

2013-11-01

Effective data reduction methods are necessary for uncovering the inherent conformational relationships present in large molecular dynamics (MD) trajectories. Clustering algorithms provide a means to interpret the conformational sampling of molecules during simulation by grouping trajectory snapshots into a few subgroups, or clusters, but the relationships between the individual clusters may not be readily understood. Here we show that network analysis can be used to visualize the dominant conformational states explored during simulation as well as the connectivity between them, providing a more coherent description of conformational space than traditional clustering techniques alone. We compare the results of network visualization against 11 clustering algorithms and principal component conformer plots. Several MD simulations of proteins undergoing different conformational changes demonstrate the effectiveness of networks in reaching functional conclusions. Copyright © 2013 Elsevier Inc. All rights reserved.

76 FR 59344 - Approval and Promulgation of Air Quality Implementation Plans; Maryland; Transportation...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-26

... Promulgation of Air Quality Implementation Plans; Maryland; Transportation Conformity Regulations AGENCY... Implementation Plan (SIP) revision submitted by Maryland to establish transportation conformity regulations. In the Final Rules section of this Federal Register, EPA is approving the State's SIP submittal as a...

78 FR 71554 - Approval and Promulgation of Air Quality Implementation Plans; New Hampshire; Transportation...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-29

...] Approval and Promulgation of Air Quality Implementation Plans; New Hampshire; Transportation Conformity and... of New Hampshire. This revision establishes transportation conformity criteria and procedures related...-R01-OAR-2012-0113,'' Anne Arnold, U.S. [[Page 71555

A systematic review and quality appraisal of international guidelines for early breast cancer systemic therapy: Are recommendations sensitive to different global resources?

PubMed

Gandhi, S; Verma, S; Ethier, J-L; Simmons, C; Burnett, H; Alibhai, S M H

2015-08-01

The breast cancer incidence in low and middle income countries (LMCs) is increasing globally, and patient outcomes are generally worse in these nations compared to high income countries (HICs). This is partly due to resource constraints associated with implementing recommended breast cancer therapies. Clinical practice guideline (CPG) adherence can improve breast cancer outcomes, however, many CPGs are created in HICs, and include costly recommendations that may not be feasible in LMCs. In addition, the quality of CPGs can be variable. The aim of this study was to perform a systematic review of CPGs on early breast cancer systemic therapy with potential international impact, to evaluate their content, quality, and resource sensitivity. A MEDLINE and gray literature search was completed for English language CPGs published between 2005 and 2010, and then updated to July 2014. Extracted guidelines were evaluated using the AGREE 2 instrument. Guidelines were specifically analyzed for resource sensitivity. Most of the extracted CPGs had similar recommendations with regards to systemic therapy. However, only one, the Breast Health Global Initiative, made recommendations with consideration of different global resources. Overall, the CPGs were of variable quality, and most scored poorly in the quality domain evaluating implementation barriers such as resources. Published CPGs for early breast cancer are created in HICs, have similar recommendations, and are generally resource-insensitive. Given the visibility and influence of these CPGs on LMCs, efforts to create higher quality, resource-sensitive guidelines with less redundancy are needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Long-range tertiary interactions in single hammerhead ribozymes bias motional sampling toward catalytically active conformations

PubMed Central

McDowell, S. Elizabeth; Jun, Jesse M.; Walter, Nils G.

2010-01-01

Enzymes generally are thought to derive their functional activity from conformational motions. The limited chemical variation in RNA suggests that such structural dynamics may play a particularly important role in RNA function. Minimal hammerhead ribozymes are known to cleave efficiently only in ∼10-fold higher than physiologic concentrations of Mg2+ ions. Extended versions containing native loop–loop interactions, however, show greatly enhanced catalytic activity at physiologically relevant Mg2+ concentrations, for reasons that are still ill-understood. Here, we use Mg2+ titrations, activity assays, ensemble, and single molecule fluorescence resonance energy transfer (FRET) approaches, combined with molecular dynamics (MD) simulations, to ask what influence the spatially distant tertiary loop–loop interactions of an extended hammerhead ribozyme have on its structural dynamics. By comparing hammerhead variants with wild-type, partially disrupted, and fully disrupted loop–loop interaction sequences we find that the tertiary interactions lead to a dynamic motional sampling that increasingly populates catalytically active conformations. At the global level the wild-type tertiary interactions lead to more frequent, if transient, encounters of the loop-carrying stems, whereas at the local level they lead to an enrichment in favorable in-line attack angles at the cleavage site. These results invoke a linkage between RNA structural dynamics and function and suggest that loop–loop interactions in extended hammerhead ribozymes—and Mg2+ ions that bind to minimal ribozymes—may generally allow more frequent access to a catalytically relevant conformation(s), rather than simply locking the ribozyme into a single active state. PMID:20921269

Total quality management in American industry.

PubMed

Widtfeldt, A K; Widtfeldt, J R

1992-07-01

The definition of total quality management is conformance to customer requirements and specifications, fitness for use, buyer satisfaction, and value at an affordable price. The three individuals who have developed the total quality management concepts in the United States are W.E. Deming, J.M. Juran, and Philip Crosby. The universal principles of total quality management are (a) a customer focus, (b) management commitment, (c) training, (d) process capability and control, and (e) measurement through quality improvement tools. Results from the National Demonstration Project on Quality Improvement in Health Care showed the principles of total quality management could be applied to healthcare.

Quantum integrable systems from conformal blocks